Method for controlling the operation of an imaging system and system for acquiring images - Patents.com

Abstract

A system and method are provided for performing minimally invasive procedures in an automated or semi-automated manner using an imaging probe having an imaging modality compatible with the presence of intraluminal media to record images that are processed to identify regions of interest, and performing media replacement operations during subsequent minimally invasive operations where replacement of the intraluminal media is advantageous. The minimally invasive procedure may include capturing images with a second imaging modality, which may be a therapeutic procedure. The method may be performed in real time, where images acquired by the first imaging modality are processed in real time to determine whether to perform a minimally invasive procedure at a given location.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 61 / 411,225, entitled "SYSTEMS AND METHODS FOR IMPROVED VISUALIZATION DURING MINIMALLY INVASIVE PROCEDURES," filed November 8, 2010, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates generally to the field of high resolution medical imaging. Specifically, the present invention relates to minimally invasive methods that include two or more imaging modalities. [Background technology]

[0003] High resolution medical imaging has a wide range of diagnostic applications including evaluation of tissue structure, anatomical structure and / or composition, planning and / or guiding interventions in localized regions of the body, and evaluating the results of interventions that alter the structure, composition or other properties of localized regions. Of the many different high resolution imaging modalities, two extremely useful tools for clinical and research use are high frequency ultrasound and optical coherence tomography.

[0004] High frequency ultrasound is a technique that is particularly useful for intravascular and intracardiac procedures. For these applications, one or more ultrasound transducers are incorporated into catheters or other devices that can be inserted into the body. Two particularly important examples of high frequency ultrasound are intravascular ultrasound (IVUS) for imaging blood vessels and intracardiac echocardiography (ICE) for imaging cardiac cavities. Both ICE and IVUS are minimally invasive and involve the placement of one or more ultrasound transducers within blood vessels or cardiac cavities to obtain high quality images of these structures.

[0005] The central frequency of IVUS is usually in the range of 3-200 MHz, more typically in the range of 8-80 MHz. Higher frequencies provide higher resolution but at the expense of poorer signal penetration, which results in a smaller field of view. The penetration depth can range from less than a millimeter to several centimeters, depending on several parameters, such as the central frequency and geometry of the transducer, attenuation by the medium in which the imaging is taking place, and implementation-specific specifications that affect the signal-to-noise ratio of the system.

[0006] High resolution imaging methods often use rotating shafts that transmit torque to an imaging device near the tip of the probe. These rotating shafts are often long, thin, and flexible, allowing them to be delivered through anatomical conduits such as the vasculature, urogenital tract, airways, and other similar body lumens. Ideally, torque cables have properties such that when a torque is applied to the cable in a particular direction, the degree of rotation at the proximal and distal ends is closely related. In this way, the rotation angle at the distal end (inside the body) of the torque cable can be a good approximation of the rotation angle at the proximal end (outside the body), facilitating the design of ultrasound catheters.

[0007] There are other imaging systems that operate without torque cables, such as vascular endoscopy catheters (which employ fiber optic bundles), phased array imaging systems, etc. Additionally, imaging systems incorporating micromotors at the tip of the catheter instead of using a torque cable have also been proposed and demonstrated.

[0008] There are also variations on high frequency ultrasound techniques in which the acquisition and / or analysis of the backscattered signal is modified to obtain or infer additional information about the imaged tissue. These include elastography, which evaluates strain in tissue as it is compressed at different blood pressures (de Korte et al Circulation. 2002 Apr 9; 105(14): 1627-30), Doppler imaging, which evaluates motion such as blood flow within anatomical structures, virtual histology, which uses the radio frequency characteristics of the backscattered signal in combination with pattern recognition algorithms to attempt to estimate tissue composition (Nair, US Patent No. 6,200,268), second harmonic imaging (Goertz et al, Invest Radiol. 2006 Aug; 41(8): 631-8), etc. Ultrasound transducers, including the use of single crystal ultrasound transducers and composite ultrasound transducers, have improved significantly.

[0009] A catheter-based system for intravascular ultrasound to provide high resolution imaging of structures within blood vessels is disclosed in Yock (U.S. Pat. No. 4,794,931). The system includes an outer sheath with an ultrasound transducer mounted within the outer sheath near the tip of a long torque cable. A motor rotates the torque cable and ultrasound transducer assembly to generate 2D cross-sectional images of the anatomical structure, e.g., blood vessel. Linear translation of the catheter or torque cable and ultrasound transducer combined with rotational motion of the ultrasound transducer allows a series of 2D images to be acquired along the length of the catheter.

[0010] Hossack et al. (WO / 2006 / 121851) disclose a forward looking ultrasound transducer using a CMUT transducer and a reflective surface.

[0011] Optical imaging modalities based on fiber optic technology used in the medical field include optical coherence tomography (OCT), angioscopy, near-infrared spectroscopy, Raman spectroscopy, and fluorescence spectroscopy. These modalities typically require the use of one or more optical fibers to transmit light energy along a shaft between an imaging site and an image detector.

[0012] Optical coherence tomography is an optical technique similar to ultrasound, offering imaging resolutions on the order of 1-30 microns, but often with a shallower tissue penetration depth than ultrasound. Optical fibers can also be used to deliver energy for therapeutic procedures such as laser ablation of tissue and photodynamic therapy. Other useful optical imaging modalities include endoscopy or other similar or related imaging mechanisms that use a probe to obtain images based on the back reflection of light. Miniaturization of detectors and light sources may allow the catheter itself to contain the light source and / or detector, eliminating the need for optical fibers that act as intermediate components in the transmission and / or detection of light.

[0013] Optical coherence tomography is limited by a shallow penetration depth (on the order of 500-3000 microns) in most biologic media. Many such media, including blood, are optically opaque. Previously, OCT required blood displacement to obtain an optically clear environment. One approach involves replacing the blood with another fluid before measurements are made with blood-incompatible imaging modalities. U.S. Patent No. 7,625,366 to Atlas discloses an example of a flush catheter that injects a flush fluid into the blood vessels and performs OCT measurements with minimal blood displacement. Fluids that have been used or contemplated for this purpose include radiopaque contrast agents or various types of saline, lactated Ringer's solution, and the like. U.S. Patent No. 7,794,446 (Bosse et al.) and U.S. Patent No. 7,747,315 (Villard et al.) disclose improved flush fluid compositions for use in OCT imaging.

[0014] Replacement of blood by introduction of other fluids with greater transparency provides a period during which optical coherence tomography imaging can be performed. This time window can be expanded by reducing flow within the vessel, for example, using a guide catheter incorporating an occlusion balloon. For example, U.S. Patent Nos. 5,722,403, 5,740,808, 5,752,158, 5,848,969, 5,904,651, and 6,047,218 to McGee et al. disclose imaging catheter systems that include an inflatable balloon incorporating an imaging device. U.S. Patent No. 7,674,240 to Webler et al. discloses an improved device for inflating and deflating a balloon to occlude a vessel.

[0015] Replacement of blood with the introduction of other fluids to enhance OCT imaging has traditionally been a manual process, where the practitioner injects a clear fluid one or more times during the imaging procedure. Such injections can be accomplished in a variety of ways, including using a manual syringe, using a pressurized fluid delivery system, or using a powered pump. A pressurized fluid delivery system may simply use gravity to create pressure, or it may be a device that applies pressure to a compressible or deformable compartment filled with the fluid of interest. For example, pressure infuser bags use an inflatable bladder, similar to a conventional blood pressure cuff, to apply pressure to a bag of fluid in a closed compartment. The inflatable bladder and the bag of fluid share a closed space. Thus, when the bladder is inflated, such as by a manual hand pump, the fluid can be infused under pressure into the patient.

[0016] Alternatively, blood may be displaced using a balloon filled with an optically transparent medium such as, for example, radiopaque contrast agent, saline, or air. The balloon may surround the area of ​​the catheter where light is emitted from the imaging probe, such as for OCT imaging or near infrared (NIR) spectroscopy.

[0017] Here, problems may occur when replacing blood from a vessel. For example, there is a small possibility that the introduction of the replaced fluid may dislodge particles from the vessel wall, resulting in embolism. If the fluid is accidentally injected too forcefully, dissections may occur between layers of the vessel wall, or if the fluid is injected near an area where a dissection already exists, the dissection may be exacerbated. Potential complications of replacing blood with another fluid in a vital organ such as the heart include ischemia and arrhythmias of the target organ. If the replacement fluid does not deliver adequate oxygen to the myocardium, hypoxia may result in cardiac arrhythmias. These may also occur due to changes in electrolyte concentrations in the myocardium.

[0018] In blood vessels that supply vital organs that are susceptible to hypoxia, such as the heart, brain, and kidneys, prolonged blood replacement and / or vascular occlusion can cause clinical problems, necessitating practitioners to minimize the period during which blood is replaced.

[0019] The need to minimize the period of blood replacement must be balanced with the desire to acquire an adequate amount of imaging data. For example, when an imaging probe is translated along the long axis of a blood vessel, the portion of the vessel that is adequately imaged by optical imaging techniques is limited by the length of time that blood replacement is adequate. When injecting optically transparent fluids, not only is the period of blood replacement important, but the amount of fluid injected can also be critical.

[0020] For example, practitioners may use radiopaque contrast agents as optically transparent media, which are known in the medical field to often have detrimental effects on renal function and contribute to acute renal failure, while insufficient blood replacement will result in suboptimal imaging.

[0021] Variations of optical coherence tomography (OCT) include polarization sensitive OCT (PS-OCT), which uses the birefringence properties of tissue components to obtain additional information about structure and composition; spectroscopic OCT, which similarly enhances information about the composition of the imaged structures; Doppler OCT, which provides information about flow and motion; elastography with OCT; and optical frequency domain imaging (OFDI), which allows imaging data to be acquired more quickly and therefore allows more regions of interest to be imaged in a shorter period of time.

[0022] Besides OCT, there are several other forms of optical fiber-based imaging. Amundson et al. disclose a system for imaging through blood using infrared light (U.S. Patent No. 6,178,346). The range of the electromagnetic spectrum used in this imaging system is selected to optimize penetration through blood, thereby providing optical imaging through blood similar to that obtained by visible spectrum angioscopes, without the need to evacuate blood from the area being imaged.

[0023] Tearney et al. (US Pat. No. 6,134,003) disclose several embodiments that provide higher resolution imaging by optical coherence tomography than is readily achievable with high frequency ultrasound or IVUS.

[0024] Dewhurst (U.S. Patent No. 5,718,231) discloses a forward looking probe for intravascular imaging in which an optical fiber extends through an ultrasound transducer to illuminate target tissue in front of the end of the probe. The light then interacts with the target tissue to generate ultrasound waves that are received by an ultrasound sensor. The system is not configured to receive and process optical images, so the images are only photoacoustic images. The ultrasound sensor used in the Dewhurst device is limited to thin film polymeric piezoelectric materials such as thin film PVDF, and only receives ultrasound energy, but does not convert electrical energy into ultrasound.

