【作者】 李萍；

【导师】 刘韶平；

【作者基本信息】 山东大学 ， 影像医学与核医学， 2011， 博士

【摘要】 第一部分彩色多普勒超声对类风湿性关节炎手腕关节病变的诊断价值背景类风湿性关节炎(rheumatoid arthritis, RA)是一种常见的自身免疫性疾病,以关节的滑膜炎、肌腱腱鞘炎、关节积液、骨侵蚀为主要特征,可损害邻近组织,进而累及心、肺、肾等系统。本病患者约占世界人口的1%,发病年龄多见于30岁以上,女性的发病率约为男性的3倍,治疗不及时,致畸致残性较高。目前国际上公认的美国纽约风湿病协会(ARA)1987年修订的类风湿性关节炎(RA)诊断标准以X线平片为影像学依据,X线平片可以显示RA关节骨质疏松、骨质破坏、关节间隙狭窄、关节周围软组织肿胀等改变,这些改变已经不属于早期病变。高频超声具有良好的软组织对比,近年来被广泛应用评价关节病变。同X线相比,超声更具敏感性和特异性,能够显示X线不能判断的滑膜炎、关节周围炎性渗出及早期骨质破坏,且性价比又优于CT、MRI。本研究应用彩色多普勒超声对未经治疗的RA患者和健康志愿者的腕关节和掌指关节进行观察,探讨超声在RA早期诊断中的应用价值。目的探讨类风湿性关节炎(RA)手腕部病变的超声影像学特点及其诊断价值。方法采用PHILIPS iu22彩色超声诊断仪,观察并记录78例RA患者和50例健康志愿者的声像图表现,观察滑膜、肌腱腱鞘、关节间隙及关节面的改变。测量双侧腕关节、掌指关节滑膜的厚度。应用彩色多普勒血流显像(CDFI)及彩色多普勒能量图(PDI)技术检测关节滑膜血流特点,将滑膜血流丰富程度按Alder半定量法分为0～3级,测量滑膜动脉阻力指数(RI)及搏动指数(PI)。结果1.RA组腕关节滑膜厚度2.95±1.50mm,掌指关节滑膜厚度1.86±0.30mm。健康对照组腕关节滑膜厚度1.53±0.20mm,掌指关节滑膜厚度1.22±0.10mm。两组差异有统计学意义(P<0.05)。2.78例RA中57例滑膜为不均匀的低回声,21例为不均匀的高回声。67例关节滑膜均可探及血流信号。随着血流分级的增加(1～3级),RI逐级减低,血流分级与RI呈负相关。随着血流分级的增加(1～3级),PI变化不大,血流分级与PI无相关。3.超声显示RA关节积液48例,其中腕关节35例,59个；掌指关节13例,37个。肌腱腱鞘炎43例,其中腕关节35例,70个；掌指关节8例。23个。关节面不规则骨侵蚀31例,腕关节19例,38个；掌指关节12例,35个。结论1.超声检查能够较好地显示RA患者手腕部的病理改变,如滑膜炎、肌腱腱鞘炎、关节积液、骨侵蚀等征象,可以弥补X线平片的不足。2.超声检查操作简便、费用低廉、无放射性,可重复进行,对于临床上疑RA的患者可以常规行手腕部超声检查,有利于提高病变的检出,有助于RA的早期诊断及合理治疗。第二部分早期类风湿性关节炎腕关节病变超声与MRI对比研究背景腕关节、手(足)小关节是RA较早、较常见累及的部位。早期诊断及时治疗不仅能够显著减轻、延缓关节的器质性损害,而且可以在获得良好疗效的同时避免不必要的药物损伤。目前,临床上对类风湿性关节炎的诊断主要依靠临床表现、血清学检查及影像学检查(X线、超声、CT、MRI). MRI和彩色多普勒超声均具有良好的软组织对比,是目前早期诊断RA最有价值的影像学方法。但两种影像学方法相比,其应用价值究竟如何却少有研究。本文选择临床确诊未经治疗的RA患者,对照比较了超声和MRI对早期RA腕关节病变诊断的优劣,旨为临床选择合理的影像学检查提供参考。目的探讨超声与MRI在诊断早期类风湿性关节炎腕关节病变中的作用和价值。方法对31例临床诊断为类风湿性关节炎的患者于治疗前行双侧腕关节超声和MRI检查,观察并记录两种影像学表现,比较两种影像学方法对RA基本病变的检出能力。结果1.31例类风湿性关节患者62个腕关节中超声显示滑膜炎62个(100%),关节积液42个(67.7%),肌腱炎38个(61.3%),骨侵蚀24个(38.8%)；MRI显示滑膜炎62个(100%),关节积液43个(69.3%),肌腱腱鞘炎41个(66.1%),骨侵蚀33个(53.2%),同时还显示骨髓水肿16个(25.8%)。2.对类风湿性关节炎腕关节滑膜炎、关节积液、肌腱炎病变的检出,两种检查方法之间差异无统计学意义(X2=0、0.01、0.33,P>0.05)。3.对骨侵蚀病变的检出,两种检查方法之间差异有统计学意义(X2=80.64,P<0.01)。结论1.超声、MRI均能显示RA的滑膜炎、肌腱腱鞘炎、关节积液、骨侵蚀等早期基本病变,可以评估炎症的活动性。MRI对骨侵蚀、骨髓水肿的显示优于超声。2.由于超声与MRI相比经济、快捷、可重复检查、可实时动态扫描,可作为RA首选的影像学检查方法,若临床怀疑RA而超声表现不典型者建议行MRI检查。第三部分类风湿性关节炎腕关节滑膜血流与VEGF表达的相关性研究背景类风性关节炎是一种慢性炎症性疾病,其早期受累部位是滑膜组织,滑膜炎症持久反复发作,继而破坏关节软骨和骨,引起关节畸形和功能障碍。血管内皮细胞生长因子(vascular endothelial growth factor, VEGF)是一种能特异性促进血管内皮细胞增殖、维持血管内皮细胞分化状态、提高微血管通透性的细胞因子,它在多种恶性肿瘤及炎症过程呈高表达,文献报道VEGF在RA的发病机制中具有重要作用。近年来,随着超声显像技术的不断改进与发展,彩色多普勒超声对于关节滑膜血流的显示与评价作用愈发受到关注。本文通过研究RA患者血清VEGF表达水平及探讨其与滑膜血流之间的关系,旨在为临床早期诊断RA、评价疗效、判断预后提供依据。目的研究类风湿性关节炎患者腕关节滑膜血流分级、动脉阻力指数(RI)与血管内皮细胞生长因子(VEGF)表达水平的关系。方法1.彩色多普勒超声检查对62例RA患者治疗前,行彩色多普勒超声检查双侧腕关节,观察并记录关节滑膜血流分级、测量动脉阻力指数(RI)。2.检测血清VEGF表达水平采用酶联免疫吸附(ELISA)法检测62例RA患者及对照组(30例健康志愿者)血清中的VEGF表达水平。分析RA滑膜血流分级、动脉阻力指数与血清VEGF表达水平的相关性。结果1.RA组血清VEGF表达水平为(1123.6±190.7)ng/l,与对照组(307.2±175.5)ng/l比较差异有统计学意义(P<0.05)。2.62例RA患者中,超声提示腕关节滑膜血流信号0级5个；1级23个；2级64个；3级32个。RA患者腕关节滑膜血流分级与血清VEGF水平呈正相关,差异有统计学意义。(r=0.903,P<0.01)3.RA组滑膜血流1～3级,滑膜动脉阻力指数与血清VEGF水平呈负相关,差异有统计学意义。(r=-0.817,P<0.01)。结论1. VEGF在RA患者血清中呈高表达,VEGF在RA的发生、发展中发挥重要作用。2.RA患者血清VEGF表达水平与滑膜超声血流分级、动脉阻力指数存在相关性。超声检查RA滑膜血流结合VEGF表达水平能够反映RA的活动性,为临床治疗方案的制定及评估预后提供帮助。更多还原

