WO2009042562A1

WO2009042562A1 - Self calibrating extravasation detection system

Info

Publication number: WO2009042562A1
Application number: PCT/US2008/077309
Authority: WO
Inventors: Paul D. Mannheimer; Michael E. Fein
Original assignee: Mallinckrodt Inc.
Priority date: 2007-09-24
Filing date: 2008-09-23
Publication date: 2009-04-02

Abstract

An extravasation detection system has an extravasation sensor and a calibration sensor for measuring first and second parameters, respectively, during a test injection and during a prescribed injection. The first parameter is indicative of whether or not there is extravasation in the subject. The second parameter is a condition that can be correlated with the first parameter. A processor receives signals from the sensors and uses the test injection signals to determine one or more criteria that it later uses in determining whether or not the prescribed injection produces extravasation in the subject. In one embodiment, the processor determines a relationship relating the first parameter to the second parameter and uses the expression to calculate an expected result for measurement of the first parameter during the prescribed injection absent extravasation. If the processor determines that there is extravasation, it activates an alarm system and/or interrupts the injection.

Description

SELF CALIBRATING EXTRAVASATION DETECTION SYSTEM

FIELD OF INVENTION

[0001] The present invention relates generally to systems and methods for injecting a substance into a subject's blood vessel, and more particularly to systems and methods for automatically detecting extravasation of an injected substance into tissue surrounding the target blood vessel.

BACKGROUND

[0002] Substances are injected into the blood vessels of people and animals for various reasons. Contrast media are injected to enhance viewing of various internal soft tissue features in X-rays, MRIs and other imaging techniques, for example. Other injection media, such as chemotherapies, pharmaceuticals, and some radiopharmaceuticals (i.e., pharmaceuticals that are radioactive), are injected for various diagnostic and therapeutic purposes.

[0003] Any injection of a substance to a target blood vessel poses a risk of extravasation (sometimes referred to as infiltration). Extravasation is injection of the injection medium into the tissue surrounding the target blood vessel rather than the blood vessel. Extravasation may be caused by failure to properly position the tip of the injection needle inside the target blood vessel. Extravasation may also result from physiological limitations on the ability of the blood vessel to withstand the increased pressure associated with the injection. The consequences of extravasation vary depending on the nature of the injection medium. For example, extravasation may cause severe discomfort for the subject, may cause tissue damage, and may result in permanent injury in severe cases. The consequences of extravasation can also depend on the amount of the injection medium that escapes into the surrounding tissue. It is important to detect extravasation early, before a large volume of the injection medium is injected into the surrounding tissue. Early detection allows the injection to be interrupted to limit the consequences of the extravasation.

[0004] Automated injectors are now commonly used to inject the injection media into subjects. Automated injectors free health care providers from the need to administer the entire injection manually, but they also make automated detection of extravasation more important. Without intervention, an automated injector can continue to inject the substance into the subject while extravasation is occurring, thereby increasing the severity of the extravasation. Further, when powerful automated injectors are used to inject the injection medium under high pressure (as is commonly the case with bolus injections of contrast media, for example), extravasation needs to be detected quickly to limit the amount of the injection medium that is injected into the surrounding tissue. Thus, there is a need for systems that can quickly and reliably detect extravasation automatically to reduce the risk of extravasation and reduce the need for health care providers to supervise injections and manually monitor for extravasation.

[0005] Various prior art extravasation sensors are available to detect extravasation. For example, optical, thermal, pressure, mechanical, and electrical impedance sensors have all been used to detect extravasation. A difficulty in the design of any extravasation detector is that the detector must distinguish between changes in the subject caused by extravasation from changes caused by the expected normal increase in pressure and volume in the target blood vessel during a successful injection. The behavior of the target blood vessel and the response of the extravasation sensor may vary significantly with variations in the injection rate and the nature of the injection medium. The behavior of the target blood vessel may also vary from one subject to the next, depending, for instance, on the tone of the smooth muscle in the wall of the target blood vessel. Because of these factors, automated detection systems have difficulty reliably determining whether or not there is extravasation, particularly in the early stages of extravasation when there is the greatest opportunity to limit the undesirable consequences of extravasation.

[0006] As a precaution against extravasation, a test injection is commonly conducted before injection of the prescribed injection medium. During the test injection, a substance that is relatively harmless when extravasated (e.g., physiological saline solution) is injected into the subject through the same needle that will be used to inject the injection medium. The health care provider palpates the tissue surrounding the injection site during the test injection to detect any changes in the tissue firmness that are indicative of extravasation. The health care provider may periodically palpate the tissue surrounding the injection site during the injection of the prescribed injection medium in a similar manner.

[0007] Many prior art extravasation detection systems interfere with or hinder manual palpation of the injection site because their sensor{s) limit access to the tissue surrounding the injection site, such as by being applied to the subject's skin in a manner that covers this tissue. This limits the ability of the health care provider to manually palpate the tissue surrounding the injection site during the test injection and during injection of the prescribed injection medium into the subject.

[0008] Thus, there is a need for improved extravasation detection systems and methods that are more reliable and robust in their ability to distinguish between extravasating and non-extravasating injections in various different individual subjects and with various injection media. Further, there is a need for such systems and methods that do not interfere with manual palpation of the injection site during the injection. SUMMARY

[0009] One aspect of the invention is an extravasation detection system for use in an injection process in which an injection system is used to conduct a test injection during which a test medium is injected into the subject and then conduct a prescribed injection during which a prescribed injection medium is injected into the subject. The extravasation detection system includes an extravasation sensor for measuring a first parameter during the test injection and during the prescribed injection. The first parameter is indicative of whether or not there is extravasation in the subject. The extravasation sensor outputs test injection signals and prescribed injection signals, respectively, representative of the first parameter. The extravasation detection system also includes a calibration sensor for measuring a second parameter during the test injection and during the prescribed injection. The second parameter is indicative of a condition in at ieast one of a target blood vessel in the subject and the injection system. The calibration sensor outputs test injection signals and prescribed injection signals, respectively, representative of the second parameter. The extravasation detection system has a processor operable to receive the test injection signals and prescribed injection signals from the extravasation and calibration sensors. The processor is operable to establish one or more criteria for determining whether or not the injection medium is being extravasated using the test injection signals received from the calibration and extravasation sensors. The processor is also operable to determine whether or not the injection medium is being extravasated using the prescribed injection signals from the calibration and extravasation sensors and said one or more criteria. Further, the processor is able to activate a warning system or interrupt the injection system if it determines that the injection medium is being extravasated.

