EP1030719A1

EP1030719A1 - System and method for endoscopically applying and monitoring photodynamic therapy and photodynamic diagnosis

Info

Publication number: EP1030719A1
Application number: EP98950947A
Authority: EP
Inventors: Eli Talmor
Original assignee: ESC Medical Systems Ltd
Current assignee: ESC Medical Systems Ltd
Priority date: 1997-10-30
Filing date: 1998-10-05
Publication date: 2000-08-30
Also published as: WO1999022814A1; EP1030719A4; IL135831A0; AU9685998A

Abstract

A system for endoscopically irradiating, and concurrently monitoring light during photodynamic treatment of an internal treatment site, the system including at least one light source (102) for providing an illuminating light for illumination of the treatment site, a fluorescence inducing light for inducing a fluorescence light emission from the treatment site, and a treating light for activating a photodynamic chemical present at the treatment site; an illumination light channel for tunneling the illumination, and fluorescence (116, 118) inducing lights from the light source to the treatment site; a working light channel for tunneling the treating light from the light source to the treatment site (122, 126, 128); an imaging light channel for retrieving light from the treatment site (132, 134); and a light analysis arrangement (136) being optically coupled to the imaging light channel for analyzing the light retrieved from the treatment site, the light analysis arrangement including a first camera for providing a reflected light image of the treatment site (138); a second camera for providing a fluorescence light image of the treatment site (140); a spectrometer (144) for providing a spectrum of at least part of the light retrieved from the treatment site; and at least one display (146, 146a-146c) for displaying the reflected light image, the fluorescent light image, and the spectrum.

Description

SYSTEM AND METHOD FOR ENDOSCOPICALLY APPLYING AND MONITORING PHOTODYNAMIC THERAPY AND PHOTODYNAMIC DIAGNOSIS

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates in general to photodynamic therapy (PDT) and photodynamic diagnosis (PDD). More particularly, the present invention relates to a system and method for applying and concurrently monitoring PDT and/or PDD. Most particularly, the present invention relates to a system and method for endoscopically applying and concurrently monitoring PDT and/or PDD to tumors of internal organs.

Electromagnetic radiation is used to treat a variety of external and internal conditions including skin rumors and parasites and tumors of internal organs. This radiation is typically applied to the treatment site from a variety of radiation sources, such as lasers that emit coherent light, flash lamps or arc lamps emitting incoherent light and microwave radiation sources, among others.

Whatever the source of electromagnetic radiation, in order to provide treatment without damaging surrounding tissue, careful consideration must be given to the problem of monitoring the course of treatment to minimize tissue damage, and to optimize treatment.

One method of treatment is called photodynamic therapy (PDT) and uses a combination of light and chemicals to treat a variety of solid tumors, including skin cancers, and cancers of the internal organs, such as, but not limited to, trachea colon, vagina, bladder and other cancers.

The PDT treatment is based on a systemic or topical application of a tumor-localizing photosensitizing agent, such as porphyrin, aminolevulinic acid (ALA), phthalocyanin, chlorine, etc., which after illumination and excitation with light of appropriate wavelength in the presence of oxygen, give rise to highly reactive and cytotoxic single molecular oxygen which causes tumor regression. Typical absorption spectra of some of these chemicals are shown in Figure 1.

During PDT treatment, light of the appropriate wavelength should be applied to the tumor until the photosensitizer agent is consumed by the beneficial chemical reaction. Once this reaction is complete and the agent is consumed, any additional light applied to the tumor may have little value. Termination of the treatment before the agent is consumed is even worse, since this may leave tumor residuals.

To prevent this, some PDT operators have used a spectrometer to sense the presence or absence of the photosensitizing agent. By measuring light emitted by a photosensitizing agent in a treated site during treatment and analyzing its spectrum, an operator may easily be able to tell whether any photosensitizing agent still exists at the treatment site.

In the past, measuring the radiation emitted from a treatment site (skin) has been difficult to co-ordinate with the treatment itself. To measure the radiation from the photosensitizing agent at the treatment site, the light source used to stimulate the photosensitivity agent was removed from the proximity of the treatment site and a spectrometer was placed in proximity to the treatment site. This process was repeated each time the spectral emissions from the treatment site was checked until the photosensitizing agent was consumed.

To provide for consistent treatment, the light source should have been replaced back at the identical spot from which it was removed to apply light to the identical area. This often did not happen, however. Each time the light source was replaced, it was often replaced at a slightly different location. In this manner, the light source "migrates" across the treatment site causing irregular and nonhomogeneous treatment of the tumor.

This procedure is not at all applicable for internal tumors, wherein endoscopes are used to deliver and/or retrieve light. Another problem with current PDT treatment methods is the difficulty in accurately orienting the light source with respect to the treatment site.

