CN110681070A - Photodynamic therapy light source capable of being regulated and controlled in personalized mode and regulation and control method - Google Patents

Photodynamic therapy light source capable of being regulated and controlled in personalized mode and regulation and control method Download PDF

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CN110681070A
CN110681070A CN201911063119.2A CN201911063119A CN110681070A CN 110681070 A CN110681070 A CN 110681070A CN 201911063119 A CN201911063119 A CN 201911063119A CN 110681070 A CN110681070 A CN 110681070A
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light source
illumination
photodynamic therapy
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刘丽娜
胡梦雪
李春林
林黎升
李步洪
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Fujian Normal University
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Abstract

The invention relates to a photodynamic therapy light source capable of being regulated and controlled in a personalized manner and a regulation and control scheme thereof. The light source can quantitatively detect the optical characteristic parameters of the lesion tissue and the concentration of a photosensitizer in the lesion tissue on the basis of identifying the shape and the size of a focus, evaluate the penetration depth and the yield of singlet oxygen of light with a specific wavelength in the lesion tissue, and realize the individualized regulation and control of the shape and the size of a light spot, the power of the light and the duration of the light of the photodynamic therapy laser according to the characteristics of the focus.

Description

Photodynamic therapy light source capable of being regulated and controlled in personalized mode and regulation and control method
Technical Field
The invention relates to the technical field of photodynamic therapy, in particular to a photodynamic therapy light source capable of being regulated and controlled in a personalized mode and a regulating and controlling method.
Background
Photodynamic therapy (PDT) is a targeted therapy technique in which a photosensitizer and molecular oxygen in target tissue undergo a series of photophysical and photochemical reactions to generate Reactive Oxygen Species (ROS) under illumination of specific wavelengths, thereby selectively damaging the target tissue. PDT has been widely used in the treatment of malignant tumors, skin diseases and infectious diseases due to its precise action, low toxic and side effects, and repeated treatments. The light source is one of the key elements of PDT treatment, and the luminous wavelength, the illumination mode and the illumination dose directly influence the curative effect. Laser light sources are widely used in current commercialized photodynamic therapy devices due to their monochromaticity, good directivity and high brightness. Different patients have different focus shapes and focus areas, and the regulation and control of the irradiation range and the irradiation power of photodynamic therapy light at target tissues is one of effective means for avoiding photodamage to surrounding normal tissues and realizing PDT accurate treatment.
At present, when photodynamic therapy illumination is clinically carried out, a single therapeutic light dose scheme is adopted mainly according to the subjective experience of doctors, and the photodynamic illumination is carried out by physically shielding normal tissues around focuses, so that the time-consuming non-precise treatment scheme hinders the application and popularization of PDT. How to adjust and control the personalized illumination range and the illumination dose according to the characteristics of different focuses is the best way for improving the PDT curative effect.
Disclosure of Invention
The invention provides a photodynamic therapy light source capable of being regulated and controlled in a personalized manner and a regulating and controlling method. On the basis of identifying the shape and the size of a focus, the optical characteristic parameters of a lesion tissue and the concentration of a photosensitizer in the lesion tissue are quantitatively detected, the penetration depth and the singlet oxygen yield of light with specific wavelength in the lesion tissue are evaluated, and the optimal regulation and control of the shape and the size of a light spot, the power of the light and the duration of the light of the photodynamic therapy laser light is realized.
