WO2002043789A2

WO2002043789A2 - Multi-site thermographic profiling catheter

Info

Publication number: WO2002043789A2
Application number: PCT/US2001/044513
Authority: WO
Inventors: Neville Crawford
Original assignee: Gmp|Vascular, Inc.
Priority date: 2000-11-29
Filing date: 2001-11-28
Publication date: 2002-06-06
Also published as: WO2002043789A3; AU2002239365A1

Abstract

Catheter-based devices (10) for measuring tissue temperature at a number of sites. In particular, the present invention relates to catheter-based devices (10) that are able to measure tissue temperature and thermal heterogeneity in the tissue to help determine the presence of inflammation of the tissues. In addition, the present invention relates to catheter devices that, if used in arteries, veins, or compartments of the heart to measure tissue temperature, do not seriously compromise blood flow through the vessel during the measurement.

Description

l o MULTI-SITE THERMOG APHIC PROFILING CATHETER

FIELD OF THE INVENTION

The present invention relates in general to devices for

15 measuring vessel tissue temperature. In particular, the present invention relates to catheter-based devices that are able to measure vessel wall temperature and thermal heterogeneity in the tissue to help determine the presence of inflammation of the vessel tissues. In addition, the present invention relates to catheter-based devices, 0 which if used in arteries, veins, or compartments of the heart to measure vessel tissue temperature, do not seriously compromise blood flow through the vessel during the measurement.

BACKGROUND OF THE INVENTION

25 Inflammation in tissues, and particularly in regions where activated macrophages have accumulated, can result in detectable localized increases in tissue temperature. Inflammatory processes are believed to have a role in the pathogenesis of coronary artery disease. It is known that inflammatory foci

30 associated with mononuclear leukocyte infiltration and localized areas of calcification can all contribute to the temperature heterogeneity observed in thermographic scanning of solid tumors.

Evidence of thermal heterogeneity in the walls of human carotid arteries with atherosclerotic plaques has also been

35 shown. Stefanadis et al. (1999) Circulation, 99: 1965-1971. This evidence has led to the postulation that the detection of heat produced by macrophages and other cellular clusters in atherosclerotic lesions may be predictive of a potential vulnerability to plaque rupture and thrombosis.

The temperature of human coronary arteries has been rarely studied in vivo but a recent publication has revealed significant heterogeneity in the surface wall temperatures of atherosclerotic vessels as compared with healthy vessels. Stefanadis et al. at 1965. Accordingly, while the vessel wall temperature of normal coronary arteries was fairly uniform and within a narrow range, the thermal heterogeneity observed in the walls of arteries of patients with coronary artery disease increased progressively from those with stable angina through unstable angina to patients with acute myocardial infarction. Stefanadis et al. at 1965.

In this latter study, temperature readings were made using a single catheter mounted thermistor probe pressed against the vessel wall by the force of the blood flow acting on a small hydrofoil. One limitation of the hydrofoil type themiography catheter lies in the fact that multiple simultaneous temperature readings over a suspect area of a vessel wall cannot be taken. Repositioning the device is required for each new reading. A further shortcoming of the device is the difficulty of maintaining good positive contact between the sensor head and the vessel wall. Balloon mounted thermistors can obviate this particular localization problem, but their value is limited because the vessel is occluded by the balloon during measurement. In addition to the ischaemic risk, the presence of the balloon perturbs the normal tissue to blood heat transfer process, which can result in artefactaul readings.

Accordingly, what are needed are devices for measuring vessel wall temperatures in a safe and effective manner. What is further needed are devices for measuring tissue surface temperatures simultaneously at a plurality of sites. These devices should also be capable of measuring vessel wall temperature in an accurate manner without occluding blood flow, and thus reduce or prevent the ischaemic risk associated with the use of the device. SUMMARY OF THE INVENTION

The present invention is directed to devices for measuring the temperature of tissues within a bodily vessel, such as a coronary artery. These devices are capable of measuring vessel tissue temperature in an accurate manner without occluding the flow of bodily fluids within the vessel. In a preferred embodiment of the present invention, the vessel is a vein or artery and the bodily fluid is blood. The present invention also comprises devices capable of measuring tissue temperatures simultaneously over a diffuse area of a vessel.