Typically, the light source obscures the treatment site, and prevents the light source from being accurately positioned with respect to the treatment site, and, in the event that a larger area is treated, prevents the light source from being relocated to an adjacent area of the treatment site without leaving an untreated gap, or without overlapping an area that has already been treated, and thus treating an area twice, unnecessarily. This problem is even more emphasized when the treated site is internal and an endoscope is used to deliver the light from the light source to the treated site.

Another application using a combination of light and chemicals is called photodynamic diagnostics (PDD). In this application, detection of the chemical in the tissue is used for tumor diagnosis, since chemical concentrations in the tumor are much higher than in healthy tissue. In this application, it is advantageous to view the tumor to determine its borders, as well as measure the spectrum of fluorescence of the chemicals to provide positive identification of the chemical signature. Applying light to the treatment site while the chemical fluorescence is monitored enhances the chemicals fluorescence and thereby provides a superior spectral analysis. As with PDT, this is awkward, since both a light source and a spectrometer must be disposed adjacent to the treatment area simultaneously. This is at all impossible when PDD is applied to internal body sites.

A device which partially solves these problems is disclosed in U.S. patent 4,768,513 to Suzuki. The device includes a white light source, a laser light source which can be switched between therapy and diagnosis modes, a color camera for imaging, a spectrometer which includes a spectroscope, a high sensitivity camera and an analyzer, monitors for displaying color images obtained from the color camera and for displaying graphical presentations of the spectra. The white light source, laser light source, color camera and the spectrometer, each employ a dedicated light guide to deliver or retrieve light, as appropriate.

The device disclosed by Suzuki suffers few limitations. First, the light employed for therapy is a laser light which renders the whole apparatus dedicated to very specific PDT or PDD compounds and which is costly. Second, the field of view of the spectrometer is not defined to the user. Third, according to Suzuki, using the disclosed device does not enable to obtain a fluorescence spectrum and a concurrent image of the treatment site. And last but not least the device disclosed fails to provide combined spatial-spectral information, such as a fluorescence image of the treatment site. U.S. patent application No. 08/708,080 by Talmor, filed August 30,

1996, which is incorporated by reference as if fully set forth herein, teaches a monitoring apparatus for monitoring an image of a treatment site and spectral emissions from a defined portion of that site.

Figure 2 illustrates a PDT/D and monitoring apparatus 10 according to U.S. patent application No. 08/708,080. Apparatus 10 includes a housing 12, with an opening 14 disposed against a treatment site 16. Housing 12 includes a camera 18 coupled to housing 12 and oriented to receive light entering housing 12 from opening 14. In this case, since opening 14 is disposed adjacent to treatment site 16, camera 18 receives images of treatment site 16 that is adjacent to opening 14.

Spectrometer 20 includes optical bench 22 disposed away from housing 12, and light guide 24 (typically an optical fiber or fiber bundle) coupled to housing 12 and optical bench 22 to direct radiation entering housing 12 through opening 14 into optical bench 22. Spectrometer 20 is preferably of the type known in the art as an optical multichannel analyzer (OMA).

A light guide 26 is coupled to housing 12 to transmit light from light source 28 into housing 12 and toward opening 14. The light is preferably generated either by a laser or a flashlamp, both of which have emissive qualities particularly suited to being coupled to housing 12. In this manner light for treatment is sent to treatment site 16.

Light source 28 is preferably a high intensity light source such as a xenon or mercury arc lamp. It may have one or more filters, such as a violet filter passing wavelengths in the range of 400 to 450 nanometers or a green filter passing wavelengths in the range of 505 to 590 nanometers. These wavelengths are particularly useful when using the system in PDT and PDD, since these are the frequencies that cause common photosensitizing chemicals to fluoresce significantly. A window 30 is provided that extends across the opening 14. Light guide 24 is coupled to window 30, preferably in the field of view of camera 18, such that an image produced by camera 18 indicates the point at which light guide 24 is coupled to window 30. Light guide 24 preferably receives light emitted from a spot on treatment site 16 measuring between 1 and 10 mm . Window 30 transmits light from light source 28 out of housing 12 and onto treatment site 16. It also transmits light emitted from treatment site 16 into housing 12 and hence into camera 18.

Optical fiber 24 preferably extends through the window such that it receives light emitted directly from treatment site 16 without having to pass through window 30. The inner and outer surfaces of window 30 preferably have an anti-reflective coating to attenuate any reflections internal to housing 12 from entering camera 18. Window 30 is preferably recessed within opening 14 of housing 12. The depth of this recess is preferably between 3 and 10 mm. Camera 18 is an electronic camera, preferably a color or black-and- white CCD camera. Camera 18 is disposed to provide an image that includes from 1 to 100 cm of treatment site 16. More preferably, the n image includes from 10 to 40 cm of treatment site 16. Most preferably, the n image includes from 15 to 25 cm of treatment site 16. Camera 18 may include a filter 32 disposed in the camera's optical path to block particular frequencies of light, such as the frequencies emitted by light source 28. For typical PDT therapies, the filter should transmit light in the range of 570 to 770 mm. This is of particular value when camera 18 is used to sense frequencies of light emitted by fluorescing photosensitizing agents (that typically emit in the 570-770 nm range) in response to the light emitted by light source 28.

