RU2382660C1 - Device and method of fluorescent diagnostics and photodynamic therapy of skin diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: device includes power unit and control unit, source of radiation in form of gas-discharge lamp, spectrum-selective chamber for registration of fluorescent images. Gas-discharge lamp is made pulse and is placed in casing provided with light-filters. Light-filters are installed on gas-discharge lamp and have zero light-emission in that spectrum range, in which light-filters of spectrum-selective chamber let through, and light-filters of spectrum-selective chamber have zero light-emission in that spectrum range, in which light-filters of gas-discharge let through. Method of fluorescent diagnostics and photodynamic therapy is realised by means of device, with application of endogenic or induced photosensibilisers of porphyrin group, with application on regions which do not have intensive own fluorescence of applicator, containing 5-aminolevulinic acid for induction of photosensibilisers. Method includes irradiation of affected skin and end of irradiation if concentration of photosensibilisers of porphyrin group decreases lower than therapeutic values. Irradiation and diagnostics are carried out simultaneously by irradiation with pulse light radiation and continuous registration of fluorescent images by means of device.

EFFECT: application of claimed invention allows to increase efficiency of photodynamic therapy realisation and eliminate painful sensations during irradiation process.

2 cl, 8 dwg, 3 ex

Description

The invention relates to medical equipment, namely to devices for the diagnosis and treatment of skin diseases.

Known devices of the above type, designed to direct high-intensity pulsed light radiation into the skin area in the wavelength range from ultraviolet to medium infrared, containing the body of the device (to accommodate electrical and electronic devices, to generate the necessary energy, to generate light radiation and to control pulsed light radiation) and a module (radiation head) located outside the housing and containing a light source. The module is preferably provided with one or more filters to cut off an undesirable part of the wavelength range.

So, there are flash phototherapy flash units Flash 1 Plus, Flash 1 Jumbo, manufactured by General Project S.r.l. (http://www.generalproject.com). The devices are intended for skin procedures, in particular for the treatment of acne, vascular pathologies, photoepilation, photorejuvenation. The apparatuses include an instrument housing containing electrical and electronic components for generating and controlling a light pulse, and a manual module located outside the housing, in which there is a lamp for emitting a high-intensity pulsed light flux and optical filters.

The disadvantage of these devices is the inability to conduct fluorescence diagnostics in order to control phototherapy during irradiation.

Closest to the proposed device (prototype) is a system for conducting and monitoring photodynamic therapy and photodynamic diagnostics (WO 9922814 A1, 05/14/1999). The system contains: (a) at least one radiation source, which can be implemented, for example, in the form of an annular gas-discharge lamp, for lighting, exciting fluorescence and activating the photodynamic process in a biological tissue or organ; (b) an illumination channel for transmitting radiation to illuminate and excite fluorescence from a source to a biological tissue or organ; (c) a therapeutic channel for transmitting radiation to activate the photodynamic process from a source to a biological tissue or organ; (d) a collecting channel for collecting radiation from a biological tissue or organ; (e) a device for analyzing radiation collected from a biological tissue or organ, optically coupled to a collecting channel. A device for analyzing radiation includes a camera for recording an image of a biological tissue or organ in visible light, a camera for recording a fluorescence image of a biological tissue or organ, and a spectrometer for recording at least a portion of the spectrum reflected from the biological tissue or radiation organ; (e) at least one monitor for simultaneously displaying an image of a biological tissue or organ in visible light, a fluorescence image of a biological tissue or organ, and a spectrum of radiation reflected from the biological tissue or organ. The system also contains a system of optical filters of the illumination and therapeutic channels (light transmission, for example, 400-750 nm and 1200-2000 nm), a spectrally selective system in the form of optical filters that block light radiation, outside the fluorescence range of photosensitizers, optically coupled to a camera for recording fluorescence images (e.g. monochromatic CCD camera). In order to select the desired range of radiation from the source, the device provides for the possibility of moving the filters using a special computer-controlled mechanism.

The disadvantage of this device is the insufficiently high efficiency of photodynamic therapy, the presence of a pain effect during irradiation, as well as the technological complexity associated with the presence of special channels (lighting, therapeutic and collecting) for transmitting radiation.

The objective of the invention is to simplify the design of the device, increase the effectiveness of photodynamic therapy and minimize the pain effect of the procedure.

