WO2006061829A1

WO2006061829A1 - Photoacoustic intravascular probe

Info

Publication number: WO2006061829A1
Application number: PCT/IL2005/001312
Authority: WO
Inventors: Benny Pesach; Ron Nagar; Gabriel Bitton
Original assignee: Glucon Inc.
Priority date: 2004-12-06
Filing date: 2005-12-06
Publication date: 2006-06-15

Abstract

Apparatus for imaging a region of a lumen of a conduit comprising: an elongate body having a distal end that can be positioned in the lumen; at least one radiating element located in a neighborhood of the distal end from which radiation is transmitted to illuminate the lumen at at least one wavelength that stimulates thermoacoustic waves in features of the lumen and/or its walls; at least one acoustic transducer that generates signals responsive to the thermoacoustic waves; at least one acoustic transducer controllable to illuminate the lumen with ultrasound; at least one acoustic transducer that generates signals responsive to acoustic energy reflected from the transmitted ultrasound by features of the lumen; and a controller that processes the signals responsive to reflected acoustic energy to generate an ultrasound image of the lumen and the signals responsive to the thermoacoustic waves to assay a component of material in the lumen and/or the lumen walls.

Description

PHOTOACOUSTIC INTRAVASCULAR PROBE RELATED APPLICATION DATA

The present application claims the benefit under 35 USC 119(e) of U.S. Provisional Application No. 60/632,956 filed on December 6, 2004 entitled "Photoacoustic Intravascular Probe", the disclosure of which is incorporated herein by reference.

FIELD OF THE INVENTION

The invention relates to intravascular apparatus for probing the lumen of a blood vessel and assessing its condition.

BACKGROUND OF THE INVENTION Atherosclerotic plaques are fibrous or fibro-fatty lesions in blood vessels that comprise connective tissue, such as collage, proteoglycans, and fibronectin elastic fibers; lipids, such as crystalline cholesterol, cholesterol esters and phospholipids; and cells, such as monocyte- derived macrophages, T lymphocytes and smooth muscle cells. However, not all atherosclerotic plaques are the same and different plaque deposits may comprise different proportions of the above noted components in different structural features. The probability of an atherosclerotic plaque precipitating a catastrophic health failure in a person and a type of therapy chosen to treat the plaque depends upon the location of the plaque in the person's vascular system and its composition and structure.

For example, rupture prone plaques in coronary arteries tend to have a thin fibrous cap having thickness of between about 0.065 to 0.150 mm and a large lipid core. Acute coronary syndromes often result from rupture of modestly stenotic plaques of this type that are not readily visible by x-ray angiography. The rupture releases the lipid core in the plaque, which forms a thrombosis that blocks the artery. On the other hand, high-risk plaques in the carotid arteries are generally severely stenotic, are relatively very fibrous and not necessarily lipid rich. These type of plaques tend to rupture as a result of an intramural hemotoma or dissection that may result from mechanical stress of the plaque generated by impact of blood during systole.

Plaque that is highly calcified tends to be mechanically rigid and prone to breakage when subjected to mechanical stress.

Therapy for treating a particular atherosclerotic lesion is ideally determined responsive to the structure and composition of the plaque. For example, balloon therapy may be advisable for lipid rich plaques, which tend to be relatively elastic. Calcified plaque on the other hand, which has a tendency to be rigid, may rupture in response to the mechanical stress of balloon therapy and may be more advantageously treated using atherectomy. Different methods are available for imaging and determining characteristics of a plaque deposit. X-ray angiography provides relatively high resolution for determining a degree of stenosis of a blood vessel caused by plaque. However this modality does not image blood vessel walls and does not provide information regarding plaque composition, for example whether or not the plaque is lipid rich that might be useful in determining how to treat the plaque.

Intravascular ultrasound (IVUS) is relatively satisfactory for imaging the lumen and walls of a blood vessel and provides information as to shape and structure of atherosclerotic lesions of the blood vessel responsive to echogenicity of lesions. However, angioscopic and histological studies indicate that IVUS shows relatively low sensitivity for detection of thrombi and identifying lipid rich plaque.

For situations in which an occlusion totally blocks a blood vessel, the occlusion often partially or totally "blinds" an intravascular device, such as a catheter or guide wire, used to treat the occlusion and increases the difficulty of operating and navigating the device in the vicinity of the occlusion. For example, a total occlusion of a blood vessel generally blurs the location of the blood vessel wall and makes it difficult to distinguish the blood vessel walls from the occlusion. As a result, there is increased danger that a catheter used to clear the occlusion or a guide wire used to guide a catheter or other device in the blood vessel will penetrate and damage the blood vessel wall. SUMMARY OF THE INVENTION

An aspect of some embodiments of the invention relates to providing an intravascular device that can image the lumen and walls of a blood vessel and/or assay components of lesions that compromise the blood vessel.

