Full-link signal-to-noise ratio estimation method for fluorescence endoscope

Abstract

The present invention belongs to the field of optical near-infrared fluorescence imaging and biomedical engineering, and relates to a method for estimating the full-link signal-to-noise ratio of a fluorescent endoscope. The method for estimating the full-link signal-to-noise ratio of a fluorescent endoscope provided by the present invention can establish a theoretical signal-to-noise ratio model of excitation light and fluorescence by tracking the radiation transmission process and the full-link imaging process of the fluorescent endoscope illumination beam, providing a theoretical method for further determining the working distance of the fluorescent endoscope, and providing theoretical guidance for the reasonable allocation of the overall design indicators of the endoscope. The method for estimating the full-link signal-to-noise ratio of a fluorescent endoscope provided by the present invention can solve the problem of separation between the signal-to-noise ratio evaluation of fluorescent endoscope imaging and the actual physical process, provide a theoretical basis for improving the detection depth and sensitivity of micro-tumors and metastatic lesions, and promote the clinical application of fluorescent endoscopes.

Description

Technical Field

[0001] The present invention belongs to the field of optical near-infrared fluorescence imaging and biomedical engineering, and in particular relates to a full-link signal-to-noise ratio estimation method for a fluorescence endoscope. Background Art

[0002] Indocyanine green, commonly known as indigo green, diagnostic green needle, and indocyanine green, is a contrast agent currently used in the clinical diagnosis of cardiovascular diseases in my country. Indocyanine green can emit fluorescent signals under the excitation of near-infrared light. Near-infrared light does not cause damage to biological tissues, has strong penetration in biological tissues, and can obtain deep information about biological tissues; near-infrared light is less affected by other factors and is widely used in research on functional imaging and abnormal tissue diagnosis. Fluorescence endoscopes combine the characteristics of near-infrared light and the fluorescent probe indocyanine green. On the basis of traditional endoscopes, near-infrared light channels are added, and indocyanine green is used to mark abnormal tissues. Under the excitation of near-infrared light, indocyanine green can emit fluorescent signals, thereby helping doctors to more accurately locate tumors, detect tiny lesions, mark tumor boundaries, and completely remove tumors.

[0003] The fluorescence endoscope system not only has the advantages of high sensitivity, non-invasiveness, and real-time imaging of general optical imaging systems, but also has many advantages such as low autofluorescence background, deep tissue penetration, and clear imaging, making it more and more widely used. The signal-to-noise ratio determines the effective information volume of the endoscopic imaging system and its ability to detect and identify targets. The imaging signal-to-noise ratio of the traditional optical imaging system is related to factors such as the radiation power radiated by the target to the detector, the response characteristics of the detector, and background noise. The imaging signal-to-noise ratio of the fluorescence endoscope system is not only affected by the above factors, but also by the irregular absorption and scattering of light caused by the composition and structural characteristics of the biological tissue itself, which will cause the energy attenuation of light during transmission in the biological tissue. In addition, in the actual application of fluorescence endoscopes, the low quantum yield of fluorescent molecular probes and weak fluorescence signals will also affect the signal-to-noise ratio of the system. Under the condition of a certain working distance, the signal-to-noise ratio of the fluorescence endoscope system is determined by the entrance pupil diameter, the irradiance of the excitation light, the concentration of the fluorescent probe, the integration time, noise, etc. The shortcomings of the existing fluorescence endoscope system are mainly the following two points:

[0004] 1. There is a lack of research on the imaging of fluorescent endoscope systems from the perspective of the entire system link. Most of the existing technologies conduct experimental analysis on external influencing factors, such as the type of fluorescent molecular probe, the concentration of fluorescent molecular probe, the wavelength of excitation light, the power of excitation light, etc., and there is no research and analysis that combines the process of excitation light transmission into the tissue, the process of fluorescence excitation, the transmission of fluorescence through the tissue and the imaging process of the optical system. Theoretical research and actual physical processes are separated from each other.