When the frequencies emitted by light source 28 are different from the frequencies emitted by the photosensitizing agents, a filter that eliminates the light source frequencies can by reducing or eliminating the intense light source frequencies provide enhanced camera perception of the fluorescing frequencies. Camera 30 is best disposed at an angle of between 10 and 20 degrees of a perpendicular which extends from the surface of treatment site 16 (e.g. a plane extending across opening 14). The apparatus according to U.S. patent application No. 08/708,080 further includes a computer coupled to the spectrometer, the camera and to a computer display. The computer receives signals from the spectrometer indicative of the spectrum of light received by spectrometer. These signals are processed by computer which then transmits an electrical signal to the display causing the display to generate a representation of the spectrum on the display. The computer also transmits signals to the display indicative of the images received by the camera.

Thus, an operator of the system can monitor the spectral emissions of the treatment site simultaneously with an image of the treatment site. Preferably, these images and spectrums are displayed in real time, as the light from the treatment site is received by the spectrometer and the camera.

This mode of operation has a synergistic effect, allowing the operator of the system to provide and monitor a treatment by viewing a computer display rather than by viewing the treatment site itself. All the information required to determine where and when to move the housing with respect to the treatment site is provided on the screen. The image also indicates the point at which spectrum has been measured.

The apparatus according to U.S. patent application No. 08/708,080 has no associated topological limitations as is the case for the device disclosed by Suzuki, however, this apparatus is bulky and is therefore not useful in treating internal body organs.

It is known that PDT involves damage to the tumor vascular bed, which in turn causes disruption of tumor blood flow and ultimately to a tissue necrosis. The vascular damage produced by the PDT treatment in the tumor, reduces its efficiency in cooling the tumor.

Hyperthermia by heating a tumor to a moderate temperature of up to

46° has been proven to be of clinical value. It has been published (S.

Kimmel et al., Lasers & Surgery medicine, 12: 432-440, 1992) that a combination of PDT with Hyperthermic therapy (hereafter referred to HPT) results in a 40 % decrease of the irradiation dose required to produce vascular damage. Various mechanisms for the synergism of PDT and HPT, were suggested which can be concluded as follows: (i) the PDT treatment increases the heat sensitivity of the tumor cells, due to a decrease of the pH; (ii) the HPT enhances the photosensitization due to an increased blood flow; and (iii) the damage repair inactivation by each of the modalities enhances another effect.

Hyperthermia has been proved to be selectively lethal to various malignant cells in the range of 41° to 46° C, thus being considered to be of a clinical value. In U.S. patent application No. 08/394,238, it was found that the combination of PDT and HPT when applied simultaneously, is much more effective and provides better results that the two separate individual treatments. The benefit from this combination, besides the decrease of about 40% of the irradiation dose required to produce vascular damage is also a better penetration.

The photochemical reaction enhancement at elevated temperatures which results from the PDT, does produce a strong cytotoxic effect and reduces the required penetration depth in the tissue which is generally in the range of between 1 to 3 mm at 630 nm. Therefor, shallow tumors might be treated by PDT alone, but an efficient treatment could not be achieved in case of deeper tumors.

It was further found that the apparatus disclosed in U.S. patent application 08/394,238, produces moderate heating of the tumor to a temperature in the range of between 41 to 46 °C. This effect called hyperthermia, imparts a synergistic effect when combined with the PDT treatment. As a result, the overall efficiency in treating deep tumors is greatly enhanced.

According to a most preferred embodiment described therein, the treatment includes the administration of between 600 to 750 nm band and simultaneously heating the tumor to a temperature of up to 46 °C. The total time of treatment is about 20 minutes, including only about 5 minutes of pure PDT, reaching the above maximum temperature during a simultaneous HPT treatment for about 15 minutes. The hyperthermal effect may be obtained by a direct heating of the tumor. However, for a better control of the maximum temperature produced, electromagnetic irradiation is preferred. For example, by a simultaneous irradiation at 1.2 to 1.7 μm, the required heating of a tumor could be produced with an irradiance of only 30 to 70 mW/sq.cm. for a period of about 20 minutes.

A preferred apparatus according to the invention described in U.S. patent application 08/394,238, is characterized by simultaneous illumination in the range of between 600 to 750 nm in the "red" and between 1200 to 1700 nm in the near infra-red.

The ratio between the power emitted in the "red" to the power emitted in the near infra-red is preferably between 2:1 and 5:1 and most preferably about 3:1. A preferred mode for applying the heating is by a CO2 laser or NdyaG laser. The absorption of hemoglobin in the blood vessels is in the range of 600 to 750 nm, which produces an increase in the temperature and an enhanced PDT reaction rate. Indeed, clinical results in three different hospitals using an apparatus as described in U.S. patent application 08/394,238, for skin cancer treatment of 150 patients, show a success of 85% even after one single treatment.

