System and method for therapy and diagnosis comprising optical components for distribution of radiation

ES 2 399 752 T3

DESCRIPTION

System and procedure for therapy and diagnosis comprising optical components for radiation distribution

The present invention relates generally to a system for therapy and diagnosis in an individual. More particularly the system and method relate to a system and method for therapy and diagnosis of tumors in a human or an animal. Even more particularly, the invention relates to a system for photodynamic therapy (PDT) and / or photothermal therapy (PTT) and / or photodynamic diagnosis (PDD) of a site in and / or within the body of a human or an animal, in which non-ionizing electromagnetic radiation is conducted to the site for reaction with the radiation, so that the system comprises an operating mode selector for distribution of radiation from, at least, a radiation source to a reaction site and / or from the reaction site to at least one radiation sensor, respectively, and wherein the reaction site is generally a site of a tumor exhibiting such a tumor like a malignant tumor.

Background of the invention

Within the field of medical therapy for tumor diseases, a series of modalities have been developed for the treatment of diseases caused by malignant tumors: operation, cytostatic treatment, treatment with ionizing radiation (gamma or particle radiation), isotope therapy and brachytherapy using needles. Radioactive agents are examples of common treatment modalities. Despite great advances in therapy, tumor diseases continue to represent great human suffering and are responsible for a high percentage of deaths in Western countries. A relatively new treatment modality, photodynamic therapy, commonly abbreviated PDT, provides an interesting complement or alternative in the field of treatment. A tumor-seeking agent, which is commonly referred to as a precursor or sensitizer, is administered to the body, for example, intravenously, orally, or topically. In general, it accumulates in malignant tumors to a greater extent than in surrounding healthy tissues. The tumor area is then irradiated with non-thermal red light, usually from a laser, driving the sensitizer to a more energetic state. Through energy transfer, from the activated sensitizer to the oxygen molecules in the tissue, oxygen is transferred from its normal triplet state to the excited singlet state. Singlet oxygen is known to be particularly toxic to tissues; the cells are eradicated and the tissues go into necrosis. Given the localization of the sensitizer in tumor cells, a unique selectivity is obtained, in which the surrounding healthy tissues are spared. Clinical experience, using in particular hematoporphyrin derivatives (HPD) and delta aminolevulinic acid (ALA) have shown good results.

Sensitizers can also display another useful property; When the substance is excited with visible or ultraviolet radiation, it provides a characteristic fluorescence signal that travels to longer wavelengths. This signal appears clearly in contrast to endogenous tissue fluorescence, which is also called autofluorescence and is used to localize tumors and to quantify the extent of absorption of the sensitizer into the tissue.

Limited tissue penetration of the red activating radiation is a major drawback of PDT. The result is that only tumors less than 5 mm thick can be treated by superficial irradiation. In order to treat thicker and / or deeper tumors, interstitial PDT (IPDT) can be used. In this case, light-conducting optical fibers are brought to the tumor using, for example, a syringe needle, in the lumen of which a fiber has been placed.

In order to achieve efficient treatment, several fibers have been used to ensure that all tumor cells are subjected to a sufficient dose of light so that the singlet toxic state is obtained. Dose calculations of absorption and scattering characteristics of tissues have been shown to be achievable. For example, in the Swedish patent SE 503 408 an IPDT system is described, in which six fibers are used for treatment and also for the measurement of the light flux that reaches a given fiber on penetration through tissues from other fibers. fibers. In this way, an improved calculation of the correct light dose for all parts of the tumor can be achieved.

According to what SE 503 408 discloses, the light from a single laser is divided into six different parts, using a beam splitter system comprising a large number of bulky mechanical components and optical components. The light is then focused on each of the six individual treatment fibers. One fiber is used as a transmitter, while the other fibers are used as receptors for radiation that penetrates the tissue. For light measurement, light detectors are mechanically moved into the beam path which is thus blocked and the weak light originating from the fibers that have collected the light that is delivered to the tissue is measured.

However, these open beam paths result in severely lossy beam splitting and the resulting light losses severely hinder light distribution as well as light measurement. Furthermore, this system must be frequently adjusted optically, which is a major drawback in relation to

ES 2 399 752 T3 clinical treatments. The system is also large and heavy and difficult to integrate into a user-friendly apparatus.

