WO2021073003A1 - Multimodal photoacoustic/ultrasonic imaging-based rheumatoid arthritis scoring system, device and application - Google Patents

Abstract

A multimodal photoacoustic/ultrasonic imaging-based rheumatoid arthritis scoring system, device and application. The application comprises the following steps: (1) collecting image information of joints by means of photoacoustic/ultrasonic bimodal imaging outside a body; (2) analyzing the collected image information and clinical data for multimodal photoacoustic/ultrasonic scoring; and (3) determining the disease activity of a rheumatoid arthritis patient on the basis of the multimodal photoacoustic/ultrasonic scoring in combination with local blood oxygen information. The multimodal system uses a handheld photoacoustic/ultrasonic probe, and is thus in line with the usage habits of clinicians; moreover, a multimodal photoacoustic/ultrasonic imaging system is used for the first time in the evaluation of rheumatoid arthritis. Typical joints are used for evaluation, and the selection thereof is consistent with the international joint selection approach for ultrasonic evaluation, and both the implementation process and calculation process are simple and feasible, thereby facilitating clinical implantation.

Description

Multimodal photoacoustic/ultrasound imaging rheumatoid arthritis scoring system, equipment and application Technical field

The invention relates to the technical field of medical diagnosis, in particular to a multimodal photoacoustic/ultrasound imaging rheumatoid arthritis scoring system, equipment and application.

Background technique

Rheumatoid arthritis (RA) is a chronic, inflammatory, and systemic disease marked by arthritis. It can occur at any age. The peak age of onset is about 50 years old, and it occurs frequently in women. The prevalence of RA in China is generally on the rise. Most patients with RA show severe clinical symptoms at the first diagnosis, and severe bone and joint structural damage may occur in the later stage of the disease, resulting in disability and inability to take care of themselves, seriously affecting the quality of life and bringing social and economic benefits Seriously burdened. Early diagnosis, treatment and prevention of RA recurrence and progression are essential to improve the prognosis of patients and improve the quality of life.

At present, the main imaging diagnostic methods of RA include X-ray, MRI and high-frequency ultrasound. X-ray examination is not sensitive to early synovial and bone lesions, and has little effect in early diagnosis; magnetic resonance imaging (MRI) can clearly show the intra-articular structure Compared with soft tissue lesions, it is expensive, time-consuming, and not suitable for routine examination. High-frequency ultrasound has played an increasingly important role in the diagnosis and treatment of RA due to its advantages of non-invasive, non-radiation, convenience, high cost performance, and good patient compliance. effect. High-frequency gray-scale ultrasound can evaluate signs of joint local synovial thickening, joint effusion, bone destruction, tenosynovitis, and power Doppler ultrasound can evaluate blood flow in thickened inflammatory lesions to determine the degree of inflammatory activity. High-frequency gray-scale and power Doppler ultrasound are currently being promoted by EULAR guidelines as a routine imaging method for RA-assisted diagnosis. And many studies have shown that ultrasound has clinical application value in multiple diagnosis and treatment links such as early diagnosis of RA, disease activity evaluation, treatment follow-up, efficacy evaluation, and recurrence prediction.

However, there are still many deficiencies in the joint ultrasound assessment of RA at this stage. First of all, ultrasound imaging and diagnosis operators are subjectively dependent, and there is still a lack of standardized imaging and scoring standards for RA ultrasound diagnosis. Secondly, conventional ultrasound imaging still lacks the ability to distinguish early lesions and tiny new blood vessels, and it is difficult to accurately assess the disease. Some studies have shown that power Doppler ultrasound cannot accurately predict the treatment response and recurrence risk of RA patients, and its role in RA disease management is still debatable. Therefore, on the basis of ultrasound imaging, exploring more accurate and sensitive joint imaging examinations, and establishing standardized imaging and evaluation programs will be of greater benefit to the improvement of the clinical diagnosis and treatment process of RA.

The photoacoustic imaging technology is based on the principle of the photoacoustic effect, that is, when the tissue is irradiated with a short pulse laser, the tissue is heated and expanded to generate ultrasonic waves, and the imaging is realized after detecting and reconstructing the image. It combines the advantages of optics and ultrasound. Based on the optical properties of tissues, multispectral imaging can be used to obtain more structural and functional information. At the same time, the resolution of deep tissues is much higher than that of traditional optical imaging. With the development and improvement of photoacoustic imaging technology, its clinical application has also been extended to joint imaging. Studies have shown that photoacoustic tomography (PAT) can visualize the anatomical structure of small joints, and display the hemoglobin content to evaluate the blood flow in the synovium of the joints. Combined with 3D imaging, the blood can be Flow to make a quantitative assessment. However, the PAT instrument is large in size, complicated to set up, and expensive, and its clinical use is obviously restricted. The multi-modal photoacoustic/ultrasound imaging platform that combines the photoacoustic imaging system with the ultrasound imaging system and is equipped with high-frequency ultrasound probes can display anatomical images through the ultrasound grayscale mode, and the photoacoustic mode provides functional information, which is in overcoming the traditional photoacoustic In addition to the shortcomings of the imaging system, the advantages of photoacoustic imaging are utilized to the greatest extent, so it has considerable potential clinical application value in joint imaging. In recent years, foreign countries have begun to develop this type of PA/US multi-modal imaging system with a portable handheld probe, and applied it to multi-wavelength photoacoustic examination of the small joints of RA patients, and successfully quantitatively determined the hemoglobin content and blood oxygen in the joints of RA patients saturation. In 2017, the research team successfully developed a photoacoustic/ultrasound dual-mode clinical real-time imaging system based on a handheld probe. The system is based on a commercial ultrasound instrument, which can provide higher resolution ultrasound and photoacoustic images, and realizes a variety of ultrasound modes (including color Doppler, power Doppler and ultrasound shear wave elastography) and photoacoustic Combined with real-time multi-modal imaging; the system is equipped with imaging analysis software, which can provide automatic quantitative analysis of photoacoustic multi-parameters, and more accurately reflect the relevant photoacoustic information of the target area; at the same time, due to the application of a handheld integrated photoacoustic/ultrasound probe , In line with the habits of sonographers, and has the advantages of being suitable for clinical staff. The results of previous studies have shown that the multi-modal imaging examination of the joints through this imaging platform can obtain the gray-scale and power Doppler ultrasound information while obtaining the micro blood flow of the local joint synovium or tendon through photoacoustic imaging analysis. The quantitative results of blood oxygen saturation and blood oxygen saturation provide more quantitative imaging information for the evaluation of the joints of RA patients.

Summary of the invention

The purpose of the present invention is to provide a multi-modal photoacoustic/ultrasound imaging rheumatoid arthritis scoring system, equipment and application, combining energy Doppler imaging, photoacoustic imaging and local blood oxygen information scoring to accurately determine RA joints The degree of imaging inflammation activity.