[0025] Vascular endoscopes, endoscopes, bronchoscopes and many other imaging devices have been disclosed that visualize internal conduits and structures (e.g., blood vessels, gastrointestinal tract and pulmonary system) within a mammalian body based on the principle of illuminating an area within a living body near the tip of a rigid or flexible shaft. Images are then generated by a photodetector array (e.g., CCD array) near the end of the shaft or by a bundle of optical fibers that transmits light from the distal end of the shaft to the proximal end, allowing the practitioner to generate or view an image representing the illuminated area. Fiber bundles have disadvantages such as being bulky and reducing the flexibility of the shaft.

[0026] Other fiber optic based approaches for minimally invasive anatomical assessment include Raman spectroscopy as described by Motz et al. (J Biomed Opt. 2006 Mar-Apr; 11(2)), near infrared spectroscopy as described by Caplan et al. (J Am Coll Cardiol. 2006 Apr 18;47(8 Suppl):C92-6), and fluorescence imaging, e.g., tagged fluorescent imaging of proteolytic enzymes in tumors (Radiology. 2004 Jun;231(3):659-66).

[0027] In recent years, probe designs have emerged that combine multiple imaging modalities within a single device. Maschke (US Patent Application Publication No. 2006 / 0116571, corresponding to US Patent Application No. 11 / 291,593) discloses an embodiment of a guidewire fitted with both an OCT imaging transducer and an IVUS imaging transducer. The invention described therein has several shortcomings. A typical guidewire diameter is usually 0.014-0.035 inches (approximately 350-875 microns), while a typical ultrasound transducer is at least 400 microns by 400 microns in size, with frequencies in the 20-100 MHz range usually having larger sizes. If the transducer is too small, the beam will be poorly focused and the signal quality will be poor. In Maschke, the IVUS imaging mechanism and the OCT imaging mechanism are located at different positions along the length of the guidewire, and a substantial disadvantage associated with this type of configuration (where the IVUS imaging means and the OCT imaging means are located at different positions along the length of the imaging shaft) is that optimal registration of the images is not possible.

[0028] Similarly, U.S. Patent No. 7,289,842 to Maschke discloses a combined IVUS and OCT imaging system on a catheter where the IVUS and OCT imaging elements are offset from one another along the length of the catheter as it rotates about its longitudinal axis, and Maschke discloses generating an image where a central portion of the image is obtained substantially from the output of the higher resolution OCT imaging portion of the system and an outer portion of the image is obtained substantially from the output of the ultrasound imaging portion of the system, taking advantage of the combination of the greater penetration depth of ultrasound and the greater resolution of OCT for tissue adjacent the catheter.

[0029] US Patent No. 6,390,978 to Irion discloses the use of high frequency ultrasound in combination with optical coherence tomography, where the ultrasound beam and the OCT beam are superimposed on one another.

[0030] U.S. Patent Application Publication No. 2008 / 0177138 to Courtney et al. discloses an improved multimodal imaging system incorporating both IVUS and OCT transducers in a compact imaging assembly capable of side-viewing and / or forward-viewing imaging. Such multimodal imaging systems can provide more diagnostic information than single-modality imaging devices. In fact, optical coherence tomography typically provides better resolution than ultrasound and is more likely to identify certain structures or portions within vessels and other tissues than ultrasound. For example, the thickness of the fibrous cap near the surface of an artery or the presence of areas of inflammation or necrosis are preferably analyzed with optical coherence tomography.

[0031] However, many multi-modality imaging devices suffer from the problem that one or more of the imaging modalities are not blood compatible. For example, in the case of a multi-modality imaging device that combines both IVUS and OCT, the IVUS transducer can function with blood present in the vessel under examination, but the OCT modality requires blood replacement. This requirement complicates the procedure and makes it difficult to coordinate and reference the results from the two imaging modalities.

[0032] Another problem that arises when using multimodality imaging devices is the potential for inaccurate registration resulting from the use of one imaging modality followed by another after blood replacement. For example, intravascular imaging such as IVUS and OCT are often used for clinical trial purposes where imaging protocols are required. Manually using one or more modalities to identify areas that need to be evaluated in more detail with one or more other modalities is subject to high operator variability. Furthermore, reproducibility of the method for examination is important for clinical trials that rely on the ability to compare vascular structure and / or composition between different patients or at different time points.

[0033] In U.S. Patent No. 7,758,499, Adler proposes using IR imaging at wavelengths below 1000 nm, which is minimally compromised by the presence of blood, in combination with other imaging modalities, such as visible light imaging, where blood replacement techniques are employed to achieve IR and / or visible light imaging to achieve multi-modality optical imaging.

[0034] Also recently, Muller et al. have proposed using multiple imaging modalities in a single imaging device (U.S. Patent Application Publication No. 2009 / 0299195). Muller discloses a method and system that combines intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy to detect multiple different abnormalities in arterial morphology during a single intravascular procedure.

[0035] However, existing methods employ manual operations for sequentially acquiring multi-modality images, require significant skill, and also include complex operations for spatially aligning the images. Thus, there remains a need for a multi-modality imaging method that overcomes the above-mentioned problems, allows for standardized image data acquisition, and provides improved performance and clinical utility. Summary of the Invention [Means for solving the problem]

[0036] Embodiments of the present invention provide systems and methods that improve the ability to identify and / or collect data from blood vessels and other tissues with an intraluminal probe capable of collecting data using two or more imaging modalities, where one or more imaging modalities can collect data through the intraluminal medium (e.g., blood) and one or more other modalities perform better when the intraluminal medium is at least partially displaced from the field of view.

[0037] In one aspect, a method of performing a medium replacement operation within a lumen or cavity to perform a minimally invasive procedure is provided, the method comprising the steps of recording a first set of images acquired by a first imaging modality while performing a first translational movement of a functional part of an imaging probe, the first imaging modality being compatible with the presence of a replaceable medium, spatially correlating the first set of images with associated positions of the functional part of the imaging probe, processing the first set of images to identify a region of interest, performing the medium replacement operation and performing a second translational movement of the functional part of the imaging probe across the region of interest, wherein the minimally invasive procedure is performed within the region of interest during the medium replacement operation.

[0038] In another aspect, a method is provided for performing a media replacement operation to perform a minimally invasive imaging procedure within a lumen or cavity, the method comprising: (a) acquiring one or more images with a first imaging modality of an imaging probe that is compatible with the presence of a replaceable medium; (b) processing the one or more images to identify a region of interest; and (c) performing a media replacement operation if the region of interest is identified, and performing the minimally invasive procedure while performing the media replacement operation.

[0039] In another aspect, a method of performing a media replacement operation with a probe to perform a minimally invasive imaging procedure in a lumen or cavity is provided, the method comprising the steps of acquiring, with an external imaging device, one or more images of an area in which the minimally invasive procedure is to be performed, identifying a region of interest in the one or more images, acquiring one or more further images with the external imaging device while translating a functional component of the probe into the region of interest, the position of the functional component being identifiable in the one or more further images, and performing the media replacement operation and a translation operation associated with the functional component of the probe within the region of interest.

[0040] In another aspect, a method of performing a media replacement operation to perform a minimally invasive imaging procedure within a lumen or cavity is provided, the method comprising the steps of recording a set of measurements obtained from a non-imaging modality when performing a first translational movement of a functional part of a probe, the non-imaging modality being compatible with the presence of a displaceable medium, spatially correlating the set of measurements with associated positions of the functional part of the probe, processing the set of measurements to identify a region of interest, performing a media replacement operation and performing a second translational movement of the functional part of the probe across the region of interest, wherein the minimally invasive procedure is performed within the region of interest during the media replacement operation.

[0041] In another aspect, a method of performing a media replacement operation to perform a minimally invasive imaging procedure within a lumen or cavity is provided, the method comprising: (a) obtaining one or more measurements by a non-imaging modality of a probe that is compatible with the presence of a replaceable medium; (b) processing the one or more measurements to identify a region of interest; and (c) performing a media replacement operation if a region of interest is identified, and performing the minimally invasive procedure while performing the media replacement operation.

[0042] The functional and advantageous aspects of the present invention will become apparent from the following detailed information and drawings. [Brief description of the drawings]

[0043] [Figure 1] FIG. 1 is a block diagram illustrating a system for performing multimodality imaging. [Diagram 2] FIG. 2 is a block diagram illustrating a second system for performing multi-modality imaging incorporating an integrated media replacement system. [Figure 3-1] 1A is a perspective view of a flexible imaging probe including a connector, conduit, and imaging assembly as an example of a multimodality imaging system incorporating both intravascular ultrasound (IVUS) and optical coherence tomography (OCT). FIG. 1B is a perspective view of an enlarged tip region of the imaging probe of FIG. 1. [Figure 3-2] (c) is a schematic diagram of how the adapter connects the rotating and non-rotating components of the imaging probe to the rest of the imaging system, and (d) is a perspective view of an example of connecting the rotating and non-rotating components of the probe to the adapter. [Figure 4] FIGS. 1A, 1B, 1C, and 1D show the tip of an imaging probe capable of both acoustic and optical imaging, with a tiltable deflection surface that allows the imaging angle to be changed as a function of the rotational speed of the imaging assembly. [Diagram 5] 1(a)-(b) show an embodiment of a side-viewing multimodality imaging assembly with an ultrasound transducer and optical fiber for combined coplanar IVUS and OCT imaging. [Figure 6] 1 is a flowchart of a method of performing a minimally invasive procedure using results obtained by a first imaging modality to acquire images using a second imaging modality in which displacement of the intraluminal medium is advantageous. [Figure 7]1 is a flowchart of a method for performing a minimally invasive procedure using results obtained by a first imaging modality in real time to acquire images using a second imaging modality in which replacement of the intraluminal medium is advantageous. [Figure 8] 1 is a block diagram of a system for performing multi-modality imaging incorporating an integrated media replacement system and an external imaging device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0044] Various embodiments and aspects of the present invention will be described below with reference to the following details. The following description and drawings are illustrative of the present invention and are not to be construed as limiting the present invention. Many specific details are described for a thorough understanding of various embodiments of the present invention. In some instances, well-known or conventional technical details are not described in order to concisely illustrate the embodiments of the present invention. In addition, the order of steps of the method disclosed herein is not limited as long as the method is effective. Furthermore, unless otherwise specified, two or more steps may be performed simultaneously or in a different order than the order shown herein.

[0045] As used herein, the terms "comprises," "comprising," and the like are to be interpreted as inclusive and non-limiting terms, rather than exclusive. Specifically, as used in the present specification and claims, "comprises" and its conjugations mean that certain features, steps, or elements are included. These terms are not to be interpreted as excluding the presence of other features, steps, or elements.

[0046] As used herein, "exemplary" means "serving as an example, instance, or illustration" and is not to be construed as preferred or advantageous over other configurations disclosed herein.