[0005] 2. There is a lack of theoretical formulas for the imaging signal-to-noise ratio of the fluorescence endoscope system. Compared with the fluorescence endoscope system, the existing imaging signal-to-noise ratio estimation method of the infrared target detection system not only does not deeply study the emission process of infrared light inside the target, but also does not have the incident light propagation process and the excitation process, so the imaging process is simpler; the factors affecting the imaging quality of the infrared target detection system are mainly the infrared light radiated by the target black body and atmospheric loss, etc. Compared with the excitation light incident process, fluorescence excitation process, fluorescence emission process of the fluorescence endoscope system, the optical parameters of the tissue body and the parameters of the fluorescent molecular probe, etc., there are fewer influencing factors, so the existing conclusions of the infrared target detection system cannot be directly applied to the signal-to-noise ratio analysis of the fluorescence endoscope system imaging. Summary of the invention

[0006] Technical purpose: In order to overcome the shortcomings of the prior art, the present invention provides a method for estimating the full-link signal-to-noise ratio of a fluorescence endoscope. It uses the principle of stimulated fluorescence emission, comprehensively considers the propagation process of illumination light in biological tissues, the fluorescence excitation process, and the response of the detector, and improves on the Monte Carlo method. By tracking the radiation transmission process of the fluorescence endoscope light and the full-link imaging process, a fluorescence theoretical signal-to-noise ratio model is established. The technical solution of the present invention is as follows:

[0007] The present invention provides a method for estimating the signal-to-noise ratio of a full-link fluorescence endoscope, comprising:

[0008] S1: Determine the optical parameters of the incident light and the tissue, and calculate the radiation transmission process of the incident light in the tissue;

[0009] S2: determining the optical parameters of the tumor tissue and the fluorescent molecular probe, and calculating the fluorescence weight excited by the incident light and its radiation transmission process in the tissue body;

[0010] S3: Determine the fluorescence radiance M on the surface of the tissue and calculate the detector entrance pupil illumination E d ;

[0011] S4: Determine the optical imaging system parameters, establish a full-link signal-to-noise ratio model, and calculate the full-link signal-to-noise ratio SNR.

[0012] Further, step S1 includes:

[0013] S1.1: According to the total power W of the incident light in , the beam waist radius ω, the number of incident photon packets N, and the distance D between the incident light exit surface and the tissue surface are determined by the incident light wavelength and the incident light emission half angle, the initial positions, incident angles, and initial energy weights of the N photon packets are determined, the positions of the N incident photon packets obey the Gaussian distribution according to formula 1, and the initial energy weights are uniformly distributed;

[0014]

[0015] S1.2: Using the improved Monte Carlo method combined with the tissue isotropy coefficient g to calculate the random step length and random direction cosine of the N photon packets after they are incident on the tissue, combined with the incident light energy weighting coefficient C and the tissue scattering coefficient μ that can improve the calculation accuracy s and the absorption coefficient μ a , calculate the energy weights and position distribution rules of the N photon packets;

[0016]

[0017] According to formula 2, the mth photon packet travels to the kth m Step, located at When the corresponding attenuated energy weight is Where m=1,2,3,···,N.

[0018] Further, step S2 includes:

[0019] S2.1: Combining the quantum yield η of the fluorescent molecular probe, the tumor center position, and the tumor radius, the excited position is used as the initial emission position of the fluorescent photon packet, and the excitation energy weight of the incident photon packet is converted into the initial energy weight of the fluorescent photon packet using Formula 3;

[0020]

[0021] S2.2: using an improved Monte Carlo method to calculate the random step length and random direction cosine of the fluorescent photon packet after it is incident on the tissue body, and combining the fluorescent energy weighting coefficient C' that can improve the calculation accuracy, to calculate the energy weight and position distribution law of all fluorescent photon packets;

[0022]

[0023] According to Formula 4, the time it takes for the nth fluorescent photon packet to travel to the kth n Step, located at position When the corresponding attenuated energy weight is

[0024] Further, step S3 includes:

[0025] S3.1: Count the locations that meet the conditions using formula 5 and The total energy of the fluorescence photon packet emitted is W F , where d is the z coordinate of the observation section;

[0026]

[0027] S3.2: Calculate the irradiance dE of the fluorescent group at the air boundary of the tissue body with the z axis as the center and the radius r by formula 6. Double integrate r and z to obtain the total irradiance E of the entire fluorescent group on the surface of the tissue body, and solve the problem of uneven irradiance distribution of the fluorescent group; the fluorescence radiance M is equal to the area of ​​the fluorescent group reaching the surface of the tissue body A F , the emission angle is θ F The total irradiance E of the fluorophore;

[0028]

[0029] S3.3: The fluorescence radiation intensity of the tissue surface is calculated by formula 7 as I F The fluorophore is emitted from the surface of the tissue and travels a distance of D with a transmittance of τ. a The angle between the gas layer and the normal line of the tissue surface is θ d The light intensity I at the entrance pupil of the detector surface d ;

[0030]

[0031] S3.4: Calculate the detector entrance pupil illumination E using formula 8 d ;

[0032]

[0033] Furthermore, the gas layer in step S3.3 is an air layer or a CO2 layer.

