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CN115474898A - Method and system for multi-modal imaging evaluation of synovial membrane oxygenation state and RA activity - Google Patents

Method and system for multi-modal imaging evaluation of synovial membrane oxygenation state and RA activity Download PDF

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CN115474898A
CN115474898A CN202210970076.1A CN202210970076A CN115474898A CN 115474898 A CN115474898 A CN 115474898A CN 202210970076 A CN202210970076 A CN 202210970076A CN 115474898 A CN115474898 A CN 115474898A
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杨萌
姜玉新
赵辰阳
王铭
张睿
李建初
李雪兰
刘思锐
纪菲
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Abstract

多模态成像测评滑膜氧合状态和RA活动度的方法与系统,更准确地获得光声成像测量的组织氧饱和度(SO2)和临床标准评分之间的关联,并确定其在评估RA疾病活动度中的潜在效用。方法包括:(1)通过超声机、可调谐光参量振荡器激光器建立多模态成像系统,在体外采集图像信息;(2)勾画滑膜感兴趣区域,计算SO2相对值;(3)进行多模态光声/超声图像评分;(4)根据SO2相对值进行氧合状态分组;(5)收集图像对应患者的临床资料和临床评分;(6)进行统计分析,统计学意义被定义为P值为小于0.05。

Figure 202210970076

A method and system for evaluating synovial oxygenation status and RA activity with multimodal imaging, to more accurately obtain the correlation between tissue oxygen saturation (SO 2 ) measured by photoacoustic imaging and clinical standard scores, and to determine its role in evaluating Potential utility in RA disease activity. The method includes: (1) establishing a multi-modal imaging system with an ultrasound machine and a tunable optical parametric oscillator laser, and collecting image information in vitro; (2) delineating the region of interest in the synovium and calculating the relative value of SO 2 ; (3) carrying out Multimodal photoacoustic/ultrasound image scoring; (4) Oxygenation status grouping according to SO2 relative value; ( 5 ) Collecting clinical data and clinical scores of patients corresponding to images; (6) Statistical analysis was performed, and statistical significance was defined For P-values less than 0.05.

Figure 202210970076

Description

多模态成像测评滑膜氧合状态和RA活动度的方法及系统Method and system for evaluating synovial membrane oxygenation status and RA activity by multimodal imaging

技术领域technical field

本发明涉及医学图像处理的技术领域,尤其涉及一种多模态成像测评滑膜氧合状态和RA活动度的方法,以及多模态成像测评滑膜氧合状态和RA活动度的系统,其主要用于获得光声成像测量的组织氧饱和度(SO2)和临床标准评分之间的关联,并确定其在评估RA疾病活动度中的潜在效用。The present invention relates to the technical field of medical image processing, in particular to a multimodal imaging method for evaluating synovial membrane oxygenation status and RA activity, and a multimodal imaging system for evaluating synovial membrane oxygenation status and RA activity. The primary purpose was to obtain the association between tissue oxygen saturation (SO 2 ) measured by photoacoustic imaging and clinical norm scores, and to determine its potential utility in assessing RA disease activity.

背景技术Background technique

超声成像(ultrasound,US)和磁共振成像(magnetic resonance imaging,MRI)是在临床被广泛使用的评估关节炎的影像学方法,二者均对软组织疾病的诊断具有较好的敏感性。由于超声成本较低,并且近来超声高频探头分辨率提高,超声成像在RA(Rheumatoidarthritis,类风湿性关节炎)评估中越来越受到重视。然而,最近关于超声在RA中的研究报道了相互矛盾的结果,使超声在RA中的作用值得商榷。一些研究表明,超声关节炎征象可以预测药物减量后的RA复发。而其他一些大型研究将超声标准纳入了RA患者管理,并与仅依据临床标准管理的患者进行了对比,结果显示超声在RA疾病管理的没有明显的附加价值。研究还显示,超声滑膜炎评分与临床疾病活动的相关性相对偏低(较低-中等,0.43-0.61)。因此,为了提高超声成像在评估RA和指导治疗方面的有效性,现阶段临床需要开发能够提供额外诊断信息以补充超声成像评估RA的新型影像学手段。Ultrasound imaging (US) and magnetic resonance imaging (magnetic resonance imaging, MRI) are imaging methods widely used in clinical assessment of arthritis, both of which have good sensitivity for the diagnosis of soft tissue diseases. Due to the low cost of ultrasound and the recent improvement in the resolution of high-frequency ultrasound probes, ultrasound imaging has received more and more attention in the evaluation of RA (Rheumatoid arthritis, rheumatoid arthritis). However, recent studies on ultrasound in RA have reported conflicting results, making the role of ultrasound in RA questionable. Several studies have shown that ultrasound signs of arthritis can predict RA recurrence after drug tapering. However, other large studies that incorporated ultrasound criteria into the management of RA patients compared with patients managed according to clinical criteria alone showed no significant added value of ultrasound in the management of RA disease. The study also showed a relatively low correlation between the ultrasound synovitis score and clinical disease activity (low-moderate, 0.43-0.61). Therefore, in order to improve the effectiveness of ultrasound imaging in evaluating RA and guiding treatment, it is necessary to develop new imaging methods that can provide additional diagnostic information to supplement ultrasound imaging in evaluating RA.

组织缺氧,也被称为低氧分压,是RA等炎性疾病的重要特征之一。低氧引发异常免疫细胞的激活和增殖,并通过复杂的信号传导途径,加剧RA的炎症反应。改善局部滑膜组织的缺氧已经成为RA治疗干预的一个靶点。因此,识别缺氧可能有助于评估疾病活动及调整治疗策略。以前的研究已经通过侵入性检测方法,验证了在RA患者炎性滑膜中为缺氧状态。然而,通过无创性方法在体内检测滑膜缺氧并揭示其在RA中的具体机制和作用仍然是一个挑战。Tissue hypoxia, also known as low oxygen partial pressure, is one of the important features of inflammatory diseases such as RA. Hypoxia triggers the activation and proliferation of abnormal immune cells, and exacerbates the inflammatory response of RA through complex signal transduction pathways. Amelioration of hypoxia in local synovial tissue has become a target of RA therapeutic intervention. Therefore, identifying hypoxia may help assess disease activity and adjust treatment strategies. Previous studies have validated hypoxia in the inflamed synovium of RA patients using invasive assays. However, it remains a challenge to detect synovial hypoxia in vivo and reveal its specific mechanism and role in RA by noninvasive methods.