[0047] As used herein, "about" and "approximately," when used in connection with a dimensional range of a particle, a composition of a mixture, or other physical property or characteristic, are intended to allow for slight variations in the upper and lower limits of the dimensional range, and not to exclude embodiments in which the majority of the dimensions fall within the range on average, but some dimensions are statistically outside the range, i.e., these embodiments are not excluded from the scope of the invention.

[0048] As used herein, the term "high resolution imaging" refers to high resolution imaging, including but not limited to ultrasound and optical imaging. As used herein, the term "high frequency ultrasound" refers to ultrasound imaging with frequencies greater than about 3 MHz, more typically in the range of 8-200 MHz.

[0049] As used herein, the term "imaging energy" refers to light energy, acoustic energy, or both. In particular, "light" and / or "optical" refer to electromagnetic waves having one or more wavelengths within the ultraviolet, visible, near infrared, and / or infrared spectra.

[0050] As used herein, the term "image analysis" refers generally to the processing of image data to identify regions of interest, which relate to one or more relevant images or portions thereof.

[0051] As used herein, the terms "translation" and "translation operation", when used in connection with an intraluminal probe, e.g., an imaging probe, refer to the translation of at least a portion of the probe, meaning that a functional portion of the probe translates relative to the lumen in which the probe is located. An example of a functional portion of the probe is the imaging assembly. A translation operation includes translating a functional portion of the probe relative to another portion of the probe, e.g., the outer sheath.

[0052] Embodiments of the present invention provide systems and methods for performing improved imaging during minimally invasive procedures using multimodal imaging catheter-based devices in which it is advantageous to replace intraluminal fluid during imaging in at least one imaging modality. Certain embodiments provide standardized and / or automated systems and methods for selecting an intraluminal region for a subsequent imaging step that involves replacement of the intraluminal medium.

[0053] In one embodiment, a multi-modality imaging system is provided that includes at least one imaging modality that is compatible with imaging in an intraluminal medium and at least one imaging modality that provides improved imaging performance through displacement of the intraluminal medium. Figure 1 is a block diagram illustrating an exemplary embodiment of a multi-modality imaging system 100. An imaging probe 105 that is intraluminally insertable and deliverable to an anatomical structure 102 (e.g., a lumen or a blood vessel) includes an imaging assembly 110 near its distal end 115, an optional imaging conduit 120 along a substantial portion of its length, and a connector 125 at its proximal end 130.

[0054] The imaging assembly 110 collectively refers to the components of the imaging probe 105 that transmit and / or receive multimodality signals (e.g., acoustic signals, optical signals) when imaging an area proximate the imaging assembly 110. The multimodality imaging assembly 110 includes components and devices for imaging using more than one imaging modality. The imaging assembly 110 may include imaging transducers, detectors, and / or imaging energy coupling devices. The imaging energy for irradiating tissue in the vicinity of the probe according to a given imaging modality may be generated by one or more transducers housed within the imaging assembly 110 and / or may be generated by one or more external transducers external to the imaging probe and delivered to the imaging assembly 110 via an imaging conduit 120 by an energy directing device (such as an optical fiber or optical waveguide). Similarly, incident imaging energy associated with a given imaging modality generated or scattered within the tissue to be imaged may be received by a detector housed within the imaging assembly 110 or may be received within the imaging assembly and delivered to an external detector via an imaging energy directing device within the imaging conduit 120. An imaging coupler and associated energy directing device may support one or more imaging modalities. For example, optical fibers and lens or mirror assemblies may be used to deliver imaging energy associated with both OCT and IR imaging modalities. Imaging energy associated with two or more imaging modalities may be generated and / or received by a common energy generating and / or receiving device and may be frequency multiplexed and / or time interleaved with one another. The imaging probe 105 may be rotatable or may include a rotatable imaging element to obtain a radial view of the interior of the lumen.

[0055] In embodiments where at least one imaging modality is optical imaging, the imaging assembly 110 typically includes a combination of optical fiber tips and optional optical components such as lenses (e.g., gradient index lenses known as ball lenses or GRIN lenses) that together can function as an optical receiver (a collection element that collects optical energy from the tissue being imaged) and an optical emitter (a focusing and / or beam directing element that focuses and / or directs the emitted optical beam to the tissue being imaged). Mirrors and / or prisms are often incorporated as part of the optical emitter and / or receiver. The imaging assembly 110, connector 125 and / or imaging conduit 120 can be immersed in a fluid such as saline. In multi-modality optical and acoustic imaging, the imaging probe 105 is compartmentalized into at least one compartment or lumen filled with gas for optical imaging and at least one compartment or chamber filled with fluid for acoustic imaging.

[0056] The imaging conduit 120 typically includes at least one optical waveguide or at least one (optionally more than one) conductor that connects the emitter and / or receiver to the adapter unit 140 via a connector 125. The imaging conduit 120 can also function as a mechanical drive force transmission mechanism for rotating or translating the imaging assembly. For example, the imaging conduit 120 may include an optical fiber encased by two layers of wire that are insulated from each other. Additionally, the imaging conduit 120 may be reinforced by other structural features, such as, for example, a helically wound wire, or other designs known to those skilled in the art that are used to construct imaging torque cables that rotate the scanning mechanism. The imaging conduit may also provide power to a micromotor at the tip of the imaging probe 105 that locally rotates one or more parts of the imaging assembly 110.

[0057] FIG. 3 is a perspective view of an exemplary embodiment of a multimodality imaging probe that may be used as part of a multimodality imaging system according to an embodiment of the present invention. The probe shown in FIG. 3 is disclosed in U.S. Patent Application No. 10 / 010,206, filed January 22, 2008, entitled "Scanning Mechanisms for Imaging Probe," and U.S. Patent Application No. 12 / 385,014, filed March 27, 2009, entitled "Scanning Mechanisms for Imaging Probe," the entire contents of which are incorporated herein by reference. Briefly, an imaging probe may include an imaging assembly that includes a movable member that directs an imaging energy beam at one or more angles in a forward looking direction. In two non-limiting examples, the orientation of the movable member may be changed by changing the rotational speed of an imaging assembly about which the movable member is pivotable, or by using magnetic forces or drive means.

[0058] An exemplary imaging probe incorporates both ultrasound (e.g., IVUS) and optical (e.g., OCT) modalities into a single catheter assembly for multimodality imaging. The system includes a flexible catheter including an optical fiber 40 and a coaxial electrical wire 50. A proximal connector includes the optical fiber 40, which may connect to an adapter that connects the optical fiber 40 to an optical imaging system "back end" for imaging. Additionally, an electrical connector 56 is provided for connecting one or more electrical conduits to, for example, electronic or power circuitry for an ultrasound processing system and / or a controller and processing unit.

[0059] The imaging conduit in this embodiment rotates about its longitudinal axis, and the connection of the rotating fiber optic probe is accomplished using a fiber optic rotary joint incorporated as part of the proximal connector of the imaging probe 10 or as part of the adapter 14. Similarly, the conductors that rotate with the imaging conduit are connected to the relatively stationary conductors of the ultrasound circuit and / or the controller and processing unit by, for example, slip rings or rotary transformers. These slip rings can be incorporated as part of the proximal connector of the imaging probe 10 or as part of the adapter 14.

[0060] FIG. 3(a) is a cross-sectional view taken along the dashed line of the center of the imaging probe of FIG. 3, showing the optical fiber 40, the guidewire port 44 and guidewire 42, the imaging conduit 34, the imaging conduit lumen 46, the outer sheath 48, and the coaxial wire 50. The outer sheath 48 is a hollow, flexible, elongated shaft formed from a biocompatible material and having a diameter suitable for inserting the hollow, elongated shaft into lumens and cavities in the body.

[0061] The imaging probe may be provided with ports at one or more locations along its length to facilitate flushing. A close-up view of the end of the imaging probe 10 shown in FIG. 3(b) shows the tip of the guidewire 42 at the end of the outer sheath 48, extending beyond the end of the outer sheath 48 and the flush port 54.

[0062] As shown in FIG. 3, the proximal end of the imaging probe 10 includes a guidewire port 55 through which the guidewire 42 is inserted, and a connector assembly 36 that includes a flush port 58 and electrical contacts 56 along the connector body.

[0063] FIG. 3(c) shows generally how the rotating and non-rotating components of the imaging probe can be connected to the rest of the imaging system by an adapter. FIG. 3(d) shows generally how the rotating components of the imaging probe can be connected to the rotating components of the adapter. Each rotating component can be electrically, optically and / or mechanically connected using connectors and other configurations known in the art. Similarly, the non-rotating components of the imaging probe can be connected to the non-rotating components of the adapter 14. The adapter 14 can include slip rings, rotary transformers, optical rotary joints and other similar components that electrically or optically connect the rotating components to the non-rotating components to enable communication of necessary electrical and optical signals with the rest of the system.

[0064] Dual-fiber optical rotary joints could also be used, but would be significantly more complicated to construct. Electrical connections between any conductors attached to rotating components in the imaging probe 12 could be connected to non-rotating conductive elements by metal slip rings and springs, metal slip rings and brushes, or other well-known techniques for making conductive contact between stationary and rotating conductors.

[0065] Although FIG. 3(d) shows the electrical, optical and mechanical connections separately, depending on the needs of a particular embodiment, some connectors may be combined into a mating connector to reduce the number of connectors that need to be individually connected between the probe and the adapter, eliminating some connectors and making the connections with fewer connectors.

[0066] 4 shows an example of the internal structure of the tip of an imaging probe incorporating a multi-modality imaging assembly. The assembly includes a tiltable component 70 that deflects imaging energy emitted and / or received by one or more components not directly attached to the tiltable component 70. An ultrasonic transducer 88 and an optical emitter 92 direct imaging energy to the tiltable component 70. The imaging energy is then deflected by an energy deflecting component attached to the tiltable component 70. For ultrasound imaging, the energy deflecting component (tiltable component 70) may include an acoustically reflective surface, such as a solid metal surface (e.g., stainless steel) or a crystalline surface such as quartz, glass, or a hard polymer.

[0067] For optical imaging, the energy deflection component (tiltable component 70) may have a light reflecting surface, such as a mirror formed from polished metal, metallized polymer such as metalized biaxially oriented polyethylene terephthalate (Mylar), sputtered or electrochemically deposited metal, metal foil or other reflective components such as thin film mirrors, etc. Metals commonly used to form mirror surfaces include aluminum, silver, steel, gold, or chromium, etc.

[0068] FIG. 4(a) shows an exemplary embodiment of the tip 29 of an imaging probe 31, where the tip is provided with an imaging assembly 30 including a tiltable part 70, which is a disk attached to a pin 72, and the disk 70 is pivotable about the pin.

