Patent Publication Number: US-2003236443-A1

Title: Methods and apparatus for the identification and stabilization of vulnerable plaque

Description:
REFERENCE TO RELATED APPLICATIONS  
     [0001] The present application is a continuation-in-part of U.S. patent application Ser. No. 10/232,429, filed Aug. 28, 2002, which is hereby incorporated by reference in its entirety, which is a continuation-in-part of U.S. patent application Ser. No. 10/127,052, filed Apr. 19, 2002. 
    
    
     
       FIELD OF THE INVENTION  
       [0002] The present invention relates to methods and apparatus for identifying and stabilizing vulnerable plaque, and for characterizing plaque. More particularly, the present invention relates to specialized catheters having both an imaging element and a thermographer for improved identification of vulnerable plaque. Apparatus of the present invention may in addition include an optional stabilization element for stabilizing the plaque.  
       BACKGROUND OF THE INVENTION  
       [0003] Vulnerable plaque is commonly defined as plaque having a lipid pool with a thin fibrous cap, which is often infiltrated by macrophages. Vulnerable plaque lesions generally manifest only mild to moderate stenoses, as compared to the large stenoses associated with fibrous and calcified lesions. While the more severe stenoses of fibrous and calcified lesions may limit flow and result in ischemia, these larger plaques often remain stable for extended periods of time. In fact, rupture of vulnerable plaque is believed to be responsible for a majority of acute ischemic and occlusive events, including unstable angina, myocardial infarction, and sudden cardiac death.  
       [0004] The mechanism behind such events is believed to be thrombus formation upon rupture and release of the lipid pool contained within vulnerable plaque. Thrombus formation leads to plaque growth and triggers acute events. Plaque rupture may be the result of inflammation, or of lipid accumulation that increases fibrous cap stress. Clearly, prospective identification and stabilization of vulnerable plaque is key to effectively controlling and reducing acute ischemic and occlusive events.  
       [0005] A significant difficulty encountered while attempting to identify and stabilize vulnerable plaque is that standard angiography provides no indication of whether or not a given plaque is susceptible to rupture. Furthermore, since the degree of stenosis associated with vulnerable plaque is often low, in many cases vulnerable plaque may not even be visible using angiography.  
       [0006] A variety of techniques for identifying vulnerable plaque are being pursued. These include imaging techniques, for example, Intravascular Ultrasound (“IVUS”), Optical Coherence Tomography (“OCT”), and Magnetic Resonance Imaging (“MRI”). Two primary IVUS techniques have been developed. The first is commonly referred to as rotational IVUS, which uses an ultrasound transducer that is rotated to provide a circumferential image of a patient&#39;s vessel. The second technique is commonly referred to as phased-array IVUS, which uses an array of discrete ultrasound elements that each provide image data. The image data from each element is combined to form a circumferential image of the patient&#39;s vessel.  
       [0007] Rotational IVUS systems are marketed by Terumo Corporation of Tokyo, Japan, and the Boston Scientific Corporation of Natick, MA, and are described, for example, in U.S. Pat. No. 6,221,015 to Yock, which is incorporated herein by reference. Phased-array IVUS systems are marketed by JOMED Inc., of Rancho Cordova, Calif., and are described, for example, in U.S. Pat. No. 6,283,920 to Eberle et al., as well as U.S. Pat. No. 6,283,921 to Nix et al., both of which are incorporated herein by reference. Optical Coherence Tomography systems are developed by Lightlab Imaging, LLC., of Westford, Mass., and are described, for example, in U.S. Pat. No. 6,134,003 to Tearney et al., which is incorporated herein by reference. U.S. Pat. No. 5,699,801 to Atalar et al., which also is incorporated herein by reference, describes methods and apparatus for Magnetic Resonance Imaging inside a patient&#39;s vessel.  
       [0008] A primary goal while characterizing plaque-type via an imaging modality is identification of sub-intimal lipid pools at the site of vulnerable plaque. In an IVUS study entitled, “Morphology of Vulnerable Coronary Plaque: Insights from Follow-Up of Patients Examined by Intravascular Ultrasound Before an Acute Coronary Syndrome” (Journal of the American College of Cardiology, 2000; 35:106-11), M. Yamagishi et al., concluded that, “the risk of rupture is high among eccentric lesions with a relatively large plaque burden and a shallow echolucent zone.” IVUS allows characterization of the concentricity or eccentricity of lesions, as well as identification of echolucent zones, which are indicative of lipid-rich cores. However, while IVUS and other advanced imaging modalities may provide a means for identifying vulnerable plaque and selecting patients likely to benefit from aggressive risk factor interventions, such imaging modalities typically require a significant degree of skill, training and intuition on the part of a medical practitioner in order to achieve a proper diagnosis.  
       [0009] In addition to imaging techniques, biological techniques also have been proposed for identifying vulnerable plaque. Biological techniques typically rely on characterization of material properties of the plaque. Biological techniques include thermography, biological markers, magnetic resonance, elastography and palpography. Biological markers typically attempt to ‘tag’ specific tissue types, for example, via chemical receptors, with markers that allow easy identification of tissue type. Magnetic resonance operates on the principal that different tissue types may resonate at different, identifiable frequencies. Techniques combining Magnetic Resonance Imaging and biological markers have also been proposed in which superparamagnetic iron oxide nanoparticles are used as MRI contrast media. It is expected that vulnerable plaque will preferentially take up the nanoparticles by virtue of macrophage infiltration, leaking vasa vasorum, and permeable thin cap (M. AbouQamar et al., Poster Abstract, Transcatheter Cardiovascular Therapeutics, 2001, Washington, D.C.).  
       [0010] Elastography and palpography seek to characterize the strain modulus, or other mechanical properties, of target tissue. Studies have shown that different plaque types exhibit different, identifiable strain moduli, which may be used to characterize plaque type. Elastography is described, for example, in U.S. Pat. No. 5,178,147 to Ophir et al., which is incorporated herein by reference. Palpography is described, for example, in U.S. Pat. No. 6,165,128 to Cespedes et al., which also is incorporated herein by reference.  
       [0011] Thermography seeks to characterize tissue type via tissue temperature. Tissue temperature may be characterized via thermographers of various types, including, for example, thermistors, thermosensors, thermocouples, thermometers, spectrography, spectroscopy, and infrared. Tissue characterization via thermographers has been known for some time; for example, U.S. Pat. No. 4,960,109 to Lele et al., which is incorporated herein by reference, describes a multi-function probe for use in hyperthermia therapy that employs at least one pair of temperature sensors.  
       [0012] It has been observed that vulnerable plaque results in a temperature increase at a vessel wall of as much as about 0.1° C. to over 2.0° C., and is typically at least 0.3° C. A review of thermographic apparatus and techniques for plaque characterization is provided by C. Stefanadis in “Plaque Thermal Heterogeneity—Diagnostic Tools and Management Implications” (Expert Presentation, Transcatheter Cardiovascular Therapeutics, Washington, D.C.). Thermography apparatus and methods are also provided in Greek Patent No. 1003158B to Diamantopoulos et al., Greek Patent No. 1003178B to Toutouzas et al., and Greek Utility Model No. 98200093U to Diamantopoulos et al., all of which are incorporated herein by reference. U.S. Pat. No. 5,445,157 to Adachi et al., which is incorporated herein by reference, describes a thermographic endoscope including an infrared image-forming device. U.S. Pat. No. 5,871,449 to Brown and U.S. Pat. No. 5,935,075 to Casscells et al., both incorporated herein by reference, describe catheters capable of detecting infrared radiation.  
       [0013] Although passing reference is made in the Abstract of the Casscells patent to using the infrared detection system with or without ultrasound, no ultrasound apparatus is described. If ultrasound were to be used, it would presumably be applied using known techniques, i.e. extravascularly or via a secondary, stand-alone IVUS catheter. Using extravascular ultrasound or a secondary, stand-alone IVUS catheter, in conjunction with an infrared catheter is expected to increase the complexity, time, and cost associated with identifying vulnerable plaque.  
       [0014] For the purposes of the present invention, in addition to temperature characterization, thermography includes characterization of tissue pH, for example, via Near-Infrared (“NIR”) Spectroscopy. T. Khan et al., have shown that inflamed regions of plaque exhibit lower pH, and that NIR Spectroscopy may be used to measure such pH (“Progress with the Calibration of A 3-French Near Infrared Spectroscopy Fiberoptic Catheter for Monitoring the pH Of Atherosclerotic Plaque: Introducing a Novel Approach For Detection of Vulnerable Plaque,” Poster Abstract, Transcatheter Cardiovascular Therapeutics, 2001, Washington, D.C.). Thus, plaque temperature and plaque pH are inversely correlated to one another. Thermography further may include other spectroscopic tissue characterization, such as tissue composition characterization.  
       [0015] Although thermography is a promising new technique for identifying vulnerable plaque, it has several drawbacks. First, since thermography doesn&#39;t provide image data, it is expected that medical practitioners will have difficulty determining proper locations at which to use a thermographer in order to characterize plaque type. Thus, secondary, stand-alone imaging apparatus may be required in order to adequately identify and characterize plaque. Requiring separate imaging and thermography apparatus is expected to increase complexity, time and cost associated with identifying vulnerable plaque. Additionally, thermography provides no indication of the eccentricity of a plaque or of the presence or magnitude of lipid pools disposed in the plaque, both of which have been shown to indicate the presence of vulnerable plaque.  
       [0016] U.S. Pat. No. 5,924,997 to Campbell and PCT Publication WO 01/74263 to Diamantopolous et al., both of which are incorporated herein by reference, describe or suggest vascular catheters providing ultrasound imaging and temperature detection. The Campbell reference contemplates thermography catheters having a lumen in which a standard ultrasonography catheter may be advanced. It is expected that the cross-sectional profile of such catheters would significantly limit their clinical applicability. Moreover, the catheters described in the Campbell patent do not appear to have any “window” for passage of the IVUS signals; thus, it is expected that such composite thermography/IVUS catheters would provide reduced bandwidth, fidelity, etc., as compared to stand-alone IVUS catheters. The Campbell reference also describes an integrated catheter having thermography and rotational IVUS, but does not clearly describe how such data could be correlated.  
       [0017] The device suggested in PCT Publication WO 01/74263 also has several drawbacks. That reference provides no enabling structure for coupling thermography data to IVUS images. Moreover, the PCT reference contemplates displaying imaging and thermography data in separate, positionally-linked windows, which is expected to increase difficulties in analyzing the data.  
       [0018] Both U.S. Pat. No. 5,924,997 and PCT Publication WO 01/74263 apparently do not acknowledge that patients may not have regions within their vasculature that are suspected of harboring vulnerable plaque. The added time, expense, etc., of using thermography in conjunction with IVUS or other imaging modalities may not be justified. Accordingly, it would be desirable to provide an imaging catheter through which separate thermography probes, e.g. functional measurement guide wires, optionally may be advanced, for example, only in patients suspected of harboring vulnerable plaque.  
       [0019] Another drawback associated with many of the prior art techniques for identifying and stabilizing vulnerable plaque is that identification and stabilization are typically achieved using separate apparatus. Stabilization techniques include both local and systemic therapy. Localized techniques include angioplasty, stenting, mild heating, photonic ablation, radiation, local drug injection, gene therapy, covered stents and coated stents, for example, drug-eluting stents. Systemic therapies include extreme lipid lowering; inhibition of cholesterol acyltransferase (Acyl-CoA, “ACAT”); matrix metalloproteinase (“MMP”) inhibition; and administration of statins, anti-inflammatory agents, anti-oxidants and/or Angiotensin-Converting Enzyme (“ACE”) inhibitors.  
       [0020] Multi-functional devices have been proposed in other areas of vascular intervention. For example, U.S. Pat. No. 5,906,580 to Kline-Schoder et al., which is incorporated herein by reference, describes an ultrasound transducer array that may transmit signals at multiple frequencies and may be used for both ultrasound imaging and ultrasound therapy. PharmaSonics, Inc., of Sunnyvale, Calif., markets therapeutic ultrasound catheters, which are described, for example, in U.S. Pat. No. 5,725,494 to Brisken et al., incorporated herein by reference. U.S. Pat. No. 5,581,144 to Corl et al., incorporated herein by reference, describes another ultrasound transducer array that is capable of operating at multiple frequencies.  
       [0021] In addition to multi-functional ultrasound devices, other multi-functional interventional devices are described in U.S. Pat. Nos. 5,571,086 and 5,855,563 to Kaplan et al., both of which are incorporated herein by reference. However, none of these devices, nor the multi-functional ultrasound devices discussed previously, are suited for rapid identification and stabilization of vulnerable plaque in accordance with the principles of the present invention.  
       [0022] In view of the drawbacks associated with previously known methods and apparatus for identifying and stabilizing vulnerable plaque, it would be desirable to provide methods and apparatus that overcome those drawbacks.  
       [0023] It would be desirable to provide methods and apparatus that reduce the skill and training required on the part of medical practitioners in order to identify and stabilize vulnerable plaque.  
       [0024] It would be desirable to provide methods and apparatus for identifying and stabilizing vulnerable plaque that reduce the cost, complexity and time associated with such procedures.  
       [0025] It would be desirable to provide methods and apparatus that are multi-functional.  
       [0026] It would be desirable to provide methods and apparatus that facilitate characterization of lesion eccentricity, echogenicity, temperature or pH, and tissue composition.  
       [0027] It would be desirable to provide methods and apparatus that combine imaging, thermography, infrared spectroscopy, biochemical sensing and/or optional vulnerable plaque stabilization elements in a single device.  
       [0028] It would be desirable to provide a variety of data characterization techniques.  
       [0029] It would be desirable to provide methods and apparatus for identifying and stabilizing vulnerable plaque that facilitate imaging and allow subsequent advancement of thermography apparatus through the imaging apparatus for detailed inspection of regions suspected of harboring vulnerable plaque.  
       SUMMARY OF THE INVENTION  
       [0030] In view of the foregoing, it is an object of the present invention to provide apparatus and methods for identifying and stabilizing vulnerable plaque that overcome drawbacks associated with previously known apparatus and methods.  
       [0031] It is an object to provide methods and apparatus that reduce the skill and training required on the part of medical practitioners in order to identify and stabilize vulnerable plaque.  
       [0032] It also is an object to provide methods and apparatus for identifying and stabilizing vulnerable plaque that reduce the cost, complexity and time associated with such procedures.  
       [0033] It is another object to provide methods and apparatus that are multi-functional.  
       [0034] It is yet another object to provide methods and apparatus that facilitate characterization of lesion eccentricity, echogenicity, temperature or pH, and tissue composition.  
       [0035] It is an object to provide methods and apparatus that combine imaging, thermography, infrared spectroscopy, biochemical sensing and/or optional vulnerable plaque stabilization elements in a single device.  
       [0036] It would be desirable to provide a variety of data characterization techniques.  
       [0037] It is an object to provide methods and apparatus for identifying and stabilizing vulnerable plaque that facilitate imaging and allow subsequent advancement of thermography apparatus through the imaging apparatus for detailed inspection of regions suspected of harboring vulnerable plaque.  
       [0038] These and other objects of the present invention are accomplished by providing apparatus for identifying vulnerable plaque comprising a catheter having both an imaging element and a thermographer. Providing both thermography and imaging in a single, multi-functional catheter is expected to decrease the cost and increase the accuracy of vulnerable plaque identification, as well as simplify and expedite identification, as compared to providing separate, stand-alone thermography and imaging. Apparatus of the present invention also may be provided with optional stabilization elements for stabilizing vulnerable plaque, thereby providing vulnerable plaque identification and stablization in a single device.  
