Abstract:
A multimodal intravascular analysis uses a structural intravascular analysis modality to compensate for a chemical analysis modality. Examples of structural analysis are IVUS, OCT, including optical coherence domain Reflectometry (OCDR) and optical frequency domain imaging (OFDI), and/or sonar range finding. Examples of chemical or functional analysis are optical, NIR, Raman, fluorescence and spectroscopy, thermography and reflectometry. In one example, the structural analysis is used to characterize the environment structurally, such as catheter head-vessel wall distance. This information is then used to select from two or more algorithms which are depth specific (e.g. shallow vs. deep), to achieve improved accuracy in the chemical or functional analysis.

Description:
BACKGROUND OF THE INVENTION 
     Intravascular ultrasound (IVUS) is a medical imaging technology. It uses a specially designed catheter that includes an ultrasound transducer. In the typical application, the catheter is inserted into the vascular system of a patient and moved to an artery or vein of interest. It allows the doctor to obtain an image of the inner walls of the blood vessels, even through intervening blood. Specifically, it allows visualization of the endothelium (inner wall) of blood vessels, and structures within the vessels walls. 
     In its typical application, IVUS is used in coronary arteries of the heart to locate, identify and characterize atherosclerotic plaques in patients. It can be used both to determine the plaque volume in the blood vessel wall and also the degree of stenosis (narrowing) of the blood vessels. In this way, IVUS is an important technology for the structural analysis of blood vessels. 
     Optical coherence tomography (OCT) is an emerging technology that also provides structural information similar to IVUS. OCT also uses a catheter that is moved through the blood vessels to regions of interest. An optical signal is emitted from the catheter head and the returning signal is analyzed for phase or coherence in a Michelson interferometer, usually. 
     OCT has potential advantages over IVUS. Generally, OCT provides the opportunity for much higher spatial resolution, but the optical signals have limited penetration through blood and attenuate very quickly when propagating through the walls of the blood vessels. 
     An objective to using systems based on OCT and IVUS structural imaging technologies is the early identification of vulnerable plaques since disruption or rupture of atherosclerotic plaques appears to be the major cause of heart attacks and strokes. After the plaques rupture, local obstructive thromboses form within the blood vessels. Both venous and arterial thrombosis can occur. A coronary thrombus often initially forms at the site of rupture of a vulnerable plaque; i.e. at the location of a plaque with a lipid-rich core and a thin fibrous cap (thin-cap fibroatheroma or TCFA). 
     Another class of intravascular analysis systems directed to the diagnosis and analysis of atherosclerosis uses chemical analysis modalities. These approaches generally rely on optical analysis including near infrared (NIR), Raman, and fluorescence spectral analysis. 
     Probably the most common and well developed of these chemical analysis modalities is NIR analysis of the blood vessel walls. Similar to OCT, NIR analysis utilizes an intravascular optical catheter. In a typical application, the catheter is driven by a pullback and rotation unit that simultaneously rotates the catheter head around its longitudinal axis while withdrawing the catheter head through the region of the blood vessel of interest. 
     During this pullback operation, the spectral response of the inner vessel walls is acquired in a raster scan operation. This provides a spatially-resolved spectroscopic analysis of the region of interest. The strategy is that by determining the spectroscopic response of blood vessel walls, the chemical constituents of those blood vessel walls can be determined by application of chemometric analysis for example. In this way, potentially vulnerable plaques are identified so that, for example, stents can be deployed in order reduce the risk of myocardial infarction. 
     In Raman spectral analysis, the inner walls of the blood vessel are illuminated by a narrow band, such as laser, signal. The Raman spectral response is then detected. This response is generated by the inelastic collisions betweens photons and the chemical constituents in the blood vessel walls. This similarly produces chemical information for the vessel walls. 
     Problems associated with Raman analysis are, however, that the Raman process is a very weak and requires the use of high power optical signals in order to generate an adequate Raman response. Fluorescence has some advantages in that the fluorescence response is sometimes much larger than the Raman response. Generally, however, fluorescence analysis does not yield as much information as Raman or NIR analysis. 