[0069] The pin 72 defines the tilt axis of the tiltable disk 70. When the imaging assembly 30 is stationary, the disk 70 remains at an arbitrary starting position. In the illustrated embodiment, this starting position is defined by a stop piece 80 corresponding to the maximum imaging angle, against which the restoring force exerted by the torsion spring 76 presses the disk 70. Figure 4(b) is a cross-sectional view taken along the vertical dashed line 2(c)-2(c) of Figure 4(a).

[0070] The tilt angle increases when the tiltable part 70 is tilted from the desired orientation by external forces, such as gravity, magnetic forces, electrostatic forces, friction with other moving parts or fluids, compression forces, leverage forces, normal forces, or other sources of incompletely opposed torque acting on the tiltable part 70 about the tilt axis.

[0071] The range of tilt angle of the tiltable component 70 may be restricted by one or more stops 80, 82. For example, the stop 80 may be a post or lip extending from a shell 84 of the imaging assembly 30, which prevents further changes in the tilt angle when the tiltable component 70 is in contact with the stop 80. Thus, the stop may be used to restrict the tilt angle from exceeding a maximum value defined by the position of the stop. Once the tilt angle reaches this maximum value, the normal force that the stop 80 exerts on the tiltable component 70 opposes the restoring mechanism. In many embodiments, this maximum tilt angle is the tilt angle reached when the imaging assembly 30 is stationary and at a low rotational speed.

[0072] Additional or alternative stops 82 may be provided to define a minimum tilt angle that the tiltable component 70 reaches when it is at the upper rotational speed of its range of motion. As will become apparent from the following description of specific embodiments, in practice, a zero tilt angle often provides no special advantage.

[0073] The imaging assembly 30 may include one or more mechanisms that contribute to increasing the tilt angle of the tiltable part 70. For purposes of explanation, such mechanisms are referred to herein as restoring mechanisms. The restoring mechanism may be a torsion spring 76 (FIGS. 4(a) and 4(c)) or a compression spring, where one end of the spring 76 is mechanically in contact with or connected to the tiltable part 70 and the other end is mechanically connected to another part of the imaging probe 31, e.g., the body of the imaging assembly.

[0074] As the imaging assembly 30 rotates, the disk 70 attempts to align itself so that the normal to the plane defined by the surface of the disk 70 is substantially parallel to the long axis. As shown in FIG. 4(c), the other stop piece 82 shown (corresponding to the minimum imaging angle) prevents the disk 70 from reaching the desired orientation at high rotational speeds of the imaging assembly. In a properly configured imaging assembly, the stop piece 82 corresponding to the minimum imaging angle corresponds to an angle of zero and provides imaging parallel to the long axis of the imaging probe.

[0075] 5 shows another embodiment of a multimodality imaging assembly for use in a multimodality imaging system as disclosed in U.S. Patent Application Serial No. 12 / 010,208, entitled "Imaging Probe with Combined Ultrasound and Optical Means of Imaging," filed Jan. 22, 2008 by Courtney et al., which is incorporated herein by reference in its entirety. As shown in FIG. 5(a), imaging assembly 550 is configured to provide imaging in the same direction by acoustic and optical means and uses an acoustic transducer that allows optical energy to be transmitted through a channel in the acoustic transducer. Essentially, assembly 550 uses an acoustic transducer 502 that has been modified to have an optically transparent channel formed through its substrate. The acoustic transducer 502 may be any type of ultrasonic transducer known in the art, such as a piezoelectric (e.g., PZT or PVDF, piezoelectric single crystal, etc.), a composite transducer, or a capacitive micromachined ultrasonic transducer (cMUT), etc.

[0076] Electrical conductors 500 are connected to conductive layers 501 on either side of the transducer's acoustic substrate 502. Optical fibers 503 provide optical conduits to enable optical imaging. One or more matching layers may be added to the output face of the transducer, such as an epoxy layer (e.g., a silver or copper conductive epoxy layer, which may serve as one or both of the electrodes that drive the transducer) or a polymer (e.g., parylene or PVDF).

[0077] Conductive layers 501 on either side of the piezoelectric material 502 are incorporated due to the need to apply a voltage across the piezoelectric. The aperture 507 is connected to an optical waveguide 503, either directly or via one or more mirrors or prisms and one or more lenses (not shown). If any optical components are included within the aperture, they may be separated from the acoustic substrate 502 by a buffer / insulation layer 506 of a compliant material, e.g., silicon or polymer, which acts as an electrical insulator or minimizes the transmission of pressure generated by the acoustic substrate 502 to the optical components.

[0078] As shown in FIG. 5( b ), the light from the fiber can be directed to a mirror 404 (or a prism) that deflects the light from the fiber into an optically transmissive channel 507 .

[0079] Yet another non-limiting example of a multimodal imaging system is shown in Figure 1 of U.S. Patent Application Publication No. 2009 / 0299195, entitled "Multimodal Catheter System and Method for Intravascular Analysis," by Muller et al., which is incorporated herein by reference in its entirety. This system combines intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy to detect multiple different abnormalities in arterial morphology with a single intravascular procedure.

[0080] The above-mentioned examples are illustrative of multi-modality imaging systems that can be used in the embodiments of the present invention described below. It should be noted that the above-mentioned examples are presented as non-limiting examples, and other multi-modality imaging probes can be used in the embodiments of the present invention.

[0081] 1, the multimodality imaging system 100 is configured to support imaging modalities in which it is advantageous to displace intraluminal media during non-invasive procedures and to move the intraluminal media during imaging. Such displacement may be provided and controlled by one of a number of devices and subsystems, including, but not limited to, a subsystem for displacement of intraluminal media by endoluminal flushing and a subsystem for displacement of intraluminal media by controlled obstruction of the lumen, as disclosed in U.S. Patent Application Publication No. 2009 / 0299195 and U.S. Patent No. 7,758,499, entitled "Method and Apparatus for Viewing Through Blood," which are incorporated herein by reference in their entireties.

[0082] In one embodiment, endoluminal flushing is accomplished by supplying flush fluid to the imaging probe 105 through an input port and forcing the flush fluid into the lumen through output ports at one or more locations along the length of the imaging probe. Alternatively, flush fluid may be supplied through a conventional guide catheter that allows fluid to be introduced into the lumen being imaged. Alternatively, flush fluid may be supplied through a dedicated flush catheter, such as that disclosed in U.S. Patent No. 7,625,366, entitled "Flush Catheter with Flow Directing Sheath," which is incorporated herein by reference in its entirety. Flush fluid, such as saline, lactated Ringer's solution, or contrast media, may be supplied manually, for example, using an external syringe. In some exemplary embodiments, flushing may be accomplished by external pressurization of the medium using an autoinjector, a pressurized infusion bag, a peristaltic pump, a syringe pump or a piston pump, a valve system, a gravity pressurization system, or automatic or manual pressure application.

[0083] In one embodiment, a medium displacement device, generally designated 135, provides and / or regulates or controls one or more medium displacement operations. As described above, the medium displacement device 135 may be connected to the imaging probe 105 via an interface, may be provided to perform the medium displacement, or may be a separate device (e.g., a guide catheter or a dedicated flush catheter). In a non-limiting example, the medium displacement device 135 may include an external pump (not shown) that controls the amount of flush fluid (from a reservoir) to the region of interest. In another example, the medium displacement device 135 may comprise an inflatable balloon housed on or within the imaging probe 110 that fully or partially occludes the lumen through controlled inflation to achieve the medium displacement.

[0084] In other embodiments, the media replacement device 135 may further include an external manual switch that performs or permits automated replacement actions only when a user or physician operates the switch. Such a switch provides a semi-automated mode of management of media replacement that requires active involvement of a human practitioner in overseeing any automated replacement actions. Non-limiting examples of suitable switches include a button or foot pedal that must be continuously depressed to perform an automated replacement (e.g., injection or inflation).

[0085] 1, the driver and adapter unit 140 provides an interface that allows for the transfer of power and / or signals over any fibers and / or wires between the imaging probe 105 and suitable control and / or processing subsystems. This may include a motor driver subsystem 145 that imparts rotational motion to rotating components of the imaging probe. The motor driver may also actuate a retraction mechanism, an advancement mechanism, or a back and forth shuttle mechanism to effect longitudinal translation of the imaging assembly 110. Such longitudinal translation of the imaging assembly 110 may be performed with longitudinal translation of an external shaft (not shown) that encases the image assembly 110 and the imaging conduit 120, or may be performed within a relatively stationary external shaft.

[0086] Further sensor subsystems may be incorporated as part of the driver and adapter unit 140, such as a position sensing subsystem 150 for sensing the angle of rotation of rotating components within the imaging probe 110 and / or the longitudinal position of the imaging assembly 110. The imaging probe 110 may also include memory components, such as an EEPROM or other programmable memory device, for storing information related to the imaging probe 110, such as information identifying the imaging probe 110 specifications and / or calibration information. The driver and adapter unit 140 may further include an amplifier 160 for improving the transfer of electrical signals or power between the imaging probe 110 and other parts of the system.

[0087] The driver and adapter unit 140 is connected to a control unit 165 via an interface. The control unit 165 includes a first imaging modality controller subsystem 170 and a second imaging modality controller subsystem 175 (the system may include additional imaging modalities and controllers in addition to the two shown) that support a multi-modality imaging device, which may include any of the following imaging modalities, including but not limited to: (1) ultrasound, (2) optical coherence tomography, (3) angiography, (4) infrared imaging, (5) near-infrared imaging, (6) Raman spectroscopy-based imaging, and (7) fluorescence imaging.

[0088] Although the first and second imaging modality controllers are shown here as separate subsystems, they may be one and the same. For example, OCT data and near infrared (NIR) spectroscopy data may be acquired via a common light source and signal acquisition system. Also, if the first and second modalities are both IVUS, one modality being a lower frequency IVUS than the other, the hardware required to generate and acquire the two sets of IVUS data may be the same, with only different operating parameters.

[0089] The optical controller may include any or all of the following components: interferometer components, one or more optical reference arms, optical multiplexers, optical demultiplexers, light sources, photodetectors, spectrometers, polarizing filters, polarization controllers, timing circuits, analog-to-digital converters, and other components known in the art that support any of the optical imaging techniques disclosed herein or incorporated by reference.

[0090] The ultrasound controller may include any or all of the following components: a pulse generator, electronic filters, analog to digital converters, parallel processing arrays, envelope detectors, amplifiers including time gain compensated amplifiers, and other well known components that aid in any of the acoustic imaging techniques disclosed herein or incorporated by reference. The control unit 165 may include one or more of the following, but is not limited to: a motor drive controller 180, a position sensing control circuit 190, timing circuits, a volumetric imaging processor, a scan converter, and other subsystems.