       [0039] In a first embodiment of the present invention, a catheter is provided having a phased-array IVUS imaging system and a plurality of thermocouples. The plurality of thermocouples may be deployed into contact with an interior wall of a patient&#39;s body lumen, thereby providing temperature measurements along the interior wall that may be compared to IVUS images obtained with the imaging system to facilitate identification of vulnerable plaque. In a second embodiment, a catheter is provided with a rotational IVUS imaging system and a fiber optic infrared thermography system. The infrared system&#39;s fiber optic is preferably coupled to the rotating drive cable of the rotational IVUS imaging system, thereby providing a full circumferential temperature profile along the interior wall of the patient&#39;s body lumen. In a third embodiment, a catheter is provided having a phased-array IVUS imaging system and a fiber optic infrared thermography system. The infrared system preferably comprises a plurality of fiber optics to provide a full circumferential temperature profile along the interior wall of a patient&#39;s body lumen.  
       [0040] In a fourth embodiment, apparatus of the present invention is provided with, in addition to an imaging element and a thermographer, an optional stabilization element. The apparatus may further comprise an optional embolic protection device to capture emboli and/or other material released, for example, during stabilization of vulnerable plaque. The stabilization element may comprise an inflatable balloon. In a fifth embodiment, the stabilization element comprises a second ultrasound transducer that resonates at therapeutic ultrasound frequencies, as opposed to ultrasonic imaging frequencies. As yet another embodiment, the imaging element of the present invention comprises an ultrasound transducer that is capable of transmitting multiple frequencies that are suited to both ultrasonic imaging and ultrasonic therapy, thereby providing both vulnerable plaque imaging and stabilization in a single element.  
       [0041] In a sixth embodiment, a catheter, preferably comprising an imaging transducer, is provided having a side exit port disposed on a lateral surface of the catheter, the side exit port defining a distal termination of a bifurcation of a single lumen or one of two lumens disposed within the catheter through which a thermographer, for example, a functional measurement guide wire, a fiber optic spectroscopy probe, or a fiber optic infrared probe, may be advanced. The catheter also may comprise a plurality of bifurcations or lumens through which a plurality of thermographers may be advanced to facilitate acquisition of a full circumferential temperature profile along the interior wall of a patient&#39;s body lumen. The distal portion of the above-mentioned lumens preferably comprise a curvature that directs advancement of the thermographer so that a distal working tip of the thermographer may be disposed in sensory proximity with the vessel wall to facilitate data acquisition.  
       [0042] Additionally, the direction provided by this curvature, along with the position of an optional imaging system disposed on the catheter distal the side exit port, e.g. an IVUS imaging system, permits the thermographer to be advanced within or immediately adjacent to the field of view of the imaging system, permitting simultaneous acquisition and real-time display of images and temperature data of the same or substantially the same axial or angular locations within the vessel. This eliminates the need to correlate and couple imaging and thermography data prior to display. Accordingly, a medical practitioner may immediately investigate potential areas within the vessel susceptible of harboring vulnerable plaque using the real-time images and temperature data. As an alternative to thermographers, higher resolution imaging probes or wires may be advanced through the side exit port to characterize vulnerable plaque. These include, for example, Optical Coherence Tomography probes or wires.  
       [0043] As yet another embodiment, rather than having a side exit port, the catheter may comprise a distal exit port disposed at the distal end of the catheter through which a thermographer of the present embodiment may be advanced. The thermographer may comprise a shape memory wire that may, upon advancement past the distal exit port, be everted to dispose the distal working end of the thermographer in sensory proximity with the vessel wall and in the field of view of the proximally disposed imaging system.  
       [0044] A still further embodiment comprises a catheter having a phased-array IVUS imaging system and a plurality of thermographers that are circumferentially disposed about the catheter and affixed thereto so that the distal portions of the thermographers radially self-expand away from the catheter when a delivery sheath is proximally retracted. Radial expansion of the plurality of thermographers permits each thermographer to contact the interior wall of a patient&#39;s body lumen.  
       [0045] Embodiments of the present invention may comprise one or more thermographers adapted to obtain the ambient temperature within the vessel. These thermographers may be disposed, for example, on the distal end of catheters made in accordance with the present invention. Additional locations will be apparent to those of skill in the art. Relative temperature increase or decrease at the vessel wall may then be determined by subtracting out the ambient temperature within the vessel.  
       [0046] These embodiments are provided only for the purpose of illustration. Additional embodiments will be apparent to those skilled in the art and are included in the scope of the present invention.  
       [0047] Imaging and thermographic data preferably are coupled in order to facilitate identification of vulnerable plaque. Coupling may be achieved using position indication techniques, for example, using an IVUS pullback system that is modified to simultaneously monitor the position of both the imaging element and the thermographer. IVUS pullback systems are described, for example, in U.S. Pat. No. 6,290,675 to Vujanic et al., U.S. Pat. No. 6,275,724 to Dickinson et al., U.S. Pat. No. 6,193,736 to Webler et al., and PCT Publication WO 99/12474, all of which are incorporated herein by reference. Additionally, relative distances between imaging elements and thermographers on catheters comprising both are preferably obtained prior to introduction of such catheters within a patient&#39;s vasculature. Measurement of such relative distances is expected to facilitate correlation of imaging and thermographic data.  
       [0048] Imaging data and thermographic data, coupled using position indication techniques and measured relative distances, preferably are simultaneously graphically displayed, for example, on a standard computer monitor. The coupled data preferably is displayed in a separate, yet overlaid fashion so that a medical practitioner may rapidly correlate temperature measurements obtained at a given position within the patient&#39;s body lumen to images obtained at that position. Rapid correlation is expected to simplify, expedite and increase the accuracy of vulnerable plaque identification, as well as facilitate plaque stabilization. The overlaid data may also be combined by, for example, color-coding the imaging data to represent temperature.  
       [0049] It is expected that additional data for additional vessel parameters also may be obtained, coupled and provided in the graphical display, for example, palpography, pressure, and pH data. Blood flow imaging, as described, for example, in U.S. Patent Nos. 5,453,575 and 5,921,931 to O&#39;Donnell et al., both of which are incorporated herein by reference, also may be provided.  
       [0050] In accordance with another aspect of the present invention, data for a vessel parameter may be displayed on an interactive 3-dimensional graph in which the data may be provided as a function of axial and angular position within the vessel. Selection of a particular value of one of the variables (e.g., vessel parameter data, axial position or angular position) may prompt display of a 2-dimensional graph in which the coordinate axes comprise the remaining two variables, or display of an image of the associated cross-section or side-section having the vessel parameter data overlaid thereon.  
       [0051] Vessel parameter data also may be conditioned to facilitate rapid bulk testing to narrow the region(s) of the vessel that may require additional analysis. Such conditioning may include computation and display of average vessel parameter values for a particular cross-section or side-section of the vessel, gradients of the individual or average vessel parameter values, and/or accentuation of shifts in individual or average vessel parameter data.  
       [0052] Methods of using the apparatus of the present invention also are provided. 
     
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
     [0053] Further features of the invention, its nature and various advantages, will be more apparent from the following detailed description of the preferred embodiments, taken in conjunction with the accompanying drawings, in which like reference numerals apply to like parts throughout, and in which:  
     [0054]FIG. 1 is a schematic cut-away view of a prior art phased-array IVUS catheter;  
     [0055]FIG. 2 is a schematic cut-away view of a prior art rotational IVUS catheter;  
     [0056]FIGS. 3A and 3B are schematic side views of a prior art thermography catheter having a plurality of thermocouples, and shown in a collapsed delivery configuration and an expanded deployed configuration, respectively;  
     [0057]FIG. 4 is a schematic cut-away view of a prior art thermography catheter having a side-viewing infrared thermographer;  
     [0058]FIG. 5 is a schematic side view of a prior art thermography catheter having a steerable distal region with a thermocouple;  
     [0059]FIG. 6A is a schematic side view of a first embodiment of a catheter in accordance with the principles of the present invention having an imaging element and a thermographer;  
     [0060]FIG. 6B is a schematic side view of an alternative embodiment of the catheter of FIG. 6A in accordance with the principles of the present invention having an imaging element and a thermographer;  
     [0061]FIG. 7 is a schematic cut-away view of a second embodiment of apparatus of the present invention having an imaging element and a thermographer;  
     [0062]FIGS. 8A and 8B are schematic cut-away side views of an alternative embodiment of the apparatus of FIG. 7;  
     [0063]FIG. 9 is a schematic side view of a fourth embodiment of apparatus in accordance with the present invention having an optional stabilization element, as well as an optional embolic protection device;  
     [0064]FIG. 10 is a schematic side view of a fifth embodiment of the present invention having an alternative stabilization element;  
     [0065] FIGS.  11 A- 11 C are schematic cut-away side views of a sixth embodiment of a catheter of the present invention having at least one side exit port for advancement of a thermographer;  
     [0066] FIGS.  12 A- 12 D are schematic side views and cross-sectional views of alternative embodiments of the present invention having an evertable thermographer;  
     [0067]FIGS. 13A and 13B are schematic side views of a further alternative embodiment of the present invention having self-expanding thermographers;  
     [0068]FIGS. 14A and 14B are schematic side views, partially in section, of the apparatus of FIG. 7 disposed at a target site within a patient&#39;s vessel, illustrating a method of using the apparatus of the present invention;  
     [0069]FIGS. 15A and 15B are schematic views of graphical user interfaces that display imaging and thermographic data, respectively, obtained, for example, via the method of FIGS.  14 , with the thermographic data of FIG. 15B obtained along side-sectional view line A-A of FIG. 15A;  
     [0070]FIG. 16 is a schematic view of a graphical user interface that couples and simultaneously displays imaging and thermographic data obtained along a cross-section of the patient&#39;s vessel;  
     [0071]FIG. 17 is a schematic view of an alternative graphical user interface that simultaneously displays coupled imaging and thermographic data along side-sectional view line B-B of FIG. 16;  
     [0072]FIG. 18 is a schematic perspective view of an illustrative vessel having a vulnerable plaque;  
     [0073]FIG. 19 is a schematic view of a graphical user interface that displays illustrative thermographic data corresponding to the vessel of FIG. 18 as a function of axial and angular position within a patient&#39;s vessel;  
     [0074]FIG. 20 is a schematic view of a graphical user interface that displays illustrative thermographic data corresponding to the vessel of FIG. 18 as a function of angular position;  
     [0075]FIG. 21 is a schematic view of a graphical user interface that displays gradients of average summation values of thermography data at multiple cross-sections of the vessel of FIG. 18;  
     [0076]FIG. 22 is a schematic cut-away view of a alternative embodiment of apparatus of the present invention comprising a forward-looking imaging element and a forward-looking infrared element;  
     [0077]FIG. 23 is a schematic perspective view illustrating construction of the phased-array IVUS imaging element of the apparatus of FIG. 22;  
     [0078]FIG. 24 is a schematic cross-sectional view of the infrared element of the apparatus of FIG. 22;  
     [0079]FIG. 25 is a side view, partially in section, illustrating a method of using the apparatus of FIG. 22 at a vascular occlusion within a patient;  
     [0080]FIG. 26 is a schematic side-sectional view of a further alternative embodiment of apparatus of the present invention comprising a radially-viewing imaging element and a radially-viewing infrared element;  
     [0081]FIG. 27 is a side-sectional view illustrating a method of using the apparatus of FIG. 26 at a stenosed region within a patient&#39;s vasculature;  
     [0082]FIG. 28 is a schematic side view of yet another alternative embodiment of the present invention comprising a radially-viewing imaging element and a single fiber side-looking infrared element;  
     [0083]FIGS. 29A and 29B are cross-sectional views illustrating a method of using and aligning the apparatus of FIG. 28 at a stenosed region within a patient&#39;s vasculature;  
     [0084]FIG. 30 is a side view of an alternative embodiment of the apparatus of claim  28 ; and  
     [0085]FIG. 31 is a schematic view of a graphical user interface that provides both cross-sectional and longitudinal side-sectional views of a vessel segment of interest, wherein thumbnail cross-sectional views are provided for reference at points along the longitudinal side-sectional view. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION  
     [0086] The present invention relates to methods and apparatus for identifying and stabilizing vulnerable plaque. More particularly, the present invention relates to specialized catheters having both an imaging element and a thermographer for improved identification of vulnerable plaque. Apparatus of the present invention may in addition include an optional stabilization element for stabilizing the plaque.  
     [0087] With reference to FIG. 1, a prior art phased-array Intravascular Ultrasound (“IVUS”) catheter is described. Catheter  10  comprises phased-array ultrasound transducer  12  having a plurality of discrete ultrasound elements  13 . Catheter  10  further comprises guide wire lumen  14 , illustratively shown with guide wire  100  disposed therein. Catheter  10  also may comprise multiplexing circuitry, amplifiers, etc., per se known, which may be disposed on and/or electrically coupled to catheter  10 . Transducer array  12  of catheter  10  is electrically coupled to an imaging system (not shown), per se known, that provides excitation waveforms to the transducer array, and interprets and displays data received from the array.  
     [0088]FIG. 2 depicts a prior art rotational IVUS catheter. Catheter  20  comprises ultrasound transducer  22  disposed on a distal region of rotatable drive cable  24 . Drive cable  24  is proximally coupled to a driver (not shown), e.g. an electric motor, for rotating the drive cable and ultrasound transducer  22 , thereby providing transducer  22  with a 360° view. Catheter  20  further comprises guide wire lumen  26  that opens in side port  28  distally of transducer  22 . Guide wire  100  is illustratively disposed within lumen  26 . As with transducer array  12  of catheter  10 , transducer  22  of catheter  20  is electrically coupled to an imaging system (not shown), per se known, that provides excitation waveforms to the transducer, and interprets and displays data received from the transducer.  
     [0089] As discussed hereinabove, it has been shown that sub-intimal lipid pools at the site of plaque, as well as the eccentricity of the plaque, are key indicators of vulnerable plaque susceptible to rupture. It has also been shown that IVUS may be used to determine the eccentricity of plaque, as well as to identify echolucent zones, which are indicative of lipid-rich cores. However, achieving proper identification of vulnerable plaque via IVUS or any of a host of other advanced imaging modalities (e.g. Magnetic Resonance Imaging or Optical Coherence Tomography) may require a significant degree of skill, training and intuition on the part of a medical practitioner.  
     [0090] With reference now to FIG. 3, a prior art thermography catheter is described. Catheter  30  comprises outer tube  34  coaxially disposed about inner tube  32 . Inner tube  32  comprises distal tip  36  and guide wire lumen  38 , in which guide wire  100  is illustratively disposed. Catheter  30  further comprises a plurality of thermocouples  40  disposed near its distal end. Each thermocouple comprises a wire  42  coupled proximally to the distal end of outer tube  34  and distally to distal tip  36  of inner tube  32 . The proximal and distal ends of each wire  42  are further electrically coupled to a processor (not shown) that captures and translates voltages generated by thermocouples  40  into temperature values, for example, via known calibration values for each thermocouple.  
     [0091] As seen in FIG. 3, catheter  30  is expandable from the collapsed delivery configuration of FIG. 3A to the expanded deployed configuration of FIG. 3B, by advancing outer tube  34  with respect to inner tube  32 . Such advancement causes thermocouples  40  to protrude from catheter  30  so that the thermocouples may contact the interior wall of a patient&#39;s body lumen. Catheter  30  is adapted for intravascular delivery in the collapsed configuration of FIG. 3A, and is adapted for taking temperature measurements at a vessel wall in the expanded configuration of FIG. 3B.  