According to U.S. patent application 08/394,238, the apparatus can also be incorporated in other systems, thus providing additional useful functions as known in the art. Thus for instance, by adding a violet filter in the range of 400-450 nm, using means of a filter wheel, it can be used for excitation of photosensitizes in the photodynamic diagnostics or monitoring. On the other hand, incorporation of a green filter in the spectral range of 505-590 nm using, can be used for a superficial PDT treatment or for various dermatologic applications such as removal of tattoos and portwine stains. The apparatus described in U.S. patent application 08/394,238, was found also to be useful with a variety of photosensitizes known in the art. The broad band excitation used, enables the utilization of PDT photoproducts, having the absorption maxima removed by 30 to 550 nm from the absorption maxima of the photosensitizer used. There is thus a widely recognized need for, and it would be highly advantageous to have, a system and method for PDT and PDD treatment and monitoring which enjoys the advantages and devoid the limitations of the device described in U.S. patent No. 4,768,513 to Suzuki and the apparatuses described in U.S. patent application Nos. 08/708,080 and 08/394,238 by Talmor.

SUMMARY OF THE INVENTION

Accordmg to the present invention there is provided a system and method for applying and concurrently monitoring PDT and/or PDD.

According to further features in preferred embodiments of the invention described below, provided is a system for endoscopically irradiating and concurrently monitoring light during photo dynamic treatment of an internal treatment site, the system comprising (a) at least one light source for providing an illuminating light for illumination of the treatment site, a fluorescence inducing light for inducing a fluorescence light emission from the treatment site and a treating light for activating a photodynamic chemical present at the treatment site; (b) an illumination light channel for tunneling the illuminating and fluorescence inducing lights from the light source to the treatment site; (c) a working light channel for tunneling the treating light from the light source to the treatment site; (d) an imaging light channel for retrieving light from the treatment site; and (e) a light analysis arrangement being optically coupled to the imaging light channel for analyzing the light retrieved from the treatment site, the light analysis arrangement including (i) a first camera for providing a reflected light image of the treatment site; (ii) a second camera for providing a fluorescence light image of the treatment site; (iii) a spectrometer for providing a spectrum of at least part of the light retrieved from the treatment site; and (iv) at least one display for displaying the reflected light image, the fluorescence light image and the spectrum.

According to still further features in the described preferred embodiments the system further comprising a mechanism for alternately optically coupling the at least one light source with the illumination light channel and the working light channel. According to still further features in the described preferred embodiments the imaging light channel is an imaging optic fiber bundle of an endoscope.

According to still further features in the described preferred embodiments the illumination light channel is an illumination optic fiber bundle of an endoscope.

According to still further features in the described preferred embodiments the working light channel includes an optic fiber insertable via a working channel of an endoscope. According to further features in preferred embodiments of the invention described below, provided is a system combining with an existing endoscope, the endoscope having an illumination light channel, a working channel and an imaging light channel, the system being for endoscopically irradiating and concurrently monitoring light during photodynamic treatment of an internal treatment site, the system comprising (a) at least one light source for providing an illuminating light for illumination of the treatment site, a fluorescence inducing light for inducing a fluorescence light emission from the treatment site and a treating light for activating a photodynamic chemical present at the treatment site; (b) a working light channel being insertable via the working channel of the endoscope for tunneling the treating light from the light source to the treatment site; (c) a mechanism for alternately optically coupling the light source with the illumination light channel and the working light channel, for tunneling the illuminating and fluorescence inducing lights from the light source to the treatment site, and for tunneling the treating light from the light source to the treatment site, respectively; and (f) a light analysis arrangement being optically coupled to the imaging light channel for analyzing light retrieved from the treatment site, the light analysis arrangement including (i) a first camera for providing a reflected light image of the treatment site; (ii) a second camera for providing a fluorescence light image of the treatment site; (iii) a spectrometer for providing a spectrum of at least part of the light retrieved from the treatment site; and (iv) at least one display for displaying the reflected light image, the fluorescence light image and the spectrum. According to still further features in the described preferred embodiments the light source is further for providing a heating light for heating the treatment site, the working light channel is further for tunneling the heating light from the light source to the treatment site.

According to still further features in the described preferred embodiments the illuminating light is a white light, the fluorescence inducing light is a blue light, the treating light is a red light and the heating light is an infrared light.

According to still further features in the described preferred embodiments the first camera is a color camera. According to still further features in the described preferred embodiments the second camera is a monochromatic camera.

According to still further features in the described preferred embodiments the spectrum is of at least part of a light fluorescing from the treatment site when illuminated with the fluorescent inducing light. According to still further features in the described preferred embodiments the light source includes a Xenon arc lamp and a filters wheel for selecting among the illuminating light, the fluorescence inducing light, the treating light and a combination of the treating light and the heating light. According to still further features in the described preferred embodiments the working light channel includes a light diffuser at its treating end.