[0010] Another aspect of the invention is a method of injecting an injection medium into a subject. The method includes using an injection system to inject a test medium into the subject to confirm that the injection system is injecting into a target blood vessel. Then the injection system is used to inject an injection medium into the subject to deliver the injection medium to the target blood vessel. First and second parameters are measured during injection of the test medium into the subject and during injection of the injection medium into the subject. The first parameter is indicative of whether or not there is extravasation in the subject. The second parameter is indicative of a condition in at least one of the injection system and the target blood vessel. The measurements of the first and second parameters corresponding to injection of the test medium into the subject, are used to establish one or more criteria for determining whether or not the injection of the injection medium is associated with extravasation in the subject. The measurements of the first and second parameters corresponding to injection of the injection medium into the subject and said one or more criteria are used to determine whether or not the injection of the injection medium is associated with extravasation in the subject.

[0011] In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained. Other objects and features will be in part apparent and in part pointed out hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012] FIG. 1 is a schematic illustration of one embodiment of an injection system and extravasation detection system of this invention;

[0013] FIG. 2 is a schematic illustration of a second embodiment an injection system and extravasation detection system of this invention;

[0014] FiG. 3 is a schematic illustration of an electrical impedance tomography sensor of this invention;

[0015] FIG. 4 is a graph showing outputs from the electrical impedance tomography sensor as a function of time during an injection of this invention;

[0016] FIG. 5 is a schematic illustration of a third embodiment of an injection system and extravasation detection system of this invention;

[0017] FIG. 6 is a schematic illustration of a plurality of optical sensors embedded in a U-shaped extravasation sensor patch of this invention; and

[0018] FIG. 7 is a schematic illustration of a fourth embodiment of an injection system and extravasation detection system of this invention.

[0019] Corresponding reference characters indicate corresponding parts throughout the drawings.

DETAILED DESCRIPTION

[0020] Referring to the drawings, first to Fig. 1 , an injection system of the present invention, generally designated 101 , is shown schematically in the process of injecting an injection medium (not shown) into a subject's blood vessel 103. The subject 102 can be any organism having a vascular system, including a human or animal.

[0021] As depicted in Fig. 1 , the injection system 101 includes a fluid delivery system 105, for moving the injection medium along a fluid flow path 107 for injection into the subject 102. In this particular embodiment, the fluid delivery system 105 comprises an automated power injector 109, which is generally conventional except as noted. The injector 109 is a syringe pump and includes a reservoir 111 defined by a barrel 113 of the syringe 110 for containing a supply of the injection medium. A motor 117 drives a piston 119 in the barrel 113 to expel the injection medium from the reservoir 111 into the subject 102 through an injection line 121 that defines at least part of the fluid flow path 107 and that is in fluid communication with the reservoir and the subject during the injection. In Fig. 1 , for example, the injection line 121 comprises a segment of flexible tubing 124 and a hypodermic needle 143 connected to the end of the tubing. The needle 143 defines an outlet 175 for delivery of the injection medium into the subject 102. As is generally known, the end of the needle 143 has a sharpened tip 141 for piercing the subject's skin and positioning the outlet 175 in the target blood vessel 103. Although the fluid delivery system 105 shown in Fig. 1 includes a syringe pump 109, other types of injection mechanisms, including manual injection systems can be used instead within the scope of the invention. Likewise, the fluid flow path may have different configurations and be defined in ways different than shown in Fig. 1 (e.g., by a flexible catheter without any needle at the end) within the scope of the invention.

[0022] As used herein, the term "injection medium" means any flowable substance that is to be injected into the subject's blood vessel 103 for any reason. The injection medium may be a substantially homogenous fluid (e.g., a liquid solution) or it may be a heterogeneous flowable substance (e.g., a colloid or emulsion). The injection medium may be a contrast medium that is used to enhance contrast of features in an X-ray, MRI, ultrasound, or other imaging procedure. The injection medium can also comprise a radioisotope (e.g., Technetium-99) for conducting any of various diagnostic and/or therapeutic procedures in the field of nuclear medicine. Likewise, the injection medium may comprise a pharmaceutical (e.g., a chemotherapeutic substance).

[0023] The injection system 101 allows a test injection to be conducted before the prescribed injection of the injection medium into the subject 102. The phrase "prescribed injection" will be used herein to distinguish the test injection from the injection of the injection medium. Use of the word "prescribed" does not require there to be a prescription for the injection medium or that the injection medium be provided by a pharmacy. The test injection enables a health care provider to check for proper positioning of the needle tip 141 in the target blood vessel 103. For example, as illustrated in Fig. 1 , the fluid delivery system 105 may include a manual access port 106 (e.g., in one branch of a conventional Y-type connector in the injection line 121 ) for manually injecting a test medium, such as a saline solution, into the subject 102.

[0024] There are other ways in which the injection system may permit a test injection within the scope of the invention. For example, it may be desirable to use the same delivery method for the test injection and the prescribed injection to reduce the number of variables that are likely to change between the test injection and the prescribed injection. In order to use the same injector 109 for both injections, another syringe (not shown) containing test medium can be loaded into the injector 109 for the test injection and replaced by the syringe 110 containing the injection medium after the test injection is complete. Also, some injection systems are equipped to automatically flush the injection line, in which case the flush option can be used to conduct the test injection.