In particular, the present invention relates to catheter- based devices comprising a support catheter and a cylindrical printed circuit board (PCB) sheet comprising one or more temperature measurement devices, wherein the cylindrical PCB sheet surrounds the support catheter. The catheter-based devices of the present invention are able to measure vessel tissue temperature and thermal heterogeneity in the vessel to help determine the presence of inflammation of the vessel tissues. In general, inflammation in tissues, and particularly in regions where activated macrophages have accumulated, can result in detectable increases in tissue temperature. Accordingly, the present invention can be used to measure the vessel tissue temperature and to determine any vessel wall temperature heterogeneity that may indicate the presence of inflammation, such as that associated with coronary artery disease or atherosclerotic changes predisposing to coronary artery disease. In addition, the present invention can be used in arteries, veins, or compartments of the heart to measure tissue temperature without compromising blood flow through the vessel during the measurement. The present invention can also be used in the diagnosis and/or prognosis of cancer through thermographic profiling of the luminal surface of other bodily vessels. The device can be used in any bodily vessel or orifice without obstructing the normal flow of fluids or gases therein.

The present invention has many different utilities. The device of the present invention may be used for thermographic profiling. The thermographic profiling of atherosclerotic vessels before percutaneous transluminal angioplasty (PTCA) or stent deployment is a relatively simple and low risk procedure that can provide an assessment of the likelihood of plaque rupture as well as the potential for the occurrence of late restenosis. The multi-site thermographic catheter of the present invention is valuable for cardiovascular research and in clinical investigations of patients with various stages of coronary heart disease. The present invention is also valuable for identifying the most suitable areas of vessel wall tissue for anastomosis during emergency by pass surgery. The present invention provides a collection of information about the inflammatory aspects of the pathogenesis of atherosclerosis, and particularly the role of (heat producing) macrophages known to be actively recruited to vessel wall lesions. A more detailed understanding of the interplay between these macrophage clusters and other cells in the circulation and in the vessel wall and the stimulated cytokine release that occurs can be used to help develop new treatment modalities for vessel wall disease. For example, vessel wall temperature measurement can be used to discriminate between stable and unstable atherosclerotic plaques. Such information would be of great value in risk assessment preparatory to interventional cardiology or coronary artery bypass surgery.

The present invention is also particularly applicable for surface mapping of the temperature of a vessel wall by simultaneous measurements made at multiple sites in both normal and lesion areas of the vessel to provide important comparative information. For example, the device may be used to determine the role of inflammation and mononuclear cell infiltration in the pathogenesis of atherosclerosis. The device can also be used to detect the presence of atherosclerotic plaques and to assess their microstructural stability and the likelihood of their rupture during interventional procedures or cardiac surgery. The device can be used during surgical reconstruction to avoid any regions of an artery that might result in insecure anastomosis. Additionally, the device can be used for the detection of localized perturbation of blood flow patterns. Also, the presence of plaque-associated platelet aggregates resulting from potentially life-threatening changes in plaque integrity can be detected. The device can also be used to determine whether treatment regimes with, anti- inflammatory drugs, such as aspirin or NSAID, for example, are associated with a decrease in lesion temperature heterogeneity. Furthermore, the invention provides a multi-site thermographic catheter that can be used in scanning tumor tissues. Therefore, the invention provides a diagnostic aid and a device for closely monitoring the effects of a therapeutic regime.

Accordingly, it is an object of the present invention to provide devices for measuring bodily vessel tissue temperature.

It is another object of the present invention to provide devices for measuring the thermal heterogeneity in a bodily vessel by simultaneous multi-site measurement of the vessel wall tissue temperature. It is another object of the present invention to provide devices that can be used to measure tissue temperature and thermal heterogeneity of the tissue without severely compromising blood flow within the vessel. More accurate measurements within blood vessels are then possible without the risk of ischaemia of nearby tissues.

These and other objects, features and advantages of the present invention will become apparent after a review of the following detailed description of the disclosed embodiments and the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows a catheter-based device for tissue temperature measurement according to its relaxed position. Figure la is an illustrative side view of a catheter-based device in its relaxed position.

Figure 2 shows a catheter-based device of the present invention for tissue temperature measurement according to its expanded position. Figure 2a is an illustrative side view of a catheter-based device in its expanded position. Figure 3 shows a composite detailed diagram of a PCB sheet (illustrated in flat form prior to mounting as a cylinder on the support catheter body) with four thermistor sensors arranged according to a preferred embodiment of the present invention.