One aspect of the present invention provides the application of multimodal photoacoustic/ultrasound imaging in a rheumatoid arthritis scoring system, which includes the following steps:

(1) Photoacoustic/ultrasound dual-modality imaging collects image information of joints in an external form;

(2) Analyze the collected image information and clinical data for multi-modal photoacoustic/ultrasound scoring;

(3) Judging the disease activity of patients with rheumatoid arthritis based on multimodal photoacoustic/ultrasound scores combined with local blood oxygen information.

For the above-mentioned application, preferably, the multimodal photoacoustic/ultrasound scores include power Doppler ultrasound imaging (PDUS) scores and photoacoustic imaging (PAI) scores, and the PDUS scores and PAI scores are both Szkudlarek, etc. The 0-3 semi-quantitative scoring system first proposed by people (see Szkudlarek M, Court-Payen M, Jacobsen S, et al. Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis. Arthritis Rheum 2003; 48:955 -62. And Szkudlarek, M., et al., Ultrasonography of the metatarsophalangeal joints in rheumatoid arthritis: comparison with magnetic resonance imaging, conventional radiography, and clinical examination. Arthritis R-12., 2004.2(7) , The maximum score of each joint is used as the final score of each joint.

For the above-mentioned applications, preferably, the PDUS score and the PAI score are evaluated by the following criteria: no ultrasound/photoacoustic signal, score 0; less than 3 ultrasound/photoacoustic signals in the same plane in the hypoechoic area of the synovium, score 1 ; Ultrasound/photoacoustic signal is detected within half (area) of the hypoechoic area of synovium, score 2; Ultrasound/photoacoustic signal is detected in more than half (area) of hypoechoic area of synovium, score 3. Specifically, the hypoechoic area of the synovial membrane is the area of synovial hyperplasia, that is, the abnormal hypoechoic tissue in the joint cavity, which is not transferable and difficult to be compressed, and may show Doppler blood flow signals. The blood flow signal score ROI area (region of interest) is the area of synovial hyperplasia.

In the above-mentioned application, preferably, the local blood oxygen information includes qualitative evaluation using color judgment. _{The SO 2} image of the photoacoustic signal SO 2 images of each examined joint thickened inflammatory lesion area (including synovitis, tenosynovitis or perianinitis) is divided into three groups: blue (mainly hypoxic blood flow signal), red (hyperoxia) Blood flow signal mainly) and red and blue phases (mixed blood flow signal), the blue is mainly hypoxic blood flow signal, the red is mainly hyperoxic blood flow signal, and the red and blue phase is mixed blood Stream signal. Preferably, the local blood oxygen information further includes checking the oxygen saturation value (SO ₂ ) of the local thickened area of the joint, and comparing it with the surrounding normal tendons to determine the condition of the joint. The oxygen saturation value SO ₂ is calculated by the following formula:

SO ₂ (r)=C _Hb (r)/(C _Hb (r)+C _deHb (r))=(PA(λ ₁ ,r)*ε _deHb (λ ₂ )-PA(λ ₂ ,r)* ε _deHb (λ ₁ ))/(PA(λ ₁ ,r)*(ε _deHb (λ ₂ )-ε _Hb (λ ₂ ))+PA(λ ₂ ,r)*(ε _Hb (λ ₁ )-ε _deHb (λ ₁ ))

Among them, Hb is endogenous oxygenated hemoglobin, deHb is deoxygenated hemoglobin,

PA(λ ₁ ,r)*=μ _a (λ ₁ ,r)=C _Hb (r)ε _Hb (λ ₁ )+C _deHb (r)ε _deHb (λ ₁ )

PA(λ ₂ ,r)*=μ _a (λ ₂ ,r)=C _Hb (r)ε _Hb (λ ₂ )+C _deHb (r)ε _deHb (λ ₂ )

λ ₁ =750 nm, λ ₂ =830 nm.

Among them, μ _a (λ,r) represents the optical absorption coefficient of blood, ε _Hb (λ) represents the molar extinction of endogenous oxygenated hemoglobin (Hb), and C _Hb (r) represents endogenous oxygenated hemoglobin (Hb) The concentration of ε _deHb (λ) represents the molar extinction of deoxyhemoglobin (deHb), and C _deHb (r) represents the concentration of deoxyhemoglobin (deHb). PA(λ ₁ ,r)* is _{the PA that ignores φ(λ 1} ,r), and PA(λ ₂ ,r)* is _{the PA that ignores φ(λ 2} ,r). The PA value can be directly collected by the ultrasound probe. Any pixels with negative _{SO 2} values were removed in the subsequent analysis.

In the above-mentioned application, preferably, the multi-modal photoacoustic/ultrasound scoring image score is selected by at least two sonographers who do not know the patient’s information to use one of the three PA imaging pictures with the strongest PA signal. Scoring, when there is a disagreement between the ultrasound radiologists, re-evaluate the image until a consensus is reached.

For the application described above, preferably, the joints in step (1) include the second metacarpophalangeal joint (MCP 2), the third metacarpophalangeal joint (MCP 3), and the second metacarpophalangeal joint (MCP 2) on the side with obvious symptoms (the dominant side of clinical symptoms). Proximal interphalangeal joint (PIP 2), third proximal interphalangeal joint (PIP 3), second metatarsophalangeal joint (MTP 2), third metatarsophalangeal joint (MTP 5) and wrist joint.

The present invention also provides a rheumatoid arthritis scoring system based on multi-modal photoacoustic ultrasound imaging, which includes an information acquisition module, an information analysis module, and an output module,

The information collection module adopts photoacoustic/ultrasound dual-modality imaging to collect image information of joints in an external form to obtain image information of the local inflammatory area of rheumatoid joints;

The information analysis module classifies and calculates the collected image information to obtain characteristic parameters of the image;

The judgment output module combines the characteristic parameters of the image to judge the disease activity of the rheumatoid arthritis patient and output data.

In the above-mentioned scoring system, preferably, the information analysis module includes a semi-quantitative scoring module for statistically calculating the sum of the power Doppler ultrasound imaging score and the photoacoustic imaging score, the power Doppler ultrasound imaging score and the light Acoustic imaging scoring uses a semi-quantitative scoring system of 0, 1, 2, and 3 points, and the maximum score of each joint is used as the final score of each joint.

According to the above-mentioned scoring system, preferably, the power Doppler ultrasound imaging score and the photoacoustic imaging score are evaluated by the following criteria: there is no ultrasound/photoacoustic signal, the score is 0; there are less than 3 ultrasound in the same plane in the hypoechoic area of the synovium /Photoacoustic signal, score 1; ultrasonic/photoacoustic signal detected within half of the hypoechoic area of the synovium, score 2; PD/PA signal detected in more than half of the hypoechoic synovial area, score 3.

In the above-mentioned scoring system, preferably, the information analysis module further includes a local blood oxygen information scoring module, which is used to calculate or process the local blood oxygen information according to a specific standard.