光声成像(photoacoustic imaging,PAI)是一种革命性的医学成像技术,可以通过多波长光声检测脱氧或含氧血红蛋白浓度来获取组织的氧饱和度,为检测RA患者局部炎性关节的组织氧合状态提供了一种新的方法。另外,光声成像可以与超声设备相结合,实现双模态光声/超声成像,适用于各种临床场景和疾病诊断,更有利于其临床推广。一些研究已经对RA患者进行了光声成像,以评估关节炎症。然而,这些研究的样本量相对较小,而且很少有研究探索光声检测的氧饱和度与炎症活动度的相关性。申请人于2020年发表的初期光声临床研究表明,通过光声成像可以检测RA患者的组织缺氧,并与患者的整体活动评估(patient global assessment,PGA)和评估者的整体活动评估(evaluator globalassessment,EGA)相关。Photoacoustic imaging (PAI) is a revolutionary medical imaging technology, which can obtain tissue oxygen saturation through multi-wavelength photoacoustic detection of deoxygenated or oxygenated hemoglobin concentration. Oxygenation status offers a new approach. In addition, photoacoustic imaging can be combined with ultrasound equipment to achieve dual-mode photoacoustic/ultrasound imaging, which is suitable for various clinical scenarios and disease diagnosis, and is more conducive to its clinical promotion. Several studies have performed photoacoustic imaging in RA patients to assess joint inflammation. However, the sample sizes of these studies were relatively small, and few studies explored the correlation between photoacoustic oxygen saturation and inflammatory activity. The initial photoacoustic clinical research published by the applicant in 2020 showed that tissue hypoxia in RA patients can be detected by photoacoustic imaging, and it is correlated with the patient global assessment (PGA) and the evaluator's global activity assessment (evaluator). globalassessment, EGA) related.

发明内容Contents of the invention

为克服现有技术的缺陷,本发明要解决的技术问题是提供了一种多模态成像测评滑膜氧合状态和RA活动度的方法,其更准确地获得光声成像测量的组织氧饱和度(SO2)和临床标准评分之间的关联,并确定其在评估RA疾病活动度中的潜在效用。In order to overcome the defects of the prior art, the technical problem to be solved by the present invention is to provide a multimodal imaging method for evaluating synovial membrane oxygenation status and RA activity, which can more accurately obtain tissue oxygen saturation measured by photoacoustic imaging. To assess the association between degree (SO 2 ) and clinical scale scores and to determine their potential utility in assessing RA disease activity.

本发明的技术方案是:这种多模态成像测评滑膜氧合状态和RA活动度的方法,其包括以下步骤:The technical solution of the present invention is: the method for evaluating synovial membrane oxygenation state and RA activity by multimodal imaging, which includes the following steps:

(1)通过超声机、可调谐光参量振荡器激光器建立多模态成像系统,在体外采集图像信息;(1) Establish a multi-modal imaging system through an ultrasound machine and a tunable optical parametric oscillator laser to collect image information in vitro;

(2)勾画滑膜感兴趣区域,计算SO2相对值;(2) Outline the region of interest in the synovial membrane and calculate the relative value of SO 2 ;

(3)进行多模态光声/超声图像评分;(3) Perform multimodal photoacoustic/ultrasound image scoring;

(4)根据SO2相对值进行氧合状态分组;( 4 ) Oxygenation status grouping according to the relative value of SO2;

(5)收集图像对应患者的临床资料和临床评分;(5) Collect the clinical data and clinical score of the patient corresponding to the image;

(6)进行统计分析,统计学意义被定义为P值为小于0.05。(6) Statistical analysis was performed, and statistical significance was defined as a P value less than 0.05.

本发明通过超声机、可调谐光参量振荡器激光器建立多模态成像系统,在体外采集图像信息,勾画滑膜感兴趣区域,计算SO2相对值,进行多模态光声/超声图像评分,根据SO2相对值进行氧合状态分组,收集图像对应患者的临床资料和临床评分,进行统计分析,从而能够更准确地获得光声成像测量的组织氧饱和度(SO2)和临床标准评分之间的关联,并确定其在评估RA疾病活动度中的潜在效用。The present invention establishes a multimodal imaging system through an ultrasonic machine and a tunable optical parametric oscillator laser, collects image information in vitro, outlines the region of interest in the synovial membrane, calculates the relative value of SO 2 , and performs multimodal photoacoustic/ultrasonic image scoring. The oxygenation status is grouped according to the relative value of SO 2 , the clinical data and clinical scores of the patients corresponding to the images are collected, and statistical analysis is performed, so that the relationship between tissue oxygen saturation (SO 2 ) measured by photoacoustic imaging and clinical standard scores can be obtained more accurately. and to determine its potential utility in assessing disease activity in RA.

还提供了多模态成像测评滑膜氧合状态和RA活动度的系统,其包括:A system for assessing synovial membrane oxygenation status and RA activity with multimodal imaging is also provided, including:

采集模块,其配置来通过超声机、可调谐光参量振荡器激光器建立多模态成像系统,在体外采集图像信息;An acquisition module configured to establish a multimodal imaging system through an ultrasound machine and a tunable optical parametric oscillator laser to acquire image information in vitro;

计算模块,其配置来勾画滑膜感兴趣区域,计算SO2相对值;a calculation module configured to delineate a region of interest in the synovial membrane and calculate a relative value of SO ;

评分模块,其配置来进行多模态光声/超声图像评分;a scoring module configured to perform multimodal photoacoustic/ultrasound image scoring;

分组模块,其配置来根据SO2相对值进行氧合状态分组;a grouping module configured to group oxygenation status according to relative SO values ;

收集模块,其配置来收集图像对应患者的临床资料和临床评分;a collection module configured to collect clinical data and clinical scores of patients corresponding to the images;

统计分析模块,其配置来进行统计分析,统计学意义被定义为P值为小于0.05。The statistical analysis module was configured to perform statistical analysis, with statistical significance defined as a P value less than 0.05.

附图说明Description of drawings

图1示出了根据本发明的多模态成像系统的多模态模式。Fig. 1 shows a multi-modal mode of a multi-modal imaging system according to the present invention.

图2是根据本发明的PAI显示SO2示意图。Fig. 2 is a schematic diagram of PAI displaying SO 2 according to the present invention.