EP-A2-0280397 discloses a small diameter sterilizable endoscope having a central bundle of coherent fibers for transporting an image to viewing media. The fiber bundle is surrounded by light fibers. The proximal end of the endoscope is provided with coupling means to align the fiber optic bundle with the optical system of the viewing device and to provide an interface with light transmitting means to transmit light from a light source along fibers. light to a body cavity to be inspected. The device can be used for the detection of cancer cells and their treatment by phototherapy. A dye is attached to the tissue under examination and is then exposed to a frequency of excitation laser light. Cancer cells will emit fluorescent light at a fluorescence with characteristic frequency. The fluorescent light is detected and displayed on the video monitor, and then light with the same frequency as this fluorescent light is transmitted by the light fibers to the cells for phototherapy treatment. However, only the use of a single wavelength light is disclosed, so it is not possible to carry out multiple diagnostics without manual change of the light source. Furthermore, it is not possible to switch between different constellations of the light fibers, that is, all the fibers always have the same function (with or without light). The coupling means mentioned in EP-A2-0280397 are only used to adjust the light path through a two-part endoscope when assembled prior to use. In addition, different fibers are used to direct therapeutic light to the cancer site and to direct diagnostic light back through the endoscope. There is no distribution between different modes of operation. This solution offers, for example, neither interactive treatment nor tomographic mapping of tumors. WO-A1-02074339 discloses a device and method for photodynamic diagnosis of tumor tissues using fluorescent cobalamins. These fluorescent cobalamins are used as diagnostic and prognostic markers to (a) distinguish cancer cells and cancer tissues from healthy cells and tissues and (b) determine whether an individual responds positively to chemotherapy using therapeutic cobalamin bioconjugates. An apparatus is disclosed that includes a camera coupled to the proximal end of a surgical telescopic device. The surgical telescopic device is used to illuminate the tissue with non-white light and detect the emitted fluorescence for diagnostic purposes. The use of dual light sources is disclosed, including a red (not white) light source and a white light. The white light source is used for conventional illumination of the fabric. A switch is mentioned for switching between the alternative light sources. The switch can be voice actuated, mechanically actuated (foot pedal), optically actuated or electronically actuated. The switch is not described in more detail, except that a mirror or prism, under mechanical or electromechanical control, can be used for switching between the two light sources. Alternatively, a light source with two physically separate outlets is also disclosed. In this case, the light input into the surgical telescopic device has to be shifted between two outputs in order to switch the light source for the tissue. The device is not suitable for therapy. The therapy has to be carried out conventionally by a surgeon removing the cancerous tissue detected by means of fluorescence. Therefore, this device is not suitable for interactive diagnosis and therapy. Furthermore, there is no indication of a suitable switch to switch between different diagnostic or therapy modalities. Furthermore, the disclosed device offers only substantially superficial treatment or diagnosis, interstitial tissues cannot be treated or diagnosed. The device is also limited to existing body cavities and has the drawback that endoscopic probes are bulky and long compared to single fiber optics.

EP-A2-0195375 discloses a catheter for laser angio surgery. The device is used to detect atherosclerotic plaque deposits by detecting fluorescent light in reaction to excitation light sent through the catheter comprising optical fibers for this purpose. The same fiber can be used to send excitation light to the plate and to receive fluorescent light from the plate. When plaque is detected, it can be removed by sending high-energy light through selected fibers in the catheter. However, this system is not suitable for the diagnosis or treatment of tumors. The fibers to be illuminated are selected by purely mechanical arrangements by moving the light source or fibers in order to align the two towards each other. This device is also bulky compared to individual fibers, similar to the aforementioned endoscope, attached to existing body cavities and functions substantially superficially. In addition, it is not selective, that is, all targeted tissues are destroyed, regardless of whether they are diseased or healthy.

Therefore, there is a need for a new compact device that allows the distribution of radiation in a system for PDD, PDT and PTT to implement an intelligent way to carry out interactive interstitial treatment. One solution would be to use intelligent mechanical constructions to switch between different modes avoiding, for example, lossy beam splitting devices and allowing automatic calibration.

This mechanical solution to the aforementioned problems has been proposed in document PCT / SE02 / 02050, in which a distributor for radiation is described that has two rotating discs, one with respect to the other. The radiation distributor couples optical fibers between different modalities by rotational movement of fibers in these discs, one with respect to another. To switch between different light sources on one fiber

ES 2 399 752 T3 passed to the patient, a set with a total of four discs is described.

