WO2015074045A2 - Therapeutic delivery catheter with imaging and tissue characterization - Google Patents

Abstract

The invention includes medical devices, such as catheters, that have imaging and therapeutic agent delivery capabilities. The therapeutic catheters of the invention allow a surgeon to image biological tissues, such as thrombus, prior to delivering therapeutic agents to the tissues, and then re-image the tissue after the procedure to gauge the success of the procedure. The invention facilitates detailed characterization of the biological tissues with, e.g., spectral analysis, thereby providing insight into the composition of the tissues and helping to determine the amount of treatment that is appropriate. Because the imaging and therapy delivery are done with a single catheter, the time required for a procedure is decreased.

Description

THERAPEUTIC DELIVERY CATHETER WITH IMAGING AND TISSUE

CHARACTERIZATION

RELATED APPLICATIONS

This application claims priority to U.S. Patent Application No. 61/905,354, filed

November 18, 2013, which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The invention relates to medical devices, such as vascular catheters, that are capable of delivering therapeutic treatment to a target, e.g., vascular tissue, while imaging and evaluating the target.

BACKGROUND

Thrombosis is a medical condition that results from the formation of a blood clot, or thrombus, within a vessel. Thrombi often develop in the valves, legs, or other lower abdomen (i.e. deep vein thrombosis), but may occur in other vessels. The clot is typically formed from a pooling of blood within the vein due to abnormally long periods of rest, e.g. when an individual is bed ridden following surgery or suffering a debilitating illness. In addition to thrombosis, atherosclerosis is another medical condition that results from the formation of a blockage in a vein. The atherosclerosis is due to the build of atheroma material along the arterial walls.

Atheroma deposits can have widely varying properties, with some deposits being relatively soft and others being fibrous and/or calcified. In the latter case, the deposits are frequently referred to as plaque. Often thrombosis and atherosclerosis are both present in the veins. For example, a thrombus develops around the atherosclerotic plaque.

The formation of thrombi and build-up of plaque can lead to a stroke or embolism that may lead to serious health issues, including death. Strokes occur when the blood clot or plaque blocks an artery supplying blood to the brain, thus depriving the brain tissue of oxygen. Without oxygen, brain cells begin to die. Embolisms occur when a blood clot travels around the body and lodges itself in an organ. For example, a pulmonary embolism is a blockage of the blood supply to the lungs that causes severe hypoxia and cardiac failure. For some blockages, surgical intervention with ultrasonic catheters may be necessary to remove the thrombus, plaque, or both, from a vessel, such as when cholesterol or anti-coagulant medications are not able to reduce the blockage. Removal of blockages with ultrasonic energy is a complicated procedure that uses a delicate balance of duration and amount of treatment to remove the blockage. If too little treatment is used, the blockage will not be cleared, or a portion of the blockage can be dislodged but not removed, leading to later complications such as stroke. If too much treatment is used, the blood vessel walls can be damaged or even perforated. This is especially dangerous because the healing of a wounded vessel wall may lead to smooth muscle cell proliferation that will occlude the vessel, a phenomenon known as restenosis.

SUMMARY

The invention is a therapeutic catheter having imaging capabilities and methods and systems that use such catheters. Catheters of the invention are well-suited for delivering therapeutic agents, such as thrombolytic agents, to vasculature while imaging the vasculature undergoing treatment. The invention allows a portion of vasculature to be assessed and treated with only a single catheter insertion, thus shortening procedure times and reducing a patient' s exposure to anesthesia and x-rays. The imaging may be ultrasound imaging, visible imaging (e.g., optical coherence tomography), or infrared imaging/spectroscopy. In some embodiments, spectral analysis tools are used in conjunction with the imaging to improve visualization of plaque and/or thrombus morphology (i.e., virtual histology) or blood flow. This additional information provides an improved understanding of vascular health in the region of the thrombus and can be used to further refine a treatment regimen. In some embodiments, the catheter is configured to deliver therapeutic energy to the vasculature in conjunction with the therapeutic agents, thus speeding the process of disrupting and/or treating occlusive tissues, such as thrombus. Devices of the invention may be used for other medical procedures that benefit from the combination of therapeutic agent delivery and imaging, such as identification and treatment of tumors.

In an embodiment, the catheter is an elongated medical device comprising a catheter body having a distal end and a proximal end, wherein the body includes a delivery lumen providing a fluid path between an opening at the distal end of the catheter body and a port at the proximal end of the catheter body. The body also includes an imaging assembly located at the distal end of the catheter body and connected to a signal connection at the proximal end of the catheter body. The imaging assembly may include an ultrasonic transducer. The openings may be interspersed with the imaging elements, or the openings may be located distal or proximal to the imaging elements. In some embodiments the imaging element is configured to move within the catheter during imaging, e.g., a pull-back type imaging element.

The invention additionally includes methods of treatment using the disclosed catheters. Such methods include inserting a catheter disclosed herein into a lumen of a vessel (i.e., vasculature) identified as needing assessment and treatment. The vessel is then imaged, and the tissues of the vessel are evaluated, e.g., using spectral analysis such as virtual histology. Once the tissues are evaluated, therapeutic agents, e.g., thrombolytic agents, are delivered to the vessel for treatment. After treatment, the vessel can be re-imaged using the catheter and the remaining tissues re-evaluated, e.g., to determine the cross-sectional area of blood flow. In some embodiments, a catheter may be configured to deliver therapeutic energy, such as ultrasonic energy, in conjunction with the therapeutic agents.

The invention also includes systems for treating vasculature. The systems comprise a catheter of the invention, an imaging controller for receiving signals from the imaging assembly, and a fluid delivery subsystem for controlling the delivery of therapeutic agents, such as thrombolytic agents. In an embodiment the imaging controller is configured to evaluate tissues of the vasculature, e.g., using virtual histology. In another embodiment, the imaging controller is in communication with an imaging engine that is configured to evaluate tissues. In an embodiment, the imaging system is an ultrasound imaging system, and includes one or more ultrasonic transducers. In an embodiment, the fluid delivery subsystem includes a syringe or a pump. In an embodiment, the catheter additionally includes a therapeutic energy source, and optionally a controller for controlling the therapeutic energy that is delivered to the vasculature in addition to the therapeutic agent.