According to further features in preferred embodiments of the invention described below, provided is a method of endoscopically monitoring a photodynamic freatment of an internal treatment site, the method comprising the steps of (a) applying to an organism a phtodynamic chemical having a strong affinity for the treatment site; (b) irradiating the treatment site with a fluorescence inducing light, the fluorescence inducing light is selected such that is induces the phtodynamic chemical to emit a fluorescent light; (c) monitoring the fluorescent light via a first camera; and (d) displaying a fluorescence image of the treatment site, thereby providing spatial data of a distribution of the phtodynamic chemical in the treatment site. According to further features in preferred embodiments of the invention described below, provided is a method of endoscopically monitoring the efficiency of a photodynamic therapy of an internal treatment site, the method comprising the steps of (a) applying to an organism a phtodynamic chemical having a strong affinity for the treatment site; (b) irradiating the treatment site with a treating light selected such that when it impinges the phtodynamic chemical a formation of free radicals is induced; (c) irradiating the treatment site with a fluorescence inducing light, the fluorescence inducing light is selected such that is induces the phtodynamic chemical to emit a fluorescent light; (d) monitoring the fluorescent light via a camera; and (e) displaying a fluorescence image of the treatment site, thereby providing spatial data of a remaining distribution of the phtodynamic chemical in the treatment site.

According to still further features in the described preferred embodiments the methods further comprising the steps of irradiating the treatment site with an illumination light; monitoring light reflected from the treatment site via a second camera; and displaying a reflected light image of the freatment site.

According to still further features in the described preferred embodiments the methods further comprising the steps of monitoring the fluorescent light via a spectrometer; and (f) displaying a fluorescence spectrum of at least some of the fluorescent light.

The present invention successfully addresses the shortcomings of the presently known configurations by providing a system and method for monitoring PDT and PDD which provides a user with spatial-spectral information on the course of treatment. BRIEF DESCRIPTION OF THE DRAWINGS

The invention herein described, by way of example only, with reference to the accompanying drawings, wherein: FIG. 1 illustrates a typical absorption spectra of monomeric porphyrins (solid line), chlorins (dashed line) and phthalocyanines (broken line);

FIG. 2 is a partial cross-sectional diagram of a monitoring apparatus in accordance with the invention disclosed in U.S. patent application No. 08/708,080; and

FIG. 3 is a schematic depiction of the system according to the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is of a system and method which can be used for applying and concurrently monitoring photodynamic therapy (PDT), combined, for example, with hiperthermic therapy (HPT), and/or photodynamic detection (PDD). Specifically, the present invention can be used to provide an endoscope for applying and concurrently monitoring PDT, HPT and/or PDD of an internal treatment site, such as, but not limited to, trachea, colon, vagina, bladder and others.

The principles and operation of the system and method according to the present invention may be better understood with reference to the drawings and accompanying descriptions. Figure 3 schematically presents a prefered embodiment of the system according to the present invention, which is referred to hereinbelow as system 100.

Thus, system 100 serves for endoscopically irradiating and concurrently monitoring light during a photodynamic freatment (PDT, HPT and/or PDD) of an internal treatment site, typically a tumor of an internal organ, such as but not limited to trachea tumor, colon tomor, vaginal tumor, bladder tumor and other tumors.

System 100 includes at least one light source 102 for providing several types of light irradiation.

One type of light is an illuminating light which serves for illumination of the treatment site. The illuminating light is typically a white light having a wavelength range of about 400-700 nm. Illuminating lights in other spectral ranges are also applicable for some applications. Another type of light is a fluorescence inducing light which serves for inducing a fluorescence light emission from the freatment site. The fluorescence inducing light is typically a blue light having a wavelength range within about 400-450 nm. The spectral range of the fluorescence inducing light is determined by the nature of chemical employed for PDT or PDD. The chemicals whose absorption specfra are presented in Figure 1 fluoresce when irradiated with light in the blue range. However, other chemicals are expected to fluoresce when irradiated with light having a wavelength range different than blue.

Yet another type of light is a treating light which serves for activating a photodynamic chemical present at the treatment site to produce free radicals. The treating light is typically a red light having a wavelength range within about 580-720 nm. The spectral range of the freating light is determined by the nature of the chemical employed for PDT. The chemicals whose absorption specfra are presented in Figure 1 become photodynamically activated as described when irradiated with light in the red range. However, other chemicals are expected to be activated when irradiated with light having a different wavelength range.

Thus, the scope of the present invention is not limited to any specific spectral range, rather it focuses on the functionality of the light employed.

Still another type of light is a heating light which serves for heating the treatment site. It is shown in U.S. patent application 08/394,238, that a combination of HPT with PDT improves the treatment results. The heating light is an infrared light having a wavelength range within about 1,200- 1,700 nm. Thus, according to prefered embodiments of the invention the heating light and treating light may be irradiated either separately or concomitantly.