Figure 4 shows a cross-sectional view taken along line 1A-1A of the catheter-based device of Figure 1.

Figure 5 shows a composite detailed diagram of a PCB sheet (illustrated in flat form prior to mounting as a cylinder on the catheter body) with eight thermistor sensors arranged according to another preferred embodiment of the present invention.

Figure 6 is a cross sectional view of a preferred PCB sheet showing the constituent layers.

DETAILED DESCRIPTION

The present invention is directed to catheter-based devices for measuring the tissue temperature within a bodily vessel. As used herein, the term "catheter-based device" 10 refers to a device comprising a support catheter 20 and a cylindrical PCB sheet 70 comprising one or more temperature measurement devices 40, wherein the cylindrical PCB sheet 70 surrounds the support catheter 20. As also used herein, the terms "bodily vessel" and "vessel" are interchangeable and include, but are not limited to, an artery, a vein, a compartment of the heart and a compartment of any other organ of the body. In a preferred embodiment, the bodily vessel is an artery or a vein. The catheter-based devices of the present invention can be used in a bodily vessel to measure the tissue temperature of the vessel without seriously compromising blood flow through the vessel during the measurement.

In particular, the present invention relates to catheter- based devices that are able to measure tissue temperature and thermal heterogeneity in the bodily vessel tissues to help determine the presence of inflammation in the tissues. It should be understood that as used herein, the term "tissues" refers to the tissues that comprise and/or line a bodily vessel. The catheter- based devices comprise a PCB sheet 70 formed into a cylinder containing a lumen. In one embodiment of the present invention, the PCB sheet 70 comprises a polyimide backing 102, a copper overlay 106 and a gold coat 108. The catheter-based devices of the present invention also comprise one or more temperature measurement devices 40.

Importantly, the present invention provides a catheter- based device that avoids occluding the vessel during measurement of tissue temperature in the vessel, and thus reduces the ischaemic risk associated with prior art devices. The catheter-based device is able to achieve these results because the catheter-based device is a cylindrical PCB sheet that is capable of expanding upon its introduction into the vessel. This expansion also allows the device to maintain a good positive contact between the one or more temperature measuring devices and the tissue to be measured. In one embodiment of the present invention, the catheter-based device is a cylindrical PCB sheet 70 having a plurality of slots 90, wherein the plurality of slots 90 allow the catheter-based device to be expanded into a "Chinese lantern" configuration. Figure 2 shows a catheter-based device expanded into a Chinese lantern configuration. In a further embodiment of the present invention, at each end of the cylinder each slot 90 terminates in a rounded opening 92, which prevents tearing upon expansion of the catheter- based device 10. When the catheter-based device 10 is expanded into a Chinese lantern configuration, the strips of PCB material between the slots 90 (herein referred to as PCB tapes) 24 separate and expand outward from the lumen of the catheter-based device 10. Expansion of the catheter-based device into the Chinese lantern configuration in a vessel results in a close juxtaposition of the middle region of the PCB tapes and the blood vessel wall.

Blood can flow through the tape interstices without occlusion of the fluid flow in the vessel.

In one embodiment of the present invention, a plurality of temperature measurement devices 40 are located on the PCB tapes 24. Each temperature measurement device 40 has a pair of electrical leads 50, 52, the first member of the pair of electrical leads 50 terminates at one end of the PCB sheet 70 and is connected to a rotary series of connectors 60 and the second member of the pair of electrical leads 52 is connected at the other end of the PCB sheet 70 to a common electrical lead 80. In one embodiment of the present invention, the plurality of temperature measurement device 50, 52 are integral to the PCB sheet 70 and are etched into a copper coating 106 on the PCB sheet 70. The term "temperature measurement devices" includes, but is not limited to, thermistor sensors. In one embodiment of the present invention, the thermistor sensors are reverse leakage semi conductor thermistors. In a preferred embodiment, the temperature measurement devices 40 are mounted on the PCB tapes 24 such that the devices protrude slightly from the PCB tapes 24. This slight protrusion facilitates a good positive contact with the tissue to be measured when the catheter-based device is expanded. In a further embodiment of the present invention, the center of the group of temperature measurement devices 40 is located approximately in the middle region of the PCB tapes 24.