In accordance with an embodiment of the invention, the device comprises a long thin rod or tube-like body, an elongate body, that may be introduced and threaded through the vascular system of a patient to position a distal end of the device in a region of a blood vessel lumen that is to be examined for lesions. The distal end includes at least one radiating element, hereinafter a "radiator", from which radiation is radiated and, optionally, at least one acoustic transducer. The radiator may be a region, feature or configuration of features comprised in the device that directs radiation that it receives so that the radiation exits the distal end. Optionally, the radiation comprises optical radiation and the radiator comprises an optical radiator having at least one optical aperture through which optical radiation exits the device. In some embodiments of the invention, the radiation comprises RF, optionally, microwave radiation, and the radiator comprises an antenna for radiating the radiation.

For convenience of presentation, in the discussion below it is assumed that the radiation is optical radiation and that the radiator is an optical element or system comprising an optical aperture. With suitable modifications readily understood by a person of the art, the discussion applies equally well to apparatus, in accordance with embodiments of the invention, for which the radiation comprises other than optical radiation, for example, microwave radiation.

Light at at least one appropriate wavelength is transmitted along the body of the device to the at least one radiator from which the .light is radiated to illuminate the region and stimulate photoacoustic waves in tissue of the region. The at least one acoustic transducer generates signals, "photoacoustic signals", responsive to acoustic energy from the photoacoustic waves that is incident on the at least one transducer. A suitable processor processes the photoacoustic signals to generate a "photoacoustic image" of the region that images features of the blood vessel walls and/or lumen and/or to assay components of the features. Optionally, an assay provided by the processor provides concentration of the components as a function of spatial location in the blood vessel. In addition, the at least one acoustic transducer is, optionally, operable to image the region with ultrasound similarly to the way a conventional intravascular ultrasound (IVUS) catheter is operated to provide an "IVUS image" of a blood vessel. An intravascular device in accordance with an embodiment of the invention, will for convenience of presentation, be referred to as a "photoacoustic intravascular ultrasound device" (PIVUSD). The nomenclature, PIVUSD is used generically to include embodiments of the invention in which radiation that generates acoustic waves comprises optical radiation and/or RF radiation and the radiator comprises an optical radiator and/or an antenna for radiating RF energy. (Acoustic waves generated in a material by radiation, not necessarily optical radiation, are often referred to as "thermoacoustic waves", of which, photoacoustic waves are a particular type or species that is generated by optical radiation.)

Assay information provided by a PIVUSD in accordance with an embodiment of the invention, can be advantageous for distinguishing composition of atherosclerotic plaque that may be present in the region and determining a therapeutic procedure for treating such plaque. Imaging information provided by the photoacoustic signals can be advantageous for determining structural detail of features of the region and for navigating a catheter or other intravascular device in the region. In particular, such imaging information can be advantageous if a highly calcified plaque deposit blocks the blood vessel region. Such a plaque deposit, because it is relatively highly reflective of ultrasound, tends to obscure details in conventional rVUS images and in particular makes it difficult to distinguish walls of the blood vessel and boundaries of the plaque in an ultrasound image. A photoacoustic image on the other hand is generally less prone to blurring by such a deposit. For example, wavelength of light used to stimulate photoacoustic waves may be chosen so that the light penetrates calcium deposits and generates photoacoustic waves in tissue inside and behind the deposit. In addition, photoacoustic waves that propagate to the at least one transducer from a location at which they are generated will in general be less affected by changes in acoustic impedance in tissue through which they propagate than transmitted ultrasound reflected from the same location. The reflected transmitted ultrasound travels twice a distance (from the at least one transducer to the reflection location and back to the at least one transducer) through the tissue as the photoacoustic waves.

In some embodiments of the invention, a processor comprised in a PIVUSD generates a composite image of a blood vessel lumen comprising an overlay of an IVUS image and/or a photoacoustic image and/or an assay of a component of the blood vessel as a function of spatial location. The composite image provides details of features of the lumen and lumen walls that generally are unavailable from an image produced using a single imaging modality. Since a same at least one acoustic transducer is optionally used to generate signals responsive to both reflected ultrasound and photoacoustic waves, reflected ultrasound and photoacoustic waves originating from a same location will generally be determined to originate from the same location with a relatively high degree of resolution. As a result, a photoacoustic image and/or an assay image and/or an IVUS image provided by a PIVUSD in accordance with an embodiment of the invention are substantially automatically spatially registered one to the other. A PIVUSD in accordance with an embodiment of the invention is therefore capable of providing an optionally real time, relatively high quality composite image with relatively moderate computational resources.