In some embodiments, systems and methods of the invention are configured to characterize tissues of the vasculature using imaging data collected from the imaging element, e.g., using any of a number of imaging modalities such as intravascular ultrasound (IVUS), forward looking intravascular ultrasound (FLIVUS), optical coherence tomography (OCT), or focal acoustic coherence tomography (FACT). Based upon this analysis, a histology image of the vasculature is prepared and displayed, facilitating faster and more accurate evaluation of thrombus and plaque before, during, or after treatment.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 depicts a catheter of the invention;

FIG. 2 depicts a catheter of the invention;

FIG. 3A illustrates the use of a catheter of the invention to image a vessel during a procedure to reduce thrombus in the vessel;

FIG. 3B illustrates the use of a catheter of the invention to image a vessel during a procedure to reduce thrombus in the vessel;

FIG. 3C illustrates the use of a catheter of the invention to image a vessel during a procedure to reduce thrombus in the vessel;

FIG. 4 depicts a system of the invention configured to treat vasculature;

FIG. 5 depicts a system of the invention configured to image a vessel with intravascular ultrasound (IVUS) while delivering therapeutic agents to the vessel;

FIG. 6 depicts a system of the invention configured to image a vessel with optical coherence tomography (OCT) while delivering therapeutic agents to the vessel;

FIG. 7 depicts an optical coherence tomography (OCT) imaging engine and patient interface module (PIM) for use with a catheter system of the invention;

FIG. 8 depicts the OCT imaging engine of FIG. 7 in greater detail;

FIG. 9 depicts an optical mixing setup for OCT image acquisition and processing;

FIG. 10 depicts an image processing subsystem for use with a catheter of the invention;

FIG. 11 depicts an image processing subsystem for use with a catheter of the invention.

FIG. 12 depicts a concave micromachined piezoelectric ultrasound element adapted for focused acoustic computed tomography (FACT);

DETAILED DESCRIPTION

The invention includes medical devices, such as catheters, that have imaging and therapeutic agent delivery capabilities. The therapeutic catheters of the invention allow a surgeon to image biological tissues, such as thrombus, prior to delivering therapeutic agents to the tissues, and then re-image the tissue after the procedure to gauge the success of the procedure. In particular, the invention facilitates detailed characterization of the biological tissues with spectral analysis, thereby providing insight into the composition of the tissues and helping to determine the amount of treatment that is appropriate. Because the imaging and therapy delivery are done with a single catheter, the time required for a procedure is decreased.

Catheters of the invention find uses for multiple medical procedures, such as removal of thrombus or plaque from veins and arteries. The catheters may be delivered through a number of entry points, such as the femoral or radial arteries. The catheters may be guided to the area for treatment with one or more external imaging systems, such as fluoroscopy, CAT, or MRI.

Typically, the catheter will be guided along a guide wire to the tissues targeted for treatment. The catheters may be used in conjunction with other procedures or catheters such as aspiration catheters. The catheters of the invention are not limited to treating diseased vasculature, however. The catheters can be used, for example, for identifying, imaging, and treating tumors that are accessible through the vasculature.

In some embodiments, the catheters of the invention are used to deliver thrombolytic agents, i.e., chemicals or compositions designed to erode, disrupt, or dissolve clotted blood, plaque, and/or fatty materials. Thrombolytic agents suitable for use with catheters of the invention include streptokinases, urokinases, and tissue plasminogen activators (TPAs) such as alterplase, reteplase, and teneteplase. The thrombolytic agents may be isolated from

microorganisms where the agents naturally occur, such as Streptococcus, or they may be generated recombinantly and purified. In some embodiments, thrombolytic agents may be administered in conjunction with anticoagulants, such as heparin, Warfarin™, or factor Xa inhibitors, such as rivaroxaban or apixaban.

In certain embodiments, the devices and methods of the present invention are designed to dissolve blood clots, such as such as emboli and thrombi and other occlusive material from body lumens. The body lumens generally are diseased body lumens and in particular coronary arteries. The defect in the body lumen can be a de novo clot or a clot resulting from a stent placement, for example. The devices and methods, however, are also suitable for treating stenosis of body lumens and other hyperplastic and neoplastic conditions in other body lumens, such as the ureter, the biliary duct, respiratory passages, the pancreatic duct, the lymphatic duct, and the like. Neoplastic cell growth will often occur as a result of a tumor surrounding and intruding into a body lumen. Delivery of therapeutic agents to such material can thus be beneficial to maintain patency of the body lumen. While the remaining discussion is directed at drug delivery, imaging, and passing through athermanous or thrombotic occlusive material in a coronary artery, it will be appreciated that the systems, devices, and methods of the present invention can be used to treat and/or pass through a variety of occlusive, stenotic, or hyperplastic material in a variety of body lumens.

A catheter 10 of the invention, configured to treat and image tissues, is shown in FIG. 1. The catheter 10 includes a body having proximal 16, middle 14, and distal 18 portions. The catheter 10 includes an imaging assembly 65 located at the distal-most end of the catheter body. Proximal to the imaging assembly 65 are a plurality of openings 45 through which therapeutic agents can be delivered to targeted vasculature. Optionally, a catheter of the invention will also include a source of therapeutic energy 85, configured to deliver therapeutic energy such as acoustic energy, thermal energy, or electromagnetic radiation to the targeted tissues. The location of the imaging assembly 65, openings 45, and source of therapeutic energy 85 need not be as shown in FIG. 1. In some embodiments, the openings 45 may be distal-most. In some embodiments, the source of therapeutic energy 85 can be distal-most. In some embodiments, the imaging assembly 65 and the openings 45 are substantially overlapping. In some embodiments, the imaging assembly 65, the openings 45, and the source of therapeutic energy 85 are substantially overlapping. Some embodiments of catheters 10 of the invention will not include a source or therapeutic energy 85.

As shown in FIG. 1, each of the imaging assembly 65, the openings 45, and the source of therapeutic energy 85 are connected to subsystems that are located outside of the body and interfaced via interface 29. For example, as shown in FIG. 1, imaging assembly 65 is connected to imaging controller 60, which receives signals from the imaging assembly 65 via connector 26. As described in greater detail below, imaging controller 60 may be capable of performing a variety of functions, including image processing, depending upon the needs of the user.