However, although these mechanical constructions are improvements of the IPDT system described above and although the problems described above are solved, these mechanical solutions have other relative limitations, for example, to mechanical inertia that limits the switching time between the different modes of a therapy and diagnostic system, such as an interactive interstitial treatment system.

Therefore, there is a need for a new compact device that allows the distribution of radiation in a system for therapy and diagnosis in a human or animal, where the therapy and diagnosis comprises PDT, PTT and PDD.

Other problems to be solved by the invention consist in providing an alternative solution that eliminates component service, for example, due to component wear, thus improving the reliability of a device for therapy and diagnosis comprising PDT, PTT and PDD. Also, the rotation of the fibers must be avoided, which further reduces the necessary dimensions of the device and increases the reliability. Furthermore, another problem solved by the invention is that the sounds or noises generated by the operation of known devices when switching between different operating modes are substantially reduced or eliminated.

Summary of the invention

The present invention overcomes the above-identified shortcomings of the art and solves, at a minimum, the above-identified problems by disclosing a system according to the appended claims, wherein a very practical and efficient implementation of interactive IPDT is achieved by the fact that different optical measurements for diagnostics and dosimetry can be carried out in an integrated and simple way by means of a system that requires minimal space. An important application of the invention is interactive, interstitial, photodynamic therapy and / or interactive photothermal tumor therapy.

The term "radiation" used below in this description refers to radiation suitable for the field of the invention, that is, photodynamic therapy (PDT) and / or photothermal therapy (PTT) and / or photodynamic diagnosis ( PDD). More specifically, this radiation "optical radiation", that is, non-ionizing electromagnetic radiation within the wavelength of infrared (IR), visible light or ultraviolet. This also applies to radiation sources, radiation conductors, radiation sensors, radiation switches, etc. within the scope of the inventive defining embodiments and claims, that is, these sources, conductors, or sensors for "radiation" are adapted to generate, conduct, measure, and the like. the aforementioned non-ionizing radiation.

According to one aspect of the invention, a system for therapy and / or diagnosis of a human or an animal comprises at least a first radiation source for emission of diagnostic radiation, and at least a second radiation source for emission of therapeutic radiation and, at a minimum, a first radiation conductor adapted to conduct radiation to the human or animal site. The system comprises an operating mode selector for optically directing said therapeutic radiation or said diagnostic radiation to the indicated site by said at least one first radiation conduit.

According to one embodiment of the invention, the human or animal therapy and / or diagnostic system is a system for interactive interstitial photodynamic tumor therapy and / or photothermal tumor therapy and / or tumor diagnosis.

The use of non-mechanical switching elements based on optical principles offers several advantages over mechanical devices. Among others, these advantages include: high switching speed between different operating modes of the system (diagnostics, photodynamic therapy, thermal therapy); compactness and stability of the system; excellent optical parameters; prolonged system life due to non-existence of mechanical component wear and due to many more switching cycles during the life cycle of the system elements and absence of switching noises, thus offering greater patient comfort.

Brief description of the drawings

In order to explain the invention in more detail, a series of embodiments of the invention will now be described with reference to the accompanying drawings in which:

Figure 1 is an illustrative schematic view of one embodiment of the invention for interactive IPDT;

Figure 2 is an illustrative schematic view of another embodiment of the invention;

Figure 3 is a schematic view of another embodiment of the invention comprising optical combiners and a non-mechanical optical combiner;

ES 2 399 752 T3

Fig. 4 is a schematic view showing the principle of the optical combiner used in an embodiment of the invention.

Figure 5 is a schematic view showing another embodiment of the invention comprising non-mechanical optical switches;

Figure 6 is a schematic view showing another embodiment of the invention comprising modules with multiple diagnostic radiation sources; Y

Fig. 7 is a view showing another embodiment of the invention comprising a 2xN non-mechanical optical switch.

Description of the achievements

Different embodiments of the system according to the invention are described below with reference to the drawings. In order to simplify the description of the embodiments, the reference numerals for similar elements shown in the drawings are not repeated throughout the figures.