In some embodiments of the invention, a PIVUSD processes photoacoustic signals to determine temperature of regions of a blood vessel wall and determine presence of plaque deposits in the blood vessel responsive to the determined temperature. An article entitled "Critical Imaging of High-Risk or Vulnerable Atherosclerotic Plaque" by Z.A. Fayad et al. in Circulation Research 2001: 89:pp 305-316, the disclosure of which is incorporated herein by reference, notes that there is indication that heat released by inflammatory cells of atherosclerotic plaque may be used to identify plaque and predict plaque disruption and thrombosis. Optionally, the PIVUSD uses methods described in PCT Publication WO 03/048704, the disclosure of which is incorporated herein by reference, to determine temperature. There is therefore provided in accordance with an embodiment of the present invention, apparatus for imaging a region of a lumen of a conduit comprising: an elongate body having a distal end that can be positioned in the lumen; at least one radiating element located in a neighborhood of the distal end from which radiation is transmitted to illuminate the lumen at at least one wavelength that stimulates thermoacoustic waves in features of the lumen and/or its walls; at least one acoustic transducer that generates signals responsive to the thermoacoustic waves; at least one acoustic transducer controllable to illuminate the lumen with ultrasound; at least one acoustic transducer that generates signals responsive to acoustic energy reflected from the transmitted ultrasound by features of the lumen; and a controller that processes the signals responsive to reflected acoustic energy to generate an ultrasound image of the lumen and the signals responsive to the thermoacoustic waves to assay a component of material in the lumen and/or the lumen walls.

Optionally, the assay is a function of spatial location in the lumen. Additionally or alternatively, the controller optionally generates a thermoacoustic image of the lumen using signals generated responsive to the thermoacoustic waves. There is also provided in accordance with an embodiment of the invention, apparatus for imaging a region of a lumen of a conduit comprising: an elongate body having a distal end that can be positioned in the lumen; at least one radiating element located in a neighborhood of the distal end from which radiation is transmitted to illuminate the lumen at at least one wavelength that stimulates thermoacoustic waves in features of the lumen; at least one acoustic transducer that generates signals responsive to the thermoacoustic waves; at least one acoustic transducer controllable to illuminate the lumen with ultrasound; at least one acoustic transducer that generates signals responsive to acoustic energy reflected from the transmitted ultrasound by features of the lumen; and a controller that processes the signals responsive to reflected acoustic energy to generate an ultrasound image of the lumen and the signals responsive to the thermoacoustic waves to generate a thermoacoustic image of the lumen.

Optionally, the controller assays a component of material in the lumen or its walls responsive to the thermoacoustic waves. Optionally, the assay is a function of spatial location in the lumen. In some embodiments of the invention, the controller generates a composite image of the lumen responsive to signals generated responsive to reflected ultrasound and signals generated responsive to thermoacoustic waves.

In some embodiments of the invention, the at least one transducer that transmits ultrasound comprises a piezoelectric material that transmits ultrasound responsive to voltage applied to the material.

In some embodiments of the invention, the at least one transmitting transducer comprises an absorber that absorbs optical energy and converts the absorbed energy to acoustic energy. The apparatus optionally comprises an optic fiber that transmits light to the absorber. In some embodiments of the invention, the radiation comprises optical radiation and the at least one radiator comprises an optical radiator. Optionally, the optical radiator comprises a region of an optic fiber that extends along the elongate body. Optionally, the optical radiator comprises a Bragg grating that diffracts light so that it exits the fiber. Optionally, the Bragg grating is blazed. In some embodiments of the invention, the optical radiator comprises a difftiser that receives optical energy and diffuses it to illuminate the lumen.

In some embodiments of the invention, the radiation comprises RF radiation and the radiator comprises an antenna that radiates the radiation. Optionally, the RF radiation comprises microwave radiation.

In some embodiments of the invention, an acoustic transducer of the at least one acoustic transducer controllable to illuminate the lumen with ultrasound is comprised in or on the elongate body and is located in a neighborhood of the distal end.

In some embodiments of the invention, the conduit is part of a body having an external surface and an acoustic transducer of the at least one acoustic transducer is located on an external surface of the body. In some embodiments of the invention, a same acoustic transducer that generates signals responsive to reflected ultrasound generates signals responsive to thermoacoustic waves. In some embodiments of the invention, the conduit is a conduit in the human body. In some embodiments of the invention, the conduit is a blood vessel.

There is further provided in accordance with an embodiment of the invention, method of determining characteristics of the lumen of a blood vessel comprising: reflecting ultrasound from features of the lumen; generating an image of the lumen responsive to the reflected ultrasound; exciting thermoacoustic waves in features of the blood vessel; assaying an analyte of the features responsive to the thermoacoustic waves; and determining a characteristic of the blood vessel lumen responsive to the ultrasound image and the assay. Optionally the method comprises generating an image of the lumen responsive to the thermoacoustic waves.

There is further provided in accordance with an embodiment of the invention, method of determining characteristics of the lumen of a blood vessel comprising: reflecting ultrasound from features of the lumen; generating an image of the lumen responsive to the reflected ultrasound; exciting thermoacoustic waves in features of the blood vessel; generating an image of the lumen responsive to the thermoacoustic waves; and determining a characteristic of the blood vessel lumen responsive to the ultrasound image and the assay. Additionally or alternatively, the method comprises generating a composite image of the lumen responsive to the reflected ultrasound and the thermoacoustic waves.