As described above, the catheter-based device can be used to provide for simultaneous measurement of tissue temperatures at a number of sites on a vessel wall when a plurality of temperature measurement devices are integral to the catheter- based device. Therefore, in one embodiment of the present invention, a catheter-based device 10 comprises a plurality of temperature measurement devices 40. In a preferred embodiment, the temperature measurement devices 40 are located on the PCB tapes 24. It is to be understood that one or more temperature measurement devices can be located on any one or more of the PCB tapes. In a further embodiment, the catheter-based device 10 comprises four temperature measurement devices 40, each of the four devices being located on a different PCB tape 24. In a preferred embodiment, the temperature measurement devices 40 are thermistor sensors and the slotted PCB cylinder 16 contains five slots 90 and four PCB tapes 24. In another embodiment of the present invention, the catheter-based device 10 comprises eight temperature measurement devices 40, each of the eight devices being located on a different PCB tape 24. In a preferred embodiment, the temperature measurement devices 40 are thermistor sensors and the slotted PCB cylinder 16 comprises nine slots 90 and eight PCB tapes 24. It is to be understood that the spacing of the temperature measurement devices 40 may be varied in accordance with the needs of the particular catheter-based device.

The design of the catheter-based devices of the present invention may vary depending on the tissue to be investigated. However, since procedural simplicity and operator familiarity are important considerations, the catheter-based devices preferably resemble, in overall profile, a conventional over the wire balloon angioplasty catheter, but without the balloon. These catheter-based devices are capable of passing smoothly through a conventional introducer that is usually shaped at the distal end according to the target vessel anatomy. During insertion into the patient, the catheter-based device can be housed in a sheath to protect the plurality of electrical leads and temperature measurement beads on the PCB tapes until the measurement site is reached. When correctly positioned, the catheter-based device can be pushed out of the protective sheath and the PCB tapes expanded for close juxtaposition to the tissue. Similarly, for ease of withdrawal of the catheter-based device from the body, the catheter-based device can be re-housed in the sheath after relaxation of the PCB tapes.

In a preferred embodiment of the present invention, the catheter-based device comprises a polyimide/copper PCB sheet containing parallel slots 90, wherein the PCB sheet 70 is formed into a cylinder to fit around a support catheter body 20 and is held by ferrules 34, 36 at each end, wherein the device further comprises a plurality of temperature measurement devices 40 slightly protruding from the device and a plurality of pairs of temperature measurement device leads 50, 52 that are integral to the PCB sheet

70. In a further preferred embodiment, one of the ferrules is fixed and the other ferrule is moveable. When the moveable ferrule is moved toward the fixed ferrule, the parallel slots 90 produce a series of PCB tapes 24 that expand into a Chinese lantern configuration. In a still further preferred embodiment, the outer surface of each PCB tape 24 has a copper coating wherein the integral temperature measurement device electrical leads are etched. A thin layer of gold preferably covers the entire PCB sheet surface to prevent oxidation.

One feature of a preferred device is that the temperature measurement device electrical leads 50, 52 are an integral part of the slotted PCB cylinder 16 mounted on the support catheter body 20 and held by a fixed distal ferrule 34 and a moveable proximal ferrule 36. By moving the moveable proximal ferrule 36 towards the fixed distal ferrule 34, the PBC tapes 24 expand, and in this manner, the catheter-based device 10 can be deployed within a vessel so that about one third to one half of the middle region of the outer surface of the slotted PCB cylinder 16 with its integral thermistors and electrical leads is closely positioned against the tissue of the vessel.

In a preferred embodiment, the support catheter 20 has an internal lumen to take a guide wire for maneuverability, torque control and other desirable properties for the catheter. In another preferred embodiment, there are one or more smaller internal lumens in the support catheter 20 for wire leads to pass through the support catheter body to energize the temperature measurement devices 40. In this embodiment, these wire leads connect to a power supply and control unit sited outside the body. In both embodiments, the lumen wire leads that connect to the temperature measurement devices 40 pass through the proximal moveable ferrule 36. A preferred catheter-based device is set forth below.