[0034] Further, step S4 includes:

[0035] S4.1: The entrance pupil area of ​​the combined detector optical system is A in , the transmittance is τ s , integration time is T, average working wavelength is The detector quantum yield is Q e , the radiation flux W on the detector pixel is calculated by formula 9 d And converted into the total number of photoelectrons N generated on the detector d ;

[0036]

[0037] S4.2: Combining Photon Noise n p , electronic read noise n read , background noise n b , dark current noise n d The total system noise N noise , the full-link signal-to-noise ratio of the fluorescence endoscope system is calculated by formula 10;

[0038]

[0039] S4.3: Use equation 11 to convert to the signal-to-noise ratio commonly used unit dB;

[0040] SNR=10lg(S / N) Formula 11.

[0041] The beneficial effects of the present invention are:

[0042] 1. A full-link signal-to-noise ratio estimation method for a fluorescent endoscope provided by the present invention can establish a theoretical signal-to-noise ratio model of excitation light and fluorescence by tracing the radiation transmission process and the full-link imaging process of the fluorescent endoscope illumination beam, thereby providing a theoretical method for further determining the working distance of the fluorescent endoscope and providing theoretical guidance for the reasonable allocation of the overall design indicators of the endoscope.

[0043] 2. The present invention provides a fluorescence endoscope full-link signal-to-noise ratio estimation method, which can solve the problem of separation between fluorescence endoscope imaging signal-to-noise ratio evaluation and actual physical process, provide a theoretical basis for improving the detection depth and sensitivity of micro-tumors and metastatic lesions, and promote the clinical application of fluorescence endoscopes. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0045] Figure 1 It is a flow chart of the full-link signal-to-noise ratio estimation method for fluorescence endoscope;

[0046] Figure 2 This is a schematic diagram of photon full-link transmission;

[0047] Figure 3 It is a simulation flow chart of the full-link signal-to-noise ratio model of fluorescence endoscope;

[0048] Figure 4 This is a schematic diagram of how photons travel within tissues;

[0049] Figure 5 It is the photon position distribution diagram of Gaussian light incident on the surface of tissue;

[0050] Figure 6 is the incident excitation light transmission distribution diagram in the tissue body;

[0051] Figure 7 is a schematic diagram of the initial energy weight of the fluorescence photon packet;

[0052] Figure 8 It is the distribution map of tumor fluorescence transmission in the tissue body;

[0053] Fig. 9 It is a schematic diagram of the energy weight and position distribution of the fluorescence photon packet at the observation section. DETAILED DESCRIPTION

[0054] The exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. It should be noted that the following description is only illustrative and exemplary in nature and is not intended to limit the present invention and its application or use. Unless otherwise specifically stated, the relative positions, numerical expressions and numerical values ​​of the components and steps described in the embodiments do not limit the scope of the present invention. In addition, techniques, methods and devices known to those skilled in the art may not be discussed in detail, but are intended to be part of the specification in appropriate circumstances.

[0055] like Figure 2 , Figure 4 As shown in the figure, when a Gaussian laser beam with a certain power is incident on the surface of the tissue model at a certain divergence angle, each incident photon packet enters the tissue with an initial weight and travels according to the length of the random step. Once the photon packet interacts with the tissue, some of the photons in the photon packet will be scattered and continue to move at the scattering deflection angle, azimuth angle and random step length until the photon terminates; at the same time, some of the photons absorbed by the tissue are absorbed by the fluorophore and re-emit fluorescence. First, the propagation direction of the excited fluorescent photon packet follows isotropy; second, the movement of the incident photon and the generated fluorescent photon is independent of each other. Once a fluorescent packet is generated, it will be tracked until it terminates, and then continue to track the movement of the next incident photon packet.

[0056] like Figure 3 As shown, the present invention starts from the end face of the illumination optical fiber, uses photometric theory to calculate the luminous intensity and the irradiance on the surface of the biological tissue at the working distance of the endoscope, and then simulates the propagation of the above-mentioned photons in the tissue body through the Monte Carlo method. Part of the fluorescence generated will be transmitted outside the tissue. The irradiance at the entrance pupil of the fluorescent endoscope is obtained by theoretically calculating the internal distribution of light in the biological tissue and the external radiation intensity. The light is focused on the CMOS detector pixel through the gain of the fluorescent endoscope optical system, and the noise of the background, detector, readout circuit, etc. is taken into account, and finally the signal-to-noise ratio of the fluorescent endoscope imaging is obtained.