The technical scheme adopted by the invention is as follows: a photodynamic therapy light source capable of being regulated and controlled in a personalized way, which is characterized in that: the device comprises a halogen tungsten lamp, a first filter wheel, a liquid crystal light pipe, a first half-transmitting half-reflecting mirror, a fluorescence excitation laser light source, a first diffuser, a second half-transmitting half-reflecting mirror, a photodynamic therapy laser light source, a second diffuser, a reflecting mirror, a digital micro-mirror array, a projection lens, a third half-transmitting half-reflecting mirror, lesion tissues, a second filter wheel, a CMOS camera and a computer; the light emitted by the halogen tungsten lamp forms uniform illumination to the first half-transmitting half-reflecting mirror through the first filter wheel and the liquid crystal light guide pipe; the fluorescence excitation laser light source emits light which passes through the first diffuser to form uniform light spots and irradiates the light to the second semi-transparent semi-reflective mirror, and the light is reflected to the first semi-transparent semi-reflective mirror by the second semi-transparent semi-reflective mirror; the light beam passing through the first half mirror is emitted to the digital micro-mirror array, is emitted to the third half mirror through the projection lens, is emitted to the lesion tissue, is reflected to the second filter wheel through the third half mirror, and is finally emitted to the CMOS camera; the CMOS camera transmits acquired image information to a computer, the computer sends a regulation and control instruction to the digital micromirror array and the photodynamic therapy laser light source, the digital micromirror array loads a focus shape image according to the computer instruction and regulates the micromirror array, the photodynamic therapy laser light source regulates and controls illumination power and illumination time according to the regulation and control instruction, light beams emitted by the photodynamic therapy laser light source are formed into uniform light spots through the second diffuser and then are emitted, and emitted laser sequentially passes through the reflector, the second semi-transparent semi-reflective mirror, the first semi-transparent semi-reflective mirror, the digital micromirror array, the projection lens and the third semi-transparent semi-reflective mirror to generate treatment illumination with specific power and light spot shapes on the surface of lesion tissues.
Further, the wavelength of the light emitted by the halogen tungsten lamp is 400-2200 nm.
Furthermore, the first filter wheel is provided with bandpass filters with different central wavelengths, and a light through hole without a filter is reserved, wherein the central wavelengths of the bandpass filters respectively correspond to the optimal excitation wavelength and the optimal emission wavelength of the fluorescence of the photosensitizer.
Further, the wavelength of the fluorescence excitation laser light source corresponds to the optimal excitation wavelength of the photosensitizer.
Further, the wavelength of the photodynamic therapy laser light source is determined according to the molar extinction coefficient and the absorption peak of the photosensitizer.
Further, under the action of an electronic switch, the micro-mirror on the digital micro-mirror array can load a focus shape graph generated by computer processing, and light spots irradiated on the micro-mirror array form light spots with the same shape as the focus and are reflected to the projection lens; the projection lens projects the light spots on the surface of the focus to form photodynamic illumination with a specific light spot shape.
Furthermore, the second filter wheel is provided with a long-wave pass filter and a light-passing hole without a filter is reserved, and the light-passing wavelength of the long-wave pass filter is larger than that of the fluorescence excitation laser light source.
The invention relates to a method for regulating a photodynamic therapy light source capable of being regulated in a personalized manner, which comprises the following steps:
step 1): turning on a halogen tungsten lamp, rotating a first filter wheel and a second filter wheel to a light through hole without a filter, illuminating a pathological change tissue by light emitted by the halogen tungsten lamp, acquiring a white light image of the pathological change tissue to be detected by a CMOS (complementary metal oxide semiconductor) camera, performing binarization processing of automatic threshold selection on the obtained white light image to obtain the shape and size of a focus, and determining the shape and size of the focus as the shape and size of a light spot for treating illumination;
