WO2010109458A1

WO2010109458A1 - System and method for inducing hyperemia

Info

Publication number: WO2010109458A1
Application number: PCT/IL2010/000241
Authority: WO
Inventors: Ronen Arbel; Yoram Tal; Michael Ortenberg
Original assignee: Spirocor Ltd
Priority date: 2009-03-23
Filing date: 2010-03-23
Publication date: 2010-09-30

Abstract

A method and system for inducing hyperemia and obtaining a measurement are provided. A The method may include inducing a hyperemic state of a cardiovascular system of a subject by guiding the subject, using a physical guidance device, to perform a predefined periodic physical activity, wherein the periodic physical activity is performed at a desired excitation frequency around 0.1 Hertz; receiving signals from the subject to monitor performance of the activity desired excitation frequency; and obtaining a measurement of a physiological parameter related to the subject while maintaining the hyperemic state of the subject.

Description

SYSTEM AND METHOD FOR INDUCING HYPEREMIA

BACKGROUND OF THE INVENTION

[0001] Achieving hyperemia or increased blood flow may be a prerequisite, prior condition in various medical procedures. For example, prior to treating stenosis of a blood vessel or another tubular structure, the location of the stenosis may be determined and the severity of the stenosis may be evaluated. The location and the severity of a stenosis are typically determined and/or evaluated by aid of angiography systems. However, subjective evaluation based on angiography alone sometimes does not provide correct estimation of the stenosis severity. Therefore the evaluation of the stenosis severity is sometimes supplemented by objective measurements, for example fractional flow reserve (FFR) measurements, coronary flow reserve (CFR) measurements, pharmacological stress test electrocardiogram (ECG) and/or stress test including imaging, e.g., Thallium perfusion test.

[0002] FFR is calculated as a ratio of two pressures where the first pressure is a coronary pressure at a point distant from the stenosis and the second pressure is an aortic pressure. Using a pressure monitoring guide wire or catheter, such two pressures may be obtained simultaneously, while the coronary tree is fully dilated during maximal hyperemia, coronary flow reserve (CFR) is defined as a ratio of two flows, the first being a hyperemic blood flow, e.g., blood flow during a hyperemic state of the cardiovascular system and the second being a flow at a rest state of the cardiovascular system, or other defined baseline. CFR may be estimated by coronary blood flow velocity or measured by applying the principle of thermo-dilution, by using echocardiography or other imaging techniques. For example, CFR may be calculated as the ratio of maximal blood flow velocity at hyperemia to maximal blood flow velocity at a baseline. Accordingly, prior to measuring FFR and CFR, a hyperemic state of the cardiovascular system is induced or achieved.

[0003] The problem is that today, hyperemia is achieved by injecting chemicals such as adenosine, papaverine, dipyridamole, ATP or dobutamine into the blood stream. While all of these agents are known to cause hyperemia by vasodilatation, they may also have severe side effects and/or risks.

BRIEF DESCRIPTION OF THE DRAWINGS

[0004] Embodiments of the invention are illustrated by way of example and not limitation in the figures of the accompanying drawings, in which like reference numerals indicate corresponding, analogous or similar elements, and in which:

[0005] Fig. 1 shows a logical block diagram of an exemplary system according to embodiments of the invention;

[0006] Fig. 2 shows a flowchart diagram illustrating an exemplary flow according to some embodiments of the present invention;

[0007] Fig. 3 shows a table of results obtained by measuring a FFR parameter using Adenosine and measuring a FFR parameter according to an embodiment of the present invention;

[0008] Fig. 4 shows a logical block diagram of an exemplary device according to embodiments of the invention; and

[0009] Fig. 5 shows a graphical representation of signals obtained when using Adenosine and when using an embodiment of the present invention.

[0010] It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

[0011] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those of ordinary skill in the art that the invention may be practiced without these specific details. In other instances, well-known methods, procedures, components, modules, units and/or circuits have not been described in detail so as not to obscure the invention.

[0012] Although embodiments of the invention are not limited in this regard, discussions utilizing terms such as, for example, "processing," "computing," "calculating," "determining," "establishing", "analyzing", "checking", or the like, may refer to operation(s) and/or process(es) of a computer, a computing platform, a computing system, or other electronic computing device, that manipulate and/or transform data represented as physical (e.g., electronic) quantities within the computer's registers and/or memories into other data similarly represented as physical quantities within the computer's registers and/or memories or other information storage medium that may store instructions to perform operations and/or processes.

[0013] Although embodiments of the invention are not limited in this regard, the terms "plurality" and "a plurality" as used herein may include, for example, "multiple" or "two or more". The terms "plurality" or "a plurality" may be used throughout the specification to describe two or more components, devices, elements, units, parameters, or the like.

[0014] Unless explicitly stated, the method embodiments described herein are not constrained to a particular order or sequence. Additionally, some of the described method embodiments or elements thereof can occur or be performed at the same point in time.

[0015] Embodiments of the invention may enable causing, inducing or otherwise bringing about and/or maintaining a hyperemic state of a cardiovascular system of a subject. Such hyperemic state may be achieved and/or maintained without introducing any medicine, drugs, medicament or any other substance to the blood stream or cardiovascular system. Accordingly, achieving a hyperemic state according to embodiments of the invention may avoid intrusive or invasive procedures of any kind. Accordingly, undesirable effects and/or risks associated with known means for causing a hyperemic state of a cardiovascular system may be avoided. According to embodiments of the invention, any medical or other measurement, procedure or treatment requiring a hyperemic state of a cardiovascular system may follow achieving, detecting and/or maintaining such state.