     [0092] Referring to FIG. 4, another prior art thermography catheter is described. Catheter  50  comprises lumen  52 , which extends from a proximal end of catheter  50  to distal side port  54 . Fiber optic  56  is disposed within lumen  52  and is proximally coupled to an infrared thermography system (not shown). Catheter  50  thereby comprises a side-viewing fiber optic thermography catheter capable of measuring ambient temperature T near distal side port  54 .  
     [0093] By disposing side port  54  of catheter  50  within a patient&#39;s body lumen, the temperature of the patient&#39;s body lumen may be measured to facilitate identification of vulnerable plaque. However, a significant drawback of catheter  50  for identification of vulnerable plaque is that fiber optic  56  has only a limited field of view, and vulnerable plaque is typically eccentric, i.e. occurs predominantly on one side of a vessel. Thus, if side port  54  of catheter  50  were not rotated to the side of the vessel afflicted with vulnerable plaque build-up, it is expected that the ambient temperature T measured with catheter  50  would not reflect the presence of vulnerable plaque.  
     [0094] With reference to FIG. 5, yet another prior art thermography catheter is described. Catheter  60  comprises steerable distal end  62  having thermistor  64  coupled thereto. Thermistor  64  is proximally attached to a processor (not shown) that converts measurements taken with thermistor  64  into temperature measurements. Catheter  60  further comprises guide wire lumen  66  having guide wire  100  illustratively disposed therein.  
     [0095] Distal end  62  of catheter  60  may be positioned against a patient&#39;s body lumen to provide temperature measurements where thermistor  64  contacts the body lumen. However, a significant drawback of catheter  60  is that thermistor  64  only provides temperature measurements at a single point at any given time. It is therefore expected that eccentric vulnerable plaque will be difficult to identify with catheter  60 , especially if distal end  62  of catheter  60  is disposed against the unaffected, or mildly affected, side of a patient&#39;s vessel suffering from eccentric vulnerable plaque.  
     [0096] Although thermography is a promising new technique for identifying vulnerable plaque, the thermography devices described hereinabove have several drawbacks. Since thermography doesn&#39;t provide image data, it is expected that medical practitioners will have difficulty determining proper locations at which to use a thermographer in order to characterize plaque type. Thus, secondary, stand-alone imaging apparatus may be required in order to adequately identify and characterize plaque. Requiring separate imaging and thermography apparatus is expected to increase complexity, time and cost associated with identifying vulnerable plaque. Additionally, thermography provides no indication of the eccentricity of a plaque or of the presence or magnitude of lipid pools disposed in the plaque, both of which have been shown to indicate the presence of vulnerable plaque.  
     [0097] With reference now to FIG. 6A, a first embodiment of apparatus in accordance with the present invention is described that provides both an imaging element and a thermographer in a single device. By providing both imaging and thermography in a single device, the present invention combines positive attributes of stand-alone imaging systems and stand-alone thermographers described hereinabove, while reducing previously-described drawbacks associated with such stand-alone systems. Apparatus  150  of FIG. 6A comprises catheter body  152 , thermographer  160  and imaging element  170 .  
     [0098] Catheter body  152  comprises outer tube  154  coaxially disposed about inner tube  153 . Inner tube  153  comprises distal tip  156  and guide wire lumen  158 , in which guide wire  100  is illustratively disposed. Thermographer  160  comprises a plurality of thermocouples  162 . Any number of thermocouples  162  may be provided. Each thermocouple comprises a wire  164  coupled proximally to the distal end of outer tube  154  and distally to distal tip  156  of inner tube  153 . The proximal and distal ends of each wire  164  are further electrically coupled to a processor (not shown) that captures and translates voltages generated by thermocouples  162  into temperature values, for example, via known calibration values for each thermocouple.  
     [0099] Thermographer  160  optionally may also comprise thermosensor  161  disposed, for example, on distal tip  156 . Thermosensor  161  may be used to determine ambient temperature within a body lumen such as a blood vessel. This ambient temperature may be subtracted from temperature measurements obtained with thermocouples  162  so that changes in temperature, as opposed to absolute temperature, at a vessel wall may be examined.  
     [0100] Imaging element  170  comprises phased-array ultrasound transducer  172  having a plurality of discrete ultrasound elements  173 . Imaging element  170  optionally may comprise multiplexing circuitry, flexible circuitry or substrates, amplifiers, etc., per se known, which may be disposed on and/or electrically coupled to apparatus  150 . Transducer array  172  of imaging element  170  is electrically coupled to an imaging system (not shown), per se known, that provides excitation waveforms to the transducer array, and interprets and displays data received from the array. The imaging system coupled to imaging element  170  and the processor coupled to thermographer  160  are preferably combined into a single data acquisition and analysis system (not shown) for capturing and interpreting data received from apparatus  150 .  
     [0101] As with catheter  30  of FIG. 3, apparatus  150  is expandable from a collapsed delivery configuration to the expanded deployed configuration of FIG. 6A, by advancing outer tube  154  of catheter body  152  with respect to inner tube  153 . Such advancement causes thermocouples  162  of thermographer  160  to protrude from catheter body  152  so that the thermocouples may contact the interior wall of a patient&#39;s body lumen. Apparatus  150  is adapted for intravascular delivery in the collapsed configuration, and is adapted for taking temperature measurements at a vessel wall in the expanded configuration. Imaging via imaging element  170  may be achieved in either the collapsed delivery configuration or the expanded deployed configuration, thereby facilitating positioning of apparatus  150  at a stenosed region within a patient&#39;s vessel.  
     [0102] Thermographer  160  comprises multiple thermography sensors, illustratively in the form of thermocouples  162 , disposed radially about catheter body  152 . Temperature measurements obtained from these sensors may be displayed graphically as a 2-dimensional map or image, for example, as a cross-sectional temperature profile within a patient&#39;s vessel. Such a cross-sectional temperature profile may be compared with a cross-sectional image of the vessel obtained at the same location, for example, via imaging element  170 . Correlation of imaging and thermography data may be facilitated by determining the distance between imaging element  170  and thermographer  160  prior to use. By advancing or retracting catheter body  152 , correlated, 2-dimensional temperature and imaging data may be extended to 3-dimensions. Translation of catheter body  152  may be achieved, for example, using position indication techniques and/or a pullback system, per se known. Illustrative methods and apparatus for displaying thermographic and imaging data are provided hereinbelow with respect to FIGS.  14 - 21 .  
     [0103] Apparatus  150  is expected to provide significant advantages over prior art, stand-alone imaging and thermography catheters, such as catheters  10  and  30 , used either alone or in combination. Specifically, apparatus  150  is expected to decrease the complexity of obtaining both temperature and imaging data at a target site, as well as to facilitate correlation of such data. Additionally, apparatus  150  is expected to reduce the cost of obtaining both temperature and imaging data, as compared to providing both a stand-alone imaging system and a stand-alone thermography system.  
     [0104] Since vascular lumens commonly afflicted with vulnerable plaque, such as the coronary arteries, are often very small, it is expected that difficulty may be encountered while trying to simultaneously position separate imaging and thermography catheters at the site of vulnerable plaque; furthermore, a stand-alone thermography catheter may block imaging of portions of the vessel wall. Apparatus  150  overcomes these drawbacks. Additionally, apparatus  150  is expected to reduce the skill required on the part of a medical practitioner to identify vulnerable plaque via IVUS, by providing a secondary indication of vulnerable plaque in the form of temperature measurements. Likewise, apparatus  150  is expected to increase the likelihood of proper vulnerable plaque identification via thermography, by providing a secondary indication of vulnerable plaque in the form of IVUS imaging that allows examination of plaque eccentricity and echogenicity. Additional advantages of the present invention will be apparent to those of skill in the art.  
     [0105] An alternative embodiment of catheter  150  of FIG. 6A is illustrated in FIG. 6B. As with catheter  150 , catheter  159  also comprises catheter body  152 , thermographer  160  comprising a plurality of thermocouples  162 , and imaging element  170  comprising phased-array ultrasound transducer  172 . The difference between catheter  159  and catheter  150  resides in the configuration of thermographer  160  with respect to imaging element  170 . Specifically, while thermographer  160  of catheter  150  is disposed longitudinally distant from imaging element  170 , thermocouples  162  may be disposed at the same axial location as imaging element  170 .  
     [0106] In addition to the advantages discussed above with reference to catheter  150 , catheter  159  provides the further advantage of disposing thermocouples  162  within the field of view of phased-array ultrasound transducer  172 . This facilitates simultaneous acquisition, real-time viewing and correlation of both temperature and imaging data at the same axial and/or angular positions within vessel V, thereby eliminating the need to correlate and couple the temperature and imaging data prior to display. In particular, a medical practitioner may be able to view a real-time, cross-sectional image of the vessel with the temperature data instantly overlaid thereon. This permits the medical practitioner to immediately acquire knowledge of, and investigate potential areas within, the vessel suspected of harboring vulnerable plaque.  
     [0107] Referring now to FIG. 7, a second embodiment of apparatus in accordance with the present invention in described. Apparatus  180  comprises catheter  182  having imaging element  184  and thermographer  186 . Imaging element  184  comprises a rotational IVUS imaging element, and thermographer  186  comprises a rotational infrared thermographer.  
     [0108] Catheter  182  further comprises rotatable drive cable  188  having lumen  190  that distally terminates at side port  192 . Catheter  182  still further comprises guide wire lumen  194  that opens in side port  196  distally of drive cable  188 . Guide wire  100  is illustratively shown disposed in lumen  194 .  
     [0109] Thermographer  186  of catheter  182  comprises fiber optic  187  disposed within lumen  190  of drive cable  188 . Imaging element  184  of catheter  182  comprises ultrasound transducer  185  disposed on rotatable drive cable  188 . Drive cable  188  is proximally coupled to a driver (not shown), e.g. an electric motor, for rotating the drive cable, as well as ultrasound transducer  185  of imaging element  184  and fiber optic  187  of thermographer  186 , thereby providing imaging element  184  and thermographer  186  with a 360° view. It will be evident to one of ordinary skill in the art that fiber optic  187  may comprise two or more fibers adjacently disposed, at least one fiber for transmitting a signal and at least one fiber for receiving the transmitted signal.  
     [0110] As with transducer  22  of catheter  20 , transducer  185  is electrically coupled to an imaging system (not shown), per se known, that provides excitation waveforms to the transducer, and interprets and displays data received from the transducer. Likewise, as with fiber optic  56  of catheter  50 , fiber optic  187  is proximally coupled to an infrared thermography system (not shown). Preferably, the imaging system of imaging element  184 , the infrared thermography system of thermographer  186 , and the driver coupled to drive cable  188 , are combined into a single data acquisition and analysis system (not shown) for capturing and interpreting data received from apparatus  180 . Alternatively, a subset of these elements may be combined. Determination of the distance between imaging element  184  and thermographer  186  prior to use is expected to facilitate correlation of imaging and thermography data.  
     [0111] Apparatus  180  provides many of the advantages described hereinabove with respect to apparatus  150 . Additionally, as compared to infrared thermography catheter  50 , described hereinabove with respect to FIG. 4, thermographer  186  of apparatus  180  provides significantly enhanced thermographic capabilities. Specifically, by coupling thermographer  186  to rotatable drive cable  188 , thermographer  186  is capable of providing a full circumferential temperature profile along the interior wall of a patient&#39;s body lumen, without necessitating potentially inaccurate manual rotation of the infrared thermographer by a medical practitioner. A stand-alone, rotatable infrared thermography catheter (not shown), similar to apparatus  180  but without imaging capabilities, is contemplated and is included in the scope of the present invention.  
     [0112] In an alternative embodiment of apparatus  180  of FIG. 7, imaging element  184 , comprising a rotational IVUS imaging element, is replaced with imaging element  170  of FIG. 6. Imaging element  170  comprises phased-array ultrasound transducer  172  having plurality of discrete ultrasound elements  173 . Apparatus  197  further comprises plurality of lumens  198  that distally terminate at plurality of side ports  199 .  
     [0113] Plurality of side ports  199  are disposed on a lateral surface of apparatus  197  at a longitudinal position that is coincident with that of ultrasound transducer  172  so that the circumferential orientation of discrete ultrasound elements  173  is interrupted at regular angular intervals to expose fiber optics  187  disposed within lumens  198 . This permits apparatus  197  to simultaneously acquire both circumferential temperature and imaging profiles at the same axial position within a patient&#39;s body lumen. As will be apparent to those of skill in the art, the plurality of lumens and side ports may comprise any number of lumens and side ports, including a single lumen and side port.  
     [0114] To provide a full circumferential image profile without the attendant interruptions of ultrasound elements  173 , side ports  199  may be shifted to a longitudinal position immediately adjacent to imaging element  170 , as illustrated in FIG. 8B. While this configuration does not permit simultaneous acquisition of temperature and imaging data at exactly the same axial position within a patient&#39;s body lumen, apparatus  200  allows simultaneous acquisition at substantially the same axial position. Specifically, the temperature data acquired by apparatus  200  corresponds to image data of the body lumen just proximal to the field of view of the imaging element. Accordingly, a medical practitioner may still obtain real-time viewing and correlation of both temperature and imaging data at approximately the same axial body lumen position for investigation of areas within the body lumen suspected of harboring vulnerable plaque.  
     [0115] In FIG. 8B, to facilitate correlation of temperature and imaging data at exactly the same axial position post-acquisition, the distance between side exit ports  199  and imaging element  170  preferably are provided or measured. The offset between the side ports and the imaging element may be subtracted out, for example, during data processing. Placing side exit ports  199  immediately adjacent imaging element  170  is expected to reduce artifacts within images obtained with the imaging element caused by placement of thermographers directly within the plane of view of the imaging element.  
     [0116] With reference to FIG. 9, a fourth embodiment of apparatus in accordance with the present invention is described that includes an optional stabilization element, in addition to an imaging element and a thermographer. The stabilization element is adapted to stabilize vulnerable plaque, thereby providing vulnerable plaque identification and stablization in a single device. Apparatus  201  comprises all of the elements of apparatus  150 , including catheter body  152 , thermographer  160  and imaging element  170 , and further comprises stabilization element  202 .  
     [0117] Stabilization element  202  comprises inflatable balloon  204 . Balloon  204  is inflatable from a collapsed delivery configuration to the deployed configuration of FIG. 9 by suitable means, for example, via an inflation medium injected into the balloon through annulus  206  formed between the inner wall of outer tube  154  and the outer wall of inner tube  153  of catheter body  152 . Additional inflation techniques will be apparent to those skilled in the art.  
     [0118] It is expected that, once vulnerable plaque has been identified in a patient&#39;s vessel via thermographer  160  and/or imaging element  170 , stabilization element  202  may be positioned at the location of the identified vulnerable plaque. Stabilization element  202  may then be deployed, i.e. balloon  204  may be inflated, at the site of vulnerable plaque to stabilize the plaque, for example, by compressing, rupturing, scaffolding and/or sealing the plaque in the controlled environment of a catheterization laboratory. In addition to balloon  204 , stabilization element  202  may be provided with additional stabilization elements (not shown), for example, a stent, a covered stent, a stent graft, a coated stent or a drug-eluting stent, to further enhance stabilization of vulnerable plaque. Additional stabilization elements will be apparent to those of skill in the art.  
     [0119] In order to facilitate identification and stabilization of vulnerable plaque, the distances between stabilization element  202 , thermographer  160  and imaging element  170  are preferably provided or measured. Furthermore, the distances between the imaging, thermography and optional stabilization elements of all embodiments of the present invention are preferably provided or measured. This facilitates coupling of thermographic and imaging data, as well as proper positioning of optional stabilization elements.  