图3是根据本发明的模拟血液SO2的光声测量示意图。Fig. 3 is a schematic diagram of photoacoustic measurement of simulated blood SO 2 according to the present invention.

图4示出了根据本发明的SO2值和三种分类的聚类分析。Figure 4 shows the cluster analysis of SO2 values and three classifications according to the present invention.

图5示出了根据本发明的增厚的滑膜组织氧合状态分组。Figure 5 shows the grouping of thickened synovial tissue oxygenation status according to the present invention.

图6示出了根据本发明的两位超声医生SO2值定量Bland-Altman图。Fig. 6 shows the quantitative Bland-Altman diagram of SO2 values of two sonographers according to the present invention.

图7示出了PDUS-血流丰富和PA-高血氧的例子。Figure 7 shows examples of PDUS-rich flow and PA-hyperoxia.

图8示出了PDUS-血流不丰富和PA-低血氧的例子。Figure 8 shows examples of PDUS-poor blood flow and PA-hypoxemia.

图9是根据本发明的综合PDUS评分和PA的氧合分类的新评分(PDPA)示意图。Figure 9 is a schematic diagram of the new score (PDPA) combining PDUS score and oxygenation classification of PA according to the present invention.

图10是根据本发明的多模态成像测评滑膜氧合状态和RA活动度的方法的流程图。FIG. 10 is a flowchart of a method for evaluating synovial membrane oxygenation status and RA activity by multimodal imaging according to the present invention.

其中:in:

SO2:Oxygen saturation血氧饱和度SO 2 : Oxygen saturation

PA-Hyperoxia:Photoacoustic Hyperoxia光声成像-高氧合状态PA-Hyperoxia: Photoacoustic Hyperoxia Photoacoustic Imaging - Hyperoxygenated State

PA-Intermediate status:Photoacoustic Intermediate status:光声成像-中等氧合状态PA-Intermediate status: Photoacoustic Intermediate status: Photoacoustic imaging - intermediate oxygenation status

PA-Hypoxia:Photoacoustic Hypoxia光声成像-低氧合状态PA-Hypoxia: Photoacoustic Hypoxia Photoacoustic Imaging - Hypoxygenated State

Red dominant:红色信号为主Red dominant: Red dominant

Mixed color:红色和蓝色信号混合Mixed color: Red and blue signals are mixed

Blue dominant:蓝色信号为主Blue dominant: blue signal is dominant

PDUS:Power Doppler Ultrasound,能量多普勒超声PDUS: Power Doppler Ultrasound, Power Doppler Ultrasound

PDPA:Power Doppler and Photoacoustic,能量多普勒和光声PDPA: Power Doppler and Photoacoustic, Power Doppler and Photoacoustic

具体实施方式detailed description

组织缺氧是炎症性疾病的特征之一。1970年首次报道RA关节滑膜呈现为缺氧状态。后来,在2010年,Ng等人使用组织氧饱和度仪在关节镜引导下测量滑膜氧饱和度。另外也有研究揭示了缺氧与滑膜组织的异常代谢有关。然而,目前仍缺乏一种无创的方法来评估体内滑膜组织氧合情况,关于滑膜缺氧在RA患者中的具体意义也尚未明确。在这项研究中,用光声成像技术无创地检测了RA患者小关节的滑膜氧合情况,并进一步探讨了滑膜组织氧合状态与临床评价的关系。与以往关于滑膜缺氧的研究相似,也在RA患者增厚的滑膜内检测到了缺氧。而且该研究首次验证了RA患者滑膜缺氧与标准临床评分的相关性。Tissue hypoxia is one of the hallmarks of inflammatory diseases. In 1970, it was first reported that the synovium of RA joints was hypoxic. Later, in 2010, Ng et al. measured synovial oxygen saturation under arthroscopic guidance using a tissue oximeter. In addition, some studies have revealed that hypoxia is related to abnormal metabolism of synovial tissue. However, there is still a lack of a noninvasive method to assess synovial tissue oxygenation in vivo, and the specific significance of synovial hypoxia in RA patients is still unclear. In this study, photoacoustic imaging was used to non-invasively detect synovial oxygenation in facet joints of RA patients, and the relationship between synovial tissue oxygenation status and clinical evaluation was further explored. Similar to previous studies on synovial hypoxia, hypoxia was also detected in the thickened synovium of RA patients. Moreover, this study is the first to verify the correlation between synovial hypoxia and standard clinical scores in RA patients.

多波长光声成像能够更加无创和方便地检测体内组织氧合情况。既往研究初步调研了光声成像在RA患者中的作用。但光声测定的RA患者的滑膜组织氧饱和度和其临床意义仍需进一步研究。基于初步的临床研究,扩大了研究的样本量,得出了关于组织氧饱和度和关节炎症之间关系的更有力的结论。Multiwavelength photoacoustic imaging can detect tissue oxygenation in vivo more non-invasively and conveniently. Previous studies have initially investigated the role of photoacoustic imaging in RA patients. However, the synovial oxygen saturation of RA patients measured by photoacoustics and its clinical significance still need further study. Based on preliminary clinical studies, the sample size of the study was expanded to draw stronger conclusions about the relationship between tissue oxygen saturation and joint inflammation.

申请人经过长时间的思考和大量的试验得到,具有丰富多普勒信号的增厚滑膜往往为高氧状态,而那些能量多普勒血流较少的滑膜则被发现具有较低的PA-SO2水平。申请人推测,这可能是由于多普勒超声可以检测到的滑膜血管是具有相对高流速的功能性血管结构,可以向局部组织输送氧气,提高组织氧合水平。因此,对于没有丰富滑膜血管的增厚滑膜,检测到的氧合水平可能会较低。After a long time of thinking and a large number of experiments, the applicant obtained that the thickened synovium with abundant Doppler signal tends to be hyperoxic, while those synovium with less energy Doppler blood flow were found to have lower PA - SO2 levels. The applicant speculates that this may be because the synovial blood vessels that can be detected by Doppler ultrasound are functional blood vessel structures with relatively high flow rates, which can deliver oxygen to local tissues and improve tissue oxygenation levels. Therefore, for thickened synovium without abundant synovial blood vessels, the detected oxygenation level may be lower.