The various types of light may be generated by any light source(s) including laser sources, which will provide monochromatic light irradiation. However, according to a prefered embodiment of the present invention light source 102 includes a Xenon arc lamp 104 supplemented with a reflector 106 which serves for reflecting the light generated by lamp 104 generally in a single direction. Light source 102 further includes a window, a wide band filter (e.g., 400-750 and 1,200-2,000 nm) 110, focusing lenses 111 and a motorized 112 filters wheel 114 for selecting among the illuminating light, fluorescence inducing light, treating light, heating light and a combination of treating light and heating light.

A Xenon arc lamp is presently prefered since it is a single light source which is capable of providing sufficient photons required for illumination, PDT, PDD and/or HPT, using a simple filters wheel. It is therefore both flexible and economic as compared with laser light sources.

System 100 further includes an illumination light channel 116 which serves for tunneling the illuminating and fluorescence inducing lights from light source 102 to the freatment site. According to a prefered embodiment of the invention illumination light channel 116 is an illumination optic fiber bundle 118 of a conventional endoscope 120. The construction and operation of a conventional endoscope is described, for example, in

PENT AX® owner's manual (upper GI fiberscopes, models FG-16X, 24X, 27X, 29X, 32X and 34X), which is incorporated by reference as if fully set forth herein.

System 100 further includes a working light channel 122 which serves for tunneling the freating light and/or the heating light from light source 102 to the treatment site. In a prefered embodiment of the invention working light channel 122 includes a light diffuser 124 at its treating end 126. In another prefered embodiment of the invention working light channel 122 includes an optic fiber 126 insertable via a working channel 128 (also known in the art as the instrument channel) of conventional endoscope 120. System 100 further includes a mechanism, indicated by arrow 130, for alternately optically coupling light source 102 with illumination light channel 116 and working light channel 122. Mechanism 130 is preferably a motorized mechanism.

System 100 further includes an imaging light channel 132 which serves for retrieving light from the freatment site for analysis. In a prefered embodiment of the present invention imaging light channel 132 is an imaging optic fiber bundle 134 of conventional endoscope 120.

System 100 further includes a light analysis arrangement 136. Arrangement 136 is optically coupled to imaging light channel 132 for analyzing light retrieved from the treatment site.

Light analysis arrangement 136 includes a first camera 138 for providing a reflected light image 146a of the freatment site. The reflected light is typically the reflection of the illuminating white light from the freatment site. First camera 138 is typically a color camera, such as, but not limited to, an RGB-CCD. A suitable color camera is distributed by SONY (Model DXC-LS1P). Camera 138 does not require a high dynamic range and is therefore simple and cost effective.

Light analysis arrangement 136 further includes a second camera 140 for providing a fluorescence light image 146b of the treatment site. The fluorescent light is typically the light fluorescing from the treatment site upon irradiance with the fluorescence inducing light. Therefore camera 140 is supplemented with a filter 142 for blocking light outside the fluorescence emission range. Second camera 140 is typically a monochromatic camera having a high dynamic range, such as, but not limited to, a monochromatic CCD. A suitable monochromatic camera is distributed by WATEC (Model WAT 704R). Selecting camera 140 monochromatic is presently prefered since is enables to employ a cost effective camera with a high dynamic range. Nevertheless, a monochromatic camera (as opposed to color camera) is sufficient to capture the distribution and intensity of fluorescence in the treatment site.

Light analysis arrangement 136 further includes a spectrometer 144 for providing a spectrum 146c of at least part of the light retrieved from freatment site. The spectrum is typically of at least part of the light fluorescing from the treatment site as a result of irradiating the treatment site with the fluorescence inducing light. Spectrometer 144 is preferably of the type known in the art as an optical multichannel analyzer (OMA). A suitable spectrometer is distributed by OCEAN OPTICS (Model S-2000).

In a prefered embodiment of the invention light arriving from imaging channel 132 is distributed among cameras 138 and 140 and spectrometer 144 via a set of beam splitters 145 and lenses 143.

Additional lenses 141 may be employed at various locations, serving various light focusing or distribution purposes. Light analysis arrangement 136 further includes at least one display 146 for displaying the reflected light image 146a, the fluorescence light image 146b and the spectrum 146c, described above.

System 100 preferably further includes a computer 150 for confrolling its operation. Computer 150 is therefore preferably coupled to and controls the operation of spectrometer 144, cameras 138 and 140, display 146, motor 112 of motorized filter wheel 114, light source 102 and mechanism 130. Computer 150 may also be coupled to and serve to control various functions of a conventional endoscope, as further detailed below. Thus, computer 150 receives signals from spectrometer 144 indicative of the spectrum of light received by spectrometer 144. These signals are processed by computer 150 which then transmits an electrical signal to display 146 causing display 146 to generate a representation 146c of the spectrum on display 146. Computer 150 also receives signals from cameras 138 and 140 indicative of the images received by cameras 138 and 140. These signals are processed by computer 150 which then transmits an electrical signal to display 146 causing display 146 to generate representations 146a/b of the images on display 146. Computer 150 also receives signals from a user indicative of the user's will with respect to the operation of motor 112 of motorized filter wheel 114, light source 102 and mechanism 130. These signals are produced by any computer signalling mechanism, such as, but not limited to, a mouse, a keyboard, an active screen, etc. These signals are processed by computer 150 which then fransmits an electrical signal to operate the listed components as required.