In some embodiment of the invention, generating thermoacoustic waves comprises illuminating the lumen with RF energy that is absorbed and/or scattered by the component. In some embodiment of the invention, generating thermoacoustic waves comprises illuminating the lumen with optical energy that is absorbed and/or scattered by the component. There is further provided in accordance with an embodiment of the invention, apparatus for imaging a region of a lumen of a conduit comprising: an elongate body having a distal end that can be positioned in the lumen; at least one radiating element located in a neighborhood of the distal end from which radiation is transmitted to illuminate the lumen at at least one wavelength that stimulates thermoacoustic waves in features of the lumen and/or its walls; at least one acoustic transducer that generates signals responsive to the thermoacoustic waves; and a controller that processes the signals responsive to the thermoacoustic waves to assay a component of material in the lumen and/or the lumen walls.

BRIEF DESCRIPTION OF FIGURES Non-limiting examples of embodiments of the present invention are described below with reference to figures attached hereto, which are listed following this paragraph. In the figures, identical structures, elements or parts that appear in more than one figure are generally labeled with a same numeral in all the figures in which they appear. Dimensions of components and features shown in the figures are chosen for convenience and clarity of presentation and are not necessarily shown to scale. Fig. 1 schematically shows a photoacoustic intravascular ultrasound device (PIVUSD) being used to analyze a region of a blood vessel, in accordance with an embodiment of the present invention; Fig. 2 schematically shows a distal end of a PWUSD, in accordance with another embodiment of the present invention;

Fig. 3 schematically shows a distal end of another PIVUSD, in accordance with an embodiment of the invention; Fig. 4 schematically shows a PIVUSD comprising a plurality of optic fibers being used to diagnose a region of a blood vessel, in accordance with an embodiment of the present invention; and

Figs. 5A-5C schematically show a PIVUSD comprising a plurality of fibers having blazed Bragg gratings formed therein being used to diagnose a region of a blood vessel, in accordance with an embodiment of the invention.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS Fig. 1 schematically shows a PIVUSD 20 being used to image a region 21 of a blood vessel 22 having a lumen 24 defined by a wall 26, in accordance with an embodiment of the invention. By way of example, wall 26 is compromised by an atherosclerotic plaque deposit 28. Only features of PIVUSD 20 and blood vessel 22 that are germane to the discussion are shown in Fig. 1.

PrVUSD 20 optionally comprises a catheter 30 having a proximal end 32 connected to a controller 40 and a distal end 34 that is positioned inside region 21. At least one acoustic transducer is optionally mounted on an external surface 38 of distal end 34. Controller 40 comprises control circuitry 41 and a processor 42 for respectively controlling the at least one transducer to optionally transmit ultrasound and to process signals that the at least one transducer generates responsive to echoes of the transmitted ultrasound.

The at least one transducer may be configured and controlled, and signals that it generates processed, using any of many different configurations, devices and algorithms known in the art and, optionally, comprises an array of transducers. In Fig. 1, by way of example, the at least one acoustic transducer comprises an array of transducers 36 optionally, configured in an azimuthally symmetric array on surface 38 of catheter 30.

In some embodiments of the invention, transducer 36 comprises piezoelectric material that is excited by electrical power transmitted along a wire or wires (not shown) that connects the at least one acoustic transducer to controller 40. In some embodiments of the invention, at least one transducer 36 comprises an absorber that absorbs optical energy and converts the optical energy to acoustic energy. Optical energy is optionally piped to the absorbers using optic fibers coupled to a suitable optical system comprised in controller 40. Optoacoustic transducers comprising optical absorbers comprised in an intravascular ultrasound (US) imaging guidewire are described in US patent application publication 2004/0067000, the disclosure of which is incorporated herein by reference.

In Fig. 1, transducers 36 are shown being operated to transmit ultrasound waves 50 that are incident on and reflected by walls 26 and plaque deposit 28. In addition to transmitting ultrasound 50, acoustic transducers 36 also, optionally, generate signals responsive to the reflected ultrasound. The signals are analyzed by processor 42 to generate an ultrasound (US) image of blood vessel 22. In some embodiments of the invention, reflected ultrasound is sensed optically. Optical detection of ultrasound is described in US patent application publication 2004/0067000 cited above and in PCT Publication WO 99/58059, the disclosure of which is incorporated herein by reference, which describes an intravascular guidewire that senses reflected ultrasound optically. In some embodiments of the invention, reflected ultrasound is "piped" from distal end 34 to proximal end 32 where the ultrasound is sensed and processed by controller 40. Optionally, the ultrasound is piped from the distal end via at least one optic fiber, optionally an optic fiber 60 discussed below, comprised in PIVUSD 20.