step 2): keeping the halogen tungsten lamp on, rotating the first filter wheel to a band-pass filter with the central wavelength same as the fluorescence excitation wavelength of the photosensitizer, and adopting a specific spatial frequency (f)x,fy) Different phases theta ═ 0,2 pi/3, 4 pi/3]The structured light irradiates analog liquid with known optical parameters, and three diffuse reflection light images I of the analog liquid are obtained by a CMOS camera1,I2,I3
Step 3): using the same step 2), obtaining the lesion tissue to be measuredMAC,sample(x,y,fx,fy) From the modulation function M of the diseased tissueAC,sample(x,y,fx,fy) Modulation function M of analog liquid with known optical characteristicsAC,ref(x,y,fx,fy) The ratio is multiplied by the known diffuse reflectance Rd,refObtaining the real reflectivity R of the tissue after calibrationd,ex
Figure BDA0002256207180000032
Step 4): rotating the first filter wheel to a band-pass filter with the central wavelength being the same as the fluorescence emission wavelength of the photosensitizer, and obtaining the diffuse reflectance R of the lesion tissue by the same step 3)d,em
Step 5): obtaining optical characteristic parameters of the lesion tissue at the fluorescence excitation wavelength and the fluorescence emission wavelength by adopting a table look-up method, using the obtained optical characteristic parameters for mathematical simulation, and determining the penetration depth of the therapeutic light and the light energy of the specific therapeutic depth;
step 6): turning off the halogen tungsten lamp, injecting photosensitizer into the pathological change tissue, turning on the fluorescence excitation laser light source when the photosensitizer is accumulated in the pathological change tissue, rotating the second filter wheel to the long-wave pass filter capable of filtering fluorescence excitation laser signals, carrying out fluorescence imaging on the pathological change tissue, and obtaining a fluorescence image FmeasuredIntrinsic fluorescence information of diseased tissue Fintrinsic
Figure BDA0002256207180000034
Photosensitizer concentration [ PS ] of diseased tissue is linear with intrinsic fluorescence intensity and is expressed as:
Figure BDA0002256207180000035
wherein Qex,emIs the fluorescence quantum yield, epsilon, of the photosensitizer under excitation of the corresponding excitation wavelengthex,emIs the molar extinction coefficient of the photosensitizer under the excitation of the corresponding excitation wavelength; performing mathematical simulation by using the measured concentration of the photosensitizer, calculating to obtain the singlet oxygen yield changing along with time, and determining the power required by therapeutic illumination and the illumination time;
step 7): and (3) starting a photodynamic therapy laser light source, adjusting the power of the therapy illumination through a computer according to the determined shape and size of the image of the therapy illumination, the power of the therapy illumination and the time of the therapy illumination, sending the projected image to the digital micromirror array, generating illumination consistent with the shape and size of the focus, and projecting the illumination to the surface of the lesion tissue.
The invention has the beneficial effects that: in the process of photodynamic therapy of diseases, a white light image, a spatial frequency domain diffuse reflection image and a fluorescence image are captured in sequence, the shape and the area of a focus are identified by adopting the white light image, an optical characteristic parameter of a tissue is obtained by adopting the diffuse reflection image, the obtained optical characteristic parameter is adopted to correct the fluorescence image to quantitatively obtain the concentration of a photosensitizer in a lesion tissue, the penetration depth of a specific illumination wavelength in the lesion tissue and the yield of generated singlet oxygen can be evaluated, and the shape and the size of a light spot irradiated by photodynamic therapy laser, the power of illumination and the duration of illumination are optimized and controlled. The invention has high cost performance and convenient use, and is expected to be popularized and applied in the field of clinical photodynamic therapy.
Drawings
The invention will be explained in further detail below with reference to the drawing,
FIG. 1 is a schematic view of a light source structure of photodynamic therapy that can be modulated individually according to the present invention;
in the figure: 1-halogen tungsten lamp, 2-first filter wheel, 3-liquid crystal light pipe, 4-first half mirror, 5-fluorescence excitation laser light source, 6-first diffuser, 7-second half mirror, 8-photodynamic therapy laser light source, 9-second diffuser, 10-reflector, 11-digital micro-mirror array, 12-projection lens, 13-third half mirror, 14-second filter wheel, 15-CMOS camera, 16-computer, 17-pathological change tissue;
FIG. 2 is a flow chart of a method for regulating a light source for photodynamic therapy, which is capable of being regulated individually.
Detailed Description
The invention is further explained below with reference to the drawings and the embodiments.