[0057] Example 1 is a method for estimating the signal-to-noise ratio of a fluorescence endoscope in the entire link disclosed by the present invention. Figure 1 As shown:

[0058] S1: Determine the optical parameters of the incident light and the tissue, and calculate the radiation transmission process of the incident light in the tissue;

[0059] S1.1: According to the total power W of the incident light in , the beam waist radius ω, the number of incident photon packets N, and the distance D between the incident light exit surface and the tissue surface are determined by the incident light wavelength and the incident light emission half angle, the initial positions, incident angles, and initial energy weights of the N photon packets are determined, the positions of the N incident photon packets obey the Gaussian distribution according to formula 1, and the initial energy weights are uniformly distributed;

[0060]

[0061] S1.2: Using the improved Monte Carlo method combined with the tissue isotropy coefficient g to calculate the random step length and random direction cosine of the N photon packets after they are incident on the tissue, combined with the incident light energy weighting coefficient C and the tissue scattering coefficient μ that can improve the calculation accuracy s and the absorption coefficient μ a , calculate the energy weights and position distribution rules of the N photon packets;

[0062]

[0063] According to formula 2, the mth photon packet travels to the kth m Step, located at When the corresponding attenuated energy weight is Where m=1,2,3,···,N.

[0064] The usage position, parameter name and parameter value of each parameter in step S1 are shown in Table 1:

[0065] Table 1: Summary of step S1 parameter input and calculation results

[0066]

[0067] S2: determining the optical parameters of the tumor tissue and the fluorescent molecular probe, and calculating the fluorescence weight excited by the incident light and its radiation transmission process in the tissue body;

[0068] S2.1: Combining the quantum yield η of the fluorescent molecular probe, the tumor center position, and the tumor radius, the excited position is used as the initial emission position of the fluorescent photon packet, and the excitation energy weight of the incident photon packet is converted into the initial energy weight of the fluorescent photon packet using Formula 3;

[0069]

[0070] S2.2: using an improved Monte Carlo method to calculate the random step length and random direction cosine of the fluorescent photon packet after it is incident on the tissue body, and combining the fluorescent energy weighting coefficient C' that can improve the calculation accuracy, to calculate the energy weight and position distribution law of all fluorescent photon packets;

[0071]

[0072] According to Formula 4, the time it takes for the nth fluorescent photon packet to travel to the kth n Step, located at position When the corresponding attenuated energy weight is

[0073] The usage position, parameter name and parameter value of each parameter in step S2 are shown in Table 2:

[0074] Table 2: Summary of step S2 parameter input and calculation results

[0075]

[0076] S3: Determine the fluorescence radiance M on the surface of the tissue and calculate the detector entrance pupil illumination E d ;

[0077] S3.1: Count the locations that meet the conditions using formula 5 and The total energy of the fluorescence photon packet emitted is W F , where d is the z coordinate of the observation section;

[0078]

[0079] S3.2: Calculate the irradiance dE of the fluorescent group at the air boundary of the tissue body with the z axis as the center and the radius r by formula 6. Double integrate r and z to obtain the total irradiance E of the entire fluorescent group on the surface of the tissue body, and solve the problem of uneven irradiance distribution of the fluorescent group; the fluorescence radiance M is equal to the area of ​​the fluorescent group reaching the surface of the tissue body A F , the emission angle is θ F The total irradiance E of the fluorophore;

[0080]

[0081] S3.3: The fluorescence radiation intensity of the tissue surface is calculated by formula 7 as I F The fluorophore is emitted from the surface of the tissue and travels a distance of D with a transmittance of τ. a The angle between the air layer and the normal line of the tissue surface is θ d The light intensity I at the entrance pupil of the detector surface d ;

[0082]

[0083] S3.4: Calculate the detector entrance pupil illumination E using formula 8 d ;

[0084]

[0085] The usage position, parameter name and parameter value of each parameter in step S3 are shown in Table 3:

[0086] Table 3: Summary of step S3 parameter input and calculation results

[0087]

[0088] S4: Determine the optical imaging system parameters, establish a full-link signal-to-noise ratio model, and calculate the full-link signal-to-noise ratio SNR.

[0089] S4.1: The entrance pupil area of ​​the combined detector optical system is A in , the transmittance is τ s , integration time is T, average working wavelength is The detector quantum yield is Q e , the radiation flux W on the detector pixel is calculated by formula 9 d And converted into the total number of photoelectrons N generated on the detector d ;

[0090]

[0091] S4.2: Combined photon noise n p , electronic read noise n read , background noise n b , dark current noise n d The total system noise N noise , the full-link signal-to-noise ratio of the fluorescence endoscope system is calculated by formula 10;

[0092]

[0093] S4.3: Use equation 11 to convert to the signal-to-noise ratio commonly used unit dB;

[0094] SNR=101g(S / N) Formula 11.