In the above-mentioned scoring system, preferably, the local blood oxygen information includes the photoacoustic signal SO ₂ image of the thickened inflammatory lesion area of the joint, and the photoacoustic signal SO ₂ image is specifically divided into three groups: blue and red Alternately with red and blue, the blue is mainly a hypoxic blood flow signal, the red is a hyperoxic blood flow signal, and the red and blue alternates are a mixed blood flow signal.

In the above-mentioned scoring system, preferably, the local blood oxygen information further includes the judgment result of comparing the oxygen saturation value of the local thickened area of the joint with the surrounding normal tendon.

_{The SO 2} value of the thickened inflammatory area was measured by calculating the ratio of the PA signal pixels in the target area at wavelengths of 750 nm and 830 nm. The joint with the highest PA signal is selected to calculate the SO ₂ for each patient. Perform three calculations for each joint and determine the average value as a representative of the oxygenation status of each patient. The patient was classified as hyperoxia with SO ₂ value >90%, and hypoxia with SO ₂ value <85%. The high level of PA signal represents inflammatory activity in the joint. Calculate the PA+SO ₂ score and comprehensively judge the degree of inflammation of the patient.

Another aspect of the present invention provides a rheumatoid arthritis scoring system based on multi-modal photoacoustic ultrasound imaging, which includes an information acquisition module, an information analysis module, and a judgment output module,

The information collection module adopts photoacoustic/ultrasound dual-modality imaging to collect image information of joints in an external form to obtain image information of the local inflammatory area of rheumatoid joints;

The information analysis module classifies and calculates the image information collected by analysis to obtain the characteristic parameters of the image;

The judgment output module combines the characteristic parameters of the image to judge the disease activity of the rheumatoid arthritis patient and output data.

Preferably, the information analysis module includes a semi-quantitative scoring module, the semi-quantitative scoring module statistically calculates the sum of the power Doppler ultrasound imaging score and the photoacoustic imaging score, the power Doppler ultrasound imaging score and the photoacoustic imaging score A semi-quantitative scoring system of 0, 1, 2, and 3 points is used, and the maximum score of each joint is used as the final score of each joint. Both the power Doppler ultrasound imaging (PDUS) score and the photoacoustic imaging (PAI) score use the 0-3 semi-quantitative scoring system first proposed by Szkudlarek et al. (see Szkudlarek M, Court-Payen M, Jacobsen S, et al. .Interobserver agreement in ultrasonography of the fingers and toe joints in rheumatoid arthritis.Arthritis Rheum 2003; 48:955–62. and

Szkudlarek,M.,et al.,Ultrasonography of the metatarsophalangeal joints in rheumatoid arthritis:comparison with magnetic resonance imaging,conventional radiography,and clinical examination.Arthritis Rheum,2004.50(7):p.2103-12.p. The maximum score of the joint is used as the final score of each joint.

Preferably, the PDUS score and PAI score are evaluated by the following criteria: no ultrasound/photoacoustic signal, score 0; less than 3 ultrasound/photoacoustic signals in the same plane in the hypoechoic area of the synovial membrane, score 1; hypoechoic synovial membrane Ultrasound/photoacoustic signal is detected within half (area) of the area, score 2; Ultrasound/photoacoustic signal is detected in hypoechoic region of synovium over half (area), score 3. Specifically, the hypoechoic area of the synovial membrane is the area of synovial hyperplasia, that is, the abnormal hypoechoic tissue in the joint cavity, which is not transferable and difficult to be compressed, and may show Doppler blood flow signals. The blood flow signal score ROI area (region of interest) is the area of synovial hyperplasia.

Preferably, the information analysis module further includes a local blood oxygen information scoring module, and the local blood oxygen information scoring module performs calculation or software calculation processing on the local blood oxygen information according to a specific standard.

Preferably, the local blood oxygen information includes a photoacoustic signal SO ₂ image of a thickened inflammatory lesion area of a joint, and a photoacoustic signal of a thickened inflammatory lesion area of each joint (including synovitis, tenosynovitis, or perianinitis) The SO ₂ images are divided into three groups: blue (mainly hypoxic blood flow signal), red (mainly hyperoxic blood flow signal) and red and blue (mixed blood flow signal), the blue is hypoxic blood flow The signal is dominant, the red is the hyperoxic blood flow signal, and the red and blue phases are the mixed blood flow signal.

Preferably, the local blood oxygen information further includes the determination result of the comparison of _{the oxygen saturation value (SO 2 value) of the inflammatory area of the local thickening of the joint with the surrounding normal tendon.} The oxygen saturation value SO ₂ is calculated by the following formula:

SO ₂ (r)=C _Hb (r)/(C _Hb (r)+C _deHb (r))=(PA(λ ₁ ,r)*ε _deHb (λ ₂ )-PA(λ ₂ ,r)* ε _deHb (λ ₁ ))/(PA(λ ₁ ,r)*(ε _deHb (λ ₂ )-ε _Hb (λ ₂ ))+PA(λ ₂ ,r)*(ε _Hb (λ ₁ )-ε _deHb (λ ₁ ))

Among them, Hb is endogenous oxygenated hemoglobin, deHb is deoxygenated hemoglobin,

PA(λ ₁ ,r)*=μ _a (λ ₁ ,r)=C _Hb (r)ε _Hb (λ ₁ )+C _deHb (r)ε _deHb (λ ₁ )

PA(λ ₂ ,r)*=μ _a (λ ₂ ,r)=C _Hb (r)ε _Hb (λ ₂ )+C _deHb (r)ε _deHb (λ ₂ )

λ ₁ =750 nm, λ ₂ =830 nm.

Among them, μ _a (λ,r) represents the optical absorption coefficient of blood, ε _Hb (λ) represents the molar extinction of endogenous oxygenated hemoglobin (Hb), and C _Hb (r) represents endogenous oxygenated hemoglobin (Hb) The concentration of ε _deHb (λ) represents the molar extinction of deoxyhemoglobin (deHb), and C _deHb (r) represents the concentration of deoxyhemoglobin (deHb). PA(λ ₁ ,r)* is _{the PA that ignores φ(λ 1} ,r), and PA(λ ₂ ,r)* is _{the PA that ignores φ(λ 2} ,r). The PA value can be directly collected by the ultrasound probe. Any pixels with negative _{SO 2} values were removed in the subsequent analysis.

_{Specifically, the SO 2} value of the thickened inflammatory area is measured by calculating the ratio of the PA signal pixels in the target area at wavelengths of 750 nm and 830 nm. The joint with the highest PA signal is selected to calculate the SO ₂ for each patient. Perform three calculations for each joint and determine the average value as a representative of the oxygenation status of each patient. The patient was classified as hyperoxia with SO ₂ value >90%, and hypoxia with SO ₂ value <85%. The high level of PA signal represents inflammatory activity in the joint. Calculate the PA+SO ₂ score and comprehensively judge the degree of inflammation of the patient.

The joints include the second metacarpophalangeal joint (MCP 2), the third metacarpophalangeal joint (MCP 3), the second proximal interphalangeal joint (PIP 2), and the third proximal joint on the side with obvious symptoms (the dominant side of clinical symptoms) Interphalangeal joint (PIP 3), second metatarsophalangeal joint (MTP 2), third metatarsophalangeal joint (MTP 5) and wrist joint.

