WO2003003923A2

WO2003003923A2 - Method and system for endovascular radiation detection

Info

Publication number: WO2003003923A2
Application number: PCT/CA2002/001025
Authority: WO
Inventors: Philippe Leblanc; Guy Leclerc; Céline SIMI; Raymond Carrier
Original assignee: Angiogene Inc
Current assignee: Angiogene Inc
Priority date: 2001-07-05
Filing date: 2002-07-05
Publication date: 2003-01-16
Anticipated expiration: 2004-01-05
Also published as: AU2002317113A1; WO2003003923A3

Abstract

A photostimulable material is introduced in a blood vessel or body cavity, within an animal or human body, where a radioactive agent (comprising for example beta-emitting 32P atoms) has been locally delivered and where radiation measurements have to be taken in order to control the delivery efficiency. The photostimulable material is exposed to radiation, carrying image information of the beta-emitting source of radiation, and a latent image is stored into the photostimulable material. Then the photostimulable material is exposed to stimulating light, which causes the photostimulable material to emit light in proportion of the amount of energy stored during radiation exposure, hence in proportion of the amount of radioactive agent present in the region of interest. The emitted light is collected by a light collection system and measured by a photoelectric device. Therefore, a two-dimensional image signal, representing the distribution of the radioactive agent in the blood vessel or body cavity, is obtained.

Description

METHOD AND SYSTEM FOR ENDOVASCULAR RADIATION DETECTION

TECHNICAL FIELD

The current invention relates to the art of imaging and optimizing the delivery of a localized radioactive agent inside a living animal or human body by producing a one- or two-dimensional map of the local drug delivery. More particularly, the invention is a special radiation detector and imager that may be introduced in a blood vessel or body cavity, within an animal or human body, to measure and image the distribution of a radioactive agent delivered locally to the said part of the body. The purpose of the detector and imager device is to provide a precise picture of the spatial distribution of a radioactive source, quantify the amount of radioactive agent present, and consequently authorize the operator to adapt the local delivery strategy. Its primary use is intended in interventional cardiology in anti-restenosis treatment. The secondary use relates to the development of new locally delivered 'tagged' therapeutic agents, by spatially imaging the distribution of their radioactive component, both in space and time.

BACKGROUND OF THE INVENTION

Local agent delivery is a strategy where the diagnostic or therapeutic agent is delivered exactly and only at the desired site of therapy. This approach is usually employed in contrast to systemic therapy either to reduce the adverse effects of an agent delivered systemically or to increase locally, at the target site, the amount of agent at a concentration level that systemic delivery could not tolerate.

Many strategies of local agent delivery have been devised to deliver locally an agent to an organ or a tubular structure of a living animal or human. Local delivery can be performed with a catheter introduced into the body with the tip (distal part) of the catheter advanced to the target site. The agent is then infused through the catheter and is deposited on the surface of the target site or into the tissue itself by use of small needles. Several catheter designs exist such as (but not limited to) those products sold under the following trade names: Infiltrator, Transport, Infusasleeve, and Dispatch. Other strategies are designed to have the agent coupled or included in a prosthesis, such as a stent, which is installed or deployed at the appropriate site of the body. Conversely, the prosthesis may have a property that preferentially attracts the agent which will localize on the prosthesis following systemic administration of the agent. The agents may be coupled to a polymer or to a biocompatible agent (herein termed carrier), such as collagen, which may be biodegradable or not. The agent-carrier complex can be delivered and implanted at the target site for diagnostic or therapeutic purposes. Finally, the agent may be coupled to an antibody that specifically recognizes a target site in the body through an antigen-antibody reaction.

When developing new therapeutic agents, it is known to attach a radioisotope to the molecules allowing detection and localization of the agents in the body with a radiation detection apparatus. The choice of radioisotope is dictated first by its availability and the configuration and chemistry of the molecule that needs to be tagged with a radioactive atom. Nonetheless to mention also that this new atom that is attached to the molecule under study should not modify the toxicology of the original molecule. Radioisotopes that are commonly used in the medical field as imaging agents are, ⁹⁹Tc99m, ²⁰⁸TI, ⁶⁷Ga, ¹³³Xe and ¹⁸F. Most of these radioisotopes are used in combination with specific molecules for diagnostic purposes to study the function of organs. To quantify the amount of these molecules which are injected systemically the radiation detection apparatus used are SPECT gamma cameras and Positron Emission Tomography scanners. These imaging modalities are possible due to the fact that the radiation emitted by the radioisotopes selected can escape the subject body without a high level of attenuation. These radioisotopes are either positrons or gamma emitters.

Another family of radioisotopes like ³²P, ¹⁸⁸Re, ⁹⁰Sr/Y are beta ray emitters. Their beta radiation is much more attenuated by matter due to their fundamental physical characteristics and cannot be used as an imaging agent with both conventional gamma cameras and PET scanners. There would be an insufficient amount of by product emitted by the radioisotopes escaping the body of the patient to produce a clinically valuable image and even if there exists a situation where there was enough signal going out, the position information provided by the beta ray escaping the patient would be deteriorated due to the nature of the multiple interactions of the beta ray with the patient before escaping the body. This is known in the field of nuclear medicine as primary and secondary diffusion. For beta rays, this effect is much more pronounced and prevents making precise imaging with a beta emitting isotope if the object to image is a volume (self attenuation) and also if it is surrounded by other tissue or material. However, routine microscope slides of cut tissues are conventionally imaged by molecular biologists using film or phosphor imager. Therefore to allow imaging with beta emitters particularly with ³²P radioisotope, the detection apparatus has to be as close as possible of the region of interest to minimize attenuation and diffusion and the object or region of interest has to be thin as compared to the range of the beta ray used.