     [0120] Providing vulnerable plaque identification and stabilization elements in a single device, in accordance with the principles of the present invention, provides all of the benefits of apparatus  150  described hereinabove, as well as the additional advantage of not having to provide stand-alone apparatus for plaque stabilization. This, in turn, is expected to decrease the cost, time and complexity associated with identifying and stabilizing vulnerable plaque, as well as to decrease the crossing profile of such apparatus, as compared to stand-alone apparatus used concurrently. Further still, providing identification and stabilization in a single device is expected to simplify accurate placement of stabilization elements at the site of identified vulnerable plaque.  
     [0121] Referring now to FIG. 10, a fifth embodiment of the present invention having an alternative vulnerable plaque stabilization element, is described. Apparatus  210  comprises all of the elements of apparatus  150 , including catheter body  152 , thermographer  160  and imaging element  170 , and further comprises stabilization element  212 . Stabilization element  212  comprises therapeutic ultrasound transducer  214 , which is capable of resonating at, and transmitting, therapeutic ultrasound frequencies. Transducer  214  may comprise a single element or an array of elements. Transducer  214  is attached to an excitation unit (not shown) capable of causing resonance within the transducer. The excitation unit is preferably combined with the imaging system (not shown) of imaging element  170 .  
     [0122] Therapeutic ultrasound frequencies, at which therapeutic transducer  214  preferably is capable of resonating and transmitting, are typically described as low frequencies, for example, frequencies below 10,000,000 Hertz, or 10 Megahertz (“MHz”), and even more preferably frequencies below about 500,000 Hertz, or 500 Kilohertz (“kHz”). Conversely, transducer array  172  of imaging element  170  preferably is capable of resonating at, and transmitting, imaging ultrasound frequencies. Imaging ultrasound frequencies are typically described as high frequencies, for example, frequencies above about 10 Megahertz (“MHz”). These frequencies are provided only for the sake of illustration and should in no way be construed as limiting.  
     [0123] It is expected that, once vulnerable plaque has been identified in a patient&#39;s vessel via thermographer  160  and/or imaging element  170 , stabilization element  212  may be positioned at the location of the identified plaque and activated, i.e. ultrasound transducer  214  may provide therapeutic ultrasound waves, to stabilize the plaque, for example, by compressing, rupturing, and/or sealing the plaque in the controlled environment of a catheterization laboratory. As with apparatus  201 , the distances between stabilization element  212 , thermographer  160  and imaging element  170  are preferably provided or measured in order to facilitate vulnerable plaque identification, as well as positioning of stabilization element  212  prior to. activation.  
     [0124] In addition to therapeutic ultrasound transducer  214 , stabilization element  212  may be provided with additional stabilization elements (not shown), for example, contrast, tissue-tag or therapeutic agents, such as drug capsules, that rupture and are released upon exposure to ultrasound waves generated by therapeutic ultrasound transducer  214 . Additional stabilization elements will be apparent to those of skill in the art. Apparatus  210  is expected to provide many of the benefits described hereinabove with respect to apparatus  150  and apparatus  201 .  
     [0125] As yet another embodiment of the present invention, apparatus may be provided in which imaging element  170  and stabilization element  212  of apparatus  210  are replaced with a single ultrasonic transducer array that is capable of transmitting multiple frequencies suited to both ultrasonic imaging and ultrasonic therapy, thereby providing both vulnerable plaque imaging and stabilization in a single element. Techniques for providing an ultrasound transducer capable of resonating at multiple frequencies are provided, for example, in U.S. Pat. No. 5,906,580 to Kline-Schoder et al., as well as U.S. Pat. No. 5,581,144 to Corl et al., both of which are incorporated herein by reference.  
     [0126] Referring to FIG. 11A, a sixth embodiment of the present invention is described. Apparatus  220  comprises functional measurement wire  221  and catheter  222  having imaging element  170 . Wire  221  preferably comprises a thermographer such as a thermocouple, thermistor, or fiber optic infrared thermographer, but may comprise other diagnostic devices to measure, for example, pressure, flow velocity, pH or tissue composition. Further alternatives may include a secondary imaging device that provides a more detailed view than IVUS imaging element  170 , such as an Optical Coherence Tomography apparatus, high frequency ultrasound transducer, Near Infrared Spectroscopy fiber optic, or Magnetic Resonance Imaging apparatus, or may comprise a stabilization device such as an ablation device, therapeutic ultrasound transducer, drug delivery device, therapeutic agent and the like for local delivery to vulnerable plaque P.  
     [0127] Catheter  222  further comprises bifurcated lumen  223  having proximal portion  224  that branches into distal portion  225  and bifurcated portion  226 . Proximal portion  224  extends to the proximal end of catheter  222 , while distal portion  225  extends through distal end  156 . Bifurcated portion  226  terminates at side port  227  disposed on a lateral face of catheter  222 . Adjacent the junction of proximal portion  224 , distal portion  225  and bifurcated portion  226 , uni-directional valve  228  is disposed within distal portion  225  to prevent advancement of thermographer wire  221  into distal portion  225  while permitting advancement of catheter  222  over guide wire  100 . Guide wire  100  is illustratively shown disposed within proximal portion  224  and distal portion  225 , whereas wire  221  traverses proximal portion  224  and bifurcated portion  226 .  
     [0128] Advantageously, bifurcated portion  226  may be curved to direct advancement of wire  221  so that distal working tip  229  of wire  221  may be advanced into the field of view of imaging element  170 , which is disposed distal to side exit port  227 . Similar to catheter  159  of FIG. 6B, this facilitates simultaneous acquisition, real-time viewing and association of both temperature and imaging data respectively obtained by functional measurement wire  221  and imaging element  170  at the same axial and/or angular positions within vessel V, thereby eliminating the need to correlate and couple the temperature and imaging data prior to display. This permits a medical practitioner to view a real-time, cross-sectional image of the vessel with the associated temperature data overlaid thereon in real time. Furthermore, using the real-time images provided by imaging element  170  as a visual guide, wire  221  may be advanced into the field of view of imaging element  170 , and a medical practitioner may steer working tip  229  to a particular location of interest within vessel V for data acquisition, for example by rotating catheter  222  and/or wire  221 .  
     [0129] In accordance with another aspect of the present invention, bifurcated portion  226  may be curved to direct disposition of working tip  229  of wire  221  in sensory proximity with (i.e., contacting or adjacent to) target vascular tissue that is suspected of harboring vulnerable plaque P. This is especially significant since a variety of working tips  229  may require contact or close proximity with the vessel wall to obtain accurate or useful measurements. Such working tips include, for example, thermocouples and Optical Coherence Tomography probes (which may be unable to visualize through blood). Furthermore, pursuant to fluid dynamics theory, blood flow velocity is slowest near the wall of vessel V. Thus, positioning working tip  229  at or near the wall is expected to reduce unwanted migration of the tip due to pressure applied to the tip by blood flowing through the vessel.  
     [0130] Alternatively, bifurcated portion  226  may be curved to direct advancement of wire  221  so that distal working tip  229  is disposed in an axial position immediately adjacent to the field of view of imaging element  170 , and a radial position in sensory proximity with target vascular tissue. This reduces potentially undesirable imaging artifacts, such as incorporation of wire  221  and distal working tip  229  within the acquired images, that may result from advancement of distal working tip  229  within the field of view of imaging element  170 . Advantageously, a medical practitioner may still simultaneously obtain both temperature and imaging data at substantially the same axial position within a patient&#39;s body lumen, thereby permitting real-time viewing, analysis and/or diagnosis.  
     [0131] It will be evident to one of ordinary skill in the art that apparatus  220  may comprise more than one curved, bifurcated portion  226 . Additional bifurcated portions may be provided and disposed to radiate from proximal portion  224 , distally terminating at side exit ports  227  circumferentially disposed on a lateral face of catheter  222  (see FIG. 11B). The additional bifurcated portions may direct advancement of distal working tips  229  of additional wires  221  into or immediately adjacent to the field of view of imaging element  170 . This permits a medical practitioner to simultaneously obtain full circumferential temperature and imaging profiles along the interior wall of a patient&#39;s body lumen.  
     [0132] Advantageously, apparatus  220  provides for optional advancement of functional measurement wire  221 , without requiring such advancement. Many patients may not have regions within their vasculature that are suspected of harboring vulnerable plaque. For these patients, the added time, expense, etc., of thermography or other data collection in conjunction with IVUS or other imaging modalities may not be justified. Apparatus  220  allows for optional use of functional measurement wire  221 , for example, only in patients suspected of harboring vulnerable plaque.  
     [0133] In accordance with yet another aspect of the present invention, functional measurement wire  221  may be proximally removed from apparatus  220  once temperature or other data has been obtained, and successively replaced with other diagnostic, secondary imaging, and/or stabilization devices, examples of which are provided above. This permits a medical practitioner to initially locate vulnerable plaque P by simultaneous temperature and visual confirmation, and then obtain additional data about and/or a more detailed image of the plaque, or provide localized delivery of stabilization devices, while simultaneously viewing the interior of the vasculature to direct advancement of wire  221  or the replacement device. In this manner, apparatus  220  may be used to perform successive, multi-functional applications without removal of catheter  222  from the vessel site of interest.  
     [0134] Alternatively, rather than having bifurcated lumen  223 , apparatus  230 , illustrated in FIG. 11C, may instead comprise catheter  231  having separate wire lumen  232  and guide wire lumen  233 . As with apparatus  220  of FIG. 10A, wire lumen  232  permits thermographer wire  221  to exit catheter  231  via side port  227  disposed on a lateral face of catheter  231 . Distal portion  234  of wire lumen  232  is curved to permit working tip  229  of steerable wire  221  to be advanced within or immediately adjacent to the field of view of imaging element  170  and disposed in sensory proximity with (i.e., contacting or adjacent to) target vascular tissue that is suspected of harboring vulnerable plaque P. Furthermore, as with apparatus  220  in FIG. 11B, apparatus  230  may comprise additional wire lumens  232  disposed within catheter  231  that terminate at side exit ports circumferentially disposed on the lateral face thereof. Again, this allows additional functional measurement wires to be used in simultaneous acquisition of full circumferential temperature and imaging profiles.  
     [0135] Referring to FIGS.  12 A- 12 C, an alternative embodiment of apparatus  220  and apparatus  230  of FIGS.  11  is described. Apparatus  240  comprises functional measurement wire  241  and catheter  242  having IVUS imaging element  170 . Alternative imaging elements will be apparent. Wire  241  preferably comprises a thermographer, but also may comprise or be exchanged for other diagnostic, secondary imaging and/or stabilization devices.  
     [0136] Unlike apparatus  220  and apparatus  230  of FIG. 11, catheter  242  comprises either single lumen  243 , as seen in FIG. 12B, or separate lumens  244  and  245 , as seen in FIG. 12C, through which wire  241  may exit catheter  242  through distal end  246 , instead of through side port  227  of FIG. 11. If catheter  242  comprises lumen  243 , both functional measurement wire  241  and guide wire  100  may be advanced therethrough. If catheter  242  comprises separate lumens  244  and  245 , wire  241  and guide wire  100  may be advanced through their respective lumens.  
     [0137] Functional measurement wire  241  of FIGS.  12 A-C preferably comprises a shape memory alloy wire, e.g., a nickel titanium alloy. When wire  241  is extended from catheter  242 , it adopts an everted curved shape that disposes distal working tip  247  of wire  241  within the field of view of imaging element  170 , which is disposed proximally of distal end  246 . In this everted configuration, a medical practitioner may rotate thermographer wire  241  and/or catheter  242  so that distal working tip  247  is in sensory proximity with target tissue P to obtain temperature (or other) data, using real-time images provided by imaging element  170  for visual guidance.  
     [0138] Once temperature data has been collected, wire  241  is retracted back into the lumen of catheter  242 , thereby returning wire  241  to its non-everted shape. In the non-everted state, wire  241  may be removed from catheter  242  and optionally replaced with another diagnostic, secondary imaging, or stabilization device that also may be everted upon exiting distal end  246  to permit disposition of the distal working tip of the replacement device within the field of view of imaging element  170 .  
     [0139] With reference to FIG. 12D, in an alternative embodiment of apparatus  240  of FIG. 12A, guide wire  100  may be eliminated. In this case, wire  241  initially may be inserted into vessel V as a straight wire. After catheter  242  is advanced along wire  241  to a general vessel location of interest, wire  241  may be extended to adopt an everted shape that disposes distal working tip  247  of guide wire  241  within the field of view of imaging element  107 . Wire  241  optionally may be provided with a removable sheath (not shown) to maintain the wire in a straight configuration for use as a guide wire while catheter  242  is advanced thereover, at which time the sheath may be removed and wire  242  may resume its everted shape.  
     [0140] Catheter  242  then may be concurrently advanced with wire  241  in its everted shape along vessel V, using curve  248  of everted guide wire  241  as an atraumatic bumper. In this manner, a medical practitioner may be able to identify potential sites of vulnerable plaque P by simultaneously viewing both real-time imaging and temperature data respectively provided by imaging element  170  and wire  241  for the same axial and/or angular locations within vessel V.  
     [0141] As in preceding embodiments, wire  241  may adopt an everted curved shape that disposes distal working tip  247  of wire  241  immediately adjacent to the field of view of imaging element  170 . This eliminates potentially undesirable imaging artifacts within the acquired images, such as the incorporation of wire  241  and working tip  247 , and yet still permits a medical practitioner to simultaneously obtain both temperature and imaging data at substantially the same axial position along a patient&#39;s body lumen for real-time viewing, analysis, and/or diagnosis.  
     [0142] Referring now to FIG. 13A, another alternative embodiment of the present invention is described. Apparatus  250  comprises delivery sheath  252  that may be distally tapered to provide an atraumatic tip for advancement of apparatus  250  through a patient&#39;s body lumen. Delivery sheath  252  is translatably and coaxially disposed around catheter  254 . As will be apparent to those of skill in the art, delivery sheath  252  may comprise, for example, a standard guiding catheter.  
     [0143] Catheter  254  of apparatus  250  comprises thermographer  256  and imaging element  170  disposed proximal of atraumatic distal tip  257 . Catheter  254  further comprises catheter body  258  having guide wire lumen  260 , within which guide wire  100  is illustratively disposed.  
     [0144] Thermographer  256  comprises a plurality of thermocouples  262  circumferentially disposed around catheter  254 . Any number of thermocouples  262  may be provided. Each thermocouple  262  comprises self-expanding wire  264  proximally coupled to catheter body  258 . The proximal end of each wire  264  is further electrically coupled to a processor (not shown) that captures and translates voltages generated by each thermocouple  262  into temperature values, for example, via known calibration values for each thermocouple.  
     [0145] Imaging element  170  comprises phased-array ultrasound transducer  172  having a plurality of discrete ultrasound elements  173  circumferentially disposed about catheter body  258  proximal of atraumatic distal tip  257 . Imaging element  170  optionally may comprise multiplexing circuitry, flexible circuitry or substrates, amplifiers, etc., per se known, which may be disposed on and/or electrically coupled to apparatus  250 . Transducer array  172  of imaging element  170  is electrically coupled to an imaging system (not shown), per se known, that provides excitation waveforms to the transducer array, and interprets and displays data received from the array. The imaging system coupled to imaging element  170  and the processor coupled thermographer  256  are preferably combined into a single data acquisition and analysis system (not shown) for capturing and interpreting data received from apparatus  250 .  