     Another advantage of NIR analysis is that the blood flow does not necessarily have to be occluded during the analysis. The judicious selection of the wavelengths of the optical signals allows adequate penetration through intervening blood to the vessels walls and back to the catheter head. 
     In an effort to obtain the valuable information from both the chemical and structural analysis modalities, hybrid IVUS/optical catheters have been proposed. For example, in U.S. Pat. No. 6,949,072, a “device for vulnerable plaque detection” is disclosed. Specifically, this patent is directed to intravascular probe that includes optical waveguides and ports for the near infrared analysis of the blood vessel walls while simultaneously including an ultrasound transducer in the probe in order to enable IVUS analysis of the blood vessel walls. 
     SUMMARY OF THE INVENTION 
     The present invention concerns multimodal intravascular analysis. It uses a structural intravascular analysis modality to compensate for a chemical analysis modality. Examples of structural analysis are IVUS, OCT, including optical coherence domain Reflectometry (OCDR) and optical frequency domain imaging (OFDI), and/or sonar rangefinding. Examples of chemical or functional analysis are optical, NIR, Raman, fluorescence and spectroscopy, thermography and reflectometry. In one example, the structural analysis is used to characterize the environment, such as catheter head-vessel wall distance. This information is then used to select from two or more algorithms that are depth specific (e.g. shallow vs. deep), to achieve improved accuracy in the chemical or functional analysis. 
     In general, according to one aspect, the invention features a method for analyzing blood vessel walls. This method comprises advancing a catheter through blood vessels to regions of interest of blood vessel walls. A first form of energy is transmitted from the head of the catheter and detected after interaction with the blood vessel walls. A second form of energy is also transmitted and detected from the blood vessel walls. The first form of energy is used to determine a structural measure associated with the blood vessel walls. Then the blood vessel walls are analyzed using the second form of energy compensated by the determined structural measure based on the detected first form of energy. 
     In this way, the present invention is directed to a hybrid system that combines the use of two different analysis modalities: a first modality associated with a more structural analysis; combined with a second modality that is largely a chemical analysis modality. In this way, the structural analysis information is used to compensate or improve the information from the chemical analysis, which has the potential of providing better direct information concerning the regions of interest and whether a specific vulnerable plaque lesion is present, or not. 
     In one embodiment, the first form of energy is ultrasonic energy. In this way, the system has an IVUS capability. In some examples, this ultrasound signal is generated photo acoustically. In other examples, the ultrasonic energy is used in a simpler sonar rangefinding implementation. In still other examples, the first form of energy is an optical signal as used in OCT analysis. 
     In the preferred embodiment, the second form of energy is optical energy. Specifically, analyzing the blood vessel walls comprises using the detected optical energy to resolve the spectral response of the blood vessel walls. In examples, the NIR, fluorescence or Raman response of the blood vessels walls is obtained. 
     In still further examples, simply the reflectances of the blood vessel walls are detected using the second form of energy. 
     In one example, the first form of energy is used to select a prediction model for analyzing the detected second form of energy. 
     In other examples, the first form of energy is used to select thresholds for analyzing the detected second form of energy. 
     In implementations, the structural measure includes a physical relationship between the head of the catheter and the blood vessel walls. In other cases, it includes the thickness of a plaque of the blood vessel walls or the thickness of the blood vessel walls themselves. In this way, by determining the distance between the catheter head and the blood vessel walls using the structural analysis modality on a point-by-point basis, the chemometric analysis generated by the NIR analysis of the blood vessel walls can be compensated with this information to thereby improve the accuracy of this chemometric analysis. 
     Depending on the various implementations, the first form of energy and the second form of energy are transmitted simultaneously while withdrawing the catheter head through the blood vessels. In other examples, the first form of energy and the second form of energy are generated and detected during successive of pullback and rotation operations of the catheter head. 