Similarly, the source of therapeutic energy 85 is connected to energy controller 80, which controls the power and duration of the energy that is delivered to the targeted tissue. In some embodiments, the energy controller 80 and the imaging controller 60 are interfaced to a higher level, system controller 550 (shown in FIGS. 5 and 6), which allows the therapeutic energy to be gated so that the energy is not delivered during imaging, which may cause distorted images. In some embodiments, imaging controller 60 is configured to analyze the collected image data to determine additional characteristics of the tissues, such as density, calcification, lipid content, or fibrin content. In some embodiments, imaging controller 60 is interfaced to an imaging engine as described below. As shown in FIG. 1, the openings 45 at the distal end of the body are connected via an interior lumen (not shown) within the catheter body to a port 35 at the proximal end. As shown in FIG. 1, the port 35 is connected via tubing to a fluid delivery subsystem that may include a pump 40 connected to a reservoir 42 that contains a therapeutic agent to be delivered to the targeted vasculature.

In some embodiments, e.g., as shown in FIG. 1, the imaging assembly uses intravascular ultrasound (IVUS). IVUS-imaging catheters may be array-type catheters, i.e., as depicted in FIG. 1, or IVUS-imaging catheters may be pull-back type catheters as depicted in FIG. 2. In some embodiments, an IVUS array is configured to image beyond the distal end of the catheter, i.e., "forward-looking" IVUS, or "FLIVUS." A pull-back catheter 100 is depicted in FIG. 2, and includes a body having distal 140, middle 150, and proximal 160 portions. As shown in FIG. 2, a plurality of openings 110 are located at the distal end 140 of the body, allowing for delivery of therapeutic agents. As in catheter 10, the plurality of openings 110 are connected via an internal lumen (not shown) to a port 190 at the proximal end of the catheter. The imaging assembly 130 is located within a transparent portion of the distal end 140, and is configured to move back and forth within the catheter and rotate. The imaging assembly 130 connects to interface 170, which provides an electrical connection (power and signal) and rotational motion to shaft 165, which is connected to imaging assembly 130. Pull-back catheter 100 can be interfaced to an imaging controller (not shown) and a fluid delivery subsystem (not shown), similar to those shown in FIG. 1, in order to control imaging assembly 110 as well as the delivery of therapeutic agents. Variations on pull-back catheter 100 may include a source of therapeutic energy.

While not shown, it is understood that catheters of the invention typically include a guide wire lumen that allows the catheter to be directed to a point of treatment. The guide wire lumen may be a distinct guide wire lumen that runs the length of the catheter. In other embodiments, the guide wire lumen may only run a portion of the length of the catheter, e.g., a "rapid exchange" guide wire lumen. The guide wire lumen may be situated on top of the therapeutic delivery lumen or the guide wire channel could be side-by-side the therapeutic delivery lumen. In other cases, it may be possible to provide a fixed or integral coil tip or guide wire tip on the distal portion of the catheter or even dispense with the guide wire entirely. For convenience of illustration, guide wires will not be shown in all embodiments, but it should be appreciated that they can be incorporated into any of these embodiments.

Catheter bodies intended for intravascular introduction will typically have a length in the range from 50 cm to 200 cm and an outer diameter in the range from 1 French to 12 French (0.33 mm: 1 French), usually from 3 French to 9 French. In the case of coronary catheters, the length is typically in the range from 125 cm to 200 cm, the diameter is preferably below 8 French, more preferably below 7 French, and most preferably in the range from 2 French to 7 French.

Catheter bodies will typically be composed of a biocompatible polymer that is fabricated by conventional extrusion techniques. Suitable polymers include polyvinylchloride,

polyurethanes, polyesters, polytetrafluoroethylenes (PTFE), silicone rubbers, natural rubbers, and the like. Optionally, the catheter body may be reinforced with braid, helical wires, coils, axial filaments, or the like, in order to increase rotational strength, column strength, toughness, pushability, and the like. Suitable catheter bodies may be formed by extrusion, with one or more channels being provided when desired. The catheter diameter can be modified by heat expansion and shrinkage using conventional techniques. The resulting catheters will thus be suitable for introduction to the vascular system, often the coronary arteries, by conventional techniques.

The distal portion of the catheters of the present invention may have a wide variety of forms and structures. In many embodiments, a distal portion of the catheter is more rigid than a proximal portion, but in other embodiments the distal portion may be equally as flexible as the proximal portion. One aspect of the present invention provides catheters having a distal portion with a reduced rigid length. The reduced rigid length can allow the catheters to access and treat tortuous vessels and small diameter body lumens. In most embodiments a rigid distal portion or housing of the catheter body will have a diameter that generally matches the proximal portion of the catheter body, however, in other embodiments, the distal portion may be larger or smaller than the flexible portion of the catheter.

In some embodiments, the catheter may include a flexible atraumatic distal tip coupled to the rigid distal portion of the catheter. For example, an integrated distal tip can increase the safety of the catheter by eliminating the joint between the distal tip and the catheter body. The integral tip can provide a smoother inner diameter for ease of tissue movement into a collection chamber in the tip. During manufacturing, the transition from the housing to the flexible distal tip can be finished with a polymer laminate over the material housing. No weld, crimp, or screw joint is usually required. The atraumatic distal tip permits advancing the catheter distally through the blood vessel or other body lumen while reducing any damage caused to the body lumen by the catheter. Typically, the distal tip will have a guide wire lumen to permit the catheter to be guided to the target tissue over a guide wire. In some exemplary configurations, the atraumatic distal tip includes a coil. In some configurations the distal tip has a rounded, blunt distal end.

A method of using a catheter of the invention is depicted in FIGS. 3A-3C. In FIGS. 3A- 3C, a catheter 300 capable of imaging a vessel 380 and associated thrombus 370 with IVUS is shown in three separate steps of the treatment, along with simulated IVUS images (to the right). Similar to FIGS. 1 and 2, catheter 300 includes a body that has an imaging assembly 310 and openings 355 at the distal end of the catheter. An interior lumen 350 is coupled to the openings 355, and allows a therapeutic agent to be delivered to the thrombus 370 from a port (not shown) at the proximal end of the catheter 300. As shown in FIG. 3A, the catheter 300 is moved to the location of a blockage. The blockage may have been identified prior to the procedure using, e.g., a radiopaque dye and fluoroscopy. As shown in FIG. 3A, because the catheter 300 is capable of imaging, the blockage is readily identifiable as a region of narrowed luminal opening, as shown in the simulated IVUS image. Additionally, the collected imaging data is analyzed to provide tissue characterization 375 that is co-registered with the IVUS image, thus providing additional information about the composition of thrombus 370. In some embodiments, blood can be colorized (typically red) to expedite determination of the size of the thrombus and to help evaluate the amount of treatment needed.