During the course of the drug development, researchers have to determine the pharmacokinetics of the local delivered drug i.e. the fraction of the drug that is remaining at the site of interest and also its variation with time during periods of minutes, hours, weeks, days and months.

Conventionally these pharmacokinetics studies of the injection and retention of the new potential drug candidate take place using a series of different animals for each time point that the drug needs to be tested. At the time point considered, the animal is sacrificed and the portion of the site of interest is then harvested and counted with an appropriate radiation detector for the remaining activity in the entire region of interest. This technique, if the pharmacokinetics of the drug requires a study over a long time period, requires a large number of animals.

SUMMARY OF THE INVENTION

It would thus be desirable to use the detection apparatus and method, measuring at each point in real time and in-situ the amount of remaining drug by means of the remaining radioactivity. This would greatly reduce the number of animals needed in the study and also reduce the component of subject variability in the drug study. Therefore a more rapid, precise and less costly determination of the pharmacokinetics parameters is rendered possible by this new apparatus and method. The current local drug delivery strategies involve controlled delivery using special tools for controlling dosage, however, no monitoring of agent delivery efficiency is presently carried out. Currently, once the delivery is performed, there are no means taken to verify the efficiency with which the agent is delivered. It is customary to take for granted that the delivery procedure was performed well enough to bring sufficient amounts of the agent to the target site. Unfortunately, most local drug delivery strategies are disappointing in terms of delivery efficiency and should mandate repetitive administration of the agent in the same procedure or during a follow-up procedure.

There is no commercial system currently available to measure and image precisely the amount and the spatial distribution of a radioactive agent delivered locally to a blood vessel or a body cavity, within an animal or human body. But there are a lot of diagnostic external X-ray imaging systems using a photostimulable phosphor plate, such as (but not limited to) any of the FUJI PHOTO FILM Computed Radiography systems (ranging from FCR 101 to FCR 9 000), the ACR 2 000 from LUMISYS, the CR System 400 Plus from KODAK, the DIGORA from SOREDEX. The first application of the imaging plate technology was in Computed Radiography, where it has brought new possibilities in diagnostic medicine, and the second major one was found in Bio Imaging Analyzer (such as the BAS 1 800 from FUJI PHOTO FILM) in the field of molecular biology. Imaging plate technology

The technology of computed radiography, using imaging plates, was developed by FUJI PHOTO FILM (patents 4 236 078 and following). An imaging plate (for example Fuji Imaging Plates CR ST-Vn or CR HR-V) is a two-dimensional sensor that temporarily stores two-dimensional images obtained by X-rays, electron beams, or other types of radiation passing through an object, modifying a photostimulable phosphor (for example a BaFX:Eu²⁺ crystal, X being either CI, Br or I), and then reproduces them as a digital image with the use of a sequential scanning laser beam. The image obtained represents the shadow of the object under an external radiation field, as opposed to autoradiography where an irradiating object exposes itself the plate to the radiation. As an X-ray diagnostic tool, the imaging plate offers several important advantages over X-ray film. As compared to the X-ray film, the imaging plate (IP) has, on one hand, a much higher sensitivity (10 to 100 times higher), which allows a reduction in radiation exposure and / or exposure time, and on the other hand, a wider dynamic range (five orders of magnitude) and an excellent linear response, meaning that the final image output is faithfully proportional to received radiation. Moreover, with the conventional screen / film system, once the combination of screen and film has been chosen, the sensitivity and image quality (gradation, sharpness, granularity) will be automatically determined; whereas with the IP, both the sensitivity and image quality can be freely selected according to the conditions of the laser optics, reading mechanism, and signal processing of the CR unit. Besides, the IP are highly sensitive sensors capable of storing energy not just from X-rays, but also from ultra-violet light, gamma rays, other electromagnetic waves, alpha rays, beta rays, electron beams, and other particle beams. Unfortunately, this property means that they also pick up stray radiation from naturally occurring radioactive isotopes in surrounding walls, containers and the earth's crust as well as from the cosmic rays constantly bombarding the earth's surface. As a result, after extended storage, a thoroughly erased IP exhibits a random pattern of small black dots, the number of dots increasing with the length of storage. Consequently, it is recommended not to leave too much time between exposure and IP reading, especially when reading with high sensitivities. Before using an IP that has been in storage for an extended period, it is also advised to expose it to light to clear it of accumulated charges. Dimensional considerations