[0095] The usage position, parameter name and parameter value of each parameter in step S4 are shown in Table 4:

[0096] Table 4: Summary of step S4 parameter input and calculation results

[0097]

[0098] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for estimating the signal-to-noise ratio of a full-link fluorescence endoscope, characterized in that: include: S1: Determine the optical parameters of the incident light and the tissue, and calculate the radiation transmission process of the incident light in the tissue; including: S1.1: According to the total power W of the incident light in , the beam waist radius ω, the number of incident photon packets N, and the distance D between the incident light exit surface and the tissue surface are determined by the incident light wavelength and the incident light emission half angle, the initial positions, incident angles, and initial energy weights of the N photon packets are determined, the positions of the N incident photon packets obey the Gaussian distribution according to formula 1, and the initial energy weights are uniformly distributed; S1.2: Using the improved Monte Carlo method combined with the tissue isotropy coefficient g to calculate the random step length and random direction cosine of the N photon packets after they are incident on the tissue, combined with the incident light energy weighting coefficient C and the tissue scattering coefficient μ that can improve the calculation accuracy s and the absorption coefficient μ a , calculate the energy weights and position distribution rules of the N photon packets; According to formula 2, the mth photon packet travels to the kth m Step, located at When the corresponding attenuated energy weight is Where m = 1, 2, 3, ···, N; S2: Determine the optical parameters of the tumor tissue and the fluorescent molecular probe, calculate the fluorescence weight excited by the incident light and its radiation transmission process in the tissue body; including: S2.1: Combining the quantum yield η of the fluorescent molecular probe, the tumor center position, and the tumor radius, the excited position is used as the initial emission position of the fluorescent photon packet, and the excitation energy weight of the incident photon packet is converted into the initial energy weight of the fluorescent photon packet using Formula 3; S2.2: using an improved Monte Carlo method to calculate the random step length and random direction cosine of the fluorescent photon packet after it is incident on the tissue body, and combining the fluorescent energy weighting coefficient C' that can improve the calculation accuracy, calculating the energy weight and position distribution law of all fluorescent photon packets; According to Formula 4, the time it takes for the nth fluorescent photon packet to travel to the kth n Step, located at position When the corresponding attenuated energy weight is S3: Determine the fluorescence radiance M on the surface of the tissue and calculate the detector entrance pupil illumination E d ;include: S3.1: Count the locations that meet the conditions using Formula 5 and The total energy of the fluorescence photon packet emitted is W F , where d is the z coordinate of the observation section; S3.2: Calculate the irradiance dE of the fluorescent group at the air boundary of the tissue body with the z axis as the center and the radius r by formula 6. Double integrate r and z to obtain the total irradiance E of the entire fluorescent group on the surface of the tissue body, and solve the problem of uneven irradiance distribution of the fluorescent group; the fluorescence radiance M is equal to the area of ​​the fluorescent group reaching the surface of the tissue body A F , the emission angle is θ F The total irradiance E of the fluorophore; S3.3: The fluorescence radiation intensity of the tissue surface is calculated by formula 7 as I F The fluorophore is emitted from the surface of the tissue and travels a distance of D with a transmittance of τ. a The angle between the gas layer and the normal line of the tissue surface is θ d The light intensity I at the entrance pupil of the detector surface d ; S3.4: Calculate the detector entrance pupil illumination E using formula 8 d ; S4: Determine the optical imaging system parameters, establish a full-link signal-to-noise ratio model, and calculate the full-link signal-to-noise ratio SNR; including: S4.1: The entrance pupil area of ​​the combined detector optical system is A in , the transmittance is τ s , integration time is T, average working wavelength is The detector quantum yield is Q e , the radiation flux W on the detector pixel is calculated by formula 9 d And converted into the total number of photoelectrons N generated on the detector d ; S4.2: Combining Photon Noise n p , electronic read noise n read , background noise n b , dark current noise n d The total system noise N noise , the full-link signal-to-noise ratio of the fluorescence endoscope system is calculated by formula 10; S4.3: Use equation 11 to convert to the signal-to-noise ratio commonly used unit dB; SNR=101g(S / N) Formula 11.

2. The method for estimating the full-link signal-to-noise ratio of a fluorescence endoscope according to claim 1, characterized in that: In step S3.3, the gas layer is an air layer or a CO2 layer.

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