Having identified the narrowing, a thrombolytic agent can be delivered with the catheter 300 without the need to perform an additional catheter placement, as is done with state-of-the-art methods. The thrombolytic agent causes the dissolution of a portion of the thrombus 370, allowing the catheter 300 to pass through the narrowed area, as shown in FIG. 3B. Once the catheter 300 can pass through the narrowing, the thrombolytic agent can be delivered to the other side of the blockage, resulting in additional thrombus 370 removal. By moving the catheter 300 through the narrowing while delivering thrombolytic agent, the narrowed section is eventually opened to nearly normal, as shown in FIG. 3C.

Using tissue characterization it is possible to readily determine when the procedure is complete, i.e., when tissues presenting risk have been eliminated. Additionally, by constantly observing the area during the treatment, it is less likely that unintended damage will occur to the vasculature 380. Thus, as exemplified in FIG. 3B, some of the at-risk tissue (represented by tissue characterization 375) is still present, suggesting that additional treatment is needed. By observing tissue characterization 375 it is straightforward for a surgeon to know when the procedure is complete, i.e., when the at-risk tissue has been removed, as shown in FIG. 3C.

The disclosed catheters make up a part of a system 400 for treating vasculature, e.g., removing thrombus or plaque, e.g., deep-vein thrombosis. The system 400 includes a catheter 410 having openings for delivery of therapeutic agents and an imaging assembly of the type described previously. The therapeutic energy transducer and the openings may be arranged in a variety of configurations, e.g., as depicted in FIGS. 1 and 2. As shown in FIG. 4, the system additionally includes a subcontroller for each function, i.e., a therapeutic agent delivery controller 440 and imaging controller 436. The imaging controller may be configured to analyze the collected image data to provide tissue or blood characterization. A system 400 of the invention may also include diagnostic sensors, such as pressure, flow, or temperature sensors (not shown) that are interfaced to a diagnostic controller 438 as well as the ability to delivery therapeutic energy, which is controlled by therapy controller 440. In some embodiments, the various subcontroUers are operatively connected to a system controller 550 that coordinates all of the functionality. The system controller 550 may also synchronize the functionality of the various functionality of the system, as discussed previously. In order to facilitate use of a system of the invention, various subcontroUers may be tied to a Patient Interface Module 430 that allows connectivity of all of the various subcontroUers to other devices with only one or two

connections. In some embodiments, the Patient Interface Module 430 may include a network controller 434 that allows the Patient Interface Module 430 to be controlled via a networked connection. In some embodiments, the Patient Interface Module 430 is connected to external image processing 460 and a display 470, for viewing images, diagnosing the vasculature, and evaluating the success of a procedure.

Two advanced embodiments of a therapeutic catheter system of the invention are shown in FIGS. 5 and 6. FIG. 5 illustrates an advanced IVUS system 500, whereas FIG. 6 represents an advanced OCT system 600. Each system includes an imaging controller specific to the imaging functionality of the system, i.e., IVUS system 500 includes an IVUS controller 555, whereas OCT system 600 includes an OCT controller 655. Both systems include other subsystems for controlling the functionality of the catheter, including image processing 560 for processing the images acquired by the imaging element, and a therapeutic agent delivery controller 530 for controlling the delivery of a therapeutic agent. As shown in both embodiments, the image processing 560 is coupled to tissue/blood characterization 590 that is configured to analyze the collected image data to determine, e.g., tissue density, tissue calcification, lipid density, fibrin density, etc. Tissue/blood characterization 590 may also be used to identify the blood lumen boundary for display with the tissue image, i.e., at display 580. The catheters of the systems shown in FIGS. 5 and 6 also include therapeutic energy delivery in the form of ultrasonic (US) energy delivery. Accordingly, systems 500 and 600 also include a US therapy controller 540 for coordinating delivery of therapeutic US energy.

As shown in FIGS. 5 and 6, the subsystems are coordinated by a system controller 550 that may control the timing, duration, and amount of imaging, therapeutic energy delivery, and therapeutic agent delivery. In the embodiments shown in FIGS. 5 and 6, the system controller 550 is additionally interfaced with image processing 560, and via image processing 560, the system controller 550 is interfaced with the tissue/blood characterization 590, thereby allowing the viewed and assessed images to be the basis for defining parameters for therapeutics delivery. The systems 500 and 600 also include a display 580 and a user interface that allow a user, e.g. a surgeon, to interact with the images (including tissue characterization) and to control the parameters of the treatment.

As mentioned previously, in some embodiments, the imaging assembly is an IVUS imaging assembly. The imaging assembly can be a phased array IVUS imaging assembly, an pull-back type IVUS imaging assembly, or an IVUS imaging assembly that uses photoacoustic materials to produce diagnostic ultrasound and/or receive reflected ultrasound for diagnostics. IVUS imaging assemblies and processing of IVUS data are described for example in Yock, U.S. Pat. Nos. 4,794,931, 5,000,185, and 5,313,949; Sieben et al., U.S. Pat. Nos. 5,243,988, and 5,353,798; Crowley et al., U.S. Pat. No. 4,951,677; Pomeranz, U.S. Pat. No. 5,095,911, Griffith et al., U.S. Pat. No. 4,841,977, Maroney et al., U.S. Pat. No. 5,373,849, Born et al., U.S. Pat. No. 5,176,141, Lancee et al., U.S. Pat. No. 5,240,003, Lancee et al., U.S. Pat. No. 5,375,602, Gardineer et at., U.S. Pat. No. 5,373,845, Seward et al., Mayo Clinic Proceedings 71(7):629-635 (1996), Packer et al., Cardiostim Conference 833 (1994), "Ultrasound Cardioscopy," Eur.

J.C.P.E. 4(2): 193 (June 1994), Eberle et al., U.S. Pat. No. 5,453,575, Eberle et al., U.S. Pat. No. 5,368,037, Eberle et at., U.S. Pat. No. 5,183,048, Eberle et al., U.S. Pat. No. 5,167,233, Eberle et at., U.S. Pat. No. 4,917,097, Eberle et at., U.S. Pat. No. 5,135,486, and other references well known in the art relating to intraluminal ultrasound devices and modalities. All of these references are incorporated by reference herein. In advanced embodiments, the IVUS systems of the invention may incorporate focused acoustic computed tomography (FACT), which is described in WO2014/109879, incorporated herein by reference in its entirety. In FACT embodiments, the ultrasonic energy used to image the tissue is focused to achieve deeper penetration into tissues, and higher contrast between different types of tissue. In some embodiments, multiple ultrasound bandwidths are used to improve resolution of structure and composition.