【Abstract】 PART ONEDiagnosis of rheumatoid arthritis on wrist and hand by CDFIBackgroudRheumatoid arthritis is a common autoimmune disease, its main pathological features are synovitis, tenosynovitis, joint effusion and bone erosion. It can damage the adjacent tissue, or even involving the heart, lung, kidney and other systems. This disease accounts for about 1% of the world’s population, more common age of onset of 30 years of age, the incidence rate in women is 3 times higher than in men, the rate of deformity and disability of this dieases is high.Now internationally recognized as the New York Rheumatism Association (ARA) 1987 revised in rheumatoid arthritis (RA) is still the diagnostic criteria for the X-ray imaging evidence, X-ray can show RA articular osteoporosis, joint space narrowing, joint swelling and bone destruction, soft tissue changes, but these changes are not part of the early lesions. High-frequency ultrasound has excellent soft tissue contrast, more evaluation of joint disease has been widely used. Compared with the X ray, ultrasound is more sensitive and specific, able to display X ray can not determine the synovitis, inflammatory exudate around the joint and early bone destruction, and cost-effective and superior to CT, MRI. In this study, untreated RA patients and healthy volunteers underwent color Doppler ultrasound, the wrist and metacarpophalangeal joints were observed, in order to probe early diagnosic value of RA in ultrasound.ObjectiveTo explore the Color Doppler flow imaging (CDFI) characteristics of wrist and hand damage in rheumatoid arthritis (RA) patients and its diagnostic value.MethodsUsing PHILIPS iu22 color ultrasound, the sonogram of 78 patients in RA and 50 healthy volunteers were observed and recorded, the synovium, tendon, joint space and articular surface changes were study. Measuring synovial thickness of bilateral wrist and metacarpophalangeal, using Color Doppler flow imaging (CDFI) and color Doppler energy (PDI) to detect synovial blood flow, Semi-quantitative method according to Alder abundance of synovial blood flow is divided into 0 to 3, synovial artery resistance index and pulse index were measured.Results1. In RA group, the thickness of synovial membrane of wrist was 2.95±1.50mm, the thickness of synovial membrane of metacarpophalangeal (MCP) jiont was 1.86±0.30mm. In healthy control group, the thickness of synovial membrane of wrist was 1.53±0.20mm, the thickness of synovial membrane of MCP was 1.22±0.10mm. The difference was statistically significant (P<0.05).2. Among the 78 cases, the synovial of 57 cases of RA is heterogeneous hypoechoic,21 cases of non-uniform high echo. With the increase of blood flow grade (1 to 3), RI progressively reduced, flow grade was negatively correlated with the RI. With the increase of blood flow grade (1 to 3), PI changed little, flow grade was no significant correlation with the PI.3. Among the 78 paients,48 cases were detected joint effusion, of which 35 cases(59 