[0091] As shown in FIG. 1, the medium replacement device 135 can be operated and / or controlled independently from the control unit 165. For example, the medium replacement device 135 can include a syringe or a manual pump. In another embodiment, shown in FIG. 2, the control unit 165 further comprises a medium replacement controller 185 that can monitor the medium replacement operation and can also automate or semi-automate the medium replacement operation. In another embodiment, the medium replacement controller 185 can be directly connected to the medium replacement device 135 via an interface. The medium replacement controller 185 can monitor information including, but not limited to, the volume of flush fluid delivered to a given medium replacement operation, the total amount of flush fluid delivered to multiple media replacement operations for a given patient and / or minimally invasive procedure, the duration a given medium replacement operation is performed, the total duration multiple media replacement operations are performed for a given patient and / or minimally invasive procedure, control signals and / or commands communicated to devices or subsystems to perform the media replacement, etc.

[0092] The media replacement controller 185 may provide input to a feedback loop used during control of a sequence of imaging and replacement operations coordinated by the processing unit 205, as will be further described below.

[0093] The control unit 165 may further include an optional cardiac sensor 200, e.g., an optional cardiac sensor controller 195, which controls an electrode sensor that acquires an electrocardiogram signal from the body of the patient being imaged. The electrocardiogram signal may be used to time the acquisition of imaging data in situations where cardiac motion affects image quality. The electrocardiogram may also serve as a trigger for initiating an acquisition sequence, e.g., for changing the rotational speed of a motor to achieve a desired scan pattern. For example, an imaging sequence may be triggered by an electrocardiogram (ECG) to acquire images during a particular phase of the cardiac cycle, such as systole or diastole. The electrocardiogram signal may optionally serve as a trigger for the system to change the infusion or inflation rate of the media replacement system to account for pulsatility or blood flow under observed physiological conditions.

[0094] The control unit 165 is connected via an interface to a processing unit 205, which includes a processor 210 and a memory and / or storage subsystem 215 connected by a bus, and performs a number of processing functions to coordinate various aspects of the system operation. Although the control unit 165 and the processing unit 205 are shown as separate subsystems, they may be included in an integrated computer system 220. Furthermore, some or all of the elements of the control unit 165 may be performed by the processing unit 205. Furthermore, the processor 210 may include a number of processing elements, such as one or more CPUs, field programmable gate arrays, GPUs, ASICs, DSP chips, and other processing elements known in the art. The processing unit 205 may also be connected to a display and user interface 225 for real-time display or display of imaging data subsequent to the time of acquisition.

[0095] Additionally, the imaging system 100 may include data storage components (e.g., memory, hard disk drives, removable storage devices, readers and recorders for portable storage media such as CDs and DVDs), which may be connected via interfaces to parts of the processing unit and / or control unit.

[0096] In one embodiment, the processing unit 205 is programmed to analyze images acquired using a first imaging modality and utilize the imaging results to automate the recording of images based on a second imaging modality where an endoluminal medium replacement operation is required or advantageous during image acquisition. The first imaging modality may be compatible with the endoluminal medium, i.e., may not require an endoluminal medium replacement operation to acquire images with sufficient diagnostic sensitivity or clinical utility.

[0097] In one embodiment where the intraluminal fluid is blood, the first imaging / detection modality may be any of the following, but is not limited to: grayscale IVUS, radio frequency IVUS (e.g., Virtual Histology™, integrated backscatter, or iMap™), elastography, NIR spectroscopy, sono-luminescent imaging, microbubble enhanced IVUS, targeted microbubble enhanced IVUS, photoacoustic imaging, fluorescence spectroscopy, biosensors such as ion selective field effect transistors, and the second imaging modality may be any of the following, but is not limited to: OCT, angioscope, NIR spectroscopy, Raman spectroscopy, IVUS, radio frequency IVUS, elastography, sono-luminescent imaging, microbubble enhanced IVUS, targeted microbubble enhanced IVUS, fluorescence spectroscopy, and photoacoustic imaging. The second imaging modality, which is optical in nature, may use wavelengths in the ultraviolet, visible, NIR and / or infrared portions of the electromagnetic spectrum.

[0098] In other embodiments, the first and second imaging modalities may be a single imaging modality, in which case an image may be acquired first in the presence of intraluminal media, and then an image enhanced by the substitution process may be acquired.

[0099] Ultrasound has reasonable penetration into blood, but the ability to identify vessel walls can be further improved or image contrast can be improved by displacing blood from the field of view of the ultrasound imaging probe. On the other hand, ultrasound has good penetration into biological media, e.g., blood and soft tissue, with a penetration depth of several millimeters or centimeters wide, which exceeds the penetration depth of optical coherence tomography.

[0100] In one embodiment, the first and second imaging modalities are both IVUS, the first modality being an IVUS having a lower frequency range than the second IVUS modality. Generally speaking, higher frequencies of ultrasound provide better resolution than lower frequencies, but the higher frequencies provide less penetration into blood. Therefore, it is desirable to displace blood when imaging with higher frequency IVUS. Separate ultrasound transducers may be provided for the two IVUS imaging frequencies, or one ultrasound transducer may have a bandwidth wide enough to support two or more imaging frequencies, where the imaging frequency is determined in part by the frequency of the pulses used by a pulser to excite the ultrasound transducer.

[0101] The ability to combine ultrasound with optical imaging modalities, such as OCT or near infrared spectroscopy, using a single imaging probe is advantageous in terms of selecting the required resolution and penetration depth. Furthermore, much of the information acquired by optical coherence tomography complements the information acquired by ultrasound, and analyzing or displaying the information acquired by both imaging modalities improves the ability to gain a deeper understanding of the examined tissue, e.g., its composition.

[0102] It should be noted that while intravascular OCT is severely hindered by the presence of blood, NIR spectroscopy is less affected and can assess plaque composition to a depth of several millimeters through the blood, however, it is not effective for larger vessels and for aneurysmal segments in vessels that would otherwise have a normal internal diameter.

[0103] FIG. 6 is a flow chart illustrating an embodiment in which an image recorded using a first imaging modality is used to perform a displacement operation when a subsequent image is acquired using a second imaging modality that is disturbed by the presence of a displaceable intraluminal medium.

[0104] In step 300, a multi-modality imaging probe, e.g., the imaging probe 105 of FIG. 1, is inserted into the lumen to acquire images by a first imaging modality compatible with the presence of a displaceable intraluminal medium. The first imaging operation may be, for example, a translation operation, such as a retraction, performed while recording imaging data using the first imaging modality. The translation operation may be automated or may be performed at a constant translation speed selected and / or optimized for the first imaging modality. Signals obtained from the first imaging modality device (provided in the imaging assembly 110 of the imaging probe 105) during the first translation operation are provided to the first imaging modality controller 170.

[0105] In this embodiment, position sensing is employed during the translational movement to determine the position of the recorded image relative to a reference position and optionally relative to a reference orientation. The recorded image is thus associated with the position and optionally the orientation of the imaging probe. Position sensing may be performed using any one of a number of well-known techniques and is shown in Figure 1 collectively as a position sensor 150 and a position sensing controller 190 (which together may form a composite subsystem).

[0106] In one embodiment, position sensing is performed by longitudinal position sensing within the lumen, for example using an encoder or other position sensor connected to the imaging probe, retraction motor, or drive element. Position sensing may be performed by spatial domain measurements or may be estimated based on time domain measurements if translation or rotation occurs at a known rate. For example, position information regarding the longitudinal position of the imaging probe may be estimated based on the period of time over which the translation occurs, assuming that the rate of change of the imaging probe position during this period is known. During the translation of the probe, the rate of change of position may be constant. Rotational angle sensing may be performed using a rotary encoder or other position sensor connected to the imaging probe, as disclosed in co-pending U.S. patent application Ser. No. 12 / 010,207, entitled "Medical Imaging Probe with Rotary Encoder," filed Jan. 22, 2008, which is incorporated herein by reference in its entirety.

[0107] In other embodiments, position sensing may be performed using detection elements within the imaging probe that determine the position of the imaging probe within an externally generated field, e.g., a magnetic field, which may be performed in combination with orientation detection. Suitable sensors provided by Mediguide Ltd. may be employed, as disclosed in U.S. Patent Application Publication No. 2009 / 0299195 to Muller et al.

[0108] After performing the first translation operation, in step 305, the image data from the first imaging modality controller 170 is provided to the processor 210 for image analysis. The processor 210 analyzes the image data based on image processing algorithms to identify regions of interest, e.g., regions of diagnostic, research, and / or clinical interest. The identified regions may represent various anatomical structures and / or features, including, but not limited to, desired tissue types for subsequent analysis, specific anatomical features, known or suspected pathological structures or features, and medical or other man-made structures. Suitable regions of interest include, but are not limited to, plaques, possible thrombi, branch points, lesions, calcified regions, implanted regions such as stents or brachytherapy implants, stenoses, thickened regions of vessel walls, lipid cores, necrotic regions, fibrous caps, dissections, masses, etc. The regions of interest may also be regions containing detected microbubbles, e.g., targeted microbubbles. Additionally, the region of interest may include an indeterminate or uncertain structure or composition such that an automated or semi-automated processing algorithm cannot definitively assess the region of interest without further imaging data.

[0109] Regions of interest may also include vascular lesions that have not yet reached clinical symptoms but are at high risk of rupture or erosion and potentially causing acute myocardial infarction. These so-called "vulnerable plaques" are of interest because it is conceptually desirable to treat these plaques to prevent adverse clinical events.

[0110] In other embodiments, the region of interest may be any region of any image obtained based on the first imaging modality that is suspected to have an inconclusive result. For example, when using NIR spectroscopy as the first imaging modality, the region of interest may be defined as a region where the vessel wall is further away from the imaging assembly of the imaging probe than is permitted by the range of the NIR spectroscopy probe in the presence of blood. Alternatively, for IVUS imaging, such a region may be defined as a region where the vessel wall is in contact with the imaging probe. IVUS may have some artifacts in the portion of the field of view closest to the catheter. These include a phenomenon called transducer ring-down and artifacts due to ultrasound reflections from the catheter sheath. OCT is substantially unaffected by such artifacts and provides good images in the portion of the field of view closest to the catheter.

[0111] In one embodiment, the region of interest may include a stent having a known geometry, structural configuration and / or imaging signal characteristics, which may include a metallic stent, a polymeric stent, a biodegradable stent, a pacemaker wire, a guidewire, etc.

[0112] The region of interest can be identified using one of many known image analysis methods. The region of interest may be identified by calculating metrics from the processed images that can be compared to expected values ​​or ranges. In another embodiment, the image analysis is performed in combination with a pattern recognition method to identify the region of interest. In one embodiment, the imaging analysis includes border detection. For example, border detection may be used to detect areas where plaque thickening occurs, which are suitable for subsequent imaging with a second imaging modality. Border detection can be performed in many different ways. As one non-limiting example, Papadogiorgaki et al. disclose border detection using a contour optimization technique (Ultrasound in Medicine and Biology 2008, Sept 34(9) 1482-98). Methods for border detection are also disclosed in, for example, U.S. Patent No. 7,359,554, entitled “System and Method for Identifying a Vascular Border,” and U.S. Patent Application Publication No. 2005 / 0249391, entitled “Method for Segmentation of IVUS Image Sequences,” both of which are incorporated herein by reference in their entireties.