In FACT embodiments the imaging assembly of a catheter 300 may comprise a concave ultrasound transducer. The function of concave ultrasound transducer 601 is shown in greater detail in FIG. 12. Transducer 601 includes a polymeric layer 621 having a first adjacent conductive layer 622a and a second adjacent conductive layer 622b. Polymeric layer 621 includes a piezoelectric polymer material made into a concave shape. In some embodiments, the polymer used in polymeric layer 621 may be a ferroelectric polymer such as polyvinylidene fluoride (PVDF). Further according to some embodiments, polymeric layer 621 may include PVDF-co- trifluoroethylene (PVDF-TrFE) as a piezo-electric material. A voltage 630 (V) is applied between conductive layers 622a and 622b in order to generate a focused ultrasound beam 650A. Likewise, incident ultrasonic energy may impinge on polymeric layer 621 and produce a surface change leading to a voltage difference V 630 between conductive layers 622a and 622b. In some embodiments, the concavity of transducer 601 may be a section of a sphere. In some embodiments, the concavity of transducer 601 is directed radially outward, in a plane

perpendicular to the catheter 300. The structure of the transducer assembly including backing, electrodes, and matching layers may determine the acoustic frequency bandwidth of transducer 601. The viscoelastic properties of the polymer material may also determine the acoustic frequency bandwidth of transducer 601. In some embodiments, the transducer 601 will be capable of producing an ultrasonic signal at a frequency between 5 and 135 MHz. In some instances, the transducer 601 will produce a broad bandwidth of ultrasonic frequencies. In other instances, the transducer 601 will produce a narrow bandwidth of ultrasonic frequencies, e.g., with a FWHM of 20 MHz, centered at 50 MHz. In other instances, the transducer 601 will produce a variety of narrow bandwidths to achieve better contrast between materials with different compositions, i.e., between calcified and non-calcified vascular tissue.

In rotational IVUS embodiments, transducer 601 rotates along with the rotational element 601, thus sweeping focused beam 650A radially in the XY plane, as shown in FIG. 12. In alternative embodiments, transducer 601 may include a planar polymeric layer 621, and an acoustic lens (not shown) may be placed adjacent to the now-planar transducer 601.

Accordingly, focused acoustic beam 650A may be generated by acoustic wave refraction through the lens. Alternatively or additionally, the material forming the catheter 300 may have an engineered acoustic impedance, thereby focusing the acoustic wave propagating through the round wall of the catheter 300.

In some instances the focal distance 610 is determined from the curvature of the surface formed by transducers 601 and the refractive index of the propagation medium of focused acoustic beam 650A. Typically, the propagation medium is blood, plasma, a saline solution, or some other bodily fluid. In some embodiments, focal distance may be as long as 10 mm, or more. Thus, the tissue penetration depth of focused ultrasonic beams 650A may be 5 mm, 10 mm, or more. Focal distance 610 and focal waist 620 may also be determined by the curvature of the aperture. In some embodiments focused acoustic beam 650A, may include a plurality of acoustic frequencies in a frequency bandwidth. The frequency bandwidth may be determined by the polymer material and the shape of polymeric layer 621. Further according to some embodiments, the material and shape of the catheter 300 or portions thereof may be selected to match the acoustic impedance of the materials in transducer 601 and the target structure (e.g., blood vessel wall). Impedance matching of the acoustic signal across all elements in the distal portion of catheter 300 is desirable to enhance the response of transducer 601 to the acoustic echo coming from the blood vessel wall.

In certain aspects, a concave transducer may be used in conjunction with a rotating mirror so that the output of the transducer or a reflecting element may be oriented to generally align with the longitudinal axis of the catheter 300, and the mirror may be swept through an arc to generate annular images transverse to the catheter 300.

In other embodiments, the imaging assembly uses optical coherence tomography (OCT). OCT is a medical imaging methodology using a miniaturized near infrared light-emitting probe, and is capable of acquiring micrometer-resolution, three-dimensional images from within optical scattering media (e.g., biological tissue). OCT systems and methods are generally described in Castella et al., U.S. Patent No. 8,108,030, Milner et al., U.S. Patent Application Publication No. 2011/0152771, Condit et al., U.S. Patent Application Publication No. 2010/0220334, Castella et al., U.S. Patent Application Publication No. 2009/0043191, Milner et al., U.S. Patent Application Publication No. 2008/0291463, and Kemp, N., U.S. Patent Application Publication No.

2008/0180683, the content of each of which is incorporated by reference in its entirety.

In OCT, a light source delivers a beam of light to an imaging device to image target tissue. Light sources can be broad spectrum light sources, or provide a more limited spectrum of wavelengths, e.g., near infra-red. The light sources may be pulsed or continuous wave. For example the light source may be a diode (e.g., superluminescent diode), or a diode array, a semiconductor laser, an ultrashort pulsed laser, or supercontinuum light source. Typically the light source is filtered and allows a user to select a wavelength of light to be amplified.

Wavelengths commonly used in medical applications include near-infrared light, for example between about 800 nm and about 1700 nm.

Methods of the invention apply to image data obtained from obtained from any IVUS or OCT system, including OCT systems that operate in either the time domain or frequency (high definition) domain. In time-domain OCT, an interference spectrum is obtained by moving a scanning optic, such as a reference mirror, longitudinally to change the reference path and match multiple optical paths due to reflections of the light within the sample. The signal giving the reflectivity is sampled over time, and light traveling at a specific distance creates interference in the detector. Moving the scanning mechanism laterally (or rotationally) across the sample produces reflectance distributions of the sample (i.e., an imaging data set) from which two- dimensional and three-dimensional images can be produced.

In frequency domain OCT, a light source capable of emitting a range of optical frequencies passes through an interferometer, where the interferometer combines the light returned from a sample with a reference beam of light from the same source, and the intensity of the combined light is recorded as a function of optical frequency to form an interference spectrum. A Fourier transform of the interference spectrum provides the reflectance distribution along the depth within the sample.

Alternatively, in swept-source OCT, the interference spectrum is recorded by using a source with adjustable optical frequency, with the optical frequency of the source swept through a range of optical frequencies, and recording the interfered light intensity as a function of time during the sweep. An example of swept-source OCT is described in U.S. Pat. No. 5,321,501.