A general description of a system 100, in accordance with the first embodiment of the invention, is provided with reference to FIG. 1. Accordingly, a system 100 for interactive IPDT comprises at least one diagnostic radiation source 110. Diagnostic radiation source 110 generates diagnostic radiation. Optical radiation from at least one diagnostic optical radiation source 110 enters a diagnostic optical radiation coupling module 120. The optical radiation is preferably transmitted via optical radiation conductors 111. In general, the conductors Radiators, described in this description of embodiments, are light guides such as optical fibers. Diagnostic radiation coupling module 120 further distributes radiation over one or more radiation conductors 122 to at least one mode selection module 140 of operation. Coupling of diagnostic radiation to radiation conductors 122 is accomplished by means of diagnostic radiation coupling module 120 comprising, for example, a non-mechanical optical switch, or alternatively, an optical combiner in series with a switch. non-mechanical optical or alternatively with an optical combiner. All of this will be explained in more detail below.

Diagnostic radiation is further conducted to one of the operating mode selection modules 140, as shown in FIG. 1. The objective of each operating mode 140 is to guide diagnostic radiation from one of the operating modes. diagnostic radiation sources 110 or therapeutic radiation from therapeutic radiation sources 130 by a conductor of a plurality of radiation conductors 142 to a treatment site 101 of a patient. All of these radiation conductors 142 can transmit radiation to reaction site 101 and can receive radiation from that site. Therefore, multiple measurements can be recorded and can be read simultaneously. Each of the fibers 142 is coupled proximally to a separate mode selection module 140, for example, fiber 141 is coupled to the mode of operation selection module 140 which is shown as the first selection module. mode of operation of a series 125 of modules 140 for selection of mode of operation / sources of therapeutic radiation 130 of FIG. 1. The distal ends of the fibers 142 are appropriately positioned at different locations at the treatment site in order to enable effective diagnosis or treatment of the patient. In addition, mode selection modules 140 couple radiation, which is transmitted from the distal end of fibers 142 back to mode selection module 140, then to at least one radiation detector 150. Alternatively, a series of radiation detectors are used with different sensitivities, or for example, one detector for each operating mode selection module. Radiation emanating from treatment site 101 is transmitted to radiation detectors 150 via radiation leads 152, such that a radiation lead 151 is shown passing from the mode of operation selection module 140 shown in FIG. upper part to radiation detector 150. The operating mode selection module 140 may comprise, for example, a non-mechanical optical switch or an optical combiner. One embodiment of an operating mode selection module 140 based on an optical combiner is described in greater detail below with reference to FIG. 4.

Figure 2 shows another embodiment of an interactive interstitial treatment system in which the diagnostic radiation coupling module 120 is subdivided into two radiation dispenser components 210 and 220. The radiation dispenser 210 is, as shown, a radiation distributor (Nx1) that is, a radiation distributor having N radiation inlets and one radiation outlet. In the example shown, radiation distributor 210 is a 3x1 radiation distributor, with a single output coupled to radiation distributor (lxn) 220, where n is the number of operating mode selection modules 125 as well as the number of radiation conductors 142 passing to / from the treatment site 101. Radiation distributors 210, 220 may comprise, similar to operating mode selection module 140, for example, a non-mechanical optical switch or an optical combiner. I know

ES 2 399 752 T3 describe exemplary radiation distributors 210, 220 in more detail below with reference to Figures 3 and 5 showing different combinations of non-mechanical optical switches and / or combiners for radiation distributors 210, 220 and selection module 140 with different advantages with respect to the operation of the system.

Figure 3 shows a system comprising a 3x1 optical combiner 310 and a 1x6 non-mechanical optical switch 320, as well as an optical combiner 330 as a selector for operating mode in six modules 325. For interstitial treatment, six sources are coupled therapeutic radiation 130, preferably laser light modules, to the six optical combiners 330. Each optical combiner 330 operates such that therapeutic radiation in therapy mode of operation is coupled through corresponding radiation conductor 142 to treatment site 101. To switch to diagnostic mode of operation, the source of therapeutic radiation is turned off. and then one of the three diagnostic radiation sources 110 is activated. In this manner, diagnostic radiation is conducted to combiner 310, where radiation from the active diagnostic radiation source is coupled to the combiner output leading to non-mechanical optical switch 320. Non-mechanical optical switch 320 couples radiation from input to the output radiation conductor 122 leading to the corresponding optical combiner 330 comprised in one of the modules 325. From combiner 330, diagnostic radiation is delivered to the treatment site via radiation conductor 142 connected to combiner 330, as shown in Figure 3. In this way, diagnostic radiation is spread at the treatment site and partially to the remaining five radiation conductors 142 and partially reflected back. The diagnostic run from the patient through combiner 330 is sent to radiation detector 150. In this way, five (= (n-1)) measurement values ​​are obtained. The non-mechanical optical switch 320 then switches the incoming diagnostic radiation from the radiation source 110 to the next combiner 330 comprised in the next module 325. In this way, another five measurement values ​​are obtained. This measurement process is repeated until all six modules 325 have been activated, resulting in six times five (= 30) measured values. These thirty measurement values ​​obtained can be used as input data for a tomographic modeling of the optical dose in different parts of the tumor during the course of treatment. This measurement process can be repeated with the remaining diagnostic radiation sources, resulting in three times thirty (N * (n-1)) or ninety tomographic measurement values. Also, diagnostic radiation reflected at site 101 of the illumination radiation connector can be used for diagnostic purposes.

