RU2424009C1 - Interstitial laser hyperthermia and photodynamic therapy apparatus and method - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine and medical equipment, namely to methods for conducting interstitial laser hyperthermia and photodynamic therapy of malignant neoplasms located under skin or in soft tissues, and apparatuses to implement said method. The apparatus comprises a laser emitter, an attached light guide, a cooling assembly for contact cooling of a tissue surface, a coolant supply means and a temperature recording device. The latter comprises an infrared chamber connected to a data displaying and processing unit connected with the laser emitter and the coolant supply means. The cooling assembly represents a seal unit with two sapphire windows. They are separated with a hollow for coolant supply. The light guide is fastened on a seal box by a bushing via a threaded connection. The data displaying and processing unit calculates a temperature value at the preset depth directly under the cooling assembly and regulates the power of the laser emitter and the rate of coolant supply by the means. The given apparatus is used in the laser hyperthermia and PDT method. The temperature is recorded on the tissue surface along the perimetre of the cooling assembly and/or at the certain distance therefrom. The input and output coolant temperature is recorded. The measured temperature values are used to derive the temperature directly under the cooling assembly at the preset depth. The temperature under the cooling assembly at the set depth is changed to the required value by regulating the laser emission power and/or coolant supply rate.

EFFECT: use of the group of inventions will allow higher effectiveness of laser hyperthermia and PDT of the malignant neoplasms located under skin or in soft tissues due to nonuniform tissue heating, enabled emission regulation of a temperature gradient position in the depth of the tissue, more effective radiation delivery, minimised skin injuries.

8 cl, 4 dwg

Description

The invention relates to medicine, namely to oncology and dermatology, and can be used for laser hyperthermia and photodynamic therapy of malignant neoplasms, namely located under the skin or in soft tissues.

Methods of exposure to localized tumor nodes are photodynamic therapy (PDT) and laser hyperthermia (LH) using the energy of laser radiation to destroy tumor cells. In PDT, the action of laser radiation energy is used in combination with the introduction of special drugs to the patient - photosensitizers (PS), which are selectively accumulated by tumor cells. Excited PS, whose concentration is an order of magnitude higher in cancer cells than in healthy ones, catalyzes a photochemical reaction that leads to the death of tumor cells. At the same time, the tissue framework from healthy cells is preserved.

In the case of LH, the laser radiation energy is used to heat the tumor site by absorbing radiation with tissue dyes (mainly hemoglobin). Heating the tissue to a temperature of 42-43 ° C leads to selective damage to malignant cells. Heating tissue to a temperature exceeding 60 ° C leads to irreversible changes in biological tissues.

PDT and LH can be used together. However, the possibilities of PDT and LH are significantly limited when the pathology is located at a certain depth. Also, with external PDT, in some cases there is a need for a deeper effect - damage to the tumor bed to prevent metastasis. The main problem that arises in the case of external radiation (without piercing and inserting a fiber under the skin) is associated with the creation of the necessary density of light energy at a certain depth in soft tissues without damaging the outer layers of the skin or organ. Biological tissues, as optical media, are highly scattering and have a high absorption of radiation from the wavelengths used in PDT and LG. This leads to the absorption of the main part of the radiation in the surface layer, the energy of which is converted into heat, and is the reason for the fast attenuation of the radiation propagating deep into the tissue. The heat generated can lead to a thermal burn of the skin or organ surface and prolonged pain after the procedure, in the presence of a residual concentration of PS in the skin, an undesirable PDT effect in the surface layers of healthy tissue is possible.

To protect the skin or the surface of the organ, skin cooling is used, which can be carried out before irradiation (by spraying the refrigerant or simultaneously with radiation through transparent cooled windows (for example, sapphire)), the application of “antireflective” upper layers of tissue gels, etc. Cooling surface not only increases the pain threshold, but allows you to shift the area of necrotic overheating deep into the tissue, allowing you to destroy subcutaneous pathology while preserving the skin.