As regards to dimensions, the standard pixel sizes generally range from 50μm to 200μm, and the image data points are gradated from 8 bits to 16 bits. On another point of view concerning dimensions, the devices that were developed for computed radiography (CR) or bio-imaging analyzer systems (BAS) are adapted for large plates (350mm x 420mm for standard plates in conventional CR, 200mm x 400mm for standard plates in molecular biology phosphor imager, and 35mm x 45mm for standard plates in intra-oral CR), whereas the present invention uses at most 4mm x 30mm plates. Consequently, the reading system provided in either conventional or intra-oral CR, or phosphor bio-imaging systems, being adapted to large plates, is not readily adapted to the size range of the present invention. Existing radiation detection devices may be found in US patent 5,811 ,814 granted to Leone et al. or US patent 5,635,717 granted to Popescu. These radiation detectors are supposed to be adapted to precise proximity radiation detection. However, as described in commonly assigned copending US application serial number unknown filed November 20, 2000, and titled "RADIATION DETECTION CATHETER" (PCT publication WO02/39898 published May 23, 2002), there are several reasons why the devices described therein are not appropriate for detecting beta rays, in a coronary artery, inside an animal or human body. When positioned at a region of interest, these detectors provide neither longitudinal nor azimuthal discrimination. Moreover, even if the detecting part of the device is moved all along the region of interest, the measurement will only give a one-dimensional map of the radiation coming from that region.

It is an object of the present invention to provide a method and apparatus for measuring radiation within a body cavity without requiring an active detector in the body cavity. A photostimulable material subjected to the radiation can be read once removed from the body cavity. Individual catheters according to the invention can be of simpler construction, can involve a reduced cost, and may be single use. It is also an object of the invention to obtain spatial information about radiation distribution in a body cavity.

According to the invention, a photostimulable material is introduced in a blood vessel or body cavity, within an animal or human body, with a catheter for example, where radiation measurement has to be taken (for example the part of a coronary artery where a localized radioactive agent has been delivered). The photostimulable material is left there a certain amount of time (usually less than one minute) in order to be exposed to the radiation field at that target site, therefore recording spatial radiation information about the region of interest. The photostimulable material is typically a photostimulable phosphor that can be deposited on a suitable substrate or carrier to make a small plate. For example, the photostimulable phosphor may be deposited on a balloon such as the ones used in interventional cardiology, but other solutions may be devised.

The invention provides a method of radiation detection in a body cavity, comprising introducing a photostimulable material in a blood vessel or body cavity at a target site where radiation measurement is to be taken; allowing the photostimulable material to be exposed to the radiation field at the target site and for a predetermined period of time to thus record spatial radiation information about the target site; withdrawing the photostimulable material from the body; and reading the photostimulable material to develop the latent image stored in the sample. Preferably, the radiation field comprises beta radiation, said photostimulable material being positioned in close proximity to said field. Also, preferably the step of introducing includes providing a catheter for leading the photostimulable material to the target site. The step of providing may include providing, as the supporting means, a balloon. The photostimulable material may be provided by a photostimulable phosphor deposited on a substrate or carrier, such as an imaging plate that is preferably formed into a tubular shape. The tubular shape material may be, once at the target site, at least partially unfolded when being exposed at the target site, and the tubular shape material may be, after measurement, refolded and withdrawn from inside the body. The tubular shape material, after withdrawal, may be unfolded so as to be read.

Also, the photostimulable material may be supported on a balloon that is deflated so it may be introduced to the target site and then inflated to place the photostimulable material in close contact with the vessel wall. After inflation, the photostimulable material may be exposed, the balloon deflated and withdrawn, to be read.

The latent image may be one-dimensional or two-dimensional. Preferably, the radiation detected is beta radiation, namely radiation that cannot be accurately measured expect by providing a very close detector. The steps of reading may include exposing the latent image to stimulating light. This exposing may cause the photostimulable material to emit stimulated light in proportion to the amount of energy stored during radiation exposure. The step of reading may also include collecting the stimulated light, preferably by an integrating sphere. The method may further include photoelectrically measuring the collected light, as well as processing the photoelectrically measured light to provide an image signal representative of the radiation source at the target site. The photostimulable material is preferably translated in front of a light beam of said stimulating light generated by the reading steps. A photomultiplier tube may be used to record the amount of emitted stimulated light for the next pixel corresponding to the next stimulated area. Preferably, during the reading step there is relative movement between a light source movement between a light source for said stimulating light and said photostimulable material, for example by deflecting the light beam from the light source. The relative movement may also be in accordance with planar translation, or alternatively in accordance with cylindrical coordinate translation. The relative movement may be in accordance with a motorized translation. Of course, the relative movement may provide two- dimensional spatial measurements. In accordance with one embodiment of the invention, the sample may be cut from a conventional imaging plate, at the desired appropriate dimensions. This may be a rectangle, according to the diameter and length of the radiation distribution. For two-dimensional imaging, it may be a rectangle folded in a tubular shape, so that it can be introduced to the target site, partially unfolded, exposed, refolded after measurement, withdrawn from inside the body, and finally unfolded to be read. In another embodiment in accordance with the invention a two-dimensional sensor may be provided from thin rectangles of a phosphor plate fixed to a balloon mounted on a catheter. The balloon may be deflated so that it may be easily maneuvered through the arterial system, and once at the target site, inflated in order to place the rectangular samples in close contact with the vessel wall, left there a certain amount of time, then deflated and withdrawn, to be read. In still another embodiment of the invention for a two-dimensional sensor, it may be formed in a tubular shape mechanically attached to a supporting catheter in order to be maneuvered easily through the arterial system. There is also provided in accordance with the present invention a method of endovascular radiation detection. This comprises the steps of, introducing a photostimulable material in a blood vessel or body cavity at a target site where radiation measurement is to be taken. This is followed by allowing the photostimulable material to be exposed to the radiation field at the target site and for a predetermined period of time to thus record special radiation information about the target site. The photostimulable material is then withdrawn from the body and the final step is one of reading the photostimulable material to develop the latent image stored in the sample.