Referring to fig. 1, the present invention provides a photodynamic therapy light source capable of being individually controlled, which includes a tungsten halogen lamp 1, a first filter wheel 2, a liquid crystal light pipe 3, a first half mirror 4, a digital micromirror array 11, a projection lens 12, a third half mirror 13, a lesion tissue 17, a second filter wheel 14, a CMOS camera 15, a computer 16, a fluorescence excitation laser light source 5, a first diffuser 6, a second half mirror 7, a photodynamic therapy laser light source 8, a second diffuser 9, and a reflector 10. The light emitted by the halogen tungsten lamp 1 is emitted into the first half mirror 4 through the first filter wheel 2 and the liquid crystal light pipe 3, then is emitted to the digital micro-mirror array 11, is emitted to the third half mirror 13 through the projection lens 12, is reflected to the lesion tissue 17, then is reflected to the second filter wheel 14 through the third half mirror 13, and is collected into focus white light images and diffuse reflection images through the CMOS camera 15; the fluorescence excitation laser light source 5 emits light which is homogenized through the first diffuser 6, the homogenized laser is reflected to the first half mirror 4 through the second half mirror 7, is emitted to the digital micro-mirror array 11, is emitted to the third half mirror 13 through the projection lens 12, is emitted to the lesion tissue 17 to excite the photosensitizer fluorescence in the lesion tissue, the fluorescence is reflected to the second filter wheel 14 through the third half mirror 13, and the fluorescence image is collected by the CMOS camera 15; the collected white light image is processed by the computer 16 and then sent to the digital micro-mirror array 11, and the focus shape is projected by the projection lens 12; the collected diffuse reflection image and the fluorescence image are simulated by a computer 16 to obtain related data and regulate and control a photodynamic therapy laser light source 8, light emitted by the photodynamic therapy laser light source 8 is homogenized through a second diffuser 9, the homogenized laser is reflected to a second half mirror 7 through a reflecting mirror 10, then is emitted to a digital micro-mirror array 11 through a first half mirror 4, and is emitted to a third half mirror 13 through a projection lens 12 to be emitted to lesion tissues 17.
Referring to fig. 1 and fig. 2, the specific implementation manner of the regulation and control scheme of the photodynamic therapy light source capable of being regulated and controlled in the embodiment is as follows:
step 1): starting a halogen tungsten lamp (SLS201L, Thorlabs, USA), enabling a first filter wheel and a second filter wheel to rotate to a light through hole without a filter, enabling light emitted by the halogen tungsten lamp to pass through a liquid crystal light guide tube (LLG03-4H, Thorlabs, USA) and then illuminate lesion tissues, acquiring a white light image of the lesion tissues to be detected through a CMOS camera (PCO. EDGE5.5, PCO, German), and performing binarization processing of automatic threshold selection on the acquired white light image to obtain the shape and size of a focus, and determining the shape and size of the focus as the shape and size of a light spot irradiated for treatment;
step 2): the tungsten halogen lamp was kept on and the first filter wheel was rotated to a bandpass filter (FB405-10, Thorlabs, USA) having a center wavelength of 405nm, with the same wavelength as the excitation wavelength of the photosensitizer fluorescence. Forming a rectangular spot of 12mm × 9mm on a digital micromirror array (0.45WXGA, TI, USA); simultaneously, the computer programming software generates a structured light image with a sinusoidal pattern as shown in formula (1) and loads the structured light image on the digital micromirror array,
Figure BDA0002256207180000051
wherein S is0Is the intensity of the illumination source, fxAnd fySpatial frequencies in the x and y directions, M, respectively0Is the modulation depth and phi is the spatial phase, at first imaging
Figure BDA0002256207180000056
Structured light with certain frequency reflected by the surface of the digital micromirror array is irradiated on analog liquid with known optical characteristic parameters through a projection assembly, a projection lens is 150mm away from an analog liquid sample, the projection area is 40mm multiplied by 30mm, and a CMOS camera (PCO. EDGE5.5, PCO, German) collects diffuse reflection light images I of the sample1And sending the data to a computer for processing. Respectively changing the phase
Figure BDA0002256207180000055
2 pi/3 and 4 pi/3, and repeating the above steps to collect diffuse reflection light image I2And I3. The collected diffuse reflectance image contains dc and ac components, which can be expressed as:
wherein M isACIs the modulation amplitude, and can be calculated according to equation (2):
Figure BDA0002256207180000053
step 3): using the same step 2) as above, obtaining M of the lesion tissue to be measuredAC,sample(x,y,fx,fy) From the modulation function M of the diseased tissueAC,sample(x,y,fx,fy) Modulation function M of analog liquid with known optical characteristicsAC,ref(x,y,fx,fy) The ratio is multiplied by the known diffuse reflectance Rd,refObtaining the real reflectivity R of the tissue after calibrationd,405