Further, the present invention also provides a device including the above-mentioned scoring system, which includes an ultrasonic probe that collects audio-visual information; the host is respectively connected to the light transmitting and light transmitting module and the ultrasonic phased array transmitting and receiving module through a two-core cable, It is used to drive the emission of laser and ultrasound signals, and receive photoacoustic signals and reflected ultrasound signals for imaging; the processor converts specific parameters of the imaging signal into specific values; the output device outputs specific images and values.

Preferably, the ultrasonic probe includes a phased array probe, a convex array probe, and a linear array probe.

Preferably, the processor is any commercially available charge-coupled device capable of converting photoacoustic images into digital signals.

Preferably, the output device is a printer.

The beneficial effects of the present invention are as follows:

The present invention uses a multi-modal photoacoustic/ultrasound imaging system and equipment for the evaluation of rheumatoid arthritis for the first time. The advantage lies in that the multi-modal system and equipment adopts a handheld photoacoustic/ultrasound probe, which conforms to the usage habits of clinicians. The scoring system of the present invention performs a semi-quantitative evaluation of the blood flow in the local inflammatory area of rheumatoid joints, determines the degree of imaging inflammation, and uses 7 typical joints for evaluation, which is consistent with the latest international traditional ultrasound assessment of joint selection methods , The implementation process and calculation process are simple and easy to implement, which is conducive to clinical implementation.

Description of the drawings

Figure 1 is an image of the wrist joint of a patient with RA. The PD score of the hypoechoic area with thickened synovium is 0 point, PA is 1 point, and the PA blood oxygen group is red, showing hyperoxic blood flow signals;

Figure 2 is an image of the wrist joint of a patient with RA. The PD score of the hypoechoic inflammatory area adjacent to the tendon sheath is 2 points, PA is 3 points, and the PA blood oxygen group is red, showing hyperoxic blood flow signals;

Fig. 3 is a block diagram of the structure of a rheumatoid arthritis scoring system based on multi-modal photoacoustic ultrasound imaging of the present invention;

Figure 4 is _{a box plot of the relative SO 2} values of 26 RA patients (PA-sum>0);

Fig. 5 is an image of the wrist joint of a female RA patient (the first person) in Example 3;

Figure 6 is a schematic diagram of the hypoechoic area of the synovial membrane, that is, the striped irregular area circled in the figure, marked with the letter A in the figure;

FIG. 7 is an image of the wrist joint of a male patient (second person) in Embodiment 3;

Figure 8 is an image of the MCP2 joint (inflammation around the tendon) of the male patient (second) in Example 3;

Figure 9 is an image of the PIP2 joint of the male patient (third person) in Example 3;

Figure 10 is an image of the MCP2 joint (inflammation around the tendon) of the male patient (third person) in Example 3;

Fig. 11 is an image of the wrist joint of a male patient (third person) in Example 3;

Fig. 12 is a structural diagram of a rheumatoid arthritis scoring device based on multi-modal photoacoustic ultrasound imaging of the present invention.

In the accompanying drawings, except for Figures 3 and 4, the upper left is an energy Doppler ultrasound image, the upper right is a photoacoustic blood oxygen saturation image, the lower left is a 750nm photoacoustic imaging image, and the lower right is an 850nm light. Acoustic imaging diagram.

Detailed ways

The following examples are used to illustrate the present invention, but not to limit the scope of the present invention. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art. The present invention will be described in detail below with reference to the drawings and embodiments.

In this embodiment, "PA" refers to photoacoustic, "US" refers to ultrasound, "PAI" refers to photoacoustic imaging, "PDUS" and "PD" refer to power Doppler ultrasound, and "CDUS" refers to Doppler ultrasound , "RA" refers to rheumatoid arthritis, "SO ₂ "refers to oxygen saturation, "Hb" refers to oxygenated hemoglobin, and "deHb" refers to deoxygenated hemoglobin.

PA/US dual-mode imaging system

The dual-mode system in this study is based on a high-end clinical ultrasound machine (Resona 7, Mindray Bio-Medical Electronics Co., Ltd.), which can perform and collect data required for PA imaging. The delay and sum algorithm is used to reconstruct the PA imaging results online. The clinical linear probe (L9-3U, Mindray Bio-Medical Electronics Co., Ltd.) has 192 elements, the size of each element is 0.2 mm, and the center frequency is 5.8 MHz. The laser source is an OPO tunable laser (Spitlight 600-OPO, Innolas laser GmbH), which generates 700-850 nm laser pulses at 10 Hz. In our study, 750nm (peak absorption of deoxyhemoglobin) and 830nm (dominant absorption of oxyhemoglobin) were used for PA functional imaging. The time division multiplexing method is used to realize real-time imaging of PA/US with two wavelengths and SO ₂ mapping at a frame rate of 5 Hz. The screen is divided into 4 parts to provide multi-modal imaging. The first part of the screen is traditional ultrasound imaging, and provides three different ultrasound mode options, including grayscale US imaging, CDUS and PDUS. The second part and the third part are PA imaging, integrated on the gray-scale US imaging, with wavelengths of 750nm and 830nm, used to detect oxyhemoglobin and deoxyhemoglobin respectively. The fourth part of the screen is the SO ₂ content in pseudo-color form, calculated by measuring oxygenated and deoxygenated hemoglobin, and integrated from two PA images of two different wavelengths. The red PA signal represents the hyperoxia of the local tissue, and the hypoxia is reflected by the blue PA signal.

patient

From August 2018 to June 2019, recruited from the Rheumatology Clinic of Peking Union Medical College Hospital (PUMCH) and diagnosed with RA by two experienced rheumatologists. All research procedures were approved by the Institutional Review Committee of Peking Union Medical College Hospital. And has received written consent notices from all recruited patients and healthy volunteers.

Example 1 Construction of a multi-modal photoacoustic/ultrasound imaging system

1. Data analysis and image acquisition

(1) Inspection procedures

Select the clinically dominant side MCP 2, MTP 3, PIP 2, PIP 3, MTP 2, MTP 5 and the wrist joint for multi-modal imaging. Prepare a white surface for the patient and place it on the table next to the imaging system. Place the probe on the back of the fingers, wrists, and toes with the gel in between. First, traditional ultrasound scanning of joints, including grayscale ultrasound, CDUS, and PDUS, is performed by an experienced ultrasound operator. After that, the same operator performs PA/US imaging on each joint. By cutting the PA button on the operation screen, the laser is turned on, and real-time PA and US imaging are played at the same time. The depth of the visual MCP and PIP joints is set to 2 cm, and the depth of the wrist is 2.5-3 cm. During the PA scan, the first part of the screen can be switched to any mode of ultrasound for a complementary comparison of US and PA imaging. The inspection time for conventional US is about 30 seconds to 1 minute, and the multimodal PA/US imaging time for each joint is about 2 minutes. The operator of ultrasound scanning and multimodal imaging has two years of experience in musculoskeletal ultrasound and has received one month of system operation training.