     In general, according to another aspect, the invention features a system for analyzing blood vessel walls. This system comprises a catheter that is advanced through blood vessels to regions of interest of the blood vessel walls. The catheter comprises a catheter head. It houses a first energy form system that transmits a first form of energy from the head of the catheter and detects the first form of energy from the blood vessel walls and a second energy form system that transits a second form of energy from the catheter and receives the second form of energy from the blood vessel walls. A pullback and rotation system is used to simultaneously withdraw the catheter head through the blood vessels while rotating the head around a longitudinal axis. Finally, an analyzer combines the information from each of the first and second form analyses in order to improve the analysis of the blood vessel walls. Specifically, the analyzer determines a structural measure using the first form of energy and then analyzes the blood vessel walls using the detected second form of energy after compensation by the determined structural measure. 
     The above and other features of the invention including various novel details of construction and combinations of parts, and other advantages, will now be more particularly described with reference to the accompanying drawings and pointed out in the claims. It will be understood that the particular method and device embodying the invention are shown by way of illustration and not as a limitation of the invention. The principles and features of this invention may be employed in various and numerous embodiments without departing from the scope of the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the accompanying drawings, reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale; emphasis has instead been placed upon illustrating the principles of the invention. Of the drawings: 
         FIG. 1  is a cross-sectional view of an intravascular probe with a guidewire in a distal end of a catheter; 
         FIG. 2  is a schematic diagram illustrating the use of the catheter system and a system controller, according to the invention; 
         FIG. 3  is a flow diagram illustrating a method for using information from a structural analysis modality to compensate information from a chemical analysis modality, according to the invention; 
         FIG. 4  is a flow diagram illustrating another method for using information from a structural analysis modality to compensate information from a chemical analysis modality, according to the invention; and 
         FIG. 5  is a schematic diagram illustrating the point by point method for chemometric model compensation according to the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       FIG. 1  shows an embodiment of an intravascular catheter system  100  that combines two analysis modalities based on two forms of energy: a first form of energy that yields spatially resolved structural information or even an image and a second form of energy that yields spatially resolved chemical information. Information from both sources is used to identify vulnerable plaques  102  in an arterial wall  104  of a patient. The combination of both: 1) chemical analysis modalities, using infrared spectroscopy to detect lipid content, and 2) morphometric analysis modalities, using IVUS to detect cap thickness or distance to vessel wall, enables greater selectivity in identifying potentially vulnerable plaques than either detection modality alone. These two detection modalities can achieve high sensitivity even in an environment containing blood. 
     In more detail, the intravascular catheter system  100  includes a guidewire lumen  110  at a distal end of the catheter system  100 . In typical operation, the intravascular catheter  100  is advanced into a blood vessel  18  using guidewire  108  that is threaded through the guidewire lumen  110 . 
     The catheter system  100  further comprises an inner scanning catheter head  112  and a sheath  114 . The combination of the scanning catheter head  112  and sheath  114  enables the inner scanning catheter head  112  to perform longitudinal translation and rotation while the sheath  114  prevents this movement from damaging the vessel  18  and specifically walls  104 . 
     At least the distal end of the sheath  114  is composed of materials that are transparent to infrared light (e.g., a polymer). The head of the scanning catheter  112  is located at the distal end of the catheter  100  and includes an optical bench  118  to transmit and receive infrared light and an ultrasound transducer  120  to transmit and receive ultrasound energy. 
     The optical bench  118  contains the terminations of a delivery fiber  122  and a collection fiber  123 , which extend between the proximal and distal ends of the catheter  100 . A light source couples light into a proximal end of the delivery fiber  122 , and a delivery mirror  124  redirects light  125  emitted from a distal end of the delivery fiber  122  towards the arterial wall  104 . A collection mirror  126  redirects light  127  scattered from various depths of the arterial wall  104  into a distal end of the collection fiber  123 . 