In accordance with an embodiment of the invention, catheter 30 is introduced into blood vessel 22 over a guidewire comprising an optic fiber 60 having an end 61 that optionally protrudes from distal end 34 of PIVUSD 20. (Only optic fiber 60 of the guidewire is shown and the optic fiber may be configured as a part of a guidewire or incorporated into a guidewire using any of various methods known in the art.) Controller 40 comprises an optical system 43 that transmits light along fiber 60 at at least one wavelength that is absorbed and/or scattered by analytes of tissue comprised in blood vessel 22. Fiber end 61 optionally comprises an optical radiator 62 that receives light transmitted along optic fiber 60 by optical system 43 and directs the light so that it exits the fiber and stimulates photoacoustic waves in the tissue. In Fig. 1, light provided by optical system 42 that is transmitted from radiator 62 to illuminate tissue in blood vessel 22 and stimulate photoacoustic waves therein is represented by wavy arrows 64. Optionally, radiator 62 comprises an optical diffuser that diffuses light transmitted along the fiber, optionally substantially laterally with a substantially same intensity in all azimuthal directions, to illuminate walls 26 of blood vessel 22 and plaque deposit 28. Optionally, radiator 62 comprises diffractive elements formed on its surface or internally that directs light received by the component so that it exits the fiber. Optionally, the radiator comprises an internal, at least partially, reflecting surface that directs light to exit the fiber. Alternatively or additionally, for a PIVUSD in accordance with an embodiment of the invention using RJF radiation, catheter 30 sheaths a microwave transmission line comprising at an end thereof a radiator having a suitable RF antenna. Controller 40 comprises a pulsed RP generator for generating RF radiation that is transmitted along the transmission line and radiated by the antenna to stimulate photoacoustic waves in tissue in region 34.

Acoustic transducers 36 receive acoustic energy from the stimulated photoacoustic waves and generate signals responsive thereto. In some embodiments of the invention, the signals are processed by processor 42 to assay components of tissue in blood vessel 22 and/or plaque deposit 28. For example, processor 42 optionally processes the signals to assay components of plaque 28 and aid in determining if the plaque is a rupture prone plaque containing a large lipid core. Controller 40 controls illumination of blood vessel 22 and processor 42 processes photoacoustic signals generated by acoustic transducers 36 to assay tissue in the blood vessel using any of various methods and procedures known in the art. Optionally, the methods and procedures are similar to those described in US Patent Number 6,846,288, the disclosure of which is incorporated herein by reference. Optionally, an assay provided by PIVUSD 20 is an "assay image" in which concentration of a component of tissue in blood vessel 22 is a function of spatial location in the blood vessel 22.

In some embodiments of the invention, processor 42 processes the photoacoustic signals to provide a "photoacoustic" image of wall 26 of blood vessel 22 and of plaque 28, as well as to assay wall and/or plaque components. Any photoacoustic imaging methods and/or procedures known in the art may be used to provide a photoacoustic image of blood vessel 22 and plaque 28. Optionally, the methods and procedures are similar to those described in US Patent Number 6,846,288 cited above.

Optionally, processor 42 combines data from a photoacoustic image of blood vessel 22 and/or an assay image and/or a US image of the blood vessel that the processor provides to provide a composite image of the blood vessel for diagnosing the condition of the blood vessel. Optionally, the composite image comprises an overly of the US and/or the photoacoustic image and/or the assay image.

In some embodiments of the invention, processor 42 processes the photoacoustic signals to determine temperature of regions of wall 26. Optionally, processor 42 determines the temperature using a method described in PCT publication WO 03/048704, referenced above. The processor determines if a plaque deposit, such as plaque 28, is present in a region of wall 26 if the region has an elevated temperature relative to a normal ambient temperature of the blood vessel wall. In some embodiments of the invention, if the temperature indicates presence of plaque, the processor determines responsive to the temperature whether the plaque is prone to disruption.

Fig. 2 schematically shows a distal end 82 of a PIVUSD 80, in accordance with another embodiment of the invention. Similarly to PIVUSD 20 shown in Fig. 1, PIVUSD 80 comprises a US catheter 30 having on a surface region 38 in a neighborhood of its distal end 82 at least one acoustic transducer 36, which by way of example comprises an array of transducers 36. However, unlike PIVUSD 20, light for stimulating photoacoustic waves in a region of a blood vessel being examined using PIVUSD 20 is piped to distal end 82 of the PIVUSD along a light pipe 84 that is concentric with and sheaths catheter 30. Features of catheter 30 thatare covered by light pipe 84 are shown with ghost lines.

In an embodiment of the invention, light pipe 84 is formed from a flexible, optically conductive material that is also substantially transparent to acoustic waves, such as an optically and acoustically transparent polymer, and comprises an optionally cylindrical optical radiator 86, which is concentric with catheter 30. Light pipe 84 is optionally configured to improve acoustic coupling of transducers 36 to a tissue environment in which it is used. For example, for a given frequency of acoustic waves, to acoustically match transducers 36 to surrounding tissue, light pipe 84 is formed having a thickness equal to an odd multiple of a quarter wavelength of the waves from a material having acoustic impedance equal to about the geometric mean of the acoustic impedances of the transducers and tissue. Radiator 86 optionally comprises a diffuser that diffuses light received by the radiator radially with a substantially same intensity in all azimuthal directions. In order for the diffuser to diffuse light with a substantially same intensity from all regions along at least part of the length of radiator 86, optionally, the radiator comprises light scattering elements having a density that increases with position along the radiator as the position approaches distal end 82 of PIVUSD. Optionally, optical radiator 86 comprises diffractive elements or reflective surfaces that direct light received by the components so that it exits the component.