[0025] The injection system 101 is accompanied by a self-calibrating extravasation detection system 131. The system 131 includes at least one extravasation sensor 133 for measuring a first parameter during the test injection and during the prescribed injection. The first parameter is indicative of whether or not there is extravasation in the subject 102. The extravasation sensor 133 can be any one of a variety of different types of sensors that are operable to measure one or more parameters indicative of whether or not there is extravasation in the subject. Suitable sensors include, but are not limited to, mechanical transducers (e.g., for measuring firmness or swelling of the subject's tissue), optical sensors (e.g., for measuring electromagnetic radiation emitted or reflected from inside the subject), thermal sensors (e.g., infrared or microwave sensors for measuring distribution of heat in the subject), electrical impedance/conductivity sensors (e.g., for measuring electrical properties inside the subject), ultrasound sensors (e.g., for measuring ultrasound reflected from inside the subject), pressure sensors, and fluid flow sensors (e.g., Doppler sensors for measuring fluid flow within the target blood vessel), just to name a few. In general, all that is required of the extravasation sensor 133 is that it is operable to measure a parameter that varies in a manner that can be correlated in some way with the likelihood that extravasation is occurring or has already occurred in the subject 102. The extravasation sensor 133 depicted in Fig. 1 , for example, is an electrical impedance sensor that is applied to the subject's skin to monitor electrical characteristics of the subject's tissue during the injections. The extravasation sensor 133 is operable to output signals representative of the first parameter.

[0026] The extravasation detection system 131 also includes at least one calibration sensor 144 for measuring a second parameter during the test injection and during the prescribed injection. The second parameter is indicative of a condition in at least one of the target blood vessel 103 and the injection system 101. For example, the second parameter may be a fluid pressure or fluid flow rate in the injection system 101 or target blood vessel 103. As is explained in more detail below, the calibration sensor 144 provides a basis for correlating the response of the extravasation sensor 133 to a non-extravasating injection with another condition that can be measured during the prescribed injection. As such, it is not necessary that the calibration sensor 144 measure a parameter that is itself indicative of whether or not there is extravasation in the subject 102. It is understood, however, that the second parameter may be indicative of whether or not extravasation is occurring without departing from the scope of the invention. Thus, the calibration sensor 144 may be another extravasation sensor. The calibration sensor 144 is preferably operable to measure a different parameter than the extravasation sensor 133. The calibration sensor is operable to output signals representative of the second parameter.

[0027] The calibration sensor 144 may be connected to the injection system 101 (e.g., connected to the fluid delivery system 105 by virtue of its being installed in the injection line 121 ) as shown in Fig. 1. However, it is also contemplated that the self-calibrating extravasation detection system may be a stand-alone unit separate from the injection system 101. In the particular embodiment shown in Fig. 1 , for example, the calibration sensor 144 is a pressure sensor connected to the injection system 101 and positioned along the injection line 121. More specifically, the pressure sensor 144 is positioned in the injection line 121 adjacent the outlet 175 (e.g., in the hypodermic needle 143 and adjacent the tip 141 of the needle) to measure fluid pressure at the outlet. Fluid pressure adjacent the outlet 175 is indicative of a condition in the injection system 101 and also in the target blood vessel 103. Suitable miniature pressure sensors for use in various parts of the injection system 101 (inciuding, but not limited to, the tubing 124 or needle 143 of the injection line 121 ) are commercially available from a number of sources.

[0028] The extravasation detection system 131 includes a processor 161 operable to receive the signals from the extravasation sensor 133 and calibration sensor 144. The schematic illustration of Fig. 1 indicates that the signals are transmitted to the processor 161 via hardwired connections 163 between the sensors 133, 144 and the processor. However, it is understood that any transmission method, including wireless transmission of signals to the processor 161 , is within the scope of the invention. To facilitate description of how the processor 161 operates, the signals from the sensors 133, 144 corresponding to the test injection will be referred to herein as "test injection signals" and the signals corresponding to the prescribed injection will be referred to as "prescribed injection signals."

[0029] The processor 161 has at least one of instructions (e.g., software) and circuitry (e.g., a hardwired circuit) such that the processor is operable to determine whether or not there is extravasation in the subject 102 during the prescribed injection, as set forth below. In one embodiment, the processor 161 is operable to use the test injection signals received from the sensors 133, 144 to establish one or more criteria for determining whether or not the prescribed injection is associated with extravasation. The processor 161 is also operable to use the prescribed injection signals from the sensors 133, 144 and the aforesaid one or more criteria (possibly in combination with other criteria)to determine whether or not there is extravasation in the subject 102 during the prescribed injection. By using the test injection signals to establish at least one criterion for distinguishing extravasating injections from non- extravasating injections, the processor 161 is able to compensate for artifacts in the signals from the extravasation sensor 133 caused by subject-to-subject variations, variations in the placement or operation of the extravasation sensor, and other variables that may change from one prescribed injection to the next.

[0030] In one particular embodiment of the invention, the processor 161 is operable to use the test injection signals to determine a relationship at least approximately relating measurement of the first parameter by the extravasation sensor 133 to measurement of the second parameter by the calibration sensor 144. The relationship may define the measurement of the first parameter by the extravasation sensor 133 as a function of a corresponding measurement of the second parameter by the calibration sensor 144, for example. One or more terms of the relationship may be determined by the processor 161 using the test injection signals from the calibration sensor 144 and the extravasation sensor 133.

[0031] One suitable relationship, for example, has the form:

Se = KI + (K2 x Sc), (Eq. 1)

[0032] wherein Se is the measurement of the first parameter by the extravasation sensor 133, Sc is the corresponding measurement of the second parameter by the calibration sensor 144, and K1 and K2 are constants. The processor 161 may be operable to apply any of various well known algorithms to the test injection signals from the sensors 133, 144 to determine values for the constants K1 and K2. Other equations are suitable for use in the present invention, as will be recognized in view of the foregoing by those skilled in the art.