[0016] According to embodiments of the invention, various periodic drills or exercises as described herein may cause a hyperemic state of the cardiovascular system of the subject performing such drills or exercises. In one embodiment, a periodic drill or exercises may be according to a frequency related to the Mayer waves. As known in the art, Mayer waves are fluctuations or waves having a frequency of 0.1 Hz, exhibited by a cardiovascular system as a result of oscillations of the chemoreceptor and baroceptors control systems. According to embodiments of the invention, performing a periodic drill or exercises with a frequency of 0.1 Hz may cause an excitation of a cardiovascular system. According to embodiments of the invention, various periodic drills or exercises may stimulate a cardiovascular system and induce a hyperemic state of the cardiovascular system. According to other embodiments various periodic effects may be used. Such effects may have a period that corresponds to the Mayer waves 0.1 Hz frequency and may induce a hyperemic state of the cardiovascular system.

[0017] According to other embodiments of the invention, various, possibly periodic, stimulations drills or exercises, e.g., deep breathing, may cause a hyperemic state of the cardiovascular system by stimulating it as described. Accordingly, in order to achieve and/or maintain a hyperemic state embodiments of the invention may expose a subject to effects as described herein or cause a subject, e.g., by providing specific instructions, to perform a predefined drill or exercise, for example, according to a predefined protocol.

[0018] According to embodiments of the invention, a subject may be instructed or otherwise caused to perform a predefined physical drill or exercise. Such predefined drill may be configured and/or designed to cause a hyperemic state of the subject's cardiovascular system. An exemplary predefined physical drill may be breathing according to a predefined breathing protocol that defines a rate or other aspects of breathing. In other embodiments of the invention, effects such as auditory effects, pressure effects, heating effects, cooling effects and/or a facilitated periodic movements effect configured and/or designed to cause a hyperemic state of the subject's cardiovascular system may be introduced. Some embodiments of the invention may combine introduction of effects as described herein with performance of a predefined physical drill.

[0019] In some embodiments, signals, e.g., vital signs as known in the art or other physiological parameters or signals related to a subject may be obtained from the subject. Obtained signals may be used to determine that a predefined physical activity is correctly performed. Obtained signals may be used to determine that a cardiovascular system of a subject is in a hyperemic state or determine a rate at which a cardiovascular system is approaching hyperemia.

[0020] Instructions provided to a subject (or to an operator of a system) may be based on signals or other information obtained from a subject. Accordingly, instructions may be changed during a procedure as described herein. Input received from a subject may be used to adjust or otherwise control introduced effects. For example, breath rate, heart rate or blood pressure may be obtained using applicable sensing devices. Obtained signals may be used to monitor the state of the cardiovascular system and determine if a hyperemic state has been reached and/or determine the reaction of the subject's cardiovascular system to introduced effects and/or to performance of a predefined activity. Upon detecting a hyperemic state of a subject's cardiovascular system, embodiments of the invention may alter, modify, adjust or otherwise control introduced effects such that the hyperemic state is maintained. Alternatively or additionally, upon detecting a hyperemic state, e.g., based on obtained signals, the subject may be instructed to perform a predefined activity, possibly different from a previously performed activity, in order to maintain a hyperemic state at a predefined level.

[0021] While a hyperemic state of a cardiovascular system is maintained, any medical or other procedures, measurements, functions or tasks may be performed. For example, FFR or CFR measurements requiring a hyperemic state of the coronary tree may be performed while a hyperemic state of a cardiovascular system is maintained. In other embodiments, e.g., when positron emission tomography (PET) imaging is used, prior to obtaining an image using a gamma camera as known in the art, a hyperemic state may be required, e.g., in order to better identify or distinguish areas, regions or anatomical objects such as blood vessels or muscles. Accordingly, after achieving a hyperemic state as described herein, a gamma camera may be used to obtain a required image. Other procedures and/or measurements that may be applicable to embodiments of the invention may be coronary computerized tomography angiography (CTA or CCTA), PET, procedures involving cardiac ultrasound, e.g., cardiac echo as known in the art, electrocardiography (ECG or EKG) and cardiac magnetic resonance imaging (MRI).

[0022] Based on measurements obtained from the subject and any applicable information, obtained from any applicable source, various parameters, indicators, values and the like may be computed, presented and stored. Any relevant data, parameters, results or other information obtained or computed during a procedure according to embodiments of the invention may be stored and used in subsequent similar or other procedures.

[0023] Reference is made to Fig. 1 showing a logical block diagram of an exemplary system 100 according to embodiments of the invention. System 100 may include sensing devices 105 that may be any applicable sensing devices. For example, sensing devices 105 may be a blood pressure sensing device, an electrocardiogram (ECG) sensing device or a breathing sensing device such as a spirometer, flow wire or breathing belt as known in the art. According to embodiments of the invention, sensing devices 105 may be attached to a tested subject and may acquire physiological signals or parameters of the patient. For example, sensing devices 105 may acquire signals indicating the breathing rate and depth of a tested subject. For example, sensing devices 105 may be configured to obtain a respiratory signal by performing direct measurement of chest wall motion, e.g., with a standard breathing belt. Alternatively or additionally, sensing devices 105 may enable acquiring PPG signals and further enable indirect measurement or computation of the respiratory sinus arrhythmia based on the PPG signal. According to embodiments of the invention, a number of different sensing devices may be simultaneously used. For example, during a particular procedure, sensing devices 105 may include a blood pressure sensing device, an electrocardiogram device and/or an oxygen saturation sensing device. Sensing devices 105 may be invasive or noninvasive devices. In some embodiments, sensing devices 105 may be suitable for obtaining specific measurements. For example, sensing devices 105 may be sensors suitable for obtaining FFR or CFR measurements.

[0024] Data acquisition unit 110 may control sensing devices 105, e.g., configure and initialize sensing devices 105. Data acquisition unit 110 may communicate with sensing devices 105 to receive measurements or other information obtained by sensing devices 105 from a subject and may provide data processing unit 115 with received information or data. Analog or other data received by data acquisition unit 110 from sensing devices 105 may be converted to digital information (digitized), e.g., prior to being provided to data processing unit 115. Data processing unit 115 may examine, evaluate, analyze or otherwise process information received from a tested subject via sensing devices 105. For example, based on processing received measurements from a patient and configuration parameters received from management unit 150, data processing unit 115 may determine if performance of a predefined activity by a subject adheres to a predefined protocol. For example, based on measured breathing rate of a subject, data processing unit 115 may determine if the subject is breathing according to^* a predefined breathing protocol. Based on received measurements, signals or input received from a subject, data processing unit 115 may determine a state of a tested subject. For example, data processing unit 115 may determine that a cardiovascular system of a tested subject is in a hyperemic state based on one or more received blood pressure measurements.