Fig. 3 schematically shows a distal end 92 of a PPVUSD 90, in accordance with an embodiment of the invention. PIVUSD 90 is similar to PIVUSD 80 and comprises an inner US catheter 30 sheathed in a concentric light pipe 94. Light pipe 94 has a beveled end 96, which functions as an optical radiator and diffracts light that is piped down light pipe 94 laterally, and optionally with substantially a same intensity in all azimuthal directions, to illuminate a region of a blood vessel in which distal end 92 is located. In some embodiments of the invention, beveled end 96 comprises diffractive optical elements that control angular distribution of light exiting the end. The diffractive elements are, optionally, formed on the surface of end 96 by molding or embossing.

Fig. 4 schematically shows a PIVUSD 100 comprising a US catheter 30 having acoustic transducers 36 and a plurality of optic fibers 102 for transmitting light to stimulate photoacoustic waves in tissue, of a region of a blood vessel 22 being examined using the PIVUSD, in accordance with an embodiment of the invention. Blood vessel 22 is shown cutaway along a cross section of the blood vessel and is, by way of example, compromised by a plaque deposit 28. Optical fibers 102 are, optionally, attached to outer surface 38 of US catheter 30 in an azimuthally symmetric configuration. Each fiber 102 optionally comprises a beveled surface 104 that functions as an optical radiator of PIVUSD 100. The beveled surface refracts and/or diffracts light transmitted along the fiber to the surface substantially laterally in a relatively narrow beam in a direction having an azimuth substantially equal to that of the position of the fiber relative to the axis 106 of US catheter 30. In some embodiments of the invention, each fiber 102 comprises a reflector in addition to or in place of beveled surface 104 that functions as a radiator to transmit light from the fibers distal end. Optionally, the reflector is a blazed

Bragg grating. Optionally, the fiber comprises a diffractive element that functions as a radiator.

Optionally, controller 40 controls optical system 43 to transmit light along each optic fiber 102 independent of transmission along the other fibers. In some embodiments of the invention, controller 40 sequentially transmits light along different optic fibers 102 sequentially to illuminate different sectors of blood vessel 22. In Fig. 4, controller 40 is schematically shown controlling optical system 43 so that only a single fiber 102 transmits light, schematically represented by wavy arrows 110, from its beveled end 104 to illuminate a sector of blood vessel 22 and stimulate photoacoustic waves in the sector. As each sector is illuminated, acoustic transducers 36 generate signals responsive to acoustic energy that is incident on the transducers from the photoacoustic waves stimulated in the sector. Processor 42 processes the signals to generate an image of the sector and/or to assay components of tissue in the sector and/or determine temperature of the region. By sequentially illuminating and imaging different sectors, PIVUSD 100 provides an image and/or an assay and/or temperature of blood vessel 22 that provides respectively image, and/or assay and/or temperature details of tissue in the blood vessel, as a function of azimuth. It is noted that an array of acoustic transducers such as array of transducers 36 shown in Figs 1-4 can be used to provide details of tissue in blood vessel 22 as a function of azimuth without an optical radiator operable to selectively illuminate different sectors of the blood vessel. However, a configuration of fibers such as fibers 102, which can be controlled to selectively illuminate different sectors of the blood vessels, can in general be operated to provide a photoacoustic image or assay having improved azimuthal resolution.

Figs. 5A-5C schematically show a distal end 122 of another PIVUSD 120 located in a region of blood vessel 22 to image and/or assay the blood vessel, in accordance with an embodiment of the invention. PIVUSD 120 is similar to PIVXJSD 100 and comprises a US catheter 30, having mounted to its external surface 38 a plurality of optic fibers 124. Dashed lines indicate portions of catheter 30 hidden by fibers 124.

Each optic fiber 124 comprises at least one blazed Bragg grating that functions as an optical radiator of the PIVUSD. By way of example, each optic fiber 124 comprises two blazed Bragg gratings 131 and 132. Each Bragg grating 131 and 132 in a same fiber 124 is formed using methods known in the art so that it diffracts out of the fiber, in a relatively narrow beam of light, a different wavelength of light transmitted along the fiber. Wavelengths of light that Bragg gratings 131 and 132 diffract are optionally wavelengths that are absorbed and/or scattered by at least one analyte of wall 26 of blood vessel 22 and/or of plaque 28. The blaze angles of Bragg gratings 131 and 132 in each fiber 124 are optionally determined so that light that they diffract illuminates substantially a same region of an azimuthal sector of tissue in blood vessel 22. Light diffracted by Bragg gratings 131 and 132 in different fibers 124 illuminate regions of different sectors of the blood vessel.

Fig. 5 A schematically shows light, represented by wavy arrows 151, from a Bragg grating 132 of a fiber 124 illuminating a region of a sector of blood vessel 22, which by way of example comprises a portion of plaque 28. Fig. 5B schematically shows light 152 from Bragg grating 131 of the same fiber 124 illuminating the same portion of plaque 28.