There is a need for devices for interstitial laser hyperthermia and photodynamic therapy, containing means for measuring temperature at the required depth both in the case of laser hyperthermia, where the value of the achieved temperature is a responsible factor, and in the case of photodynamic therapy, where an excess of a certain temperature level is unacceptable, leading to a change in the optical parameters of the tissue, random distortion of the light field, etc.

The existing devices provide devices for determining the temperature on the surface of the tissue in the form of a temperature sensor and it is possible to equip a device for calculating the temperature field deep into the tissue depending on the cooling time, laser radiation parameters. A non-contact device for measuring temperature on the surface of the fabric using an infrared camera is also used.

A known device for the dynamic cooling of biological tissues during laser exposure [application WO 01/13811 A1, publ. 03/01/2001] contains a laser radiation source, a fiber for delivering laser radiation, a device for spraying refrigerant from the tank and a pump, a fast infrared detector, the optical axis of the optical fiber, the optical axis of the infrared detector and the spraying direction of the pump intersecting in the irradiation plane on the surface of the biological tissue. An infrared detector is coupled to a digital delay control device having control leads to a pump of a refrigerant atomization device and a laser source.

The disadvantage of this device is the inability to use as a source of laser radiation a laser with a continuous generation mode for PDT and LG.

Another disadvantage of the device is the limited time in the cycle during which the tissue remains cooled, which limits the value of the dose of energy that can be communicated to the subcutaneous formation, i.e. the scope of the device is limited to the treatment of point subcutaneous formations.

A known method of dynamic cooling of biological tissues during laser exposure [application WO 01/13811 A1, publ. 03/01/2001], in this case one or several skin cooling operations are carried out sequentially by dosing a liquid refrigerant with temperature registration at the surface, laser irradiation for a limited time or a sequence of laser pulses, various combinations of these operations.

The disadvantage of this method is that the need for alternating operations makes flexible adaptive regulation of the depth and degree of influence on biological tissues impossible, the optical and heat-conducting properties of which vary significantly for different organs from patient to patient.

The closest in the set of essential features and the achieved technical result is a device for the treatment of skin and subcutaneous formations [application US 2004/0073079 A1, publ. 04/15/2004]. The device includes a laser radiation source, a light guide, a sapphire plate-shaped cooling element, a coolant supply device, a monitoring device, a point contact temperature sensor located on the edge of the cooling plate, connected to a monitoring device, which in turn has a laser radiation source control channel and a coolant supply device.

The device forms zones of thermal damage under the skin by laser radiation with simultaneous cooling of the skin surface, continuously monitoring the skin temperature during irradiation in order to avoid dangerous overheating by a point contact temperature sensor.

The disadvantage of this device is the use of a point temperature sensor. A small temperature control area in the event that a point sensor falls into a position where it measures a temperature that is less absorbing in the light energy of the area, and therefore less heated, leads to the risk of thermal damage to areas of the skin with high absorption and higher induced temperature outside the temperature control point . This limits the use of the device for interstitial laser hyperthermia and photodynamic therapy of tissues in the presence of a malignant process, especially after preliminary surgical treatment, when the optical characteristics of the tissue at different points, their heat transfer parameters can vary.

The closest in the set of essential features and the technical result achieved is a method for carrying out laser hyperthermia of blood vessels, fat cells and other components with high-intensity laser radiation with surface cooling, while the specified temperature at a given tissue depth is provided by controlling the laser radiation power, and regulating the skin temperature in the zone irradiation at the required level is ensured by simultaneously changing the flow rate of the liquid spine, and power control of the laser radiation [Application US 2004/0073079 A1, publ. 04/15/2004]. An important circumstance taken into account in the entire spectrum of applications of this device is protection against overheating of the upper layers of the dermis, for which the skin temperature is continuously measured, including when irradiating large surfaces with a shift of the hyperthermia zone along any direction.

The disadvantage of this method is the lack of consideration of possible irregularities in tissue heating caused, inter alia, by an unequal dose level of the reported tissue when the heating zone is shifted. Another disadvantage of this method is the narrow orientation of the temperature control to "not exceed" a certain critical temperature on the skin surface, and the exposure mode for the destruction of the "targets" is selected from those recommended before irradiation, which makes it impossible to dynamically adjust the depth and degree of exposure during irradiation.

