A Photodynamic Therapy Power Control Method and System
By collecting fluorescence emission spectrum and dual-ring control models in real time, dynamically adjusting the output power of excitation light source in photodynamic therapy, solving the problem of inaccurate light source power in photodynamic therapy, and achieving the accuracy and safety of the treatment effect.
Patent Information
- Application Number
- CN202510564409.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-30
- Publication Date
- 2025-07-11
- Estimated Expiration
- 2045-04-30
AI Technical Summary
In existing photodynamic therapy, the output power of the excitation light source is usually calculated using fixed values or empirical formulas, resulting in inaccurate power of the treatment light source, affecting the treatment effect and safety, and lacking real-time feedback on the dynamic changes in the treatment area.
By collecting the total fluorescence emission spectrum of the treatment area in real time, obtaining the fluorescence intensity of the photosensitizer and light products, building a dual-ring control model to dynamically adjust the output power of the excitation light source, and combining multi-dimensional monitoring to build a safety protection system.
Real-time matching of the light source output power and the treatment area is achieved, improving the accuracy and robustness of power control, and ensuring the safety and effectiveness of treatment.
Smart Images

Figure CN120079047B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of photodynamic therapy, and particularly relates to a method and system for controlling the power of photodynamic therapy. Background Art
[0002] Photodynamic therapy (PDT) is a treatment method that uses a photosensitizer and excitation light of a specific wavelength to act on a diseased tissue to generate reactive oxygen species (ROS) to kill diseased cells, and is widely used in the fields of tumor treatment and the like. However, in the existing photodynamic therapy process, the output power of the excitation light source is usually calculated by a fixed value or an empirical formula, resulting in inaccurate power of the treatment light source. This inaccuracy may reduce the treatment effect and may also cause side effects during the treatment process, affecting the safety of the treatment.
[0003] In view of the above problems, in recent years, researchers have tried to optimize the output power of the excitation light source during the treatment process by preset parameters such as the concentration of the photosensitizer and the treatment time. However, the existing photodynamic therapy still has deficiencies in monitoring the dynamic changes in the treatment area, especially lacking effective means for separating and quantifying the fluorescence intensities of the photosensitizer and the photoproducts. This deficiency results in the inability to provide real-time feedback on the dynamic changes in the treatment area, such as the excitation state of the photosensitizer, the generation state of the photoproducts, and the light absorption characteristics of the tissue, etc., making it difficult to match the output power of the light source with the real-time treatment requirements during the treatment process and difficult to achieve precise control of the output power of the light source. Summary of the Invention
[0004] The purpose of the present invention is to provide a method and system for controlling the power of photodynamic therapy, enabling the output power of the light source to dynamically match the real-time reaction state of the treatment area and improving the accuracy and robustness of power control.
[0005] In a first aspect, the present invention provides a method for controlling the power of photodynamic therapy, including the steps of:
[0006] Setting an initial value of the output power of the excitation light source, and starting the excitation light source to perform photodynamic therapy operations on the treatment area;
[0007] Real-time collecting the total fluorescence emission spectrum of the treatment area, and obtaining the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct according to the total fluorescence emission spectrum;
[0008] Adjusting the output power of the excitation light source according to the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct;
[0009] The obtaining the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct according to the total fluorescence emission spectrum includes the steps of:
[0010] Obtaining the background-normalized spectrum, the photosensitizer-normalized spectrum, and the photoproduct-normalized spectrum;
[0011] The background fluorescence emission spectrum is obtained based on the output power of the excitation light source and the background-normalized spectrum, and the fluorescence emission spectrum of the target is obtained by calculating the difference between the total fluorescence emission spectrum and the background fluorescence emission spectrum;
[0012] The fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct are obtained based on the photosensitizer-normalized spectrum, the photoproduct-normalized spectrum, and the fluorescence emission spectrum of the target.
[0013] As a preferred solution of the first aspect of the present invention, the obtaining of the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct based on the photosensitizer-normalized spectrum, the photoproduct-normalized spectrum, and the fluorescence emission spectrum of the target includes the steps of:
[0014] Construct a relationship model for the fluorescence emission spectrum of the target, the photosensitizer-normalized spectrum, and the photoproduct-normalized spectrum;
[0015] Construct an error function according to the relationship model, and solve for the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct through the error function.
[0016] As a preferred solution of the first aspect of the present invention, the relationship model is expressed as:
[0017] ;
[0018] Wherein, represents the fluorescence intensity of the fluorescence emission spectrum of the target at wavelength ; represents the fluorescence intensity coefficient of the photosensitizer-normalized spectrum at wavelength ; represents the fluorescence intensity coefficient of the photoproduct-normalized spectrum at wavelength ; is the fluorescence intensity of the photosensitizer, is the fluorescence intensity of the photoproduct; represents the error term;
[0019] The error function is expressed as:
[0020] ;
[0021] Wherein, represents the error function, and Q represents the set of characteristic wavelengths.