申请人经过长时间的思考和大量的试验得到,低氧滑膜患者的疾病活动性高于中间氧合状态的患者,这与有关缺氧在炎症中的作用的知识相一致。申请人推断,高氧滑膜的病人可能处于炎症的活跃期,局部组织的新陈代谢不断增加,其氧气供应随后通过增加的滑膜血管得到加强。相反,对于没有丰富滑膜血管的增厚滑膜,由于供氧不足,检测到较低的组织氧饱和度水平。而在多普勒血流较少的关节中,那些缺氧的滑膜可能代表较高的疾病活动度。因此,滑膜的组织氧合状态可能是评估RA疾病活动度的一个有效指标。Applicants have concluded after long thought and extensive testing that patients with hypoxic synovium have higher disease activity than patients with intermediate oxygenation, consistent with knowledge about the role of hypoxia in inflammation. Applicants theorize that patients with hyperoxic synovium may be in an active phase of inflammation, with increased metabolism of local tissues whose oxygen supply is subsequently enhanced through increased synovial vasculature. In contrast, for thickened synovium without abundant synovial vessels, lower tissue oxygen saturation levels were detected due to hypoxia. Whereas in joints with less Doppler flow, those hypoxic synovium may represent higher disease activity. Therefore, the tissue oxygenation status of the synovium may be an effective indicator for evaluating the disease activity of RA.

基于上述分析,将PDUS评分和PA-SO2结合起来,以提高PDUS在评估RA方面的诊断表现。多普勒血流较少和滑膜缺氧的患者,可能有更高的疾病活动度,本发明提出的综合评分PDPA可以识别这部分患者,并在评分中给予较高的分数。结果显示,与单独的PDUS评分相比,综合评分PDPA与临床参数和标准评分有更好的相关性,表明光声测量的组织氧饱和度可以作为RA评估中补充超声成像的一个重要影像学参数。Based on the above analysis, the PDUS score and PA-SO 2 were combined to improve the diagnostic performance of PDUS in evaluating RA. Patients with less Doppler blood flow and synovial hypoxia may have higher disease activity, and the comprehensive score PDPA proposed by the present invention can identify these patients and give higher scores in the score. The results showed that the composite score PDPA correlated better with clinical parameters and standard scores than the PDUS score alone, suggesting that photoacoustic measurement of tissue oxygen saturation can be an important imaging parameter to complement ultrasound imaging in the assessment of RA .

在本发明中,对RA患者进行了多模态光声/超声成像,并通过双波长光声成像评估了患者增厚滑膜的组织氧合状态。与高氧状态相比,在氧饱和度相对较低的增厚滑膜内,能量多普勒超声检测到的血管可能较少。与中等氧合状态滑膜的患者相比,缺氧滑膜的患者倾向于有更高的疾病活动。进一步提出综合光声/超声结果的评分,该评分与临床活动度评分的相关系数高于单独PDUS评分,表明光声测定的组织氧合状态在RA疾病诊疗中的临床潜力。In the present invention, multimodal photoacoustic/ultrasound imaging was performed on RA patients, and the tissue oxygenation status of the patient's thickened synovium was assessed by dual-wavelength photoacoustic imaging. In thickened synovium with relatively low oxygen saturation, there may be fewer blood vessels detected by power Doppler ultrasonography compared with the hyperoxic state. Patients with hypoxic synovium tended to have higher disease activity compared with patients with moderately oxygenated synovium. A score for the integrated photoacoustic/ultrasound results was further proposed, and the correlation coefficient between the score and the clinical activity score was higher than that of the PDUS score alone, indicating the clinical potential of tissue oxygenation status measured by photoacoustics in the diagnosis and treatment of RA diseases.

如图10所示,这种多模态成像测评滑膜氧合状态和RA活动度的方法,其包括以下步骤:As shown in Figure 10, this multimodal imaging method for evaluating synovial membrane oxygenation status and RA activity includes the following steps:

(1)通过超声机、可调谐光参量振荡器激光器建立多模态成像系统,在体外采集图像信息;(1) Establish a multi-modal imaging system through an ultrasound machine and a tunable optical parametric oscillator laser to collect image information in vitro;

(2)勾画滑膜感兴趣区域,计算SO2相对值;(2) Outline the region of interest in the synovial membrane and calculate the relative value of SO 2 ;

(3)进行多模态光声/超声图像评分;(3) Perform multimodal photoacoustic/ultrasound image scoring;

(4)根据SO2相对值进行氧合状态分组;( 4 ) Oxygenation status grouping according to the relative value of SO2;

(5)收集图像对应患者的临床资料和临床评分;(5) Collect the clinical data and clinical score of the patient corresponding to the image;

(6)进行统计分析,统计学意义被定义为P值为小于0.05。(6) Statistical analysis was performed, and statistical significance was defined as a P value less than 0.05.

本发明通过超声机、可调谐光参量振荡器激光器建立多模态成像系统,在体外采集图像信息,勾画滑膜感兴趣区域,计算SO2相对值,进行多模态光声/超声图像评分,根据SO2相对值进行氧合状态分组,收集图像对应患者的临床资料和临床评分,进行统计分析,从而能够更准确地获得光声成像测量的组织氧饱和度(SO2)和临床标准评分之间的关联,并确定其在评估RA疾病活动度中的潜在效用。The present invention establishes a multimodal imaging system through an ultrasonic machine and a tunable optical parametric oscillator laser, collects image information in vitro, outlines the region of interest in the synovial membrane, calculates the relative value of SO 2 , and performs multimodal photoacoustic/ultrasonic image scoring. The oxygenation status is grouped according to the relative value of SO 2 , the clinical data and clinical scores of the patients corresponding to the images are collected, and statistical analysis is performed, so that the relationship between tissue oxygen saturation (SO 2 ) measured by photoacoustic imaging and clinical standard scores can be obtained more accurately. and to determine its potential utility in assessing disease activity in RA.

优选地,所述步骤(1)中,多模态成像系统还包括配备光学元件的手持式线性光声/超声探头,光声成像模式是将光声信号以伪彩形式叠加至超声灰阶图像上;在多模态成像模式下,超声和光声模块以时分复用的方式运行并同时呈现。Preferably, in the step (1), the multimodal imaging system further includes a hand-held linear photoacoustic/ultrasound probe equipped with optical elements, and the photoacoustic imaging mode is to superimpose photoacoustic signals on the ultrasonic grayscale image in a pseudo-color form Above; in multimodal imaging mode, ultrasound and photoacoustic modules operate in a time-multiplexed fashion and are presented simultaneously.