Figure BDA0002256207180000054
Step 4): the same procedure was used to obtain diffuse reflectance R of the diseased tissue by rotating the first filter wheel to a bandpass filter (FB620-10, Thorlabs, USA) centered at 620nmd,620
Figure BDA0002256207180000061
Step 5): and obtaining optical characteristic parameters of the lesion tissue at the fluorescence excitation wavelength and the fluorescence emission wavelength by adopting a table look-up method. Using the obtained optical characteristic parameters for mathematical simulation, and determining the penetration depth of the therapeutic light and the light energy of a specific therapeutic depth;
step 6): the halogen tungsten lamp is turned off, the photosensitizer HMME is injected into the tissue, after the HMME is accumulated in the lesion tissue,an LD light source (LaserBoxx405, Oxxius, France) is turned on, and a light beam emitted by the laser light source is homogenized by a first diffuser (ED1-S20, Thorlabs, USA) to form a uniform rectangular light spot to be emitted on the digital micromirror array. Structured light with certain frequency reflected by the surface of the digital micromirror array is irradiated on lesion tissues through a projection module, a second filter wheel rotates to a long-wave pass filter (FELH0450, Thorlabs, USA) capable of filtering fluorescence excitation laser signals, and a CMOS camera acquires a fluorescence image FmeasuredSending to a computer, and calculating intrinsic fluorescence information F in the lesion tissue according to the formula (6)intrinsic
Figure BDA0002256207180000062
Photosensitizer concentration [ PS ] within the diseased tissue is linear with intrinsic fluorescence intensity and is expressed as:
Figure BDA0002256207180000063
wherein Q405,620Is the fluorescence quantum yield, ε, of HMME excited at 405nm excitation wavelength405,620Is the molar extinction coefficient of HMME under excitation at an excitation wavelength of 405 nm. Performing mathematical simulation by using the measured concentration of the photosensitizer, calculating to obtain the singlet oxygen yield changing along with time, and determining the power required by therapeutic illumination and the illumination time;
step 7): starting a photodynamic therapy laser light source (HPL-532-CW, New Enchangchun industry, electro-optic technology, Inc., China), adjusting the power of the therapy illumination through a computer according to the determined shape and size of the image of the therapy illumination, the power of the therapy illumination and the time of the therapy illumination, sending the projected image to a digital micro-mirror array, generating illumination consistent with the shape and size of a focus, and projecting the illumination to the surface of a lesion tissue.
The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the present invention.

Claims (8)

1. A photodynamic therapy light source capable of being regulated and controlled in a personalized way, which is characterized in that: the device comprises a halogen tungsten lamp, a first filter wheel, a liquid crystal light pipe, a first half-transmitting half-reflecting mirror, a fluorescence excitation laser light source, a first diffuser, a second half-transmitting half-reflecting mirror, a photodynamic therapy laser light source, a second diffuser, a reflecting mirror, a digital micro-mirror array, a projection lens, a third half-transmitting half-reflecting mirror, lesion tissues, a second filter wheel, a CMOS camera and a computer; the light emitted by the halogen tungsten lamp forms uniform illumination to the first half-transmitting half-reflecting mirror through the first filter wheel and the liquid crystal light guide pipe; the fluorescence excitation laser light source emits light which passes through the first diffuser to form uniform light spots and irradiates the light to the second semi-transparent semi-reflective mirror, and the light is reflected to the first semi-transparent semi-reflective mirror by the second semi-transparent semi-reflective mirror; the light beam passing through the first half mirror is emitted to the digital micro-mirror array, is emitted to the third half mirror through the projection lens, is emitted to the lesion tissue, is reflected to the second filter wheel through the third half mirror, and is finally emitted to the CMOS camera; the CMOS camera transmits acquired image information to a computer, the computer sends a regulation and control instruction to the digital micromirror array and the photodynamic therapy laser light source, the digital micromirror array loads a focus shape image according to the computer instruction and regulates the micromirror array, the photodynamic therapy laser light source regulates and controls illumination power and illumination time according to the regulation and control instruction, light beams emitted by the photodynamic therapy laser light source are formed into uniform light spots through the second diffuser and then are emitted, and emitted laser sequentially passes through the reflector, the second semi-transparent semi-reflective mirror, the first semi-transparent semi-reflective mirror, the digital micromirror array, the projection lens and the third semi-transparent semi-reflective mirror to generate treatment illumination with specific power and light spot shapes on the surface of lesion tissues.