Time- and frequency-domain systems can further vary based upon the optical layout of the systems: common beam path systems and differential beam path systems. A common beam path system sends all produced light through a single optical fiber to generate a reference signal and a sample signal whereas a differential beam path system splits the produced light such that a portion of the light is directed to the sample and the other portion is directed to a reference surface. Common beam path systems are described in U.S. Pat. 7,999,938; U.S. Pat. 7,995,210; and U.S. Pat. 7,787,127 and differential beam path systems are described in U.S. Pat. 7,783,337; U.S. Pat. 6,134,003; and U.S. Pat. 6,421,164, the contents of each of which are incorporated by reference herein in their entireties.

In certain embodiments, the invention provides a differential beam path OCT system with intravascular imaging capability as illustrated in FIG. 7. For intravascular imaging, a light beam is delivered to the vessel lumen via a fiber-optic based imaging catheter 826. The imaging catheter is connected through hardware to software on a host workstation. The hardware includes imagining engine 859 and a handheld patient interface module (PIM) 839 that includes user controls. The proximal end of imaging catheter 826 is connected to PIM 839, which is connected to imaging engine 859 as shown in FIG. 7.

An embodiment of imaging engine 859 is shown in FIG. 8. Imaging engine 859 (i.e., the bedside unit) houses power distribution board 849, light source 827, interferometer 831, and variable delay line 835 as well as a data acquisition (DAQ) board 855 and optical controller board (OCB) 851. PIM cable 841 connects imagining engine 859 to PIM 839 and engine cable 845 connects imaging engine 859 to the host workstation (not shown).

FIG. 9 shows an exemplary light path in a differential beam path system which may be used in an OCT system suitable for use with the invention. Light for producing the

measurements originates within light source 827. This light is split between main OCT interferometer 905 and auxiliary interferometer 911. In some embodiments, the auxiliary interferometer is referred to as a "clock" interferometer. Light directed to main OCT

interferometer 905 is further split by splitter 917 and recombined by splitter 919 with an asymmetric split ratio. The majority of the light from splitter 917 is guided into sample path 913 while the remainder goes into reference path 915. Sample path 917 includes optical fibers running through PIM 839 and imaging catheter core 826 and terminating at the distal end of the imaging catheter, where the sample is measured.

The reflected light is transmitted along sample path 913 to be recombined with the light from reference path 915 at splitter 919. A variable delay line (VDL) 925 on the reference path uses an adjustable fiber coil to match the length of reference path 915 to the length of sample path 913. The reference path length is adjusted by a stepper motor translating a mirror on a translation stage under the control of firmware or software.

The combined light from splitter 919 is split into orthogonal polarization states, resulting in RF-band polarization-diverse temporal interference fringe signals. The interference fringe signals are converted to photocurrents using PIN photodiodes 929a, and 929b, on optical controller board (OCB) 851. The interfering, polarization splitting, and detection steps are done by a polarization diversity module (PDM) (not shown) on OCB 851. Signal from OCB 851 is sent to DAQ 855, shown in FIG. 8. DAQ 855 includes a digital signal processing (DSP) microprocessor and a field programmable gate array (FPGA) to digitize signals and

communicate with the host workstation and PIM 839. The FPGA converts raw optical interference signals into meaningful reflectivity measurements. DAQ 855 also compresses data as necessary to reduce image transfer bandwidth, e.g., to lGbps, e.g., by compressing frames with a glossy compression JPEG encoder.

As shown in FIG. 10, in some embodiments the system controller 550 is interfaced to an image processing computer 1060 that is capable of synthesizing the images and tissue measurements into easy-to-under stand images. The image processing computer is also configured to analyze the spectrum of the collected data to determine tissue characteristics, a.k.a. virtual histology. As discussed in greater detail below, the image processing will deconvolve the reflected acoustic waves or interfered infrared waves to produce distance and/or tissue measurements, and those distance and tissue measurements can be used to produce an image, for example an IVUS image or an OCT image. The image processing may additionally include spectral analysis, i.e., examining the energy of the returned acoustic signal at various

frequencies. Spectral analysis is useful for determining the nature of the tissue and the presence of foreign objects. A plaque deposit, for example, will typically have different spectral signatures than nearby vascular tissue without such plaque, allowing discrimination between healthy and diseased tissue. Also a metal surface, such as a stent, will have a different spectral signal. Such signal processing may additionally include statistical processing (e.g., averaging, filtering, or the like) of the returned ultrasound signal in the time domain. The spectral analysis can also be used to determine the tissue lumen/blood border. Other signal processing techniques known in the art of tissue characterization may also be applied,

Other image processing may facilitate use of the images or identification of features of interest. For example, the border of a lumen may be highlighted or thrombus or plaque deposits may be displayed in a visually different manner (e.g., by assigning thrombus a discernible color) than other portions of the image. Other image enhancement techniques known in the art of imaging may also be applied. In a further example, similar techniques can be used to

discriminate between vulnerable plaque and other plaque, or to enhance the displayed image by providing visual indicators to assist the user in discriminating between vulnerable and other plaque. Other measurements, such as flow rates or pressure may be displayed using color mapping or by displaying numerical values. In some embodiments, the open cross-sectional area of the lumen is colorized with red to represent the blood flux.

A system of the invention may be implemented with a variety of architectures. An embodiment of a system 1100 of the invention is shown in FIG. 11. The core of the system 1100 is a computer 1060 or other computational arrangement comprising a processor 1065 and memory 1067. The memory has instructions which when executed cause the processor to determine a baseline measurement prior to conducting a therapeutic procedure and determine a post-therapy measurement after conducting the therapeutic procedure. The instructions may also cause the computer to compare the post-therapy measurement to the baseline measurement, thereby determining the degree of post-therapy improvement after conducting the therapeutic procedure. In the system of the invention, the physiological measurement data of vasculature will originate with a catheter 100 as discussed above, whose function is controlled with a system controller 550. Having collected the image data, the processor then processes the data to build images and identify flow and/or structures and then outputs the results. The results are typically output to a display 580 to be viewed by a physician or technician.

In advanced embodiments, system 1100 may comprise an imaging engine 1059 that has advanced image processing features, such as image tagging, that allow the system 1100 to more efficiently process and display intravascular and angiographic images. The imaging engine 1059 may automatically highlight or otherwise denote areas of interest in the vasculature, such as tissue density or composition. The imaging engine 1059 may also produce 3D renderings or other visual representations of the physiological measurements. In some embodiments, the imaging engine 1059 may additionally include data acquisition functionalities (DAQ) 1055, which allow the imaging engine 1059 to receive the physiological measurement data directly from the catheter 100 or system controller 550 to be processed into images for display.