Thus, an operator of system 100 can monitor the spectral emissions of the treatment site simultaneously with a fluorescence image of the treatment site. Preferably, these images and spectrums are displayed in real time, as the light from the treatment site is received by spectrometer 144 and camera 140. This mode of operation has a synergistic effect, allowing the operator of the system to provide and monitor a treatment by viewing computer display 146 rather than by viewing the treatment site itself. All the information required to determine where and when to move endoscope 120 with respect to the treatment site is provided on the screen.

In a preferred embodiment the image also indicates the point or area at which spectrum has been measured.

The operator may also be provided with a reflected light, color image of the freatment site.

As far as treatment is concerned the operator may apply PDT or HPT or a combination of HPT and PDT for more effective results.

The system according to the present invention is combinable with existing endoscopes. A suitable endoscope to which the system may combine is distributed by PENTAX® (Model FG-34X).

Such an endoscope typically has an illumination light channel, a working channel and an imaging light channel, all as further described above. Such an endoscope typically further includes water, air and suction channels, as well known in the art. Further according to the present invention provided is a method of endoscopically monitoring a photodynamic treatment of an internal treatment site. The method includes the following steps.

First, a phtodynamic chemical having a strong affinity for the treatment site is applied to an organism, e.g., systemically (by injection, orally) or locally, etc.

Second, the treatment site is irradiated with a fluorescence inducing light, the fluorescence inducing light is selected such that is induces the phtodynamic chemical to emit a fluorescent light. For most used chemicals the fluorescence inducing light would be in the blue range. Third, the fluorescent light is monitored via a first camera

And fourth, a fluorescence image of the treatment site is displayed, thereby providing spatial data of a distribution of the phtodynamic chemical in the treatment site. Further according to the present invention provided is a method of endoscopically monitoring the efficiency of a photodynamic therapy of an internal treatment site. The method includes the following steps.

First, a phtodynamic chemical having a strong affinity for the freatment site is applied to an organism, e.g., systemically (by injection, orally) or locally, etc.

Second, the treatment site is irradiated with a treating light selected such that when it impinges the phtodynamic chemical a formation of free radicals is induced. The treating light is typically in the red range.

Third, the freatment site is irradiated with a fluorescence inducing light, the fluorescence inducing light is selected such that is induces the phtodynamic chemical to emit a fluorescent light. For most used chemicals the fluorescence inducing light would be in the blue range.

Fourth, the fluorescent light is monitored via a first camera

And fifth, a fluorescence image of the freatment site is displayed, thereby providing spatial data of a distribution of the phtodynamic chemical in the treatment site.

According to a prefered embodiment of the invention any of the methods further include the steps of irradiating the treatment site with an illumination light, monitoring light reflected from the freatment site via a second camera, and displaying a reflected light image of the freatment site.

According to another prefered embodiment of the invention any of the methods further include the steps of monitoring the fluorescent light via a spectrometer, and displaying a fluorescence spectrum of at least some of the fluorescent light. While the invention has been described with respect to a limited number of embodiments, it will be appreciated that many variations, modifications and other applications of the invention may be made.

Claims

WHAT IS CLAIMED IS:

1. A system for endoscopically irradiating and concurrently monitoring light during photo dynamic treatment of an internal treatment site, the system comprising:

(a) at least one light source for providing an illuminating light for illumination of the freatment site, a fluorescence inducing light for inducing a fluorescence light emission from the treatment site and a treating light for activating a photodynamic chemical present at the freatment site;

(b) an illumination light channel for tunneling said illuminating and fluorescence inducing lights from said light source to the treatment site;

(c) a working light channel for tunneling said treating light from said light source to the treatment site;

(d) an imaging light channel for retrieving light from the freatment site; and

(e) a light analysis arrangement being optically coupled to said imaging light channel for analyzing said light retrieved from the treatment site, said light analysis arrangement including: (i) a first camera for providing a reflected light image of the freatment site; (ii) a second camera for providing a fluorescence light image of the treatment site; (iii) a spectrometer for providing a spectrum of at least part of the light retrieved from said freatment site; and (iv) at least one display for displaying said reflected light image, said fluorescence light image and said spectrum.

2. The system of claim 1, wherein said light source is further for providing a heating light for heating the treatment site, said working light channel is further for tunneling said heating light from said light source to the treatment site.

3. The system of claim 2, wherein said illuminating light is a white light, said fluorescence inducing light is a blue light, said treating light is a red light and said heating light is an infrared light.

4. The system of claim 2, wherein said light source includes a Xenon arc lamp and a filters wheel for selecting among said illuminating light, said fluorescence inducing light, said treating light and a combination of said treating light and said heating light.