     The ultrasound transducer system  120 , which is longitudinally adjacent to the optical bench  118 , includes one or more transducers that direct ultrasound energy  130  towards the arterial wall  104  and receive ultrasound energy  132  reflected from the arterial wall  104 . Using time multiplexing in one implementation, a single ultrasound transducer both generates the transmitted energy  130  and transduces received energy  132  into an electrical signal carried on wires  128 . For example, during a first time interval, an electrical signal carried on wires  128  actuates the ultrasound transducer  120  to emit a corresponding ultrasound signal  130 . Then during a second time interval, after the ultrasound signal  130  has reflected from the arterial wall  104 , the ultrasound transducer  120  produces an electrical signal carried on wires  128 . This electrical signal corresponds to the received ultrasound signal  132 . The received electrical signal  132  is used to reconstruct the shape of the arterial wall, including cap thickness t c  of any plaque  102  and/or a distance D(wall) between the head or distal end of the scanning catheter  112  and the vessel wall  104 , for example, for each spatially resolved point along the wall  104  as the head is scanned through the vessel  18 . 
     In other embodiments, the ultrasound signal is generated photo-acoustically by sending a light pulse through optical fiber with enough energy to create an acoustic event that is detected by the IVUS transducer system  120 . 
     Inside the sheath  114  is a transmission medium  134 , such as saline or other fluid, surrounding the ultrasound transducer  120  for improved acoustic transmission. The transmission medium  134  is also selected to be transparent to the infrared light emitted from and received by the optical bench  118 . 
     A torque cable  136  is attached to a scanning catheter housing  116  and surrounds the optical fibers  122 ,  123  and the wires  128 . This cable  136  transmits the torque from a pullback and rotation system through to the scanning catheter head  112 . This feature enables the scanning catheter head  112  to rotate within sheath  114  to circumferentially scan the arterial wall  104  with light  125  and ultrasound energy  130 . 
       FIG. 2  illustrates an exemplary system for detecting and analyzing the spectral responses in two energy-form scanning. 
     The system generally comprises the catheter  100 , a controller  300 , and a user interface  320 . 
     In operation, first the guide wire and then the catheter  100  are inserted into the patient  2  via a peripheral vessel, such as the femoral artery  10 . The catheter head  112  is then moved to a desired target region, such as a coronary artery  18  of the heart  16  or the carotid artery  14 . This is achieved by moving the catheter head  112  up through the aorta  12 , riding on the guidewire. 
     When at the desired site, NIR radiation is generated, in one embodiment. In preferred embodiment, a tunable laser in the chemical analysis subsystem  312  generates a narrowband optical signal that is wavelength scanned over a scan band in the NIR, covering one or more spectral bands of interest. In other embodiments, one or more broadband sources are used to access the spectral bands of interest. In either case, the optical signals are coupled into the single mode delivery fiber  122  of the catheter  100  to be transmitted to the optical bench  118 . 
     In other examples, reflectances are measured. This is based on the discovery that lipid-rich plaques are “brighter” than other plaques, and blood is typically “darker” than tissue in the NIR. So, just a brightness measurement, corrected for blood depth, sometimes yields adequate accuracy for detection. 
     In the current embodiment, optical radiation in the near infrared (NIR) spectral regions is used for spectroscopy. Exemplary scan bands include 1000 to 1450 nanometers (nm) generally, or 1000 nm to 1350 nm, 1150 nm to 1250 nm, 1175 nm to 1280 nm, and 1190 nm to 1250 nm, more specifically. Other exemplary scan bands include 1660 nm to 1740 nm, and 1630 nm to 1800 nm. 
     However, in other optical implementations, broad band signals, other scan bands, or single frequency excitation signals appropriate for fluorescence and/or Raman spectroscopy are generated by the chemical analysis subsystem  312 . In still other implementations, scan bands in the visible or ultraviolet regions are used. 
     In the current embodiment, the returning light is transmitted back down multimode collection fiber  123  of the catheter  100 . The returning radiation is provided to the chemical analysis subsystem  312 , which can comprise one or multiple optical detectors or spectrometers. 