     [0146] Each wire  264  is proximally affixed to catheter body  258  and is distally unfettered so that apparatus  250  may expand from the collapsed delivery configuration of FIG. 13A to the expanded deployed configuration of FIG. 13B. More specifically, when delivery sheath  252  is proximally retracted relative to catheter  254  (or catheter  254  is distally advanced with respect to delivery sheath  252 ), thermocouples  262  radially self-expand away from distal tip  257  to contact the interior wall of a patient&#39;s body lumen, remaining in the field of view of imaging element  170 . In order to provide visual guidance during positioning of apparatus  250  at a stenosed region within the patient&#39;s body lumen in the delivery configuration, distal tip  257  and imaging element  170  of catheter  254  may be disposed partially protruding from the distal end of delivery sheath  252 .  
     [0147] Alternatively, wires  264  may be configured so that, in the deployed configuration, thermocouples  256  contact the interior wall of the patient&#39;s body lumen immediately adjacent to the field of view of imaging element  170 . This permits thermographer  256  and imaging element  170  to simultaneously obtain both temperature and imaging data at substantially the same axial position within the patient&#39;s body lumen without incorporating imaging artifacts within the acquired images.  
     [0148] Of course, it will be evident to one of ordinary skill in the art that the catheter embodiments of FIGS. 6 and 9- 13  also may be provided as rapid exchange type catheters similar in configuration to that of FIGS. 2, 7 and  8 . Specifically, rather than having guide wire lumens that span the entire longitudinal length of the catheter, the catheters of embodiments of the present invention may comprise a guide wire lumen, such as guide wire lumen  194  of FIG. 7, that proximally terminates at a side port disposed on a lateral face of the catheter. This permits a medical practitioner to rapidly exchange the catheters of the present invention with other therapeutic or diagnostic catheters.  
     [0149] With reference to FIG. 14, a method of using apparatus of the present invention is provided, illustratively using apparatus  180  described hereinabove. In FIG. 14, vessel V is afflicted with eccentric vulnerable plaque P that manifests only mild stenosis within vessel V. Catheter  182  of apparatus  180  is percutaneously advanced into vessel V, for example, over guide wire  100 , such that imaging element  184  and thermographer  186  are disposed distally of distal edge x 0  of vulnerable plaque P, as seen in FIG. 14A. Drive cable  188  is rotated via its driver (not shown) such that imaging element  184  and thermographer  186  are provided with a full 360° view.  
     [0150] Catheter  182  is then withdrawn proximally across the stenosis until imaging element  184  and thermographer  186  are disposed proximally of proximal edge x 2  of vulnerable plaque P, as seen in FIG. 14B. Imaging and thermography data are collected via imaging element  184  and thermographer  186 , respectively, during proximal retraction of catheter body  182  across the stenosis. Proximal retraction may be achieved manually or using a pullback system. Pullback systems are described, for example, in U.S. Pat. No. 6,290,675 to Vujanic et al., U.S. Pat. No. 6,275,724 to Dickinson et al., U.S. Pat. No. 6,193,736 to Webler et al., and PCT Publication WO 99/12474, all of which are incorporated herein by reference.  
     [0151] As will be apparent to those of skill in the art, catheter  182  alternatively may be advanced distally across vulnerable plaque P during data acquisition, or catheter  182  may be held stationary at a location of interest, for example, location x 1  in the middle of vulnerable plaque P. Additionally, when vulnerable plaque P has been identified, apparatus  180  optionally may be provided with stabilization elements capable of compressing, rupturing, sealing, scaffolding and/or otherwise treating the plaque in the controlled environment of a catheterization laboratory. Exemplary stabilization elements include balloon  204  of apparatus  201 , and therapeutic ultrasound transducer  214  of apparatus  210 . Additional stabilization elements will be apparent to those of skill in the art.  
     [0152] With reference now to FIG. 15, in conjunction with FIG. 14, graphical user interfaces for displaying and interpreting imaging and thermography data, collected, for example, using the methods of FIG. 14, are described. FIG. 15A provides cross-sectional IVUS image  280  formed from imaging data obtained at location x 1  within the patient&#39;s vessel V. Image  280  is eccentric and comprises echolucent zone E, which is indicative of a shallow lipid pool. Both the eccentricity and echogenicity of image  280  are indicative of vulnerable plaque P, with increased risk of rupture, at location x 1  within vessel V.  
     [0153]FIG. 15B displays temperature measurements T as a function of position x. Graphing temperature as a function of position requires that the position of the thermographer be recorded. Such position indication may be achieved, for example, using a pullback system, such as those described hereinabove.  
     [0154] In FIG. 15B, temperature measurements are obtained and graphed along angular position Y of section line A-A in FIG. 15A during proximal retraction of catheter  182  within vessel V from distal edge x 0  to location x 1  to proximal edge x 2  of vulnerable plaque P. The reference temperature within vessel V at locations proximal and distal of vulnerable plaque P is approximately T 0 . All temperatures may be provided on an absolute scale, as in FIG. 15B, or temperatures may be provided as a relative change in temperature with respect to reference temperature T 0 . Alternatively, an ambient reference temperature within the vessel may be obtained, for example, via thermosensor  161  of apparatus  150  of FIG. 6A, and all temperatures may be provided as a relative change with respect to the measured ambient temperature.  
     [0155] As seen in graph  282 , as catheter  182  is proximally retracted across vulnerable plaque P, the temperature at the interior wall of vessel V along point Y rises from reference temperature T 0  to local maximum temperature T 1 . Temperature T 1  is obtained at location x 1  within vessel V. The temperature within the vessel recedes back to reference temperature T 0  while catheter body  182  is further retracted from location x 1  to proximal edge x 2  of vulnerable plaque P. The increase in temperature from reference temperature T 0  to temperature T 1 in the region surrounding location x   1  within the vessel may be as much as about 0.10° C. to over 2.0° C., and is typically at least 0.3° C. This range is provided only for the purpose of illustration and should in no way be construed as limiting.  
     [0156] The increase in temperature from T 0  to T 1  is indicative of vulnerable plaque susceptible to rupture. By comparing and correlating the thermographic data of graph  282  of FIG. 15B to IVUS image  280  of FIG. 15A, identification of vulnerable plaque P is corroborated and confirmed. Thus, providing both imaging and thermography simplifies vulnerable plaque identification while reducing a level of skill required on the part of a medical practitioner in order to properly diagnose such plaque.  
     [0157] In addition to graphing temperature measurements as a function of position, temperature measurements alternatively may be displayed as dynamic, individual measurements (not shown) obtained at the current position of the thermographer. As yet another alternative, temperature measurements may be displayed for an entire vessel cross-section (see FIG. 16), such as a cross-section of temperature measurements obtained at location x 1 . Cross-sections of thermography and imaging data at a given position may be compared to provide rapid and proper identification of vulnerable plaque.  
     [0158] Referring now to FIG. 16, a graphical user interface for concurrently displaying both imaging and thermography data is described. In FIG. 16, imaging and thermography data are correlated and coupled prior to display, for example, using position indication techniques and/or a pullback system, such as an IVUS pullback system that is modified to simultaneously monitor the position of both the imaging element and the thermographer. Determination of the distance between imaging elements and thermographers on integrated catheters of the present invention is also expected to facilitate coupling. Optional stablization elements also may be monitored via position indication techniques and/or a pullback system. IVUS pullback systems are described hereinabove.  
     [0159] In FIG. 16, imaging and thermography data, are simultaneously displayed on separate scales in a graphical, overlaid fashion, for example, on a standard computer monitor. Graphical user interface  290  comprises imaging cross-section  292  and thermography cross-section  294 . Both imaging cross-section  292  and thermography cross-section  294  were obtained at location x 1  within vessel V. Imaging cross-section  292  is eccentric and contains echolucent zone E, which is indicative of a shallow lipid pool.  
     [0160] Thermography cross-section  294  is displayed with reference to temperature intensity scale S that ranges between T 0  and T 1. Scale S may be provided as a color shift, an intensity shift, or a combination thereof. Furthermore the line width along thermography cross-section 294 may be altered to indicate changes in temperature. Additionally, the range of scale S may be extended beyond T   0  and T 1 , or may be displayed as a change in temperature ΔT from a reference background temperature, such as T 0 . Additional scales S will be apparent to those of skill in the art and are included in the present invention. As can be seen in FIG. 16, the intensity of thermography cross-section  294 , and thus the temperature within vessel V, increases along eccentric echolucent zone E of imaging cross-section  292 , which is indicative of vulnerable plaque.  
     [0161] Overlaying imaging and thermography data on separate scales facilitates rapid correlation of the temperature at a given position within vessel V to the image obtained at that position. Rapid correlation is expected to simplify, expedite and increase the accuracy of vulnerable plaque identification. As will be apparent to those skilled in the art, as an alternative to providing temperature and imaging data on separate scales within the same graphical user interface, the imaging data may be color-coded (not shown) to indicate temperature. Additional data may also be obtained, coupled and provided in the graphical display, for example, elastography or palpography data (not shown). Palpographic techniques are described, for example, in U.S. Pat. No. 6,165,128 to Cespedes et al., which is incorporated herein by reference. Blood flow imaging may also be provided (not shown). Blood flow imaging is described, for example, in U.S. Pat. Nos. 5,453,575 and 5,921,931 to O&#39;Donnell et al., both of which are incorporated herein by reference.  
     [0162] Referring now to FIG. 17, an alternative graphical user interface that simultaneously displays coupled imaging and thermography data is described. Graphical user interface  300  overlays imaging and thermography data in a manner similar to interface  290  of FIG. 16. However, interface  300  displays data obtained along side-sectional view line B-B of FIG. 16 during retraction or advancement of apparatus of the present invention across vulnerable plaque P. Retraction or advancement across plaque P is preferably achieved using a modified IVUS pullback system, as described hereinabove.  
     [0163] Graphical user interface  300  comprises imaging side-section  302  and thermography side-section  304 . Imaging side-section  302  is eccentric and comprises echolucent zone E, which is most pronounced in the region around location x 1  within vessel V. Likewise, thermography side-section  304  is of greatest intensity in the region around echolucent zone E of imaging side-section  302 . Concurrent analysis of imaging side-section  302  and correlated thermography side-section  304  is expected to facilitate improved identification of vulnerable plaque. As with the cross-sectional view of graphical user interface  290  of FIG. 16, image side-section  302  may alternatively be color-coded to indicate temperature (not shown). Furthermore, additional information, for example, palpography information or blood flow information, may be provided within the side-sectional view of graphical user interface  300 , in order to further facilitate plaque identification. The additional data, e.g. the palpography data or the blood flow data, is preferably obtained concurrently with imaging data, for example, via the imaging element.  
     [0164] As will be apparent to those of skill in the art, as an alternative to presenting imaging and thermographic data as side-sections and/or cross-sections, such data may be provided as partial or complete 3-dimensional reconstructions (not shown).  
     [0165] In accordance with another aspect of the present invention, temperature measurements (as well as imaging intensity or echogenicity, etc.) alternatively may be displayed on a 3-dimensional graph as a function of both axial vessel position and angular position. For example, FIG. 19 illustratively provides 3-dimensional graph  310  having coordinate axes that correspond to temperature T, axial position x and angular position θ. Graph  310  illustratively provides temperature data that may be obtained by any of the embodiments of the present invention, for example, by catheter  182  of FIG. 14 when catheter  182  is retracted and rotated in the manner described above within vessel V of FIG. 18. In particular, graph  310  provides illustrative temperature measurements along the vessel wall as a function of axial position x and angular position θ, approximately bounded by an area coincident with vulnerable plaque P. This area approximately is limited within the angular measurements θ 0  to θ 2 , and axial positions x 0  to x 2 . Clearly, an entire 360° angular view alternatively may be provided. The reference temperature within vessel V at locations peripheral to and outside of this area is approximately T 0 . All temperatures may be provided as a relative change in temperature with respect to reference temperature T 0 , or temperatures may be provided on an absolute scale, as in FIG. 19.  
     [0166] As seen in graph  310 , as catheter  182  is rotated and/or retracted across vulnerable plaque P, the temperature at the interior wall of vessel V increases from reference temperature T 0  to local maximum temperature T 1 . The temperature within vessel V recedes back to reference temperature T 0  as catheter  182  is rotated and/or retracted past vulnerable plaque P.  
     [0167] In accordance with another aspect of the present invention, graph  310  may be interactive, allowing a medical practitioner to examine areas of interest, such as a local maximum or minimum, in greater detail by selecting indicia along the coordinate axes. For example, if angular position θ 1  is selected, a graphical user interface then may provide a 2-dimensional graph, such as graph  282  of FIG. 15B, of temperature measurements along the vessel wall at angular position θ 1 . Alternatively, selection of angular position θ 1  may provide a side-sectional view of vessel V with thermography data overlaid thereon, such as graphical user interface  300  of FIG. 17.  
     [0168] Likewise, upon selection of a specific axial position, a 2-dimensional graph of temperature along the vessel wall as a function of angular position θ may be provided at that specific axial position. For example, if axial position x 1  is selected on graph  310  of FIG. 19, graph  320  of FIG. 20 may be provided. As may be seen from graph  320 , the temperature at the vessel wall at angular positions less than  74   0  and greater than θ 2  approximately equal reference temperature T 0 , whereas the temperature at angular positions between θ 0  and θ 2  are approximately equivalent to local maximum temperature T 1 . The higher temperature of the vessel between θ 0  and θ 2  is indicative of the presence of vulnerable plaque P with an increased risk of rupture. Alternatively, instead of graph  320 , selection of axial position x 1  may display a cross-sectional view of vessel V at axial position x 1  with the temperature data overlaid thereon, as illustrated in graphical user interface  290  of FIG. 16.  
     [0169] The user also may elect to obtain more detailed information about a specific temperature value. For example, selection of temperature T 1  on graph  310  of FIG. 19 would provide a 2-dimensional graph, chart or table of the angular positions θ and axial positions x at which the temperature measured at the vessel wall equaled temperature T 1 . The apparatus of the present invention then may be advanced to those identified positions for additional investigation.  
     [0170] Of course, one of ordinary skill in the art will recognize that, while the graphs and graphical user interfaces of FIGS.  15 - 20  display temperature measurements, other vessel parameters VP also may be displayed without departing from the present invention. As discussed previously, stiffness, strain and elasticity information may be obtained from elastography or palpography measurements. These parameters, along with blood flow imaging, pressure, pH and flow velocity, also may be displayed individually or simultaneously with combinations thereof. If these parameters are simultaneously displayed, the different datasets may be displayed in an overlaid fashion or as independent datasets. These vessel parameters are provided for illustrative purposes only and should in no way be construed as limiting.  
     [0171] In accordance with yet another aspect of the present invention, measurements of vessel parameter VP (e.g., temperature, strain, pressure and pH) may be provided as an average summation value along a cross-section or side-section of vessel V. Average summation values may be used in rapid bulk testing to narrow the region(s) within vessel V that require additional analysis. Mathematically, the average summation of vessel parameter VP may be computed, for example, as follows:  
               VP   avg     =       (       ∑     i   =   1       i   =   n            VP   i       )     /   n             EQ   .              1                       
 
     [0172] wherein VP is the vessel parameter of interest, such as temperature; n is the number of VP measurements taken along a given region of interest, such as a side-section or cross-section of vessel V; and i is the specific measurement of VP being examined.  
     [0173] As one of ordinary skill in the art will recognize, n will depend on the frequency of data acquisition, the number of imaging transducers or elements within an imaging transducer, the number of thermographers, etc., disposed within the apparatus of the present invention.  
     [0174] The value VP avg  may be displayed in a variety of ways, such as a numerical display, a color/intensity coded value in which the color/intensity is representative of the magnitude of the value and/or as an audio frequency in which the frequency increases with increasing magnitude of the value.  