Also, in accordance with the present invention there is provided a system for endovascular radiation detection that comprises a photostimulable material and a support means for the photostimulable material for introducing the photostimulable material in a blood vessel or body cavity at a target site where radiation measurement is to be taken. The photostimulable material is exposed to the radiation field at the target site for a predetermined period of time to thus record special radiation information about the target site. A reader is employed for reading the photostimulable material after having been withdrawn from the body and to develop the latent image stored in the sample. The reader includes a light source for exposing the latent image to stimulating light. The emitted light is collected by a light collection system and measured by a photoelectric device and a two-dimensional image signal, representing the distribution of the radioactive agent in the blood vessel of body cavity, is thus obtained.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be better understood by way of the following detailed description of a preferred embodiment with reference to the appended drawings, in which:

Fig. 1 illustrates the recording of a latent image on the photostimulable material by exposure to the radiation field of the radioactive element;

Fig. 2A illustrates the first configuration of the reading system for two- dimensional imaging, with the movement, in two directions in Cartesian coordinate, of the exposed sample in front of a stimulation laser beam, the emitted light being detected by a photomultiplier tube; Fig. 2B illustrates the second configuration of the reading system for two- dimensional imaging, with the movement, in two directions in cylindrical coordinate, of the exposed sample in front of a stimulation laser beam, the emitted light being detected by a photomultiplier tube;

Fig. 3 illustrates the erasing of the residual latent image on the photostimulable material;

Figs. 4A and 4B show one embodiment of photostimulable material folded in a tubular shape in both folded and unfolded condition;

Figs. 5A and 5B illustrate another embodiment of the invention in which the photostimulable material is in the form of plural fin rectangles mounted on an angioplasty balloon;

Fig. 6 is still another embodiment of the invention showing a tubular photostimulable sample fixed on a supporting catheter; Figs. 7A and 7B illustrate still another embodiment of the present invention employing an angioplasty balloon with a double wall with the photostimulable tubular sample inserted between the walls of the balloon; and

Figs. 8A and 8B illustrate variant embodiments in which the catheter includes an optical fiber in communication with a scintillating fiber with photostimulable material being provided within a double wall angioplasty balloon, the scintillating fiber being located within the balloon and at a distal end of the balloon, respectively.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Reference is now made to Fig. 1 as well as alternate embodiments of the reading system illustrated in Figs. 2A and 2B. For a one- or two-dimensional imaging of the source, the detecting and imaging device comprises, a photostimulable material sample 1 , mounted on a catheter or any supporting device 2 that could lead the material to the target site. The reading system, such as illustrated in Figs. 2A and 2B comprises a stimulation laser 6, a light collection device 12, a photodetector 15 and a scanning device 16a or 16b. The system also includes a signal-processing unit 17 and, as illustrated in Fig. 3, an erasing system 19. The phosphor (described in US patent Kotera et al. 4,261 ,854) is a material whose electrons have predefined energy bands. Energy of exposure radiation raises the electrons from a ground level to an intermediate energy level, where the electrons remain. Like X-ray films, the number of electrons raised to that intermediate level varies with the amount of received exposure radiation, therefore giving a latent image of the exposure radiation field.

The electrons stay in that intermediate level until phosphor is exposed to predetermined stimulating light which raises the electrons to a higher energy unstable level. Then each electron quickly drops back to its initial ground level emitting a photon of light of a predetermined wavelength. Consequently, the amount of light emitted by the photostimulable material is proportional to the amount of energy stored during radiation exposure. In other terms, if we follow the photograph analogy, the latent image contained in the material is 'developed' or read-out. The photostimulated light is then collected by a light collection system, guiding the light onto the photodetector. The light collection system may be made of diffuse or reflective surface. For example, it could either be an integrating sphere (diffuse surface) (see Figs. 2A and 2B) or an elliptical mirror (reflective surface), or any other optic light guide system. That collected light is detected by a photomultiplier tube (see tube 15 in Figs. 2A and 2B), which serves as a photodetector, and the signal is processed to an image signal, representing the amount of radiation to which the photostimulable material was exposed.

The image signal is obtained by moving the photostimulable sample and the laser beam (such as laser beam 9A and 9B in Figs. 2A and 2B, respectively) relatively to each other, which may be done by either translating the photostimulable material in two directions, or deflecting the laser beam in two directions with an optical scanner, or combining both ways. The signal coming from the photodetector represents then a precise two-dimensional picture of the radiation that was recorded in the photostimulable material during radiation exposure.

The photostimulable material is typically a photostimulable phosphor that can be deposited on a suitable substrate or carrier to make a small plate. In our preferred embodiment (see Fig. 1 ), the sample 1 is cut down from a conventional imaging plate, at the desired appropriate dimensions. In one-dimensional imaging, it is cut to a 1 mm x 20mm rectangle, according to the diameter and length of the radiation distribution (be it the infused vessel wall or a radioactive stent, the tubular radiation distribution has a diameter, corresponding to the artery size, of 2 to 3 mm, and a length of 15 to 20 mm), and mechanically attached to a supporting device such as a catheter, in our preferred embodiment.