Other advanced embodiments use the I O functionalities 1062 of computer 1060 to control the detector or to trigger the light source or acoustic transducer for the catheter. While not shown here, it is also possible that computer 1060 may control a manipulator, e.g., a robotic manipulator, connected to catheter 100 to improve the placement of the catheter 100.

A system 1100 of the invention may also be implemented across a number of

independent platforms which communicate via a network 1109, as shown in FIG. 11. Methods of the invention can be performed using software, hardware, firmware, hardwiring, or

combinations of any of these. Features implementing functions can also be physically located at various positions, including being distributed such that portions of functions are implemented at different physical locations (e.g., imaging apparatus in one room and host workstation in another, or in separate buildings, for example, with wireless or wired connections).

As shown in FIG. 11, the system controller 550 facilitates obtaining the data, however the actual implementation of the steps can be performed by multiple processors working in communication via the network 1109, for example a local area network, a wireless network, or the internet. The components of system 1100 may also be physically separated. For example, terminal 1167 and display 580 may not be geographically located with the catheter 100 or the system controller 550.

As shown in FIG. 11, imaging engine 1159 communicates with host workstation 1133 as well as optionally server 1113 over network 1109. In some embodiments, an operator uses host workstation 1133, computer 1060, or terminal 1167 to control system 1100 or to receive images. An image may be displayed using an I/O 1062, 1137, or 1171, which may include a monitor. Any I/O may include a monitor, keyboard, mouse, or touch screen to communicate with any of processor 1065, 1141, or 1175, for example, to cause data to be stored in any tangible, nontransitory memory 1067, 1145, or 1179. In some embodiments, the I/O will include controls that allow a user to toggle between color schemes that accentuate particular features of the vasculature, such as lumen borders or tissue composition. Server 1113 generally includes an interface module 1125 to communicate over network 1109 or write data to a data file. In some embodiments, server 1113 writes data to a remote storage server, a.k.a. a cloud server.

In some embodiments, the system may render three dimensional imaging of the vasculature or the intravascular images. An electronic apparatus within the system (e.g., PC, dedicated hardware, or firmware) such as the host workstation 1133 stores the three dimensional image in a tangible, non-transitory memory and renders an image of the 3D tissues on the display 580. In some embodiments, the 3D images will be coded for faster viewing. In certain embodiments, systems of the invention render a GUI with elements or controls to allow an operator to interact with three dimensional data set as a three dimensional view. For example, an operator may cause a video affect to be viewed in, for example, a tomographic view, creating a visual effect of travelling through a lumen of vessel (i.e., a dynamic progress view). In other embodiments an operator may select points from within one of the images or the three dimensional data set by choosing start and stop points while a dynamic progress view is displayed in display. In other embodiments, a user may cause an imaging catheter to be relocated to a new position in the body by interacting with the image.

Methods of the invention can be performed using software, hardware, firmware, hardwiring, or combinations of any of these. Features implementing functions can also be physically located at various positions, including being distributed such that portions of functions are implemented at different physical locations (e.g., imaging apparatus in one room and host workstation in another, or in separate buildings, for example, with wireless or wired

connections). In certain embodiments, host workstation 1133 and imaging engine 1059 are included in a bedside console unit to operate system 1100.

Processors suitable for the execution of computer program include, by way of example, both general and special purpose microprocessors, and any one or more processor of any kind of digital computer. Generally, a processor will receive instructions and data from a read-only memory or a random access memory or both. The essential elements of computer are a processor for executing instructions and one or more memory devices for storing instructions and data. Generally, a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto-optical disks, or optical disks. Information carriers suitable for embodying computer program instructions and data include all forms of non-volatile memory, including by way of example semiconductor memory devices, (e.g., EPROM, EEPROM, NAND-based flash memory, solid state drive (SSD), and other flash memory devices); magnetic disks, (e.g., internal hard disks or removable disks); magneto-optical disks; and optical disks (e.g., CD and DVD disks). The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.

To provide for interaction with a user, the subject matter described herein can be implemented on a computer having an I/O device, e.g., a CRT, LCD, LED, or projection device for displaying information to the user and an input or output device such as a keyboard and a pointing device, (e.g., a mouse or a trackball), by which the user can provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well. For example, feedback provided to the user can be any form of sensory feedback, (e.g., visual feedback, auditory feedback, or tactile feedback), and input from the user can be received in any form, including acoustic, speech, or tactile input.

The subject matter described herein can be implemented as one or more computer program products, such as one or more computer programs tangibly embodied in an information carrier (e.g., in a non-transitory computer-readable medium) for execution by, or to control the operation of, data processing apparatus (e.g., a programmable processor, a computer, or multiple computers). A computer program (also known as a program, software, software application, app, macro, or code) can be written in any form of programming language, including compiled or interpreted languages (e.g., C, C++, Perl), and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. Systems and methods of the invention can include programming language known in the art, including, without limitation, C, C++, Perl, Java, ActiveX, HTML5, Visual Basic, or JavaScript. A computer program does not necessarily correspond to a file. A program can be stored in a portion of file that holds other programs or data, in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub-programs, or portions of code). A computer program can be deployed to be executed on one computer or on multiple computers at one site or distributed across multiple sites and interconnected by a communication network. A file can be a digital file, for example, stored on a hard drive, SSD, CD, or other tangible, non-transitory medium. A file can be sent from one device to another over network 1109 (e.g., as packets being sent from a server to a client, for example, through a Network Interface Card, modem, wireless card, or similar).

In certain embodiments, display 580 is rendered within a computer operating system environment, such as Windows, Mac OS, or Linux or within a display or GUI of a specialized system. Display 580 can include any standard controls associated with a display (e.g., within a windowing environment) including minimize and close buttons, scroll bars, menus, and window resizing controls. Elements of display 580 can be provided by an operating system, windows environment, application programming interface (API), web browser, program, or combination thereof (for example, in some embodiments a computer includes an operating system in which an independent program such as a web browser runs and the independent program supplies one or more of an API to render elements of a GUI). Display 580 can further include any controls or information related to viewing images (e.g., zoom, color controls, brightness/contrast) or handling files comprising three-dimensional image data (e.g., open, save, close, select, cut, delete, etc.). Further, display 580 can include controls (e.g., buttons, sliders, tabs, switches) related to operating a three dimensional image capture system (e.g., go, stop, pause, power up, power down), or to toggle co-registered images that relate to tissue characterization.