     [0175] When VP avg  is calculated for multiple cross-sections or side-sections, a 2-dimensional graph may be presented in which the multiple VP avg  values are respectively displayed as a function of axial or angular position within vessel V.  
     [0176] To further facilitate rapid bulk testing, a number of methods may be used to accentuate atypical shifts or deviations in VP avg  values, which may be indicative of the presence of vulnerable plaque susceptible to rupture. A first method comprises raising each individual measurement of vessel parameter VP to a power, e.g., squared. The resultant average summation value may be calculated as follows:  
               VP     shift                 indictor                 avg       =       (       ∑     i   =   1     n            (     VP   i     )     2       )     /   n             EQ   .              2                       
 
     [0177] Alternatively, shifts in VP avg  values may be accentuated by multiplying each individual measurement of vessel parameter VP by a scaling factor C:  
               VP     scaled                 avg       =       (       ∑     i   =   1       i   =   n            C        (     VP   i     )         )     /   n             EQ   .              3                       
 
     [0178] Yet another alternative method to accentuate shifts in VP avg  values subtracts out a normal value VP normal  from each individual measurement of vessel parameter VP as follows:  
               VP     normalized                 avg       =       (       ∑     i   =   1       i   =   n            (       VP   i     -     VP   normal       )       )     /   n             EQ   .              4                       
 
     [0179] An illustrative value for VP normal  may comprise a reference value of vessel parameter VP, such as T 0  for temperature. When VP normalized     —     avg  is greater or less than zero, the cross-section or side-section corresponding to that VP normalized avg  value may require additional examination.  
     [0180] Shifts in VP avg  may be further accentuated by raising the difference between each individual value of vessel parameter VP and VP normal  to a power, e.g., squared, as follows:  
               VP     normalized                 shift                 indicator                 avg       =       (       ∑     i   =   1       i   =   n              (       VP   i     -     VP   normal       )     2       )     /   n             EQ   .              5                       
 
     [0181] An alternative method to further accentuate shifts in VP avg  comprises multiplying the difference between each individual value of vessel parameter VP and VP normal  by scaling factor C as follows:  
               VP     normalized                 scaled                 avg       =       (         ∑   C       i   =   1       i   =   n            (       VP   i     -     VP   normal       )       )     /   n             EQ   .              6                       
 
     [0182] As discussed with reference to EQ. 1, average summation values calculated using EQS. 2-6 may be provided as a numerical display, a color/intensity coded value, or an audio frequency.  
     [0183] It also may be desirable to examine vessel parameter VP in a third dimension. Gradients may be calculated to detect rapid changes in the average summation values VP avg  between successive cross-sections or side-sections of vessel V. Large gradients may be indicative of areas within vessel V that require additional examination or the presence of vulnerable plaque P susceptible to rupture. To determine the change in average summation values VP avg  between successive cross-sections or side-sections of vessel V, the following calculation may be made: 
     ∇( VP   avg )= VP   avg,p+1 −VP avg,p   EQ. 7 
     [0184] wherein p, the specific measurement of VP avg  being examined, ranges from 1 to m, wherein m is the number of cross-sections or side-sections for which VP avg  has been calculated along the length or angular section of vessel V that is of interest.  
     [0185] To display the gradients computed with EQ. 7, ∇(VP avg ) may be graphed as a function of axial position x if values of ∇(VP avg ) are calculated for successive cross-sections of vessel V, or as a function of angular position θ if values of ∇(VP avg ) are calculated for successive side-sections of vessel V.  
     [0186] Graph  330  of FIG. 21 illustrates EQ. 7, wherein temperature T is used as vessel parameter VP. Axial positions x 0 −x 3  correspond to the same axial positions denoted in FIG. 18. Specifically, axial positions x 0  and x 2  respectively represent the distal and proximal ends of vulnerable plaque P, x 1  represents an axial location in the middle of vulnerable plaque P, and x 3  represents an axial position proximal to vulnerable plaque P. As discussed previously, the temperature at axial positions x 0 , x 2  and x 3  are approximately equal to reference temperature T 0 , whereas the temperature at axial position x 1  approximately equals elevated temperature T 1 . Accordingly, T avg  of the cross-sections of vessel V that correspond to axial positions x o , x 2  and X 3  would equal T 0 , while T avg  of the cross-section at axial position x 1  (i.e., (T avg ) x=x1 ) would be greater than T 0 . When EQ. 7 is applied to each axial position, illustrative results of which are shown on graph  330  of FIG. 21, gradient shifts  331  and  332  are noticeable between axial positions x 0  and x 2 . In addition to visual confirmation from images provided by imaging element  184 , shifts  331  and  332  may be indicative and may provide notice of the presence of vulnerable plaque P in vessel V with increased risk of rupture.  
     [0187] As in EQ. 1, an average gradient value for ∇(VP avg ) may be calculated for the length or angle of interest as follows:  
               ∇       (     VP   avg     )     avg       =       (       ∑     p   =   1       p   =   m            (       VP     avg   ,     p   +   1         -     VP     avg   ,   p         )       )     /   m             EQ   .              8                       
 
     [0188] Furthermore, as in EQS. 2 and 5, shifts in gradients ∇(VP avg ), such as shifts  331  and  332  of FIG. 21, may be accentuated by raising each gradient to a power, e.g., squared, as follows: 
     ∇( VP   avg ) shift indicator =( VP   avg, p+1   −VP   avg, p ) 2   EQ. 9 
     [0189] Likewise, as in EQS. 3 and 6, shifts in gradients ∇(VP avg ) also may be accentuated by multiplying each gradient by scaling factor C as follows: 
     ∇( VP   avg ) scaled   =C ( VP   avg, p+1   −VP   avg, p )  EQ. 10 
     [0190] As discussed in reference to EQ. 7, the gradients calculated by EQS. 9 and 10 may be displayed on a 2-dimensional graph as a function of axial position x or angular position θ.  
     [0191] Of course, one of ordinary skill in the art will recognize that ∇(VP avg ) shift indicator of EQ. 9 and ∇(VP avg ) scaled  of EQ. 10 may be averaged over a length or angle of vessel segment that is of interest to facilitate rapid determination of whether that vessel segment requires further examination. To calculate ∇(VP avg ) shift indicator avg  or ∇(VP avg ) scaled avg , EQ. 8 may be used in which ∇(VP avg ) is replaced with ∇(VP avg ) shift indicator  or ∇(VP avg ) scaled , respectively.  
     [0192] It is also noted that the equations given above may be modified for use with individual measurements of vessel parameter VP. Specifically, to accentuate shifts in measurements of vessel parameter VP, and thereby facilitate rapid bulk testing, each measurement value may be raised to a power (e.g., squared), multiplied by scaling factor C, added to normal value −VP normal , or modified by combinations thereof as follows:  
               VP     shift                 indicator       =     VP   2             EQ   .              11                 VP   normalized     =     VP   -     VP   normal               EQ   .              12                 VP     normalized                 shift                 indicator       =       (     VP   -     VP   normal       )     2             EQ   .              13                 VP   scaled     =     C        (   VP   )               EQ   .              14                       
 
     [0193] The resultant modified vessel parameter may be displayed as a numerical display, a color/intensity coded value, and/or an audio frequency.  
     [0194] Gradients also may be calculated for a particular axial or angular section of interest by calculating the difference in successive values obtained for vessel parameter VP, as follows 
     ∇ VP=VP   q+1   −VP   q   EQ. 15 
     [0195] wherein q ranges from 1 to s, s being the number of measurements of vessel parameter VP that have been obtained at a particular axial or angular section of vessel V that is of interest. Furthermore, shifts in gradient values calculated using EQ. 15 may be accentuated to facilitate rapid bulk testing by using EQS. 11 and 14, wherein vessel parameter VP may be replaced by ∇VP. These gradients may be displayed in a 2-dimensional graph as a function of axial position x or angular position θ.  
     [0196] Furthermore, rapid bulk testing may further be facilitated if average summation values are provided for the- above described gradients. Specifically, the following calculations may be made and displayed as a numerical display, a color/intensity coded value, or a radio frequency:  
                 (     ∇   VP     )     avg     =       (       ∑     q   =   1     s          (       VP     q   +   1       -     VP   q       )       )     /   s             EQ   .              16                   (     ∇   VP     )       shift                 indicator                 avg       =       (       ∑     q   =   1     s            (       VP     q   +   1       -     VP   q       )     2       )     /   s             EQ   .              17                   (     ∇   VP     )       scaled                 avg       =       (       ∑     q   =   1     s          C        (       VP     q   +   1       -     VP   q       )         )     /   s             EQ   .              18                       
 
     [0197] It will be obvious to one of ordinary skill in the art that the above discussed values also may be determined as a function of radial dimension r. Likewise, the equations also may be applied to spherical and Cartesian coordinates, as well as any other coordinate system.  
     [0198] Imaging through blood is a complex function of absorption and scattering or diffraction. As water is its dominant component, absorption behavior in blood is somewhat similar to that in water. Images with excessive absorption appear ‘dark’, as if greater illumination (power) is required.  
     [0199] Excessive absorption can typically be overcome by increasing power, changing illumination wavelength and/or changing media. However, if power is increased, substantial heat may be generated. Thus, at high powers the light source may need to be pulsed to reduce heat generation/energy transfer to the media.  
     [0200] When wavelength is altered, absorption tends to increase with wavelength. However, significant localized absorption minima and maxima appear due to molecular resonance, etc. It is preferable to image near absorption minima, thereby reducing required power.  
     [0201] Absorption in blood may also be overcome by changing the media, e.g. an alternative media may be injected, such as saline. Alternatively, blood flow may be blocked (e.g. with a balloon). However, it is important to ensure that ischemia doesn&#39;t develop.  
     [0202] In contrast to absorption, scattering cannot be mitigated by increasing power. Images with excessive scattering appear blurry and unfocused. As a generalization, scattering decreases as wavelength increases (i.e. as the particles—in this case blood cells—become small relative to the wavelength of the light). In part, scattering results from a change in index of refraction between a media and particles in that media; injection of alternative media or blockage of flow may dilute the concentration of particles (i.e. blood cells), thereby decreasing scattering. If alternative media is injected, it should preferably closely match the index of refraction of the blood cells, which have an index of refraction of about 1.29. Plasma has an index of refraction of about 1.35.  
     [0203] U.S. Pat. No. 6,178,346 to Amundson et al., incorporated herein by reference, describes scattering and absorption phenomena in significant detail. That reference outlines a few wavelength regions where an optimal balance of absorption and scattering may be obtained. It defines near infrared (“IR”) wavelengths as 800-1400 nm, mid-IR wavelengths as 1500-6000 nm, and far-IR wavelengths as 6000 to 15000 nm. Optimal properties are found at 1500-1800 nm, 2100-2400 nm, 3700-4300 nm, 4600-5400 nm, and 7000-14000 nm. U.S. patent application publication 2001/0047137 to Moreno et al., incorporated herein by reference, found optimal properties at 1450-1950 nm, and even more preferably at 1600-1800 nm. Higher wavelength techniques theoretically can visualize greater distances; however, they require significantly more power (and thereby have a significantly higher potential for heat generation) to overcome increased absorption with increased wavelength. Thus, for intravascular use, the Amundson patent recommends the 1500-1800 nm and the 2100-2400 nm ranges, and even more preferably about 1600-1700 nm or 2100-2200 nm.  
     [0204] US2001/0047137, to Moreno et al. also describes various light sources that may be used. Preferred light sources are wavelength tunable, which may be achieved, for example, with a filter, a monochromator (e.g. a 1000W tungsten-halogen lamp), an interferometer, or a laser (e.g. an Nd:YAG laser). One or more detectors may be provided for detecting back scattered and reflected light. A single detector is sufficient for spectrometry. A detector array is needed for imaging, and has been achieved with an Indium Antinomide focal plane array video camera. A CMOS or CCD sensor may also/alternatively be provided. The detector(s) may be coupled to an Analog/Digital converter, and an image analysis system, such as a computer with a video display. Imaging and/or data may also be recorded.  
     [0205] US2001/0047137 further describes the use of infrared imaging for both spatial and chemical analysis. Chemical analysis is based on a comparison of detected light with reference absorption curves for various compounds. Potential compounds for analysis include lipoproteins (including high-density lipoproteins “HDL” and low-density lipoproteins “LDL”, as well as 128 KD lypoprotein in necrotic plaques), Group V Secretory Phospholipase  2  “sPLA 2 ”, lysophosphatidylcholine “LPC”, serum amyloid A “SAA”, cholesterol esters and cholesterol monohydrate. These compounds may indicate the presence and/or progression of plaque, including vulnerable plaque. Chemical analysis via infrared imaging may help determine a course of treatment, including, for example, lipid lowering with statins, modulation of matrix metalloproteinases “MMPs” (e.g. via specific tissue inhibitors of metalloproteinases “TIMPS”, via non-specific inhibitors such as 2-macroglobulin, via synthetic inhibitors such as those produced by Agouron Inc., or via gene therapy), and/or inhibition of sPLA 2 .  
     [0206] As discussed previously, vulnerable plaques typically exhibit a thin fibrous cap with a large lipid/atheromatous core, and macrophage infiltration. Both imaging and therapy may be achieved with an IR source, as described in US2001/0047137. Specifically, therapy may be achieved by illuminating at a sufficient power to cause calcification of the fibrous cap. For example, when using an Nd:YAG laser source, short pulses of less than about 10 ms may be provided at a power of about 100 mJ to achieve calcification.  
     [0207] US2001/0047137 also discusses normalization of an IR spectrum to reduce the effects of variation in water content. As for transmission of light from the light source to the media/tissue, and receipt of backscattered light from the media/tissue, fiber optic cable(s) may be provided. US2001/0047137 describes separate fiber optics for transmission and receipt. U.S. Pat. No. 6,178,346 describes the use of a beam splitter so that transmission and receipt may be achieved with the same fiber(s), thereby potentially reducing the crossing profile of catheters having an IR/light-based probe. Additionally, various optics may be provided at the distal end of the fibers to enhance, focus, redirect, etc., signal transmission and receipt. Optics arrangements are shown, for example, in U.S. Pat. No. 6,178,346 (See FIGS. 11B and 12B), US2001/0047137 (See FIGS.  13 - 15 ), as well as U.S. patent application publication 2002/0068853 to Adler (See FIGS. 2 and 4), U.S. Pat. No. 6,445,939 to Swanson et al. (See FIGS. 2 and 4- 12 ), U.S. Pat. No. 6,134,003 to Tearney et al. (See FIGS. 6, 7 and  10 - 12 ) and U.S. Pat. No. 6,010,449 to Selmon et al, all of which are incorporated herein by reference in their entirety.  
     [0208] Infrared imaging involves illumination of a target site with IR light, and measurement of backscattered/reflected light to construct an image. Conversely, infrared thermography measures naturally-emitted radiation from the target site, and constructs an image/measures temperature based on the naturally-emitted radiation. Infrared thermography does not require an illuminating light source. Radiation from body tissue typically occurs in the mid- to far-IR spectrum, from about 1500-15000 nm. There is a need in the art for an intravascular device capable of both infrared imaging and infrared thermography.  
