KR20160106582A - Catheter or guidewire device including flow sensing and use thereof - Google Patents

Abstract

An apparatus and method for performing a procedure on tissue while monitoring flow using a flow sensor is provided. The apparatus includes a elongate member and at least one flow sensor disposed in the elongate member. The flow sensor includes at least one temperature sensor and at least one heating element having a cavity. At least a portion of at least one temperature sensor is received in the cavity. The temperature measurement of the temperature sensor provides an indication of the flow rate of the fluid close to the flow sensor.

Description

CATHETER OR GUIDEWIRE DEVICE INCLUDING FLOW SENSING AND USE THEREOF FIELD OF THE INVENTION [0001]

Cross-reference to related application

RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 60/1992, filed on July 5, 2012, entitled METHOD AND APPARATUS FOR DENERVATION, each of which is incorporated herein by reference in its entirety, U.S. Provisional Application No. 61 / 728,653, filed November 20, 2012, entitled " RENAL DENERVATION ", entitled " Which claims priority to U.S. Provisional Application No. 61 / 733,575, filed December 5, 2012, entitled " INCREASING THE RESOLUTION OF TEMPERATURE MEASUREMENT FOR FLOW DETECTION IN THE RENAL ARTERY " CATHETER DEVICE INCLUDING FLOW SENSING "filed on March 15, 2013, which is a continuation-in-part of U.S. Patent Application No. 13 / 844,677.

Diseases such as heart disease, stroke and hypertension are global pandemic diseases that affect billions of people worldwide. Hypertension leads to various debilitating diseases, including heart disease and stroke. Despite the widespread use of antihypertensive drugs against high blood pressure, the prevalence of hypertension is surprisingly high and puts significant economic burdens on health care.

The blood pressure is mostly controlled by the sympathetic nervous system. The sympathetic nervous system includes various organs responsible for adjusting blood pressure, such as the brain, heart, and kidneys. Kidneys are a key factor in long - term blood pressure control. Hypertension or high blood pressure is caused by extremely active kidney nerves. This can eventually lead to heart, kidney, and vascular injury.

Other body systems of the body in which nerve activity can affect fluid flow include carotid artery, carotid body, vagus nerve, pulmonary artery, abdominal ganglion and bladder triangle.

The inventors have recognized that the ability to monitor procedures during treatment of tissue is advantageous. For example, kidney resection is a useful and potentially safe technique. Due to the lack of detectability after procedures such as ablation, its applicability may be limited.

As noted above, the various examples described herein are not limited to overall neural nerve and / or neural pacing procedures, but are directed to systems, apparatus, and methods that enable monitoring and / or verification of results of such procedures. will be. The results of surveillance and / or verification may be used to determine the clinical endpoint of the denervation and / or pacing procedure. In addition, the system and method described herein enables establishing a reliable endpoint in neurotomy, including renal sympathetic neurotization.

The system and method described herein provides a novel device comprising a catheter device or guidewire device having diagnostic capabilities for assessing the condition of tissue after each procedure comprising each ablation cycle in a series of ablation cycles .

The systems and methods described herein are not limited to each ablation cycle in a series of ablation cycles, but in a series of such procedures, after each procedure, assess the status of tissue in other tissue systems, including pulmonary veins, coronary arteries and peripheral blood vessels A catheter device having a diagnostic capability to < RTI ID = 0.0 > a < / RTI >

In one example, the present systems, apparatus and methods can be implemented to measure blood flow or other fluid flow, combined with pacing and / or denervation of the nerve, using a single smart catheter or guide wire device Thereby providing a novel device.

In one example, monitoring of the performance of the denervation and / or pacing procedure performed in one or more tissue systems, such as but not limited to carotid artery, carotid body, vagus nerve, pulmonary artery, abdominal ganglion, bladder triangulation or renal artery, / RTI > the system, apparatus, and method of the present disclosure may be implemented in order to enable verification and / or verification.

In one example, a system, apparatus, and method based on thin device islands are provided that include integrated circuit (IC) chips that are encapsulated in an encapsulant and / or extendable and / or flexible interconnections.

In one example, the present systems, apparatus, and methods may be implemented to perform procedures on a portion of an organization, where the procedure is a neurostimulation or nerve stimulation procedure. In one example, the procedure may be a carotid artery, a carotid body, a vagus nerve, a pulmonary artery, a celiac ganglion, a bladder triangulation, or an exenteration.

In one example, a system, apparatus, and method are provided for determining a flow rate of a fluid proximate to a portion of tissue. An exemplary apparatus according to this principle includes a elongate member having a proximal and distal portion, and a flow sensor disposed proximate a distal portion of the elongate member. The flow sensor includes at least one temperature sensor and at least one heating element for heating an area adjacent the elongate member, at least a portion of the at least one heating element forming a cavity. At least a portion of the at least one temperature sensor is housed in a portion of the cavity. The temperature measurement of the temperature sensor provides a first indication of the flow rate of the fluid in proximity to the flow sensor.

In one example, the device may further comprise an inflatable and / or expandable body having a proximal and distal portion coupled to a portion of the elongate member. The distal portion of the inflatable and / or expandable body is disposed proximate to the flow sensor. An exemplary device may further include electronic circuitry coupled to the expandable and / or expandable body, wherein the electronic circuitry includes at least one extendible interconnect, wherein the electronic circuitry is extendable and the electronic circuitry is inflatable 0.0 > and / or < / RTI > accommodating expansion of the expandable body. The electronic circuit may further include at least one passive electronic component and / or at least one active electronic component, wherein the at least one extendable interconnecting portion electrically couples at least two electronic components of the electronic circuit.

In one example, the device may include at least one heating element comprised of a wound resistive wire, wherein the hollow portion of the wound resistive wire forms a cavity. In another example, the at least one heating element may comprise a thin film patterned resistive element, and at least one heating element is formed in a substantially cylindrical shape including a cavity. In another example, the thin film patterned resistive element may comprise a pattern of resistive elements disposed on the stretchable and / or flexible substrate. The resistive element can be formed in a linear pattern, a serpentine pattern, a boustrophedonic pattern, a zigzag pattern, a wavy pattern, a polygonal pattern, or a substantially circular pattern.

In one example, the present systems, apparatus, and methods are provided for displaying a representation of a parameter of an expandable body and / or an expandable body disposed proximate to a portion of the tissue. In one example, the inflatable body and / or the expandable body includes a plurality of sensors coupled to the inflatable body and / or at least a portion of the expandable body. An exemplary apparatus may include a user interface, at least one memory for storing processor executable instructions, and at least one processing unit communicatively coupled to the at least one memory. Depending on the execution of the processor executable instructions, at least one processing unit may control the user interface to display at least one representation of the parameters. At least one representation includes: (A) a first representation of the state of the expandable body and / or the expandable body; and (B) a second representation of the state of at least one sensor of the plurality of sensors. The first representation includes (i) a first feature indicative that the expandable body and / or the expandable body is in an expanded and / or expanded state, or (ii) a first feature indicative of the expandable body and / And a second shape indicator indicating that the second shape indicator is in a folded state. (I) a first operational indicator indicating that at least one sensor of the plurality of sensors measures less than a threshold value, or (ii) at least one sensor of the plurality of sensors exceeds a threshold value or a threshold value And a second operating indicator indicative of measuring approximately the same signal as the first operating indicator.

In an exemplary implementation of the device, a signal below a specified (threshold) value indicates that at least one sensor is not in contact with a portion of tissue, and a signal that exceeds or is approximately the same as the specified (threshold) Indicating that the sensor is in contact with a portion of the tissue.

In an exemplary implementation of the apparatus, the first operational indicator and the second operational indicator may be represented as binary visual and / or quantitative visual representations corresponding to the magnitude of the signal.

In an exemplary implementation of the apparatus, the at least one processing unit is configured such that the second representation is displayed if the second representation is not displayed while the first representation is the first shape indicator and the first representation is the second feature indicator And may be used to control the user interface to display the first and second representations in the process.

In an exemplary implementation of the apparatus, the at least one processing unit is configured to further display an indication of at least one step of a procedure performed on a portion of the tissue and / or an indication of an endpoint of a procedure performed on a portion of the tissue, Can be used to control the user interface.

In one example, the present systems, apparatus, and methods may be implemented to perform medical treatment procedures. An exemplary method includes providing a device comprising a elongated member having a proximal and distal portion, at least one flow sensor disposed proximate a distal portion of the elongate member, and a reference temperature sensor disposed proximally of the elongate member, And placing them in close proximity. The at least one flow sensor each include at least one temperature sensor and at least one heating element disposed proximate to the at least one temperature sensor. An exemplary apparatus may include a control module coupled to at least one flow sensor and a reference temperature sensor. An exemplary method includes using a control module to maintain a temperature difference between a reference temperature sensor and a temperature sensor of the at least one flow sensor in the performing of the medical treatment procedure. The application of the exemplary control module may include monitoring the value of the temperature measurement of the reference temperature sensor and / or the value of the temperature measurement of the temperature sensor of at least one flow sensor, and monitoring at least one heating element And controlling the first signal to the at least one heating element to cause the heating element to emit or to interrupt the heat emission.

In an exemplary embodiment of this method, the temperature difference may be a constant temperature difference or a time varying temperature difference. In one example, the temperature difference may be a constant temperature difference, and the constant temperature difference is about 1.5 占 폚, about 2.0 占 폚, about 2.5 占 폚, about 3.0 占 폚, about 3.5 占 폚, about 4.0 占 폚, or about 4.5 占 폚.

In an exemplary implementation, an exemplary control module includes a proportional-integral-derivative (PID) controller or an anemometer. If the control module comprises a PID controller, the method comprises comparing the value of the temperature measurement of the reference temperature sensor with the temperature measurement of the temperature sensor of at least one flow sensor, and comparing the PID Applying the controller and using the control module to determine a first signal to the at least one heating element based on the second signal.

In an exemplary implementation of the method, the steps of the method may be repeated until the difference falls within a specified range of values.

In one example, the present systems, apparatus and methods may be implemented to monitor hemodynamic effects during medical treatment procedures performed on vascular tissue. An exemplary method comprises the steps of: providing an elongate member having a proximal and distal portion, at least one flow sensor disposed proximate to a distal portion of the elongate member, and at least one flow sensor proximate the distal portion of the elongate member, And placing the device including at least one component coupled to the elongate member proximate the tissue. An exemplary method includes operating at least one component to perform a medical treatment procedure on a portion of tissue, administering a substance that causes a dimensional change of the vascular tissue, and administering to the medical treatment procedure Using at least one flow sensor to perform at least one flow measurement that provides data indicative of a change in flow, the flow of fluid to determine at least one parameter indicative of a change in the hemodynamics of the fluid, And analyzing the data representing the data. Reduced changes in fluid hemodynamics are used to provide an indication of the efficacy of a medical therapeutic procedure.

In an exemplary implementation of the method, the steps of the method may be repeated until the rate of decrease of the hemodynamic change of the fluid falls below a specified value. An exemplary method may further include generating an indication of an endpoint of the medical treatment procedure when the rate of decrease of the change in hemodynamics of the fluid falls below a specified value.

In an exemplary embodiment of the method, the material may comprise an endogenous substance or an exogenous substance. For example, the substance may include dopamine, adenosine, prostacyclin, saline or nitric oxide. If the medical treatment procedure is a neurotomy, the at least one component may be a resection component.

Exemplary systems, devices, and methods of the present disclosure provide a catheter or guide wire device for performing procedures on tissue. The catheter or guidewire device includes an inflatable and / or expandable body disposed proximate the distal end of the catheter and at least one flow sensor disposed in the inflatable and / or expandable body. At least one component is coupled to the catheter or guide wire to perform a resection procedure on a portion of the tissue of the kidney artery. The at least one flow sensor includes a heating element, each heating an area proximate the inflatable and / or expandable body, the heating element including a cavity and a temperature sensor disposed at least partially within the cavity of the heating element. The measurement of the temperature sensor provides an indication of the flow rate of the fluid close to the inflatable and / or expandable body.

The following publications, patents and patent applications are hereby incorporated by reference in their entirety:

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It is to be understood that all combinations of the above-described concepts and the additional concepts described below in greater detail (unless such concepts are mutually inconsistent) are considered to be part of the gist of the invention disclosed herein. It is also to be understood that the terms that appear in any disclosure incorporated by reference as a term explicitly employed herein should be accorded the best meaning consistent with the specific concepts disclosed herein.

Those skilled in the art will appreciate that the drawings described herein are exemplary only and that the drawings are not intended to limit the scope of the teachings set forth in any way. In some instances, various aspects or features may be shown exaggerated or enlarged to facilitate an understanding of the concepts of the invention described herein (the drawings are not necessarily drawn to scale, and instead, (Emphasis is placed on illustrating). In the drawings, like elements throughout the various views are generally designated with the same reference numerals for functionally similar and / or structurally similar elements.
Figures 1A-1C illustrate exemplary voltage waveforms for stimulating the nerves in accordance with the principles described herein.
Figure 2 is a plot of the percentage change in renal blood flow according to the integrated voltage delivered during pacing according to the principles described herein.
Figure 3A illustrates an exemplary apparatus that may be used to perform procedures in accordance with the principles described herein.
Figure 3B illustrates an exemplary flow sensor in accordance with the principles described herein.
Figures 4A and 4B illustrate an exemplary implementation of an exemplary apparatus in accordance with the principles described herein.
FIG. 5 illustrates an exemplary implementation of an electronic circuit and flow sensor in accordance with the principles described herein.
6A-6D illustrate an exemplary flow sensor or exemplary heating element in accordance with the principles described herein.
FIG. 7A illustrates another exemplary apparatus in accordance with the principles described herein.
Figure 7B illustrates another exemplary apparatus in accordance with the principles described herein.
Figures 8A and 8B illustrate the operation of the exemplary flow sensor of Figures 7A and 7B in accordance with the principles described herein.
Figure 9 shows an exemplary simple schematic diagram of a differential pre-amplifier according to the principles described herein.
10 illustrates an exemplary operation of a 3 -ω acquisition system in accordance with the principles described herein.
11 illustrates the operation of an exemplary flow sensor in accordance with the principles described herein.
12 illustrates an exemplary block diagram of an exemplary PID controller coupled to an exemplary flow sensor in accordance with the principles described herein.
13 shows an example of synchronous demodulation according to the principle described in this section.
Figures 14A-14C illustrate cross-sectional layer structures of various components of an exemplary device in accordance with the principles described herein.
Figure 15 shows a flow diagram of an exemplary method for performing an exemplary evaluation in accordance with the principles described herein.
Figure 16 shows an exemplary plot of flow measurement in accordance with the principles described herein.
17 shows a block diagram of an exemplary system including an evaluation module in accordance with the principles described herein.
18A illustrates an exemplary flow sensor in accordance with the principles described herein.
18B illustrates an exemplary measurement using an exemplary flow sensor in accordance with the principles described herein.
19 illustrates an exemplary method of performing a procedure in accordance with the principles described herein.
Figure 20 illustrates an exemplary structure of an exemplary computer system in accordance with the principles described herein.
Figures 21A and 21B illustrate the results of an exemplary measurement using an exemplary apparatus according to the principles described herein.
Figures 22A and 22B illustrate the results of an exemplary use of an exemplary apparatus in accordance with the principles described herein.
23A-23G illustrate examples of multiple electrode and balloon catheter devices in accordance with the principles described herein.
24A-24D illustrate an example of a catheter device.
24E and 24F illustrate an exemplary form of sensing in accordance with the principles described herein.
Figure 25 illustrates a non-limiting example of a flow sensor on a catheter in accordance with the principles described herein.
Figure 26 shows an example of a flow sensor on a spiral catheter according to the principles described herein.
27 illustrates a catheter having bipolar electrodes and metal interconnects in accordance with the principles described herein.
Figures 28A-28D illustrate exemplary representations of data or analysis in accordance with the principles described herein.
29 illustrates an exemplary representation of data and plots in accordance with the principles described herein.

Various concepts associated with devices and systems incorporating thinned chips in flexible polymers and embodiments of such devices and systems are described in more detail below. It is to be understood that the concepts described above are not limited to any particular mode of implementation, and that various concepts introduced above and described in greater detail below may be implemented in any number of ways. Certain embodiments and applications are provided primarily for illustrative purposes.