[0022] As a preferred solution of the first aspect of the present invention, the obtaining of the background fluorescence emission spectrum based on the output power of the excitation light source and the background-normalized spectrum is specifically:
[0023] The background fluorescence emission spectrum is calculated based on the background fluorescence linear compensation coefficient, the output power of the excitation light source, and the background-normalized spectrum; the background fluorescence emission spectrum is expressed as:
[0024] ;
[0025] Wherein, represents the fluorescence intensity of the background fluorescence emission spectrum at wavelength ; represents the background normalized spectrum, represents the background fluorescence linear compensation coefficient, represents the output power of the excitation light source.
[0026] As a preferred solution of the first aspect of the present invention, the background fluorescence linear compensation coefficient is obtained through the following steps:
[0027] S201. Set the test power of the excitation light source and irradiate the treatment area with the excitation light source;
[0028] S202. Capture the background fluorescence emission spectrum through multispectral imaging, and obtain the fluorescence intensity of the background characteristic peak according to the background fluorescence emission spectrum;
[0029] S203. Repeat steps S201 and S202 several times, and fit the background fluorescence linear compensation coefficient according to several test powers and their corresponding background characteristic peak fluorescence intensities.
[0030] As a preferred solution of the first aspect of the present invention, the adjustment of the output power of the excitation light source according to the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct includes the steps:
[0031] Output the adjustment amount of the output power of the excitation light source through a double-loop control model composed of an outer loop controlled by the photoproduct concentration and an inner loop controlled by the photosensitizer concentration; the input of the outer loop controlled by the photoproduct concentration is the deviation of the photoproduct fluorescence intensity, and the output is the target fluorescence intensity of the photosensitizer; the input of the inner loop controlled by the photosensitizer concentration is the deviation of the photosensitizer fluorescence intensity, and the output is the adjustment amount of the output power of the excitation light source.
[0032] As a preferred solution of the first aspect of the present invention, the outer loop controlled by the photoproduct concentration is expressed as:
[0033] ;
[0034] Wherein, represents the target fluorescence intensity of the photosensitizer, represents the deviation of the photoproduct fluorescence intensity, , and are the proportional, integral and differential coefficients of the outer loop controlled by the photoproduct concentration respectively;
[0035] The inner loop controlled by the photosensitizer concentration is expressed as:
[0036] ;
[0037] Among them, represents the adjustment amount of the output power of the excitation light source, represents the deviation of the fluorescence intensity of the photosensitizer, , and are respectively the proportional, integral and differential coefficients of the inner loop for controlling the concentration of the photosensitizer.
[0038] As a preferred solution of the first aspect of the present invention, the double-loop control model further includes a power adjustment amount constraint; the power adjustment amount constraint is expressed as:
[0039] ,
[0040] ,
[0041] Among them, is the reference temperature, which is set according to the tissue type of the treatment area; is the difference between the temperature of the treatment area and the reference temperature; is the current output power of the excitation light source; is the fitting constant.
[0042] As a preferred solution of the first aspect of the present invention, adjusting the output power of the excitation light source according to the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct further includes the steps of:
[0043] Triggering a fixed power mode or turning off the excitation light source according to the fluorescence intensity of the photosensitizer, the temperature of the treatment area and the blood oxygen saturation obtained in real time.
[0044] In a second aspect, the present invention also provides a photodynamic therapy power control system, including an excitation light source, a spectral acquisition module, a spectral processing module and a light source control module;
[0045] The spectral acquisition module is used to collect the total fluorescence emission spectrum of the treatment area in real time;
[0046] The spectral processing module is used to obtain the background-normalized spectrum, the photosensitizer-normalized spectrum and the photoproduct-normalized spectrum, obtain the background fluorescence emission spectrum according to the output power of the excitation light source and the background-normalized spectrum, calculate the difference between the total fluorescence emission spectrum and the background fluorescence emission spectrum to obtain the target fluorescence emission spectrum, and obtain the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct according to the photosensitizer-normalized spectrum, the photoproduct-normalized spectrum and the target fluorescence emission spectrum;
[0047] The light source control module is used to adjust the output power of the excitation light source according to the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct;
[0048] The excitation light source is used to perform photodynamic therapy operations on the treatment area according to the output power of the excitation light source.
[0049] The beneficial effects of the present invention are as follows:
[0050] The photodynamic therapy power control method of the present invention monitors the photodynamic reaction in the treatment area in real time by collecting the total fluorescence emission spectrum of the treatment area in real time. The background fluorescence emission spectrum is calculated through the output power of the excitation light source, so as to accurately separate the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct, and accurately evaluate the progress and effect of photodynamic therapy. By dynamically adjusting the output power of the excitation light source according to the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct, the output power of the light source can dynamically match the real-time reaction state of the treatment area, improving the accuracy and robustness of power control.
[0051] In the embodiment of the present invention, the adjustment amount of the output power of the excitation light source is output through a double-loop control model composed of an outer loop controlled by the concentration of the photoproduct and an inner loop controlled by the concentration of the photosensitizer, realizing hierarchical dynamic control, taking into account both the response speed and stability, and improving the smoothness and convergence of power adjustment.
[0052] In the embodiment of the present invention, a hierarchical safety protection system is constructed through multi-dimensional monitoring of the fluorescence intensity of the photosensitizer, the temperature of the treatment area, and the blood oxygen saturation, which can balance the efficacy and safety in complex treatment scenarios and provide reliable full-cycle protection for photodynamic therapy. BRIEF DESCRIPTION OF THE DRAWINGS
[0053] The drawings herein are incorporated into the specification and form a part of this specification, indicating the embodiments consistent with the present invention, and are used together with the specification to explain the principles of the present invention.