The problem to which the invention is directed, is to create a device and method for conducting photodynamic therapy and laser hyperthermia.

The technical result achieved by the implementation of the claimed invention is to increase the effectiveness of hyperthermia and PDT of malignant neoplasms located under the skin or in soft tissues, due to:

allowance for possible uneven heating of the irradiated tissue region,

the ability to control the position of the temperature gradient in the depth of the tissue during irradiation,

more efficient delivery of laser radiation directly to the neoplasm,

minimizing skin damage in the irradiation zone,

a significant reduction in pain when using high laser radiation powers,

more accurate location of the irradiating fiber relative to the subcutaneous nodular tumor.

The specified technical result is achieved due to the fact that the device for carrying out laser hyperthermia and / or photodynamic therapy, including a laser radiation source, a fiber connected to it, a cooling unit for contact cooling of the tissue surface, means for supplying a cooling liquid, a temperature recording device, including an infrared camera connected to the means of display and processing of information associated with the source of laser radiation and means for supplying coolant, while The information processing is arranged to calculate the temperature at a given depth directly below the cooling unit by the temperature value on the fabric surface along the perimeter of the device of the cooling unit and / or at a certain distance from it, with the ability to control the power of the laser radiation source and the feed rate of the coolant by means of supply coolant, depending on the result of the calculation.

The presence of means for displaying and processing information associated with the laser radiation source and means for supplying coolant to the cooling zone, while the information processing means is configured to calculate the temperature at a given depth by temperature parameters on the surface of the fabric and with the ability to control the power of the laser radiation source and speed coolant supply, depending on the calculation result, allows you to control the process of heating the fabric to a predetermined depth in the car In the mathematical mode, taking into account the possible uneven heating of the irradiated tissue area, the cooling unit is made in the form of a sealed box with two sapphire windows - upper and lower, between which there is a cavity for the coolant supplied by the coolant supply means, the optical fiber is mounted with the possibility of mounting on an airtight box with a sleeve on a threaded connection.

In addition, the information display and processing means comprises a dose display device.

In addition, the optical fiber contains at least one radiation-delivering optical fiber and at least one diagnostic fiber connected to a spectroscopic diagnostic tool.

The technical result is also achieved due to the fact that the method of carrying out laser hyperthermia and photodynamic therapy involves irradiating the tissue with laser radiation while cooling the irradiated tissue, while during the irradiation of the tissue surface and / or cooling of the tissue surface, the temperature on the tissue surface is continuously recorded around the perimeter of the cooling unit at a certain distance from it, the temperature of the coolant entering the cooling unit, the temperature of the coolant at the outlet of the cool the waiting unit, after which, using the measured temperature values, the temperature is calculated directly below the cooling unit at a predetermined depth, and then the temperature under the cooling unit is changed at a predetermined depth to the desired temperature by changing the laser radiation power and / or coolant supply speed in accordance with with the given algorithm.

In addition, the tissue is irradiated with the constant laser radiation necessary for the PDT method. During photodynamic therapy, the total dose of laser radiation per unit volume at the required depth is calculated, which is the main parameter of PDT.

In addition, the temperature measurement on the surface of the fabric around the perimeter of the cooling unit and / or at a certain distance from it, the temperature of the cooling liquid entering the cooling unit, the temperature of the cooling liquid at the outlet of the cooling unit is carried out by means of an infrared camera connected to the information display and processing means .

In addition, spectroscopic diagnostics is carried out during laser hyperthermia and photodynamic therapy.

The proposed device and method are illustrated by the following drawings:

figure 1 - Device for laser hyperthermia and / or photodynamic therapy.

figure 2 - Display of a temperature registration system with markings for calculating temperatures with markers to determine the temperature of the coolant (2) and the temperature in the vicinity of the sapphire window of the cooling unit (3).

figure 3 - Options for the location and shape of the markers linear (1, 2), zone (3), dual-zone (4).

figure 4 - Adaptive control in a closed loop.