(2) PUS and PAI score

The 0-3 semi-quantitative PDUS scoring method first proposed by Szkudlarek et al. was used in this study. For the PA score, we use a 0-3 point semi-quantitative scoring method similar to the PDUS score as a reference, see the scoring standard for details. Evaluation of synovitis and tenosynovitis/peritendinitis PDUS and PA evaluation according to the scoring system of each joint. The maximum score (0-3) of synovitis or tenosynovitis/peritenonitis observed from the back, palm, or lateral side is used as the final score for each joint. Calculate the sum of each participant's PDUS score (0-21) and PA score (0-21).

The scoring criteria are: score 0, no PD/PA signal; score 1, PD/PA signal less than 3 bar in the same plane; score 2, PD/PA signal in the hypoechoic area of hypertrophic synovium, tenosynovitis, and perianinitis With a score of 3, PD/PA signals in more than half of the inflammation area. The traditional US and PA/US images are evaluated by two sonographers who do not know the patient's information and only examine the clinical manifestations of the joints. One of the three images of PA imaging with the strongest PA signal will be selected for scoring. The inter-observer agreement of the two radiologists was evaluated. When a discrepancy is found between the two sonographers, the images are re-evaluated until a consistent score is obtained.

2. Statistical analysis

Statistical analysis was performed using SPSS statistical software (SPSS, Chicago, 21.0). The mean ± standard deviation of quantitative parameters, including imaging scores, clinical scores, and laboratory data. The correlation between the imaging scores (PDUS score and PA score) was evaluated by the two-sided accurate Spearman correlation coefficient. The observer agreement between the two sonographers is measured by the kappa statistic.

3. Results

A total of 30 RA patients were recruited in this study, including 26 women and 4 men, with an average age of 50.8 years.

Two radiologists used the aforementioned scoring system to evaluate the results of PD and PA imaging. The kappa value of the two physicians was 0.82, which represented good inter-observer agreement. Table 1 summarizes the three clinical scores and the PDUS and PA scores of the patients;

Table 2 shows the three clinical scores calculated by spss and the patient’s average PDUS and PA scores and standard deviation (SD). The three clinical scores include disease activity score (DAS28), clinical disease activity index (CDAI) and simplified disease activity Index (SDAI), three clinical scoring standards: DAS28 evaluation of disease activity level can be interpreted as remission (DAS28<2.6), low (2.6≤DAS28<3.2), moderate (3.2≤DAS28≤5.1) or high (DAS28>5.1) ); CDAI evaluation of disease activity level can be interpreted as remission (CDAI≤2.8), low (2.8<CDAI≤10), moderate (10<CDAI≤22) or high (CDAI>22); SDAI evaluation of disease activity level can explain To relieve (SDAI≤3.3), low (3.3<SDAI≤11), moderate (11<SDAI≤26), or high (SDAI>26); clinical scoring uses existing conventional scoring standards (see Anderson JK, Zimmerman L, Caplan L, Michaud K. Measures of rheumatoid arthritis disease activity: Patient (PtGA) and Provider (PrGA) Global Assessment of Disease Activity, Disease Activity Score (DAS) and Disease Count Activity Score, with 28-Joint Activity Score, with 28-Joint Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Patient Activity Score (PAS) and Patient Activity Score-II (PASII), Routine Assessment of Patient Index Data (RAPID), Rheumatoid Activity and Arthritis Disease Index (Activity AI) Disease Activity Index-5 (RADAI-5), Chronic Arthritis Systemic Index (CASI), Patient-Based Disease Activity Score With ESR(PDAS1) and Patient-Based Disease Activity Score without ESR (PDAS2), and Mean Overall Index for Rheumatoid Arthritis (MOI-RA). Arthritis care&research.2011; 63Suppl 11:S14-36.). The PA score was significantly higher than the PD score, and the p value was <0.001. A total of 175 joints were examined using the PA/US system, including MCP, PIP, MTP and wrist joints. The 16 joints are divided into the highest level of PA imaging and PDUS, that is, the score is 3 points. In PA imaging, 15 joints were scored as 1 point, but no signal was detected in PDUS. According to the data in Table 2, the average value of DAS28 is 4.08, the disease activity index is medium, the SDAI value is 23.74, the disease activity index is medium, the CDAI value is 22.01, and the disease activity index is high. The inventor's preliminary judgment is that the average PDUS score is greater than or equal to The disease activity index at 2.87 is medium or above, and the average PA score is 4.43 or higher. The disease activity index is medium or above.

Table 3 lists the correlation between multimodal photoacoustic/ultrasound scores, imaging scores and clinical scores. PA scores and PDUS scores have a strong correlation with each other (r=0.821, p<0.0001). The PA score was significantly correlated with the three clinical scores (r=0.680, 0.721,0.700, respectively), and the p value was <0.001. On the other hand, in this study, the PDUS score of the joint is correlated with the three clinical scores (r=0.532, 0.564, 0.564, respectively), with p value<0.01. According to Table 3, it can be seen that the PA and PD scores are respectively All of them are significantly positively correlated with the three clinical scores, and have passed the hypothesis test, indicating that the PA and PD scores are clinically verified and accurate.

Table 1 Clinical score and multimodal photoacoustic/ultrasound score data

Serial number	DAS28	SDAI	CDAI	PDUS score	PAI score
1	4.29	23.65	23.00	9	9
2	4.51	19.70	18.20	8	8
3	6.00	43.78	42.00	15	15
4	7.32	60.11	57.00	1	12
5	2.60	5.23	5.00	2	3
6	4.60	22.06	21.40	3	3
7	2.87	13.06	13.00	0	2
8	6.41	46.20	39.4	2	3
9	5.02	27.64	26.00	3	5
10	5.25	28.3	27	2	7
11	2.22	5.48	5.00	3	3
12	4.61	24.264	23.9	4	5
13	3.68	18.25	18.00	3	3
14	1.92	5.11	5	1	3
15	6.6	70.6	67	5	7
16	3.99	22.62	22.6	5	7
17	4.59	25.38	24.5	2	2

18	6.28	51.6	39	7	9
19	5.38	32.05	25.5	1	2
20	5.39	36.22	35	3	5
twenty one	1.18	1.05	1	0	2
twenty two	4.83	29.94	29.3	3	5
twenty three	1.68	1.9	1.5	0	1
twenty four	1.21	1.54	1.5	0	2
25	6.84	55.72	51	2	7
26	2.84	8.86	8.5	2	3

Table 2 Clinical scores and average of multimodal photoacoustic/ultrasound scores

Table 3 Correlation of multimodal photoacoustic/ultrasound scores and clinical scores