As used herein, the term " includes "is intended to include but is not limited to, including " including" The term "based on" means at least partly by reference. As used herein, the term " disposed on "or " disposed above" is defined to include "at least partially embedded.

For substrates or other surfaces described herein in connection with the various examples of the present principles, any reference to "top surface" and "bottom surface" And / or orientation of the components, and these terms do not necessarily represent any particular frame of reference (e.g., a reference gravity frame). Therefore, the criteria for the "bottom" of the substrate or layer does not necessarily require that the indicated surface or layer is facing the ground. Likewise, terms such as "over," "under," "above," "below," and the like do not necessarily denote any particular frame of reference such as a reference gravity frame , Are used primarily to indicate the relative location, alignment and / or orientation of the substrate (or other surface) and various elements / components to each other. "Disposed on" The term " disposed in "and" disposed over "include the meaning of" embedded " . It should also be noted that the criteria for feature A to be placed on feature B ", "placed between" or "above " A and Feature B, respectively.

Renal neuronotherapy can be used to break the kidneys through resection, including applying energy to the nerves in the form of RF energy, heating, or cryogenic (extremely cool) form. This can be done by inserting a tube or catheter into the inguinal area and guiding the device into the renal artery. Nephrotic neurotomy is not usually configured to provide a measure of the efficacy of a procedure.

Other non-limiting examples of ablation energy that may be applied using catheters with flow sensing in accordance with the principles described herein include radio frequency (RF), ultrasound energy, cryogenic ablation, drug-based ablation, alcohol injection, microwave energy ablation And light based ablation (laser energy).

Although the description of the evaluation is described with respect to the procedure for the renal artery, the evaluation of the efficacy of the procedure can be performed in other tissue systems. For example, an assessment to determine the efficacy of a procedure using the flow measurements described herein may be based on the use of other tissues such as pulmonary veins, coronary arteries, peripheral blood vessels, heart lumens and any other lumen, It can be applied to a procedure performed in a lumen.

Dennation therapy is not limited to carotid arteries, carotid arteries, vagal nerves, pulmonary arteries, the parietal ganglia, or the bladder triangles, but in other such systems (such as RF energy, heating, or cryogenic ) Can be used to divide the nerve through ablation, including the application of any of the forms described herein.

Increased blood flow in the renal arteries can be used as an indicator of the degree of efficacy of the renal sympathetic denervation (RSDN) procedure. For example, an indication of an increase in blood flow may be considered as an indicator that the RSDN procedure is effective in achieving the desired degree and / or amount of denervation in the targeted tissue. An indication of this degree of efficacy can be assumed to convey an endpoint signal to the procedure if the blood flow rate is approaching the desired level. As another example, an indication that the blood flow volume is small or that there is no change in the blood flow is considered as an index indicating that the RSDN procedure is ineffective or marginally effective in achieving the desired degree and / or amount of denervation in the target tissue . An indication of the degree of such efficacy may be assumed to be used to determine the expected outcome or the expected number of additional procedures to be performed to achieve a potential change that may be made to make the RSDN procedure more effective.

According to the principles described herein, exemplary devices and methods for determining the efficacy of neurotomy, or pacing or other stimulation procedures, are described. An exemplary method for monitoring changes in blood flow or other fluid flow before and / or after a denervation or pacing (or other stimulation) procedure to monitor the steps of the procedure or to determine the end point of the performance of the procedure is disclosed do.

This disclosure is directed to a flow measurement system that can be implemented to determine the efficacy of an interventional procedure including, but not limited to, renal or neurosurgical (or other stimulation) procedures. According to the examples and methods described herein, changes in the flow rate of blood through the tissue lumen can be used to provide an indication of the effectiveness of the procedure performed on the tissue (although not limited to the kidney arteries) . This procedure may be any procedure for dissecting the nerve through ablation, including, for example, applying energy to the nerve in the form of RF energy, heating or cryogenic (extremely cold) form. An exemplary application of the flow measurement system, apparatus, and method described herein is to provide the physician with an indication that the clinical procedure is successful.

According to the principles described herein, exemplary devices and methods for use in establishing a clinical endpoint in the treatment of kidney arteries or other tissues are described. In an exemplary system and method, measurements of blood flow in the kidney artery or other tissue prior to and / or following the procedure may be used to provide an indication of the efficacy of the procedure. In another example, during pre- and / or post-procedure cycles, blood flow measurements may include splitting the nerves through ablation, including applying energy to the nerve, for example in the form of RF energy, heating or cryogenic Can be used to establish the clinical endpoint of the procedure being performed for the patient.

Sympathetic activity controls blood pressure and flow through vasoconstriction. The delivery of electrical stimulation to the sympathetic nerve, eventually, is used to stimulate the nerves to regulate blood flow or other fluid flow. Exemplary devices and methods for measuring changes in local blood flow and / or pressure during, but not limited to, RSDN procedures in accordance with the principles described herein are described.

At present, most forms of high performance electronics and electrodes are rigid, bulky, inherently densely cylindrical and have a cylindrical cuff shape that is incompatible with the complex phase of softness of the arteries. In various exemplary embodiments, a novel micromachining technique for constructing an array of soft and flexible nanomembrane flow sensing, and a method for providing feedback about the renal blood flow while simultaneously delivering pacing energy and / or ablation energy A novel multifunction catheter device is described which includes an electrode element that is capable of being actuated. In various examples described herein, to achieve a high performance flexible flow sensor and electrode array in a catheter device, such as but not limited to a helical balloon catheter that simultaneously measures flow and applies RF energy and pacing energy inside the renal artery, New design strategies and processing techniques using processing are described.

An exemplary catheter device in accordance with the principles set forth herein may include at least one pacing electrode. In the pacing procedure, a potential is applied to a portion of the tissue proximate to the nerve to stimulate blood flow. Figures 1A-1C illustrate exemplary voltage waveforms that may be used to stimulate the nerve. Figure 2 is a plot of the percentage change in renal blood flow according to the integrated voltage delivered during pacing. Figures 1A-1C and 2 show that the blood flow can be changed in the renal artery due to the programmed nerve stimulation (during pacing). In one example, such pacing may be performed during a procedure performed in accordance with the principles described herein. For example, to provide electrical stimulation to tissue prior to, during, and / or after a procedure, for example, in the area of a nerve source, at least one pacing electrode may be placed in the exemplary catheter device As shown in FIG. The procedure may be any procedure that disrupts the kidney via ablation, including applying energy to the nerve in the form of RF energy, heating or cryogenic (extremely cool) form.

Exemplary devices and methods in accordance with the principles set forth herein are described that combine a single catheter device with a component that performs procedures for tissue and a component that senses the flow rate of blood. In addition, an exemplary apparatus and method in accordance with the principles described herein combining a component that performs nerve stimulation (e.g., using a pacing electrode) and a component that senses the flow rate of blood in a single catheter device is described. In one example, an indication of blood flow based on measurements using a catheter device can be used to establish a clinical endpoint during the procedure, including RSDN procedures.

Figure 3A illustrates an exemplary device 300 that may be used to perform a procedure, in accordance with the principles described herein. Exemplary apparatus 300 includes an inflatable and / or expandable body 302, a flow sensor 304 disposed in a portion of the inflatable and / or expandable body 302, And an electronic circuit 306 disposed in the body 302. The electronic circuit 306 includes a number of components that accommodate inflation of the inflatable and / or expandable body 302. In Fig. 3A, the flow sensor 304 is shown positioned on the distal portion of the inflatable body. In another example, the flow sensor may be disposed at or proximate to the proximal portion of the inflatable and / or expandable body.

In an exemplary embodiment, the flow sensor may be formed as shown in Figure 3B. Figure 3B illustrates an exemplary flow sensor 306'including a heating element 307 disposed proximate a temperature sensor 308. [ The heating element 307 and the temperature sensor 308 may be disposed or encapsulated in the support 309. The support portion 309 may be made of a thermally conductive material. In various examples, the heating element 307 may be separated from the temperature sensor 308 by a separation "x". The parameter "x" can be about 1 mm, about 2 mm, about 3 mm, about 5 mm, about 8 mm, about 10 mm, about 12 mm, about 18 mm, about 24 mm, about 30 mm or more. The temperature sensor 308 may include a thermocouple, a resistance temperature detector (RTD) temperature sensor, a junction temperature sensor (including sensors that use voltage measurements across the junction as an indicator of temperature), a thermistor, an integrated circuit temperature sensor Or a semiconductor temperature sensor. An exemplary flow sensor 306 'may provide a measure of the flow rate of blood within the tissue lumen based on the temperature measurement of the temperature sensor. In operation, the heating element is used to maintain the temperature sensor at a specified temperature reading. Any fluid flow past the heating element and the temperature sensor may slightly vary or vary the temperature measurement of the temperature sensor. The heating element is configured to attempt to maintain the temperature sensor at a stable specified temperature measurement value. A change in the fluid flow rate that causes a slight variation in the measured value of the temperature sensor causes the heating element to increase or decrease its heat output to drive the temperature sensor to the specified measured value. A faster flow rate of the fluid (e.g., blood) in the region of the flow sensor may cause the heating element to increase the heat output. A slower flow rate of the fluid (e.g., blood) in the region of the flow sensor may cause the heating element to reduce the heat output. Thus, a change in the operating point of the heating element can be used to provide an indication of the flow rate of the fluid measurement of the temperature sensor, and provides an indication of the flow rate of the fluid proximate the inflatable and / or expandable body 302 Can be used.

3B, the support 309 may be configured to separate the heating element 307 from the fluid by a value of "y" as shown in Fig. 3B. The parameter "y " may be about 2 mm, about 3 mm, about 5 mm, about 8 mm, about 10 mm, about 12 mm, about 15 mm or more. In different exemplary implementations, the parameters "x" and "y" may be modified to vary the dynamic range of the resulting exemplary flow sensor. For example, to increase the overall range of the exemplary flow sensor, "x" may be larger and "y" may be smaller. If the value of "y " is smaller, the heat can flow into the region fluid more easily. If the value of "x" is greater, greater power may be required to generate sufficient heat to flow to the position of the temperature sensor "x" to move the temperature sensor to the desired specific measurement set point. Accordingly, the flow sensor can be operated over a larger overall range including the range of operating signals to the heating element. For example, as described below, the level / magnitude of the signal to the heating element can be used to provide an indication of the flow rate of the fluid. A larger range of operating signals to the heating elements in accordance with this principle can provide a greater range of values and larger data asset values for use in determining the fluid flow rate. In an exemplary embodiment, the system may include a plurality of flow sensors, wherein the two or more flow sensors are configured such that the values of "x" and "y" are different between the heating element and the temperature sensor of each flow sensor. Accordingly, the exemplary system presents a flow sensor that exhibits various measurement ranges.

An exemplary flow sensor in accordance with the principles described herein may include a temperature sensor proximate to a thermal 'radiation' source. According to any of the exemplary systems, methods, and apparatus described herein, a non-limiting example of a heating element that can provide thermal radiation is any type of heater that can be combined with a catheter, including a resistive heater or a thermoelectric heater And a heater.

In any of the exemplary devices according to the principles described herein, the temperature sensor may be a resistance temperature detector (RTD) temperature sensor, a thermocouple, a junction temperature sensor (including sensors that use voltage measurements across junctions as an indication of temperature) , A thermistor, an integrated circuit temperature sensor (including the LM35 series temperature sensor), and a semiconductor temperature sensor. In various examples, sensors of known impedance are used. Other non-limiting examples of sensors that can be used according to any of the systems and methods described herein include a deposition resistor and a ceramic thermistor. In another example, other materials such as foil may be used.

In one example, a calibration standard for the flow sensor 306 'may be developed to correlate the operating point of the heating element to the flow rate. For example, a training sample can be used to convert flow measurements, and each training sample is a fluid that flows at a specific flow rate. For a given amount and / or rate of change of the operating point of the heating element by the heating element, the operating point of the flow sensor is obtained for each training sample. The flow rate of each training sample is known (considered to be preset for the training sample). The amount and / or speed of heating supplied by the heating element is also known. To obtain calibration data, calibration standards may be developed to correlate known supply heating with known flow rates. An exemplary calibration standard may be used to convert the flow sensor measurements to a flow rate for a fluid having properties similar to those used in the training standard.

In an exemplary embodiment, the exemplary device of Figs. 3A and 3B may further include a flow sensor disposed in a portion of the catheter that is coupled to the proximal portion of the inflatable and / or expandable body.

In one example, electronic circuitry 306 may include a plurality of electrodes disposed in an inflatable and / or expandable body 302. The electrodes may be used to perform procedures in accordance with the principles described herein. For example, at least one of the electrodes may be a radio frequency (RF) electrode that carries RF energy to a portion of the tissue surface proximate to the RF electrode. According to the principles described herein, the delivered RF energy is used to correct tissue, including disrupting the kidney nerves.

In another example, device 300 may include components that perform procedures using other aspects. For example, the device 300 may include components for dissecting the kidney nerve via ablation, including, for example, applying energy to the nerve in the form of RF energy, heating or cryogenic (extremely cool) form.

In another example, electronic circuitry 306 of device 300 may include at least one pacing electrode. The pacing electrode may be implemented to deliver electrical stimulation to a portion of tissue proximate to the pacing electrode (such as but not limited to the kidney arteries). As described above, the pacing electrode can be used to stimulate the nerve at various stages of the procedure. For example, prior to delivering energy to divide the nerve, though not limited to ablation, including applying energy to the nerve in the form of RF energy, heating or cryogenic (extremely cool) Stimulation can be applied to a portion of the tissue to stimulate the nerves. In another example, subsequent to delivering energy to dissociate the nerve through, but not limited to, ablation, including applying energy in the form of RF energy, heating or cryogenic (extreme cold) energy to the nerve, Electrical stimulation may be applied to a portion of the tissue to stimulate the nerve.

In another example, electronic circuit 306 may also include a temperature sensor disposed proximate to an electrode of electronic circuit 306, respectively.

In another example, the device 300 may be an inflatable and / or expandable device, such as but not limited to a pacing electrode, a light emitting device, a touch sensor, an image detector, a pressure sensor, a biological activity sensor, And may include one or more other components disposed on the body.

FIGS. 4A and 4B illustrate a non-limiting exemplary embodiment of an exemplary apparatus 400. FIG. Exemplary apparatus 400 includes an inflatable and / or expandable body 402, a flow sensor 404 disposed in a portion of the inflatable and / or expandable body 402, And an electronic circuit 406 disposed in the body 402. The electronic circuitry 406 includes a number of components that accommodate the expansion of the inflatable and / or expandable body 402. As shown in FIGS. 4A and 4B, the flow sensor 404 may be located distal to the inflatable and / or expandable body 402. As a non-limiting example, a portion of the distal region of the expandable and / or expandable structure may be extended to form a protrusion. The flow sensor 404 may be mounted to the protrusion. In another example, the flow sensor 404 may be disposed at or proximate to the proximal portion of the inflatable and / or expandable body.

In an exemplary embodiment, the flow sensor 404 may be configured to include a heating element 407 disposed proximate the temperature sensor 408. In various examples, the heating element 407 may be separated from the temperature sensor 408 by about 1 mm or about 2 mm. As a non-limiting example, the heating element 407 may be a temperature controlled heating element. As a non-limiting example, temperature sensor 408 may be a thermistor.

In the non-limiting example of Figures 4A and 4B, the electronic circuitry may include a plurality of electrodes 410 disposed in an inflatable and / or expandable body 402. The electrodes may be used to perform procedures in accordance with the principles described herein. For example, at least one of the electrodes 410 may be a radio frequency (RF) electrode that transmits RF energy to a portion of the tissue surface proximate the RF electrode. According to the principles described herein, the delivered RF energy is used to correct tissue, including disrupting the kidney nerves.

4A and 4B, the electronic circuitry 406 of the exemplary device 400 includes an extendible and / or expandable body 402 having a surface of a stretchable interconnect 412 ). As shown in FIG. 4B, the extendable interconnect can be used to electrically couple at least one of the plurality of electrodes 410 to an external circuit.