A device for carrying out laser hyperthermia and photodynamic therapy of subcutaneous neoplasms (Fig. 1) contains a laser source 1, a light guide 2, a cooling unit 3, including a sealed box 9 with lower and upper sapphire windows 4 and 4a, a sleeve 11 and a threaded connection 12, means for supplying coolant 5. The distal end of the light guide 2 is perpendicular to the upper sapphire window 4 of the cooling unit 3. The light guide 2 may include at least one radiating optical fiber 2a and at least re, one diagnostic optical fiber 2b connected to a spectroscopic diagnostic tool 10. The device also includes a temperature recording device 6, including an infrared camera 7 and information display and processing means 8. Information display and processing means 8 is connected to a laser radiation source 1 and a supply means coolant 5. The light guide 2 is mounted on an airtight box 9 by a sleeve 11 by means of a threaded connection 12.

The proposed device operates as follows: on the tissue surface above the irradiated tumor node, a cooling unit 3 is installed so that the sapphire window 4 of the airtight box 9 is firmly pressed against the surface of the fabric, and the surface of the fabric is pre-cooled by applying coolant 5 to the cavity between the two sapphire windows 4 and 4a of the airtight box 9. After cooling the surface of the fabric, it is irradiated through sapphire windows 4 and 4a with an optical fiber of the light guide 2a connected to the source laser radiation 1. In this case, the area of irradiation and / or cooling of the tissue surface is located in the field of view of the infrared camera 7, which records the temperature of the tissue, along the perimeter of the cooling unit 3 and / or in the area located near the irradiation zone. The image of the infrared camera, each pixel of which carries information about the temperature of the object, is transmitted to the means for processing and displaying information 8. The means for processing and displaying information 8 according to the values of the maximum or average temperature along the markers assigned by the operator in the image (figure 2) and the current power level of the continuous laser radiation, taking into account its wavelength according to a given algorithm, calculates the current temperature value at the desired exposure depth. Temperature markers near the cooling unit, depending on the irradiation conditions, can be specified linear, zone, dual-zone (figure 3). Next, control the power of the laser radiation and / or the flow rate of the coolant in such a way as to ensure that the current temperature is equal to the desired temperature for heating the fabric at a given depth. The diameter of the laser spot under the window 4 is controlled by displacing the sleeve 11 in the threaded connection 12. The diagnostic optical fiber 2a transmits the optical signal from the irradiation zone to the spectroscopic diagnostic tool 10, where it is processed by assessing the biochemical state / composition of the tissue to plan further therapeutic exposure, control the correct choice of the position of the optical fiber 2 relative to the biological tissue.

An example implementation of the control method is illustrated in figure 4. Adaptive closed loop control is implemented. Preliminarily, the doctor sets the data, such as the required temperature (To) at the desired tissue warming depth (Lo). Next, the system starts, while controlling the laser radiation source 1 and the coolant supply speed is performed by the information processing and display device 8. Laser radiation of a certain power (P) is supplied to the exposure area. Next, the biological tissue 14 is heated to a certain temperature (T ₁ ), which is recorded by the IR camera 7.

In the process of heating the biological tissue 14, the information processing and display means 8 measures temperatures along the markers, the applied laser radiation power (P), and also the flow rate of the coolant. Based on these data, a mathematical model is constructed for the heating of biological tissue in the input / output variables in the identifier. The identifier 8a is part of the information processing and display device 8 and can be implemented both software and hardware. Further, the data on the obtained model by identifier 8a is transferred to optimizer 8b, in which, in accordance with the model of the biological tissue heating process, the required laser radiation power (P) and the refrigerant supply speed (V) necessary to achieve a preset temperature (T0) at a given depth (L0 ) After the necessary calculations, the optimizer sets the necessary laser power and coolant speed to achieve the preset parameters. Next, the cycle repeats first.

The proposed method is illustrated by the following example.