In two-dimensional imaging, it could be a 8mm x 20mm rectangle folded in a tubular shape 40 (see Fig. 4A), so that it could be easily maneuvered onto the target site, then partially unfolded (see Fig. 4B) when being exposed at the target site, refolded after measurement, then withdrawn from inside the body, and finally completely unfolded to be read by the reading system. The appropriate photostimulable material (rectangle or folded rectangle) is mechanically attached upon a supporting device, such as the distal end of a catheter, for example. Another way of obtaining a two-dimensional sensor would be to cut down several thin 1mm x 20mm rectangles 50, from a standard phosphor plate, and to fix three (or four) of them, for example, on a balloon 52 mounted on a catheter 54, thus forming a triangle- (or square-) parallelepiped shape. Refer to Fig. 5A. The balloon would be deflated so that it may be maneuvered easily through the arterial system, and once at the target site, inflated in order to place the rectangular samples in close contact with the vessel wall, left there a certain amount of time, then deflated and withdrawn, to be read by the reading system.

The photostimulable material may be also encapsulated in a waterproof overwrap package, such as a thin layer of parylene (SPECIALTY COATING SYSTEMS, Indianapolis, Indiana), in order to protect the photostimulable material from any interaction with body fluids.

Another way of obtaining a two-dimensional sensor would be to cut down, from a standard phosphor plate, a rectangle such that, when gluing the long edges together in a tubular shape, it would be a cylinder 60 of small diameter (1 or 2mm for example), that would be mechanically attached to a supporting catheter 62, in order to be maneuvered easily through the arterial system. Such a device would not allow the photostimulable material to come in close contact with the vessel wall, thereby providing a lower resolution, but it would still give a two- dimensional measure.

With reference to FIG.1 , the exposure system includes the said photostimulable phosphor sample 1 , which is mounted on a catheter or any supporting device 2. The photostimulable sample is positioned at the region of interest, in order that it may be closely exposed to the irradiating object 3, therefore recording the field of radiation 4 as a latent image 5a. During exposure, all parts should remain as steady as possible, one relatively to the other, in order to avoid as much as possible a blur effect. After a predetermined exposure time (less than one minute), the sample is refolded (if needed) and withdrawn from the region of interest with the catheter or said supporting device. Depending on the configuration of the reading system, the photostimulable material is disengaged or not from the supporting device.

In order to develop the latent image, the photostimulable material is driven to the reading system. Figs. 2A and 2B illustrate two separate embodiments of the present invention. In the following description certain items are common to these two embodiments and thus reference will me be made in this regard to either embodiment. Later in the description reference is made to the specific differences between these embodiments. With reference to Figs. 2A and 2B, the sample 1 is placed in front of a laser beam 9 of a predetermined wavelength, so that the photostimulable material 1 may be photostimulated. In response to that excitation light 9, the sample 1 emits photostimulated light 11 of another predetermined wavelength. In a preferred embodiment, the stimulation laser is a diode laser (such as DLS-500-660S-35 from LASIRIS, St-Laurent, Quebec) whose wavelength is 660nm, according to several emission and stimulation spectra found in literature. The emitted photostimulated light 11 , is collected by a light collection system, which is an integrating sphere 12 (such as the IS-040-SF from LABSPHERE, North Sutton, New Hampshire) in the preferred embodiment, but it could be elliptical mirrors or any optic light guide. In the preferred embodiment, a photomultiplier tube 15 (such as the HC135-01 from HAMAMATSU, Middlesex, New Jersey), which serves as a photodetector, is plugged onto the sphere 12, in order to measure the amount of emitted light 11 , at a particular point in time, and for the particular area 10 that was stimulated. In order to measure the very emitted light, and not the laser light, an optical filter 14 (such as the 400DF80 from OMEGA OPTICAL, Brattleboro, Vermont) is inserted just before the photodetector 15, blocking the known laser wavelength.

For one-dimensional imaging, the photostimulable sample 1 is then preferably translated in front of the laser beam 9, so that the photomultiplier tube 15 may record the amount of emitted light for the next 'pixel', meaning the next stimulated area. For the translation of the sample, a motorized translation stage 16a, as in Fig. 2A,is preferably used in the configuration of our preferred embodiment, but, if the configuration of the light collection system allows it, the laser 6 itself might be translated, or the laser beam 9 might be deflected with an optical galvanometer. For two-dimensional imaging, two of the precedent translation methods are to be chosen. In our preferred embodiment, we have two configurations of that scanning device : the first one 16a, per Fig. 2A,uses a motorized translation stage, in two directions in Cartesian coordinate, and the second one 16b, per Fig. 2B,uses a translation and rotation motorized device, in two directions in cylindrical coordinate. In another embodiment, the primary translation would be obtained with the same motorized translation stage as for the one-dimensional reading, and the secondary translation would be obtained with an optical galvanometer deflecting the laser beam in a raster scan fashion.