[0113] In one embodiment, the region of interest is identified by image processing techniques including tissue characterization techniques. In embodiments where the first imaging modality is IVUS or variations thereof, the region of interest may be determined by radio frequency characteristics of the backscattered ultrasound signal in combination with a pattern recognition algorithm, for example as disclosed in U.S. Patent No. 6,200,268 to Nair, which is incorporated herein by reference in its entirety. Alternatively, the tissue characterization technique may employ intensity analysis of grayscale pixels. For example, in the generated image, pixels with a certain intensity range are likely to represent soft plaque, which may further include lipid-rich regions. Alternatively, a tissue analysis algorithm may be used, such as a wavelet decomposition algorithm or an algorithm that evaluates statistical properties of the imaging data. Alternatively, a heuristic algorithm that detects known properties of certain tissue components may be used. For example, the algorithm may detect acoustic shadows in IVUS imaging that are known to be highly correlated with the presence of calcification.

[0114] It may be desirable to input some imaging data parameters into a pattern recognition algorithm that can identify the most likely tissue composition for a particular region. Such pattern recognition algorithms may be neural networks, fuzzy logic algorithms, data classification trees, nearest neighbor methods, or some other pattern recognition method. Such pattern recognition algorithms may be trained with imaging data where the actual underlying composition of the tissue is known, such as by histology, radiography, spectroscopy, ultrasound, optical imaging, or some other combination. Such pattern recognition algorithms not only identify the likely underlying composition of the tissue for a given region of interest, but also provide an estimate of the likelihood of correctness. Alternatively, the pattern recognition algorithm may simply identify regions where the underlying composition is uncertain according to a first imaging modality, prompting the need for further analysis by a second imaging modality.

[0115] Additionally or alternatively, the region of interest may be determined based on a non-imaging method, for example, based on temperature heterogeneity. A specific example of a method for detecting temperature heterogeneity is disclosed in, for example, "Stefanidis C, et al., "Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo: a new method of detection by application of a special thermography catheter", Circulation 1999;99;1965-71". A temperature sensor may be incorporated into the tip of the probe 115 to detect changes in temperature of the arterial wall, and areas with higher temperatures are likely to correspond to areas of inflammation. In yet another embodiment, the region of interest may be determined based on areas with minimal concentrations of a marker of inflammation that detects a biological analyte, for example, C-reactive protein (CRP), locally detected by a local biosensor, such as an ion-selective field effect transistor (ISFET) with a selective detection molecular species, for example, an antibody or aptamer bound thereto.

[0116] The automated systems and methods for identifying regions of interest for further analysis by a second imaging modality as described above may include settings that allow a user to adjust or change parameters that affect the identification of the region of interest. For example, such settings may allow a user to select particular pathological features or structures, such as identification of regions having at least a selected amount of plaque, a selected minimum vessel wall thickness, or a selected degree of eccentricity of wall thickness. It is known that plaque is unlikely to be present in areas with a minimum amount of vessel wall thickening, and plaque is likely to be present in areas with eccentricity of vessel wall thickening.

[0117] In other embodiments, one or more threshold parameters may be configurable to trigger the identification of a region of interest. Such embodiments are particularly important when contrast, saline, or other flushing fluid is injected during a media replacement operation. By controlling one or more threshold parameters for identifying a region of interest, a clinician or practitioner can control or limit the amount of flushing fluid delivered during a minimally invasive procedure, ensuring that the impact on the patient of the amount of flushing fluid used is controlled or minimized.

[0118] While the embodiments described above include automated techniques for identifying the region of interest, a user or practitioner may manually define the region of interest by reviewing the resulting images acquired from a first translational (e.g., back) operation and select the region of interest for an automated or semi-automated second translational operation in which the region of interest is imaged with a second imaging modality while a media replacement operation is being performed, as described further below.

[0119] The region of interest may also be defined or identified based on more than one imaging modality. For example, an imaging probe may include multiple imaging modalities that are compatible with the presence of intraluminal media, and the region of interest may be identified by processing the multiple imaging modalities based on the methods described above.

[0120] 6, after acquiring one or more regions of interest in step 305, regions of interest are selected in step 310 to be imaged by the second imaging modality during the second retraction motion. This step may involve automatically selecting all of the regions of interest identified in step 305, or alternatively, this step may involve selecting a subset of the regions of interest identified in step 310. In the latter case, the selection of the subset of regions of interest may be performed by a user operating the system via the user interface 225, or may be performed by pre-selecting the types of identified regions desired for subsequent analysis.

[0121] For example, in step 305, broadly related regions of interest, such as normal anatomy, implants, tissue types, pathological structures or indications, etc., may be identified, but the system may be configured to image only detected implants using a second imaging modality. Alternatively, the system may rank the regions of interest identified in step 305 based on, for example, but not limited to, plaque size, likelihood of being a thin-capped fibroatheroma, location within the vasculature, and / or some other criteria. Once the regions of interest are ranked, a subset, e.g., a group of the highest ranked regions of interest based on the criteria used, may be selected.

[0122] After selecting a region of interest for imaging with a second imaging modality (either automatically or through user intervention), a second retraction operation is performed to image the selected region of interest, which may be performed according to a number of embodiments, as described below.

[0123] First, the imaging probe (and / or its functional components) is translated to the region of interest selected in step 315. This translation may be performed manually, with feedback from a position sensing system determining that the probe has been moved to the appropriate position, or, additionally or alternatively, the imaging probe may be translated automatically to place the imaging assembly in the required position.

[0124] Automatic translation of the imaging probe to the desired location can be aided or guided by image comparison techniques. Cross-correlation techniques can be used to identify images or regions within an imaging dataset that are similar to one another. In its simplest form for 2D images, the intensity of each pixel in one image is multiplied by the intensity of the corresponding pixel in the other image, and the sum of these products is calculated. The more similar the images are, the higher the sum of the products. By repeatedly shifting, rotating and / or morphing one image relative to the other and repeating the cross-correlation operation, an estimate of the similarity of the two images can be produced that takes these changes into account.

[0125] The cross-correlation technique can be extended to 3D imaging data sets or can be focused on localized regions within the 2D imaging data sets. The cross-correlation technique can also be applied to 2D imaging data sets derived from 3D imaging data. For example, rather than applying cross-correlation to cross-sectional images, a longitudinal 2D image can be used that is generated by extracting any plane from a series of 2D cross-sectional images that are stacked together to form a 3D data set. In this embodiment, cross-correlation of preliminarily selected images or imaging data sets corresponding to the start and stop points identified during the first retraction is applied to the imaging data acquired during the second retraction to more accurately identify the start or stop points for the media replacement operation.

[0126] Prior to image acquisition by the second imaging modality, a displacement operation is initiated in step 325 to displace displaceable media within the lumen to support imaging by the second imaging modality. As discussed above, any suitable displacement operation may be performed, including but not limited to flushing or dilating. The displacement operation may be initiated prior to completion of the translation step 320, in which case the system may predict when the selected region of interest may be evaluated by the second imaging modality, and by the time the imaging probe is properly positioned for the second imaging modality in the translation step 320, the displacement operation may properly displace the intraluminal media to evaluate the selected region of interest with minimal or no time delay. While the media is being displaced, a retraction operation is performed in step 330 to image the region of interest using the second imaging modality.

[0127] In one embodiment, during the translational movement to acquire images by the second imaging modality step 330, further images may be acquired by the first modality to adjust or correct positional errors or deviations, such as tissue movement and / or errors in the position detection system. If the imaging modalities are correctly aligned, the simultaneous acquisition of images by the first and second modalities provides images of the same position without errors due to tissue movement (i.e., cardiac and respiration, etc.). In one embodiment, the displacement, retraction and imaging movements are automated by the imaging system to image the selected region of interest. The displacement may be performed continuously during the second retraction movement, or may be performed intermittently or at intervals. The automated injection movement may be activated or performed by the user during steps 325, 330, for example, by continuously operating a switch, such as a button or foot pedal. Such a management mode of imaging automation may ensure that all media displacement movements are performed in the presence of the practitioner. The practitioner may, for example, interrupt the procedure if the amount of flushing fluid used is deemed to exceed a preselected amount.

[0128] Alternatively, one or more of steps 330 and 335 may be performed manually. In one embodiment, both steps 330, 335 are performed manually, and the locations at which to perform the replacement and imaging operations are indicated to the user based on the selected region identified in step 315. For example, the practitioner may translate the imaging probe, and the system can indicate to the user (e.g., via the user interface 225) the locations at which to perform the replacement and imaging. The user can then manually perform the replacement operation using the manually actuated media replacement device 135 shown in FIG. 1.

[0129] In other embodiments, the practitioner can manually translate the imaging probe and the imaging system can perform automated injection and imaging as the imaging probe passes over the region of interest selected in step 315, for example, using the integrated media displacement device 135 of FIG. 2 and the system's associated monitor / driver and controller.

[0130] In yet another embodiment, the imaging probe may be automatically translated and the imaging system may indicate to the practitioner where a displacement action is required to acquire images by the second imaging modality. In such an embodiment, the system automatically acquires images using the second imaging modality once a displacement action is performed by the practitioner.

[0131] In one embodiment, the replacement operations are monitored, for example, by media replacement monitor 155 shown in Figure 2. As discussed above, monitored parameters may include the volume of flush fluid delivered to a given media replacement operation, the total amount of flush fluid delivered to multiple media replacement operations for a given patient and / or minimally invasive procedure, the duration a given media replacement operation is performed, the total duration multiple media replacement operations are performed for a given patient and / or minimally invasive procedure, control signals and / or commands communicated to devices or subsystems to perform the media replacement, etc.

[0132] In one embodiment, the monitored displacement parameters are used to provide feedback to the imaging system. A threshold range or maximum value for the monitored displacement parameters may be set in the system. Exceeding such a threshold may trigger a visual or audible warning. Alternatively, exceeding the threshold may automatically stop or abort a given displacement operation (optionally notifying the practitioner of this event). The monitored displacement parameters may be stored and made available to the practitioner or physician after the minimally invasive procedure, for example, included in a documentation record associated with the procedure. Alternatively, monitoring of the displacement operation may be used to determine the duration or interval at which steps 325, 330 are performed. For example, the imaging probe may be translated to the region of interest in step 320, a displacement operation may be initiated in step 325, the intraluminal medium may be displaced, and the imaging probe may be further translated while imaging until the monitored displacement threshold is reached.