Combiner 310 may be a commercially available fiber combiner, for example, from Polymicro Technologies or Sedi Fibers Optiques.

As the basis for the non-mechanical optical switch 320, a commercially available fiber optic switch from Piezosystem Jena Inc or Agiltron Inc. can be used. The principle of operation of combiner 330 is shown in Figure 4. Combiner 330 is also used. I was able to rely on the commercially available fiber binder from Polymicro Technologies. The combiner has three input fibers 401, -403, in which radiation is transmitted by these fibers in the directions indicated by arrows 421-423. The fibers 401-403 are carried together forming a single fiber along a stretch indicated by arrow 411 or fused at the junction of 401, 402, 403 and 424. The combiner as a whole has a length, as described above. indicated by arrow 410. In this way, the optical radiation is transmitted via the fibers 401 and 402 to the single fiber at 400 and the radiation from the single fiber at 400 is transmitted in the opposite direction mainly to the fiber 403. In the embodiment according to FIG. 3 , fiber 401 is connected to the therapeutic radiation source, fiber 402 is connected to the diagnostic radiation source, and fiber 403 is connected to the radiation detector. Combiner 330 can be made to transmit the main part of diagnostic radiation originating from tissue site 101 via fibers 400 to fibers 403, ensuring efficient utilization of eventually weak diagnostic radiation. The combiner does not transmit radiation directly from fibers 401, 402 to fiber 403.

FIG. 5 is a schematic diagram showing another embodiment of the present invention, in which a non-mechanical optical switch 510 switches between different sources of diagnostic radiation 110. Another non-mechanical optical switch 530 functions as a mode of operation selector, in which either the therapeutic radiation source is coupled to the treatment site, the diagnostic radiation source is coupled to the treatment site, or the treatment site is coupled to the radiation detector. The non-mechanical optical switch 320 operates in a similar manner to what has been described above. This embodiment has the advantage that the time to switch from one diagnostic radiation source to another is not determined by the diagnostic radiation sources. Compared to an optical combiner, the non-mechanical optical switch 510 determines the time required to switch between different radiation sources. This is generally more reproducible than disconnecting a light source at one input of a combiner and connecting another light source at another input of a combiner, such that both light sources are coupled to the same output of the combiner. Furthermore, a non-mechanical optical switch generally exhibits lower radiation losses than an optical combiner, which means that less powerful diagnostic radiation sources can be used than with the optical combiner 310. However, a non-mechanical optical switch has to be actively controlled while an optical combiner is a passive component. In addition, the non-mechanical optical switch 530 prevents reflected diagnostic radiation from the radiation detector from entering.

ES 2 399 752 T3 by means of a combiner, for example combiner 330. This unforeseen diagnostic radiation passing to the detector can lead to saturation ("blooming") of the detector 150. Instead of using a series of detectors 150 to avoid This phenomenon, a single detector may be sufficient, which limits the costs of the system, according to the present embodiment.

Fig. 6 is a schematic diagram showing another embodiment of the present invention. An optical combiner 630 is used in a similar manner to optical combiner 330. A series of diagnostic radiation sources 610, each of which has a corresponding combiner 620 in a series of diagnostic radiation source modules 615, is comprised in this embodiment, rather than an optical switch that distributes radiation from diagnostics to a series of mode selection modules 140. Thus, the cost for an optical switch, eg, switch 320 is avoided. Furthermore, the diagnostic radiation sources 610 can be modulated, so that the diagnostic radiation can be detected simultaneously by means of, for example, a "lock-in" technique or by multiplexing the signals.