The problem is solved by the fact that the proposed device for fluorescence diagnosis and photodynamic therapy of skin diseases, including a power supply and control unit, a radiation source in the form of a discharge lamp, a spectrally selective camera for recording fluorescence images, in which the discharge lamp is made pulsed and placed in a casing, equipped with light filters, while the filters mounted on a discharge lamp have zero light transmission in the spectral range in which light is transmitted the filters of the spectrally selective chamber, and the filters of the spectrally selective chamber have zero light transmission in the spectral range in which the filters of the discharge lamp are passed.

Figure 1 presents a schematic representation of the proposed device, in which:

1 - power supply and control unit, which houses electrical and electronic devices for generating the necessary energy to generate pulsed light radiation and to control this radiation;

2 - a radiating head;

3 - a cable connecting the power supply and control unit and the radiation head, which serves to transfer electric energy from the power supply to the discharge lamp and to synchronize the operation of the flash lamp and camera;

4 - camera for recording fluorescence images;

5 - video information display system.

Figure 2 shows a schematic illustration of a radiating head, in which:

6 - annular gas discharge lamp for generating pulsed radiation;

7 - a casing for focusing radiation, containing an annular gas discharge lamp;

8 - spectrally selective camera system;

9 is a spectrally selective gas discharge lamp system.

The proposed device operates as follows. An annular flash lamp (6) located in the radiation focusing casing (7) irradiates a skin area. Energy management of the light pulse and lamp power is carried out by the power and control unit (1) using a cable (3). The operation of a gas discharge flash lamp and a camera (4) registering fluorescence images is synchronized in such a way that the image is fixed at the moment of applying a light pulse. Those. The light pulse serves both to initiate photochemical and photobiological processes in the irradiated tissue area, which determines the therapeutic effect of the procedure, and at the same time to excite fluorescence fluorophores, which allows the diagnosis and control of photodynamic therapy. The resulting fluorescence image is displayed on the monitor (5). The filters installed on the gas discharge lamp and the chamber are made in such a way that the filters of the chamber (8) have zero light transmission in the spectral range in which the filters of the gas discharge lamp (9) pass, and vice versa, they transmit light in the spectral range in which the filters gas discharge lamps have zero light transmission, and the light transmission range of the chamber is located in the region of large wavelengths, relative to the light transmission range of the gas discharge lamp. The specified system of light filters provides the ability to use the radiation of a flash lamp to excite fluorescence recorded by the camera.

The invention relates to medicine, namely to methods for diagnosing and treating skin diseases.

The technique, which involves the use of intense pulsed light to activate photochemical and photobiological processes, is widely used in clinical and aesthetic dermatology for the treatment of skin diseases: acne therapy, psoriasis, age spots removal, etc.

A known method of photodynamic therapy of acne using a pulsed radiation source with topical application of 5-aminolevulinic acid or without it (J. Rojanamatin, P. Choawawanich. Treatment of Inflammatory Facial Acne Vulgaris with Intense Pulsed Light and Short Contact of Topical 5-Aminolevulinic Acid: A Pilot Study // Dermatol Surg. 2006. 32. pp. 991-997). When implementing the method, a water-oil emulsion was prepared containing 5-aminolevulinic acid in a concentration of 20%. The resulting emulsion was applied to the skin of one of the patient's cheeks, the duration of application was 30 minutes, the second cheek was irradiated without the application of 5-aminolevulinic acid. Then, the affected areas of the skin were irradiated using a pulsed light source manufactured by Quantum SR, ESC Medical Systems Ltd., Yokneam, Israel. The irradiation was carried out in a double pulse mode (the first pulse 2.4-3.6 ms, the second 4-6 ms, a delay of 20-40 ms) at wavelengths 560-590 nm, the total energy density was 25-30 J / cm ² . The study showed that both methods - with and without the use of 5-aminolevulinic acid - provide effective treatment for acne. However, the application of 5-aminolevulinic acid can significantly increase the effectiveness of therapy.

A significant drawback of the above method of photodynamic therapy of acne using a pulsed light source is the lack of control of the concentration of exogenous or endogenous photodynamic agents in the skin during the procedure and, as a consequence, the inability to vary the used light dose.

Closest to the proposed method (prototype) is the method of fluorescence diagnosis and photodynamic therapy of acne, described in RF Patent No. 2265463 A61N 5/067 (2005). The method offers the following. Diagnosis is by measuring the fluorescence spectra of the affected areas. Areas with intrinsic fluorescence are irradiated with light with a wavelength of 630 +/- 10 nm and an energy density of 10-4500 J / cm ² , an applicator containing 2-20% solution of 5-aminolevulinic acid is applied to areas that do not have intrinsic fluorescence , and after exposure and removal of the applicator is irradiated with light with a wavelength of 630 +/- 10 nm and an energy density of 10-4500 J / cm ² . The progress of the irradiation process is monitored by recording the fluorescence spectra on the affected areas of the skin before irradiation, after applying an applicator containing 5-aminolevulinic acid, after irradiation, and irradiation is stopped when the concentration of porphyrins is lower than therapeutic values.