The electronic circuitry 406 of the exemplary device 400 may also include a main bus 414, as shown in the non-limiting example of Figures 4A and 4B. As shown in FIG. 4B, the extendable interconnect 412 electrically couples the electrode 410 to the main bus 414. 4B, the main bus 414 may extend beyond the inflatable and / or expandable body 402 to facilitate electrically coupling the electrode 410 to external circuitry .

In another example, at least one of the electrodes 410 of the electronic circuitry 406 of the device 400 may be a pacing electrode. The pacing electrode may be implemented to deliver electrical stimulation to a portion of tissue proximate to the pacing electrode (such as but not limited to the kidney arteries). As described above, the pacing electrode can be used to stimulate the nerve at various stages of the procedure. For example, prior to delivering energy to divide the nerve, though not limited to ablation, including applying energy to the nerve in the form of RF energy, heating or cryogenic (extremely cool) Stimulation can be applied to a portion of the tissue to stimulate the nerves. In another example, subsequent to delivering energy to dissociate the nerve through, but not limited to, ablation, including applying energy in the form of RF energy, heating or cryogenic (extreme cold) energy to the nerve, Electrical stimulation may be applied to a portion of the tissue to stimulate the nerve.

In another example, device 400 may include components that perform procedures using other aspects. For example, device 400 may include components for dissecting the kidney via ablation, including, for example, applying energy to the nerve in the form of RF energy, heating or cryogenic (extremely cool) form.

In another example, device 400 may be an inflatable and / or expandable device, such as but not limited to a pacing electrode, a light emitting device, a touch sensor, an image detector, a pressure sensor, a biological activity sensor, And may include one or more other components disposed on the body.

In another example, device 400 may also include a temperature sensor disposed proximate electrodes 410 of electronic circuitry 406, respectively.

FIG. 5 illustrates a non-limiting exemplary embodiment of an electronic circuit 506 and flow sensor 504 that may be disposed on a catheter and extend into a shaft of an exemplary apparatus according to the principles described herein. The electronic circuit 506 includes a plurality of electrodes 510. In various examples, the electrode 510 may be a suitable electrode that conforms to the surface of the expandable and / or expandable body. As shown in FIG. 5, the flow sensor 504 includes a heating element 507 disposed proximate a temperature sensor 808. As a non-limiting example, the heating element 507 may be a temperature controlled heating element. As a non-limiting example, the temperature sensor 508 may be a thermistor.

In the non-limiting example of FIG. 5, at least one of the electrodes 510 may be a radio frequency (RF) electrode that transmits RF energy to a portion of the tissue surface proximate the RF electrode. According to the principles described herein, the delivered RF energy is used to correct tissue, including disrupting the kidney nerves. At least one of the electrodes 510 may be a pacing electrode that transmits electrical stimulation to the nerve, as described herein.

As shown in the non-limiting example of FIG. 5, the electronic circuit 506 includes a stretchable interconnect 512 disposed on the surface of the inflatable and / or expandable body. The extendable interconnect 512 may be used to electrically couple at least one of the plurality of electrodes 510 to an external circuit.

In addition, as shown in the non-limiting example of FIG. 5, the electronic circuit 506 also includes a main bus 514. As shown in FIG. 5, the extendable interconnect 512 electrically couples the electrode 510 to the main bus 514. 5, the main bus 514 includes connection pads 516 that facilitate the electrical coupling of the electrode 510 to external circuitry.

6A illustrates a portion of an exemplary apparatus 600 that may be used to perform procedures in accordance with the principles described herein. Exemplary apparatus 300 includes a elongate member 602 and a flow sensor 604 disposed distally of elongate member 602. In Figure 6a, the flow sensor 604 is shown as being positioned distal of the elongate member. In another example, the flow sensor may be disposed at or proximate to the proximal portion of the elongate member, or may be disposed at the proximal or distal portion of the expandable and / or expandable body coupled to the elongate member.

In this exemplary embodiment, a flow sensor may be formed as shown in FIG. 6A and includes a heating element 606 and a temperature sensor 608. The heating element 606 includes a cavity 607. At least a portion of the temperature sensor 608 is received in a portion of the cavity 607, as shown in FIG. 6A. Similar to that described above with reference to the flow sensor of FIGS. 3A and 3B above, the heating element 606 can be used to heat an area adjacent the elongate member 602. The temperature measurement of the temperature sensor 608 can be used to provide an indication of the flow rate of the fluid proximate to the flow sensor 604. [ For example, if a fluid has a higher flow rate and absorbs heat from a region close to the heating element, the temperature sensor can record a different measurement than that obtained when the fluid flow rate is lower.

In operation, the heating element is used to maintain the temperature sensor at a specified temperature reading. Any fluid flow past the heating element and the temperature sensor may slightly vary or vary the temperature measurement of the temperature sensor. The heating element is configured to attempt to maintain the temperature sensor with a stable specified temperature measurement value. A change in the fluid flow rate that causes a slight variation in the measured value of the temperature sensor causes the heating element to increase or decrease its heat output to drive the temperature sensor to the specified measured value. A faster flow rate of the fluid (e.g., blood) in the region of the flow sensor may cause the heating element to increase the heat output. A slower flow rate of the fluid (e.g., blood) in the region of the flow sensor may cause the heating element to reduce the heat output. Thus, a change in the operating point of the heating element can be used to provide an indication of the flow rate of the fluid measurement of the temperature sensor, and provides an indication of the flow rate of the fluid proximate the inflatable and / or expandable body 302 Can be used.

Also, as described above in connection with the flow sensors of FIGS. 3A and 3B, the temperature sensor 608 may include a thermocouple, a resistance temperature detector (RTD) temperature sensor, a junction on-site sensor (voltage across the junction as an index of temperature Thermistors, integrated circuit temperature sensors (including LM35 series temperature sensors), or semiconductor temperature sensors. In various examples, sensors of known impedance are used. Other non-limiting examples of sensors that can be used according to any of the systems and methods described herein include a deposition resistor and a ceramic thermistor. In another example, other materials such as foil may be used.

Exemplary flow sensors in accordance with the principles described in connection with FIG. 6A may include any type of thermal 'radiation' source. Non-limiting examples of heating elements that can be implemented to provide thermal radiation include any type of heater that can be combined with the elongate member and configured to have a cavity. As a non-limiting example, the heating element may be a resistive heater or a thermoelectric heater, but is not limited thereto.

FIG. 6B illustrates an implementation 620 of an exemplary flow sensor 624 in accordance with the principles of FIG. 6A. Exemplary flow sensor 624 includes a heating element 626 and a temperature sensor 628. The heating element 626 is formed of a spiral, helical, or other wound resistive wire having a hollow core that provides a cavity. The resistive wire can be made of a high resistivity electrical material to enable higher power dissipation. 6A, at least a portion of the temperature sensor 628 is received in a portion of the cavity. As shown in this example, heating element 626 and temperature sensor 628 may be at least partially encapsulated in a thermally conductive encapsulant. Similar to that described above with reference to the flow sensor of Figs. 3A and 3B above, the heating element 626 can be used to heat an area adjacent the elongate member to which the flow sensor is coupled. The temperature measurement of the temperature sensor 628 may be used to provide an indication of the flow rate of the fluid proximate to the flow sensor 624.

6C shows another embodiment 630 of an exemplary flow sensor according to the principle of FIG. 6A. Exemplary flow sensors include a heating element 636 and a temperature sensor (not shown). The heating element 636 is formed of a patterned thin film of a resistive material 631 on the flexible and / or stretchable substrate 633. In this example, the thin film is patterned in a right-angle pattern. The heating element 636 can be wound with a more compact shape factor and at least a portion is formed with a hollow core to provide a cavity. The resistive wire can be made of a high resistivity electrically conductive material to enable higher power dissipation. Similar to that described above with reference to the flow sensor of Figs. 3A and 3B above, the heating element 636 can be used to heat an area adjacent the elongate member to which the flow sensor is coupled. The temperature measurement of the temperature sensor that is at least partially disposed within the cavity can be used to provide an indication of the flow rate of the fluid proximate the flow sensor 634. [

6C shows another embodiment 630 of an exemplary flow sensor according to the principle of FIG. 6A. Exemplary flow sensors include a heating element 636 and a temperature sensor (not shown). The heating element 636 is formed of a patterned thin film of a resistive material 631 on the flexible and / or stretchable substrate 633. In this example, the thin film is patterned in a right-angle pattern. In another example, other linear patterns may be used. The heating element 636 may be formed with a compact shape factor, and at least a portion thereof is formed to have a cavity 637. The thin film may be made of a high resistivity electrically conductive material to enable higher power dissipation. Similar to that described above with reference to the flow sensor of Figs. 3A and 3B above, the heating element 636 can be used to heat an area adjacent the elongate member to which the flow sensor is coupled. The temperature measurement of the temperature sensor that is at least partially disposed within the cavity can be used to provide an indication of the flow rate of the fluid proximate the flow sensor.

Figure 6d illustrates another embodiment 640 of an exemplary flow sensor coupled to a portion of elongate member 642 in accordance with the principles of Figure 6a. An exemplary flow sensor includes a heating element 646 and a temperature sensor (not shown). The heating element 646 is formed of a patterned thin film of a resistive material 641 on the flexible and / or extendable substrate 643. As shown in this example, the thin film can be patterned into a stretchable pattern. The stretchable pattern allows the elongate member to bend more while compensating for surface strain. While the example of Figure 6d shows a serpentine pattern, the stretchable pattern may be a zigzag pattern, a wavy pattern, or another stretchable pattern comprising a wavy pattern. The heating element 646 may be formed with a compact shape factor, at least a portion of which is formed to have a cavity. The thin film may be made of a high resistivity electrically conductive material to enable higher power dissipation. Similar to that described above with reference to the flow sensor of Figs. 3A and 3B above, the heating element 646 can be used to heat an area adjacent the elongate member to which the flow sensor is coupled. The temperature measurement of the temperature sensor that is at least partially disposed within the cavity can be used to provide an indication of the flow rate of the fluid proximate the flow sensor.

7A illustrates another exemplary device 700 that may be used to perform procedures in accordance with the principles described herein. Exemplary apparatus 700 includes an inflatable and / or expandable body 702, a pair of flow sensors 704-a, 704-b, and an inflatable and / or expandable body 702 Electronic circuitry 706. Apparatus 700 is coupled to the distal portion of shaft 708. The electronic circuitry 706 includes a number of components that accommodate the expansion of the inflatable and / or expandable body 702. In Figure 7a, one of the flow sensors 704-a is shown positioned proximally to the inflatable body. It is shown that another flow sensor (reference flow sensor 704-b) is located at a portion of the shaft 708 away from the inflatable and / or expandable body 702 at some distance. 7A, the flow rate can be measured based on a comparison of the measurements of the pair of flow sensors 706-a and 706-b. For example, the flow rate can be measured according to a comparison of the voltage measurements of a pair of flow sensors 706-a, 706-b.

FIG. 7B illustrates another exemplary device 700 'that may be used to perform procedures in accordance with the principles described herein. Exemplary apparatus 700 'includes an inflatable and / or expandable body 702, a pair of flow sensors 704-a, 704-b, and an inflatable and / or expandable body 702 An electronic circuit 706, a shaft 708 and an identical component (not repeating) to the exemplary device 700. [ In addition, the exemplary apparatus 700 'includes a shaft 710 that can be placed over a reference electrode 704-b during a procedure or flow measurement. In addition, the exemplary device 710 may be retracted such that the reference flow sensor 704-b is exposed.

In various examples described herein, the reference sensor may be located on the shaft at a position that can be covered with an envelope. Figure 7B shows a non-limiting example of a catheter device including a shell member that can be positioned to cover at least a portion of a reference sensor. In an exemplary embodiment, the distance may be determined to be at least about 10 cm from the proximal end of the balloon. In another exemplary embodiment, this distance may be determined to be less than about 10 cm from the proximal end of the balloon. For example, reference flow sensor 704-b may be located at a distance of at least about 5 cm, at least about 8 cm, at least about 10 cm, at least about 13 cm, at least about 15 cm, or more, in the shaft of the catheter . In an exemplary embodiment, the envelope may be included and used to guide, guide, and steer the catheter. The envelope may be a member that surrounds / surrounds at least a portion of the circumference of the shaft of the catheter or may be coaxial with the shaft of the catheter. During the procedure, the reference sensor may be held under the skin. The envelope can be configured to provide a stable known environment and to provide a chamber that can contain blood when there is no flow. In this example, blood enters the sheath, but flow may stop due to the presence of a stopcock or flow switch. Blood can be maintained at body temperature, but does not flow, thus providing useful comparisons close to the reference sensor. Measurements performed using a reference sensor in an environment where blood does not flow can serve as a reference for comparison with the renal artery sensor.

The inner shaft near the reference sensor may include a surface feature in the form of a bump or track that provides a channel for blood. The blood forms an insulating layer on the reference sensor, allowing the reference quiescent blood temperature to be measured. The surface feature can be designed and configured to allow blood to circulate freely and prevent the shaft from contacting the sheath in the area. For example, the shaft may include one or more spacers (also referred to as protrusions) to retain a shaft spaced from a portion of the surface of the shell. Separating the shaft from the sheath helps to maintain a static layer of static blood between the sheath and the shaft.

Figures 8A and 8B illustrate the operation of the flow sensor of Figures 7A and 7B. 8A illustrates an embodiment of an electronic device 806 that includes an inflatable and / or expandable body 802, a pair of flow sensors 804-a and 804-b, and electronic circuitry 806 disposed on the inflatable and / ), A shaft 808, and an enclosure 810. As shown in FIG. The flow sensor 804-b is coupled to the shaft and is covered with a shell 810. In the example of Fig. 8B, blood flows in the aorta and kidney arteries, but the blood stays static in the sheath due to the stopcock or flow switch. This allows for differential measurement of flow in the renal arteries for static flow within the envelope. This also allows better use of the dynamic range in that the measurement is limited between the two sensors. Also, as shown in Figure 8b, the inflatable or expandable structure may be retracted or retracted during the flow sensor measurement.

In an exemplary embodiment, the methods associated with Figures 8A and 8B can be used to analyze small temperature changes in the body. Exemplary systems, devices, and methods consistent with the principles set forth herein may be used to measure signals of interest associated with a procedure and to reject information not related to the signal of interest, thereby increasing resolution and reducing the need for expensive signal processing Lt; / RTI >

Exemplary systems, apparatus, and methods in accordance with the principles set forth herein may be used to measure differential flow, as described in connection with Figures 8A and 8B. In an exemplary implementation, two (or more) sensors are used to measure flow through a change in flow sensor operating point. As shown in Figs. 8A and 8B, at least one reference sensor may be located in the shaft of the catheter used to perform the measurements described herein. A non-limiting exemplary catheter may include one or more renal artery flow sensors and / or one or more other sensors including one or more ablation components and / or one or more pacing electrodes. The reference sensor may be disposed in the vicinity of the inflatable or expandable member of the catheter, such as, but not limited to, a balloon, an expandable mesh, or a deployable network. The reference sensor may be disposed at a sufficient separation distance from the proximal end of the balloon so that the reference sensor is covered by the sheath of the catheter when the reference sensor is close to the tissue of the body. At least one kidney artery sensor may be located at or near the proximal end of the balloon. Each measurement performed can be compared or displayed with reference to the measurement of the reference sensor.

Systems, methods, and apparatus that can be used to increase the dynamic range of a measurement by focusing on a signal of interest are described herein. In an exemplary embodiment, each flow sensor including an arbitrary reference sensor may be operated using the same control current source. In an exemplary implementation, each sensor can be measured using a instrumentation amplifier. Figure 9 shows a non-limiting, exemplary, schematic diagram of a differential preamplifier that can be used to measure voltage differences. An exemplary differential preamplifier circuit can be implemented to compare the measurements of the flow sensor according to the principles of Figures 8A and 8B. In this non-limiting example, the flow sensor may comprise a thermistor. In another example, the flow sensor may include a resistance temperature detector (RTD) temperature sensor, a thermocouple, a junction temperature sensor (including sensors that use voltage measurements across junctions as an indication of temperature), integrated circuit temperature sensors And a semiconductor temperature sensor. In various examples, sensors of known impedance are used. Other non-limiting examples of sensors that can be used according to any of the systems and methods described herein include a deposition resistor and a ceramic thermistor. In another example, other materials such as foil may be used.