jionts) in wrist,13 cases(37 jionts) in MCP .43 cases were found tendon tenosynovitis,35 cases(70 jionts) in wrist,8 cases(23 jionts) in MCP.31 cases were detected irregular bone erosion on articular surface,19 cases (38 jionts)in wrist,12 cases (35 jionts)in MCP. Conclusion1. Ultrasonography is simple, inexpensive, non-radioactive, can be repeated, can show the basic lesions of joint synovitis, tenosynovitis tendon, joint effusion, bone erosion of wrist in RA, can make up for lack of X-ray in diagnosis of RA.2. For patients with clinically suspected of RA, the wrist should undergo ultrasound examination routinly in order to improve the detection rate of lesions. Ultrasound can contribute to early diagnosis and reasonable treatment of RA.PART TWODiagnosis of Wrists in Early Rheumatoid Arthritis with Ultrasonography and Magnetic Resonance Imaging:Comparison StudyBackgroudSmall joints of wrist, hand, foot is the most commonly involved site of the early Rheumatoid arthritis. Early diagnosis and timely treatment can significantly reduce, slow organic joint damage, and early diagnosis can be a good effect of drugs while avoiding unnecessary damage. Currently, the clinical diagnosis of rheumatoid arthritis mainly relies on clinical manifestations, serological tests and imaging (X ray, ultrasound, CT, MRI). MRI and color Doppler ultrasound has a good soft tissue contrast, early diagnosis of RA is the most valuable imaging method. But the two imaging methods, the diagnostic value of how there were few studies.Our selection of clinical diagnosis of untreated RA patients, ultrasound and MRI were compared on the merits of early diagnosis of RA, aims to provide a reference for clinical choice. ObjectiveTo evaluate quantitative observation with ultrasonography and MRI in the diagnosis of wrist jiont lesions of rheumatoid arthritis.Methods31 patients of clinically diagnosed as RA with bilateral wrists underwent ultrasound and MRI before treatment, two imaging features were observed and recorded, the ability of these two techniques to reveal the changes of RA was compared.Results1. On US,62 (100%) wrist jionts (of 31 patients) were showed synovitis,42 (67.7%) with jiont effusion,34 (61.3%) with tendinitis,24 (38.8%) with bone erosions. On MRI,62(100%) were showed synovitis,43(69.3%) with jiont effusion, 37 (66.1%) with tendinitis,33 (53.2%) with bone erosions,16 (25.8%) with marrow edema.2. Two methods were of no significant difference statistically (P> 0.05) in detection synovitis, jiont effusion, and tendinitis of early RA.3. Two methods were of significant difference statistically (P<0.01) in detection bone erosions.Conclusion1. Ultrasound and MRI can show synovitis, tenosynovitis tendon, joint effusion, bone erosion of basic early lesions with RA, can assess the activity of inflammation. MRI is superior to ultrasound in detection of bone erosion and bone marrow edema.2. Ultrasound has characteristics of economic, fast, repeatable inspection, real-time dynamic