优选地,所述步骤(1)中,多模态光声/超声成像系统的设置为:水平和垂直分辨率小于1毫米,在5毫米至20毫米的深度范围内,该系统的信噪比为27.5分贝;组织表面的光通量小于20mJ2/cm,波动小于5%;将光声成像增益值从45分贝调整到55分贝,以减少PA噪音;能量多普勒超声PDUS成像参数包括:600-1000赫兹脉冲重复频率、50-100赫兹壁式滤波器、85-90%最大增益、3厘米/秒刻度、使用无角度的矩形采样盒;Preferably, in the step (1), the setting of the multimodal photoacoustic/ultrasonic imaging system is: the horizontal and vertical resolution is less than 1 mm, and the signal-to-noise ratio of the system is within the depth range of 5 mm to 20 mm. It is 27.5 decibels; the luminous flux on the tissue surface is less than 20mJ2/cm, and the fluctuation is less than 5%; the photoacoustic imaging gain value is adjusted from 45 decibels to 55 decibels to reduce PA noise; power Doppler ultrasound PDUS imaging parameters include: 600-1000 Hz pulse repetition rate, 50-100 Hz wall filter, 85-90% maximum gain, 3 cm/s scale, using a rectangular sampling box without angles;

在多模态模式下,实时成像的屏幕被分成四部分:左上部分显示的是正常的超声成像,这个区域选择灰阶超声或多普勒超声;底部屏幕的两个部分是750nm和830nm的光声成像,是通过在灰阶图像上叠加PA伪彩信号而形成的;右上部分为氧合度的伪彩图谱,它是将750nm和830nm两个PA图像的信号的像素值进行拟合来表示氧饱和度。In multi-modality mode, the real-time imaging screen is divided into four parts: the upper left part shows normal ultrasound imaging, this area selects grayscale ultrasound or Doppler ultrasound; the two parts of the bottom screen are 750nm and 830nm light Acoustic imaging is formed by superimposing the PA pseudo-color signal on the gray-scale image; the upper right part is the pseudo-color spectrum of the oxygenation degree, which is the pixel value of the two PA image signals at 750nm and 830nm by fitting to represent oxygen saturation.

优选地,所述步骤(2)中,氧合血红蛋白HbO2和脱氧血红蛋白Hb的光吸收在600-700nm的波长处有明显变化,在红外线范围内则几乎相似。在这个系统中,使用λ1=750nm和λ2=830nm的信号计算SO2值,表示为公式(1)Preferably, in the step (2), the light absorption of oxyhemoglobin HbO 2 and deoxyhemoglobin Hb has obvious changes at the wavelength of 600-700nm, and is almost similar in the infrared range. In this system, the SO2 value is calculated using the signals at λ 1 =750nm and λ 2 =830nm, expressed as Equation (1)

Figure BDA0003796214240000071
Figure BDA0003796214240000071

CHb和CHbO2分别是Hb和HbO2含量;

Figure BDA0003796214240000072
分别是Hb和HbO2在λ1和λ2的消光系数;Aλ1、Aλ2分别是波长λ1和λ2的光声强度。CHb and CHbO2 are the Hb and HbO2 contents, respectively;
Figure BDA0003796214240000072
are the extinction coefficients of Hb and HbO 2 at λ 1 and λ 2 , respectively; Aλ 1 and Aλ 2 are the photoacoustic intensities of wavelengths λ 1 and λ 2 , respectively.

优选地,所述步骤(2)中,还包括验证PA-SO2在乳腺组织和血液模型、动物和人体上的可靠性:首先,将不同比例的NiSO4-CuSO4混合物加入到含TiO2的乳腺组织模型中,模拟血液中的四种SO2水平100%、90%、80%和70%,结果表明,光声/超声系统可以在不同深度测量不同水平的SO2,并且具有良好的准确性;然后,将该系统应用于计算比格犬股动脉的血氧饱和度,并与血氧仪测量的舌部血氧进行比较,该实验也确定了两种测量的良好相关性;此外,该系统还在健康志愿者的桡动脉上成功进行了验证,志愿者吸入不同氧浓度的空气,以改变血氧分压,检测出血氧分压的变化。Preferably, in the step (2), it also includes verifying the reliability of PA-SO 2 on mammary gland tissue and blood models, animals and humans: first, adding different proportions of NiSO 4 -CuSO 4 mixtures to the TiO 2 -containing In the mammary gland tissue model, four SO 2 levels in blood were simulated 100%, 90%, 80% and 70%. The results showed that the photoacoustic/ultrasound system could measure different levels of SO 2 at different depths, and had good accuracy; then, the system was applied to calculate the oxygen saturation of the beagle femoral artery and compared with the tongue blood oxygen measured by the oximeter, and the experiment also determined a good correlation of the two measurements; in addition , the system was also successfully verified on the radial artery of healthy volunteers. Volunteers inhaled air with different oxygen concentrations to change the blood oxygen partial pressure and detect changes in the blood oxygen partial pressure.

优选地,所述步骤(3)中,超声医生对患者临床优势侧的背侧第2和第3掌指关节MCP、第2和第3近端指间关节PIP、第2和第5跖趾关节MTP和手腕进行光声/超声成像检查,该小关节选取参考超声7关节评价方法,对健康志愿者进行了腕部的光声成像,并取正常滑膜周围组织的光声信号进行分析;在开始进行光声成像之前,首先进行灰阶超声和能量多普勒超声来定位和评估滑膜炎;根据EULAR-OMERACT评分标准评估GSUS评分和PDUS评分,该标准根据滑膜肥厚程度和多普勒信号定义关节炎的程度进行0-3分评分。Preferably, in the step (3), the sonographer conducts the dorsal second and third metacarpophalangeal joints MCP, the second and third proximal interphalangeal joints PIP, and the second and fifth metatarsophalangeal joints on the clinically dominant side of the patient. The MTP of the joint and the wrist were examined by photoacoustic/ultrasound imaging. The small joint was selected with reference to the ultrasound 7 joint evaluation method. The photoacoustic imaging of the wrist was performed on healthy volunteers, and the photoacoustic signal of the normal synovial tissue was taken for analysis; Prior to initiating photoacoustic imaging, first perform grayscale and power Doppler ultrasonography to localize and evaluate synovitis; evaluate GSUS and PDUS scores according to the EULAR-OMERACT scoring criteria, which are based on the degree of synovial hypertrophy and Doppler The Le signal defines the degree of arthritis on a 0-3 point scale.