[0054] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, for those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.
[0055] Figure 1 It is a flowchart of the photodynamic therapy power control method according to an embodiment of the present invention;
[0056] Figure 2 It is a schematic flowchart of obtaining the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct according to the total fluorescence emission spectrum according to an embodiment of the present invention;
[0057] Figure 3 It is a schematic flowchart of setting the output power of the excitation light source according to the tissue absorption coefficient and the tissue scattering coefficient according to an embodiment of the present invention;
[0058] Figure 4 It is a schematic structural diagram of the photodynamic therapy power control system according to an embodiment of the present invention. Detailed implementation manners
[0059] The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.
[0060] It should be noted that all directional indications (such as up, down, left, right, front, back...) in the embodiments of the present invention are only used to explain the relative positional relationship and movement conditions between components in a specific posture (as shown in the accompanying drawings). If this specific posture changes, the directional indications will also change accordingly.
[0061] In addition, the descriptions involving "first", "second", etc. in the present invention are only for descriptive purposes, and cannot be understood as indicating or implying their relative importance or implicitly indicating the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include at least one of such features. In addition, the technical solutions between various embodiments can be combined with each other, but it must be based on the fact that those of ordinary skill in the art can implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such a combination of technical solutions does not exist and is not within the protection scope required by the present invention.
[0062] Photodynamic Therapy (PDT) is a treatment method that acts on diseased tissues through photosensitizers and excitation light of a specific wavelength to generate reactive oxygen species (ROS) to kill diseased cells, and is widely used in the field of tumor treatment and other fields. However, in the existing photodynamic therapy process, the output power of the excitation light source is usually calculated by a fixed value or an empirical formula, resulting in inaccurate power of the treatment light source. This inaccuracy may reduce the treatment effect and may also cause side effects during the treatment process, affecting the safety of the treatment.
[0063] To address the above problems, in recent years, researchers have tried to optimize the output power of the excitation light source during the treatment process by preset parameters such as the concentration of photosensitizer and treatment time. However, the existing photodynamic therapy still has deficiencies in monitoring the dynamic changes in the treatment area, especially in the lack of effective means for separating and quantifying the fluorescence intensities of photosensitizers and photoproducts. This deficiency leads to the inability to provide real-time feedback on the dynamic changes in the treatment area, such as the excitation state of the photosensitizer, the generation state of the photoproduct, and the light absorption characteristics of the tissue, resulting in a mismatch between the output power of the light source and the real-time treatment requirements during the treatment process, and it is difficult to achieve precise control of the output power of the light source.
[0064] Example 1
[0065] Please refer to Figure 1 and Figure 2 , the present invention provides a method for controlling the power of photodynamic therapy, comprising the steps of:
[0066] Set the initial value of the output power of the excitation light source, and start the excitation light source to perform photodynamic therapy on the treatment area;
[0067] Collect the total fluorescence emission spectrum of the treatment area in real time, and obtain the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct according to the total fluorescence emission spectrum;
[0068] Adjust the output power of the excitation light source according to the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct;
[0069] The step of obtaining the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct according to the total fluorescence emission spectrum includes the steps of:
[0070] Obtain the background-normalized spectrum, the photosensitizer-normalized spectrum, and the photoproduct-normalized spectrum;
[0071] Obtain the background fluorescence emission spectrum according to the output power of the excitation light source and the background-normalized spectrum, and calculate the difference between the total fluorescence emission spectrum and the background fluorescence emission spectrum to obtain the target fluorescence emission spectrum;
[0072] Obtain the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct according to the photosensitizer-normalized spectrum, the photoproduct-normalized spectrum, and the target fluorescence emission spectrum.
[0073] The method for controlling the power of photodynamic therapy of the present invention monitors the photodynamic reaction of the treatment area in real time by collecting the total fluorescence emission spectrum of the treatment area in real time. The background fluorescence emission spectrum is calculated through the output power of the excitation light source, so as to accurately separate the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct, and accurately evaluate the progress and effect of photodynamic therapy. By dynamically adjusting the output power of the excitation light source according to the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct, the output power of the light source can dynamically match the real-time reaction state of the treatment area, improving the accuracy and robustness of power control.
[0074] Specifically, the following content is used to elaborate on each step of a method for controlling the power of photodynamic therapy in Example 1 of the present invention:
[0075] A method for controlling the power of photodynamic therapy, comprising the steps of:
[0076] S1. Set the initial value of the output power of the excitation light source, and start the excitation light source to perform photodynamic therapy on the treatment area;
[0077] Further, setting an initial value of the output power of the excitation light source and starting the excitation light source to perform a photodynamic therapy operation on the treatment area includes the steps of:
[0078] S11. Measuring the tissue absorption coefficient and tissue scattering coefficient of the treatment area;
[0079] In the embodiment of the present invention, a frequency-domain OCT (optical coherence tomography) device with high resolution and fast imaging ability is used to perform three-dimensional scanning on the treatment area to obtain the spectral structure information of the tissue, and then the absorption coefficient and tissue scattering coefficient are obtained by analyzing the spectral structure information. Among them, the tissue absorption coefficient reflects the degree of light absorption by the tissue, and the tissue scattering coefficient reflects the degree of light scattering.