Preferably, gold coated thermistor sensor leads are etched in a polyimide base of a PCB sheet 70. These thermistor sensor leads terminate in thermistor sensors arranged in an array on the middle region of the outer surface of the PCB tapes 24. The array may be any desired configuration, though a helical array is preferred. The number of thermistor sensors deployed on the device will vary depending on the size of the device and the size of the target tissue area to be measured. As set forth in further detail below, the device preferably includes four thermistor sensors, though the device may include six, eight or more thermistor sensors, as needed.

Within the proximal end ferrule 36 of the PCB sheet 70, all of the single leads from the thermistor sensors and the return common lead connecting all four thermistor sensors pass through lumens within the support catheter 20 to an electrical power supply and measuring unit at the proximal end 12 of the catheter-based device 10 that is located outside the patient's body. At the proximal end 12 of the catheter-based device

10, the thermistor sensor leads terminate in a ring of connectors, electrically arranged so that each of the thermistor sensors can be successively switched into the circuitry for temperature measurement. The temperature dependent change in each thermistor sensor resistance is processed in a multi-channel processor with appropriate computer software. The voltage change/temperature relationship is pre-determined for each thermistor sensor and this pre-calibration is fed into the multichannel processor for reference. As shown in Figure 1, the catheter-based device 10 has a proximal end 12 and a distal end 14. In one embodiment of the present invention, the proximal end 12 of the catheter-based device 10, in a position normally occupied by an angioplasty balloon, is a short (~ 4-6 cm) slotted PCB cylinder 16, mounted around and parallel to a support catheter body 20. The slotted PCB cylinder 16, comprises one or more thermistor sensors mounted on one or more PCB tapes 24. The PCB tapes 24 are formed by the slots 90 in the PCB sheet 70. The slotted PCB cylinder 16 additionally comprises thermistor sensor electrical leads that are etched into the PCB tapes 24. When the catheter-based device 10 is relaxed as shown in Figure 1, the PCB tapes 24 and thermistor sensor electrical leads lie close to the support catheter body 20 for ease in passing the device down an introducer, along a vessel, or in withdrawal of the catheter-based device 10 into the sleeve and out of the body after use.

As further shown in Figure 2, the PCB tapes 24 of the catheter-based device 10 can be expanded. The PCB tapes 24 are preferably expanded when the catheter-based device 10 is located in a bodily vessel. Since the middle region of the expanded PCB tapes 24 have the thermistor sensors mounted thereupon in one embodiment, a majority of the thermistor sensors are closely juxtaposed to the vessel tissue to be investigated. In a further preferred embodiment, this middle region of the PCB tapes 24 whereupon the thermistor sensors are mounted, is slightly thickened in order to facilitate uniform expansion of the PCB tapes 24. Although the PCB tape 24 array is radio opaque, positioning of the catheter-based device 10 in a vessel to be investigated may be further assisted by strategically positioning radio opaque markers integral to the support catheter body 20.

In one embodiment of the present invention, the ferrule rings 34, 36 hold the slotted PCB cylinder 16 in position on the support catheter 20. As used herein, the term "ferrule" refers to a ferrule ring. The ferrule rings 34, 36 may be made from any material such as metal or plastic. Both ferrule rings 34, 36 are bonded to the slotted PCB cylinder 20, but only the distal ferrule 34 is bonded to the support catheter 20. The ferrule 36 at the proximal end 12 is therefore able to move axially back and forth along the support catheter body 20.

In operation, the catheter-based device 10 is placed near the tissue to be investigated. When the catheter-based device 10 is in a position such that at least a portion of the PCB tapes 24 and thermistor sensors are adjacent to the vessel tissue to be investigated, the proximal ferrule ring 36 is moved toward the distal ferrule ring 34 resulting in an expansion of the PCB tapes 24. The degree of expansion of the PCB tapes 24 will depend on the bore of the artery, but such expansion is controlled so that the thermistor sensors press firmly on the vessel wall tissue. To affect expansion of the PCB tapes 24, the proximal end of the proximal ferrule 36 is held stationary using a close fitting outer guide catheter sleeve 38. The outer guide catheter sleeve 38 is sleeved over the support catheter body XX from the proximal end 12 until it abuts the proximal end of the proximal ferrule 36. While holding the outer guide catheter sleeve 38 in position against the proximal ferrule 36, the support catheter 20 is then slowly drawn back towards the proximal end 12. Movement of the outer guide catheter sleeve 38 toward the proximal end of the catheter-based device 10 while holding the proximal ferrule 36 stationary forces the PCB tapes 24 to expand outward from the support catheter 20 so that the thermistor sensors are pressed firmly against the vessel tissue to be investigated. This reciprocal manipulation of the support catheter 20 and outer guide catheter sleeve 38 can be pre-calibrated for different degrees of PCB tape 24 expansion appropriate to the vessel bore in the area to be investigated. If needed, the expansion/relaxation sequence may be mechanized using a motorized ratchet device that controls the movement of the support catheter 20. Additionally, in a further preferred embodiment, the catheter-based device has a guide wire lumen and has a smooth outer diameter profile in the thermistor region when relaxed that allows its introduction via a guide catheter.