[0133] In the above described embodiments, it may be desirable to control and / or optimize the speed of translation and / or rotation of the imaging probe using feedback from processed images. The retraction or advancement speed and / or the rotation speed of the torque cable may be controlled by the processing unit 205 and / or the controller unit 165. These speeds may be modified, determined and / or optimized separately for each imaging modality. Furthermore, the speed may be modified based on the images processed by the processing unit 205. For example, when evaluating images obtained by a first imaging modality, if the first imaging modality detects an area where a second imaging modality is applied, it may be desirable to increase the speed of retraction and / or the rotation speed of the torque cable while using the second imaging modality (e.g. OCT). By accelerating image acquisition during the operation of an imaging modality that requires displacement of the intraluminal medium, the duration of the displacement or the amount of displacement medium, such as contrast agent, that needs to be introduced when acquiring the images may be reduced.

[0134] In one embodiment, it may be desirable to selectively stop one or more of the imaging modalities while adjusting the rotation or translation speed. For example, a first modality may identify an area of ​​interest that initiates a media replacement operation, activates a second imaging modality, changes the rotation speed, and / or changes the retraction speed. If operation at a different rotation and / or retraction speed reduces the usefulness of the first modality, it may be desirable to temporarily stop the first modality until the controller determines to terminate the second modality.

[0135] For example, if the first imaging modality is IVUS, the system can operate at a rotation speed ranging from 5 to 100 frames per second during IVUS analysis, where IVUS identifies the region of interest. However, during imaging with a second imaging modality, such as OCT, the rotation speed can be increased to greater than 50 frames per second and the retraction speed can be increased to greater than 2 mm / s. While the rotation speed limit for useful IVUS image acquisition varies depending on the instance or application, it may be reasonable to stop or remove IVUS images during OCT acquisition that employs high rotation speeds. In such cases, the end of the region of interest may be identified by the second imaging modality or by any of the parameters described above for identifying the end of the region of interest independent of the first imaging modality, such as elapsed time, amount of displacement medium used, or reaching a known position based on position sensor data from the retraction mechanism.

[0136] In yet other embodiments, image processing of images acquired using the second imaging modality may be performed in real time during steps 325 and 330 to assess image quality. For example, image quality may be assessed by comparing the intensity, signal attenuation, or texture of a portion of the image, such as a sector, to a pre-set desired range or threshold. For example, the image may be analyzed by processing unit 205 to ensure that anatomical boundaries are relatively or sufficiently similar (e.g., as defined by a pre-selected metric) to a clearly defined border between the vessel wall and the lumen that would be expected with proper flushing.

[0137] Alternatively, sections of the image may be analyzed to detect or estimate the presence of intraluminal media such as blood. Blood typically has a signature or range of appearances for each modality based on signal intensity, signal attenuation, or, in the case of NIR imaging, spectral content. Image quality may be ensured, at least in part, by ensuring that no blood signature is present in each section of the image where blood replacement is desired.

[0138] The image quality readings may then be used to provide feedback to regulate the media replacement operation in step 325. For example, if the image signal to noise ratio is deemed poor, the rate of delivery of flush fluid, the amount of flush fluid, the time profile of the flush volume, or the amount of inflation of the replacement balloon may be altered.

[0139] Alternatively, data from a non-invasive imaging modality may be used to assess the adequacy of displacement of the intraluminal medium. For example, the angiogram may be processed in real time or immediately after the displacement means is actuated and the resulting images processed to determine whether the blood vessels have been completely opacified by contrast agent. This may be done by assessing changes in pixel intensity in the angiogram or by assessing the sharpness of the blood vessel boundaries in the angiogram.

[0140] In one embodiment, the image quality obtained with the second imaging modality is evaluated in real time and feedback is provided to adjust parameters associated with the replacement operation to minimize aspects of the replacement operation, for example, image quality may be evaluated to minimize the duration of the replacement operation, the rate of delivery of flush fluid, and / or the amount of flush fluid.

[0141] In other embodiments, after flushing has adequately improved the field of view based on real-time image analysis, a second retraction motion of step 330 may be initiated, after which the imaging probe continues translating to the end of the region of interest for image acquisition. If the image quality at the field of view becomes inadequate during this period, the retraction controller stops or steps back and resumes translation after the field of view is determined to be adequate based on the image quality evaluation.

[0142] After performing step 330 to acquire an image of the given region of interest using the second imaging modality, steps 320-330 may be repeated, as indicated at 335, to acquire images of the further region of interest selected in step 315. Thus, the method may be performed by identifying and selecting a region of interest by performing a complete back out operation in step 300, followed by successive back out and replace operations of steps 320-330 to acquire images of the selected region of interest using the second imaging modality.

[0143] Alternatively, the initial retraction movement 300 may be performed as a partial retraction movement over only a portion of the entire anatomical region being imaged. The image analysis step 305 may be performed in real time to identify regions of interest "on the fly" and display such regions of interest to the user, for example in a back and forth manner, for selection in real time and subsequent automation of the second retraction, replacement and imaging movement in steps 320-300. Alternatively, the regions of interest may be automatically selected for subsequent analysis and steps 320-330 may be performed automatically, as described above. After performing steps 300-330 based on the partial retraction movement, further partial retraction movements are repeated as indicated at 340 until the minimally invasive procedure is deemed complete.

[0144] In one embodiment, image processing is used to help identify the start and stop points of the region of interest during the second retraction motion. In general terms, using multiple position sensors to accurately determine the relative position of the imaging probe for the second retraction motion may be somewhat inaccurate due to relaxation of the imaging conduit, cardiac motion, flow, and the possibility of inadvertent erroneous movement of the catheter by the user, etc.

[0145] In one embodiment, a positioning system is used for a first estimate of when to start and / or stop the second retraction motion, and one or more original images acquired near the start / stop point from the first retraction motion are compared with a current image acquired during the second retraction motion until a suitable match is found to precisely identify the start of the region of interest. Such relative positioning schemes can be improved by using normal anatomical landmarks, such as bifurcations of the vascular anatomy, in addition to the pathological region of interest.

[0146] Image comparison to determine the exact start location of the region of interest during the second imaging operation may be performed by one of several known image comparison methods. In one embodiment, image cross-correlation is employed. In another embodiment, the size of the vessel lumen is employed. In yet another embodiment, the shape of the vessel boundary (between the media and adventitial layers) is employed. In yet another embodiment, the geometric boundary of the lumen is employed. In yet another embodiment, the presence, shape or size of one or more features detected by the first imaging modality, e.g., calcifications, bifurcations, implants, plaque, thrombus, etc. In one embodiment, a combination of position sensor information, image comparison techniques, and / or geometric features of the region are used to assist in identifying the start and / or stop points.

[0147] In one embodiment, real-time processing of images is performed to support real-time displacement and imaging by the second imaging modality without the need for a second retraction movement. This real-time embodiment is illustrated in the flow chart of FIG. 7. In step 400, one or more images are acquired using the first imaging modality after placing the imaging probe at an initial position. In step 410, the images are processed according to the method disclosed in the above embodiment. The real-time image processing includes processing each image individually to determine whether an image corresponding to the current position of the imaging probe is a region of interest for the second imaging, or determining whether the current position corresponds to a region of interest based on an analysis of images collected in a spatial region preceding the current position. Alternatively, the real-time image processing may include processing a series of images corresponding to a 3D data set to provide greater certainty regarding the presence of a potential region of interest for imaging by the second modality.

[0148] In step 420, a determination is made as to whether the current location corresponds to the region of interest. If the results from the image processing step indicate that the current location does correspond to the region of interest, step 430 is executed to perform a media replacement operation. In another embodiment, this determination can be made based on information from a fiducial marker (such as, but not limited to, angiographically detectable marker bands). As mentioned above, this may be performed in an automatic manner or in a semi-automatic manner where the system prompts the practitioner to perform or activate the media replacement. After the media replacement operation is initiated, in step 440, an image of the current location is acquired using a second imaging modality. Then, in step 450, the imaging probe is translated to a new location and the process is repeated according to step 460.

[0149] Now, if in step 420 it is determined that the current position does not correspond to the region of interest, steps 430, 440 are bypassed and step 450 is performed to translate the imaging probe to a new position, and the process is then repeated according to step 460. The above described real-time processing may be performed in a stop-start manner, with the imaging probe stationary when the media replacement and second imaging steps are performed, as described above, or under continuous retraction motion.

[0150] Although the embodiments have been described thus far as a series of discrete steps, it will be apparent that other variations of the embodiments are conceivable. For example, in a variation of the above embodiment, the imaging probe may be translated using a motor or other drive system that is not immediately stopped while the image processing steps are being performed, in which case, by the time a decision is made to identify the region of interest, the probe (or functional parts of the probe) may have translated slightly from the position at which the image was acquired. In one implementation, this may be corrected by translating the functional parts of the imaging probe back an appropriate distance before commencing the displacement operation. Alternatively, if the pass-by distance is sufficiently short, the displacement operation may be initiated directly without a corrective return movement. In other embodiments, the imaging probe may be translated continuously while performing one or more of steps 400-430 of FIG. 7.

[0151] In one embodiment employing continuous retraction, the controller for the second imaging modality can identify that sub-optimal imaging data has been acquired and can declare (e.g., via a notification) that an error has occurred, which may be responded to by reversing the direction of translation of the imaging probe until the region corresponding to the error is traversed, then resuming translation in the normal direction and performing steps 430-450 again.

[0152] Alternatively, in step 430, a media replacement operation may be initiated based on a particular location identified as an area of ​​interest, and the process may be repeated until a new location is reached that is not identified as an area of ​​interest, in which case the media replacement operation may be terminated after performing step 420 and before performing step 450. Such an embodiment provides for the automation of a series of measurement cycles in which second imaging is performed at multiple successive locations without the need to terminate and restart the media replacement operation.

[0153] As a variation of the above technique, it may be desirable to translate the imaging probe in the reverse direction a short distance before performing the media replacement operation. Alternatively, after automatically identifying the start of the region of interest, a small backstep step (e.g., less than 20 mm, more preferably less than 5 mm) may be performed, so that the beginning of the region of interest is included in the imaging data collected after replacing the blood. For example, a backstepping movement may be performed until the region of interest is identified, at which point a backstepping (e.g., forward) step of about 2 mm may be performed following initiation of the media replacement operation. The backstepping movement may then be resumed for imaging with the second (and optionally the first) imaging modality until the end of the region of interest is identified, at which point the replacement operation is terminated. This method may be repeated to identify and image the next region of interest.

[0154] An imaging probe for use in the real-time embodiments described above may include a proximal sensor for detection of a region of interest based on a first imaging modality (compatible with the intraluminal medium) and a distal sensor based on a second imaging modality whose performance is enhanced by detection of the region of interest by the proximal sensor and replacement of the intraluminal medium.

[0155] More generally, an imaging probe for use in the real-time embodiments described above may include a sensor positioned or oriented on the probe for detection of a region of interest based on a first imaging modality (compatible with the intraluminal medium) to evaluate a potential region of interest, after which a second sensor based on a second imaging modality is positioned or oriented to evaluate a corresponding region of interest, the performance of which is enhanced by detection of the region of interest by the first sensor and displacement of the intraluminal medium.