2. The personalizable modulatable photodynamic therapy light source of claim 1, characterized in that: the wavelength of the light emitted by the halogen tungsten lamp is 400-2200 nm.
3. The personalizable modulatable photodynamic therapy light source of claim 1, characterized in that: the first filter wheel is provided with bandpass filters with different central wavelengths, and a light through hole without a filter is reserved, wherein the central wavelengths of the bandpass filters respectively correspond to the optimal excitation wavelength and the optimal emission wavelength of the fluorescence of the photosensitizer.
4. The personalizable modulatable photodynamic therapy light source of claim 1, characterized in that: the wavelength of the fluorescence excitation laser light source corresponds to the optimal excitation wavelength of the photosensitizer.
5. The personalizable modulatable photodynamic therapy light source of claim 1, characterized in that: the wavelength of the photodynamic therapy laser light source is determined according to the molar extinction coefficient and the absorption peak of the photosensitizer.
6. The personalizable modulatable photodynamic therapy light source of claim 1, characterized in that: under the action of an electronic switch, the micro-mirror on the digital micro-mirror array can load a focus shape graph generated by computer processing, and light spots irradiated on the micro-mirror array form light spots with the same shape as the focus and are reflected to the projection lens; the projection lens projects the light spots on the surface of the focus to form photodynamic illumination with a specific light spot shape.
7. The personalizable modulatable photodynamic therapy light source of claim 1, characterized in that: and the second filter wheel is provided with a long-wave pass filter and a light through hole without the filter, and the light through wavelength of the long-wave pass filter is greater than that of the fluorescence excitation laser light source.
8. The method for regulating a light source for photodynamic therapy according to any one of claims 1 to 7, wherein: which comprises the following steps:
step 1): turning on a halogen tungsten lamp, rotating a first filter wheel and a second filter wheel to a light through hole without a filter, illuminating a pathological change tissue by light emitted by the halogen tungsten lamp, acquiring a white light image of the pathological change tissue to be detected by a CMOS (complementary metal oxide semiconductor) camera, performing binarization processing of automatic threshold selection on the obtained white light image to obtain the shape and size of a focus, and determining the shape and size of the focus as the shape and size of a light spot for treating illumination;
step 2): keeping the halogen tungsten lamp on, rotating the first filter wheel to a band-pass filter with the central wavelength same as the fluorescence excitation wavelength of the photosensitizer, and adopting a specific spatial frequency (f)x,fy) Different phases theta ═ 0,2 pi/3, 4 pi/3]The structured light irradiates analog liquid with known optical parameters, and three diffuse reflection light images I of the analog liquid are obtained by a CMOS camera1,I2,I3
Figure FDA0002256207170000021
Step 3): the same step 2) is adopted to obtain M for the pathological change tissue to be detectedAC,sample(x,y,fx,fy) From the modulation function M of the diseased tissueAC,sample(x,y,fx,fy) Modulation function M of analog liquid with known optical characteristicsAC,ref(x,y,fx,fy) The ratio is multiplied by the known diffuse reflectance Rd,refObtaining the real reflectivity R of the tissue after calibrationd,ex
Figure FDA0002256207170000022
Step 4): rotating the first filter wheel to a band-pass filter with the central wavelength being the same as the fluorescence emission wavelength of the photosensitizer, and obtaining the diffuse reflectance R of the lesion tissue by the same step 3)d,em