One of the novel and important features of the present invention is that since the temperature measurement devices 40 are present in the middle region of the PCB tapes 24, after expansion of the PCB tapes 24, the temperature measurement devices 40 are positioned on the vessel wall or tissue. There are adequate open interstices in the remainder of the PCB tapes 24 closer to the support catheter body 20 for the bodily fluid to flow through the vessel during measurement. The catheter-based devices of the present invention are greatly advantageous over catheters having sensors positioned on the surface of an occlusive balloon in terms of reducing ischaemic risk.

As shown in Figures 3, 4 and 5, in one preferred embodiment of the present invention, the device uses a PCB sheet 70 as the base whereupon the temperature measurement devices 40 and temperature measurement device electric leads 50 reside. The

PCB sheet 70 comprises a base/metal sandwich. In a further preferred embodiment, the base is polyimide and the metal is copper. The present invention also encompasses PCB sheets wherein the metal of the base and metal sandwich includes, but is not limited to, gold, platinum, silver and titanium. In one embodiment, the base and metal sandwich is a rectangle with the short sides being of a length equal to the circumference of the support catheter 20 such that when the sheet is rolled into a cylinder to fit into the ferrules 34, 36 on the support catheter 20, there is no overlap. The length of the longer side of the rectangle is determined by the amount of PCB tape 24 expansion required for a particular application. In a further preferred embodiment, PCB tapes 24 are formed by making a series of parallel slots 90 in the middle region of a flexible rectangular PCB sheet 70. The slotted PCB is rolled into a cylinder and affixed to within the two ferrules of a support catheter body 20. The slots 90 do not extend the full length of the

PCB sheet, and an uncut connected region 94 is left at each end of the PCB sheet for fitting into the ferrules 34, 36. The distal ferrule 34 is fixed to the support catheter body 20 while the proximal ferrule 36 is free to move axially. In a further preferred embodiment, the temperature measurement device leads 50, 52 are etched into the metal of the base and metal sandwich. Each temperature measurement device is connected to a pair of electrical leads 50, 52 and the paired thermistor electrical leads are etched into the metal by a conventional procedure familiar to those skilled in the art of PCB manufacture. Preferably, the entire PCB is coated with a thin layer of gold on its upper metal surface.

In a preferred catheter-based device, the uncut connected region of the PCB sheet 92 described above contains electrical tracks that are etched to connect the first of each pair of the thermistor electrical leads and to connect the second of each pair of thermistor electrical leads to a separate position at the same end of the PCB sheet, thus creating a common lead 80. The areas of connection on the PCB sheet are termed "collecting plates". In a preferred embodiment, the collecting plates are oriented such that, when the PCB plate is rolled into a cylinder, the collecting plates are located at opposite sides of the catheter-based device. The commercial procedure for making such conductive tracks in the copper is familiar technology to those skilled in the art of integrated circuitry manufacture, minicomputer motherboard production and other forms of micro circuitry instrumentation. The thermistor electrical leads may be coated with a thin layer of gold after production if desired. This coating prevents oxidation processes occurring on the electrical leads that affect their efficiency. In one embodiment of the present invention, PCB tapes 24 have a plurality of temperature measurement devices 40 mounted thereupon, which measurement devices are used to measure the temperature of the vessel tissue. Desirably, these measurement devices 40 comprise thermistors. Thermistors are a good choice for the present invention due to their accepted use in catheter and other medical applications, their high sensitivity to small temperature changes and their ability to withstand long cable lengths. Micro-thermistors" available from a variety of companies that measure on the order of 0.36 - 0.5mm [0.014 - 0.020in].