     The chemical analysis subsystem  312  monitors the response of the detector, while controlling the source or tunable laser in order to resolve the spectral response of vessel walls  104  including a target area, typically on an inner wall of a blood vessel  18  and through the intervening blood or other unwanted signal sources. This spectral response is further spatially resolved as the catheter head is rotated and pulled back through the vessel  18 . 
     As a result, the chemical analysis subsystem  312  is able to collect spectra. When the acquisition of the spectra is complete, chemical analysis subsystem  312  then provides the data to the multimodal analyzer  316 . 
     The structural analysis subsystem  310  uses the information from the ultrasound transducer  120 , in one embodiment, to generate one or more structural measures. In other examples, these structural measures are generated by an OCT, sonar rangefinding, or other structural analysis subsystem  310 . The structural analysis subsystem  310  produces structural information, such as structural measures, which are also spatially-resolved with respect to the vessels as the head  112  is scanned through the vessels  18 . This structural information, such as structural measures, is provided to the multi modal analyzer  316 . 
     In more detail, the structural analysis subsystem  310  comprises the drive electronics for driving the ultrasound transducer  120  and analyzing the response of the transducer  120  to determine the structural measure of interest in a IVUS-type system. In other examples, where the second energy source is an OCT system, the structural analysis subsystem  310  is often an interferometer that resolves the phase or coherence of the light returning from the scanning catheter  112 . 
     Generally, the analyzer  316  makes an assessment of the state of the blood vessel walls  104 , which is presented to the operator via interface  320 . The collected spectral response is used to determine whether each region of interest of the blood vessel wall  104  comprises a lipid pool or lipid-rich atheroma, a disrupted plaque, a vulnerable plaque or thin-cap fibroatheroma (TCFA), a fibrotic lesion, a calcific lesion, and/or normal tissue. 
     In should be noted that the apparent separation between the structural analysis subsystem  310 , chemical analysis subsystem  312 , multimodal analyzer  316 , and the user interface  320  is provided to describe the various processing performed in the preferred embodiment and is thus only a notional separation in some implementations. That is, the data processing function of structural analysis subsystem  310 , chemical analysis subsystem  312 , multimodal analyzer  316  and the user interface  320  are performed by one a single or one or more computer systems in different implementations. 
     The analyzer  316  uses the structural analysis information from the structural analysis subsystem  310  to compensate information from the chemical analysis subsystem  312 . Specifically, the structural analysis system produces a structural measure that is used by the multimode analyzer  316 . Examples of structural measures include the instantaneous distance between the head of the catheter  112  and the blood vessels walls  104  (D(wall)) and/or the thickness of the blood vessel walls. Another structural measure is the cap thickness (t c ) of the lesion  102 . This information is used to compensate information from the chemical analysis subsystem  312  such as serving as an input to a chemometric algorithm that has dependencies on the instantaneous or average distance between the catheter head  112  and the blood vessels walls  104 . Still another structural measure is the lateral extents of plaques in the blood vessel walls. 
     The pullback and rotation and rotation unit  105  is used both for the mechanical drive to the scanning catheter  112  and also to couple the information or optical signals from both the IVUS and the NIR analysis portions of the catheter. Specifically, the pullback and rotation unit  105  drives the scanning catheter  112  to rotate and withdraw through the outer sheath  114 . 
       FIG. 3  is a flow diagram illustrating the operation of the multimodal analyzer  316  in one embodiment. 
     Specifically, the NIR spectral response  410  is produced by the chemical analysis subsystem  312 . Structural information  413  is further obtained from the structural analysis subsystem  310 . 
     Depending on the implementation, the structural analysis information  413  and the chemical analysis information  410  are produced during the same or different scans of the scanning catheter  112 . For example, in one implementation, the chemical analysis information  410  produced by the NIR analysis and structural information  413  produced by the IVUS analysis are captured simultaneously while withdrawing and rotating the scanning catheter  112  through the blood vessels  104 . In other implementations, the chemical analysis information  410  produced by the NIR analysis and structural information  413  produced by the IVUS analysis are captured during different pullback and rotation operations of the scanning catheter  112 . Then the chemical analysis information  410  data set produced by the NIR analysis and structural information  413  data set are spatially aligned with respect to each other. This alignment includes compensation for the offset distance D(offset) between the IVUS transducer  120  and the optical bench  118 , see  FIG. 1 . 