In our preferred embodiment, the whole reading system (stimulation light, scanning device, photodetector) is synchronized and controlled by a computer 17, which serves as the synchronization device 18. As the photostimulable material sample 1 is exposed to the stimulation light source 6, the amount of emitted light 11 from that particular stimulated area 10 is integrated by the photodetector 15, and sent to the host computer 17 as the corresponding pixel value. Then, the host computer 17 generates one step translation 16 of the sample 1 (for example), pulses on both the stimulation light device 6 and the photodetector 15, integrates the photodetector output signal, pulses off both the stimulation light device 6 and the photodetector 15, and records the value of the current pixel 10, before translating again for the following pixel. For example, in two-dimensional imaging, for a 8mm x 20mm rectangular sample, the final image would be an array of 40 x 100 pixels, if the chosen pixel size is 200μm (which is determined by the choice of the translation step and / or the laser spot size). As it takes 5 to 10ms per pixel to integrate the emitted light and send the value to the host computer, the scanning time for the whole sample would be in the range of one minute, taking into account the amount of time needed for the translations. The computer finally processes the data to an image signal, in order to visualize the spatial variations of the recorded radiation field, hence the spatial distribution of the radioactive agent previously delivered locally to the said part of the body.

The last step is to restore the sample 1 to a reusable state. In this regard refer to the illustration of Fig. 3. The residual latent image 5b in the photostimulable material 1 is eliminated by bathing it in a uniform illumination of visible light 20, thanks to an erasure lamp 19. Therefore, the erased photostimulable sample may be used again, for another radiation exposure.

Reference has been made hereinbefore to various embodiments of the photostimulable material or sensor. The embodiment illustrated in Figs. 4A and 4B illustrate a tubular shape 40 shown in both folded and unfolded positions. The embodiment in Figs. 5A and 5B illustrate a plurality of this rectangles 50 supported on a balloon 52. The embodiment illustrated in Fig. 6 is also a cylinder 60 of a small diameter mechanically attached to a supporting catheter 62. Finally, a further embodiment of the present invention is illustrated in Figs. 7A and 7B. This illustrates a catheter 72 for supporting a balloon 74. The angioplasty balloon is one having a double wall, as illustrated. A photostimulable tubular sample 76 is inserted between the walls of the balloon 74. The thickness of the layer of the sample 76 is preferably 100 to 200 microns of Fuji standard imaging plates.

With respect to the drawings illustrated herein, there is also now presented the following table that illustrated reference characters and their associate respective descriptions.

1 Photostimulable material

2 Support material

3 Radiation-emitting element

4 Field of radiation (β-, γ-, X-rays, ...)

5a Latent image

5b Residual latent image

6 Laser

7 First entrance port of 12

8a Second entrance port of 12 (first configuration of the reading system)

8b Second entrance port of 12 (second configuration of the reading system)

9 Laser beam (stimulation light)

10 Laser spot (stimulated area)

11 Photostimulated emission light

12 Integrating sphere

13 Detector port of the integrating sphere

14 Optical filter

Description of a typical procedure

This device is to be used in the course of a conventional cardiology intervention, in order to image and quantify the amount of radioactive agent that was locally delivered to the target site, in a therapeutic way or in order to visualize the pharmacokinetics of another therapeutic agent, containing the radioactive agent. The animal or human patient undergoes the classic steps of an angiotherapy procedure. A femoral cutdown is performed and the artery is punctured with a needle to allow the insertion of a metallic introducer guide wire. The needle is removed, leaving only the introducer guide wire in place. An introducer is then placed over the introducer guide wire and advanced in the femoral artery. The introducer guide wire is withdrawn, leaving the introducer in place. With₍ a guide wire adapted to the target artery, the guiding catheter is inserted through the introducer, under fluoroscopic monitoring, towards the aortic cross, aiming at the target coronary artery. Then, while injecting a contrast media, an angiography is performed in order to assess the size of the target artery, therefore determining the precise location of the delivery target site. The precise location of the delivery site may also be done using Intra-Vascular Ultra-Sound system (IVUS). The guide wire is then advanced furthermore in the coronary artery, passing through the target site. The radioactive agent is loaded in the local delivery catheter, which is advanced onto the target site, using the guide wire, under fluoroscopic monitoring, and the radioactive agent is locally delivered at the target site, into the walls of the coronary artery. If the radioactive agent is enclosed in a stent, this loaded stent is mounted on a stent delivery system, using for example a dilatation balloon. The stent delivery catheter is advanced onto the target site, using the guide wire, under fluoroscopic monitoring, and at the target site, the balloon is inflated a certain amount of time, then deflated and withdrawn, leaving the radioactive stent and the guide wire in place.

The photostimulable sample, mounted on a catheter or any other supporting device, is then advanced onto the target delivery site, using the guide wire, in order to place the photostimulable material in front of the delivery site for radiation exposure. The acute positioning of the radiosensitive part (i.e. the photostimulable material) under fluoroscopic monitoring raises some difficulties because the photostimulable sample would then also record the X-ray monitoring field, which would most probably mask the radiation field coming from the sample. This issue could be sidetracked with over-exposure of the sample, by leaving the sample in place as long as necessary to discriminate the target radiation from the monitoring radiation, but that is not really preferred. Other more appropriate positioning solutions will be discussed later.