[0156] In some of the above-mentioned embodiments, a second retraction motion in combination with the displacement motion acquires images using a second imaging modality, but the second imaging step may be performed by advancing the probe in a direction opposite to the retraction direction. In particular, such an advancing motion may be preferred since it allows imaging of the vessel with a given volume of displacement fluid, since the imaging assembly moves in the same direction as the volume of displacement fluid (this is because the imaging core follows the displacement fluid, rather than moving in the opposite direction). It is also clear that the retraction motion may be achieved by retracting the entire imaging probe or by retracting a core part of the imaging probe.

[0157] In other embodiments, the images acquired by the first and second imaging modalities may be processed to provide a score or index indicative of how well the minimally invasive procedure involving the combined imaging modalities has been performed. For example, the score or index may be determined by calculating the percentage or absolute value of the recession distance at which adequate replacement of the intraluminal media has occurred. Such a score or index may be used to determine which data set provides adequate quality for the purposes of a particular study or trial. Alternatively, the score or index may be used as an indication of whether the minimally invasive procedure should be repeated, possibly with altered parameters such as sensitivity and / or speed.

[0158] It is noted that while the embodiments described above relate to methods and systems relating to a multi-modality imaging probe including two imaging modalities, the imaging probe may include more imaging modalities. In one embodiment, multiple imaging modalities that are compatible with the presence of an intraluminal medium may be used to identify the region of interest. Additionally, multiple imaging modalities where displacement of the displaceable intraluminal medium is advantageous may be used to image the region of interest.

[0159] The embodiments described above have been described with emphasis on procedures in which the area or field of view assessed by one or more sensors is determined by a substantially translational motion, e.g., a back or forward motion. The methods and devices described herein apply equally to other imaging systems in which the area imaged, assessed or treated by the first and second modalities is determined by a motion other than translation. For example, the imaging probe 31 shown in Figures 4a-4d can image a large area by both optical imaging and ultrasound imaging, with the imaging angle determined in part by the tilt angle of the deflectable component 70. For such probes, the translational motion of the embodiments for controlling media replacement as described above with Figures 6 and 7 can be replaced by a deflection motion. For example, if the imaging angle is large, ultrasound imaging may determine that there is no area of ​​interest in the current field of view that requires further analysis by the second imaging modality. Areas of interest where a media replacement motion would be beneficial may be identified at imaging angles in a more forward looking direction.

[0160] Similarly, electronic steering methods such as linear array ultrasound transducers or phased array transducers used in 2D or 3D ultrasound probes do not rely solely on translation or deflection to determine the area imaged. Such arrays may be incorporated into minimally invasive imaging probes and may be used as the first or second imaging modality or both of the present invention and may benefit from media displacement operations.

[0161] In yet another embodiment, an external imaging device can be part of the system. Examples of external imaging modalities include angiography, CT angiography, magnetic resonance imaging, externally applied ultrasound, etc. In the embodiment shown in FIG. 8, the system 500 can include a fluoroscopic imaging device 510, which is optionally connected to the computer system 220 (e.g., connected to the processing unit 205). While performing the translational motion to acquire images by the first or second imaging modality, an image acquisition trigger signal can be provided to the external imaging device to trigger the external system to acquire one or more image frames during one or more translational motions of the imaging probe. In one embodiment, the signal can be provided at intervals of interest, which can be regular intervals in time or intervals along the range of translational motion. Alternatively, the intervals can be time intervals related to the start or end of a media replacement motion or intervals at which the imaging probe images a determined region of interest.

[0162] In other embodiments, an external imaging device may be used to identify one or more regions of interest that may then be used for subsequent imaging using an imaging probe imaging modality in which displacement of the intraluminal medium is advantageous. In one embodiment, the first imaging modality is a fluoroscopic imaging device and the system is configured to deliver a contrast agent (e.g., during a cardiac angiography procedure). During initial operation, the fluoroscopic imaging device is used to image an area that includes the lumen through which the imaging probe may be moved.

[0163] In the case of fluoroscopic imaging, one or more initial fluoroscopic images may be acquired first while delivering contrast agent into the lumen using the imaging probe or an additional flush catheter. The acquired one or more initial fluoroscopic images may be used to identify one or more regions of interest to be imaged by the imaging probe imaging modality. The one or more regions of interest may be manually identified by observing the one or more initial images. For example, the one or more regions of interest may correspond to locations where the lumen is narrowed.

[0164] In one embodiment, an external diagnostic device may be used to guide the imaging catheter to a region of interest identified in one or more initial images. For example, the imaging probe may include fiducial markers, such as radiopaque markers (e.g., radiopaque marker bands), that allow the external imaging device to identify the location of the imaging assembly. Thus, the external imaging device may be used to position the imaging probe for translation through a path known to include one or more regions of interest, and the external diagnostic device may be used to track the position of the imaging probe during the translation movement and compare with the initial images to identify whether a media replacement is required at the current location.

[0165] In yet another embodiment including an external imaging diagnostic device, the imaging probe can include first and second imaging modalities, where the first imaging modality is compatible with the presence of intraluminal medium and the second imaging modality is advantageous for displacement of the intraluminal medium. Regions of interest for acquiring images by the second imaging modality (while performing a medium displacement operation) may be identified by both the external diagnostic device (as described above) and the first imaging modality (during the initial translation and imaging operation with the first imaging modality).

[0166] Intraluminal medium may generally be any medium that may impair the performance of an imaging modality. Furthermore, although the above-described embodiments relate to intraluminal probe-based imaging methods that include displacement of intraluminal fluid, it will be apparent that the above-described methods may be applied to any medical imaging application in which a first imaging modality is used to direct displacement of a displaceable medium to improve or support imaging based on a second imaging modality.

[0167] Applications suitable for the above-described embodiments of the present invention include imaging of the gastrointestinal system, the cardiac system (including coronary arteries, peripheral vasculature and neurological vasculature), the respiratory system, the eye (including the retina), the auditory system, the genitourinary system and many others.

[0168] Additionally, while the above-described embodiment discloses a method in which the process of acquiring images by a second imaging modality is assisted by a media replacement operation, it is clear that the use of a second imaging modality is merely one example of a second minimally invasive procedure assisted or improved by a media replacement operation. Thus, in other embodiments, the above-described method may be adapted to provide a minimally invasive procedure that automatically or semi-automatically performs a treatment on a region of interest where, for example, a media replacement operation is necessary or advantageous. For example, the second imaging step in the above-described method may be combined with or replaced by a treatment operation performed on the region of interest while performing the media replacement operation. Therapeutic minimally invasive procedures include, but are not limited to, photodynamic therapy, laser ablation, application of electrical energy such as radio frequency energy, etc., where the delivery of the treatment is guided by the region of interest identified during a retraction operation involving a first imaging modality that is compatible with the presence of an intraluminal medium.

[0169] The specific embodiments described above are illustrative, and various modifications and alternatives to these embodiments are contemplated. Furthermore, the claims are not limited to the specific forms disclosed herein, but rather cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present invention.

Claims

1. 1. A system for acquiring images of an interior of a body lumen, comprising: an imaging probe configured for insertion into a lumen, the imaging probe comprising an imaging assembly configured to acquire images according to a first imaging modality and a second imaging modality; a driver and adapter unit for interfacing with the imaging probe; at least one processor capable of interfacing with the imaging assembly via the driver and adapter unit, the at least one processor comprising: controlling the driver and adapter unit to direct a retracting movement of the imaging assembly; acquiring a first set of images from the first imaging modality during the retraction movement; identifying a region of interest in the first set of images or receiving an input identifying the region of interest; controlling the driver and adapter unit to direct forward translational movement of the imaging assembly; acquiring a second set of images of the region of interest from the second imaging modality during the forward translation; [0023] The present invention is configured to The system further comprises a medium replacement means for replacing a replaceable medium in the lumen by injection of a replacement fluid; the medium replacement means may be controlled to inject the replacement liquid when acquiring the second set of images. system.

2. the first imaging modality is compatible with the presence of the displaceable medium within the lumen; the second imaging modality is incompatible with the presence of the displaceable medium within the lumen or cavity; The system of claim 1 .

3. the first imaging modality is an intravascular ultrasound imaging device and the second imaging modality is an optical coherence tomography imaging device; The system of claim 1 .

4. 2. The system of claim 1, wherein said media replacement means is controllable according to input from an operator.

5. the medium replacement means being autonomously controlled by the at least one processor to automatically spray the replacement liquid when the second set of images is acquired. The system of claim 1 .

6. the forward translational motion occurs at a speed greater than 2 mm / s when acquiring the second set of images from the second imaging modality. The system of claim 3.

7. the driver and adapter unit is configured to rotate the imaging assembly; the at least one processor is configured to control the driver and adapter unit such that the second set of images is acquired at a rate greater than 50 frames per second. The system of claim 3.

8. The at least one processor, prior to initiation of the forward translation movement, the medium displacement means is controlled to inject the displacement fluid and an initial set of images is acquired from the second imaging modality; The initial set of images is processed in real time to determine when the replacement fluid has adequately improved the field of view. It is configured as follows: The system of claim 1 .

9. The at least one processor further comprises: monitoring parameters related to media replacement; generating an alert or terminating the injection of substitution fluid if the parameter is not within a predetermined range of values; 4. The method according to claim 1, The system of claim 1 .

10. the at least one processor is configured to process the first set of images to identify the region of interest. The system of claim 1 .

11. the at least one processor is configured to identify the region of interest in real time; the forward translation motion is performed automatically after identifying the region of interest. The system of claim 1 .

12. 11. The system of claim 10, wherein processing the first set of images by the at least one processor comprises identifying tissue type by performing a method selected from the group consisting of grayscale pixel analysis, high frequency analysis, texture analysis, and heuristic analysis.

13. the at least one processor is configured to identify the region of interest by comparing the first set of images to known or expected characteristics; the known or expected characteristic is a spatial profile and / or tissue type of one or more of a normal anatomical feature, a pathological anatomical feature, or a medical implant; The system of claim 10.

14. The system of claim 10 , wherein the at least one processor is configured to identify the region of interest using a pattern recognition algorithm.

15. The system of claim 10 , wherein the at least one processor is configured to identify the region of interest according to a user-configurable threshold parameter.

16. The at least one processor processing the first set of images to identify a plurality of regions of interest; ranking the regions of interest according to predetermined criteria; selecting a subset of the regions of interest according to the ranking; controlling the driver and adapter unit to direct a forward translational movement of the imaging assembly for each region of interest in the subset; acquiring images from the second imaging modality and controlling the medium displacement means to inject the displacement fluid during each of the forward translational movements; 4. The method according to claim 1, The system of claim 1 .

17. The at least one processor controlling a display to present the first set of images to an operator; receiving input from the operator, the input identifying the region of interest; and configured to identify the region of interest by The system of claim 1 .

Images