[0080] S12. Setting the output power of the excitation light source according to the tissue absorption coefficient and tissue scattering coefficient;
[0081] Further, please refer to Figure 3 , setting the output power of the excitation light source according to the tissue absorption coefficient and tissue scattering coefficient includes the steps of:
[0082] S121. Setting a target absorption power according to the selected photosensitizer and tissue type;
[0083] The target absorption power refers to the specific absorption power that is desired to be achieved in the treatment area during the photodynamic therapy process. The target absorption power is set according to the specific conditions of the patient (such as tissue type, photosensitizer type, etc.).
[0084] S122. Obtaining a penetration compensation coefficient according to the tissue absorption coefficient and tissue scattering coefficient;
[0085] The penetration compensation coefficient is expressed as:
[0086] ;
[0087] Among them, represents the tissue absorption coefficient, represents the tissue scattering coefficient.
[0088] S123. Setting the output power of the excitation light source according to the penetration compensation absorption coefficient and the target absorption power.
[0089] The output power of the excitation light source is expressed as:
[0090] ;
[0091] Among them, represents the target absorption power.
[0092] This embodiment combines the target absorption power and the penetration compensation coefficient to calculate the initial value of the output power of the excitation light source, ensuring that the light energy reaches the required absorption power in the treatment area.
[0093] S2. Real-time collect the total fluorescence emission spectrum of the treatment area, and obtain the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity according to the total fluorescence emission spectrum;
[0094] In the embodiment of the present invention, based on the aforementioned output power of the excitation light source, a multi-wavelength light source is used to irradiate the treatment area, covering the visible light and near-infrared bands. Then, the total fluorescence emission spectrum of the treatment area is collected in real time through multispectral imaging.
[0095] In this embodiment, the real-time collection of the total fluorescence emission spectrum of the treatment area specifically refers to the real-time capture of the total fluorescence emission spectrum within the first wavelength range through multispectral imaging. The first wavelength range is set according to the characteristic peak wavelengths of the photosensitizer and the photoproduct. During the treatment process, a specific light source is continuously used to irradiate the target area. The wavelength of this light source is called the excitation wavelength, and its function is to excite the photosensitizer in the treatment area to enter the excited state, thereby emitting fluorescence. These excitation wavelengths are usually selected to be consistent with the absorption peaks of the photosensitizer, enabling the photosensitizer to efficiently absorb energy. After the excitation light irradiation, the treatment area emits fluorescence. The intensities of these fluorescence signals vary with different wavelengths. Through multispectral imaging technology, the total fluorescence emission spectrum composed of fluorescence signals in different wavelength ranges can be recorded simultaneously.
[0096] The total fluorescence emission spectrum refers to the superimposed information of the background fluorescence emission spectrum, the photosensitizer fluorescence emission spectrum, and the photoproduct fluorescence emission spectrum within the first wavelength range of the treatment area obtained through multispectral imaging. The photosensitizer fluorescence emission spectrum is the fluorescence spectrum emitted by the photosensitizer after being excited at the excitation wavelength. The photoproduct fluorescence emission spectrum is the fluorescence spectrum emitted by the photoproduct generated after the photosensitizer degrades or reacts with other molecules during the treatment. The background fluorescence emission spectrum refers to the fluorescence spectrum emitted by the tissue in the treatment area due to endogenous fluorophores (such as collagen, NADH, flavin) when excited by light.
[0097] In this embodiment, the photoproduct is mainly singlet oxygen ( ). Singlet oxygen is a highly reactive free radical with extremely strong oxidation ability and is one of the main forms of reactive oxygen species in photodynamic therapy.
[0098] Obtain the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity according to the total fluorescence emission spectrum. The goal is to separate the fluorescence signals of the photosensitizer and its photoproducts from the total fluorescence observed during photodynamic therapy. Further, the obtaining of the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity according to the total fluorescence emission spectrum includes the steps:
[0099] S21. Obtain the background-normalized spectrum, photosensitizer-normalized spectrum, and photoproduct-normalized spectrum;
[0100] In the present invention, the normalized spectrum refers to normalizing the corresponding emission spectrum relative to the peak value, so that the relationship between its fluorescence intensity and the characteristic peak within the set first wavelength range is standardized, making the data measured under different excitation light source output powers more comparable. Specifically, the normalized spectrum is obtained through existing literature or experimental determination, including the background-normalized spectrum, photosensitizer-normalized spectrum, and photoproduct-normalized spectrum. The horizontal axis of the normalized spectrum represents the wavelength within the set wavelength range, and the vertical axis represents the fluorescence intensity coefficient. The fluorescence intensity coefficient is the ratio of each fluorescence intensity to the fluorescence intensity peak value, and its value range is [0, 1].