Example. Patient M. 70 l. Diagnosis: cancer of the right breast, combined treatment in 2000. Relapse of the disease in 2007, in the area of the right shoulder joint, the formation of 3 × 3 × 1 mm, axillary area on the right 5 neoplasms up to 4-5 mm in size, in the area of the scar scar 6 neoplasms up to 3-4 mm, only twelve . Four PDT sessions were conducted with the Photosens drug (a mixture of sodium salts of di-, tri- and tetrasulfophthalocyanine hydroxyaluminium) in conjunction with hyperthermia for intravenous chest metastases on the right and shoulder.

Four irradiation sessions were carried out using the inventive device (for interstitial laser hyperthermia and photodynamic therapy) in the mode of simultaneous hyperthermia with laser radiation with a wavelength of 810 nm - a laser radiation power of 6 W and photodynamic therapy with a radiation wavelength of 630 nm - a laser radiation power of 0.8 W . As a result of four sessions of percutaneous irradiation, the skin over the tumor was not changed; partial regression of the tumor was achieved with long-term stabilization of the process.

Thus, the above information indicates that the inventive device for interstitial laser hyperthermia and photodynamic therapy and the method of their implementation have advantages compared with the known means of treating similar diseases. Using in clinical practice the inventive device and method allows to achieve the following positive therapeutic results:

- apply various tactics for treating a nodular tumor, requiring control (movement) of the thermal gradient inside the tissue, for example, sequential thermal damage to the tumor bed with the subsequent rise of the maximum induced temperature to the surface for thermal damage to the node;

- reduce the duration of a session of photodynamic therapy and hyperthermia in conditions of applying high laser radiation power to 0.8-1 W with PDT and 6-8 W with hyperthermia at the output of the fiber;

- eliminate thermal damage to inhomogeneous tissues in the zone of laser exposure and its halo in the tissues with given parameters of radiation power;

- to achieve the full therapeutic dose of light exposure when exposed to a tumor of large volume for 1-4 sessions of exposure.

Thus, a device and method for carrying out hyperthermia and photodynamic therapy of malignant tumors by contact method have been proposed, which can significantly increase the effectiveness of carrying out hyperthermia and PDT of malignant neoplasms located under the skin or in soft tissues.

Claims (8)

1. A device for carrying out laser hyperthermia and photodynamic therapy, including a laser irradiation source, a light guide connected thereto, a cooling unit for contact cooling of a tissue surface, a coolant supply means, a temperature recording device, characterized in that the temperature recording device includes an infrared camera connected to the means for displaying and processing information associated with the laser radiation source and the coolant supply means, the cooling unit it is made in the form of a sealed unit with two sapphire windows, between which there is a cavity for supplying coolant supplied by means of supplying coolant, the fiber is mounted with the possibility of fastening on a sealed box by a sleeve by means of a threaded connection, and the means for displaying and processing information is configured to calculate the temperature at predetermined depth directly below the cooling unit and with the ability to control the power of the laser source and the cooling feed rate Liquids means for supplying coolant. 2. The device according to claim 1, characterized in that the means for displaying and processing information comprises a dose display device. 3. The device according to claim 1, characterized in that the optical fiber contains at least one radiation-delivering optical fiber and at least one diagnostic fiber. 4. The device according to claim 3, characterized in that the diagnostic fiber is associated with a spectroscopic diagnostic tool. 5. The method of carrying out laser hyperthermia and photodynamic therapy by irradiating the tissue with laser radiation and cooling the surface of the irradiated tissue while continuously recording the temperature on the tissue surface during irradiation and / or cooling and controlling the laser radiation power and the coolant supply speed, characterized in that the temperature is recorded on the fabric surface around the perimeter of the cooling unit of the device according to claim 1 and / or at a certain distance from it, the temperature of the coolant is recorded entering and leaving the cooling unit, after which the temperature directly below the cooling unit at a given depth is calculated from the measured temperature values and the temperature under the cooling unit at a specified depth is changed to the desired temperature by controlling the laser radiation power and / or coolant supply speed . 6. The method according to claim 5, characterized in that the irradiation of the tissue is carried out by constant laser radiation. 7. The method according to claim 5, characterized in that it further calculates the total dose of the applied laser radiation. 8. The method according to claim 5, characterized in that in the process of photodynamic therapy and laser hyperthermia, spectroscopic diagnostics are carried out.

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