If the sample is a folded rectangle in a tubular shape, such as in Figs. 4A and 4B, it is then partially unfolded, until it reaches the vessel dimensions so that it may be in close contact with the vessel wall and therefore record the target radiation field. The photostimulable material is left there a certain amount of time (less than one minute) in order to be exposed to the radiation field at that delivery site, therefore recording spatial radiation information about that particular region of interest. After the predetermined exposure period, the sample is refolded (if needed), and the catheter supporting the photostimulable sample is withdrawn from inside the body. Finally, the sample, carrying image information of the source of radiation, is completely unfolded (in the case of a folded rectangle), and is driven to the reading device.

Concerning the above-mentioned positioning, several solutions may be proposed. For example, a simple way is to position the supporting catheter device with reference to a reference wire, comprising two radio-opaque markers at its distal end, which would allow one to visualize and choose, under fluoroscopic monitoring, where the photostimulable sample will be afterwards positioned. The first step would be to advance, under fluoroscopic monitoring, the reference wire until the markers are positioned in such a way that the target delivery site is centered with respect to the markers. When the appropriate positioning has been determined, the reference wire is fixed in that position. Then, without X-ray monitoring, the supporting catheter device is introduced and slid over the reference wire until external and visible markers on both the reference wire and the supporting catheter come in coincidence, meaning that the photostimulable sample is centered between the markers of the reference wire, hence that the photostimulable material is located in front of the target delivery site.

Another solution for the positioning would be to use, when advancing the supporting catheter, a monitoring device that does not use radiation, such as the Intra-Vascular Ultra-Sound system (IVUS) that uses ultra-sound. That system, allowing one to locate precisely the delivery target site, before delivery, and may also locate with the same precision the very site of delivery, afterwards. More particularly, the IVUS system enables one to visualize the metallic structure of a stent. As a consequence, if the sample is attached distally to the IVUS catheter (without disturbing the measure), the operator may then monitor the correct positioning of the sample at the target delivery site, using the previously recorded information about the delivery site. End of the typical Procedure After radiation exposure and withdrawal of the sample from within the body, the reading system 'develops' the latent image stored in the sample, by exposing it to stimulating light, which cause the photostimulable material to emit light in proportion of the amount of energy stored during radiation exposure. As described before, the emitted light is collected by a light collection system and measured by a photoelectric device 15, which sends the data to a processing unit. Therefore, after appropriate processing, an image signal, representing the radiation source in the target coronary artery, is obtained.

Consequently, the detector and imager device provides a precise picture of the spatial distribution of the radioactive source, quantifies the amount of the agent present, and therefore authorizes the operator to adapt the local delivery strategy. Several measures can also be made in the minutes, hours, or days to come, to have a precise pharmacokinetic curve of the delivered agent, if needed. Real Time Measurements

A modification of the present invention can be made possible to allow for the measurement in real time of the radiation field around the photostimulable material while maneuvering it towards the target delivery site. As shown in Figs. 8A and 8B, the catheter supporting the photostimulable sample may comprise a radiation detection device which is adapted to real time proximity radiation detection, like the one described in our copending US application entitled "Radiation Detection Catheter", Attny Docket Number 12168-15US, serial number 09/715,137 filed November 20, 2000, corresponding to PCT publication WO02/39898. For example, a scintillating fiber coupled with an optic light guide fiber can be inserted into the catheter, and connected to a photodetector in order to measure in real time the amount of radiation to which the sample is exposed. Consequently, that double device would combine the advantages of the two methods: the operator would have access both to a real time measurement, provided by the scintillating material, and to a two-dimensional measurement, provided by the photostimulable material. Moreover, that double device would also eliminate the positioning difficulty, as the scintillating material would react instantly to radiation shifts, and therefore could pinpoint the very target delivery site. In the embodiment of Fig. 8A, the scintillating fiber is located at the same position as the photostimulable material, which is placed between the inner and outer wall of the balloon structure. The measurement using the scintillation fiber is used online to help position the balloon with respect to the source, while the photostimulable material may be used to acquire a better 2-D measurement. In the embodiment of Fig. 8B, the scintillating fiber is located at the distal side of the photostimulable material, which is also placed between the inner and outer wall of the balloon structure. The online detection of the radiation field and catheter positioning is thus done in a first step, with the latent imaging using the photostimulable material in the balloon done in a second step. Relative Measurements With regard to sensitivity and image quality, they both can be freely selected according to the choice of configuration of the reading system, and more particularly of the data processing device. The final image, gradated in grey levels, illustrates the relative measurements of the amount of photostimulated light emitted from each stimulated area, from one pixel to the next. The background grey level corresponds to regions of the sample that were not exposed to the radiation field coming from the locally delivered radioactive agent, meaning that those regions have recorded the natural ambient radiation field. Consequently, the data points corresponding to the regions of the sample that were exposed to the locally delivered radioactive agent are coded in signal grey levels relatively to that said background grey level, in relation with the sensitivity of the photostimulable material and the exposure time. Calibrated Measurements A modification of the present invention can be devised in order to have a calibration of the measurements. In order to compare the radiation measurements of the locally delivered agent with calibrated radiation measurements of a known radioactive source, the photostimulable material have to be exposed during the same amount of time for both measurements. For example, when the photostimulable material is put in presence of the locally delivered agent, a special thin wire, which distal section would be radioactive, could be advanced onto the region of interest, then withdrawn when the photostimulable sample would be about to be removed. That modification would allow one to have, all along the sample, a thin line of darkened pixels, the 'over-darkening' being in proportion to the added exposure due to the radioactive thin wire. Supposing that the activity of the radioactive section of the wire is well known, and that both introduction and withdrawal of the wire may be coordinated with the other actions, the 'over- darkening' of the over-exposed pixels would give access to a calibration of the other pixels of the final image. Erasing Procedure