     [0209] Referring now to FIGS.  22 - 25 , a further alternative embodiment of the present invention is described that provides both an imaging element and an infrared element in a single device. By providing both imaging and infrared elements in a single device, the present invention combines advantages associated with stand-alone imaging and infrared devices into a single device. In particular, an image map may be constructed using, e.g., IVUS, as described in detail hereinabove, while chemical, thermographic and/or emissivity analyses of vessel characteristics may be performed using infrared techniques. Therefore, a medical practitioner may identify vulnerable plaque using IVUS, and then use the infrared element to provide a secondary indication or confirmation of vulnerable plaque via a secondary analysis of the vessel. Furthermore, therapy may be achieved using the infrared source, e.g., by illuminating a region of vulnerable plaque at a power sufficient to cause calcification of the fibrous cap of the vulnerable plaque. Accordingly, apparatus  400  of the present invention may serve as an imaging tool, a chemical, thermographic and/or emissivity analysis tool, and a vulnerable plaque treatment or stabilization tool, all in one.  
     [0210] Referring now to FIG. 22, apparatus  400  of the present invention comprises catheter body  402 , IVUS imaging assembly  403 , and infrared analysis assembly  404 . IVUS imaging assembly  403  is disposed at a distal region of catheter body  402  and preferably is forward-looking, as described, for example, in U.S. Pat. No. 6,457,365 to Stephens et al., which is hereby incorporated by reference in its entirety.  
     [0211] In particular, IVUS imaging assembly  403  comprises plurality of transducer elements  416  that are arranged in a cylindrical array centered about a longidutinal axis of catheter body  402  for transmitting and receiving ultrasonic energy. Transducer elements  416  are mounted on an inner wall of substrate  414  that comprises, for example, a flexible circuit material that has been rolled in the form of a tube. A transducer backing material  412  having proper acoustical properties surrounds transducer elements  416 . End cap  424 , which covers a distal end of transducer elements  416 , may be used to insulate the transducer elements from external fluid, such as blood.  
     [0212] Referring to FIG. 23, a preferred method of fabricating IVUS imaging element  403  is briefly described to facilitate understanding of the operation of IVUS imaging element  403  of FIG. 22. A detailed description of the preferred method of fabricating IVUS imaging element  403  is described in applicant&#39;s pending U.S. patent application Ser. No. 10/233,870, which is hereby incorporated by reference in its entirety.  
     [0213] In FIG. 23, transducer elements  416  may have a number of individual elements, each of which is aligned in parallel with illustrative element  430  shown in FIG. 4. Transducer elements  416  are mounted on flex circuit  414 , e.g., a flexible substrate material such as polyimide, which is electrically insulating. If desired, the flex circuit may be formed from a substance having a relatively high acoustical impedance for flexible polymeric materials.  
     [0214] Electrical conductors  334  are formed on the surface of flex circuit  414 , as shown in FIG. 23. The electrical conductors may be formed, for example, from a malleable metal such as gold or copper. A suitable adhesion layer such as a thin layer of chromium may be used to facilitate adhesion of the conductor material to the flex circuit. Metal layers may be deposited by sputtering, evaporation, or any other suitable technique. Wet or dry etching, or other suitable patterning techniques, may be used to pattern the deposited metal to form electrical conductors  34 .  
     [0215] Each transducer element  430  may have two opposing electrodes. The main portion of the electrodes is located on the upper and lower surfaces of the transducer array when the array is oriented as shown in FIG. 23. Smaller portions of the electrodes extend over the ends  435  and  436  of the elements  430  in transducer array  416 . Electrical signals may be conducted between the conductors  434  and the main portions of the electrodes by forming electrical contacts between the conductors  34  and the end portions  435  and  436 .  
     [0216] By connecting the electrodes on each transducer element  430  to corresponding conductors  434 , drive signals for the transducer elements  30  may be conveyed to the elements  430 . Similarly, electrical signals that are produced by the elements  430  when reflected acoustic waves are detected by elements  430  may be conveyed from the elements.  
     [0217] In some transducer arrays (e.g., arrays with  64  elements or more), there may be so many conductors  434  that it is cumbersome to route all of these conductor lines to processing equipment in a single cable along the length of catheter body  402 . Accordingly, integrated circuits  410  (e.g., time-division multiplexing circuits or other suitable multiplexing circuits) may be used to reduce the relatively large number of conductors  434  that are directly connected to transducer array  416  into a smaller number of conductors  434  at the input/output  440 . The conductors at input/output  440  may be soldered, welded, or otherwise electrically connected to wires in a suitable cable (not shown) that runs along the length of catheter body  12  to suitable image processing equipment. If desired, integrated circuits  410  may include drive circuitry for generating drive signals and/or preprocessing circuitry for at least partially processing the electrical signals that are produced when the transducer elements  430  in array  428  are used to detect acoustical information.  
     [0218] After circuits  410  and transducer array  28  have been mounted on flex circuit  414 , as shown in FIG. 23, flex circuit  414  and its mounted components is formed into a cylindrical shape and attached to the distal section of catheter body  402 , as shown in FIG. 22.  
     [0219] Integrated circuits  410  and array  416  preferably are wrapped about a fiber optic bundle of infrared analysis element  404 , which is described in detail hereinbelow. End cap  424  also may be disposed partially between IVUS imaging element  403  and infrared analysis element  404  to isolate ends  436  of elements  430  of array  416  from blood flow. Backing material  412 , as described hereinabove, also is disposed between IVUS imaging element  403  and infrared analysis element  404 , as shown in FIG. 22.  
     [0220] Referring to FIG. 22, infrared analysis assembly or element  404  preferably comprises a fiber optic bundle, which is disposed within IVUS imaging apparatus  403 . A plurality of fiber optic strands may be disposed within the fiber optic bundle of infrared element  404  for transmitting and receiving infrared signals. Alternatively, as will be described hereinbelow, a single fiber may be used to transmit and receive signals, e.g., using a beamsplitter or timed pulses.  
     [0221] Referring now to FIG. 24, a cross-sectional view along a longitudinal axis of the fiber optic bundle of infrared element  404  of FIG. 22 is shown. As seen in FIG.  24 , the fiber optic bundle is preferably similar to an arrangement described in patent publication No. U.S. 2001/0047137 (“the &#39;137 publication”), incorporated by reference. The fiber optic bundle of infrared element  404  includes centrally disposed fiber optic strand  406 , which is used to transmit signals, and a plurality of fiber optic strands  405  concentrically disposed about centrally disposed strand  406 . A proximal end of transmitting strand  405  is coupled to a source, while each receiving strand  405  is coupled to a detector. The source and detector in turn are coupled to a processor configured to analyze the spectra detected by the detectors and produce color images of the backscattered light.  
     [0222] In vivo apparatus described in the &#39;137 publication is adapted for side-viewing infrared analysis, but is not suited for in vivo forward-looking infrared analysis, as in the embodiment of FIGS.  22 - 25 . Furthermore, in the present invention, infrared analysis is conducted in conjunction with IVUS imaging techniques described hereinabove using a single catheter. The relative positions of imaging element  402  and infrared element  404  are preferably known to facilitate correlation of imaging and infrared data.  
     [0223] Referring back to FIG. 22, optional optics  408 , e.g. a concave lens, may be fixedly disposed at a distal end of catheter body  402 . As an alternative to a concave lens, optics  408  may comprise positioning optical fibers  405  and  406  flush with a distal end of catheter body  402 , and specifying their numerical aperture (“NA”) to provide a cone of light with desired angular shape, for example, between about 30° and 80°. Additional optics schemes are provided, for example, in U.S. Pat. No. 6,445,939 to Swanson et al., U.S. Pat. No. 6,178,346 to Amundson et al., U.S. Pat. No. 6,134,003 to Tearney et al., and U.S. Pat. No. 6,010,449 to Selmon et al., all of which are incorporated herein by reference. Optics  408  preferably are configured to enhance, focus and/or redirect light that is transmitted from transmitting fiber optic strand  406  to a patient&#39;s tissue. Furthermore, optics  408  preferably are configured to enhance, focus and/or redirect light that is backscattered from the tissue to receiving fiber optic strands  405 .  
     [0224] Apparatus  400  optionally may comprise a guide wire lumen (not shown), disposed, for example, along catheter body  402  between integrated circuit  410  and the fiber optic bundle of infrared element  404 . Alternatively, a small tube (not shown) may be attached to an exterior surface of catheter body  402  to serve as a guide wire lumen, e.g. a rapid exchange guide wire lumen. Additional placements and configurations for a guide wire lumen will be apparent to those skilled in the art.  
     [0225] Referring now to FIG. 25, a preferred method of using apparatus  400  of FIG. 22 in the detection and characterization of vascular stenosis, illustratively a total vessel occlusion, is described. In a first step, catheter body  402  of FIG. 22 is percutaneously inserted into vessel V, e.g. over a guide wire. Catheter body  402  is advanced until a distalmost region of catheter body  402  is disposed proximal of stenosis S, as shown in FIG. 25.  
     [0226] A processor and graphical user interface are provided for displaying and interpreting imaging and infrared data provided by apparatus  400 . As described hereinabove with respect to FIG. 15A, the graphical user interface may generate a cross-sectional IVUS image similar to image  280  of FIG. 15A and/or a longitudinal or side-sectional image similar to image  300  of FIG. 17. The image provided by IVUS imaging assembly  403  may indicate the presence of a total occlusions when catheter body  402  is disposed proximal of the stenosis S. The IVUS image further may indicate echolucent zones within the total occlusion or shadowed, which are indicative of tissue-type.  
     [0227] In accordance with principles of the present invention, the forward-looking IVUS image generated from IVUS imaging apparatus  403  is used in conjunction with data obtained from infrared analysis assembly  404 , to facilitate characterization of the vascular occlusion. Specifically, when the distal end of catheter body  402  is positioned proximal of the occlusion formed by stenosis S in vessel V, light is transmitted from a light source (not shown) that is operatively connected to transmitting fiber optic strand  406 . Transmitting fiber optic strand  406  then directs the light through optional optics  408 , and the light is focused and directed onto a desired region of the occlusion.  
     [0228] A bolus of fluid, e.g, saline, optionally may be provided to reduce scattering of the infrared light. Fluid with an index of refraction similar to blood is preferred. Alternatively, blood flow optionally may be occluded temporarily to reduce scattering.Backscattered light reflected from stenosis S then is directed into receiving fiber optic strands  405 . Receiving fiber optic strands  405  direct the light to at least one detector coupled to an image analysis system.  
     [0229] A detector array, such as an Indium Antinomide focal plane array video camera, may be used to faciliate imaging of the backscattered and reflected light. A CMOS or CCD sensor may also be used, either alone or in combination with an array video camera. The detector array may be coupled to an analog/digital converter, which is coupled to the image analysis system, such as a computer or processor with a video display and/or recording means.  
     [0230] The image analysis system preferably provides a chemical analysis of the spectra detected by the detection means, based on a comparison of detected light with reference absorption curves for various compounds. These compounds may indicate the presence and/or progression of plaque, including vulnerable plaque. Potential compounds for analysis include lipoproteins (including high-density lipoproteins “HDL” and low-density lipoproteins “LDL”, as well as 128 KD lypoprotein in necrotic plaques), Group V Secretory Phospholipase  2  (“sPLA 2 ”), lysophosphatidylcholine (“LPC”), C-reactive proteins, serum amyloid A (“SAA”), cholesterol esters and cholesterol monohydrate. Chemical analysis via infrared imaging may help determine a course of treatment, including, for example, lipid lowering with statins, lowering of C-reactive proteins, modulation of matrix metalloproteinases (“MMPs”), e.g., via specific tissue inhibitors of metalloproteinases (“TIMPS”), via non-specific inhibitors such as  2 -macroglobulin, via synthetic inhibitors such as those produced by Agouron Inc., or via gene therapy), and/or inhibition of sPLA 2 .  
     [0231] In accordance with one aspect of the present invention, the infrared imaging data collected may be used in conjunction with an IVUS image to indicate the presence of the above-described compounds on an IVUS image. This is advantageous for detecting a vulnerable plaque, total occlusion, thrombus, or other stenosis and characterizing the chemical composition of the stenosis, confirming the characterization, and selecting an appropriate treatment based on the data provided by the imaging and the infrared apparatus.  
     [0232] Various light sources may be used in conjunction with infrared analysis apparatus  404  to transmit light to a patient&#39;s vessel. The light source preferably is adapted for generating a spectrum of light having one or more wavelengths in a range from about 800 to 14000 nm. The light source is preferably wavelength-tunable, which may be achieved, for example, using a filter, a monochromator, e.g., a 1000W tungsten-halogen lamp, an interferometer, or a laser, such as an Nd:YAG laser.  
     [0233] The transmission of light between the light source and a patient&#39;s vessel may be accomplished using different fiber optic strands for transmitting and receiving light, or alternatively may be accomplished using a single fiber to transmit and receive light. For example, timed pulses may be used to transmit a pulse of light on a single fiber and receive backscattered light from the pulse on the same fiber, before sending a subsequent pulse to gather additional data. Alternatively, a beamsplitter may be used to transmit and receive light using a single fiber, for example, as described in U.S. Pat. No. 6,178,346 to Amundson et al., which is incorporated herein by reference in its entirety.  
     [0234] Referring back to FIG. 25, apparatus  400  may further preferably comprises a means for treating total occlusion S, such as an ablation device. The means for treating may include using radiofrequency (RF) ablation by switching the frequency of the signal employed to image/chemically analyze vessel V to a signal suitable for RF ablation. Alternatively, a separate ablation device, such as a laser, RF or acoustic ablation device, or an atherectomy device, may introduced into vessel V to treat total occlusion S after apparatus  400  has been withdrawn from the vessel.  
     [0235] In addition, or as an alternative, to conducting chemical analysis with infrared element  404  of apparatus  400 , thermography may be achieved by simply detecting naturally-emitted infrared radiation from stenosis S and/or vessel V to determine temperature without transmitting light from element  404 . Blood flow is preferably temporarily occluded, e.g. with a balloon catheter, when element  404  is used as a thermographer. Furtherstill, infrared element  404  may be used to measure emmisivity of stenosis S and/or vessel V by first heating the target tissue, and then detecting naturally-emitted infrared radiation. Heating of the target tissue may be achieved, for example, by transmitting an electromagnetic frequency capable of heating from infrared element  404 .  
     [0236] Referring now to FIG. 26, an alternative embodiment of the present invention is described for use in detecting and characterizing plaque, e.g. vulnerable plaque. Apparatus  500  of FIG. 26 comprises a catheter body  502  having side-viewing imaging apparatus  503 , illustratively side-viewing IVUS imaging apparatus, as well as side-viewing infrared analysis apparatus  504 .  
     [0237] IVUS imaging apparatus  503  preferably is provided in accordance with IVUS imaging apparatus  403  of FIGS.  22 - 23 . Specifically, after integrated circuits  510  and transducer array  516  are mounted on flex circuit  514 , as shown in FIG. 23, the flex circuit and mounted components are formed into a cylindrical shape and attached to the distal section of catheter body  502 .  
     [0238] Catheter body  502  may have a guidewire tube  522  (e.g., a high-density polyethlyene tube) surrounded by outer tube  553 , e.g., a medium-density polyethylene tube and a corresponding extension tube  543 . Integrated circuits  510  and transducer array  516  may be wrapped around optically transmissive marker tube  548 , e.g., comprising polycarbonate, and backing material  512 .  
     [0239] At the input/output of flex circuit  514 , cable wire  541  is connected to conductors mounted on the flex circuit, for example, using a solder or weld. Catheter  502  may have a longitudinal lumen through which cable wire  541  extends and connects to image processing and display equipment disposed proximal of the catheter body.  
     [0240] A distal end of catheter body  502  may be affixed to extension tube  543  using cyanoacrylate adhesive  546 . Cyanoacrylate adhesive also may be used as the adhesive  546  for affixing outer tube  553  and extension tube  543  to optically transmissive marker tube  548 . An ultraviolet-curable adhesive  544  may be used to seal and attach other regions of IVUS imaging apparatus  503  to the rest of catheter  502 .  