[0025] Patient guidance unit 125 may cause a physical output device to provide guidance to a patient. For example, patient guidance unit 125 may cause a display or other physical guidance tool or device to provide visual, e.g., textual or graphical instructions to a patient or it may cause a speaker to provide audible instructions. Effects control unit 120 may cause output devices to introduce effects that may stimulate a cardiovascular system of a subject. For example, effects control unit 120 may cause a display to introduce periodic or alternating visual effects that may stimulate the cardiovascular system of a subject and consequently cause a hyperemic state of the cardiovascular system. As shown, output unit 130 may comprise a display 135 that may be a display screen and a speaker 140 that may be any device capable of producing audible effects. Output unit 130 may comprise any applicable devices, for example, an array of light emitting diodes (LED), buzzer or a controllable physical device. Management unit 150 may control or manage data acquisition unit 110, data processing unit 115, patient guidance unit 125 and effects control unit 120. Management unit 150 may coordinate operations requiring coordination between components of system 100 as further described herein. For example, management module 150 may initiate a procedure described herein including prompting a user to enter various parameters, e.g., patient name and/or other data or provide other user interface (UI) functionalities. Management module 150 may interact, e.g., via input devices and/or output devices, with an operator and/or a tested subject. For example, management module 150 may provide instructions, indications, warnings, prompt for input, and receive instructions, choices or selections from an operator or tested subject. Management unit 150 may provide other units with configuration parameters, e.g., a desired breath rate, a predefined protocol related to a physical drill etc.

[0026] According to embodiments of the invention, a predefined breathing protocol may be used to cause or induce hyperemia. Accordingly, patient guidance unit 125 may cause display 140 to display instructions to a patient that may include any information that may help the patient to breath according to the predefined protocol. For example, patient guidance unit 125 may cause display 140 to alternatively display texts such as "inhale" and "exhale" according to a predefined rate. Additionally or alternatively, patient guidance unit 125 may cause speaker 135 to sound similar information at an appropriate rate, e.g., 0.1 Hz.

[0027] In such embodiments, sensing devices 105 may include a spirometer or breathing belt capable of measuring the breathing rate of a subject. Data acquisition unit 110 may communicate with such sensing devices to obtain measurements related to a breathing of the subject and may provide data processing unit 115 with parameters or information. For example, data acquisition unit 110 may receive analog information from a breathing belt, may convert such analog information to digital information reflecting a breathing rate and may provide data processing unit 115 with such information. Data processing unit may examine received information and may determine if the subject is breathing according to a predefined protocol. For example, management unit 150 may provide data processing unit 115 with an expected breathing rate, accordingly, data processing unit 115 may compare the measured breathing rate of the subject with such expected breathing rate and thus determine if the subject is breathing according to a predefined breathing protocol.

[0028] Based on provided and/or processed information, data processing unit 115 may determine if the subject is correctly performing the predefined breathing protocol. Data processing unit 115 may inform management unit 150 if the subject is correctly performing the predefined protocol. Data processing unit 115 may inform management unit 150 if the subject fails to comply with the predefined protocol. Data processing unit 115 may provide management unit 150 details or parameters pertaining to such failure. For example, by comparing a measured breathing rate with an expected breathing rate, data processing unit 115 may determine a subject is not breathing fast enough and accordingly, inform management unit 150 that the subject is breathing too slow. Management unit 150 may, in response, cause patient guidance unit 120 to change the instructions provided to the subject. For example, the patient may be instructed to breath faster or slower, hold his breath after inhaling etc.

[0029] Based on provided and/or processed information, data processing unit 115 may determine the state of the cardiovascular system of the patient. For example, other than a breathing sensing device as described herein, sensing devices 105 may include blood pressure sensing devices, for example, a flow wire as known in the art. Based on information received from appropriate sensing devices, data processing unit 115 may determine if the cardiovascular system of the subject is in a hyperemic state. Data processing unit 115 may check for a hyperemic state continuously, periodically or when instructed, for example by management unit 150.

[0030] Upon detecting a hyperemic state, data processing unit 115 may inform management unit 150 and/or patient guidance unit 120 that such state was detected. Management unit 150, when notified a hyperemic state has been detected may inform an operator and/or the subject of such detection. For example, management unit 150 may cause display 140 to display a message indicating that a hyperemic state was detected. Upon being notified of a hyperemic state, management unit 150 may cause patient guidance unit 120 to change the instructions provided to the subject. For example, a first physical drill may be best suited for achieving hyperemia while a second physical drill may be best suited for maintaining hyperemia. For example, the first drill may be any drill as described herein while the second drill may be similar to the first drill but may be a relaxed, less demanding version. Accordingly, upon detecting a hyperemic state, management unit 150 may cause patient guidance unit 120 to provide instructions best suited for maintaining a hyperemic state. For example, the depth of a breathing required for maintaining hyperemia may differ, e.g., be less then that required for achieving hyperemia, accordingly, instructions provided to the subject may be changed when hyperemia is detected as described herein.

[0031] According to embodiments of the invention, obtaining signals, e.g., vital signs from a subject, checking for existence of a hyperemic state, and/or altering instructions provided to the subject may all be performed automatically and/or simultaneously and/or sequentially. In some embodiments, such tasks may be performed in a loop, e.g., obtain signals, check cardiovascular state, and alter instructions. Either performed in a loop, continuously and/or simultaneously, a procedure may be limited by various parameters. For example, if a hyperemic state is not detected within a predefined or user configured period of time management unit 150 may terminate the procedure and inform an operator and/or subject of a failure to achieve hyperemia.