优选地,所述步骤(4)中,对图像进行系统聚类分析和K-means聚类分析;Preferably, in the step (4), the image is subjected to systematic cluster analysis and K-means cluster analysis;

在系统聚类分析中,用组间平均联系法和欧氏距离的平方作为距离测量,将数据分为2-240个聚类,然后生成聚类表,提取不同划分方法的距离系数来描绘碎石图;通过层次聚类分析计算每一种分类的距离系数,并绘制距离系数的碎石图,根据肘部规则确定最佳聚类数为3;然后通过K-means聚类确定三个类别的聚类中心分别为89.64%、78.48%、65.73%,范围分别为>84%、70-84%、<70%;随后应用F检验,验证聚类方法分离度的有效性,得到P值<0.0001,表明其对SO2值的分类是有效的。In the system cluster analysis, the average connection method between groups and the square of the Euclidean distance are used as the distance measurement, the data are divided into 2-240 clusters, and then the cluster table is generated, and the distance coefficients of different division methods are extracted to describe the fragmentation. Stone map; calculate the distance coefficient of each classification through hierarchical cluster analysis, and draw the gravel map of the distance coefficient, and determine the optimal number of clusters as 3 according to the elbow rule; then determine the three categories through K-means clustering The clustering centers were 89.64%, 78.48%, 65.73%, respectively, and the ranges were >84%, 70-84%, <70%; then the F test was applied to verify the effectiveness of the separation degree of the clustering method, and the P value < 0.0001, indicating that it is valid for the classification of SO2 values.

优选地,所述步骤(4)中,根据聚类分析和假彩色的类型,将关节的氧合状态分为:高氧状态,定义为SO2值大于84%,以红色信号为主;中等氧合状态,定义为SO2值为70-84%,以红色和蓝色信号混合为特征;低氧状态,定义为SO2值小于70%,以蓝色信号为主。Preferably, in the step (4), according to the cluster analysis and the type of false color, the oxygenation state of the joint is divided into: a hyperoxic state, defined as an SO2 value greater than 84%, with a red signal as the main; medium The oxygenated state, defined as an SO2 value of 70-84%, is characterized by a mixture of red and blue signals; the hypoxic state, defined as an SO2 value of less than 70%, is characterized by a predominantly blue signal.

优选地,所述步骤(6)中,正态分布的数据用平均值±标准差SD描述,并通过Student’s-t检验进行分析;非正态数据以中位数表示,并通过Mann-Whitney U检验进行分析。Preferably, in the step (6), the normally distributed data is described by mean ± standard deviation SD, and analyzed by the Student's-t test; the non-normal data is expressed by the median, and analyzed by Mann-Whitney U Check for analysis.

本领域普通技术人员可以理解,实现上述实施例方法中的全部或部分步骤是可以通过程序来指令相关的硬件来完成,所述的程序可以存储于一计算机可读取存储介质中,该程序在执行时,包括上述实施例方法的各步骤,而所述的存储介质可以是:ROM/RAM、磁碟、光盘、存储卡等。因此,与本发明的方法相对应的,本发明还同时包括一种多模态成像测评滑膜氧合状态和RA活动度的系统,该系统通常以与方法各步骤相对应的功能模块的形式表示。该系统包括:Those of ordinary skill in the art can understand that all or part of the steps in the method of the above-mentioned embodiments can be completed by instructing related hardware through a program, and the program can be stored in a computer-readable storage medium. When executed, it includes the steps of the method in the above embodiments, and the storage medium may be: ROM/RAM, magnetic disk, optical disk, memory card, etc. Therefore, corresponding to the method of the present invention, the present invention also includes a multimodal imaging system for evaluating synovial membrane oxygenation status and RA activity, which is usually in the form of functional modules corresponding to each step of the method express. The system includes:

采集模块,其配置来通过超声机、可调谐光参量振荡器激光器建立多模态成像系统,在体外采集图像信息;An acquisition module configured to establish a multimodal imaging system through an ultrasound machine and a tunable optical parametric oscillator laser to acquire image information in vitro;

计算模块,其配置来勾画滑膜感兴趣区域,计算SO2相对值;a calculation module configured to delineate a region of interest in the synovial membrane and calculate a relative value of SO ;

评分模块,其配置来进行多模态光声/超声图像评分;a scoring module configured to perform multimodal photoacoustic/ultrasound image scoring;

分组模块,其配置来根据SO2相对值进行氧合状态分组;a grouping module configured to group oxygenation status according to relative SO values ;

收集模块,其配置来收集图像对应患者的临床资料和临床评分;a collection module configured to collect clinical data and clinical scores of patients corresponding to the images;

统计分析模块,其配置来进行统计分析,统计学意义被定义为P值为小于0.05。The statistical analysis module was configured to perform statistical analysis, with statistical significance defined as a P value less than 0.05.

以上所述,仅是本发明的较佳实施例,并非对本发明作任何形式上的限制,凡是依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与修饰,均仍属本发明技术方案的保护范围。The above are only preferred embodiments of the present invention, and are not intended to limit the present invention in any form. Any simple modifications, equivalent changes and modifications made to the above embodiments according to the technical essence of the present invention are still within the scope of this invention. The protection scope of the technical solution of the invention.

Claims (10)