10033] The processor 161 may be operable to use the relationship obtained by its analysis of the test injection signals to produce an expected result for measurement of the first parameter by the extravasation sensor 133 corresponding to the prescribed injection. For example, the processor 161 may be operable to plug prescribed injection signals received from the calibration sensor 144 into the relationship to determine the expected results from the extravasation sensor 133. The processor 161 may be operable to monitor the difference between the expected results and actual prescribed injection signals from the extravasation sensor 133 and to characterize the injection as an extravasating injection whenever that difference exceeds a threshold amount. However, the processor may also give some weight to other criteria, including one or more criteria that are not based on information from the test injection within the scope of the invention.

[0034] The processor 161 may be operable to activate an extravasation alarm (e.g., display a visual warning and/or sound an auditory warning) and/or interrupt the injection system 101 to limit the severity of the extravasation if it determines that there is extravasation in the subject 102. In Fig. 1 , for example, the extravasation alarm comprises an LED warning light 165 controlled by the processor 161. Further, the injector 109 in Fig. 1 is at least partially under the control of the processor 161 so that the processor can automatically shut the injector off (e.g., by interrupting power supplied to the motor 117 via a power line 167) to limit extravasation of additional fluids.

[0035] To use the injection system 101 , a health care provider inserts the needle 143 into the subject 102 with the aim of positioning the tip 141 of the needle (and the outlet 175 defined thereby) in the target blood vessel 103. The health care provider also positions the extravasation sensor 133 to measure the first parameter, suitably along the target blood vessel 103 within a few centimeters of the injection site. In the embodiment shown in Fig. 1, for instance, the health care provider applies the extravasation sensor 133 to the subject's skin to overlie the target blood vessel 103 (using an estimated position of the target blood vessel if no other information is available). The extravasation sensor 133 is suitably positioned remotely from the injection site (e.g., more than five centimeters from the injection site as shown in Fig. 1 ) to allow manual palpation of the injection site by the health care provider. The position of the outlet 175 in the subject 102 generally defines the location of the injection site. It will be recognized that the outlet 175 is commonly positioned upstream or downstream in the target blood vessel 103 relative to the site where the injection line 121 enters the subject 102. For example, it is common practice to orient a hypodermic needle so that it is inclined only slightly relative to the orientation of a target blood vessel because this facilitates positioning the tip of the needle in the target blood vessel. Thus, the outlet 175 of the needle 143 may be positioned slightly upstream or downstream in the target blood vessel 103 relative to the point of entry into the subject. An injection could also be conducted with a flexible catheter (not shown) at the end of the injection line rather than the needle 143. Further, some catheters can be used to thread the injection line through the target blood vessel 103 to position the outlet at a location that is several centimeters or more from the point of entry into the subject. If this is the case, the extravasation sensor 133 can be positioned as needed to maintain the same (or a similar) position relative to the injection site.

[0036] The health care provider also positions the calibration sensor 144 to measure the second parameter, if necessary. In the embodiment shown in Fig. 1 , the calibration sensor 144 is installed in the needle 143 so there is no need to attend to positioning the calibration sensor other than by inserting the needle into the subject 102. However, there may be a need for the health care provider to position the calibration sensor 144 separately, such as if the extravasation detector is a stand-alone unit.

[0037] After setup of the injection system 101 and extravasation detection system 131 is complete, the test medium is injected into the subject 102 with the aim of injecting the test medium into the target blood vessel 103. In one embodiment, for instance, the health care provider injects the test medium into the injection iine 121 using the access port 106 shown in Fig. 1 , thereby delivering the test medium into the subject 102 through the needle 143. In other embodiments, the injection system is operated in flush mode to inject the test medium into the subject 102. During the test injection, the health care provider may manually palpate the tissue surrounding the injection site to help confirm that the test medium was injected into the target blood vessel 103 and did not result in extravasation.

[0038] The extravasation and calibration sensors 133, 144 measure the first and second parameters, respectively, during the test injection and transmit the test injection signals to the processor 161. In one embodiment, measurement of the first parameter comprises measuring at least one of the following: a tissue firmness of the subject 102, an amount of tissue swelling of the subject, a characteristic of electromagnetic radiation (e.g., light) reflected by or emanating from the subject, a temperature of the subject, a characteristic of ultrasound reflected from inside the subject, and an electrical characteristic of the subject. For instance, in the embodiment shown in Fig. 1 the extravasation sensor 133 measures an electrical impedance/conductance of the subject 102. Measurement of the first parameter is preferably conducted at a location that is remote from the injection site (e.g., more than five centimeters away from the outlet 175). Likewise, in the embodiment shown in Fig. 1 , the calibration sensor 144 measures a pressure in the injection line 121 adjacent the outlet 175.

[0039] The processor 161 uses the test injection signals to establish one or more criteria that witl to be used to determine whether or not the prescribed injection is associated with extravasation in the subject 102. For example, in the example of the processor 161 discussed above, the processor determines a relationship at least approximately relating measurement of the first parameter to measurement of the second parameter. In one embodiment, operation of the processor 161 includes defining the first parameter as a function of the second parameter, using a curve fitting algorithm, a look-up table, or other suitable methods known in the art to determine one or more terms of the relationship (e.g., the values for K1 and K2 appearing in equation 1) from the test injection signals. The relationship of the first and second parameters during the prescribed injection should be consistent with observations during the non-extravasating test injection, as indicated by the test injection signals from the sensors 133, 144. Failure of the measurements of the first and second parameters to maintain the same relationship during the prescribed injection can be a sign of extravasation.