4. Local blood oxygen information

_{Among the 30 patients, relative SO 2} values were calculated for a total of 26 patients with detectable PA signals. _{The SO 2} value of the thickened inflammatory area was measured by calculating the ratio of the PA signal pixels in the target area at wavelengths of 750 nm and 830 nm. Using a high-end clinical ultrasound machine (Resona 7, Mindray Bio-Medical Electronics Co., Ltd.), the sonographer can _{perform the SO 2} calculation process by tracking the target area _{on the SO 2 interface on the screen.} After drawing ROIs (regions of interest), the SO ₂ value will automatically be displayed in the lower right corner of the screen. The joint with the highest PA signal is selected to calculate the SO ₂ for each patient. Three calculations were performed for each joint, and the average value was determined as a representative of the oxygenation status of each patient. _{The SO 2} values of the joints in 26 patients ranged from 67.15% to 98.15%, the average was 87.5+10.1%, and the median was 93.11%. Figure 4 shows the _{box plot of the relative SO 2} values of the patients. From it, it can be observed that the relative blood oxygen value of 26 patients presents a binary distribution with obvious high and low trends on the box plot, and there is a two-category distribution between the two. A blank area ranging from about 85% to 90%. Based on this, we classified 15 patients as hyperoxia, that is, the relative SO ₂ value was less than 90%, and 11 patients were classified as hypoxia, that is The relative SO ₂ value is less than 85%.

Patients with a PA score of <5 were identified as low PA signals, and patients with ≥5 were identified as high PA signals. According to the sum of the PA signal and SO ₂ value, all patients were divided into 5 groups, as a grade variable, with a score of 0-5, where (1) 0: no PA signal; (2) 1: low PA score and hyperoxia; (3) 2: Low PA score and hypoxia; (4) 3: High PA score and hyperoxia; (5) 4: High PA score and hypoxia. The association between the PA+SO ₂ score and the clinical score was also evaluated (see Table 4).

4 without PA signal scored 0, 7 scored 1, 6 scored 2, 8 scored 3, and 5 scored 4. Significant differences in clinical scores were also verified among the 5 groups of PA+SO _{2 scores (see Table 5).} The PA+SO ₂ score also has a good correlation with the clinical score (see Table 6). (Respectively DAS28=0.664, SDAI=0.681, CDAI=0.702, p value<0.001). Considering the relationship between PA score and clinical score, the high level of PA signal represents the inflammatory activity in the joint. In joints with high levels of PA signaling, hypoxic individuals tend to have higher clinical scores, which means a more severe inflammatory state. Hypoxia may be a potential indicator of a high incidence of disease.

In summary, the _{higher the comprehensive score of PA+SO 2} , the more severe the patient's inflammatory state.

Table 4 Clinical scores of PA+SO _{2 scores in 5 groups}

Table 5 Comparison of PA+SO _{2 1-4 points}

Table 6 Correlation between PA+SO ₂ score and clinical score

**. That is, a significant correlation (two-sided) at the level of p = 0.01

Example 2. Rheumatoid arthritis scoring system based on multimodal photoacoustic/ultrasound imaging

As shown in Figure 3,

A scoring system for rheumatoid arthritis based on multi-modal photoacoustic ultrasound imaging, including an information acquisition module, an information analysis module, and an output module,

The information collection module adopts photoacoustic/ultrasound dual-modality imaging to collect image information of joints in vitro to obtain image information of the local inflammatory area of rheumatoid joints;

The information analysis module classifies and calculates the collected image information to obtain the characteristic parameters of the image;

The judgment output module combines the characteristic parameters of the image to judge the disease activity of patients with rheumatoid arthritis and output data.

The information analysis module includes a semi-quantitative scoring module, as well as a local blood oxygen information scoring module, which is used for statistical calculation of the power Doppler ultrasound imaging score and the sum of the photoacoustic imaging scores. Both power Doppler ultrasound imaging scores and photoacoustic imaging scores are used A semi-quantitative scoring system of 0, 1, 2, and 3 points, and the maximum score of each joint is used as the final score of each joint. The local blood oxygen information scoring module is used to calculate or process the local blood oxygen information according to specific standards.

Preferably, the power Doppler ultrasound imaging score and the photoacoustic imaging score are evaluated by the following criteria: no ultrasound/photoacoustic signal, a score of 0; less than 3 ultrasound/photoacoustic signals in the same plane in the hypoechoic area of the synovium, a score of 1. ; Ultrasound/photoacoustic signal detected within half of the hypoechoic area of the synovium, score 2; PD/PA signal detected in more than half of the hypoechoic synovial area, score 3.

Preferably, the local blood oxygen information includes a photoacoustic signal SO ₂ image of a thickened inflammatory lesion area of a joint, and the photoacoustic signal SO ₂ image is specifically divided into three groups: blue, red, and red and blue. Blue is a hypoxic blood flow signal, the red is a hyperoxic blood flow signal, and the red and blue phases are mixed blood flow signals. Still preferably, the local blood oxygen information further includes a determination result of comparing the oxygen saturation value of the local thickened area of the joint with the surrounding normal tendon.

_{The SO 2} value of the thickened inflammatory area was measured by calculating the ratio of the PA signal pixels in the target area at wavelengths of 750 nm and 830 nm. The joint with the highest PA signal is selected to calculate the SO ₂ for each patient. Perform three calculations for each joint and determine the average value as a representative of the oxygenation status of each patient. The patient was classified as hyperoxia with SO ₂ value >90%, and hypoxia with SO ₂ value <85%. The high level of PA signal represents inflammatory activity in the joint. Calculate the PA+SO ₂ score and comprehensively judge the degree of inflammation of the patient.

Embodiment 3. Rheumatoid arthritis scoring system and equipment based on multimodal photoacoustic/ultrasound imaging

As shown in Figure 3,

A scoring system for rheumatoid arthritis based on multi-modal photoacoustic ultrasound imaging, including an information acquisition module, an information analysis module, and an output module,

The information collection module adopts photoacoustic/ultrasound dual-modality imaging to collect image information of joints in vitro to obtain image information of the local inflammatory area of rheumatoid joints;

The information analysis module classifies and calculates the collected image information to obtain the characteristic parameters of the image;

The judgment output module combines the characteristic parameters of the image to judge the disease activity of patients with rheumatoid arthritis and output data.

The information analysis module includes a semi-quantitative scoring module, as well as a local blood oxygen information scoring module, which is used for statistical calculation of the power Doppler ultrasound imaging score and the sum of the photoacoustic imaging scores. Both power Doppler ultrasound imaging scores and photoacoustic imaging scores are used A semi-quantitative scoring system of 0, 1, 2, and 3 points, and the maximum score of each joint is used as the final score of each joint. The local blood oxygen information scoring module is used to calculate or process the local blood oxygen information according to specific standards.

Preferably, the power Doppler ultrasound imaging score and the photoacoustic imaging score are evaluated by the following criteria: no ultrasound/photoacoustic signal, a score of 0; less than 3 ultrasound/photoacoustic signals in the same plane in the hypoechoic area of the synovium, a score of 1. ; Ultrasound/photoacoustic signal detected within half of the hypoechoic area of the synovium, score 2; PD/PA signal detected in more than half of the hypoechoic synovial area, score 3.