1.多模态成像测评滑膜氧合状态和RA活动度的方法,其特征在于:其包括以下步骤:1. The method for evaluating synovial membrane oxygenation state and RA activity by multimodal imaging, is characterized in that: it comprises the following steps: (1)通过超声机、可调谐光参量振荡器激光器建立多模态成像系统,在体外采集图像信息;(1) Establish a multi-modal imaging system through an ultrasound machine and a tunable optical parametric oscillator laser to collect image information in vitro; (2)勾画滑膜感兴趣区域,计算SO2相对值;(2) Outline the region of interest in the synovium and calculate the relative value of SO 2 ; (3)进行多模态光声/超声图像评分;(3) Perform multimodal photoacoustic/ultrasound image scoring; (4)根据SO2相对值进行氧合状态分组;( 4 ) Oxygenation status grouping according to the relative value of SO2; (5)收集图像对应患者的临床资料和临床评分;(5) Collect the clinical data and clinical score of the patient corresponding to the image; (6)进行统计分析,统计学意义被定义为P值为小于0.05。(6) Statistical analysis was performed, and statistical significance was defined as a P value less than 0.05. 2.根据权利要求1所述的多模态成像测评滑膜氧合状态和RA活动度的方法,其特征在于:所述步骤(1)中,多模态成像系统还包括配备光学元件的手持式线性光声/超声探头,光声成像模式是将光声信号以伪彩形式叠加至超声灰阶图像上;在多模态成像模式下,超声和光声模块以时分复用的方式运行并同时呈现。2. The method for evaluating synovial membrane oxygenation status and RA activity by multimodal imaging according to claim 1, characterized in that: in the step (1), the multimodal imaging system also includes a hand-held device equipped with optical elements In the photoacoustic imaging mode, the photoacoustic signal is superimposed on the ultrasonic gray-scale image in the form of pseudo-color; in the multimodal imaging mode, the ultrasonic and photoacoustic modules operate in a time-division multiplexed manner and simultaneously presented. 3.根据权利要求2所述的多模态成像测评滑膜氧合状态和RA活动度的方法,其特征在于:所述步骤(1)中,多模态光声/超声成像系统的设置为:水平和垂直分辨率小于1毫米,在5毫米至20毫米的深度范围内,该系统的信噪比为27.5分贝;组织表面的光通量小于20mJ2/cm,波动小于5%;将光声成像增益值从45分贝调整到55分贝,以减少PA噪音;能量多普勒超声PDUS成像参数包括:600-1000赫兹脉冲重复频率、50-100赫兹壁式滤波器、85-90%最大增益、3厘米/秒刻度、使用无角度的矩形采样盒;3. the method for evaluating synovial membrane oxygenation state and RA activity by multimodal imaging according to claim 2, is characterized in that: in described step (1), the setting of multimodal photoacoustic/ultrasonic imaging system is : The horizontal and vertical resolution is less than 1 mm, and the signal-to-noise ratio of the system is 27.5 dB in the depth range of 5 mm to 20 mm; the light flux on the tissue surface is less than 20 mJ2/cm, and the fluctuation is less than 5%; Values adjusted from 45 to 55 dB to reduce PA noise; power Doppler ultrasound PDUS imaging parameters include: 600-1000 Hz pulse repetition frequency, 50-100 Hz wall filter, 85-90% maximum gain, 3 cm /second scale, using a rectangular sampling box without angles; 在多模态模式下,实时成像的屏幕被分成四部分:左上部分显示的是正常的超声成像,这个区域选择灰阶超声或多普勒超声;底部屏幕的两个部分是750nm和830nm的光声成像,是通过在灰阶图像上叠加PA伪彩信号而形成的;右上部分为氧合度的伪彩图谱,它是将750nm和830nm两个PA图像的信号的像素值进行拟合来表示氧饱和度。In multimodal mode, the real-time imaging screen is divided into four parts: the upper left part shows normal ultrasound imaging, and this area selects grayscale ultrasound or Doppler ultrasound; the two parts of the bottom screen are 750nm and 830nm light Acoustic imaging is formed by superimposing the PA pseudo-color signal on the gray-scale image; the upper right part is the pseudo-color spectrum of the oxygenation degree, which is the pixel value of the two PA image signals at 750nm and 830nm by fitting to represent oxygen saturation. 4.根据权利要求3所述的多模态成像测评滑膜氧合状态和RA活动度的方法,其特征在于:所述步骤(2)中,氧合血红蛋白HbO2和脱氧血红蛋白Hb的光吸收在600-700nm的波长处有明显变化,在红外线范围内则几乎相似;在这个系统中,使用λ1=750nm和λ2=830nm的信号计算SO2值,表示为公式(1)4. the method for evaluating synovium oxygenation state and RA activity by multimodal imaging according to claim 3, is characterized in that: in described step ( 2 ), the light absorption of oxygenated hemoglobin HbO and deoxygenated hemoglobin Hb There is a clear change at wavelengths of 600-700nm , and almost similar in the infrared range; in this system, the SO2 value is calculated using the signals of λ1 = 750nm and λ2 = 830nm, expressed as equation ( 1 )
Figure FDA0003796214230000021
Figure FDA0003796214230000021
CHb和CHbO2分别是Hb和HbO2含量;
Figure FDA0003796214230000022
分别是Hb和HbO2在λ1和λ2的消光系数;Aλ1、Aλ2分别是波长λ1和λ2的光声强度。
CHb and CHbO2 are the Hb and HbO2 contents, respectively;
Figure FDA0003796214230000022
are the extinction coefficients of Hb and HbO 2 at λ 1 and λ 2 , respectively; Aλ 1 and Aλ 2 are the photoacoustic intensities of wavelengths λ 1 and λ 2 , respectively.
5.根据权利要求4所述的多模态成像测评滑膜氧合状态和RA活动度的方法,其特征在于:所述步骤(2)中,还包括验证PA-SO2在乳腺组织和血液模型、动物和人体上的可靠性:首先,将不同比例的NiSO4-CuSO4混合物加入到含TiO2的乳腺组织模型中,模拟血液中的四种SO2水平100%、90%、80%和70%,结果表明,光声/超声系统可以在不同深度测量不同水平的SO2,并且具有良好的准确性;然后,将该系统应用于计算比格犬股动脉的血氧饱和度,并与血氧仪测量的舌部血氧进行比较,该实验也确定了两种测量的良好相关性;此外,该系统还在健康志愿者的桡动脉上成功进行了验证,志愿者吸入不同氧浓度的空气,以改变血氧分压,检测出血氧分压的变化。5. The method for evaluating synovial membrane oxygenation status and RA activity by multimodal imaging according to claim 4, characterized in that: in the step ( 2 ), it also includes verifying that PA-SO is in breast tissue and blood Reliability on models, animals and humans: First, different ratios of NiSO 4 -CuSO 4 mixtures were added to TiO 2 -containing mammary gland tissue models to simulate four SO 2 levels in blood 100%, 90%, 80% and 70%, the results showed that the photoacoustic/ultrasound system could measure different levels of SO 2 at different depths with good accuracy; then, the system was applied to calculate the oxygen saturation of the beagle femoral artery, and Compared with tongue blood oxygen measured by an oximeter, the experiment also determined a good correlation between the two measurements; in addition, the system was successfully validated on the radial artery of healthy volunteers, who inhaled different oxygen concentrations The air to change the blood oxygen partial pressure and detect the change of the blood oxygen partial pressure. 