[0040] After the test injection, the injection medium (e.g., contrast medium) is injected into the subject 102, suitably (but not necessarily) through the same outlet 175 used for the test injection (e.g., through the same needle 143 and at least a portion of the same injection line 121 , as is apparent in Fig. 1 ) to reduce the number of variables that are likely to vary between the test injection and the prescribed injection. For instance, in the injection system 101 of Fig. 1 , the motor 117 drives the piston 119 into the syringe barrel 113 to expel the injection medium from the reservoir 111 through the injection line 121 and into the subject 102. If desired, the health care provider can manually palpate the tissue surrounding the injection site during the prescribed injection.

[0041] During the prescribed injection, the extravasation and calibration sensors 133, 144 measure the first and second parameters, respectively, and transmit the prescribed injection signals to the processor 161. The processor 161 determines whether or not there is extravasation in the subject 102 using the prescribed injection signals from the sensors 133, 144. For example, in one embodiment, the processor 161 calculates one or more expected results from the extravasation sensor 133 by plugging one or measurements of the second parameter as indicated by the prescribed injection signals received from the calibration sensor 144 into the relationship. If the difference between the expected results and actual prescribed injection signals from the extravasation sensor 133 exceeds a threshold amount, this indicates that there may extravasation in the subject 102. The processor 161 may characterize the prescribed injection as an extravasating injection whenever the difference between the expected and actual results of measurement of the first parameter by the extravasation sensor 133 exceeds the threshold amount. However, in other embodiments additional criteria, including criteria determined without reference to the test injection, are given some weight in determining whether or not there is extravasation in the subject. Examples of such additional criteria include measurements from other extravasation sensors, predetermined standards for an absolute maximum or minimum of measurement of the first parameter by the extravasation sensor 133, information about the subject 102 (e.g., the subject's age).

[0042] If the processor 161 detects extravasation in the subject 102, it suitably activates the alarm system (e.g., light the LED warning light 165, in Fig. 1 ) and/or interrupts the injection system (e.g., cuts supply of power to the motor 117 via the power line 167).

[0043] Another embodiment of the invention is shown in Fig. 2. !n this embodiment, the calibration sensor 144 is a pressure sensor connected to the fluid delivery system 105 of the injection system 101 at a point upstream of the outlet 175 in the fluid flow path 107 rather than adjacent the outlet in the needle 143. When the calibration sensor 144 measures the second parameter, it measures fluid pressure in the injection line 121. Otherwise, the injection system 101 and extravasation detection system 131 is constructed and operates in substantially the same way as described above in connection with the embodiment of Fig. 1. It wili be recognized from the foregoing, that the pressure sensor 144 can be positioned elsewhere in the injection system 101 , including anywhere along the injection line 121 without departing from the scope of the invention.

[0044] Although the extravasation sensor 133 shown in Figs. 1 and 2 and described above is relatively simple, more sophisticated sensors can be used to obtain desirable results. For example, Figs. 3 and 4 illustrate an electrical impedance tomography extravasation sensor 240 that is suitable for use in the extravasation detection system 131 in accordance with another embodiment of the invention. Figure 3 is a schematic cross section of the subject's limb 181 and the sensor 240. The electrical impedance tomography sensor 240 replaces the extravasation sensor 133 shown in Figs. 1 and 2 and is connected to the processor 161 in a similar manner. The electrical impedance tomography sensor 240 includes a plurality of electrodes 244 spaced {e.g., substantially equidistantly) at intervals circumferentially around at least a part of the subject's limb 181. The electrodes can be applied individually to the subject 102 or provided in a band (e.g., an armband) designed to wrap around the subject's limb 181. The electrodes 244 work in cooperation with one another to localize impedance characteristics inside the subject 102. For example, small high frequency electrical currents can be fed sequentially through pairs of the electrodes 244 and the voltages at the other electrodes recorded. The voltages recorded at the electrodes 244 can be input into a back-projection algorithm to generate an impedance image of the slice of the limb 181 surrounded by the electrodes 244. The processing required to generate an impedance image is similar to the processing used in CAT scans. Therefore, the electrical impedance tomography image processing techniques do not need to be described further herein. The sensor 240 can be considered a 2-D sensor in that the electrodes 244 are generally positioned along a common plane, which results in the sensor 240 detecting for the most part features located on (or at least in close proximity to) the common plane of the electrodes.

[0045] Figure 4 is a display of six outputs from the extravasation sensor 240 plotted as a function of time. Outputs Q1-Q4 in Fig. 4 correspond to the average impedance in corresponding sectors of the subject's limb 181 , (e.g., in each of four quadrants q1-q4 as labeled on Fig. 3). Together, the outputs Q1-Q4 represent a crude four pixel image of features of the limb 181 in cross section. Output C corresponds to the average impedance in the central portion of the subject's limb 181. There is some overlap between the central portion of the limb 181 represented by output C and the portions of the limb in the four quadrants q1-q4. Although the sectors q1-q4 of the limb 181 shown in Fig. 3 are depicted as being distinct, the sectors may also overlap one another within the scope of the invention. Output A on Fig. 4 is an average of outputs Q1-Q4 and C. It will be apparent to the skilled person that other suitable outputs could be obtained from the sensor 240 within the scope of the invention.

[0046] Referring to Fig. 4, time T1 marks the beginning of a prescribed injection. Before time T1 , the outputs Q1 -Q4, C, and A from the sensor 240 are at their baseline levels. After the injection begins however, some of the outputs, such as Q1 Q2, Q4, C, and A change because of impedance changes in the subject 102 caused by the prescribed injection. The impedance changes are indicated in Fig. 4 as increases in the height of the corresponding outputs on the graph over time. The impedance change in some of the quadrants (e.g., q1 as indicated by output Q1 ) may be consistent with a non-extravasating injection. On the other hand, the much larger increase in output Q4 is suspicious and may indicate extravasation. In fact, the data displayed in Fig. 4 was generated by an extravasating injection that resulted in a pool of extravasated injection medium, primarily located in the q4 quadrant of the limb 181. Thus, it is possible to base extravasation detection on whether or not any of the impedance changes indicated by one or more of the sensor outputs Q1-Q4, C, and A exceed a predetermined threshold.