Optionally, an end 134 of a fiber 124 functions as an additional optical output port of the fiber that transmits light, which is transmitted along fiber 124 and not diffracted by Bragg gratings 131 or 132, "forward" substantially along axis 136 of catheter 30. The forward transmitted light illuminates regions of blood vessel 22 in front of distal end 122 of PIVUSD 120. Optionally, end 134 is formed using methods known in the art with a suitable lens that directs light transmitted from the end in a beam having a desired configuration and forward direction. For example, the lenses at ends 134 of a plurality of fibers 124 may be formed so that light from each end 134 of the plurality of fibers illuminates substantially a same region along axis 136 in front distal end 122 of PIVUSD 120 and thereby a same region, optionally, along the axis of a blood vessel. Alternatively, the lenses may be formed so that light from ends 134 of different fibers 124 is transmitted in substantially parallel beams of light that illuminate regions at different azimuthal locations in front of distal end 122. Fig. 5C schematically shows light 153 exiting an end 134 of a fiber 124 to illuminate a region in front of distal end 122 of PIVUSD 120.

In accordance with an embodiment of the invention, controller 41 controls optical system 43 comprised in the PIVUSD 120 sequentially to transmit light along different fibers 124 at different wavelengths of light that are diffracted by Bragg gratings 131 and 132 and at wavelengths which are transmitted by the Bragg gratings and exit the fiber through their respective ends 134. By sequentially illuminating blood vessel 22 with light from different fibers 124 and at different wavelengths, PIVUSD 120 is able to provide images and/or assays and temperatures of regions of blood vessel 22 at different azimuths that are located at the sides of distal end 82 and/or in front of the distal end.

Whereas in the above embodiments of the present invention, photoacoustic waves are sensed by acoustic transducers mounted to a distal end of a PIVUSD, in some embodiments of the invention, photoacoustic waves are sensed using acoustic transducers mounted externally to the patient's body. In some embodiments of the invention, externally mounted transducers are used in place of transducers mounted to the PIVUSD. In some embodiments of the invention, the external transducers are used in addition to transducers mounted to the PIVUSD.

In embodiments of the invention, in which photoacoustic waves are sensed by acoustic transducers located outside the body, optionally, only an "illuminating" guide wire, such as for example a guide wire comprising optic fiber 60 shown in Fig. 1, is introduced into a blood vessel to probe the blood vessel. The cross section dimensions of such a guide wire are optionally substantially the same or possibly smaller than conventional guidewires that are used to guide introduction of catheters into the vascular system. (A conventional guide wire typically has a diameter of about 1 French, which is equal to 1/3 mm). For such embodiments, the relatively small size of the guide wire enables investigation, in accordance with an embodiment of the invention, of relatively small blood vessels and conduits in the body. As with other embodiments of the present invention, embodiments comprising an illuminating guidewire and external transducers may be used to detect the shape and structure of occlusions that totally block a blood vessel. Whereas embodiments of the invention have been shown being used to determine characteristics of blood vessels compromised by plaque, a PIVUSD in accordance with an embodiment of the invention may be used for other applications. For example a PIVUSD in accordance with an embodiment of the invention may be introduced through the urethra of a male patient and have its distal end positioned in or near to the patient's prostate gland. Once positioned, the PIVUSD may be operated to assay oxygenated and deoxygenated hemoglobin and identify hypoxic tissue regions indicative of cancer.

It is also noted that it is of course possible to operate a PIVUSD or to have a configuration of a PIVUSD in accordance with an embodiment of the invention that produces diagnostic data responsive only to photoacoustic waves. For example, a PIVUSD may be configured to provide a photoacoustic image and/or an assay and/or an assay image.

In the description and claims of the present application, each of the verbs, "comprise" "include" and "have", and conjugates thereof, are used to indicate that the object or objects of the verb are not necessarily a complete listing of members, components, elements or parts of the subject or subjects of the verb.

The present invention has been described using detailed descriptions of embodiments thereof that are provided by way of example and are not intended to limit the scope of the invention. The described embodiments comprise different features, not all of which are required in all embodiments of the invention. Some embodiments of the present invention utilize only some of the features or possible combinations of the features. Variations of embodiments of the present invention that are described and embodiments of the present invention comprising different combinations of features noted in the described embodiments will occur to persons of the art. The scope of the invention is limited only by the following claims.

Claims

1. Apparatus for imaging a region of a lumen of a conduit comprising: an elongate body having a distal end that can be positioned in the lumen; at least one radiating element located in a neighborhood of the distal end from which radiation is transmitted to illuminate the lumen at at least one wavelength that stimulates thermoacoustic waves in features of the lumen and/or its walls; at least one acoustic transducer that generates signals responsive to the thermoacoustic waves; at least one acoustic transducer controllable to illuminate the lumen with ultrasound; at least one acoustic transducer that generates signals responsive to acoustic energy reflected from the transmitted ultrasound by features of the lumen; and a controller that processes the signals responsive to reflected acoustic energy to generate an ultrasound image of the lumen and the signals responsive to the thermoacoustic waves to assay a component of material in the lumen and/or the lumen walls.