6.根据权利要求5所述的多模态成像测评滑膜氧合状态和RA活动度的方法,其特征在于:所述步骤(3)中,超声医生对患者临床优势侧的背侧第2和第3掌指关节MCP、第2和第3近端指间关节PIP、第2和第5跖趾关节MTP和手腕进行光声/超声成像检查,该小关节选取参考超声7关节评价方法,对健康志愿者进行了腕部的光声成像,并取正常滑膜周围组织的光声信号进行分析;在开始进行光声成像之前,首先进行灰阶超声和能量多普勒超声来定位和评估滑膜炎;根据EULAR-OMERACT评分标准评估GSUS评分和PDUS评分,该标准根据滑膜肥厚程度和多普勒信号定义关节炎的程度进行0-3分评分。6. The method for assessing synovial membrane oxygenation status and RA activity by multimodal imaging according to claim 5, characterized in that: in the step (3), the ultrasound doctor conducts the second phase on the dorsal side of the clinically dominant side of the patient. The third metacarpophalangeal joint MCP, the second and third proximal interphalangeal joint PIP, the second and fifth metatarsophalangeal joint MTP, and the wrist were subjected to photoacoustic/ultrasound imaging. The small joints were selected with reference to the ultrasonic 7-joint evaluation method. The photoacoustic imaging of the wrist was performed on healthy volunteers, and the photoacoustic signals of the normal synovial tissues were taken for analysis; before starting the photoacoustic imaging, gray-scale ultrasound and power Doppler ultrasound were first performed to locate and evaluate Synovitis; GSUS and PDUS scores were assessed according to the EULAR-OMERACT scoring criteria, which are scored on a 0-3 scale based on the degree of synovial hypertrophy and Doppler signal to define the degree of arthritis. 7.根据权利要求6所述的多模态成像测评滑膜氧合状态和RA活动度的方法,其特征在于:所述步骤(4)中,对图像进行系统聚类分析和K-means聚类分析;7. the method for evaluating synovial membrane oxygenation state and RA activity by multimodal imaging according to claim 6, is characterized in that: in described step (4), system cluster analysis and K-means aggregation are carried out to image class analysis; 在系统聚类分析中,用组间平均联系法和欧氏距离的平方作为距离测量,将数据分为2-240个聚类,然后生成聚类表,提取不同划分方法的距离系数来描绘碎石图;通过层次聚类分析计算每一种分类的距离系数,并绘制距离系数的碎石图,根据肘部规则确定最佳聚类数为3;然后通过K-means聚类确定三个类别的聚类中心分别为89.64%、78.48%、65.73%,范围分别为>84%、70-84%、<70%;随后应用F检验,验证聚类方法分离度的有效性,得到P值<0.0001,表明其对SO2值的分类是有效的。In the system cluster analysis, the average connection method between groups and the square of the Euclidean distance are used as the distance measurement, the data are divided into 2-240 clusters, and then the cluster table is generated, and the distance coefficients of different division methods are extracted to describe the fragmentation. Stone map; calculate the distance coefficient of each classification through hierarchical cluster analysis, and draw the gravel map of the distance coefficient, and determine the optimal number of clusters as 3 according to the elbow rule; then determine the three categories through K-means clustering The clustering centers were 89.64%, 78.48%, 65.73%, respectively, and the ranges were >84%, 70-84%, <70%; then the F test was applied to verify the effectiveness of the separation degree of the clustering method, and the P value < 0.0001, indicating that it is valid for the classification of SO2 values. 8.根据权利要求7所述的多模态成像测评滑膜氧合状态和RA活动度的方法,其特征在于:所述步骤(4)中,根据聚类分析和假彩色的类型,将关节的氧合状态分为:高氧状态,定义为SO2值大于84%,以红色信号为主;中等氧合状态,定义为SO2值为70-84%,以红色和蓝色信号混合为特征;低氧状态,定义为SO2值小于70%,以蓝色信号为主。8. The method for evaluating synovial membrane oxygenation state and RA activity by multimodal imaging according to claim 7, characterized in that: in the step (4), according to the type of cluster analysis and false color, the joint The oxygenation status is divided into: hyperoxic state, defined as an SO2 value greater than 84%, dominated by red signal ; intermediate oxygenated state, defined as SO2 value of 70-84%, with a mixture of red and blue signals as Characteristics; hypoxic state, defined as SO2 value less than 70%, dominated by blue signal. 9.根据权利要求8所述的多模态成像测评滑膜氧合状态和RA活动度的方法,其特征在于:所述步骤(6)中,正态分布的数据用平均值±标准差SD描述,并通过Student’s-t检验进行分析;非正态数据以中位数表示,并通过Mann-Whitney U检验进行分析。9. The method for assessing synovial membrane oxygenation state and RA activity by multimodal imaging according to claim 8, characterized in that: in the step (6), the normally distributed data are average ± standard deviation SD Described and analyzed by Student's-t test; non-normal data are presented as median and analyzed by Mann-Whitney U test. 10.多模态成像测评滑膜氧合状态和RA活动度的系统,其特征在于:其包括:10. A system for evaluating synovial membrane oxygenation status and RA activity by multimodal imaging, characterized in that it includes: 采集模块,其配置来通过超声机、可调谐光参量振荡器激光器建立多模态成像系统,在体外采集图像信息;An acquisition module configured to establish a multimodal imaging system through an ultrasound machine and a tunable optical parametric oscillator laser to acquire image information in vitro; 计算模块,其配置来勾画滑膜感兴趣区域,计算SO2相对值;a calculation module configured to delineate a region of interest in the synovial membrane and calculate a relative value of SO ; 评分模块,其配置来进行多模态光声/超声图像评分;a scoring module configured to perform multimodal photoacoustic/ultrasound image scoring; 分组模块,其配置来根据SO2相对值进行氧合状态分组;a grouping module configured to group oxygenation status according to relative SO values ; 收集模块,其配置来收集图像对应患者的临床资料和临床评分;a collection module configured to collect clinical data and clinical scores of patients corresponding to the images; 统计分析模块,其配置来进行统计分析,统计学意义被定义为P值为小于0.05。The statistical analysis module was configured to perform statistical analysis, with statistical significance defined as a P value less than 0.05.
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