[0032] According to embodiments of the invention, in addition to, or instead of, guiding a patient as described herein, various effects may be introduced. Accordingly, management unit 150 may cause effects control unit 120 to cause output devices such as display 140 and/or speaker 135 to produce such effects. Similarly to causing patient guidance unit 125 to modify instructions provided to a patient as needed, management unit 150 may instruct effects control unit 120 to alter introduced effects as needed. For example, data processing unit 115 may determine that introduced effects do not have an expected result, e.g., a stimulation of the cardiovascular system is not detected. Accordingly, management unit 150 may instruct effects control unit 120 to change, e.g., intensify introduced effects. For example, a sound level of an audible effect may be increased or colors of a periodic visual may be altered. Another example of altering effects based on signals obtained from a subject may be maintaining of a hyperemic state. For example, upon detecting a hyperemic state, e.g., as described herein, effects that may have been introduced in order to achieve a hyperemic state may be altered, modified or replaced by other effects better suited for maintaining a hyperemic state. For example, while the frequency of such effects may be maintained, their intensity may be diminished to a level that is sufficient for maintaining a hyperemic state. While a hyperemic state is maintained, procedures requiring such state, e.g., measuring FFR, may be conducted. In some embodiments, drills and effects may be combined. For example, a subject may be instructed or caused to perform a periodic drill as described herein until a hyperemic state is achieved and, upon detecting hyperemia as described herein, the subject may be instructed to cease performance of the drill and visual or audio effects designed to maintain a hyperemic state may be initiated. It will be understood that operations of system 100 as described herein may all be automatic.

[0033] Reference is made to Fig. 2 depicting an exemplary flowchart of a method of causing and/or maintaining a hyperemic state of a cardiovascular system according to embodiments of the invention. As shown by block 210, the method may include instructing a subject to perform a predefined physical activity. Stimulation of a cardiovascular system may be achieved by various physical drills and/or other means as descried herein. For example, in one preferred embodiment, the cardiovascular excitation or stimulation may comprise a controlled breathing protocol characterized by a predefined frequency of breaths (e.g., about 0.1 Hz). A controlled breathing at a frequency of 0.1 Hz may stimulate the autonomic nervous system, and other physiological systems, such as the cardiovascular system that may, as a result, enter a hyperemic state. Accordingly, a patient may be instructed to perform a sequence of breaths at a low and steady rate, for example, at a frequency of 0.1 Hz (e.g., 5 seconds inspiration and 5 seconds expiration), for 30-300 seconds (e.g., 3-30 cycles of 10 seconds each).

[0034] It should be noted, however, that according to embodiments of the invention, other methods for achieving and/or maintaining a hyperemic state by stimulating the cardiovascular system may be used. Detailed below are several illustrative non- exhaustive examples of methods of stimulating the cardiovascular system in accordance with the present invention. Other suitable stimulation methods are likewise applicable. According to embodiments of the invention, the cardiovascular system may be stimulated into a hyperemic state by any applicable, periodic or other physical drills or activities. A non-exhaustive list of possible physical drills or activities may include sit- ups, arm-waving, walking, and/or sitting/standing cycles. Yet other possible cardiovascular system stimulations may include facilitated periodic movements, whereby the subject's body may be harnessed to an external oscillator capable of causing the entire body or body parts to move in a cyclic or periodic fashion. Accordingly, a subject may be instructed or caused to perform such activities, for example, by patient guidance unit 125 via display 140 or speaker 135.

[0035] According to other embodiments of the invention, a hyperemic state may be induced, achieved, caused and/or maintained by stimulating of its cardiovascular system. Stimulating the cardiovascular system of a subject may include periodic visual stimulation, namely, subjecting the subject, for example, to periodically changing images or visual patterns, periodic auditory stimulation, namely, subjecting the subject, for example, to periodic sound or music or periodic pressure application where the body or body parts (in particular the thorax or the neck) may be subjected to periodic external pressure, by for example, pneumatic, hydraulic, or mechanical means. Such effects or means may be caused by effects control unit 120 when in control of applicable devices. Any effects described herein, e.g., auditory effects, pressure effects, heating and/or cooling effects or facilitated periodic movements effects may be controlled by effects control unit 120.

[0036] Heating cycles which may include periodic and/or alternating heating and cooling of body parts, especially the face, activating the mammal diving reflex may also be used for stimulating of the cardiovascular system. It will be recognized that although typically the subject may be a human, embodiments of the invention are not limited by such constraint. Accordingly, while causing a subject to perform a predefined physical activity may comprise instructing a human patient to perform the physical activity it may include any means of causing, brining about or otherwise affecting of a predefined physical activity. For example, embodiments of the invention may be applicable to animals, e.g., horses or dogs. Accordingly, instructing to perform a predefined drill may not be applicable. Young children may be another example where instructing to perform a predefined drill may not be suitable. Accordingly, the subject may be exposed to various effects that may cause and/or maintain a stimulation and a resulting hyperemic state of its cardiovascular system. For example, forced cyclic limbs movement may be used.

[0037] As shown by block 215, the method may include obtaining physiological vital sign signals or other signals or parameters from the subject. Obtaining physiological vital sign signals of the subject may be performed during any stage, phase, point or part of the method. Typically, a patient may be connected to vital sign signals measuring devices at the beginning of a procedure. Accordingly, vital sign signals may be collected or obtained at any point in time after the relevant measuring devices have been properly connected, fixed, placed or installed. In some embodiments, collecting of vital or other signs signals may be performed after verification was made that the predefined activity is adequately performed. In other embodiments, vital and/or other signs may be collected continuously, e.g., from the point in time the measurement devices are capable of providing them until the relevant procedure is terminated. Vital or other signs signals obtained may be stored, for example on a storage device as described herein. Accordingly, metadata may be added, for example, in order to identify stored signals that are associated with a period of time when the activity was performed correctly. Such marking may enable various computations to be performed on verified or otherwise suitable data. For example, marking data collected during a period of time a protocol was correctly performed or a hyperemic state was detected may enable off-line processing of relevant data.