5. The system of claim 1, further comprising a mechanism for alternately optically coupling said at least one light source with said illumination light channel and said working light channel.

6. The system of claim 1 , wherein said first camera is a color camera.

7. The system of claim 1, wherein said second camera is a monochromatic camera.

8. The system of claim 1, wherein said spectrum is of at least part of a light fluorescing from the treatment site when illuminated with said fluorescent inducing light.

9. The system of claim 1, wherein said working light channel includes a light diffuser at its freating end.

10. The system of calim 1, wherein said imaging light channel is an imaging optic fiber bundle of an endoscope.

11. The system of calim 1 , wherein said illumination light channel is an illumination optic fiber bundle of an endoscope.

12. The system of calim 1, wherein said working light channel includes an optic fiber insertable via a working channel of an endoscope.

13. A system combining with an existing endoscope, the endoscope having an illumination light channel, a working channel and an imaging light channel, the system being for endoscopically irradiating and concurrently monitoring light during photodynamic freatment of an internal treatment site, the system comprising:

(a) at least one light source for providing an illuminating light for illumination of the treatment site, a fluorescence inducing light for inducing a fluorescence light emission from the treatment site and a freating light for activating a photodynamic chemical present at the treatment site;

(b) a working light channel being insertable via the working channel of the endoscope for tunneling said freating light from said light source to the treatment site;

(c) a mechanism for alternately optically coupling said light source with the illumination light channel and said working light channel, for tunneling said illuminating and fluorescence inducing lights from said light source to the freatment site, and for tunneling said treating light from said light source to the treatment site, respectively; and

(f) a light analysis arrangement being optically coupled to the imaging light channel for analyzing light retrieved from the freatment site, said light analysis arrangement including: (i) a first camera for providing a reflected light image of the treatment site; (ii) a second camera for providing a fluorescence light image of the treatment site; (iii) a specfrometer for providing a spectrum of at least part of the light retrieved from said treatment site; and (iv) at least one display for displaying said reflected light image, said fluorescence light image and said spectrum.

14. The system of claim 13, wherein said light source is further for providing a heating light for heating the treatment site, said working light channel is further for tunneling said heating light from said light source to the freatment site.

15. The system of claim 14, wherein said illuminating light is a white light, said fluorescence inducing light is a blue light, said freating light is a red light and said heating light is an infrared light.

16. The system of claim 14, wherein said light source includes a Xenon arc lamp and a filter wheel for selecting among said illuminating light, said fluorescence inducing light, said treating light and a combination of said treating light and said heating light.

17. The system of claim 13, wherein said first camera is a color camera.

18. The system of claim 13, wherein said second camera is a monochromatic camera.

19. The system of claim 13, wherein said spectrum is of at least part of a light fluorescing from the treatment site when illuminated with said fluorescent inducing light.

20. The system of claim 13, wherein said working light channel includes a light diffuser at its treating end.

21. A method of endoscopically monitoring a photodynamic freatment of an internal freatment site, the method comprising the steps of:

(a) applying to an organism a phtodynamic chemical having a strong affinity for the freatment site;

(b) irradiating the freatment site with a fluorescence inducing light, said fluorescence inducing light is selected such that is induces said phtodynamic chemical to emit a fluorescent light; (c) monitoring said fluorescent light via a first camera; and

(d) displaying a fluorescence image of said freatment site, thereby providing spatial data of a distribution of said phtodynamic chemical in the freatment site.

22. The method of claim 21 , further comprising the steps of:

(e) irradiating said treatment site with an illumination light;

(f) monitoring light reflected from said treatment site via a second camera; and

(g) displaying a reflected light image of said treatment site.

23. The method of claim 21, further comprising the steps of:

(e) monitoring said fluorescent light via a spectrometer; and

(f) displaying a fluorescence spectrum of at least some of said fluorescent light.

24. A method of endoscopically monitoring the efficiency of a photodynamic therapy of an internal treatment site, the method comprising the steps of:

(a) applying to an organism a phtodynamic chemical having a strong affinity for the treatment site;

(b) irradiating the treatment site with a treating light selected such that when it impinges said phtodynamic chemical a formation of free radicals is induced;

(c) irradiating the treatment site with a fluorescence inducing light, said fluorescence inducing light is selected such that is induces said phtodynamic chemical to emit a fluorescent light;

(d) monitoring said fluorescent light via a camera; and

(e) displaying a fluorescence image of said treatment site, thereby providing spatial data of a remaining distribution of said phtodynamic chemical in the freatment site.

25. The method of claim 24, further comprising the steps of: (f) irradiating said treatment site with an illumination light;

(g) monitoring light reflected from said treatment site via a second camera; and

(h) displaying a reflected light image of said treatment site.

26. The method of claim 24, further comprising the steps of:

(f) monitoring said fluorescent light via a spectrometer; and

(g) displaying a fluorescence spectrum of at least some of said fluorescent light.