In order to restore the sample to a reusable state after image reading, the residual image information in the photostimulable material of the sample must be eliminated. After processing in the reading device, the photostimulable sample is next conveyed to the image-erasing unit and flooded with strong visible light. Consequently, the erased photostimulable sample can be used repeatedly to store radiation latent images. The expected life of the plate is limited mainly by mechanical damage such as scratches, it is not limited by physical fatigue of the photostimulated luminescence phenomenon. Light Conditions

As regards to light conditions, the reading of the photostimulable sample requires a subdued light environment, as the light detection system is very sensitive to ambient light. For example, the reading system could be placed in a dark room or at least in a dark box, in order to avoid the photomultiplier to record any other light source than the emitted photostimulated light.

It is to be noted that many alterations and modifications may be made by those skilled in the art without departing from the spirit and scope of the invention. The illustrated embodiments have been shown only for purposes of clarity and examples, and should not be taken as limiting the invention.

Claims

1. A system for radiation detection in a body cavity, comprising: a photostimulable material; a support means for the photostimulable material for introducing the photostimulable material in a blood vessel or body cavity at a target site where radiation measurement is to be taken; said photostimulable material being exposed to the radiation field at the target site for a predetermined period of time to thus record spatial radiation information about the target site; and a reader for reading the photostimulable material after having been withdrawn from the body to develop the latent image stored in the sample.

2. A system as claimed in claim 1 wherein said support means comprises a catheter.

3. A system as claimed in claim 1 wherein said support means comprises a balloon.

4. A system as claimed in claim 1 wherein said photostimulable material comprises an imaging plate.

5. A system as claimed in claim 1 wherein said photostimulable material is in a tubular shape.

6. A system as claimed in claim 5 wherein said tubular shape has a folded position and an unfolded position with the folded position being used for insertion and withdrawal thereof and the unfolded position being used at the target site and for reading.

7. A system as claimed in claim 1 wherein said photostimulable material includes a plurality of separate thin imaging plates affixed to an angioplasty balloon.

8. A system as claimed in claim 1 wherein said photostimulable material is tubular and fixed about a supporting catheter.

9. A system as claimed in claim 1 wherein said photostimulable material is of tubular shape fitting between the double walls of an angioplasty balloon.

10. A system as claimed in claim 1 wherein said supporting means comprises a catheter and further including a scintillating fiber coupled with an optic light guide fiber inserted into the catheter and connected to a photo detector in order to measure in real time the amount of radiation to which the sample is exposed.

11. An endovascular detecting and imaging system, comprising: a photostimulable material; a supporting device for the photostimulable material; catheter means for introducing the photostimulable material and supporting device to a target site in a blood vessel or body cavity and for a predetermined period of time to thus record spatial radiation information about the target site, and enabling withdrawal of the photostimulable material and supporting device for the purpose of the reading thereof.

12. A device as claimed in claim 11 wherein said photostimulable material is a strip.

13. A device as claimed in claim 11 wherein said supporting device is a balloon.

14. A device as claimed in claim 11 wherein said photostimulable material is in a tubular configuration.

15. A device as claimed in claim 14 wherein said supporting device is adapted to be easily removed from said catheter means for reading.

16. A device as claimed in claim 11 wherein said supporting device is an angioplasty balloon and said photostimulable material are strips of imaging plate despised on said balloon.

17. A device as claimed in claim 16 wherein said angioplasty balloon is a double wall balloon and said photostimulable material is a tubular configuration between the walls of said balloon.

18. A reading system for reading a photostimulable material that has been exposed to radiation at a target site in a blood vessel or body cavity and withdrawn, for reading, from said target site, said reading system comprising: a laser beam source; means for rotatably supporting the photostimulable material in the beam of the source about a lengthwise axis of the material so that the photostimulable material may be photostimulated to thus emit photostimulated light; an optical collection means for receiving said photostimulable light; a photodetector coupled to said optical collecting means to measure the amount of emitted light.

19. A reading system as claimed in claim 18 wherein said optical collecting means comprises an integrating sphere.

20. A reading system as claimed in claim 18 wherein said optical collecting means comprises an elliptical mirror.

21. A reading system as claimed in claim 18 further including scanning means for providing relative movement between the laser beam and the photostimulable material.

22. A reading system as claimed in claim 21 wherein said scanning means follow a Cartesian coordinate mechanism.

23. A reading system as claimed in claim 21 wherein said scanning means follow a cylindrical coordinate mechanism.

24. A reading system as claimed in claim 21 wherein primary translation by the scanning means is obtained by a first mechanism and secondary translation is obtained with an optical galvanometer deflecting the laser beam in a raster scan fashion.

25. A reading system as claimed in claim 21 wherein the scanning means provides two-dimensional imaging.