[0101] S22. Obtain the background fluorescence emission spectrum based on the excitation light source output power and the background-normalized spectrum, and calculate the difference between the total fluorescence emission spectrum and the background fluorescence emission spectrum to obtain the target fluorescence emission spectrum;
[0102] Based on the foregoing content, the total fluorescence emission spectrum includes the background fluorescence emission spectrum, photosensitizer fluorescence emission spectrum, and photoproduct fluorescence emission spectrum. In order to separate the fluorescence signals of the photosensitizer and photoproduct, it is necessary to remove the background fluorescence from the total fluorescence emission spectrum. By taking the difference between the total fluorescence emission spectrum and the background fluorescence emission spectrum, the target fluorescence emission spectrum is obtained, that is, it only contains the photosensitizer fluorescence emission spectrum and the photoproduct fluorescence emission spectrum.
[0103] S23. Obtain the photosensitizer fluorescence intensity and photoproduct fluorescence intensity based on the photosensitizer-normalized spectrum, photoproduct-normalized spectrum, and target fluorescence emission spectrum.
[0104] The target fluorescence emission spectrum can be regarded as a linear combination of the photosensitizer fluorescence emission spectrum and the photoproduct fluorescence emission spectrum. In this embodiment, the least squares fitting can be used to process the target fluorescence emission spectrum, so as to obtain the photosensitizer fluorescence intensity and photoproduct fluorescence intensity by minimizing the sum of the squares of the errors in the fitting process.
[0105] Furthermore, obtaining the photosensitizer fluorescence intensity and photoproduct fluorescence intensity based on the photosensitizer-normalized spectrum, photoproduct-normalized spectrum, and target fluorescence emission spectrum includes the steps of:
[0106] S231. Construct a relationship model of the target fluorescence emission spectrum, photosensitizer-normalized spectrum, and photoproduct-normalized spectrum; the relationship model is expressed as:
[0107] ;
[0108] wherein, represents the target fluorescence emission spectrum at wavelength Fluorescence intensity at; Indicates the fluorescence intensity coefficient of the photosensitizer normalized spectrum at wavelength ; Indicates the fluorescence intensity coefficient of the photoproduct normalized spectrum at wavelength ; Is the fluorescence intensity of the photosensitizer, Is the fluorescence intensity of the photoproduct; Indicates the error term, caused by background noise or measurement error.
[0109] It can be understood that the product of the fluorescence intensity coefficient of the photosensitizer normalized spectrum at wavelength and the fluorescence intensity of the photosensitizer Is the fluorescence intensity of the photosensitizer fluorescence emission spectrum at wavelength ; The product of the fluorescence intensity coefficient of the photoproduct normalized spectrum at wavelength and the fluorescence intensity of the photoproduct Is the fluorescence intensity of the photoproduct fluorescence emission spectrum at wavelength ;
[0110] S232. Construct an error function according to the relational model, and solve the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct through the error function.
[0111] The error function is expressed as:
[0112] ;
[0113] Wherein, Indicates the error function, Q represents the set of characteristic wavelengths, and the set of characteristic wavelengths includes the characteristic peak wavelengths of several photosensitizer normalized spectra and photoproduct normalized spectra; the error function Needs to sum all wavelengths λ in the set of characteristic wavelengths to minimize the error over the entire spectral range.
[0114] In one embodiment, the obtaining of the background fluorescence emission spectrum according to the output power of the excitation light source and the background normalized spectrum is specifically:
[0115] Calculate the background fluorescence emission spectrum according to the background fluorescence linear compensation coefficient, the output power of the excitation light source, and the background normalized spectrum.
[0116] The background fluorescence emission spectrum is expressed as:
[0117] ;
[0118] Wherein, Indicates the fluorescence intensity of the background fluorescence emission spectrum at wavelength ; Indicates the background normalized spectrum, Represents the background fluorescence linear compensation coefficient, Represents the output power of the excitation light source.
[0119] During implementation, the background fluorescence emission spectrum changes with the change of the output power of the excitation light source, and the background fluorescence intensity has an approximate linear relationship with the output power of the excitation light source. In order to eliminate the influence of factors such as the output power of the excitation light source and measurement conditions on the spectrum, the background normalized spectrum has been obtained through prior knowledge.
[0120] Furthermore, the background fluorescence linear compensation coefficient is obtained through the following steps:
[0121] S201. Set the test power of the excitation light source and irradiate the treatment area with the excitation light source;
[0122] S202. Capture the background fluorescence emission spectrum through multispectral imaging, and obtain the background characteristic peak fluorescence intensity according to the background fluorescence emission spectrum; the background fluorescence emission spectrum represents the background fluorescence intensity corresponding to each wavelength within the set wavelength range; the background characteristic peak fluorescence intensity is the fluorescence intensity corresponding to the selected characteristic peak in the background fluorescence emission spectrum.
[0123] S203. Repeat steps S201 and S202 several times, and fit the background fluorescence linear compensation coefficient according to several test powers and their corresponding background characteristic peak fluorescence intensities.
[0124] The greater the test power of the excitation light source, the more light energy is irradiated onto the tissue per unit time, and the excitation light source will excite more endogenous fluorophores, resulting in the emission of more fluorescent photons. In this embodiment, the fluorescence linear compensation coefficient is fitted by setting several test powers and obtaining their corresponding background characteristic peak fluorescence intensities. The fluorescence linear compensation coefficient is used to calculate the background fluorescence emission spectrum according to the actual output power of the excitation light source during the actual treatment process.