In the example of FIG. 9, the difference in voltage may be measured between flow sensors (such as but not limited to a thermistor) driven by an excitation current. Signal C is the difference between the signal from a flow sensor (inflated flow sensor measurement - signal A) proximate to the inflatable and / or expandable body and the signal from the reference flow sensor (reference flow sensor measurement - signal B).

The instrumentation amplifier can be used to reject the common mode signal and provide a higher fidelity signal. In a non-limiting example, the apparatus or system described herein may include a thermistor (in this example, used as a flow sensor) that is a good match. The absolute value of the thermistor measurement can be used. The advantage of measuring the reference thermistor and the renal artery thermistor is that the dynamic range can be improved by measuring the difference in value between the sensors as compared to using absolute values. Limiting the measurement between the reference sensor and the renal artery sensor may enable improvement of the dynamic range of the measurement.

An exemplary implementation for performing measurements is described. In one example, the impedance of the flow sensor is known, and the application of excitation current using a flow sensor produces a measured voltage using the instrumentation amplifier. The amplifier is used to measure the voltage correlated to the flow rate. A change in blood flow may cause a change in the operating setpoint of at least one of the flow sensors. The flow rate can be quantified by comparing the value of the measured voltage using the reference sensor with the value of the measured voltage using a flow sensor disposed proximate the expandable and / or inflatable body. With this comparison, the appliance voltage in the absence of flow can also be eliminated. In one example, the value of the voltage measured using the reference sensor may be subtracted from the renal artery sensor voltage to provide an indication of the device voltage when there is no flow. In one example in which the reference flow sensor is surrounded by an envelope, the blood in the envelope is physically static. That is, it does not flow and is maintained at body temperature. Blood in the renal arteries also maintains body temperature, but flows at a slight rate (required to be measured).

Differential voltage comparisons can be calculated based on the following flow sensor measurement data:

Differential measurement (C) = renal artery sensor voltage (A) - reference sensor voltage (B), which can also be expressed as: C = A - B

Effectively, in an exemplary implementation, this equation can be expressed as: < RTI ID = 0.0 >

Differential measurement = (Voltage _BodyTemp + Voltage _RenalFiow ) - (Voltage _BodyTemp + 0), where V _SheathFlow = 0.

Differential measurement = Voltage _RenalFlow

A gain can be added to any of the instrument amplifiers to increase the amplitude of the signal.

In an exemplary implementation, one or more flow sensors can be calibrated. By positioning the catheter at a known temperature and flow rate and measuring the difference between the two sets of sensors, the offset value between the flow sensor and the reference flow sensor disposed proximate the inflatable and / or expandable body can be eliminated . Measurements may be performed and / or an offset value may be derived during manufacture of the catheter and / or during assembly of the flow sensor having an inflatable and / or expandable body of the catheter. The offset value can be stored and / or displayed as a written value or a barcode or other type of identification (ID). In one example, an integrated circuit or memory device or other means may be used to provide these values and IDs to a console that is in communication with a catheter (including a flow sensor that is disposed on or proximate to an inflatable and / or expandable body) Can be used. Such an offset value may be programmed with a catheter. When the catheter is coupled with the console, the console can use an offset value to compensate for the offset of the measurement during flow cycling.

Detecting a change in the measured value of the thermistor, as in one example of implementation described in connection with FIGS. 7A, 7B and 8, can provide an indication of the velocity of the fluid flow. Detecting changes in flow rate in the renal arteries may require a high resolution measurement.

For example, the differential measurements described in connection with FIGS. 7A, 7B and 8 may be performed in a manner such as peak-to-peak measurement, synchronous-demodulation (lock-in), and 3 omega It can be used with other methods. In a different exemplary embodiment, a differential measurement may be used to measure the peak-to-peak output, or may be input to a lock-in amplifier or 3ω acquisition system as shown in FIG. The 3? Method can be implemented using a micro-machined metal pattern that acts as a resistive heater. The alternating current (AC) voltage signal energizes the resistive element at frequency ω. Periodic heating generates vibration in the electrical resistance of metal lines at a frequency of 2ω. As a result, it induces the third harmonic 3? In the voltage signal. The third harmonic is used according to an exemplary implementation to determine the magnitude of the temperature oscillation. Temperature oscillation can be used to provide an indication of the flow rate of the fluid. For example, the frequency dependence of this temperature oscillation can be used to derive the thermal properties of the specimen (e.g., fluid). Data representing the thermal properties of the sample may be used to derive data representative of the flow rate of the fluid.

In any of the examples described herein, a flow sensor (including three omega sensors) may be placed in the exemplary device such that when the exemplary device is placed in the lumen, the flow sensor is located within the midpoint of the tissue lumen have. The midpoint of the lumen in the tissue (including the renal artery lumen) may be the position of the maximum flow rate. Placing the flow sensor centrally can enable a more accurate measurement of the fluid flow rate by sampling the area of maximum flow.

11 illustrates a flow sensor 1154 disposed distal to a rod catheter or guide wire 1152 and a reference temperature sensor 1156 disposed proximally to the rod catheter or guide wire 1152 and a sheath 1158 ≪ / RTI > The reference temperature sensor 1156 is coupled to the shaft and may be covered by the sheath 1158 or may remain uncovered. In the example of FIG. 11, the system can be operated such that a specified difference between the value of the temperature measurement of the reference temperature sensor 1156 and the value of the temperature measurement of the temperature sensor of the flow sensor 1154 can be maintained. As will be described in more detail below, the temperature difference can be maintained at a value of the temperature difference of about 1.5 DEG C, about 2.0 DEG C, about 2.5 DEG C, about 3.0 DEG C, about 3.5 DEG C, about 4.0 DEG C, have. While the example of Figures 7A-8B is described as having a reference flow sensor 704-b or 810, each system has a reference flow sensor that is replaced with a reference temperature sensor and operates as described in connection with Figure 11 .

In an exemplary embodiment, an apparatus according to any of the principles of the present principles and any of the figures comprising Figures 3A-B or 11 may be implemented to perform medical treatment procedures for the following tissues . An exemplary apparatus includes a elongate member, a flow sensor disposed proximate a distal portion of the elongate member, and a reference temperature sensor disposed proximate to the proximal portion of the elongate member. The flow sensor and the reference temperature sensor are in communication with the control module. In this example, the control module is used to maintain the temperature difference between the measurement of the reference temperature sensor and the measurement of the temperature sensor of the flow sensor. For example, at various stages of the procedure being performed, the control module may be used to monitor the temperature measurement of the reference temperature sensor and / or the temperature sensor of the flow sensor. Depending on the monitoring, the control module can generate a signal to the heating element to cause the heating unit to emit heat or to stop the heat emission, so that the temperature difference is maintained. The signal applied to the heating element can be stored in a memory and / or communicated using a communication interface or communication protocol and / or can be read to a user interface (display, etc.).

The temperature difference can be maintained as a constant temperature difference or a time varying temperature difference. For example, a constant temperature difference can be maintained at about 1.5 ° C, about 2.0 ° C, about 2.5 ° C, about 3.0 ° C, about 3.5 ° C, about 4.0 ° C, or about 4.5 ° C.

In one example, the control module includes a proportional-integral-derivative (PID) controller. Figure 12 illustrates an exemplary control system for implementing a PID controller control loop. As shown in FIG. 11, the PID controller receives as input the voltage signal 1202 from the temperature sensor of the flow sensor and the voltage signal 1204 from the reference temperature sensor. At 1206, the PID controller applies an algorithm and associated method to determine three-term control of the proportional value (P), the integral value (L) and the derivative value (D). Based on these calculations, the PID controller determines the error or degree of deviation of the measured signal from the temperature sensor from the expected value that can maintain the desired temperature difference between them. To determine the signal to be transmitted to the voltage controlled current source 1210 for the heating element 1212, the PID controller applies the heating element control algorithm (and associated method) in a combination of P value, I value and D value. The signal transmitted to the voltage controlled current source 1210 regulates the power to the heating element or causes the heating element to release heat or to stop the heat emission. That is, the application of the PID controller may include comparing the temperature measurement value of the reference temperature sensor with the temperature measurement of the temperature sensor of the flow sensor, determining a signal, e.g., a PID correction signal, And using the control module to determine the signal to the heating element based on the signal. As a result of the feedback from the temperature sensor to the PID controller, the system can minimize the deviation of the measured signal from the temperature sensor from the expected value that can maintain the desired temperature difference between them. In one example, the system may include hardware that has a fixed frequency but generates a sinusoidal current with a different amplitude for the heating element.

In an exemplary embodiment, the control module may be configured to maintain a constant temperature difference between, but not limited to, about 2 ° C between the reference temperature sensor and the temperature measured at the temperature sensor of the flow sensor. For example, the heating element may be powered to heat the temperature sensor of the flow sensor (e.g., a thermistor) to about 39 ° C. The use of a control module as described herein maintains this temperature difference so that the reference temperature sensor is maintained at a constant temperature difference of about 2 [deg.] C, i.e., about 37 [deg.] C. The signal applied to the heating element may be stored in a memory and / or communicated using a communication interface and / or may be read into a user interface (display, etc.).

In other exemplary embodiments, the control module may be configured to maintain a constant temperature difference during the procedure, e.g., during nerve stimulation, ablation, or other neurotreatment, while the exemplary device is being used. As the fluid flow rate increases during the procedure, the increased fluid flow removes heat from the area of the flow sensor (the combined heating element and temperature sensor). The control module determines from the control loop that the temperature difference is deviated from the target value (e.g., the temperature difference falls below about 2 ° C). The control module generates a signal that causes the heating element to release heat to return the temperature difference to a target value (e.g., a value of about 2 ° C). The signal applied to the heating element may be stored in a memory and / or communicated using a communication interface and / or may be read into a user interface (display, etc.). In this case, the signal transmits a control to cause the heating element to emit heat, so that the signal can show an increase.

In an exemplary embodiment in which the step of the procedure reduces the fluid flow rate, the reduced fluid flow removes less heat from the area of the flow sensor (combined heating element and temperature sensor). The control module determines that the temperature difference from the control loop is deviated from the target value (e.g., the temperature difference may increase by more than about 2 ° C). The control module generates a signal that causes the heating element to stop emitting heat to return the temperature difference to a target value (e.g., a value of about 2 ° C). The signal applied to the heating element may be stored in a memory and / or communicated using a communication interface and / or may be read into a user interface (display, etc.). In this case, the signal transmits a control to cause the heating element to stop emitting heat, so the signal may show a decrease.

More precise temperature measurements, that is, measurements that prevent the effects of changes in body temperature, can be obtained through the use of differential temperature measurements in accordance with the principles of this volume. The differential temperature measurement may be performed using two or more temperature sensors including a reference temperature sensor that is not coupled to the heating element and a sensing temperature sensor that is coupled to the heating element (which forms the flow sensor) and thereby heated. The temperature sensor associated with the heating element is not limited to a rod catheter or guide wire but may be located distal or proximal to such a elongate member or may be located on a distal or proximal portion of a elongate member including an inflatable and / . In one example, the reference temperature sensor may be spaced from the flow sensor at a distance of at least about 0.5 cm, at least about 1 cm, at least about 1.5 cm, or at least about 2 cm or more.

In one example, an apparatus in accordance with any of the principles of the present principles and according to any of the figures of the drawings including Figures 3A-8B or 11 may comprise two or more flow sensors comprising a plurality of flow sensors. More than one flow sensor may be coupled to a single reference temperature sensor via a control module, or each flow sensor may be coupled to a respective reference temperature sensor. In an exemplary embodiment, the signal to the heating element may be a time varying voltage signal. For example, the operation of the temperature sensor of the heating element and the flow sensor can be accomplished using a large AC frequency relative to the inverse of the tissue response time. As a non-limiting example, a signal at an AC frequency in the range of about 1 kHz to about 100 kHz may be used to drive the flow sensor to reduce the risk of accidental fretting. Operation at this range of frequencies also allows for greater current leakage.

In an exemplary embodiment, the signal to the heating element may be a voltage signal, a current signal, a digital signal, or any other signal that conveys a command to cause the heater to heat at a desired temperature to maintain the desired temperature difference. The signals can be read and / or constructed, stored in memory, communicated or communicated.

In an exemplary implementation, the control signal may be mapped to the flow rate through analysis of a plurality of data runs and measurements to generate a standard or other calibration chart associated with the value of the control signal for the physiological flow rate.

In one example, a novel signal processing algorithm and associated method and control module (including PID controller software) are provided for sensing and / or quantifying fluid flow rates.

13 illustrates an exemplary demodulation that may be implemented to extract a signal from a noise in a signal to a heating element. In a non-limiting example, a processor executable instruction to generate a phase locked loop (PLL) may be applied with a synchronous demodulation method to reject the noise and derive the signal. At least one phase-locked loop can be used to lock the sense signal into the control signal and the sense signal into the heater signal for synchronous demodulation. Since the same frequency is used to demodulate the data, the desired signal is extracted as a DC signal (representing amplitude modulation). Synchronous demodulation provides a narrowband filter to reject the noise injected by the environment of the device, which can interfere with the desired signal.

The ability to measure the temperature difference and the control module facilitate the measurement of pulsatile flow over a wide dynamic range. Accordingly, the system and method of the present invention are not limited to the treatment of carotid artery intracranial nerve, carotid artery fibrillation, vagus nerve stimulation, pulmonary artery denervation, laparoscopic ganglionectomy, bladder triangular resection or renal neurotomy, And provides a method for determining an end point.

In one example, any system or device in accordance with the principles set forth herein may be wholly or at least partially encapsulated by an encapsulant material, such as a polymeric material (including any of the polymeric materials described herein) . The encapsulant material can be any material that can be used to laminate, planarize, or embed at least one component of the system or apparatus described herein, including any electronic or other type of component. For example, a method of fabricating any system or device in accordance with the principles described herein may further comprise encapsulating the system or device. In one example, the encapsulant material may be disposed on, or otherwise applied to, an apparatus comprising an expandable and / or expandable body and an electronic circuit or a plurality of electrodes. In one example, polyurethane may be used as the encapsulating material. In another example, the encapsulant material may be the same material as the expandable and / or extensible body material. Sealing any part of the system or apparatus described herein increases the mechanical stability and the robustness of the system or apparatus or increases the electronic performance of electronic components of the system or apparatus against stress or strain applied to the system or apparatus during use Lt; / RTI >

In any of the exemplary devices according to the principles described herein, the encapsulant material may be comprised of any material having elastic properties. For example, the encapsulation may be formed of a polymeric or polymeric material. Non-limiting examples of applicable polymeric or polymeric materials include, but are not limited to, polyimide, polyethylene terephthalate (PET), silicone or polyurethane. Other non-limiting examples of applicable polymeric or polymeric materials include, but are not limited to, plastics, elastomers, thermoplastic elastomers, elasto plastic, thermostats, thermoplastic plastics, acrylates, acetal polymers, biodegradable polymers, cellulosic polymers, fluoropolymers, nylons, Polyimide, polymethyl methacrylate, polymethacrylate, polymethacrylate, polymethyl methacrylate, polymethyl methacrylate, polymethyl methacrylate, polymethyl methacrylate, polymethyl methacrylate Methyl, polymethylpentene, polyphenylene oxide and polyphenylene sulfide, polyphthalamide, polypropylene, polyurethane, styrene resin, sulfone resin, vinyl resin, or any combination of these materials. In one example, the polymer or polymer material of the present disclosure may be silicone, such as, but not limited to, DYMAX ^® polymer (Dymax Corporation, Torrington, CT) or other UV curable polymer, or ECOFLEX ^® (BASF, Florham Park, NJ) .

For application in biomedical devices, the encapsulant should be biocompatible. The stretchable interconnect may be implemented as a polyimide serving as a mechanical reinforcement.

In one example, any of the systems or devices in accordance with the principles of the present subject matter may be constructed as an inflatable and / or airtight device such that the functional layer of the system or device is placed on a neutral mechanical plane (NMP) or neutral mechanical surface (NMS) Or may be disposed in an expandable body. The NMP or NMS is placed in a position that passes through the thickness of the device layer to the system or device if any applied strain is minimized or substantially zero. In one example, the functional layer of a system or device according to the principles described herein includes a stretchable electronic system comprising a plurality of sensing elements, a coupling bus and / or a flexible annular interconnect and a plurality of electrodes.