[0047] However, there is some variation in the impedance response from the various sectors q1-q4 of the limb 181 to the injection. For example, the graph in Fig. 4 indicates there is very little impedance response to the injection in the q3 quadrant as indicated by output Q3. Further, the characteristics of the response of the outputs Q1-Q4, C, and A to a non- extravasating injection can vary significantly from one subject to the next. Thus, operation of the sensor 240 can be improved by using the test injection to establish criteria that can be used to distinguish the response of the extravasation sensor 240 to a successful non- extravasating injection from its response to extravasation.

[0048] Another embodiment of a self-calibrating extravasation detection system 131', which is substantiaily the same as described above except for the substitution of the extravasation sensor 240 for the extravasation sensor 133, is shown in Fig. 5. The processor 161 is operable to establish extravasation criteria for one or more of the outputs Q1-Q4, C, and A from the extravasation sensor 240 using the test injection signals as described above to facilitate identification of extravasation in the subject during the prescribed injection. For example, the processor 161 may be operable to determine one or more relationships relating measurement of the second parameter to one or more of outputs Q1-Q4, C, and A using the test injection signals from the extravasation sensor 240. The processor 161 can then monitor the prescribed injection signals from the calibration sensor 144 and calculate one or more expected results (e.g., expected outputs for one or more of Q1-Q4, C, and A) from the extravasation sensor 240 corresponding to the prescribed injection. If the difference between the expected results and the actual results indicated by the prescribed injection signals from the extravasation sensor 240 exceed a threshold amount, the processor 161 recognizes this as a sign indicative of extravasation and gives it at least some weight when determining whether or not there is extravasation.

[0049] The electrical impedance tomography sensor concept can be extended, as shown in Fig. 5, to further enhance extravasation detection. Figure 5 shows a new 3-D impedance tomography sensor 340, which includes a series of 2-D electrical impedance tomography extravasation sensors 240 (e.g., four sensors) distributed along the length of the target blood vessel 103. As depicted in Fig. 5, for instance, each of the 2-D sensors 240 may be substantially similar to the extravasation sensor 240 shown in Fig. 3 and described above. Each of the 2-D sensors 240 can also be operated in the same manner described above to generate a series of impedance images of the tissue slices enclosed by the electrodes 244 of the sensors at various locations along the limb 181 to detect extravasation. Further, alternatively or in addition to the impedance images of the tissue slices, the 2-D sensors 240 can be used together to obtain a 3-D impedance image of the subject's limb 181. For example, by averaging the outputs for Q1 taken for adjacent tissue slices by two adjacent 2-D sensors 240, the 3-D sensor 340 can assign an approximate impedance for the volume of tissue in the Q1 quadrant and bounded by the two adjacent 2-D sensors. Each such volume of tissue wilt be referred to as a "voxel," by analogy to a 2-D pixel. One voxei V is highlighted in Fig. 5. There are a total of twelve voxels in the embodiment shown in Fig. 5, Although the voxels shown in Fig. 5 are distinct, a 3-D impedance tomography sensor can be designed to have overlapping voxels within the scope of the invention. It will also be recognized that it may be desirable to ignore impedance measurement for some voxels (e.g., those on the side of the limb 181 opposite from the injection) that are less likely to be impacted by any extravasation that may occur. The processor 161 can use test injection signals from the extravasation sensor 340 to determine one or more criteria {e.g., on a voxel-by-voxel basis) to be used to determine whether or not there is extravasation in the subject and monitor for extravasation during the prescribed injection, in substantially the same manner described above for the outputs Q1-Q4, C, and A from the 2-D sensor 240.

[0050] Another new extravasation detector, generally designated 401 and shown in Fig. 6, will be described to provide yet another example of the capabilities of the self- calibrating extravasation detection system of this invention. The extravasation detector 401 comprises a U-shaped substrate 415, such as a flexible rubber pad or other support structure, sized and shaped so that the two generally parallel arms 417 of the substrate can be positioned on the subject 102 on opposite sides of the target blood vessel 103 as shown in Fig. 7. A plurality of optical sensors (e.g., an array of sensors) are embedded in the substrate 415 at intervals along its length. [0051] For example, in the embodiment shown in Figs. 6 and 7, three optical sensors 433, 433', and 433" are embedded in the substrate. Each of the optical sensors shown in Fig. 6 includes an emitter 435, 435', 435" (e.g., an infrared emitting LED or diode laser) that emits electromagnetic radiation and a detector 437, 437', 437" that detects electromagnetic radiation incident on the detector. The emitters 435, 435', 435" are arranged in the substrate 415 to direct light into the subject 102 and the detectors 437, 437', 437" are arranged in the substrate to detect light from inside the subject. The detected light may be light that has been reflected from inside the subject 102 or light that was emitted inside the subject {e.g., fluorescent light) in response to the lighted directed into the subject by the emitters. The emitters 435, 435', 435" are embedded in one arm 417 of the substrate 415 and the detectors 437, 437', 437" are embedded in the other arm so that the emitters can be positioned on the subject 102 on one side of the target blood vessel 103 while the detectors are on the opposite side of the target blood vessel 103. The number of sensors in the substrate 415 can vary, and may include up to eight emitter detector pairs or more. Because the sensors are embedded in the same substrate 415, application of multiple extravasation sensors to the subject is facilitated. Further, the substrate 415 maintains a desired spacing of the sensors 435, 435', 435" relative to one another, thereby further facilitating use of multiple sensors to detect extravasation.