[0125] S3. Adjust the output power of the excitation light source according to the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity.
[0126] In one embodiment, the adjusting the output power of the excitation light source according to the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity includes the steps of:
[0127] S31. Output the adjustment amount of the excitation light source output power through a double-loop control model composed of an outer loop for controlling the photoproduct concentration and an inner loop for controlling the photosensitizer concentration; the input of the outer loop for controlling the photoproduct concentration is the deviation of the photoproduct fluorescence intensity, and the output is the target fluorescence intensity of the photosensitizer; the input of the inner loop for controlling the photosensitizer concentration is the deviation of the photosensitizer fluorescence intensity, and the output is the adjustment amount of the excitation light source output power.
[0128] In this embodiment, the fluorescence intensity deviation of the photoproduct is the difference between the current fluorescence intensity of the photoproduct and the target fluorescence intensity of the photoproduct. The fluorescence intensity deviation of the photosensitizer is the difference between the current fluorescence intensity of the photosensitizer and the target fluorescence intensity of the photosensitizer. Among them, the target fluorescence intensity of the photoproduct is evaluated and set according to the actual situation of the treatment process, and the target fluorescence intensity of the photosensitizer is the output of the outer loop of the photoproduct concentration control. The current fluorescence intensity of the photoproduct and the photosensitizer is obtained through step S2.
[0129] In this embodiment, the output power adjustment amount of the excitation light source is output through a dual-loop control model composed of an outer loop of photoproduct concentration control and an inner loop of photosensitizer concentration control, realizing hierarchical dynamic control, taking into account the response speed and stability, and improving the smoothness and convergence of power adjustment.
[0130] Further, the outer loop of the photoproduct concentration control is expressed as:
[0131] ;
[0132] Among them, represents the target fluorescence intensity of the photosensitizer, represents the fluorescence intensity deviation of the photoproduct, , and are the proportional, integral, and differential coefficients of the outer loop of the photoproduct concentration control, respectively.
[0133] The inner loop of the photosensitizer concentration control is expressed as:
[0134] ;
[0135] Among them, represents the output power adjustment amount of the excitation light source, represents the fluorescence intensity deviation of the photosensitizer, , and are the proportional, integral, and differential coefficients of the inner loop of the photosensitizer concentration control, respectively.
[0136] Further, the parameters of the dual-loop control model are tuned by the Ziegler-Nichols method. In the actual application process, the purpose of parameter tuning of the outer loop of the photoproduct concentration control tends to ensure that the fluorescence intensity of the photoproduct converges smoothly to the target value, avoiding overshoot or oscillation; while the purpose of parameter tuning of the inner loop of the photosensitizer concentration control tends to quickly respond to the change of the fluorescence intensity of the photosensitizer to ensure the timeliness of power adjustment. Based on the above parameter tuning purposes, in one embodiment, the initial parameter tuning settings are , , ; , , .
[0137] Furthermore, the dual-loop control model further includes a power adjustment amount constraint, which is expressed as:
[0138] ,
[0139] ,
[0140] wherein, is the reference temperature, which is set according to the tissue type of the treatment area; is the difference between the temperature of the treatment area and the reference temperature; is the current output power of the excitation light source; is the fitting constant. In one embodiment, the temperature of the treatment area is obtained by a micro-thermocouple array.
[0141] Furthermore, the step of adjusting the output power of the excitation light source according to the fluorescence intensity of the photosensitizer and the fluorescence intensity of the photoproduct further includes the steps of:
[0142] S32. Trigger a fixed power mode or turn off the excitation light source according to the fluorescence intensity of the photosensitizer, the temperature of the treatment area, and the blood oxygen saturation obtained in real time.
[0143] During the photodynamic therapy process of the present invention, the dual-loop control model is default used to output the power adjustment amount of the excitation light source output to adjust the excitation light source output power. To further intelligently balance the efficacy and safety in complex treatment scenarios, step S32 dynamically evaluates the treatment safety state by real-time monitoring of three core parameters: the fluorescence intensity of the photosensitizer, the temperature of the treatment area, and the blood oxygen saturation, and accordingly triggers a predefined power control strategy to switch the control mode of the excitation light source output power from the dual-loop control model to a fixed power mode or turn off the excitation light source.
[0144] For the fluorescence intensity of the photosensitizer, when the fluorescence intensity of the photosensitizer continuously decreases (such as more than 20% per minute), it indicates that the photosensitizer may have insufficient effective concentration due to over-activation or bleaching. At this time, the system automatically switches to a fixed low power mode (such as 50 mW / cm²) to slow down the degradation rate of the photosensitizer while maintaining the basic treatment effect. If the fluorescence intensity further drops below the safety threshold, the excitation light source is completely turned off to avoid damage to normal tissues caused by ineffective energy irradiation.
[0145] For the temperature of the treatment area, the temperature of the treatment area is obtained by a micro-thermocouple array to identify the risk of local overheating. If the temperature rises above the preset safety threshold ( ), the system immediately activates a gradient power reduction mechanism to proportionally reduce the current power output to ensure that the temperature rise rate is controlled. When the temperature reaches the critical value ( When (the situation occurs), the excitation light source is forcibly turned off, and the cooling device is activated to prevent tissue necrosis caused by thermal damage.