However, in the indicated method, accumulation assessment and therapy are implemented as separate procedures and using various devices, and the choice of time for measuring fluorescence spectra or obtaining fluorescence images in order to control photodynamic therapy is carried out by a doctor, i.e. subjective. The disadvantages of the method include the insufficiently high efficiency of the photodynamic therapy of skin diseases and the high morbidity of photodynamic therapy with 5-aminolevulinic acid when using continuous radiation.

The present invention solves the problem of increasing the effectiveness of the photodynamic therapy of skin diseases and reducing the pain effect of the irradiation procedure.

These problems are solved by the fact that a method for fluorescence diagnosis and photodynamic therapy of skin diseases using endogenous or induced photosensitizers of the porphyrin group using an applicator containing 5-aminolevulinic acid to induce photosensitizers, including irradiating the affected area of the skin and irradiation with a decrease in the concentration of photosensitizers of the porphyrin group below the therapist values in which irradiation and diagnostics are carried out simultaneously by irradiation with pulsed light radiation and continuous registration of fluorescence images using the device according to claim 1.

The method is implemented as follows. Using the proposed device, a fluorescence diagnostic procedure is carried out by recording an autofluorescence image of a skin area in the red spectrum when a single light pulse is applied in the wavelength range from ultraviolet to red in order to excite fluorescence. The intensity of autofluorescence in the resulting image assesses the concentration of endogenous porphyrins in various areas of the skin to be treated. In areas that do not have intense intrinsic fluorescence, i.e. having a low concentration of endogenous porphyrins, apply an applicator containing a 2-20% solution of 5-aminolevulinic acid. After exposure and removal of the applicator using the proposed device, re-register the fluorescence image of the skin using the above modes in order to assess the accumulation of ALA-induced protoporphyrin IX. In case of sufficient accumulation using the proposed device is irradiated with light in the wavelength range from ultraviolet to red, the energy density of the irradiating light is 10-4500 J / cm ² . The progress of the irradiation process is controlled using the proposed device by registering fluorescence images of the affected areas, recorded directly during the application of a light pulse to the skin. In this case, irradiation is stopped when the concentration of porphyrins decreases below therapeutic values.

The proposed method is illustrated by the following examples.

Example 1

Patient L., 53 years old, diagnosed with actinic keratosis, localization - cheek.

An autofluorescence image of the pathological site was recorded, as a result of which it was found that the concentration of intrinsic porphyrins is low and the use of 5-aminolevulinic acid is necessary. A 10% solution of 5-aminolevulinic acid was used, the duration of application was 2 hours. After the application was removed, a fluorescence image of the skin was re-recorded in order to assess the accumulation of ALA-induced protoporphyrin IX. Sufficient accumulation of ALA-induced protoporphyrin IX was sufficient for therapy. Then irradiation was carried out using a device for fluorescence diagnosis and photodynamic therapy of skin diseases. The energy density in one light pulse was 5 J / cm ² . The fluorescence image of the irradiated area was recorded at each pulse. After the implementation of 15 pulses (total energy density of 75 J / cm ² ), it was noted that the fluorescence intensity indicates that the concentration of ALA-induced protoporphyrin IX dropped below the therapeutic value and radiation was stopped. After 24 hours, a second procedure was carried out in an identical manner. The patient did not experience pain during photodynamic therapy.

The result of photodynamic therapy is presented in Figure 3, which shows the images of the pathological area in visible light obtained before treatment (A) and 5 days after photodynamic therapy (B). Complete regression was noted. Figure 4 presents the fluorescence images of the pathological area obtained using the proposed device. Images were obtained prior to the application of 5-aminolevulinic acid (A) - the figure shows that the concentration of intrinsic porphyrins is insufficient for photodynamic therapy, 2 hours after application (B), therapeutic accumulation of ALA-induced protoporphyrin IX is noted, after therapy (C) - the image was obtained during the 15th pulse, as can be seen from the presented figure, the concentration of ALA-induced protoporphyrin IX dropped below the therapeutic value, as a result of which the radiation was stopped.