The location of the NMP or NMS can be changed for the layer structure of the system or device through the introduction of materials that assist in deformation insulation in the various layers of the system or device. In various examples, the polymeric material described herein can be introduced to serve as a modified insulating material. For example, the encapsulant material described herein can be used to position an NMP or NMS by, for example, varying the encapsulation material type and / or layer thickness. For example, the thickness of the encapsulant disposed over the functional layer described herein may be modified (i. E., Reduced or increased) to lower the functional layer with respect to the overall system or device thickness, The position of the NMS can be changed. In another example, the type of encapsulation includes any difference in the elastic (young) modulus of the encapsulant material.

In another example, in order to position the NMP or NMS with respect to the functional layer, at least a partial intermediate layer of material capable of providing modified insulation may be disposed between the functional layer and the expandable and / or expandable body. In one example, the intermediate layer may be comprised of any of the polymeric materials described herein, an aerogel material, or any other material having the applicable elastic mechanical properties.

Based on the principles described herein, an NMP or NMS may be positioned closely, contiguously, or proximately to the side of a system or device that includes, but is not limited to, a functional layer, such a strain sensitive component. This layer can be considered "strain sensitive" if it is susceptible to failure in response to the level of deformation that is likely to break or its performance is different. In one example where the NMP or NMS does not match and is close to the strain sensitive component, the location of the NMP or NMS may be substantially lower than the strain that would otherwise be applied to the strain sensitive component in the absence of the strain resistant layer , Can continue to provide mechanical advantages for strain sensitive components. In various embodiments, the NMS or NMP layer can be used to provide a reduction in at least 10%, 20%, 50% or 75% of the deformation in a strain sensitive component for a given applied deformation when the expandable body is expanded, for example. Sensitive < / RTI > sensitive component, which provides < / RTI >

In various examples, the encapsulant material and / or the intermediate layer material may be disposed at a position consistent with the strain sensitive component comprising the functional layer. For example, portions of the encapsulant material and / or the intermediate layer material may be interspersed with the strain sensitive component, including locations within the functional layer.

In any of the exemplary devices according to the principles described herein, portions of the extendable interconnect, electrodes, and portions of the main bus may be made of a conductive material. In any of the examples described herein, the conductive material may be, but is not limited to, a metal, a metal alloy, a conductive polymer, or other conductive material. In one example, the metal or metal alloy of the coating is selected from aluminum, stainless steel, or transition metal (including copper, silver, gold, platinum, zinc, nickel, titanium, chromium, or palladium, But is not limited to, any applicable metal alloy including alloys with carbon. In another non-limiting example, a suitable conductive material may comprise a semiconducting conductive material comprising a silicon based conductive material, indium tin oxide or other transparent conductive oxide or III-IV conductors (including GaAs). The semiconducting conductive material can be doped.

In any of the exemplary structures described herein, the extendable interconnect may have a thickness of about 0.1, about 0.3, about 0.5, about 0.8, about 1, about 1.5, about 2, Lt; / RTI > The buffer structure and / or the flexible base may have a thickness of about 5 μm, about 7.5 μm, about 9 μm, about 12 μm or more. In any of the examples herein, the encapsulant can have a thickness of about 100 μm, about 125 μm, about 150 μm, about 175 μm, about 200 μm, about 225 μm, about 250 μm, about 300 μm or more.

Figs. 14A and 14B show cross-sectional layer structures of various parts of the exemplary device described herein, which can be micromachined. 14A shows a layer structure of an electrode comprising a polymer layer 1402, a layer of conductive material 1404, and an annular structure of polymer 1406 around the electrode. 14B shows a layer structure of a stretchable interconnect including a polymer layer 1402, a layer of conductive material 1404, and a layer of polymer 1406. Fig. Figure 14C illustrates an embodiment of a method of forming an electrode structure in an expandable and / or expandable body, including a polymer layer 1402, a layer of conductive material 1404, a layer of polymer 1406, a flow sensor 1408, and an encapsulant layer 1410 Fig. 5 shows the layer structure of a flow sensor to be disposed. In one example, the part may be fabricated on a carrier substrate, released from the carrier substrate, or disposed on an expandable and / or expandable body.

A non-limiting exemplary fabrication process for the exemplary device of Figures 14A and 14B is described below. The electrodes can be fabricated using microfabrication and transfer printing processes to have a thickness between about 1 micron and about 5 microns. The sensor can be a 3-omega sensor (described below), and surface mount components (including flow sensors) can be fabricated using pure gold or CU-AU-Ni processing techniques. The fabricated electronic structure is integrated into the surface of the inflatable and / or expandable body (such as but not limited to the balloon of the catheter). In the exemplary device structure of Figures 14A and 14B, the polyimide may have a thickness of about 25 microns. Polyurethane made of resin and solvent can be used as an encapsulant to planarize the array of electrodes and other components on the surface of the expandable and / or expandable body. The encapsulant helps to provide durability during encapsulation of the exemplary device into the tissue lumen.

In one example, the microfabricated flow sensor, the electrode array (including the ablative RF electrode), the electronics of the exemplary device, and other components are ultra thin, mechanical properties that are substantially similar or consistent with the mechanical properties of the expandable or expandable surface Respectively.

Systems and methods are described for performing procedures on tissues comprising the renal arteries, using any of the exemplary devices described herein. An exemplary method includes the steps of placing an exemplary device proximate to the tissue, applying therapy to tissue, providing a flow of the flow sensor as described herein to provide an indication of the flow rate of fluid proximate the exemplary device, And recording the measurement.

In one example, treatment may include applying ablation, or applying energy to the tissue in the form of RF energy, heating, or cryogenic (extreme cold) energy. In one example, treatment is performed to disrupt neurons proximate the tissue.

In one example, the method may be configured to have an exemplary apparatus comprising a flow sensor element configured as a heating element proximate to a temperature sensor. In this example, the operating point of the heating element may be monitored to provide an indication of the flow rate. In one example, recording the flow measurement of the flow sensor may be performed following the step of applying RF energy to the surface of the tissue proximate to the RF electrode. In another example, recording the flow measurement of the flow sensor may be performed prior to applying RF energy to the surface of the tissue proximate the RF electrode.

In one example, to obtain an indication of the flow rate of the fluid (blood, etc.) before and after the treatment procedure being performed, the temperature measurement may be performed before and after the application of RF energy.

In one example, the system, method, and apparatus monitor efficacy and determine a clinical endpoint for the procedure. According to the principles described herein, the procedure is not limited to ablation, including application to the nerves of energy in the form of RF energy, heating or cryogenic (extreme cold), but may be any procedure that disrupts such renal nerves have. The procedure is not blindly completed without feedback on the success of the procedure, which poses a potential risk of tissue damage. Exemplary systems, methods, and devices described herein provide an evaluation of renal neuroendoscopy based on renal hemodynamics (including those based on measurements of fluid flow).

In any of the examples described herein, an evaluation module is provided in accordance with the systems and methods described herein, wherein the evaluation module includes a processor and a memory that stores processor executable instructions. Execution of the processor executable instructions causes the evaluation module to perform the operations associated with any of the methods described herein, including using data indicative of the flow rate to provide an indication of the effectiveness of the clinical procedure.

In one example, the exemplary method uses an indication of an increase in the flow rate of the fluid following the performance of treatment as an indicator of the efficacy of the therapeutic procedure to divide the nerve (including the efficacy of applying RF energy to tissue) . For example, a predetermined value of the fluid flow rate or a percentage increase in the clinically desired flow rate can be used as an indicator of the efficacy of the procedure, including that used as an indication of the end point of the performance of the procedure. As a non-limiting example, the baseline flow rate can be measured using the flow sensor described herein prior to the performance of a procedure that divides the nerve. A desired predetermined value of the fluid flow rate or a percentage increase in the clinically desired flow rate can be determined based on the baseline flow rate. For example, a predetermined value of the fluid flow rate or a percentage increase in the clinically desired flow rate can be set as the amount necessary to return the flow rate to the mean or median range of the renal blood flow value. In the feedback evaluation, the procedure may be performed, the flow rate may be subsequently remeasured / redetermined based on the flow sensor measurement data in accordance with the principles described herein, and the remeasured flow rate may be a predetermined value of the fluid flow rate Or can be compared with a clinically desired percentage increase in flow rate. If a desired predetermined value of the fluid flow rate or a percentage increase in the clinically desired flow rate is not achieved, the procedure can be repeated and the flow rate can be re-measured. If a desired predetermined value of the fluid flow rate or a percentage increase in the clinically desired flow rate is achieved, the end point is signaled and the procedure can be interrupted. In one example, the exemplary method is used as an indication of a lack of therapeutic efficacy (including the efficacy of administering RF energy to the tissue) or as an indication that the treatment procedure should be repeated, stopped or modified, And subsequently using an indication that there is little or no increase in the flow rate of the fluid. If a desired predetermined value of the fluid flow rate or a percentage increase in the clinically desired flow rate is not achieved, the procedure may be modified to achieve the desired performance. In one example, the procedure can be repeated until feedback is signaled to the end point to perform the procedure, re-measure the flow rate, and compare it to a predetermined value of the fluid flow rate or a clinically desired percentage increase in flow rate.

Although evaluation is described with respect to procedures for the renal arteries, evaluation of the efficacy of the procedure may be performed in other systems. For example, an assessment to determine the efficacy of a procedure using the flow measurements described herein may be based on the use of other tissues such as pulmonary veins, coronary arteries, peripheral blood vessels, heart lumens and any other lumen, It can be applied to a procedure performed in a lumen.

In one example, the method may include operating at least one pacing electrode of the exemplary device to deliver an electrical stimulus to a portion of the tissue proximate the pacing electrode. For example, the method may include delivering an electrical stimulus to a portion of the tissue proximate the pacing electrode prior to recording the flow measurement (including recording the flow measurement of the flow sensor).

A non-limiting exemplary procedure for performing procedures for renal artery tissue using an exemplary device configured as a balloon catheter is as follows:

Perform initial measurements (eg, obtain baseline flow)

· Expansion of catheter balloon to block blood flow

Measure elongational flow using any of the exemplary devices or methods described herein

Pacing the kidney arteries (e.g., applying electrical signals to tissue using electrodes of the system)

Contraction of catheter balloon

Measure the "pre-excision" flow using any of the exemplary apparatus or methods described herein

· Expansion of catheter balloon

Perform resection of the renal artery (e.g., energizing tissue to induce lesions and necrosis, including RF energy, heating and cryoablation)

Contraction of catheter balloon

· Measure "after ablation" flow using any of the exemplary apparatus or methods described herein

A non-limiting exemplary procedure for renal denervation to renal artery tissue using an exemplary device configured as a balloon catheter is as follows:

Pacing the kidney arteries (e.g., applying electrical signals to tissue using electrodes of the system)

· Measure the "pre-ablation" flow rate using any of the exemplary apparatus or methods described herein

Perform resection of the renal artery (e.g., energizing tissue to induce lesions and necrosis, including RF energy, heating and cryoablation)

Pacing the kidney arteries (e.g., applying electrical signals to tissue using electrodes of the system)

· Measure "after ablation" flow using any of the exemplary apparatus or methods described herein

The flowchart of FIG. 15 illustrates another non-limiting exemplary method for performing an evaluation during the performance of a procedure including ablation procedures. In this example, the double or triple increase in blood flow in the renal artery is a preset condition used as an indicator of the end point to which the procedure is applied in the feedback assessment. At block 1502, the baseline flux is measured. At block 1504, this procedure is performed for the tissue, although not limited to the procedures performed using the exemplary apparatus described herein. At block 1506, the flow rate is subsequently remeasured / redetermined based on the flow sensor measurement data in accordance with the principles described herein. At block 1508, in the feedback evaluation, the remeasured flow rate is compared to a predetermined value of the fluid flow rate or a percentage increase in the clinically desired flow rate. If a desired preset value of the fluid flow rate or a percentage increase in the clinically desired flow rate is achieved (block 1510), the end point may be signaled (1512) and the procedure stopped. If a desired predetermined value of the fluid flow rate or a percentage increase in the clinically desired flow rate is not achieved (block 1514), the procedure may be repeated (block 1516) and the flow rate may be re- Or a percentage increase 1518 of the clinically desired flow rate. If a desired predetermined value of the fluid flow rate or a percentage increase in the clinically desired flow rate is achieved (block 1520), the end point may be signaled 1512 and the procedure may be interrupted. If a desired preset value of the fluid flow rate or a percentage increase in the clinically desired flow rate is not achieved (block 1522), the procedure may be modified to achieve the desired outcome. For example, as shown in block 1524, the location of the device may be changed to some other area of the tissue and the treatment procedure may be repeated. In one example, the procedure can be repeated until feedback is signaled to the end point to perform the procedure, re-measure the flow rate, and compare it to a predetermined value of the fluid flow rate or a clinically desired percentage increase in flow rate.

In one example, an evaluation module is provided in accordance with the systems and methods described herein, wherein the evaluation module includes a processor and a memory that stores processor executable instructions. Execution of the processor executable instructions allows the evaluation module to perform any of the exemplary methods described herein, including those associated with FIG.

Exemplary systems, methods, and apparatus of the present disclosure may be used to improve the monitoring of the steps of performing the procedure as well as the completion of the procedure. Measurement of the pulsatile fluid flow prior to performing the procedure may be used to provide a quantitative value of the parameter indicative of the baseline fluid flow. The measurement of the pulsatile fluid flow during previous and subsequent cycles during the performance of the procedure can be used to provide feedback to the clinician or other practitioner in the efficacy of the procedure, for example. Based on the analysis of the flow measurement, the end point of the procedure can be determined. For example, the method may be implemented for detection and treatment in tissue lumens. For example, in renal degenerative surgery, the elongated body can be inserted into the envelope and guided through the femoral vein until it reaches the renal artery. The sensor can be used to map renal nerves, acquire images, deliver ablation energy, or monitor tissue properties, along with measurement of fluid flow, before, during, and after ablation or other procedures.

In one example, the effectiveness of performing the steps of the procedure can be monitored through analysis of the time dependence of the fluid flow rate. For example, a change in the time constant associated with the flow rate can be used as a measure of efficacy at a given stage of performance of the procedure. An exemplary method based on the analysis of time constants is as follows. Any of the exemplary devices herein, including any of the flow sensors, may be disposed proximate to the tissue. In this example, the device includes at least one component configured to apply pacing, ablation, denervation or any other treatment procedure performed. At least one component is operated to perform a treatment procedure on a portion of tissue, and at least one flow sensor is used to perform at least one flow measurement. The at least one flow measurement may be used to provide data indicative of a change in flow following each treatment procedure of the fluid adjacent to the device. Analysis of the data representing the flow of the fluid may be used to determine at least one time constant associated with the data. For example, as shown in Fig. 16, the time constant tau 0 may be associated with the flow response before the procedure is performed, while obtaining flow with a different time constant (id) is considered as an indicator of the end point of the procedure . The at least one time constant associated with the data may be compared to a time constant representing the flow of fluid prior to the execution of the treatment procedure and any observed difference may be used to provide an indication of the efficacy of the treatment procedure.

In one example, the plurality of steps of the procedure may be repeated until the difference is lowered or belongs to a previously specified range value. Based on this analysis, an indication of the end point of the treatment procedure can be provided or displayed.

In one example, the time constant may be analyzed to provide a measure of the rate of change of the flow from the highest value following a treatment procedure from a later time to a steady-state value. An exemplary method may include determining a first order rate of change with time of at least one time constant and / or a second rate of change with time of at least one time constant. Another exemplary method includes comparing a first order change rate with respect to time of at least one time constant to a standard for a first order change rate, the comparison providing a second indication of the efficacy of the medical treatment procedure. Comparing the second order rate of change with time of the at least one time constant to the standard of second rate of change can be used to provide an indication of the effectiveness of the medical treatment procedure.