Fig. 7 is a schematic diagram showing another embodiment of the present invention. The embodiment comprises a 2xn optical switch 710 that couples two diagnostic input n output radiation sources of the switch 710. The switch 710 has two inputs that can be arbitrarily routed to the different outputs. These components are commercially available, for example, from Pyramid Optics. The operating mode selector / radiation source module is a drive mode selector module 525, as described with reference to Figure 5, but it could also be replaced by a combiner module 625. In this way, achieves a more compact solution, since there is one less component in the system, for example, combiner 310 or switch 510. An optical switch also has lower losses than a combiner, as noted above.

The radiation conductors can be coupled to the different elements of the system, or they can be connected according to the invention by suitable methods or means, including fiber optic connectors of different types, such as SMA, ST or FC connectors. Alternatively, the radiation conductors may be fixed in holes by appropriate methods, for example gluing or mechanical fixing, for example by spring-loaded elements.

For the purposes of calibrating the system according to the invention, the overall performance of the system is recorded prior to treatment by direct measurements on a calibrated test tissue, for example a sterile intralipid water solution or a sterile test solid made in, for example, example, Delrin^®. The performance of therapeutic radiation sources can be controlled by internal and / or external power meters.

The non-mechanical optical switches that have been described can operate according to different principles. Beam switching and deflection is based on optical principles without mechanical movement of components such as prisms or mirrors. Examples of switching principles are, for example, beam deflection by acoustic-optical means, or acoustic-magnetic means or by an electrically controlled variation of the refractive index of a material through which the beam is shifted, thereby deflecting , an optical beam to different input / output fibers. Examples of materials having a suitable variable refractive index for electro-optical switches are, for example, LiNbO3, LiTaO3, GaAs, HgS, CdS, KDP, ADP or SiO2. The Agiltron Company^TM provides commercially available optical switches of this type, namely the CrystaLatch Solid State Fiber Optic Switch^TM constituting a family or the NanoSpeed^TM which is a series of optical switches. These optical switches feature fast response and ultra-high reliability exceeding 100 billion switching cycles. The Agiltron^TM they are an example of truly non-mechanical optical switches (zero moving parts), which are activated by an electrical impulse within an inorganic optical glass to facilitate switching, according to the state of the art. The switching is furthermore carried out in an intrinsically stable manner against temperature fluctuation and fatigue, providing another advantage of non-mechanical switches. In addition, Agiltron switches^TM They provide holding capacity against failure, thus maintaining its position indefinitely when the power supply is removed. The switches are conveniently controllable by a low voltage signal in direct current or digitally.

In the following section, principles related to the system according to the invention will be described, on which the description of an exemplary system with three sources 110 of diagnostic radiation and six conductors 142 of radiation for patients is based, preferably , optical fibers.

By reaction or site of treatment, it is intended in the present context to mean a site where photodynamically active compounds will react in a tumor when subjected to radiation therapy, for example, carried out by conductors of radiation directed through, by example, the opening of injection needles that are placed in the tumor. These radiation conductors 142 are then attached to reaction site 101. The radiation leads are then moved forward to reach out of the distal end of the needle. The same radiation conductor 142 is used continuously during treatment for integrated diagnostics and dosimetry and also to prevent the patient from being subjected to multiple functions.

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Preferably, the diagnostic radiation sources 110 are lasers and / or light emitting diodes of which one is of the same wavelength as the lasers 130 used for laser irradiation for photodynamic therapy of tumors, but could be of a power lower output. Suitable filters may be provided for insertion into the light path of radiation sensor 150, in order to ensure that the correct dynamic range is used for all measurement tasks and in order to prevent the aforementioned "blooming" effect of the radiation detector. radiation.

Some of the diagnostic radiation sources 110 are used to study the extent to which radiation (light, as defined above), of the corresponding wavelength penetrates through the tumor tissue at the treatment site 101 . When radiation from a radiation source is transmitted through a specific radiation conductor through the above-described arrangements into tissue, one of the radiation conductors 142 functions as a transmitter into the tumor and the other five radiation conductors 142 in the tumor will act as receptors and collect the diffuse flow of radiation that reaches them. The collected radiation is conducted back to radiation sensor 150, as described above, and five different radiation intensities can be recorded on the detector device.