Examples of sources include Alpha Sensors, San Diego, California; Sensor Scientific, Inc., Fairfield, New Jersey; Exacon Scientific, Roskilde, Denmark.

In one embodiment of the present invention, the thermistor specifications are as follows:

Head width Approximately 0.5 mm or less

Temperature accuracy Approximately 0.05°C Response time Approximately 2-300 ms

Protrusion from PCB Approximately 0.2-0.5 mm

Linear correlation of Over a range of 33 °C-43 °C response/temperature

The present invention may be constructed such that multiple temperature measurement devices 40 are connected to a single lead pair 42. Alternatively, sharing one of two leads among several temperature measurement devices 40 may also used.

As shown in Figure 3, by using a Chinese lantern expanding PCB tape configuration, the temperature measurement devices 40 may be mounted to the surface of the flexible circuit by either potting each temperature measurement device 40 in a flexible material, leaving it partially exposed, or soldering the temperature measurement device between the lead pair on the circuit. In a preferred embodiment, the temperature measurement devices 40 protrude outwardly from the surface of the PCB tapes 24 such that when the PCB tapes 24 are expanded, there is good positive contact between the temperature measurement device 40 and the vessel wall tissue.

An alternate means of deploying the tip of a temperature measurement device 40 outward toward the walls of a vessel is to mount each temperature measurement device 40 on the end of a pair of wires that act as both the conductor pair and the deployment mechanism. Pulling one of the wires in the pair proximally while holding the second fixed axially would cause the second wire to bend. By controlling the location and direction of bending, several of these arrangements would produce a radial contact pattern on the vessel wall. Spacing them at several points axially along the catheter would allow temperature measurements at known separation distances to show a gradient along a vessel segment. This configuration could be easily collapsed to the original profile to allow for further advancement or retraction of the catheter.

Depending on the size and thickness of the PCB tapes 24, an additional support layer may be needed in the middle one third of the cylinder in order to ensure that the PCB tapes 24 expand outward and make good contact with the vessel walls. This additional support may be accomplished by providing a second layer of polyimide to the underside of the PCB tapes 24. In one embodiment, the second layer of polyimide is applied in the middle region of the underside of the PCB tapes 24. Alternatively, when forming the temperature measurement device leads 50, 52, it may be possible to control the etching process to selectively etch certain portions of the PCB sheet 70 such that the leads on the PCB tapes 24 have greater structural strength in the bonded regions.

In a preferred embodiment, within the proximal end ferrule 36 of the catheter-based device 10, all the single electrical leads from the temperature measurement devices 40, and the return common electrical lead 80 connecting all of the temperature measurement devices 40 pass through lumens within the support catheter 20 to the electrical power supply and measuring unit at the proximal end 12 of the catheter-based device 10.

In use, the devices of the preferred embodiments of the present invention are constructed and arranged such that at the proximal end 12 of the catheter-based device 10, the temperature measurement device electrical leads 50, 52 terminate in a ring of connectors, electrically arranged so that each of the temperature measurement devices can be successively switched into the circuitry for temperature measurement. The temperature dependent change in temperature measurement device resistance is processed in a multi-channel processor with appropriate software. The voltage change/temperature relationship is pre-determined for each temperature measurement device and this precalibration is fed into the microprocessor for reference. After taking one set of measurements, the expanded catheter-based device is relaxed and moved further down the artery to an appropriate new position. The catheter-based device is re-expanded to reposition the temperature measurement device on the vessel wall and another set of temperature measurements taken.

At the same time as the intralumenal temperature profiling of the vessel wall, the patient's mouth temperature is taken with a pre-calibrated temperature measurement device of exactly the same characteristics as those mounted on the catheter- based device 10. This reading serves as the reference (or background) value for the incremental differences recorded at the multiple sites in the patient's vessel or vessels. The microprocessor is programmed to present the vessel temperature heterogeneity profile as a three dimensional chart. The temperature mapping achieved by use of the present invention can be directly correlated with intravascular ultrasound scanning of the same region of the vessel. Additionally, if required, micromanometer and Doppler flow probes (for pressure and flow measurements) can be incorporated within the structure of the catheter-based device of the present invention for simultaneous measurement.