[0052] The extravasation detector 401 also comprises a disposable barrier 441 that is positioned between the substrate 415 and the subject 102 when the extravasation detector is being used. The disposable barrier 441 is suitably a transparent sterile film similar in shape to the substrate 415. The barrier 441 has a peripheral outline that is suitably significantly larger than the peripheral outline of the substrate 415. Also as shown in Fig. 6, the barrier 441 is suitably constructed to have a plurality of detents 445 (e.g., nipples) configured to snap into pockets 447 in the substrate 415 to releasably connect the barrier to the substrate and maintain registration between the substrate and the barrier during use with the subject 102. After use, the disposable barrier 441 can be removed, discarded, and replaced with a new barrier (not shown) to alleviate concerns about sanitation associated with reuse of the extravasation detector 401 with another subject.

[0053] Referring again to Fig. 6, the extravasation detector 401 may include several features to increase convenience of using the detector. A proximity sensor 451 is optionally embedded in the substrate 415 of the extravasation detector 401 (e.g., at the base of the U- shaped pad) to sense when the sensor side of the substrate 415 is in close proximity to another object disable operation of the emitters 435, 435', 435" unless the substrate is placed emitter side down on a surface (e.g., placed on the subject 102). This may be desirable to prevent the emitters 435, 435', 435" from emitting light into open space, particularly if the emitters are infrared lasers that emit invisible laser beams. The extravasation detector 401 may also include an indicator light 455 (e.g., LED) that indicates whether or not the emitters 435, 435', 435" are emitting light. This may be particularly desirable when the emitters 435, 435', 435" emit light that is outside the visible spectrum. Further, al! electrical wiring 461 required to operate the emitters 435, 435', 435", detectors 437, 437', 437", the proximity sensor 451 , and the indicator light can be embedded in the substrate 415 {e.g., by being molded into the substrate) as shown in Fig. 6. The wiring 461 in the substrate can feed into a single electrical line 163 connecting the extravasation detector 401 to the processor 161 in the same manner as the extravasation sensor 133 described above.

[0054] Figure 7 shows another embodiment of a self-calibrating extravasation detection system 131", which is substantially the same in construction and operation as the extravasation detection system 131 described above except that the extravasation sensor 133 has been replaced with the extravasation detector 401. In use, each of the extravasation sensors 433, 433', 433" measures an optical characteristic of the subject 102 at a different location (e.g., along the length of the target blood vessel) during the test injection and prescribed injection. Further, each of the sensors 433, 433", 433" sends test injection signals and prescribed injection signals indicative of the measured optical characteristic to the processor 161. The processor 161 uses the test injection signals to determine one or more extravasation criteria for each of the sensors 433, 433', 433", as described above. In one particular embodiment, for example, the processor determines for each sensor 433, 433', 433" a relationship (e.g., similar to equation 1 ) relating measurement of the optical characteristic by the respective sensor to measurement of the second parameter by the calibration sensor 144. The processor 161 then plugs measurements from the calibration sensor 144 as indicated by the prescribed injection signals from the calibration sensor into the respective relationships to generate expected results for measurement of the optical characteristic by each of the sensors 433, 433", 433" at its location in the same manner described above. The processor 161 uses the expected results are used as the basis for extravasation detection criteria and monitors outputs from the sensors 433, 433', 433" during the prescribed injection to detect any extravasation in the subject 102 in substantially the same manner described above.

[0055] It will be apparent from the foregoing to the skilled person that many different kinds of extravasation sensors can be used in the present invention. Further the invention can be used to monitor for extravasation during injections into various different body parts of the subject. Likewise, it is possible to use the extravasation detection system to monitor for extravasation during a manual injection that is conducted with any automated injectors.

[0056] When introducing elements of the present invention or the preferred embodiments thereof, the articles "a", "an", "the", and "said" are intended to mean that there are one or more of the elements. The terms "comprising", "including", and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.

[0057] As various changes could be made in the above constructions and methods without departing from the scope of the invention, it is intended that all matter contained herein and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

Claims

What is claimed is:

1. An extravasation detection system for use in an injection process in which an injection system is used to conduct a test injection during which a test medium is injected into a subject and then to conduct a prescribed injection during which an injection medium is injected into the subject, the extravasation detection system comprising: an extravasation sensor for measuring a first parameter during the test injection and during the prescribed injection and outputting test injection signals and prescribed injection signals, respectively, representative of the first parameter, the first parameter being indicative of a potential extravasation in the subject; a calibration sensor for measuring a second parameter during the test injection and during the prescribed injection and outputting test injection signals and prescribed injection signals, respectively, representative of the second parameter, the second parameter being indicative of a condition in at least one of a target blood vessel in the subject and the injection system; and a processor operable to receive the test injection signals and prescribed injection signals from the extravasation and calibration sensors, the processor having at least one of instructions and circuitry for: (A) confirming the potential extravasation of the injection medium using the test injection signals received from the calibration and extravasation sensors; (B) confirming the potential extravasation of injection medium using the prescribed injection signals from the calibration and extravasation sensors and said one or more criteria; and (C) performing an action if the processor determines that the injection medium is being extravasated, wherein the action is selected from the group consisting of (i) activating a warning system; and (ii) interrupting the injection system.

2. An extravasation detection system as set forth in claim 1 , wherein the calibration sensor is a pressure sensor for measuring a fluid pressure in at least one of the injection system and the target blood vessel.

3. An extravasation detection system as set forth in claim 2 in combination with the injection system, wherein the calibration sensor is connected to the injection system.

4. An extravasation detection system and injection system in combination as set forth in claim 3, wherein the injection system comprises an injection line defining at least part of a flow path for flow of the test medium and injection medium into the subject, the calibration sensor being positioned along the injection line.

5. An extravasation detection system and injection system in combination as set forth in claim 4, wherein the injection iine has an outlet at one end for delivery of the injection medium and test medium into the subject, the calibration sensor being positioned adjacent the outlet.

6. An extravasation detection system as set forth in claim 1 , wherein said at least one of said instructions and circuitry comprises instructions or circuitry for: (i) determining a relationship between the measurement of the first parameter by the extravasation sensor to the measurement of the second parameter by the calibration sensor, the relationship being determined using the test injection signals received from the extravasation and calibration sensors; and (ii) using the prescribed injection signals received from the calibration sensor and said relationship to determine an expected result for measurement of the first parameter by the extravasation sensor corresponding to injection of the injection medium into the subject, said one or more criteria including a criterion based on said expected result.