[0038] Conveniently, the signals may be measured in a limb or extremity, including but not limited to an arm, a hand, a finger, ear, wrist, ankle, leg, toe, neck, or chest, of the subject. Any signals that may be used in order to monitor an effect of the predefined activity and/or introduced effects on the subject may be obtained. For example, the breathing rate of the subject may be monitored thus enabling monitoring a compliance with a predefined breathing protocol. Other physiological signals, e.g., heart rate, blood pressure or oxygen level may be obtained and used as described herein. The scope of the invention is not limited by the way physiological signals of the subject are obtained. Accordingly, any tools, measuring or other devices, methods or means may be used by embodiments of the invention to obtain physiological signals of the subject as shown by block 215. [0039] As shown by block 220, the method may include guiding the performance of the predefined physical activity. Guiding or otherwise aiding a subject to perform a predefined activity may comprise any applicable means. For example, visual, auditory or other means may be used to help a subject coordinate his or her activity with a predefined protocol. For example, instructions such as "inhale" and "exhale" may be displayed on a display screen or sounded via speakers, e.g., by patient guidance unit 125 via display 140 or speaker 135. According to embodiments of the invention, advice, instructions, directions and/or any form of guidance or assistance may be provided, e.g., automatically by system 100. For example, a display screen may graphically display the rate at which a patient is breathing while at the same time display a predefined desirable rate thus enabling the patient to change and/or correlate his or her breathing rate with the desired rate. Audible means may be utilized, for example, a periodic sound may enable a tested patient to know whether he or she are breathing too fast or slow. Visual means for guiding or otherwise assisting a subject in performing a predefined activity may be used. For example, a dial displayed on a display 140 may indicate to a patient his breathing rate and a desired rate and may thus help the patient to regulate his breathing. Any applicable means may be used in order to guide and/or assist a subject in performing a predefined activity without departing from the scope of the invention.

[0040] As shown by block 225, the method may include verifying adherence of performance of a predefined physical activity to a predefined protocol. According to embodiments of the invention, correct performance or adherence may be verified by relating values, parameters or other aspects of signals obtained from the subject as described herein to applicable, expected values, parameters or other aspects. For example, a breathing rate or frequency of 0.1 Hz may be expected according to a predefined breathing protocol. Accordingly, by observing a breathing rate of a subject, e.g., by examining an obtained breathing rate signal, embodiments of the invention, e.g., data processing unit 115, may verify that the predefined breathing protocol is being correctly performed, followed and/or adhered to.

[0041] Any collected, measured or otherwise obtained signals, data, information and/or parameters may be used in order to determine whether a predefined activity is correctly performed, a protocol was adhered to or followed and/or assert that any applicable conditions were met. Any applicable currently or previously obtained parameters may be used. For example, parameters or indications such as, but not limited to, blood pressure, body temperature, metabolism rate, breathing rate, level of oxygen or other substances in the patients blood or exhaled gases may all be used in order to determine if the predefined activity is performed correctly, as expected or otherwise according to predefined protocol or criteria.

[0042] Verifying adherence as described herein may comprise taking into account various parameters, rules, information, thresholds, criteria or aspects. For example, any environmental aspects, e.g., temperature, humidity, oxygen level may be taken into account when assessing signals obtained from a patient. Since environmental aspects may affect or influence obtained signals they may be factored in or otherwise be relevant to determining a protocol is followed or an activity is properly performed. Other information involved in verifying adherence of performance of a predefined physical activity to a predefined protocol may be any patient related data. For example, expected results for a young female may be different from those for an elderly male. Accordingly, verifying adherence as described herein may comprise examining information, e.g., age, height, weight, gender, known diseases and possibly factoring the results or adjusting various scales, thresholds or other parameters as part of the verification process. Information used as described herein may be provided to a system implementing embodiments of the invention by an operator, patient, or it may be obtained from a storage. For example, such information may be retrieved from a local storage, e.g., a hard disk or it may be retrieved over a network from a remote storage, e.g., from a medical facility's database. Various diseases or conditions of a tested subject may also influence calculated expected results and/or obtained signals as described herein. Accordingly, such conditions or aspects may be taken into account when verifying and/or determining proper conduction of a predefined activity. For example, based on information such as gender, age, weight and health condition of a patient management unit 150 may calculate a suitable period or frequency. For example, to induce hyperemia, a higher frequency or cycle of a periodic breathing protocol may be better suited for a young child while an adult may require a somewhat lower frequency. [0043] Although not shown in Fig. 2, the method may include controlling introduced effects. As described herein, various effects may be introduced. Such effects may be controlled based on their effect on the tested subject. Effects introduced may be controlled according to various considerations. For example, any specific information such as subject's age, weight, known diseases and the like may be used in order to determine an expected reaction of the subject to introduced effects. For example, expected breathing rate, blood pressure or blood oxygen level may be computed and compared to actual, measured levels or parameters. Introduced effects may be altered, modified or otherwise controlled based on signals obtained from a tested subject. For example, lack of stimulation and/or progress towards a hyperemic state of a cardiovascular system may cause embodiments of the invention, e.g., management unit 150, to modify introduced effects. For example, the pace, rate, intensity or level of an introduced effect as described herein may be changed or altered. Controlling of introduced effects may be performed such that a desirable reaction is caused or achieved, e.g., a hyperemic state of a subject's cardiovascular system is induced, reached and/or maintained. Accordingly, a closed-loop technique may be employed, e.g., by management unit 150, whereby signals obtained from a subject as described herein are used as input for altering introduced effects. Accordingly, tuning or controlling effects may comprise a self learning, automatic logic designed to achieve hyperemia by introduced effects.