     This structural information is used in step  412  to determine whether or not the instantaneous, i.e., spatially resolved, NIR spectral signal was obtained from a distance of greater than 3 millimeters between the head of the scanning catheter  112  and the blood vessel wall  104 . 
     If the distance was greater than 3 millimeters, then a real time update is performed on preprocessing algorithms. In one example, such preprocessing algorithms are described in U.S. Patent Publication Number is US 2004/0024298-A1, Publication Date Feb. 5, 2004, entitled Spectroscopic Unwanted Signal Filters for Discrimination of Vulnerable Plaque and Method Therefor. This application is incorporated herein by this reference in its entirety. Specifically, these preprocessing algorithms process the near infrared information differently depending upon the distance between the catheter head  112  and the blood vessel wall  104  when the information was obtained. 
     In step  416 , a discrimination model is selected based upon the 0 to 2 millimeters distance. The prior preprocessing step corrects dataset generated at greater than 3.0 mm such that they can not be analyzed with a discrimination model based on 0-2 mm distances. 
     In more detail, one of five thresholds  422 ,  426 ,  430 ,  434 ,  438  is applied based upon a more the precise determination of the distance between the catheter head  112  and the blood vessel walls  104  produced by the structural analysis  413 . That is, for each location along the vessel wall, the corresponding NIR data are processes according to the distance between the catheter head  112  and the wall when the data were obtained by reference to the structural analysis information  413 . In the examples, the granularity for the different thresholds is less than 0.5 mm (step  420 ), 0.5-1.0 mm (step  424 ), 1.0-1.5 mm (step  428 ), 1.5-2.0 mm (step  432 ), and 2.0-2.5 mm (step  436 ). The data at each location along the wall is then processed using a separate one of the one of five thresholds  422 ,  426 ,  430 ,  434 ,  438 . 
     Thus, based upon the distance between the catheter head  112  and the vessel wall  104  when each NIR spectral signal is obtained, a different threshold is applied. The application of the threshold is used to determine whether or not there is a high probability of a thin cap atheroma or not, in one example in step  440 . 
       FIG. 4  shows an alternative embodiment. This similarly uses preprocessing if the blood distance is greater than 3 millimeters in step  414 . Then based upon the distance between the catheter head and the vessel walls when the data were obtained, different local models are applied in steps  510 ,  512 ,  514 ,  516 ,  518 . These are chemometric models that are used to assess the NIR spectral signal  410 . 
     Here, IVUS blood depth information is used to improve prediction accuracy. Different chemometric prediction models  510 ,  512 ,  514 ,  516 ,  518  are built for different blood depths: less than 0.5 mm (step  420 ), 0.5-1.0 mm (step  424 ), 1.0-1.5 mm (step  428 ), 1.5-2.0 mm (step  432 ), and 2.0-2.5 mm (step  436 ). 
     In some examples, the blood depths are determined “manually”. The user inputs the blood depth after measuring the IVUS image. 
     In other examples, NIR prediction models are augmented with the IVUS blood depth information. 
       FIG. 5  illustrates still another embodiment of the invention. Specifically, this illustrates that the point-by-point NIR analysis (Analysis (Pn)) of the blood vessels walls is compensated in each case by the instantaneous information from the IVUS or first energy form (distance Pn). In this way, adjacent points in the scan of the inner walls and their different NIR responses, (response of P 1 ) and (response of P 2 ), are combined with the instantaneous distance to the vessel walls, (distance P 1 ) and (distance P 2 ) when the NIR signal data  310  was obtained to obtain distance compensated analyses Analysis (P 1 ) and Analysis (P 2 ). In this way, the first energy form information is used at a very high level of granularity in order to compensate the NIR spectral signal information at the spatial resolution of the chemical and/or structural analysis modality. 
     While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.