Figure FDA0002256207170000023
Step 5): obtaining optical characteristic parameters of the lesion tissue at the fluorescence excitation wavelength and the fluorescence emission wavelength by adopting a table look-up method, using the obtained optical characteristic parameters for mathematical simulation, and determining the penetration depth of the therapeutic light and the light energy of the specific therapeutic depth;
step 6): turning off halogen tungsten lamp, injecting into pathological tissueIrradiating photosensitizer, starting a fluorescence excitation laser light source when the photosensitizer is accumulated in the pathological change tissue, rotating a second filter wheel to a long-wave pass filter capable of filtering fluorescence excitation laser signals, carrying out fluorescence imaging on the pathological change tissue, and obtaining a fluorescence image FmeasuredIntrinsic fluorescence information of diseased tissue Fintrinsic
Figure FDA0002256207170000024
Photosensitizer concentration [ PS ] of diseased tissue is linear with intrinsic fluorescence intensity and is expressed as:
Figure FDA0002256207170000031
wherein Qex,emIs the fluorescence quantum yield, epsilon, of the photosensitizer under excitation of the corresponding excitation wavelengthex,emIs the molar extinction coefficient of the photosensitizer under the excitation of the corresponding excitation wavelength; performing mathematical simulation by using the measured concentration of the photosensitizer, calculating to obtain the singlet oxygen yield changing along with time, and determining the power required by therapeutic illumination and the illumination time;
step 7): and (3) starting a photodynamic therapy laser light source, adjusting the power of the therapy illumination through a computer according to the determined shape and size of the image of the therapy illumination, the power of the therapy illumination and the time of the therapy illumination, sending the projected image to the digital micromirror array, generating illumination consistent with the shape and size of the focus, and projecting the illumination to the surface of the lesion tissue.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111701145A (en) * 2020-06-23 2020-09-25 山西医科大学 Photodynamic therapy device for oncology department
CN115253090A (en) * 2022-09-30 2022-11-01 北京心联光电科技有限公司 Photodynamic therapy equipment at somatic cell level
CN117797362A (en) * 2024-01-10 2024-04-02 北京大学口腔医学院 Photosensitive therapeutic device and assembling method thereof

Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000071019A1 (en) * 1999-05-23 2000-11-30 Velde Frans J Van De Scanning laser ophthalmoscope for selective therapeutic laser
CN101101613A (en) * 2007-08-06 2008-01-09 天津炜辐医疗科技有限公司 Photodynamic therapy plot software
CN101268964A (en) * 2007-03-20 2008-09-24 深圳市微创医学科技有限公司 Optical power therapentic equipment with fluorescence diagnostic function and operation method
CN101269257A (en) * 2007-03-20 2008-09-24 深圳市微创医学科技有限公司 Optical power therapentic equipment
CN101862510A (en) * 2010-05-12 2010-10-20 中国科学院半导体研究所 Two-photon excitation based tumor diagnosis and photodynamic tumor-treatment instrument
US20130053699A1 (en) * 2011-08-30 2013-02-28 National Applied Research Laboratories Instrument Technology Research Center Apparatus and method for performing photodynamic diagnosis and photodynamic therapy
CN103933671A (en) * 2014-04-22 2014-07-23 天津大学 Precision photodynamic therapy system
CN203728848U (en) * 2014-01-22 2014-07-23 浙江大学 Device for generating ultraviolet (UV) stimulation array for nerve cells
RU2013156699A (en) * 2013-12-19 2015-06-27 государственное бюджетное образовательное учреждение высшего профессионального образования "Северо-Западный государственный медицинский университет им. И.И. Мечникова" Министерства здравоохранения Российской Федерации METHOD FOR TREATING PATIENTS WITH PERIODONTITIS