As an alternative to a specific wavelength, radiation from an optically wide light source, such as a white light source and / or broadband light emitting diodes and / or light sources, can be coupled to the specific active radiation conductor 142. Lineal light. As it passes through the tissue into the receiving radiation conductor 142 in the patient, the well-defined spectral distribution of the radiation source will be modified by absorption of the tissue. Thus, oxygenated blood provides a different signal than non-oxygenated blood, allowing tomographic determination of the oxygen distribution, using the thirty different spectral distributions that are read, five spectra each time in the six different possible constellations. Such determination of oxygenation in the tumor is important since the PDT process requires oxygen access to the tissue.

Finally, in the case that element 140 is a combiner, a radiation source for visible or ultraviolet light, for example a laser, can be coupled to the specific active radiation conductor 142. Then, fluorescence is induced in the tissue. and a sensitizer is administered to the tissue showing a characteristic fluorescence distribution shifted towards longer wavelengths. The intensity of the corresponding signal allows a rough quantification of the level of the sensitizer in the tissue.

Since short wavelength radiation has very low tissue penetration, the fluorescence induced from this source will be a local measurement at the distal tip of the radiation lead. For this function, a filter can be inserted in front of detector 150 to reduce reflected radiation at site 101, since reflected radiation will be many magnitudes or orders higher than fluorescent radiation. A suitable stand-alone team to carry out this work is described in Rev. Sci. Instr. 71, 510004 (2000).

By sequentially switching diagnostic radiation source 110 through the different modules 125, fluorescence, which is a specific function of sensitizer concentration, is measured sequentially at the tips of the six radiation leads. Since the sensitizer is bleached by the intense red treatment light, being especially intense around the tip of the radiation conductor 142 that conducts radiation to the patient, it is essential to perform this measurement prior to the start of treatment.

If the tips of the radiation conductors 142 are further treated with a material, on which the fluorescence properties of the temperature depend, marked fluorescence lines are obtained on excitation and the intensity of these lines and their relative power depend on the temperature. at the tip of the radiation conductor 142 that is used for treatment. Examples of such materials are salts of transition metals or rare earth metals. In this way, the temperature can also be measured at the six positions of the six radiation conductors, one at a time or simultaneously. The measured temperatures can be used to ascertain whether blood coagulation with associated light attenuation has occurred at the tip of radiation conductor 142 and for studies regarding the use of possible synergistic effects between PDT and thermal interaction. Since the lines obtained are sharp, they can be easily extracted from the wider band endogenous fluorescence distribution of the tissue.

The sensitizer level can be measured for certain substances in an alternative way. In this case, the red light used for light propagation studies is used to induce red or near infrared fluorescence . Fluorescence penetrates through tissue at the tips of radiation receiving conductors 142 and is simultaneously displayed as a spectrum obtained on radiation sensor 150. A tomographic calculation of the sensitizer distribution can be carried out based on the thirty total measurement values ​​at each measurement opportunity.

After diagnostic measurements and calculations have been carried out, the optically coupled fibers 142 to the patient can be used for therapy by disconnecting the diagnostic radiation sources and connecting the therapeutic radiation sources 130, and also by switching optical switches, if present on them. the system, correspondingly, so that the therapeutic radiation sources are coupled to the fibers 142 of the patient. The therapeutic radiation sources are preferably laser sources with a wavelength chosen to suit the absorption band of the sensitizer. In the photo-dynamic treatment of a tumor,

ES 2 399 752 T3 preferably uses a dye laser or a laser diode with a wavelength that is selected with respect to the sensitizer used. For example, for Photofrin® the wavelength is 630 nm, for δ-aminolevulinic acid (ALA) it is 635 nm and for phthalocyanines it is approximately 670 nm, there are several other sensitizers that have these characteristic wavelengths. Individual lasers are regulated during treatment for a desirable individual power output. If desired, they can have built-in or external control detectors.

Therapeutic treatment can be interrupted, and new diagnostic data can be processed in an interactive procedure, until an optimal treatment has been reached. This procedure can include synergy between PDT and hyperthermia, in which an increased temperature is reached for increased fluxes of laser radiation. The entire process is controlled using a computer, which not only carries out all the calculations, but is also used for regulation and control of the system.

The present invention has been described above with reference to specific embodiments. However, other embodiments than those previously indicated as preferred, are equally possible within the scope of the appended claims, for example, optical couplers different from those described above, carrying out the indicated procedure by means of hardware or software, etc.

Furthermore, the term "comprising / comprising", when used in this description does not exclude other elements or steps, the terms "a" and "one" do not exclude a plurality and a single processor or other units can fulfill the functions of several of the circuit units indicated in the claims.