7. An extravasation detection system as set forth in claim 6, wherein said relationship defines the first parameter as a function of the second parameter.

8. An extravasation detection system as set forth in claim 7, wherein the relationship has the form:

Se = K1 + (K2 x Sc),

wherein Se is the first parameter, Sc is the second parameter and K1 and K2 are constants.

9. An extravasation detection system as set forth in claim 8, wherein said at least one of instructions and circuitry comprises instructions or circuitry for determining K1 and K2 using the test injection signals from the extravasation and calibration sensors corresponding to injection of the test medium.

10. An extravasation detection system as set forth in claim 6, wherein the extravasation sensor is a first extravasation sensor, the system further comprising one or more additional extravasation sensors for taking one or more additional measurements of the first parameter to obtain measurements of the first parameter at multiple locations, the additional extravasation sensors being operable to output test injection signals and prescribed injection signals representative of the first parameter to the processor, and wherein said at least one of instructions and circuitry further comprises instructions or circuitry for: (D) determining additional relationships at ieast approximately relating measurement of the first parameter by said one or more additional extravasation sensors, respectively, to measurement of the second parameter by the calibration sensor, wherein one or more terms of each of the additional relationships are determined using test injection signals received from said one or more additional extravasation sensors, respectively, and the calibration sensor; and (E) determining additional expected results for measurement of the first parameter by the one or more additional extravasation sensors, respectively, using the prescribed injection signals received from the calibration sensor and said additional relationships, said one or more criteria including criteria based on said additional expected results.

11. An extravasation detection system as set forth in claim 10, wherein the first extravasation sensor and said one or more additional extravasation sensors are arranged in an extravasation sensor array configured to measure the first parameter at multiple locations along the target blood vessel.

12. An extravasation detection system as set forth in claim 1 , wherein the extravasation sensor comprises a sensor selected from the group consisting of mechanical transducers, optical sensors, thermal sensors, microwave sensors, pressure sensors, and electrical impedance sensors.

13. A method of detecting potential extravasation, the method comprising: using an injection system to inject a test medium into the subject to confirm that the injection system is injecting into a target blood vessel and then using the injection system to inject an injection medium into the subject to deliver the injection medium to the target blood vessel; measuring first and second parameters during injection of the test medium into the subject and during injection of the injection medium into the subject, the first parameter being indicative of whether or not there is extravasation in the subject, the second parameter being indicative of a condition in at least one of the injection system and the target blood vessel; establishing one or more criteria for determining whether or not the injection of the injection medium is associated with extravasation in the subject using the measurements of the first and second parameters corresponding to injection of the test medium into the subject; and determining whether or not the injection of the injection medium is associated with extravasation in the subject using the measurements of the first and second parameters corresponding to injection of the injection medium into the subject and said one or more criteria.

14. A method as set forth in claim 13, wherein the measuring of the second parameter comprises measuring a fluid pressure in at least one of the injection system and the target blood vessel.

15. A method as set forth in claim 14, wherein the test medium and injection medium are injected into the subject at an injection site, the measuring of the fluid pressure comprising measuring the fluid pressure at a location adjacent the injection site.

16. A method as set forth in claim 14, wherein the test medium and injection medium are injected into the subject at an injection site, the measuring of the fluid pressure comprising measuring the fluid pressure in the injection system at a location upstream from the injection site.

17. A method as set forth in claim 13, wherein the test medium and injection medium are injected by the injection system into the subject at an injection site, the measuring of the first parameter comprising measuring the first parameter at a location that is more than about five centimeters away from the injection site.

18. A method as set forth in claim 13, wherein the establishing comprises: (A) determining a relationship between the measurement of the first parameter to measurement of the second parameter, one or more terms of the relationship being determined using the measurements of the first and second parameters corresponding to injection of the test medium into the subject; and (B) using a measurement of the second parameter corresponding to injection of the injection medium and said relationship to calculate an expected result for measurement of the first parameter by the extravasation sensor during the injection of the injection medium into the subject, said one or more criteria including a criterion based on said expected result.

19. A method as set forth in claim 18, wherein determining the relationship comprises defining the first parameter as a function of the second parameter.

20. A method as set forth in claim 19, wherein the relationship has the form:

Se = K1 + (K2 x Sc), wherein Se corresponds to the first parameter, Sc corresponds to the second parameter and K1 and K2 are constants.

21. A method as set forth in claim 20, wherein the determining of the relationship comprises using the measurements of the first and second parameters corresponding to injection of the test medium to determine values for K1 and K2.

22. A method as set forth in claim 18, wherein the measuring of the first parameter during the injection of the test medium and during injection of the injection medium each comprises measuring the first parameter at a plurality of different locations in the subject, the method further comprising: (C) determining the relationships at least approximately relating measurement of the first parameter at multiple ones of the plurality of locations, respectively, to measurement of the second parameter, wherein one or more terms of each of the relationships are determined using the measurement of the first parameter during injection of the test medium corresponding to the respective location and the measurement of the second parameter corresponding to injection of the test medium; and (D) using the measurement of the second parameter corresponding to injection of the injection medium and said relationships to calculate additional expected results for measurement of the first parameter at the multiple locations, said one or more criteria including a criterion based on said additional expected results.

23. A method as set forth in claim 13, wherein measuring the first parameter comprises measuring at least one of the following a tissue firmness of the subject, an amount of tissue swelling of the subject, a characteristic of electromagnetic radiation reflected by or emanating from the subject, a temperature of the subject, a characteristic of ultrasound reflected from inside the subject and an electrical impedance of the subject.

24. A method as set forth in claim 13, wherein injecting the injection medium comprises injecting a contrast medium.