CN205268849U (en) * 2015-12-14 2016-06-01 中国医学科学院生物医学工程研究所 Antibiotic photosensitive therapeutic instrument
CN105664379A (en) * 2016-03-02 2016-06-15 中国人民解放军第四军医大学 Deep tumor treatment system for photodynamic combined radiotherapy
CN106687176A (en) * 2014-04-29 2017-05-17 锡拉莱斯科技有限公司 Apparatus and method for multiwavelength photodynamic therapy
CN107329280A (en) * 2008-09-25 2017-11-07 纽约市哥伦比亚大学托管会 Device, the apparatus and method of light stimulus and structure imaging are provided
US20190064736A1 (en) * 2017-08-08 2019-02-28 California Institute Of Technology Focusing light inside scattering media with magnetic particle guided wavefront shaping
CN109497959A (en) * 2019-01-11 2019-03-22 福建师范大学 A kind of fluoroscopic imaging systems and method of quantitative detection photosensitizer spatial distribution
CN209108426U (en) * 2017-12-29 2019-07-16 深圳开立生物医疗科技股份有限公司 A kind of endoscope apparatus

Patent Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000071019A1 (en) * 1999-05-23 2000-11-30 Velde Frans J Van De Scanning laser ophthalmoscope for selective therapeutic laser
CN101268964A (en) * 2007-03-20 2008-09-24 深圳市微创医学科技有限公司 Optical power therapentic equipment with fluorescence diagnostic function and operation method
CN101269257A (en) * 2007-03-20 2008-09-24 深圳市微创医学科技有限公司 Optical power therapentic equipment
CN101101613A (en) * 2007-08-06 2008-01-09 天津炜辐医疗科技有限公司 Photodynamic therapy plot software
CN107329280A (en) * 2008-09-25 2017-11-07 纽约市哥伦比亚大学托管会 Device, the apparatus and method of light stimulus and structure imaging are provided
CN101862510A (en) * 2010-05-12 2010-10-20 中国科学院半导体研究所 Two-photon excitation based tumor diagnosis and photodynamic tumor-treatment instrument
US20130053699A1 (en) * 2011-08-30 2013-02-28 National Applied Research Laboratories Instrument Technology Research Center Apparatus and method for performing photodynamic diagnosis and photodynamic therapy
RU2013156699A (en) * 2013-12-19 2015-06-27 государственное бюджетное образовательное учреждение высшего профессионального образования "Северо-Западный государственный медицинский университет им. И.И. Мечникова" Министерства здравоохранения Российской Федерации METHOD FOR TREATING PATIENTS WITH PERIODONTITIS
CN203728848U (en) * 2014-01-22 2014-07-23 浙江大学 Device for generating ultraviolet (UV) stimulation array for nerve cells
CN103933671A (en) * 2014-04-22 2014-07-23 天津大学 Precision photodynamic therapy system
CN106687176A (en) * 2014-04-29 2017-05-17 锡拉莱斯科技有限公司 Apparatus and method for multiwavelength photodynamic therapy
CN205268849U (en) * 2015-12-14 2016-06-01 中国医学科学院生物医学工程研究所 Antibiotic photosensitive therapeutic instrument
CN105664379A (en) * 2016-03-02 2016-06-15 中国人民解放军第四军医大学 Deep tumor treatment system for photodynamic combined radiotherapy
US20190064736A1 (en) * 2017-08-08 2019-02-28 California Institute Of Technology Focusing light inside scattering media with magnetic particle guided wavefront shaping
CN209108426U (en) * 2017-12-29 2019-07-16 深圳开立生物医疗科技股份有限公司 A kind of endoscope apparatus
CN109497959A (en) * 2019-01-11 2019-03-22 福建师范大学 A kind of fluoroscopic imaging systems and method of quantitative detection photosensitizer spatial distribution

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DAVID J. MANSUR等: "High dynamic range digital micromirror device-based", 《J. MICRO/NANOLITH. MEMS MOEMS》 *
万仁亮等: "光动力疗法中组织氧的测量技术", 《中国医学激光杂志》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111701145A (en) * 2020-06-23 2020-09-25 山西医科大学 Photodynamic therapy device for oncology department
CN111701145B (en) * 2020-06-23 2022-03-29 山西医科大学 Photodynamic therapy device for oncology department
CN115253090A (en) * 2022-09-30 2022-11-01 北京心联光电科技有限公司 Photodynamic therapy equipment at somatic cell level
CN117797362A (en) * 2024-01-10 2024-04-02 北京大学口腔医学院 Photosensitive therapeutic device and assembling method thereof

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