[0146] Regarding the blood oxygen saturation, the blood oxygen saturation reflects the oxygen supply status of the treatment area. If the blood oxygen level continuously drops below the safety limit (such as 90%), it indicates that the oxygen consumption of the photodynamic reaction exceeds the tissue oxygen supply capacity, and there is a risk of hypoxia. The system first limits the power to a fixed low-power mode to reduce oxygen consumption; if the blood oxygen further decreases (such as below 85%), the light source is immediately cut off, the treatment is terminated, and at the same time, the auxiliary oxygen supply process is started to ensure the safety of the patient.
[0147] When multiple parameters trigger anomalies simultaneously, the system executes responses according to the preset priority (blood oxygen > temperature > photosensitizer status). All operations are implemented through the state machine logic to ensure that there are no conflicts in the control instructions, and the abnormal events are recorded throughout the process for post-event analysis.
[0148] In this embodiment, through the multi-dimensional monitoring of the photosensitizer fluorescence intensity, the temperature of the treatment area, and the blood oxygen saturation, a hierarchical safety protection system is constructed, which can intelligently balance the efficacy and safety in complex treatment scenarios and provide reliable full-cycle guarantee for photodynamic therapy.
[0149] Embodiment 2
[0150] Please refer to Figure 4 , a photodynamic therapy power control system, including an excitation light source, a spectral acquisition module, a spectral processing module, and a light source control module;
[0151] The spectral acquisition module is used to collect the total fluorescence emission spectrum of the treatment area in real time;
[0152] The spectral processing module is used to obtain the background-normalized spectrum, the photosensitizer-normalized spectrum, and the photoproduct-normalized spectrum, obtain the background fluorescence emission spectrum according to the output power of the excitation light source and the background-normalized spectrum, calculate the difference between the total fluorescence emission spectrum and the background fluorescence emission spectrum to obtain the target fluorescence emission spectrum, and obtain the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity according to the photosensitizer-normalized spectrum, the photoproduct-normalized spectrum, and the target fluorescence emission spectrum;
[0153] The light source control module is used to adjust the output power of the excitation light source according to the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity;
[0154] The excitation light source is used to perform photodynamic therapy operations on the treatment area according to the output power of the excitation light source.
[0155] In the embodiments provided in the present application, it should be understood that the disclosed systems and methods can be implemented in other ways. For example, the system embodiments described above are merely illustrative. For example, the division of the modules is only a logical function division. In actual implementation, there can be other division methods. For example, multiple modules or component libraries can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the displayed or discussed couplings or direct couplings or communication connections to each other can be through some interfaces. The indirect couplings or communication connections of the modules can be in electrical, mechanical or other forms.
[0156] The modules described as separate components may or may not be physically separated. The components shown as modules may or may not be physical modules, that is, they can be located in one place or distributed to multiple grid modules. Some or all of the modules can be selected according to actual needs to achieve the purpose of the solution of this embodiment.
[0157] In addition, the functional modules in the various embodiments of the present application can be integrated in a processing module, or each module can exist physically alone, or two or more modules can be integrated in one module. The above-mentioned integrated modules can be implemented in the form of hardware or in the form of software functional modules.
[0158] If the integrated module is implemented in the form of a software functional module and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present application, in essence, or the part that contributes to the prior art, or all or part of this technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to enable a computer device (which can be a personal computer, a server, or a grid device, etc.) to execute all or part of the steps of the methods described in the various embodiments of the present application. The foregoing storage medium includes: USB flash drives, dynamic hard disks, read-only memories (ROM, read-only memory), random access memories (RAM, random access memory), magnetic disks or optical discs and other various media that can store program codes.
[0159] The above description is only the specific implementation manners of the present invention, enabling those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but rather to the broadest scope consistent with the principles and novel features claimed herein.
Claims
1. A method for controlling the power of photodynamic therapy, characterized in that: Including the steps: Set an initial value for the output power of the excitation light source; Collect the total fluorescence emission spectrum of the treatment area in real time, and obtain the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity based on the total fluorescence emission spectrum; Adjust the output power of the excitation light source according to the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity; The obtaining of the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity based on the total fluorescence emission spectrum includes the steps: Obtain the background-normalized spectrum, the photosensitizer-normalized spectrum, and the photoproduct-normalized spectrum; Obtain the background fluorescence emission spectrum based on the output power of the excitation light source and the background-normalized spectrum, and calculate the difference between the total fluorescence emission spectrum and the background fluorescence emission spectrum to obtain the target fluorescence emission spectrum; Obtain the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity based on the photosensitizer-normalized spectrum, the photoproduct-normalized spectrum, and the target fluorescence emission spectrum.
2. The method for controlling the power of photodynamic therapy according to claim 1, characterized in that: The obtaining of the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity based on the photosensitizer-normalized spectrum, the photoproduct-normalized spectrum, and the target fluorescence emission spectrum includes the steps: Construct a relationship model of the target fluorescence emission spectrum, the photosensitizer-normalized spectrum, and the photoproduct-normalized spectrum; Construct an error function according to the relationship model, and solve for the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity through the error function.