[0044] As shown by block 230, the method may include determining that a physical activity was performed correctly and selecting a course of action based on such determination. For example, if it is determined that a predefined protocol was correctly performed during a predefined period of time, e.g., three minutes, then the method or procedure may continue as shown by block 231. Otherwise, e.g., if it is determined that the predefined activity has not been performed during a minimum period of required time then the procedure may be continued as shown by block 235. Checking for adherence to a predefined protocol as shown by block 230 may be done any applicable or preconfigured number of times according to a preconfigured frequency. For example, management unit 150 may probe data processing unit 110 every ten (10) seconds and determine that a predefined protocol was adhered to upon detecting adherence in consecutive 5 such probes. For example, if a subject is found to breath at an expected rate during two (2) minutes it may be determined that the subject is correctly performing a predefined breathing protocol.

[0045] As shown by block 235, if it is determined that the physical activity was not performed or conducted correctly, the method may include providing a non adherence indication. For example, a message may be displayed on a display screen of a computing device indicating that the physical activity was not performed or conducted correctly or a protocol was not followed. The indication may include specific reasons and/or further instructions, advice or suggestions. For example, an indication provided as shown by block 235 may indicate the subject breathing rate was too slow and further suggest faster breathing in a subsequent test. As shown by block 240, in cases where it was determined that a predefined activity was not performed or conducted properly, the method may include providing an option to retiy or repeat the method or procedure. A user, operator and possibly the tested subject may select to repeat the method or terminate the procedure. If retry is selected, the method may repeat the procedure by returning to block 210 as shown by the arrow connecting blocks 240 and 210. Alternatively, as shown by the arrow connecting blocks 240 and 255, the method or procedure may terminate.

[0046] As shown by block 231, the method may include determining whether a hyperemic state of cardiovascular system is detected. Such determination may comprise relating of any applicable signals or parameters computed or obtained from the subject with predefined and/or computed values or parameters. For example, a detected combination of predetermined values of heart rate, blood pressure, respiratory values and/or other parameters may cause data processing unit 110 to determine that a hyperemic state of the cardiovascular system has been achieved and/or maintained.

[0047] According to embodiments of the invention, a loop comprising checking or determining if a hyperemic state of the cardiovascular system was achieved and altering an introduction of effects or altering instructions to the subject may be repeated any applicable number of times. For example, signals obtained from the tested subject may be periodically or continuously examined by data processing unit 110 and based on such examination, it may be determined if a hyperemic state of the cardiovascular system has been reached or achieved. If a hyperemic state is not reached or achieved, introduced effects may be altered or they may be introduced unaltered for a period of time. Similarly, instructions or guidance provided to the tested subject regarding performance of a physical activity may be changed. Repeating such course may be continued until a hyperemic state is achieved or until a predefined condition is met. For example, a system may be configured to attempt to cause a hyperemic state of cardiovascular system during a period of five (5) minutes and report failure if a hyperemic state is not achieved within such time limit. In other embodiments, detecting a heart rate or other physiological parameter of the subject crossed a predefined threshold may cause automatic termination of a procedure. Any other conditions, limits or thresholds may be used by embodiments of the invention to determine failure to cause or maintain a hyperemic state of cardiovascular system. As shown by the arrow connecting blocks 231 and 240, upon determining failure to achieve or maintain a hyperemic state, a user, operator and/or subject may be provided with a selection choice and may choose to repeat the method as shown by the arrow connecting blocks 240 and 210 or terminate the method as shown by the arrow connecting blocks 240 and 255. For example, an operator may check all measuring devices and/or wires are correctly installed or the operator may verbally explain to a patient how to best perform a predefined activity. Subsequent to such exemplary actions, the method may be repeated as shown by the arrow connecting block 240 and 210.

[0048] Embodiments of the invention may detect and maintain a hyperemic state with or without causing or inducing such state. For example, obtaining physiological signals of the subject as shown by block 215 may commence or be performed prior to causing a subject to perform a predefined activity and/or introducing predefined effects as shown by block 210. Accordingly, if and/or when a hyperemic state is detected, some procedures, steps or parts of a method, e.g., parts of the method described herein, may be skipped or omitted. Upon detecting a hyperemic state, e.g., based on signals obtained as described herein, embodiments of the invention may perform any applicable function or task such that the hyperemic state is sustained or maintained. For example, upon detecting a hyperemic state, effects introduced as described herein may be altered or modified such that their effect may maintain or sustain the hyperemic state of the subject's cardiovascular system. For example, upon being informed by data processing unit 115 that a hyperemic state was detected, management unit 150 may instruct effects control unit 120 to alter effects introduced to effects that may maintain or sustain the hyperemic state. Accordingly, while effects introduced and controlled as described herein may cause a hyperemic state, such effects may be modified, altered or controlled upon detecting a hyperemic state such that the hyperemic state is maintained for a period of time that may be preconfigured or controlled. For example, an operator may instruct or otherwise cause system 100 to cease introduction of effects that cause a hyperemic state to be maintained.

[0049] As shown by block 245, the method may include computing an indicator reflecting a condition of a cardiovascular system. Any number of possibly different indicators, parameters or values may be computed as shown by block 245. For example, FFR or CFR may be computed based on signals received from sensing devices 105. It will be noted that FFR, CFR or other measurements, indicators or parameters may be computed based on signals obtained during a hyperemic state induced by a physical drill or other means described herein and without administering any substances or compounds used by prior art in order to bring about a hyperemic state. Any applicable indicators, parameters or other medical data may be computed as shown by block 245. Though not shown, information from any suitable source, e.g., a remote database, may be retrieved and results may be computed based on such retrieved or otherwise obtained information. For example, information used for computing results may include lab results obtained from a hospital or other medical facility, any information manually provided, e.g., typed in through a keyboard etc.