In Figure 6, a preferred embodiment of the PCB sheet composition 100 is provided. This embodiment includes a flexible polyimide base layer 102, a copper layer 106 that contains the etched electrical leads and a glue or other adhesive layer 104 for binding the polyimide layer 102 to the copper layer 106.

Additionally, the PCB sheet composition 100 includes a gold coating 108 on the copper layer 106. Preferably, the polyimide base layer 102 is about 50 microns in thickness, the glue or adhesive layer 104 is about 25 microns in thickness, the copper layer 106 is about 17.5 microns in thickness and the gold coating 108 is about 2 microns in thickness. However, while these are the preferred dimensions, PCB sheets are commonly made that are sufficiently flexible such that they may be rolled into a cylinder having a radius as small as ten times their thickness. One skilled in the art will recognize that by reducing the thickness of the polyimide/copper PCB sheet, by reducing the electrical lead spacing and slot edge to electric lead track spaces, and/or by varying the number of paired electric lead tracks, it would be possible to fabricate a PCB sheet that is capable of fitting onto a 2-3 ram outer diameter support catheter body, or smaller. Additionally, the length of the PCB rectangular sheet on its longest side may be selected as needed. The PCB sheet length may be varied to allow for different expansion diameters and also to customize the catheter-based device for measurement of short or long segments of the target vessel tissue.

As can be seen by the preceding, the present invention provides a catheter-based device that is able to measure tissue temperature and consistent thermal heterogeneity profile of a vessel wall to help determine the presence of inflammation of the tissue. In addition, the present invention provides a catheter-based device that, if used in arteries, veins, or compartments of the heart to measure tissue temperature, does not seriously compromise blood flow through the vessel during the measurement. The catheter may also be equipped with known auxiliary functional mechanisms, such as means for electronic stimulation, stent delivery and the like. It should be understood that the foregoing relates to preferred embodiments of the present invention and that numerous changes may be made therein without departing from the scope of the invention as defined by the following claims.

Claims

CLAIMSWe claim:

1. A catheter-based device for measuring tissue temperature in a body vesicle comprising: a catheter having a proximal end, a distal end and a middle region; an electrode network at the distal end of the catheter comprising a plurality of electrodes and having a proximal end, a distal end and a middle region; and a plurality of thermal sensors on the electrode network for measuring the tissue temperature at a plurality of locations, wherein the electrode network is constructed and arranged such that when the electrode network is in a relaxed position, the electrodes lie substantially flat and when the electrode network is in an expanded position, the electrodes are juxtaposed to the target tissues without occluding fluid flow through the body vesicle.

2. The catheter-based device of Claim 1, wherein the electrodes comprise a plurality of printed circuit board electrode strips.

3. The catheter-based device of Claim 2, wherein the printed circuit board electrode strips comprise a conductive metal layer attached to a base material.

4. The catheter-based device of Claim 3, wherein the metal layer is copper.

5. The catheter-based device of Claim 3, wherein the base material is polyimide.

6. The catheter-based device of Claim 2, wherein the printed circuit board electrode strips are formed by a process comprising: attaching a flat metal sheet to a base material sheet to form a rectangular sheet having one side longer than the other; etching electrode tracks and cutting parallel slots in the rectangular sheet to form the plurality of printed circuit board strips; and rolling the rectangular sheet such that the rolled sheet is able to comprise the electrode network.

7. The catheter-based device of Claim 1, further comprising a ferrule located at the distal end of the electrode network and a ferrule located at the proximal end of the electrode network.

8. The catheter-based device of Claim 7, wherein the distal end ferrule and the proximal end ferrule are constructed and arranged such that the distal end ferrule is fixed on the catheter while the proximal end ferrule is capable of sliding axially along the catheter thereby causing the electrode network to be either in the relaxed position or the expanded position.

9. The catheter-based device of Claim 1, wherein the sensors are located in the middle region of the electrode network.

10. The catheter-based device of Claim 1, wherein the sensors comprise a thermistor.

11. The catheter-based device of Claim 1, wherein the device includes at least four sensors.

12. A method measuring tissue temperature comprising: providing the catheter-based device of Claim 1 ; expanding the electrode network such that one or more temperature sensors contact the target tissues without occluding fluid flow through the body vesicle; and measuring the tissue temperature using the sensors.