Preferably, the local blood oxygen information includes a photoacoustic signal SO ₂ image of a thickened inflammatory lesion area of a joint, and the photoacoustic signal SO ₂ image is specifically divided into three groups: blue, red, and red and blue. Blue is a hypoxic blood flow signal, the red is a hyperoxic blood flow signal, and the red and blue phases are mixed blood flow signals. Still preferably, the local blood oxygen information further includes a determination result of comparing the oxygen saturation value of the local thickened area of the joint with the surrounding normal tendon.

As shown in Figure 12, the present invention also provides a device including the above-mentioned scoring system, including an ultrasonic probe 1 for collecting sound and image information; The receiving module is connected to drive the emission of laser and ultrasound signals, and to receive photoacoustic signals and reflected ultrasound signals for imaging; the processor 3 converts specific parameters of the imaging signal into specific values; the output device 4 outputs specific images and values.

Preferably, the ultrasonic probe 1 includes a phased array probe, a convex array probe, and a linear array probe.

Preferably, the processor 3 is any commercially available charge coupled device capable of converting photoacoustic images into digital signals.

Preferably, the output device 4 is a printer.

Preferably, the local blood oxygen information includes a photoacoustic signal SO ₂ image of a thickened inflammatory lesion area of a joint, and the photoacoustic signal SO ₂ image is specifically divided into three groups: blue, red, and red and blue. Blue is a hypoxic blood flow signal, the red is a hyperoxic blood flow signal, and the red and blue phases are mixed blood flow signals. Still preferably, the local blood oxygen information further includes a determination result of comparing the oxygen saturation value of the local thickened area of the joint with the surrounding normal tendon.

_{The SO 2} value of the thickened inflammatory lesion area was measured by calculating the ratio of the PA signal pixels in the target area at the wavelengths of 750 nm and 830 nm. The joint with the highest PA signal is selected to calculate the SO ₂ for each patient. Perform three calculations for each joint, and determine the average value as a representative of the oxygenation status of each patient. The patient was classified as hyperoxia with SO ₂ value >90%, and hypoxia with SO ₂ value <85%. The high level of PA signal represents inflammatory activity in the joint. Calculate the PA+SO ₂ score and comprehensively judge the degree of inflammation of the patient.

Example 4. Scoring application example

In April 2019, a 45-year-old female patient who was clinically diagnosed with RA was selected for multimodal imaging examination (first place). A total of 7 joints with obvious clinical manifestations were examined. There was no obvious blood flow signal in the joint synovium, tendon sheath and peripheral area PD/PA of MTP2, MTP3, MCP2, MCP3, PIP2, and PIP3. The imaging findings of the wrist joint are shown in Figure 5. The synovium of the wrist joint is obviously thickened, and the color Doppler (PD) blood flow signal can be seen in the thickened area. Both sonographers scored 2 points. In the two wavelengths of photoacoustic (PA) images, more signals are selected The two doctors scored 3 points for the 830nm image, the patient’s multimodal imaging color Doppler (PD) total score was 2 points, the photoacoustic (PA) total score was 3 points, and the blood flow signal They are divided into the red group, which means hyperoxic blood flow. The DAS28 score of this patient was 2.60 points, SDAI was 5.23 points, CDAI was 5.20 points, SO ₂ value: 93.52 (hyperoxia), PA+SO ₂ score was 1 point. The comprehensive score of the patient by the method of this application is low, the disease activity level is low, and the multimodal photoacoustic/ultrasound score is consistent with the clinical score.

A 68-year-old male RA patient (the second) was selected in June 2019, complaining of pain in both fingers and wrist joints. A total of 7 joints with obvious clinical manifestations were examined. The results are shown in Figure 7-9. The synovium of the MCP2 joint cavity is significantly thickened, the photoacoustic (PA) score is 2 points, the color Doppler (PD) score is 2 points, the PIP2 and PIP3 joint synovium is thickened, and the photoacoustic (PA) score is 2 points. PA) score is 2 points, color Doppler (PD) score is 1 point, wrist synovial membrane is obviously thickened, photoacoustic (PA) and color Doppler (PD) can show abundant blood flow signals, both scores are 3. Minute. The patient’s DAS28 score was 6.28 points, SDAI was 51.60 points, CDAI was 39.00 points, SO ₂ value: 97.33 (hyperoxia), PA+SO ₂ score was 3 points, the patient’s comprehensive score was higher by the method of this application, and the disease The activity level is in a highly active period, and further medication is needed. The patient's multimodal imaging examination results showed that the color Doppler ultrasound semi-quantitative scoring results and the photoacoustic semi-quantitative scoring results were basically the same, and consistent with the clinical score.

A 43-year-old male RA patient (the third) was selected in June 2019. He complained of pain in both fingers and wrist joints. A total of 7 joints with obvious clinical manifestations were examined. The results are shown in Figure 10-11. The synovium of the joint cavity of MCP2 is obviously thickened. The photoacoustic (PA) score is 3 points, and the color Doppler (PD) score is 2 points. The synovial membrane of the wrist joint is obviously thickened. ) The score is 2 points, and the color Doppler (PD) score is 1 point. The patient’s DAS28 score was 4.83 points, SDAI was 29.94 points, CDAI was 29.30 points, SO ₂ value: 79.01 (hypoxia), PA+SO ₂ score was 4 points, the patient had a high comprehensive score by the method of this application, and disease activity The level is in a period of high activity, and further medication is needed. The patient's multimodal imaging examination results showed that the color Doppler ultrasound semi-quantitative scoring results and the photoacoustic semi-quantitative scoring results were basically the same, and consistent with the clinical score.

Although the present invention has been described in detail above with general descriptions and specific implementations, some modifications or improvements can be made on the basis of the present invention, which is obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention belong to the scope of the present invention.

Industrial applicability

The multi-modal photoacoustic/ultrasound imaging rheumatoid arthritis scoring system, equipment and application of the present invention can be used in industry and have industrial practicability.