[0050] As shown by block 250, the method may include providing a computed indication reflecting a condition of a cardiovascular system. In one embodiment of the invention, a computed indicator, e.g., FFR or CFR may be displayed on a display screen, printed on paper, communicated to a remote server, stored in a storage device or otherwise provided. The indicator may be displayed numerically or it may be provided graphically, e.g., as a bar or other suitable graphical object, possibly accompanied by bars or other suitable graphical object indicating high and low thresholds enabling quick and intuitive observation, interpretation and/or understanding of a state of a tested subject.

[0051] Computing an indication reflecting a condition of a cardiovascular system may comprise involving various data, information, parameters, rules, thresholds, criteria, context, or aspects. For example, information from historical or previous procedures, tests and/or indications may be examined and taken into consideration. For example, a graph showing an evolution of a specific parameter or indicator, e.g., FFR may be displayed, possibly showing the FFR results in the past couple of years. As known in the art, a trend, gradient or evolution of a physiological indicator may sometimes be no less important than its current nominal value. Accordingly, any historical related information may be involved in a computation of an indication of a condition of a cardiovascular or other system as described herein.

[0052] According to embodiments of the invention, computing an indication reflecting a condition of a cardiovascular system may include predicting values or other aspects of indicators, parameters or other information. For example, based on previous results, trends, known condition of the tested subject, statistical information, a subject's age, gender and/or known diseases, an expected value of a specific indicator may be computed or predicted. Such predicted indicators, values, conditions or parameters may be displayed and compared with actual indicators computed as described herein. Such comparison may provide further insights regarding a subject's condition.

[0053] Other aspects that may be taken into account when computing an indication according to embodiments of the invention may be patient specific information, e.g., gender, age, weight known diseases and the like or statistical information, e.g., a Framingham score as known in the art. For example, a specific value of an FFR indicator related to a young male may be viewed differently than when related to an old female. Physical condition, known diseases or other relevant aspect may similarly be taken into account. Accordingly, computing an indication may comprise "factoring in" or "factoring out" various aspects or otherwise adjusting a final result or scale displayed and/or recorded according to any applicable data, information, parameters, rules, thresholds, criteria, settings, configuration, context or other aspects. Any computed data, information, parameters, rules, thresholds, indications, criteria, context or other aspects as described herein may be presented or otherwise provided as shown by block 250.

[0054] As shown by block 250, the method may include providing results and indications. Any applicable indications, data, information, parameters, rules, thresholds, criteria, settings or other aspects may be provided as shown by block 250. For example, response curves to external stimulations or effects introduced as described herein may be presented. Displaying results as shown by block 250 may comprise displaying scales or other means for evaluating medical aspects of the patient. For example, expected values (e.g., of a standard healthy similar subject) may be displayed along side values of the tested subject or historical values, previously obtained from, and/or computed for the tested subject may be presented. Various graphs, plots or gradients may be presented. Any applicable parameters or other information computed or obtained as described herein may be displayed as shown by block 250.

[0055] Termination of the method or procedure as shown by block 255 may comprise a number of activities or procedures. For example, results may be printed or information may be stored. For example, any relevant parameters computed, collected or otherwise obtained through the method or procedure may be stored and further used, for example, as described herein, in a subsequent procedure. For example, results from a current procedure may be used in order to provide historical or trend views in subsequent procedures. Upon termination as shown by block 255, results, obtained signals or computed parameters or any applicable information may be stored locally or communicated to a remote computing device, e.g,, a database of a medical or other facility. Accordingly, such communicated information may be retrieved and used in subsequent procedures. For example, any information or parameters obtained or computed as described herein with reference to the flowchart depicted in Fig. 2 may be stored upon termination of the method as shown by block 255 and may further be retrieved.

[0056] Reference is made to Fig. 3 which shows a table 300 of results obtained by measuring a FFR parameter using Adenosine as known in the art and measuring a FFR parameter according to an embodiment of the present invention. The term "Pd" shown in Fig. 3 is distal coronary pressure (distal to the stenosis) and the term "Pa" is aortic pressure. The two modes of achieving hyperemia are denoted as Adenosine and Respiratory in table 300, where Adenosine denotes the mode where hyperemia was achieved by administering Adenosine and Respiratory denotes a mode where hyperemia was achieved by conducting a breathing protocol as described herein. As reflected by column 340, systolic and diastolic blood pressure measurements were obtained. Accordingly, rows 315 and 320 show systolic and diastolic blood pressures obtained before the blockage or stenosis (Pa) and after the blockage or stenosis (Pd) for both Adenosine and Respiratory modes. Row 325 shows calculated mean blood pressures in both locations (Pa and Pd) for both modes (Adenosine and Respiratory). Finally, row 330 shows the calculated FFR value for both modes is the same. The calculated FFR value was derived by dividing a mean Pd value to a mean Pa value where the mean values were calculated based on the values shown in table 300. Evidently, embodiments of the invention enable obtaining a measurement requiring hyperemia that is adequate yet omits usage of chemicals such as adenosine thus avoiding risks and/or side effects associated with such chemicals.

[0057] Reference is additionally made to Fig. 5 which shows two graph sets 510 and 515. Graph sets 510 and 515 are a representation of blood pressures obtained when using Adenosine (515) and when using a predefined respiration drill according to an embodiment of the present invention (510). Pa and Pd shown in Fig. 5 denote aortic and distal pressures respectively and as described herein. The graph sets shown in Fig. 5 are related to table 300 shown in Fig. 3, namely, values in table 300 and graph sets 510 and 515 are related to the same experiment involving an actual patient. As clearly shown by both table 300 and graph sets 510 and 515, embodiments of the invention enable achieving required hyperemia without subjecting a patient to risks involved with drugs such as Adenosine.