2. Apparatus according to claim 1 wherein the assay is a function of spatial location in the lumen.

3. Apparatus according to claim 1 or claim 2 wherein the controller generates a thermoacoustic image of the lumen using signals generated responsive to the thermoacoustic waves.

4. Apparatus for imaging a region of a lumen of a conduit comprising: . an elongate body having a distal end that can be positioned in the lumen; at least one radiating element located in a neighborhood of the distal end from which radiation is transmitted to illuminate the lumen at at least one wavelength that stimulates thermoacoustic waves in features of the lumen; at least one acoustic transducer that generates signals responsive to the thermoacoustic waves; at least one acoustic transducer controllable to illuminate the lumen with ultrasound; at least one acoustic transducer that generates signals responsive to acoustic energy reflected from the transmitted ultrasound by features of the lumen; and a controller . that processes the signals responsive to reflected acoustic energy to generate an ultrasound image of the lumen and the signals responsive to the thermoacoustic waves to generate a thermoacoustic image of the lumen.

5 Apparatus according to claim 4 wherein the controller assays a component of material in the lumen or its walls responsive to the thermoacoustic waves.

6. Apparatus according to claim 5 wherein the assay is a function of spatial location in the lumen.

7. Apparatus according to any of the preceding claims wherein the controller generates a composite image of the lumen responsive to signals generated responsive to reflected ultrasound and signals generated responsive to thermoacoustic waves.

8. Apparatus according to any of the preceding claims wherein the at least one transducer that transmits ultrasound comprises a piezoelectric material that transmits ultrasound responsive to voltage applied to the material.

9. Apparatus according to any of the preceding claims wherein the at least one transmitting transducer comprises an absorber that absorbs optical energy and converts the absorbed energy to acoustic energy.

10. Apparatus according to claim 9 and comprising an optic fiber that transmits light to the absorber.

11. Apparatus according to any of the preceding claims wherein the radiation comprises optical radiation and the at least one radiator comprises an optical radiator.

12. Apparatus according to claim 11 wherein the optical radiator comprises a region of an optic fiber that extends along the elongate body.

13. Apparatus according to claim 12 wherein the optical radiator comprises a Bragg grating that diffracts light so that it exits the fiber.

14. Apparatus according to claim 13 wherein the Bragg grating is blazed.

15. Apparatus according to any of claims 12-14 wherein the optical radiator comprises a diffuser that receives optical energy and diffuses it to illuminate the lumen.

16. Apparatus according to any of the preceding claims wherein the radiation comprises RF radiation and the radiator comprises an antenna that radiates the radiation.

17. Apparatus according to claim 16 wherein the RF radiation comprises microwave radiation.

18. Apparatus according to any of the preceding claims wherein an acoustic transducer of the at least one acoustic transducer controllable to illuminate the lumen with ultrasound is comprised in or on the elongate body and is located in a neighborhood of the distal end.

19. Apparatus according to any of claims 1-18 wherein the conduit is part of a body having an external surface and an acoustic transducer of the at least one acoustic transducer is located on an external surface of the body.

20. Apparatus according to any of claims 1-19 wherein a same acoustic transducer that generates signals responsive to reflected ultrasound generates signals responsive to thermoacoustic waves.

21. Apparatus according to any of the preceding claims wherein the conduit is a conduit in the human body.

22. Apparatus according to claim 20 wherein the conduit is a blood vessel.

23. A method of determining characteristics of the lumen of a blood vessel comprising: reflecting ultrasound from features of the lumen; generating an image of the lumen responsive to the reflected ultrasound; exciting thermoacoustic waves in features of the blood vessel; assaying an analyte of the features responsive to the thermoacoustic waves; and determining a characteristic of the blood vessel lumen responsive to the ultrasound image and the assay.

24. A method according to claim 23 and comprising generating an image of the lumen responsive to the theπnoacoustic waves.

25. A method of determining characteristics of the lumen of a blood vessel comprising: reflecting ultrasound from features of the lumen; generating an image of the lumen responsive to the reflected ultrasound; exciting thermoacoustic waves in features of the blood vessel; generating an image of the lumen responsive to the thermoacoustic waves; and determining a characteristic of the blood vessel lumen responsive to the ultrasound image and the assay.

26. A method according to claim 24 or claim 25 and comprising generating a composite image of the lumen responsive to the reflected ultrasound and the thermoacoustic waves.

27. A method according to any of claims 23-26 wherein generating thermoacoustic waves comprises illuminating the lumen with RF energy that is absorbed and/or scattered by the component.

28. A method according to any of claims 23-27 wherein generating thermoacoustic waves comprises illuminating the lumen with optical energy that is absorbed and/or scattered by the component.

29. Apparatus for imaging a region of a lumen of a conduit comprising: an elongate body having a distal end that can be positioned in the lumen; at least one radiating element located in a neighborhood of the distal end from which radiation is transmitted to illuminate the lumen at at least one wavelength that stimulates thermoacoustic waves in features of the lumen and/or its walls; at least one acoustic transducer that generates signals responsive to the thermoacoustic waves; and a controller that processes the signals responsive to the thermoacoustic waves to assay a component of material in the lumen and/or the lumen walls.