Claims (20)

1. The application of multimodal photoacoustic/ultrasound imaging rheumatoid arthritis scoring system is characterized in that it includes the following steps:

   (1) Photoacoustic/ultrasound dual-modality imaging collects image information of joints in an external form;

   (2) Analyze the collected image information for multi-modal photoacoustic/ultrasound scoring;

   (3) Judging the disease activity of patients with rheumatoid arthritis based on the results of multimodal photoacoustic/ultrasound scores combined with local blood oxygen information.
2. The application of claim 1, wherein the multi-modal photoacoustic/ultrasound scores include power Doppler ultrasound imaging scores and photoacoustic imaging scores, and the power Doppler ultrasound imaging scores and photoacoustic imaging scores The scoring uses a semi-quantitative scoring system of 0, 1, 2, and 3 points, and the maximum score of each joint is used as the final score of each joint.
3. The application according to claim 2, wherein the power Doppler ultrasound imaging score and the photoacoustic imaging score are evaluated by the following criteria: no ultrasound/photoacoustic signal, score 0; less than 3 in the same plane in the hypoechoic area of synovium Ultrasound/photoacoustic signal of the strip, score 1; Ultrasound/photoacoustic signal detected within half of the hypoechoic area of the synovium, score 2; PD/PA signal detected in more than half of the hypoechoic area of the synovium, score 3.
4. The application according to claim 1, wherein the local blood oxygen information is measured by calculating the ratio of the PA signal pixels of the thickened inflammatory area at 750nm and 830nm wavelengths, and the measured thickened inflammatory area SO ₂ A value> 90% is judged as a hyperoxia state, and a SO ₂ value <85% is judged as a hypoxic state.
5. The application according to claim 1, wherein the local blood oxygen information further includes a determination result of comparing the oxygen saturation value of the local thickened area of the joint with the surrounding normal tendon, and the oxygen saturation value SO ₂ passes the following Formula calculation:

   SO ₂ (r)=C _Hb (r)/(C _Hb (r)+C _deHb (r))=(PA(λ ₁ ,r)*ε _deHb (λ ₂ )-PA(λ ₂ ,r)* ε _deHb (λ ₁ ))/(PA(λ ₁ ,r)*(ε _deHb (λ ₂ )-ε _Hb (λ ₂ ))+PA(λ ₂ ,r)*(ε _Hb (λ ₁ )-ε _deHb (λ ₁ ))

   Among them, Hb is endogenous oxygenated hemoglobin, deHb is deoxygenated hemoglobin,

   PA(λ ₁ ,r)*=μ _a (λ ₁ ,r)=C _Hb (r)ε _Hb (λ ₁ )+C _deHb (r)ε _deHb (λ ₁ )

   PA(λ ₂ ,r)*=μ _a (λ ₂ ,r)=C _Hb (r)ε _Hb (λ ₂ )+C _deHb (r)ε _deHb (λ ₂ )

   λ ₁ =750 nm, λ ₂ =830 nm.
6. The application according to claim 1, wherein the joints in step (1) include the second metacarpophalangeal joint, the third metacarpophalangeal joint, the second proximal interphalangeal joint, and the third proximal joint with obvious symptoms. Interphalangeal joints, second metatarsophalangeal joints, third metatarsophalangeal joints and wrist joints.
7. A rheumatoid arthritis scoring system based on multi-modal photoacoustic ultrasound imaging is characterized in that it includes an information acquisition module, an information analysis module, and an output module,

   The information collection module adopts photoacoustic/ultrasound dual-modality imaging to collect image information of joints in an external form to obtain image information of the local inflammatory area of rheumatoid joints;

   The information analysis module classifies and calculates the collected image information to obtain characteristic parameters of the image;

   The judgment output module combines the characteristic parameters of the image to judge the disease activity of the rheumatoid arthritis patient and output data.
8. The scoring system according to claim 7, wherein the information analysis module comprises a semi-quantitative scoring module for statistical calculation of the energy Doppler ultrasound imaging score and the total of the photoacoustic imaging score, and the energy Doppler ultrasound Both imaging score and photoacoustic imaging score adopt a semi-quantitative score system of 0, 1, 2, and 3 points, and the maximum score of each joint is used as the final score of each joint.
9. The scoring system according to claim 8, wherein the power Doppler ultrasound imaging score and the photoacoustic imaging score are evaluated by the following criteria: no ultrasound/photoacoustic signal, the score is 0; in the same plane of the hypoechoic area of the synovium, it is less than 3 ultrasonic/photoacoustic signals, score 1; ultrasonic/photoacoustic signals detected within half of the hypoechoic area of the synovial membrane, score 2; PD/PA signals detected in more than half of the hypoechoic synovial area, Score 3.
10. 8. The scoring system according to claim 7, wherein the information analysis module further comprises a local blood oxygen information scoring module, which is used to calculate or process the local blood oxygen information according to a specific standard.
11. A rheumatoid arthritis scoring system based on multi-modal photoacoustic ultrasound imaging is characterized in that it includes an information acquisition module, an information analysis module, and an output module,

    The information collection module adopts photoacoustic/ultrasound dual-modality imaging to collect image information of joints in an external form to obtain image information of the local inflammatory area of rheumatoid joints;

    The information analysis module classifies and calculates the collected image information to obtain characteristic parameters of the image;

    The judgment output module combines the characteristic parameters of the image to judge the disease activity of the rheumatoid arthritis patient and output data.
12. The scoring system according to claim 11, wherein the information analysis module comprises a semi-quantitative scoring module for statistical calculation of the energy Doppler ultrasound imaging score and the total of the photoacoustic imaging score, the energy Doppler ultrasound imaging Both imaging score and photoacoustic imaging score adopt a semi-quantitative score system of 0, 1, 2, and 3 points, and the maximum score of each joint is used as the final score of each joint.
13. The scoring system of claim 12, wherein the power Doppler ultrasound imaging score and the photoacoustic imaging score are evaluated by the following criteria: no ultrasound/photoacoustic signal, the score is 0; in the same plane of the hypoechoic area of the synovium, it is less than 3 ultrasonic/photoacoustic signals, score 1; ultrasonic/photoacoustic signals detected within half of the hypoechoic area of the synovial membrane, score 2; PD/PA signals detected in more than half of the hypoechoic synovial area, Score 3.
14. The scoring system according to claim 11, wherein the information analysis module further comprises a local blood oxygen information scoring module, which is used to calculate or process the local blood oxygen information according to a specific standard.
15. The scoring system according to claim 14, wherein the local blood oxygen information includes a photoacoustic signal SO ₂ image of a thickened inflammatory lesion area of a joint, and the photoacoustic signal SO ₂ image is specifically divided into three groups: Blue, red, and red and blue are alternated, the blue is mainly a hypoxic blood flow signal, the red is a hyperoxic blood flow signal, and the red and blue alternates are a mixed blood flow signal.
16. The scoring system according to claim 14, wherein the local blood oxygen information further comprises a determination result of comparing the oxygen saturation value of the local thickened area of the joint with the surrounding normal tendon.
17. The equipment comprising the scoring system according to any one of claims 11-16, characterized in that it comprises an ultrasonic probe that collects sound and image information; the host is connected to the light emission and light transmission module and the ultrasonic phased array emission and ultrasonic phased array through a two-core cable. The receiving module is connected to drive the emission of laser and ultrasonic signals, and to receive the photoacoustic signal and the reflected ultrasonic signal imaging; the processor converts the specific parameters of the imaging signal into specific values; the output device outputs specific images and values.
18. The device according to claim 17, wherein the ultrasonic probe includes a phased array probe, a convex array probe, and a linear array probe.
19. 17. The device of claim 17, wherein the processor is any commercially available charge-coupled device capable of converting photoacoustic images into digital signals.
20. The apparatus according to claim 17, wherein the output device is a printer.

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