In one example, flow data collected from a plurality of subjects having a value of time constant and / or known conditions may be used to provide an indication of the degree of success of the procedure or an indication of the likelihood of recovery from a procedure of a non-classified subject . Analysis of the value of the time constant and / or flow data collected from a plurality of previously classified subjects can be used to provide a parameter indicative of the likelihood of success of the procedure, the expected recovery time, and / or the risk of recurrence of the subject . The classified subject has previously performed any one or more of the procedures. The value of the time constant and / or the flow rate data may be collected before, during and / or after completion of one or more procedures. The value of the time constant may comprise a first order measurement of the time constant, a first order rate of change of the time constant (first derivative) and / or a second order rate of change of the time constant (second derivative). Any number of known subjects can be classified according to the degree of success of the procedure performed, the observed recovery time, and / or the recurrence of the subject. Values of time constants collected from a plurality of objects and / or flow data and classified parameters of known conditions can be used to train the classifier. The classifier can be generated as a lookup table, a calibration standard, or a machine learning tool. For example, time constant values and / or flow data collected from a plurality of objects and classified parameters of known conditions can be used to train machine learning tools to provide a target classifier (or patient classifier) .

The classifier may be used to take input data from a non-classifier object and generate an indication of the classification of the subject's condition as an output. For example, a classifier can be used to classify objects according to the likelihood of success of the procedure, the expected recovery time, and / or the risk of recurrence. In operation, data indicative of the flow rate of the non-classified object may be collected before, during, and / or after the completion of the procedure and may be provided as input to the classifier. The classifier may output an indication of the classification of the object. In one example, the results from the classification of a non-classified subject may be modified (e.g., if the classifier indicates the likelihood of a recurrence) during the procedure being performed and / or used as an indication of the end point of the procedure and / The optimal recovery or rehabilitation therapy can be judged. In one example, the classification of an object using a classifier can be used to determine at least one drug, biological agent, or other substance to be administered to a subject.

Exemplary machine learning tools may be instructed learning tools (including support vector machines), unsupervised learning tools (including clustering analysis), or semi-supervised learning tools. In a non-limiting example, the learning tool may be an artificial neural network (ANN), a Bayesian network, a decision tree, or any other applicable tool.

In one example, a system, apparatus and method are provided for monitoring hemodynamic effects during medical treatment procedures performed on vascular tissue. The parameters that represent the hemodynamics of the fluid flow represent the motion and equilibrium states of the fluid. The method may be applied to an exemplary apparatus according to the principles described herein (although not limited to the exemplary apparatus described in connection with any of Figs. 3A-8B, 11, or 23-27) And placing them in close proximity. At least one component of the exemplary device for performing a medical treatment procedure on a portion of the tissue is operated. A substance that changes the size of the vascular tissue is administered. At least one flow sensor of the exemplary apparatus is used to perform at least one flow measurement. The at least one flow measurement provides data indicative of a change in fluid flow proximate the exemplary device subsequent to the medical treatment procedure. The data representing the flow of the fluid is analyzed to determine at least one parameter indicative of a change in the hemodynamics of the fluid. Reduced changes in fluid hemodynamics can be used as an indicator of the efficacy of a medical therapeutic procedure.

The at least one component may be but not limited to a cut-out component. The medical treatment procedure may be but is not limited to neurotomy.

In one example, the various steps of the method may be repeated until the rate of decrease of the hemodynamic change of the fluid falls below a specified value. In one example, an indication of the end point of the medical treatment procedure may occur when the rate of decrease of the change in the hemodynamics of the fluid falls below a specified value. An exemplary method may include displaying an indication of an end point of the medical treatment procedure on the display, as described in more detail below.

The materials may include endogenous and / or exogenous materials. For example, the substance may comprise a calcium channel blocker, a cAMP-mediated stimulator or a nitropathic vasodilator. In another example, the substance may comprise dopamine, adenosine, prostacyclin, saline or nitric oxide. The material may include a vasodilator or a vasoconstrictor.

Figure 17 shows a block diagram of an exemplary system including an evaluation module in accordance with the systems and methods described herein. A non-limiting example of system 1700 in accordance with the principles described herein is shown in FIG. The system 1700 includes at least one communication interface 1711, at least one memory 1712, and at least one processing unit 1713. At least one processing unit 1713 is communicatively coupled to at least one communication interface 1711 and at least one memory 1712. At least one memory 1712 is configured to store processor executable instructions s (1714) and evaluation modules (1715). As will be described in greater detail herein, the assessment module 1715 may be used to perform differential comparisons of flow sensor measurements or to evaluate the efficacy of procedures performed on tissue (including, but not limited to, To determine an indication of the flow rate of the fluid within the tissue lumen based on the flow sensor measurement data 1716, including using the measured value of the flow rate to provide an indication of the fluid flow. In a non-limiting example, at least one processing unit 1713 executes processor executable instructions 1714 stored in memory 1712 to provide at least the feedback described herein during the course of the procedure. The at least one processing unit 1713 may also include at least one of an indication of the flow rate, an indication of the end point of the procedure, an indication of the efficacy of the procedure, and a suggested correction of the procedure, for example, Executable instructions 1714 to control the memory 1712 or to store or control the communication interface 1711 to communicate (1717) to the controller for the interface or any of the example devices.

In any exemplary embodiment in accordance with the principles described herein, the measurements of a 3-omega sensor can be used as a flow sensor in any of the devices described herein to provide an indication of the flow rate of the fluid have. The 3-omega sensor has a manufacturing and processing step similar to a pacing electrode or ablation electrode. Figure 18A shows a non-limiting example of a 3-omega sensor. The 3-omega sensor has a complex filament pattern, which can withstand extreme mechanical bending and twisting and maintain performance. The 3-omega sensor measures blood flow by evaluating minute changes in local temperature. Exemplary results collected in a perfusion chamber with a preset flow rate are shown in Figure 18B. The 3-omega sensor (including the distal portion of the catheter) may be disposed proximate an inflatable and / or expandable body. The 3-omega sensor can be placed in the exemplary device such that the 3-omega sensor is located at three different locations within the midpoint of the tissue lumen (the location of the maximum flow rate) and near the wall of the tissue lumen. In this configuration, the data collected across multiple 3-omega sensors can enable flow measurement at multiple locations inside the tissue lumen. The sensitivity of the 3-omega sensor (such as the example of Fig. 18A) is within a range compatible with the blood flow rate (-5 to 50 cm / s flow rate) present in the body.

In any exemplary implementation consistent with the principles described herein, flow sensing may be performed using other techniques. For example, an ultrasound measurement may be performed to provide an indication of the flow rate of the fluid prior to and / or after the renal exenteration procedure to determine the endpoint of the procedure and to provide feedback to determine whether the procedure should be corrected . As another example, an optical measurement may be performed to provide an indication of the flow rate of fluid prior to, and / or after, the renal exenteration procedure, and / or to provide feedback to determine whether the procedure should be corrected Can be used. Other applicable flow sensing techniques are the time-of-flight method, in which the flow behavior of the tracker fluid introduced into the renal artery is measured to be used to provide an indication of fluid flow rate prior to and / time-of-flight measurement.

Fluid flow monitoring before, during, and after delivery of neuro-pacing and delivery of therapy (including resection energy) in accordance with the principles described herein may be performed in a single helical catheter, Including the ability to improve the efficacy of a set of powerful. Blood flow fluctuations change the local steady-state temperature measured by a 3-omega sensor. The absence of adjustment of the renal blood flow during pacing can indicate that the ablation is successful and allows the physician to determine the end point of the renal neurotomy.

In an exemplary embodiment, the flow in the perfusion chamber, which provides a programmable fluid volume velocity to check the sensitivity of the measurement system, can be systematically measured. Fluid flow rates can be systematically characterized at various ambient temperatures, ionic strengths, and viscosities to examine how heat flux, electroosmosis (during electrical stimulation), and fluid boundary layer thickness affect flow. The perfusion chamber may be equipped with an electrical sensor that allows for side-by-side inspection of the pacing and ablation.

An exemplary method for performing the procedure is described in connection with FIG. An exemplary method includes positioning 1902 an exemplary device adjacent to tissue in accordance with the principles described herein, including a catheter, at least one flow sensor disposed at a portion of the catheter, At least one component coupled to the at least one flow sensor and configured to perform ablation procedures for a portion of the tissue proximate the catheter and to receive data indicative of at least one flow measurement from the at least one flow sensor and based on data representative of the at least one flow measurement And an evaluation module coupled with the flow sensor to provide an indication of the efficacy of the ablation procedure. The exemplary method also includes applying (1904) a resection procedure to the surface of the tissue proximate the catheter, and recording (1906) a measurement of the flow sensor to provide an indication of the efficacy of the resection procedure.

20 illustrates an exemplary structure of an exemplary computer system 2000 that may be employed in implementing any of the systems and methods described herein. The computer system 2000 of Figure 20 includes a memory 2025, one or more communication interfaces 2005 and one or more output devices 2010 (e.g., one or more display units) and one or more input devices 2015 Lt; / RTI >

20, the memory 2025 may include any computer-readable storage medium, and may be a computer-readable storage medium, such as processor-executable instructions for implementing the various functionality described herein for each system, Commands, and any data associated with or derived therefrom or received by a communication interface or input device. The processor 2020 shown in FIG. 20 can be used to execute instructions stored in the memory 2025 and can also read various information processed and / or generated according to the execution of the instructions from the memory, As shown in FIG.

In addition, the exemplary computer system 2000 includes an evaluation module 2030. The evaluation module may perform any of the methods described herein, for example, to provide an indication of the flow rate, or to provide an indication of the efficacy of the procedure to divide the nerve based on the measured value of the flow rate ≪ / RTI > The processor 2020 may be used in connection with the evaluation module 2030 to execute processor executable instructions.

In addition, the processor 2020 of the computer system 2000 shown in FIG. 20 can be communicatively coupled to or control the communication interface 2005 to transmit or receive various information as the execution of the command. For example, the communication interface 2005 may be coupled to a wired or wireless network, a bus, or other communication means so that the computer system 2000 can send the information to another device (e.g., another computer system) And / or receive information from other devices. Further, the communication interface 2005 may be connected to the external network 2035. [ In some implementations, the communication interface may provide a web site or application program (App) of a portable device as a connection portal to at least some aspects of the computer system 2000 (e.g., via various hardware components or software components) Lt; / RTI > Non-limiting examples of such portable devices are tablets, slates, smart phones, electronic readers, or other similar portable electronic devices.

For example, an output device 2010 of the computer system 2000 shown in Fig. 20 may be provided to allow various information to be observed or otherwise associated with the execution of the command. For example, to allow a user to perform manual adjustments, perform a selection, enter data or various other information, or interact with the processor in any of a variety of ways during the execution of an instruction, the input device 2015 May be provided.

Figures 21A and 21B illustrate the results of an exemplary measurement using an exemplary apparatus according to the principles described herein. Figures 21A and 21B show data from flow sensor measurements over a dynamic range of flow rates (from about 100 ml / min to about 600 ml / min) for strategically regulated flow sensors for renal hemodynamics. Figure 21A shows measurements made for a 50 microAmps sensor. Figure 21A shows measurements made for a 20 microAmps sensor.

Figures 22A and 22B show the use of an electrode for performing ablation procedures at power of about 0.2 W to about 0.3 W using various times of exposure (5 seconds, 10 seconds, 15 seconds, 30 seconds, 60 seconds) Illustrate the results of an exemplary use of an exemplary apparatus for use in accordance with the principles described herein. The resection electrode is shown to generate lesions within about 5 seconds of contact with the tissue, without carbonization. Once the electrode is in contact with the tissue, a lesion develops and it is observed that soft contact is sufficient to cause lesions without excessive pressure.

A non-limiting exemplary measurement implementation is described. A system according to the principles described herein can be used to process differential measurements. If one sensor is used, the body temperature of the object can be taken into account with the static flow of the object. This may require different calibrations depending on the patient, so the results may be less accurate, or it may be necessary to have the physician perform the procedure slowly, in addition to measuring renal artery flow, in order to perform a separate thermostatic blood flow measurement .

Non-limiting examples of epoch-making ideas described in the present invention include:

a) expedite clinical procedures;

b) to provide more accurate results for end points of therapy; And

c) reducing the amount of calculations required.

In a non-limiting example, the temperature sensing device may be used in combination with a catheter to provide flow measurement. Electrical circuits can be used to provide differential measurements. Thin, stretchable, flexible and / or conformal electronics may be used to provide a thin conformal means for placing the sensor described herein in the balloon of the catheter. The flow sensing systems, apparatus and methods described herein may be used for blood flow quantification and for other types of fluid flow.

In a different exemplary embodiment, the change in flow can be reported to the clinician via a direct value. The change in flow can be used to indicate the degree of progress, progress, or success of the procedure being performed, for example, by noting the ablation procedure by, for example, displaying the procedure status on a console or display device. For example, a change in flow rate beyond a defined value or threshold can be used to signal an action or trigger an action. In one example, the action may be to turn on an indicator of the catheter device or to display an icon, numerical value or chart on the display. In one example, the signal or actuation of the action may be used to indicate the degree of progress, progress, or success of the procedure.

In accordance with the present exemplary system, method and apparatus, a sensing technology onboard catheter is described that employs a thin conformal array of sensors that can be modified to have a curved structure of various balloons and helical catheters. The ability to integrate a conformal sensor with a helical extrusion and a balloon together with a silicon-based electronic device was first described by the inventors of the present invention in a multi-mode sensor element, a micro light emitting diode (μLED) and an integrated circuit building block (ie, amplifier and logic gate) Allowing integration ways to optimize sensing while not affecting mechanical properties.

23A-23G illustrate examples of multiple electrode and balloon catheter devices in accordance with the principles described herein. 23A-23G illustrate examples of multiple sensing elements (including multiple electrodes) devices and catheter devices. 23A to 23D include passive wires having a polyimide-based encapsulation. The wires are exposed in the selected area to form electrode contacts. The electrode array may include, for example, 64 electrodes. 23E-23G illustrate balloon-based ablation catheters that can be used to respectively apply cryogenic, laser, and high intensity ultrasound-type therapies when positioned close to the tissue. Any system in accordance with the principles set forth herein may be implemented using any of the catheters shown in Figures 23A-23G.

Other non-limiting examples of catheters applicable to the systems, methods and devices described herein include but are not limited to mallecot catheters, helical coil catheters, mesh catheters, single rod catheters, compliant balloon-based catheters, non- compliant balloon-based catheters, snare-shaped catheters, multi-spline catheters, dilatation balloon catheters, and angioplasty balloon catheters.

Examples of devices of this kind are shown in Figs. 24A to 24D. Electrodes, flow sensors and μLEDs can withstand significant mechanical deformation caused by repeated balloon inflation and deflation cycles due to their nanomembrane shape coefficients and the serpentine interconnect geometry that helps to absorb mechanical strain . Figures 24e and 24f highlight alternative forms of sensing-conformal substrate temperature sensors, electrodes and flow sensors. Flow sensing and electrode elements are useful for RSDN catheters because the evaluation of blood flow can be accomplished quickly without the need for a separate diagnostic device.

In one example, a 3-omega sensor array is used to measure other thermal, mechanical, and material properties related to thermal conductivity and thermal conductivity. To measure the flow, the sensors are each positioned perpendicular to the flow direction. This configuration can be compatible with the design of the helical catheter system. An AC current is applied across each sensor, and the resulting AC voltage is measured. This measured voltage monotonously decreases with increasing flow rate, and increases as the blood stagnates or slows down. Calculation of the measured voltage in accordance with any of the exemplary devices of the present disclosure can be calculated using a perfusion chamber and flow is assumed according to the Hagen-Poiseuille equation and their respective assumptions. Measurements using 3-omega sensor technology are versatile in that they can be used to extract a variety of different physical parameters that can be associated with the clinician. This sensing aspect can be used, for example, to serve as an executable platform for the catheter that can be used to perform renal derangement.