[0058] Reference is made to Fig. 4 showing a logical block diagram of an exemplary device 410 according to embodiments of the invention. Computing device 410 may include a memory 430, a controller, e.g., a central processing unit processor (CPU) 405, storage device 440, an operating system 415, a speaker 470, a display 475, input device(s) 420 and an output device 445. Computing device 410 may be operatively coupled to a one or more sensing devices 455. Sensing devices 455 may be any suitable devices or systems configured to obtain any applicable signals from a tested subject. For example, sensing device may be any sensor quipped device for measuring and/or obtaining vitals signs or other physiological signals from a tested subject. Exemplary measured parameters may include blood pressure, electrocardiogram (ECG), blood gases, respiration, PPG etc. Embodiments of the invention are not limited by the number, type, nature or other aspects of sensing devices 455 that may be any suitable, possibly commercial or off-the-shelf devices or equipment. A tested subject may be a human, e.g., a patient in a medical facility or a private individual at a home. Alternatively, a tested subject may be any living organism or animal, e.g., a horse or a dog.

[0059] According to embodiments of the invention, storage device 440 may be any suitable storage device, e.g., a hard disk or a universal serial bus (USB) storage device. Input devices 420 may include a mouse, a keyboard, a touch screen or pad or any suitable input devices. Display 475 may be any suitable display screen. Speaker 470 may be any suitable speaker or audio system. Any applicable input/output (I/O) devices may be connected to computing device 410 as shown by blocks 420 and 445. For example, a network interface card (NIC), a printer or facsimile machine may all be included in input devices 420 and output device 445.

[0060] As shown by blocks 433, applications such as programs, scripts or any executable code may be loaded into memory 430 and may be executed by controller 405. For example, applications 433 may include data acquisition 432, data processing 115, patient guidance 125, effects control 120 and/or management 150 described herein. Although not shown, computing device 410 may comprise additional hardware or firmware, e.g., an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or a chip. Accordingly, data acquisition 432, data processing 115, patient guidance 125, effects control 120 and/or management 150 may be implemented by computing device 410 using software, hardware, firmware or any combination thereof. [0061] As described herein, computing device 410 and connected devices may be, or may be used as, an implementation of system 100 described herein. For example, sensing devices 455 may be similar to sensing devices 105, display 475 may be similar to display 140 etc. As described herein, management unit 150, data acquisition unit 110, data processing unit 115, effects control unit 120 and patient guidance unit 125 may be implemented by executable software loaded into memory 430, by hardware or by firmware (not shown) or by a combination thereof.

[0062] Some embodiments of the present invention may be provided in a computer program product that may include a machine-readable medium, stored thereon instructions, which may be used to program a computer, or other programmable devices, to perform methods as disclosed above. Embodiments of the invention may include an article such as a computer or processor readable medium, or a computer or processor storage medium, such as for example a memory, a disk drive, or a USB flash memory, encoding, including or storing instructions, e.g., computer-executable instructions, which when executed by a processor or controller, carry out methods disclosed herein.

[0063] While certain features of the invention have been illustrated and described herein, many modifications, substitutions, changes, and equivalents may occur to those skilled in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention.

Claims

CLAIMSWhat is claimed is:

1. A method comprising: inducing a hyperemia state of a cardiovascular system of a subject by guiding the subject, using a physical guidance device, to perform a predefined periodic physical activity, wherein the periodic physical activity is performed at a desired excitation frequency around 0.1 Hertz; receiving signals from the subject to monitor performance of the activity at the desired excitation frequency; and obtaining a measurement of a physiological parameter related to the subject while maintaining the hyperemic state of the subject.

2. The method of claim 1, wherein obtaining the measurement comprises measuring, by a catheterization sensing device, at least one of a fractional flow reserve (FFR) measurement and a coronary flow reserve (CFR) measurement.

3. The method of claim 1, wherein obtaining the measurement is related to a procedure involving one of: a positron emission tomography (PET), a cardiac ultrasound, a coronary computerized tomography, an electrocardiography (ECG or EKG) and a cardiac magnetic resonance imaging (MRI).

4. The method of claim 1, wherein said predefined periodic physical activity comprises breathing according to a predefined breathing protocol at the excitation frequency.

5. The method of claim 1 , comprising: instructing said subject to perform a first predefined physical activity; determining that said cardiovascular system is in the hyperemic state; and instructing said subject to perform a second predefined physical activity such that the hyperemic state is maintained.

6. The method of claim 4, wherein said breathing protocol comprises a predefined frequency of 0.1 breaths per second.

7. The method of claim 1 comprising: introducing a periodic effect, said effect is at least one of an auditory effect, a pressure effect, a heating effect, a cooling effect and a movement effect.

8. The method of claim 1 comprising: verifying based on the signals received from the subject that the predefined periodic physical activity is correctly performed.

9. The method of claim 1, comprising: providing said subject with instructions related to said predefined periodic physical activity; and changing said instructions based on said signals of said subject.

10. The method of claim 1, wherein the signals are at least one of: a heart rate signal, a blood pressure signal, an oxygen level signal, a temperature signal and a breath rate signal.

11. The method of claim 4 comprising: verifying adherence to said predefined breathing protocol based on input from a sensing device wherein the sensing device is one of: a flow wire, a spirometer and breathing belt.

12. The method of claim 1, comprising: determining a failure to achieve the hyperemic state of said cardiovascular system; providing an indication of said failure; providing a reason for said failure; and providing a suggestion for a subsequent attempt to obtain said measurement.

13. A system comprising: a physical guidance device to guide a subject in performing a predefined periodic physical activity at a desired excitation frequency around 0.1 Hertz, wherein the periodic physical activity is designed to induce a hyperemic state of a cardiovascular system of the subject; a sensor able to receive signals from the subject for monitoring performance of the activity at the desired excitation frequency; and a measurement device to obtain a measurement of a physiological parameter related to the subject.

14. The system of claim 13, wherein the measurement device is a catheterization sensing device for performing at least one of a fractional flow reserve (FFR) measurement and a coronary flow reserve (CFR) measurement.

15. The system of claim 13, wherein the measurement is a positron emission tomography (PET) device, a cardiac ultrasound device, a coronary computerized tomography device, an electrocardiography (ECG or EKG) device or a cardiac magnetic resonance imaging (MRI) device.