3. The method for controlling the power of photodynamic therapy according to claim 2, wherein: The relationship model is expressed as: , Among them, represents the fluorescence intensity of the target fluorescence emission spectrum at wavelength ; represents the fluorescence intensity coefficient of the photosensitizer normalized spectrum at wavelength ; represents the fluorescence intensity coefficient of the photoproduct normalized spectrum at wavelength ; is the fluorescence intensity of the photosensitizer, is the fluorescence intensity of the photoproduct; represents the error term; The error function is expressed as: , Among them, represents the error function, and Q represents the set of characteristic wavelengths.
4. A photodynamic therapy power control method according to claim 1, characterized in that: The obtaining of the background fluorescence emission spectrum based on the output power of the excitation light source and the background-normalized spectrum is specifically: Calculate the background fluorescence emission spectrum based on the background fluorescence linear compensation coefficient, the output power of the excitation light source, and the background-normalized spectrum; the background fluorescence emission spectrum is expressed as: , Among them, represents the fluorescence intensity of the background fluorescence emission spectrum at the wavelength ; represents the background normalized spectrum, represents the background fluorescence linear compensation coefficient, represents the output power of the excitation light source.
5. A photodynamic therapy power control method according to claim 4, characterized in that: The background fluorescence linear compensation coefficient is obtained through the following steps: S201. Set the test power of the excitation light source, and use the excitation light source to irradiate the treatment area; S202. Capture the background fluorescence emission spectrum through multispectral imaging, and obtain the fluorescence intensity of the background characteristic peak based on the background fluorescence emission spectrum; S203. Repeat steps S201 and S202 several times, and fit the background fluorescence linear compensation coefficient according to several test powers and their corresponding fluorescence intensities of the background characteristic peaks.
6. A method for controlling the power of photodynamic therapy according to claim 1, characterized in that: The adjusting of the output power of the excitation light source according to the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity includes the steps: Output an adjustment amount of the output power of the excitation light source through a dual-loop control model composed of an outer loop for controlling the concentration of the photoproduct and an inner loop for controlling the concentration of the photosensitizer; the input of the outer loop for controlling the concentration of the photoproduct is the deviation of the photoproduct fluorescence intensity, and the output is the target fluorescence intensity of the photosensitizer; the input of the inner loop for controlling the concentration of the photosensitizer is the deviation of the photosensitizer fluorescence intensity, and the output is the adjustment amount of the output power of the excitation light source.
7. A photodynamic therapy power control method according to claim 6, characterized in that: The outer loop for controlling the concentration of the photoproduct is expressed as: , Among them, represents the target fluorescence intensity of the photosensitizer, represents the fluorescence intensity deviation of the photoproduct, , and are the proportional, integral and differential coefficients of the outer loop for controlling the concentration of the photoproduct, respectively; The inner loop for controlling the concentration of the photosensitizer is expressed as: , Among them, represents the adjustment amount of the output power of the excitation light source, represents the fluorescence intensity deviation of the photosensitizer, , and are the proportional, integral, and differential coefficients of the inner control loop of the photosensitizer concentration respectively.
8. A method for controlling the power of photodynamic therapy according to claim 6, characterized in that: The dual-loop control model also includes a constraint on the adjustment amount of the power; the constraint on the adjustment amount of the power is expressed as: , , Among them, is the reference temperature, which is set according to the tissue type of the treatment area; is the difference between the treatment area temperature and the reference temperature; is the current output power of the excitation light source; is the fitting constant.
9. A photodynamic therapy power control method according to claim 6, characterized in that: The adjusting of the output power of the excitation light source according to the photosensitizer fluorescence intensity and the photoproduct fluorescence intensity further includes the steps: Trigger a fixed power mode or turn off the excitation light source according to the photosensitizer fluorescence intensity, the temperature of the treatment area, and the blood oxygen saturation obtained in real time.
10. A photodynamic therapy power control system, characterized in that: Including an excitation light source, a spectrum acquisition module, a spectrum processing module, and a light source control module; The spectral acquisition module is used to collect the total fluorescence emission spectrum of the treatment area in real time; The spectral processing module is used to obtain the background-normalized spectrum, photosensitizer-normalized spectrum, and photoproduct-normalized spectrum, obtain the background fluorescence emission spectrum according to the output power of the excitation light source and the background-normalized spectrum, calculate the difference between the total fluorescence emission spectrum and the background fluorescence emission spectrum to obtain the target fluorescence emission spectrum, and obtain the photosensitizer fluorescence intensity and photoproduct fluorescence intensity according to the photosensitizer-normalized spectrum, photoproduct-normalized spectrum, and target fluorescence emission spectrum; The light source control module is used to adjust the output power of the excitation light source according to the photosensitizer fluorescence intensity and photoproduct fluorescence intensity; The excitation light source is used to perform photodynamic therapy operations on the treatment area according to the output power of the excitation light source.
Citation Information
Patent Citations
Photodynamic precise treatment system based on hyperspectrum and fluorescence imaging guidance
CN110478625A
Singlet Oxygen Production and Dosimetry for Photodynamic Therapy
US20120209125A1