In one example, mechanical modeling of flow sensors and electrodes during mechanical stresses can be performed. Using modeling simulations, dynamic materials and mechanical properties can be characterized for a conformal sensor array of balloon and helical catheters undergoing significant bending and torsion during operation. This involves the analytical and finite element modeling of the mechanics of the flexible electronic devices secured to the balloon catheter. The strain distribution obtained through analytical and computational modeling quantitatively captures strain characteristics in the electronic device layer. Characterization of effective deformation and displacement distributions in sensor islands and twisty interconnects provides important insight into critical breaking deformation and buckling phenomena. This characterization of conformal sensors can dramatically improve the manner in which nanomembrane flow sensors and electrodes are designed and implemented in highly deformable substrates (i.e., deflectable catheters). This approach also maintains a prospect of increasing understanding of the mechanical stresses involved in the placement of catheters in the body.

Figure 25 shows a non-limiting example of a flow sensor in a rod shaped catheter comprising a "clover shaped" flow sensor. The metal rectangle is the electrode of the catheter. In some of the exemplary catheters of Fig. 25, the flow sensor includes an angioplasty balloon having a resection electrode (circular pad). In our new exemplary system, the clover flow sensor is coupled to a balloon electrode in a single device.

According to the systems and methods described herein, ablation electrodes can be embedded in an angioplasty balloon with a clover flow sensor on the proximal and distal sides of the balloon of the catheter extrusion. According to the present novel system and method, a multi-function balloon catheter has (i) an array of electrodes associated with a flow sensor, and (ii) a flow sensor embedded in the shaft of the catheter proximate to the balloon. In some instances, the balloon catheter may include other sensors, such as but not limited to LEDs, touch sensors, pressure sensors, biological activity sensors and temperature sensors on the balloon.

In an exemplary embodiment, a catheter having a balloon is placed in proximity to the kidney tissue (or in another portion of the kidney system) in a contracted state. For example, once the catheter is in the renal artery, fluid flow (including blood flow) can be measured. Once captured, the balloon can be inflated and ablation can be performed. Once the ablation is complete or at a selected point during the ablation, the balloon may retract and the flow is again sensed to see what the measured change is. In this example, an increase in flow can be used to serve as an indicator of a successful ablation procedure.

In another exemplary embodiment, the nerve can be faced and the flow can be measured before ablation. Ablation cycles can be performed. Once the ablation is complete or at a selected point during the ablation, the nerve can be paced and the flow can be measured again (including post-ablation measurements). Once the pacing is determined to cause a flow change, it can be used as an indicator that the nerve is still activated. If the pacing does not cause a flow movement, it can be used as an indicator that the nerve has successfully undergone nerve entrapment. A flow sensor combined with a resection electrode in accordance with the systems and methods described herein enables this novel analysis and determination of the clinical endpoint.

Figure 26 shows a non-limiting example of a flow sensor of a helical catheter. Figure 27 shows a catheter having bipolar electrodes and metal interconnects disposed on its surface.

For example, an exemplary design and fabrication of four flow sensors, four pacing electrodes, and four resection electrodes, all located together in a spiral catheter, is described. A custom data acquisition system is implemented and the initial functionality of the flow sensor and electrodes is checked by placing it in a fluid flow chamber. Exemplary combined functionality of flow sensors, pacing electrodes and resection electrodes in the renal arteries of a live pig model is also described. A spiral catheter, including a sensor and an electrode, is used to measure blood flow during and immediately after nephrectomy. A comparative analysis of catheter system performance, ease of use, and procedure time for other renal resection devices used in clinical settings to gain insight into how to have a clinical endpoint in RSDN to help improve overall procedure efficacy and safety Is performed.

A non-limiting example of a flow sensor, pacing and resection electrode of a multifunctional spiral catheter in a perfusion device is described. The confined space in the renal artery can reduce the number of devices that can be positioned inward. Thus, it may be difficult to place multiple devices in a confined space such as within the renal arteries. The multifunctional RSDN catheter is configured to have an electrode in a helical extrusion that is small enough to fit into the kidney artery to enable electrical stimulation delivery without affecting the measurement. Mechanically optimized nanomembrane electrodes are integrated with 3-Omega flow sensors that contact the limited space of the kidney arteries. In one example, up to eight electrodes (0.25 x 0.25 mm ² ) and four (1 x 1 mm ² ) sensors can be fabricated to measure renal blood flow before and after ablation. A data acquisition system (National Instruments Inc.) in conjunction with an electrical stimulator console (Medtronic Inc.) is implemented to deliver 5 to 10 W of energy to pace and ablate the kidney nerve. Can be used. Using this new system, the fundamental limitations of resection and pacing electrodes with in vitro tissue can be characterized. In addition, a custom perfusion chamber may be constructed to inspect flow sensing capability. Taking these new designs, micro-machining approaches, and measurements using in vitro models together can provide insight into the optimal configuration of the electrode and flow sensors needed to determine flow rate changes due to renal dysfunction.

Non-limiting exemplary pacing and ablation electrodes and in vitro testing in spiral catheters are described. The ultra-thin geometry gives flexibility to rigid and brittle materials in other cases. The ultra-thin conformal nanomembrane sensor (-250 nm) embedded in a thin polyimide and elastomer substrate (-50 to 100 μm) in a neutral mechanical plane layout accommodates significant mechanical durability with a radius of curvature of less than about 1 mm. To achieve a conformal sensor with this design, an array of electrodes may be formed in the silicon. Lithographic processing and vertical trench wet etching techniques produce insulated chiplets (-0.25 x 0.25 mm < ² > and a thickness of -1 to 5 [mu] m) that remain tied to the base wafer through an anchor structure . This process can be used to produce an electrode called " printable " because of its ability to be removed and positioned at a target substrate with a soft elastomeric stamp and to be delivered to a helical catheter. The attractive features of this approach include: (1) an ultra-thin circuit layout for mechanical flexibility to accommodate a limited space within the kidney artery; and (2) compatibility with other elements such as contact or flow sensors.

The practicality of the nanomembrane electrode is checked so that ablation measurements can be performed by driving RF energy (5 to 10 W) to indicate that the renal nerve fibers can be ablated through the arterial blood vessels. In order to examine the performance of the nanomembrane electrode array (as a result of protein coating and / or electroosmosis) and to verify whether the surface properties of the electrode vary with time, histological evaluations were performed on the nerves before and after the ablation cycle . Measurements performed in the heart and in ablated muscle tissue yield prospective results of pacing and ablation with these new grades of nanomembrane electrodes.

A non-limiting exemplary data acquisition system is described. A stimulated waveform in the form of a rectified triangular pulse having a fixed amplitude of 10 to 20 V and a duration of 100 to 150 ms may be transmitted through the pacing electrode using a command programmed with a machine readable instruction. The waveform pattern is strategically chosen to induce renal nerve activity and cause vasoconstriction or change local blood flow. In order to measure blood flow, induce nerve stimulation, and deliver ablation energy, the data acquisition system includes three modules. To perform an evaluation of efficacy as described in connection with any of the examples described herein, data from any of the three modules may be communicated to the evaluation module. National Instruments Inc. controlled with custom machine-readable instructions (including LAB VIEW ™ software). The PXI-6289 (multifunctional M Series data acquisition (DAQ) system) controls the voltage across the sensor.

Non-limiting exemplary flow sensing, pacing and ablation using multifunctional spiral catheters in a living animal model is described. Multifunctional balloons and helical catheters described in Section 1 above apply to flow sensing and ablation measurements in live animal models. A balloon catheter may be used. In one example, a balloon catheter may have a larger profile that may affect flow. In a non-limiting example, a spiral catheter may be used instead of a balloon to minimize the effect of the catheter on blood flow. The flow can be measured according to the initial placement in the renal artery for several minutes to determine the initial average flow rate. Once set, pacing can be ensured and at the same time the flow can be monitored. If the kidney nerves are functioning properly, a flow reduction of 20-30% may be expected during this step. Once this initial calibration has been completed, the same set of procedures may be performed after the renal resection cycle. It is possible that the renal blood flow can be shifted to a different baseline as compared to the initial measurement. In one example, this is not used as an indicator of successful ablation. If ablation is successful, there may be an interpretable effect that may be evident during pacing. That is, since the vasoconstrictive properties of the nerves can have a functional disorder, the movement of the flow during pacing can be small, which can serve as the clinical end point of the procedure.

In one example, an exemplary method of determining the renal dégnence endpoint when blood pressure and flow is adjusted to nitroglycerin is described. Fluctuations in blood flow caused by nitroglycerin lead to changes in blood pressure and renal blood flow before and after ablation can be monitored to determine how flow changes can be assessed with the sensors described herein. Systemic infusion of nitroglycerin can cause a shift in blood pressure that can cause changes in renal blood flow. In addition, the injection of nitroglycerin can be monitored to re-determine the effect on blood flow before and after pacing.

In one example, leakage current and encapsulation are described. The conformal flow sensor array can be fabricated using a multi-layer process with thin layer polyimide as the encapsulating layer. The horizontal and vertical interconnect layers are insulated using this thin layer of polyimide. In an exemplary system, the leakage current may escape and lead to noise-sensitive recording, bubble formation in the fluid, or sensor degradation over time. In one example, additional polymer encapsulation (UV curable polyurethane or parylene) can be coated on the sensor to prevent leakage current in such a system, creating an additional ~ 10 m encapsulant layer to withstand current leakage effects. For several hours (RSDN operation), the leakage current may be manageable with polyurethane, parylene, and UV curable encapsulation strategies.

Data visualization and signal fidelity are described. A data acquisition system developed for recording flow, pacing and ablation may not be provided in a single module. Visualization of measurement record and stimulant applications may require feedback from multiple physicians. Real-time interpretation of the flow data can be difficult. A first generation data acquisition system for measuring and displaying flow is described. In one example, the user interface may be provided on the same LAB VIEW ™ display as a control for pacing and ablation so as to provide both catheter control features in a single console. Such a system structure may be appropriate for product development implementation.

The kidney nerve stimulation is explained. In some instances, the nerve pacing electrode may be disconnected from the arterial wall. Such good contact variability can result in poor denervation results. To cope with this effect, x-ray image processing and electrode impedance recording can be monitored to restore proper contact with the blood vessel wall.

In addition, a user interface that can be used during the procedure is provided herein to monitor the progress of the procedure and / or provide an indication of the endpoint of the procedure. A user interface may be provided that utilizes an apparatus that displays a representation of the parameters of the expandable body and / or the expandable body disposed proximate to a portion of the tissue being treated. According to the present principles, the inflatable body and / or the expandable body may comprise a plurality of sensors coupled to the inflatable body and / or at least a portion of the expandable body. The apparatus may include a user interface, at least one memory for storing processor executable instructions, and at least one processing unit coupled to the at least one memory. At least one processing unit controls the user interface to display at least one representation of the parameters of the expandable body and / or the expandable body, in accordance with the execution of the processor executable instructions.

28A and 28B illustrate non-limiting examples of the types of representations of the parameters of the expandable body and / or the expandable body that may be displayed on the display. 28A illustrates an exemplary first representation of the condition of the expandable body and / or the expandable body. The expandable body and / or expandable body may be represented using a first feature indicator 2802 that indicates that it is in an inflated / expanded state, or may be represented using a second feature indicator 2804 that indicates a contracted / collapsed state . 28B illustrates an example of a type of representation that may be used to indicate the status of at least one of the plurality of sensors coupled to the expandable body and / or the expandable body. One or more of the sensors may be represented using a first operational indicator 2852 indicating that each sensor measures less than a threshold value, or each sensor may be represented by a signal that is greater than or equal to a threshold value And a second operation indicator 2854 indicating that the measurement is to be performed.

In one example, the first operating indicator 2852 and the second operating indicator 2854 may be used to indicate that the portion of the expandable body and / or the expandable body is in contact with the tissue. A signal below the threshold value can be interpreted as indicating that at least one sensor is not in contact with a portion of tissue, and a signal that exceeds or is approximately equal to the threshold value indicates that at least one sensor is in contact with a portion of the tissue .

In one example, the first operational indicator and the second operational indicator may be displayed as a binary visual representation, e.g., ON / OFF or other binary representation.

In one example, the first operational indicator and the second operational indicator may be displayed as a quantitative visual representation corresponding to the magnitude of the signal. For example, as shown in Fig. 28C, the display may display a feature (e.g., arrow or bar) that changes to indicate the magnitude of the signal of the sensor. The example of Figure 28c shows the values of "contact" or "noncontact". In another example, the feature of the display can be used to indicate the relative size of any other parameter measured using the sensor. In one example, a graph plot as shown in Fig. 28D may also be used to indicate the magnitude of the signal.

In one example, the sensor may be a flow sensor and is a quantitative visual representation of the magnitude of such parameters, but not limited to the instantaneous velocity, volume flow or vascular resistance of the fluid flow measured at each sensor, The second operation indicator can be displayed.

In one example, the first shape index and the second shape index can be displayed as chromatic coded codes. Each color coded code can be used to indicate a range of values of signal magnitudes. For example, green may be used to denote a lower range of values below a first threshold, and yellow may be used to denote a signal belonging to an intermediate range of values up to a second threshold, Lt; RTI ID = 0.0 > a < / RTI >

In one example, the first feature index and the second feature index may further be used to provide an indication of the spatial location of the at least one sensor corresponding to the expandable body and / or the expandable body. For example, indicators 2852 and 2854 can be used to indicate the spatial location of the operating sensor.

In one example, the user interface may be configured to display an expression of the expandable body and / or the expandable body and a representation of the state of operation of the sensor during the step. While the representation of the expandable body and / or the expandable body is a first shape indicator (indicating a contracted / collapsed state), the representation of the operating state of the sensor may not be displayed. Once the representation of the expandable body and / or the expandable body is a second feature indicator (indicating an expanded / expanded state), a representation of the operating state of the sensor may be displayed. That is, the expression of the operating state of the sensor may not be displayed until the expandable body and / or the expandable body is expanded / expanded to some extent (even if not fully expanded or expanded).

In one example, the user interface may be configured to display instructions to the practitioner (including the physician) at various stages of the procedure being performed. In an example, the display may be configured to indicate when an end point of the procedure has been reached. If the procedure does not reach the end point, it may be necessary to continue the procedure or to modify the procedure (e.g., moving the catheter, guide wire or other elongated body or expandable body and / or expandable body, (E.g., ablation), the display may be configured to display a command to indicate to the practitioner. In addition, the user interface may be configured to display an indication of at least one step of the procedure being performed on a portion of the tissue.

In one example shown in Figure 29, the user interface can be used to display the vascular resistance value in numerical form and / or as a graph versus time. In addition, the user interface is not limited to systolic inclination, pulsatile flow and pulsatile pressure, but can be used to display data representing such parameters. The user interface can be configured to display a value indicative of instantaneous / volumetric flow in a short time duration graph representing granular flow measurements. The user interface can be used to identify changes before and after treatment (such as but not limited to ablation) over a long time scale graph, e.g., the duration of the procedure (e.g., 1 hour procedure) May be configured to display the value of the flow.

While various embodiments of the present invention have been illustrated and described herein, it will be appreciated by those of ordinary skill in the art that a variety of other means and / or structures for performing functions and / or obtaining the results and / , Each of these variations and / or modifications are considered to be within the scope of the embodiments of the invention described herein. More generally, it will be understood by those of ordinary skill in the art that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations may vary depending upon the particular application, ≪ / RTI > Those skilled in the art will recognize, and be able to ascertain using no more than routine experimentation, numerous equivalents to the specific embodiments of the invention described herein. It is therefore to be understood that the above-described embodiments are presented by way of example only, and that the embodiments of the invention may be practiced otherwise than as specifically described. Embodiments of the present invention are directed to each individual feature, system, article, material, kit and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits and / or methods may be used to determine the scope of the present invention unless the features, systems, articles, materials, kits and / .

The above-described embodiments of the present invention may be implemented in any of a number of ways. For example, some embodiments may be implemented using hardware, software, or a combination thereof. If any aspect of an embodiment is at least partially implemented in software, whether it be a single device or a computer or distributed among multiple devices / computers, the software code may be executed on any suitable processor or set of processors.

Further, the techniques described herein may be implemented as a method in which at least one example is provided. The actions performed as part of the method can be sequenced in any suitable manner. Thus, although the embodiments are shown in sequential order in the illustrated embodiment, the actions may be performed in a different order than illustrated, and may include concurrently performing some action.

It is to be understood that all definitions defined and used herein are to be regulated in the generic sense of the dictionary definition, the definitions contained in the references included by reference, and / or the defined terms.