     [0241] Additionally, optically transmissive film  550  is disposed about optically transmissive marker tube  548  and is situated between transducer array  516  and outer tube  553 , as shown in FIG. 26. Optically transmissive film  550  is substantially flush with an outer surface of flex circuit  514 . In a preferred embodiment, a first radiopaque marker tube washer  545  is disposed between catheter  502  and IV/US imaging assembly  503 , and a second radiopaque marker tube washer  545  is disposed between optically transmissive film  550  and outer tube  553 .  
     [0242] It will be apparent to those skilled in the art that the above-described arrangement is merely one suitable arrangement for mounting flex circuit  514  and components such as integrated circuits  510  and transducer array  516  to catheter  502 . Any suitable arrangement may be used if desired. For example, separate tubes may be provided as unitary structures. Single tubes or structures may be provided in the form of individual parts that are affixed using adhesives or other suitable arrangements, and different types of tubing or adhesives may be used. Additionally, stiffening member  542  may be used to stiffen a proximal portion of catheter  502 , particularly during advancement of the catheter into a patient&#39;s vessel. Furthermore, imaging elements other than IVUS imaging elements may be used, including, for example, MRI and OCT imaging elements.  
     [0243] In accordance with principles of the present invention, IVUS imaging assembly  503  is used in conjunction with infrared analysis assembly  504  to facilitate detection and characterization of plaque, e.g. vulnerable plaque, in a patient&#39;s vessel. Preferably, data obtained from imaging assembly  503  and infrared assembly  504  lie within the same imaging plane I.  
     [0244] Infrared analysis assembly  504  preferably comprises substantially cylindrical shaped housing  530 , which houses reflector element  531 . Reflector element  531  preferably comprises an inverted parabolic shape, as depicted in FIG. 27. Housing. 530  further preferably comprises a closed distal end formed of a suitable material, such as glass. A similar infrared assembly is described in the &#39;137 patent publication, discussed hereinabove and incorporated by reference.  
     [0245] Assembly  504  comprises a fiber optic bundle, which extends the length of catheter  502  and is concentrically disposed within IVUS imaging assembly  503 , just proximal of reflector element  531 . The fiber optic bundle preferably is provided in accordance with the fiber optic bundle described hereinabove with respect to the embodiment of FIGS. 22 and 24, so that a single transmitting fiber strand transmits lights onto reflector element  531 , while a plurality of receiving strands receive backscattered light via reflector element  531 , as described in detail hereinbelow with respect to FIG. 27. Alternatively, a single fiber optic strand may be used in lieu of a fiber optic bundle, in which case beamsplitting or timed pulses may be used to separate transmitting and receiving pulses. Beamsplitting techniques are described, for example, in U.S. Pat. No. 6,178,346, incorporated herein by reference.  
     [0246] In a preferred embodiment, outer diameter of catheter  502  and flex circuit  514  is less than about 4 French. A distal region of apparatus  500  preferably has a reduced outer diameter B of about 2.0 French, and further has a reduced diameter distal end C of about 1.8 French. Alternative dimensions will be apparent to those of skill in the art.  
     [0247] Referring now to FIG. 27, a preferred method of using apparatus  500  of FIG. 26 to facilitate detection and characterization of vulnerbale plaque is described. In FIG. 27, vessel V is afflicted with eccentric vulnerable plaque P that manifests only mild stenosis within vessel V. In a first step, catheter  502  is percutaneously advanced into vessel V, for example, over guide wire  560  via guide wire side port  551 . Guide wire side port  551  transitions into guide wire lumen  555  to permit a medical practitioner to rapidly exchange the catheters of the present invention with other therapeutic or diagnostic catheters.  
     [0248] Catheter  502  of apparatus  500  is percutaneously advanced into vessel such that transducer array  516  of IVUS imaging apparatus  503  and housing  530  of infrared imaging apparatus  504  are disposed distally of a distal edge of vulnerable plaque P. Catheter  502  may be withdrawn proximally across the stenosis, e.g., manually or using a pullback system, as described hereinabove, until tranducer array  516  and housing  530  are disposed proximal of a proximal edge of vulnerable plaque P.  
     [0249] As catheter  502  is retracted within vessel V, transducer array  516  provides cross-sectional images of vessel V over a range of longitudinal locations within the vessel. A side view of vessel V, for example, as shown in FIG. 17 hereinabove, may be generated on a computer display using information gathered from transducer array  516 .  
     [0250] In accordance with principles of the present invention, the side-viewing IVUS imaging data generated from IVUS imaging apparatus  503  is used in conjunction with data obtained from infrared element  504 , to facilitate characterization of vulnerable plaque within a vessel. Specifically, as catheter  502  is retracted within vessel V, light is transmitted from a light source that is operatively connected to a transmitting fiber optic strand, e.g., strand  406  of FIG. 24. Transmitting fiber optic strand  406  then directs the light onto reflector element  531 , which then redirects the light in a direction depicted in FIG. 27. Light is directed through optically transmissive marker tube  548 , optically transmissive film  550 , and onto a region of vessel V coinciding with the IVUS imaging data, such as plaque P, as shown in FIG. 27. Scattered light reflected from the region then is directed back into recieving fiber optic strands  405  of FIG. 24, which then direct the light to at least one detector coupled to an image analysis system.  
     [0251] As described hereinabove with respect to FIG. 25, the image analysis system provides an analysis of the spectra detected by the detection means, based on a comparison of detected light with reference absorption curves for various compounds, as described, for example with respect to patent publication US2001/0047137, incorporated herein by reference. In accordance with one aspect of the present invention, the infrared data collected may be used in conjunction with imaging to indicate the presence of above-described compounds on an image formed from the imaging data. This is advantageous for detecting and characterizing vulnerable plaque P within vessel V, so that an appropriate treatment based on the data provided by the IVUS and infrared apparatus may be selected.  
     [0252] As will be apparent to those skilled in the art, catheter  502  alternatively may be advanced distally across vulnerable plaque P during data acquisition, or catheter  502  may be held stationary at a location of interest, for example, in the middle of plaque P, e.g. vulnerable plaque. Additionally, when vulnerable plaque P has been identified, apparatus  500  optionally may be provided with stabilization elements capable of compressing, rupturing, sealing, scaffolding and/or otherwise treating the plaque in the controlled environment of a catheterization laboratory. Exemplary stabilization elements include balloon  204  of apparatus  201 , and therapeutic ultrasound transducer  214  of apparatus  210 . Additional stabilization elements will be apparent to those of skill in the art.  
     [0253] As with the previous embodiment, infrared analysis may be enhanced by using a bolus of fluid to reduce scattering of light by blood, or flow may temporarily be blocked.  
     [0254] Referring now to FIG. 28, an alternative embodiment of the device of FIGS.  26 - 27  is described for use in detecting and characterizing vulnerable plaque using an IVUS imaging element in conjunction with an infrared imaging/analysis element. In FIG. 28, apparatus  600  comprises catheter  602  having infrared imaging element  603  and IVUS imaging element  608 . IVUS imaging element  608  preferably comprises a side-viewing array of transcuder, as described in detail with respect to IVUS imaging element  503  of FIG. 26 hereinabove.  
     [0255] Infrared imaging element preferably comprises fiber optic  604 . Fiber optic  604  may include distinct transmitting and receiving strands, for example, as described hereinabove with respect to FIG. 24, or alternatively may comprise a single strand that uses beamsplitting or timed pulses to transmit and receive light.  
     [0256] Fiber optic  604  extends through lumen  605  of catheter  602 , which terminates distally at side port  607 . A proximal end of fiber optic  604  is coupled to a transmitting light source, and further coupled to backscattered light detectors and image display and processing apparatus, as described hereinabove with respect to the embodiment of FIGS.  22 - 25 . A distal end of fiber optic  604  transmits light, optionally via optics, through side port  607  and onto a region of interest in a patient&#39;s vessel.  
     [0257] In operation, catheter  602  is percutanously advanced into a patient&#39;s vessel over guidewire  610 . Catheter  602  may comprise guidewire lumen  609 , which spans the length of catheter  602 , or alternatively may comprise a rapid exchange side port, e.g., as shown in FIG. 26. Catheter  602  is positioned at a desired location within vessel V, and an IVUS cross-sectional image may be provided, as shown in FIG. 29A. The cross-sectional IVUS image may provide a physician with a first indication of of the character of plaque P within vessel V, e.g., as indicated by echolucent zones characteristic of lipid pools and vulnerable plaque, or highly reflective zones indicative of calcium.  
     [0258] Advantageously, in accordance with principles of the present invention, infrared element  603  then is used in conjunction with imaging element  608  to provide a secondary confirmation and/or characterization of plaque P. If a physician suspects the presence of vulnerable plaque P from the IVUS image, then catheter  602  may be rotated so that side port  607  faces vulnerable plaque P to direct light onto the vulnerable plaque, as shown in FIG. 29B. The presence of vulnerable plaque may be confirmed by analyzing the spectra detected by the detection means, based on a comparison of detected light with reference absoprtion curves for various compounds. These compounds may indicate the presence and/or progression of plaque, including vulnerable plaque, as described previously.  
     [0259] Referring now to FIG. 30, an alternative embodiment of the device of FIG. 28 is described for use in detecting and characterizing vulnerable plaque. Apparatus  620  is constructed in accordance with apparatus  600  of FIG. 28, with the exception that fiber optic  604  and side port  616  terminate on a lateral surface of catheter  602  at a longitudinal position that is coincident with that of ultrasound transducer  608 . The circumferential orientation of discrete ultrasound elements  612  may be interrupted at regular angular intervals to expose fiber optic  604  disposed within lumen  605 . Apparatus  620  then may be used to provide a cross-sectional image of a patient&#39;s vessel and characterize and/or confirm the presence of plaque, according to techniques described in FIG. 29 hereinabove.  
     [0260] The infrared analysis elements described hereinabove optionally may be removed, and/or separately advanced, with respect to the imaging elements of the catheters of the present invention.  
     [0261] Referring now to FIG. 31, preferred imaging display techniques are provided for use in conjunction with apparatus of the present invention to facilitate detection and characterization of vulnerable plaque. In FIG. 31, image display apparatus  650 , for example, a monitor that may be coupled to an image-processing computer, displays cross-sectional image  652  and side-sectional or longitudinal image  654 , e.g. IVUS images. Side-sectional image  654  is constructed by stacking up a plurality of cross-sectional IVUS images along an axis of interest, for example, using a pullback technique, per se known. Specifically, as a catheter is retracted within lumen  660  of vessel V, e.g., using a pullback system, discrete cross-sectional IVUS images are displayed adjacent one another to form side sectional-image  654 .  
     [0262] A plurality of discrete cross-sectional IVUS images are displayed on image display apparatus  650  as thumbnails  656 . Thumbnails  656  preferably are disposed adjacent side-sectional image  654  at locations approximately corresponding to longitudinal locations of the thumbnail images with respect to the side-sectional image. Advantageously, a physician viewing display apparatus  650  may quickly bring up full cross-sectional images  653  at any longitudinal location in vessel V simply by clicking on a desired region in side sectional image  654 , or by clicking on a thumbnail  656  of interest.  
     [0263] For example, in FIG. 31, the image displayed appears to be eccentric and comprises echolucent zone E, which is indicative of a shallow lipid pool. A physician may click on the region of side sectional image  654  indicated by the horizontal arrow, and the corresponding cross-sectional image will be displayed as image  653 . Alternatively, a physician may click on any thumbnail  656  to bring up an enlarged view of a corresponding cross-sectional image  653 .  
     [0264] Buttons  659  may be provided on image display  650  so that a physician may perform a range of functions, including, for example, saving a cross-sectional image  653  for later reference, and switching from viewing a still image to viewing real-time images within a patient&#39;s vessel.  
     [0265] Additionally, temperature, palpography, or other data may be obtained from an IVUS catheter of the present invention. Techniques for concurrently displaying both imaging and thermography data are described hereinabove. Palpographic techniques are described, for example, in U.S. Pat. No. 6,165,128 to Cespedes et al., which is incorporated herein by reference.  
     [0266] Referring again to FIG. 31, imaging and thermography data may be correlated and coupled prior to display, for example, using position indication techniques and/or a pullback system, then displayed in, for example, an overlaid, color-coded fashion on image display  650 . Scale  662 , which illustratively is color-coded, may serve as a reference scale for color-coded images within display  650 , or may serve as a temperature indicator at adjacent points within side-sectional image  654 .  
     [0267] Rapid correlation of IVUS images and temperature data within vessel V is expected to simplify, expedite and increase the accuracy of vulnerable plaque identification. Additional data may also be obtained, coupled and provided in the graphical display, for example, elastography or palpography data (not shown).  
     [0268] While preferred illustrative embodiments of the present invention are described hereinabove, it will be apparent to those of skill in the art that various changes and modifications may be made therein without departing from the invention. For example, the specific structures of the imaging elements, thermographers, and stabilization elements of the preferred embodiments of are provided only for the sake of illustration. Contemplated imaging elements include, but are not limited to, ultrasound transducers, linear-array ultrasound transducers, phased-array ultrasound transducers, rotational ultrasound transducers, forward-looking ultrasound transducers, radial-looking ultrasound transducers, magnetic resonance imaging apparatus, angiography apparatus, optical coherence tomography apparatus, and combinations thereof. Contemplated thermographers include, but are not limited to, thermocouples, thermosensors, thermistors, thermometers, spectrography devices, infrared thermographers, fiber optic infrared thermographers, ultrasound-based thermographers, spectroscopy devices, near infrared spectroscopy devices, and combinations thereof.  
     [0269] Contemplated stabilization elements include, but are not limited to, balloons, stents, coated stents, covered stents, stent grafts, eluting stents, drug-eluting stents, magnetic resonance stents, anastamosis devices, ablation devices, photonic ablation devices, laser ablation devices, RF ablation devices, ultrasound ablation devices, therapeutic ultrasound transducers, sonotherapy elements, coronary bypass devices, myocardial regeneration devices, sonotherapy devices, drug delivery devices, gene therapy devices, atherectomy devices, heating devices, localized heating devices, devices for heating in a range between about 38-44 degrees Celsius, cell apoptosis-inducing apparatus, growth factors, cytokines, plaque rupture devices, secondary-substance modifiers, therapeutic agents, contrast agents, drug capsules, tissue-type tags, extreme lipid lowering agents, cholesterol acyltransferase inhibitors, matrix metalloproteinase inhibitors, statins, anti-inflammatory agents, anti-oxidants, angiotensin-converting enzyme inhibitors, radiation elements, brachytherapy elements, local drug injection elements, gene therapy elements, photodynamic therapy elements, photoangioplasty elements, cryotherapy elements, and combinations thereof. Additional imaging elements, thermographers, and optional stabilization elements will be apparent to those of skill in the art. The appended claims are intended to cover all combinations of imaging elements, thermographers, and, optionally, stabilization elements that fall within the true spirit and scope of the present invention.  
     [0270] Furthermore, apparatus of the present invention may optionally be provided with an embolic protection device, such as distally-located expandable basket filter  335  of FIG. 9. Alternatively, embolic protection may be achieved with a proximally-located suction device. Embolic protection may be provided in order to capture emboli and/or other material released, for example, during stabilization of vulnerable plaque. Embolic protection devices are described,. for example, in U.S. Pat. No. 6,348,062 to Hopkins et al., and U.S. Pat. No. 6,295,989 to Connors, III, both of which are incorporated herein by reference. Additional embolic protection devices, per se known, will be apparent to those of skill in the art.