In certain embodiments, display 580 includes controls related to three dimensional imaging systems that are operable with different imaging modalities. For example, display 580 may include start, stop, zoom, save, etc., buttons, and be rendered by a computer program that interoperates with IVUS, OCT, FACT, or angiogram modalities. Thus display 580 can display an image derived from a three-dimensional data set with or without regard to the imaging mode of the system.

Thus, the invention provides catheters capable of imaging and delivering therapeutic compounds. Once the target tissues are identified and the catheter positioned, thrombolytic drugs are delivered to the biological material via a plurality of openings. Thereafter, the operator can move the entire device through the vasculature, using the imaging data to guide the operator. The device is then used to monitor the thrombolysis of the blood clot inside of the vessel. When it is determined that the blood clot or other obstructive material has been removed, the catheter can be removed from the body lumen.

Incorporation by Reference References and citations to other documents, such as patents, patent applications, patent publications, journals, books, papers, web contents, have been made throughout this disclosure. All such documents are hereby incorporated herein by reference in their entirety for all purposes

Equivalents

Various modifications of the invention and many further embodiments thereof, in addition to those shown and described herein, will become apparent to those skilled in the art from the full contents of this document, including references to the scientific and patent literature cited herein. The subject matter herein contains important information, exemplification and guidance that can be adapted to the practice of this invention in its various embodiments and equivalents thereof.

Claims

1. A method for imaging and delivering a therapeutic agent to biological material inside a vessel, the method comprising:

providing an elongated medical device comprising: a catheter body configured to fit within a lumen of a vessel, the catheter body comprising an opening at the distal end of the catheter body and in fluid communication with a port at the proximal end of the catheter body, and the catheter body comprising an imaging assembly coupled to the body;

inserting the device into a lumen of a vessel;

imaging biological material inside the vessel to create image data;

characterizing the biological material by analyzing the image data; and

delivering a therapeutic agent to the biological material.

2. The method of claim 1, further comprising delivering therapeutic energy to the biological material.

3. The method of claim 1, wherein imaging comprises imaging the biological material before and after delivery of the therapeutic agent.

4. The method of claim 3, wherein characterizing comprises characterizing the biological material before and after delivery of the therapeutic agent.

5. The method of claim 1, wherein imaging comprises imaging the biological material simultaneously with delivery of the therapeutic agent.

6. The method according to claim 1, wherein the imaging assembly is an ultrasound assembly, an optical imaging assembly, or an infrared imaging assembly.

7. The method according to claim 6, wherein the ultrasound assembly comprises an opto-acoustic sensor.

8. The method of claim 1, wherein characterizing comprises evaluating imaging assembly-position-dependent changes in the spectrum of the image data.

9. The method of claim 1, wherein characterizing comprises determining the density of the biological material.

10. The method of claim 1, wherein characterizing comprises determining the composition of the biological material.

11. The method of claim 1, wherein characterizing comprises determining a blood- tissue border of the lumen of the vessel.

12. The method of claim 11, further comprising displaying an image comprising a cross section of the lumen of the vessel and the determined blood-tissue border of the lumen of the vessel.

13. The method of claim 12, further comprising colorizing the image to show the blood-tissue border of the lumen.

14. The method of claim 13, wherein colorizing comprises displaying an area within the blood-tissue border of the lumen as red.

15. The method according to claim 1, wherein the biological material is thrombus.

16. The method of claim 1, wherein the therapeutic agent is a thrombolytic agent.

17. The method according to claim 16, wherein the thrombolytic agent is selected from streptokinase, urokinase, alteplase, reteplase, and tenecteplase.

18. A system for treating vasculature, comprising:

an elongated medical device comprising: a catheter body configured to fit within a lumen of the vasculature, the catheter body comprising an opening at the distal end of the catheter body and in fluid communication with a port at the proximal end of the catheter body, and the catheter body comprising an imaging assembly coupled to the body;

an imaging controller for receiving signals from the imaging assembly;

an image processing subsystem for analyzing the received signals and characterizing the vasculature; and

a fluid delivery subsystem for controlling delivery of therapeutic agents to the vasculature.

19. The system of claim 18, wherein the elongated medical device additionally comprises a therapeutic energy source for delivering therapeutic energy to the vasculature.

20. The system of claim 18, wherein the fluid delivery subsystem additionally comprises a syringe or a pump.

21. The system of claim 18, wherein the imaging assembly is an ultrasound imaging assembly.

22. The system of claim 21, wherein the ultrasound imaging assembly comprises an array of ultrasound transducers.

23. The system of claim 21, wherein the ultrasound imaging assembly is configured to move within the catheter body while imaging the body lumen.

24. The system of claim 21, wherein the ultrasound imaging assembly comprises an opto-acoustic sensor.

25. The system of claim 21, wherein the ultrasound imaging assembly images portions of the body lumen distal from the distal end of the catheter body.

26. The system of claim 18, wherein the imaging assembly is an optical imaging assembly.

27. The system of claim 26, wherein the optical imaging assembly is configured for optical coherence tomographic measurements.

28. The system of claim 18, wherein the image processing subsystem is configured to determine a blood-tissue border of the lumen of the vessel.

29. The system of claim 28, further comprising a display for displaying an image comprising a cross section of the lumen of the vessel and the determined blood-tissue border of the lumen of the vessel.

30. An elongated medical device for evaluating a body lumen and delivering therapy thereto, comprising:

a catheter body having a distal end and a proximal end, and including a delivery lumen providing a fluid path between an opening at the distal end of the catheter body and a port at the proximal end of the catheter body; and

an imaging assembly located at the distal end of the catheter body and connected to a signal connection at the proximal end of the catheter body.

31. The medical device of claim 30, further comprising an energy source located at the distal end of the catheter body and configured to deliver a therapy to the body lumen.

32. The medical device of claim 31, wherein the energy source is an acoustic energy source, a thermal energy source, or an electromagnetic radiation source.

33. The medical device of claim 30, wherein the delivery lumen is in fluid communication with a plurality of openings at the distal end of the catheter body.

34. The medical device of claim 30, wherein the imaging assembly is located distal to the opening.

35. The medical device of claim 30, wherein the imaging assembly is located proximal to the opening.

36. The medical device of claim 30, wherein the imaging assembly is located on an external wall of the catheter, opposite the opening.