As used herein, the indefinite articles "a" and "an" should be understood to mean "at least one ", unless expressly stated otherwise.

The phrase "and / or" as used herein should be understood to mean a combined element, i.e., either or both of the elements present in combination in some cases and present in separate cases in other cases. The plural elements recited in "and / or" should be construed in the same manner, that is, interpreted as "one or more" There may optionally be other elements besides those specifically identified in the "and / or" clauses, whether or not associated with these specifically identified elements. Thus, as a non-limiting example, when referring to " A and / or B "when used with unlimited linguisticization such as " comprising ", in one embodiment, only A ≪ / RTI >optionally); In another embodiment, only B (optionally including elements other than A) may be referred to; In yet another embodiment, both A and B may refer to (optionally including other elements).

As used herein, "or" should be understood to have the same meaning as "and / or" as defined above. For example, the separator item "or" or "and / or" in the list is to be interpreted as inclusive, that is to say including at least one but not limited to a list of a plurality of elements or elements, But will also be understood to include a plurality of elements. Quot; or " consisting "of " consisting only of" or "consisting of " In general, the term "or" as used herein refers to an exclusive alternative (i.e., "one or " One or the other but not both ").

As used herein, the phrase "at least one" is at least one element selected from any one or more of the elements in the list of elements when referring to the list of one or more elements, It should be understood that it does not necessarily include at least one of the specifically listed elements and all of the elements and does not exclude any combination of elements from the list of elements. This definition also allows elements to be selectively present in addition to those specifically identified in the list of elements referred to by the phrase "at least one ", whether or not associated with such specifically identified elements. Thus, by way of non-limiting example, "at least one of A and B" (or equivalently "at least one of A or B," or equivalently, "at least one of A and / or B" In an example, without B, at least one (and optionally including elements other than B), optionally including a plurality, is A; In another embodiment, at least one (and optionally including elements other than A), B, optionally including a plurality, without A; In yet another embodiment, at least one (and optionally including other elements) of B, including at least one and optionally a plurality of B, optionally including a plurality; And so on.

Claims (70)

An apparatus for determining a flow rate of a fluid proximate to a portion of tissue,
A elongated member having a proximal portion and a distal portion;
A flow sensor disposed proximate a distal portion of the elongate member, the flow sensor comprising: at least one temperature sensor; and at least one heating element for heating an area proximate the elongate member, the at least one heating element including at least one A flow sensor including a heating element,
At least a portion of the at least one temperature sensor is received in a portion of the cavity,
Wherein the temperature measurement of the temperature sensor provides a first indication of the flow rate of fluid proximate to the flow sensor. The method according to claim 1,
Further comprising an inflatable and / or expandable body associated with a portion of the elongate member and having a proximal and distal portion, the distal portion of the inflatable and / or expandable body being disposed proximate the flow sensor, . The method of claim 2,
The electronic circuit of claim 1, further comprising an electronic circuit coupled to the expandable and / or expandable body, the electronic circuit comprising at least one extendible interconnect, the electronic circuit being extendable and the electronic circuit being connectable to the inflatable and / Or accommodate expansion of the expandable body. The method of claim 3,
Wherein the electronic circuit further comprises at least one passive electronic component and / or at least one active electronic component, wherein the at least one extendable interconnect is electrically coupled to at least two electronic components of the electronic circuit. The method of claim 3,
Wherein the electronic circuit further comprises a plurality of electrodes, at least one of the plurality of electrodes being a radio frequency electrode for delivering radio frequency energy to a surface proximate the radio frequency electrode. The method of claim 3,
Wherein the electronic circuit comprises at least one ablation element. The method according to claim 1,
Wherein the device is configured to perform a procedure on a portion of the tissue, wherein the procedure is a neurostimulation or nerve stimulation procedure. The method of claim 7,
Wherein the procedure is a carotid cochlear nerve, carotid body fissure, vagus nerve stimulation, pulmonary artery denervation, celiac ganglion dissection, bladder triangulation or extensor nerves. The method according to claim 1,
Wherein the temperature sensor is a thermistor or a thermocouple. The method according to claim 1,
Wherein the elongate member is a catheter or guide wire. The method according to claim 1,
Further comprising a reference temperature sensor disposed proximally of the elongate member. The method of claim 11,
Wherein comparing the temperature measurement of the reference temperature sensor with the measurement of the flow sensor provides a second indication of the flow rate of the fluid. The method according to claim 1,
Wherein the at least one flow sensor is a plurality of flow sensors. The method according to claim 1,
Wherein the fluid is blood and a first indication of the flow rate of the fluid is indicative of a hemodynamic characteristic of the fluid. The method according to claim 1,
Further comprising at least one component configured to perform ablation procedures. 16. The method of claim 15,
Further comprising at least one pacing electrode disposed in the inflatable and / or expandable body to deliver electrical stimulation to a portion of the tissue proximate the pacing electrode. 18. The method of claim 16,
Wherein the electrical stimulus is applied to a portion of the tissue prior to performing the ablation procedure. The method according to claim 1,
Wherein the operation of the heating element and the temperature sensor is combined to provide a measure of the temperature change caused by a change in the flow rate of the fluid. The method according to claim 1,
Wherein the flow sensor is encapsulated in a thermally conductive encapsulant. The method according to claim 1,
Wherein the at least one heating element comprises a wound resistive wire and the hollow portion of the wound resistive wire forms the cavity. The method according to claim 1,
Wherein the at least one heating element comprises a thin film patterned resistive element and the at least one heating element is formed in a substantially cylindrical shape comprising the cavity. 23. The method of claim 21,
Wherein the thin film patterned resistive element comprises a pattern of resistive elements disposed in a stretchable and / or flexible substrate. 23. The method of claim 22,
Wherein the resistive element is formed in a linear pattern, a serpentine pattern, a boustrophedonic pattern, a zigzag pattern, a wavy pattern, a polygonal pattern, or a substantially circular pattern. 10. An apparatus for indicating a representation of a parameter of an expandable body and / or an expandable body disposed proximate to a portion of tissue, the expandable body and / or the expandable body comprising at least an expandable body and / A plurality of sensors coupled to the portion, the device comprising:
User interface;
At least one memory for storing processor executable instructions; And
At least one processing unit communicatively coupled to the at least one memory,
In response to execution of the processor-executable instructions, the at least one processing unit,
The user interface controlling the user interface to display at least one representation of the parameter, the at least one representation being:
(A) a first representation of a state of the inflatable body and / or the expandable body, the first representation of the inflatable body and / or the expandable body, the first representation of the inflatable body and / ; Or (ii) a first feature comprising a second feature indicative of the expandable body and / or the expandable body in a contracted and / or folded condition; And
(B) a second representation of the state of at least one of the plurality of sensors, the first representation indicating: (i) at least one sensor of the plurality of sensors measures a signal less than a threshold value; Or (ii) a second indication comprising a second behavior indicator indicating that at least one sensor of the plurality of sensors measures a signal that exceeds or is approximately equal to a threshold value. 27. The method of claim 24,
Wherein a signal below said threshold value indicates that said at least one sensor is not in contact with a portion of tissue, and wherein a signal exceeding or approximately equal to said threshold value indicates that said at least one sensor is in contact with a portion of tissue. . 27. The method of claim 24,
Wherein the first operational indicator and the second operational indicator are displayed as a binary visual representation. 27. The method of claim 24,
Wherein the first operational indicator and the second operational indicator are displayed as a quantitative visual representation corresponding to the magnitude of the signal. 27. The method of claim 24,
Wherein the first shape index and the second shape index are represented as chromatic coded codes, and each chromatic coded code represents a range of values of signal magnitudes. 27. The method of claim 24,
Wherein the first feature index and the second feature index further provide an indication of a spatial location of at least one sensor corresponding to the expandable body and / or the expandable body. 27. The method of claim 24,
Wherein upon execution of the processor executable instructions, the at least one processing unit controls the user interface to display the first representation and the second representation in a stepwise manner,
The second representation is not displayed while the first representation is the first shape indicator,
And when the first representation is the second shape indicator, the second representation is displayed. 27. The method of claim 24,
And upon execution of the processor executable instructions, the at least one processing unit controls the user interface to further display an indication of at least one step of a procedure performed on a portion of the organization. 27. The method of claim 24,
And upon execution of the processor executable instructions, the at least one processing unit controls the user interface to display an indication of an end point of a procedure performed on a portion of the organization. 27. The method of claim 24,
Wherein the second expression represents a magnitude of an instantaneous velocity, a volume flow or a vascular resistance. CLAIMS What is claimed is: 1. A method of performing a medical treatment procedure on a tissue,
A elongated member having a proximal portion and a distal portion; At least one flow sensor disposed proximate to a distal portion of the elongate member, the at least one flow sensor comprising at least one temperature sensor and at least one heating element disposed proximate the at least one temperature sensor, ; A reference temperature sensor disposed at a proximal portion of the elongate member; And a control module coupled to the at least one flow sensor and the reference temperature sensor proximate the tissue;
Using the control module to maintain a temperature difference between the reference temperature sensor and the temperature sensor of the at least one flow sensor at a stage of performing a medical treatment procedure, :
Monitoring a value of a temperature measurement of the reference temperature sensor and / or a value of a temperature measurement of the temperature sensor of the at least one flow sensor;
Controlling the first signal to the at least one heating element to cause the at least one heating element to release heat or to cease heat release such that the temperature difference is maintained. 35. The method of claim 34,
Wherein the temperature difference is a constant temperature difference or a time varying temperature difference. 36. The method of claim 35,
Wherein the temperature difference is a constant temperature difference and wherein the constant temperature difference is about 1.5 DEG C, about 2.0 DEG C, about 2.5 DEG C, about 3.0 DEG C, about 3.5 DEG C, about 4.0 DEG C, or about 4.5 DEG C. 35. The method of claim 34,
Wherein the control module comprises a proportional-integral-derivative (PID) controller or an anemometer. 37. The method of claim 37,
Wherein the control module comprises a PID controller,
Comparing the value of the temperature measurement of the reference temperature sensor to the temperature measurement of the temperature sensor of at least one flow sensor and applying the PID controller to determine a second signal based on the comparison;
And using the control module to determine a first signal to the at least one heating element based on the second signal. 35. The method of claim 34,
Wherein the device further comprises at least one component that performs ablation procedures for a portion of the tissue. 42. The method of claim 39,
Applying the ablation procedure to a portion of the tissue;
Using the control module to monitor a temperature measurement of a temperature sensor of at least one flow sensor to monitor a flow rate of fluid proximate to a portion of the tissue; And
Further comprising the step of using the control module to control the first signal to the at least one heating element to cause the at least one heating element to release heat or to stop the heat emission such that the temperature difference is maintained How to. 35. The method of claim 34,
Further comprising the step of recording said first signal to said at least one heating element. 35. The method of claim 34,
Wherein the first signal to the at least one heating element is a time varying voltage signal. 35. The method of claim 34,
Wherein at least a portion of the at least one heating element forms a cavity and at least a portion of the at least one temperature sensor is received in a portion of the cavity. 35. The method of claim 34,
Wherein said medically treating procedure comprises a neurostimulation or nerve stimulation procedure. 35. The method of claim 34,
Wherein said medically treating procedure is a carotid artery intratumoral nerve, carotid body shedding, vagus nerve stimulation, pulmonary artery denervation, celiac ganglion dissection, bladder triangulation or nephrectomy. 35. The method of claim 34,
Wherein the temperature sensor is a thermistor or a thermocouple. 35. The method of claim 34,
Wherein the elongate member is a catheter or guide wire. 35. The method of claim 34,
Wherein the at least one flow sensor is a plurality of flow sensors. A method for determining the efficacy of a medical treatment procedure performed on a tissue,
A) an elongated member having a proximal portion and a distal portion; at least one flow sensor disposed proximate to a distal portion of the elongate member; and at least one flow sensor positioned proximate to the distal portion of the elongate member, Placing an apparatus comprising at least one component coupled to the member proximate to the tissue;
B) actuating the at least one component to perform the treatment procedure on a portion of the tissue;
C) using the at least one flow sensor to perform at least one flow measurement that provides data indicative of a change in flow subsequent to a treatment procedure of the fluid proximate the device;
D) analyzing the data indicative of fluid flow to determine at least one time constant associated with the data;
E) comparing the at least one time constant associated with the data to a time constant representing a flow of fluid prior to performing the treatment procedure,
Wherein the difference provides an indication of the efficacy of the therapeutic procedure. 55. The method of claim 49,
Wherein steps (B), (C), (D) and (E) are repeated until the difference falls within a specified range of values. 52. The method of claim 50,
Further comprising generating an indication of an end point of the treatment when the difference falls within a specified range of values. 54. The method of claim 51,
Further comprising displaying an indication of the end point of the treatment procedure on the display. 55. The method of claim 49,
Wherein said medically treating procedure is a carotid artery intratumoral nerve, carotid body shedding, vagus nerve stimulation, pulmonary artery denervation, celiac ganglion dissection, bladder triangulation or nephrectomy. 55. The method of claim 49,
Wherein the time constant provides a measure of the rate of change of flow from the highest value following a treatment procedure from a later time to a steady-state value. 55. The method of claim 49,
Further comprising determining a first order rate of change with time of at least one time constant and / or a second rate of change with time of at least one time constant. 55. The method of claim 55,
Further comprising: comparing the first order change rate with the standard for the first order change rate over time of the at least one time constant, wherein the comparison provides a second indication of the efficacy of the medical treatment procedure, Way. 55. The method of claim 55,
Further comprising: comparing the second rate of change with time of the at least one time constant to a standard for the second rate of change, the comparison providing a third indication of the efficacy of the medical treatment procedure, Way. 55. The method of claim 49,
Wherein the at least one component is a resection component and the medical treatment procedure is a neurotomy. CLAIMS 1. A method for monitoring hemodynamic effects during a medical treatment procedure performed on vascular tissue,
A) an elongated member having a proximal and distal portion, at least one flow sensor disposed proximate to a distal portion of the elongate member, and at least one flow sensor positioned proximate to the elongate member, Placing an apparatus comprising at least one component coupled to the elongate member proximate the tissue;
B) actuating the at least one component to perform the medical treatment procedure on a portion of the tissue;
C) administering a substance that alters the size of the vascular tissue;
D) using the at least one flow sensor to perform at least one flow measurement that provides data indicative of a change in flow subsequent to a medical treatment procedure of the fluid proximate the device;
E) analyzing data representative of fluid flow to determine at least one parameter indicative of a change in the hemodynamics of the fluid,
Wherein a decrease in the change in the hemodynamics of the fluid provides an indication of the efficacy of the medical treatment procedure. 55. The method of claim 59,
Wherein steps (B), (C), (D), and (E) are repeated until the rate of decrease of the change in hemodynamics of the fluid is less than a specified value. 61. The method of claim 60,
Further comprising generating an indication of the endpoint of the medical treatment procedure when the rate of decrease of the change in hemodynamics of the fluid falls below a specified value. 62. The method of claim 61,
Further comprising displaying on the display an indication of the end point of the medical treatment procedure. 55. The method of claim 59,
Wherein the substance comprises an endogenous substance or an exogenous substance. 63. The method of claim 63,
Wherein said substance comprises a calcium channel blocker, a cAMP-mediated stimulator or a nitropathic vasodilator. 63. The method of claim 63,
Wherein the substance comprises dopamine, adenosine, prostacyclin, saline or nitric oxide. 55. The method of claim 59,
Wherein the substance comprises a vasodilator or a vasoconstrictor. 55. The method of claim 59,
Wherein the at least one component is a resection component and the medical treatment procedure is a neurotomy. 55. The method of claim 59,
Wherein the elongate member comprises an inflatable and / or expandable body, the inflatable and / or expandable body being disposed proximate a distal portion of the elongate member. 69. The method of claim 68,
Wherein the inflatable and / or expandable body is a balloon, an expandable helical coil, an expandable mesh, or a deployable mesh. 69. The method of claim 68,
Wherein the inflatable and / or expandable body includes an electronic circuit coupled to a portion of the inflatable and / or expandable body, the electronic circuit comprising at least one extendable interconnect, And is adapted to allow the electronic circuit to accommodate the expansion of the inflatable and / or expandable body.

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