Example 2

Patient F., 21 years old, diagnosed with acne, localization - face.

An autofluorescence image of the pathological site was recorded, as a result of which it was found that the concentration of intrinsic porphyrins is low and the use of 5-aminolevulinic acid is necessary. A 10% solution of 5-aminolevulinic acid was used, the duration of application was 2 hours. After removal of the application, a fluorescence image of the skin was re-recorded in order to assess the accumulation of ALA-induced protoporphyrin IX. Sufficient accumulation of ALA-induced protoporphyrin IX was sufficient for therapy. Then irradiation was carried out using a device for fluorescence diagnosis and photodynamic therapy of skin diseases. The energy density in one light pulse was 5 J / cm ² . The fluorescence image of the irradiated area was recorded at each pulse. After the implementation of 20 pulses (total energy density of 100 J / cm ² ), it was noted that the fluorescence intensity indicates that the concentration of ALA-induced protoporphyrin IX dropped below the therapeutic value and radiation was stopped. Another 6 procedures were carried out with an interval between procedures of 72 hours according to an identical scheme. The patient did not experience pain during photodynamic therapy.

The result of photodynamic therapy is presented in Figure 5, which shows the patient’s skin condition before treatment (A) and 15 days after photodynamic therapy (B). A significant decrease in the number and density of rashes is seen. Figure 6 presents the fluorescence images of the pathological area obtained using the proposed device. Images were obtained before the application of 5-aminolevulinic acid (A) - the figure shows that the concentration of intrinsic porphyrins is insufficient for photodynamic therapy, 2 hours after application (B), therapeutic accumulation of ALA-induced protoporphyrin IX is noted, after the treatment (C) image obtained during the 20th pulse, as can be seen from the figure, the concentration of ALA-induced protoporphyrin IX dropped below the therapeutic value, as a result of which the irradiation was stopped.

Example 3

Patient R., 19 years old, diagnosed with acne, localization - face.

An autofluorescence image of the pathological site was recorded, as a result of which it was found that the concentration of intrinsic porphyrins is sufficient for photodynamic therapy. Next, irradiation was carried out using a device for fluorescence diagnosis and photodynamic therapy of skin diseases. The energy density in one light pulse was 6 J / cm ² . The fluorescence image of the irradiated area was recorded at each pulse. After the implementation of 18 pulses (total energy density of 108 J / cm ² ), it was noted that the fluorescence intensity indicates that the concentration of intrinsic porphyrins dropped below the therapeutic value and radiation was stopped. Another 7 procedures were carried out with an interval between procedures of 48 hours in an identical manner. The patient did not experience pain during photodynamic therapy.

The result of photodynamic therapy is presented in Fig.7, which shows the patient’s skin condition before treatment (A) and 20 days after photodynamic therapy (B). A significant decrease in the number and density of rashes is seen. On Fig presents fluorescence images of the pathological area obtained using the proposed device. Images were obtained before irradiation (A) - the figure shows that the concentration of intrinsic porphyrins is sufficient for photodynamic therapy; after therapy (B), the image was obtained during the 18th pulse, as can be seen from the presented figure, the concentration of intrinsic porphyrins dropped below the therapeutic value as a result of which the exposure was discontinued.

Thus, the proposed device for fluorescence diagnostics and photodynamic therapy of skin diseases and the method of its application provide effective photodynamic therapy and are characterized by the absence of pain during irradiation.

Claims (2)

1. A device for fluorescence diagnostics and photodynamic therapy of skin diseases, including a power supply and control unit, a radiation source in the form of a gas discharge lamp, a spectrally selective camera for recording fluorescence images, characterized in that the gas discharge lamp is pulsed and placed in a casing equipped with light filters, in this case, the filters mounted on the discharge lamp have zero light transmission in the spectral range in which the filters pass spectrally selective to measures and filters spectrally-selective light transmission chamber have a zero in the spectral range in which the color filters passed the discharge lamp. 2. A method for the fluorescence diagnosis and photodynamic therapy of skin diseases using endogenous or induced photosensitizers of the porphyrin group, using, in areas that do not have intense intrinsic fluorescence, an applicator containing 5-aminolevulinic acid to induce photosensitizers, including irradiating the affected area of the skin and stopping irradiation with a decrease in exposure the concentration of photosensitizers of the group of porphyrins below therapeutic values, characterized in that about and treatment and diagnosis are carried out simultaneously by irradiating the pulsed light and the continuous recording fluorescent images using the device of claim 1.

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