scanning, as for diagnosis of early RA, ultrasonography examination is the first choice, and for atypical ones, MRI follows. PART THREEStudy on the Correlation between Synovial flow on wrist and Serum VEGF Expression in Rheumatoid ArthritisBackgroudRheumatoid arthritis is a chronic inflammatory disease, its early targets is the synovial tissue, synovitis lasting recurrent disease, followed by destruction of articular cartilage and bone, causing joint deformity and dysfunction. Vascular endothelial growth factor (vascular endothelial growth factor, VEGF) is able to specifically promote the proliferation of endothelial cells, vascular endothelial cell differentiation to maintain and improve the microvascular permeability of cytokines, which in many cancers and inflammatory process showed a high expression of VEGF reported in the pathogenesis of RA play an important role.In recent years, ultrasound imaging technology continues to improve, color Doppler ultrasound for the display and evaluation of synovial blood flow creats more and more attention. The purpose of this study is to explore the relationship between serum levels of VEGF expression and synovial blood flow in patients with RA, to provide the basis of early diagnosis, evaluateing treatment and assessing prognosis of RA.ObjectiveTo study the relationship between the synovial flow degree, arterial resistance index on wrist and serum level of VEGF expression in rheumatoid arthritis.Methods1. Color Dopple ultrasoundBilateral wrists of sixty-two patients with RA underwent ultrasonography before treatment, synovial blood flow grade was observed and recorded, the arterial resistance index was measured.2. Serum level of VEGF expression Serum level of VEGF expression were detected in 62 patients with RA and control group (30 healthy volunteers) by Enzyme linked immunosorbent assay (ELISA), analysing the correlation between synovial flow grade, arterial resistance index and serum levels of VEGF expression of RA.Results1. The expression level of serum VEGF in RA group was 1123.6±190.7 ng/1 , significantly different from the level seen in control group(307.2±175.5) ng/1 (P<0.05).2. Among 62 patients of RA, the wrist joint synovial blood flow signal 0 degree was 5,1 degree was 23,2 degree was 64,3 degree was 32. There was positive correlation between the degree of synovial blood and the level of VEGF with RA, the difference was statistically significant, (r=0.903, P<0.01)3. There was passive correlation between the arterial RI and the level of VEGF, the difference was statistically significant, (r=-0.817, P<0.01)Conclusion1. Serum VEGF in synovial tissue of patients with RA showed high expression, VEGF in RA pathogenesis and development play an important role.2. There are correlation between the expression level of serum VEGF, synovial flow grade and arterial resistance index in RA. The combination of synovial blood with ultrasound and the serum level of VEGF can pedict the activity of RA, it is helpful for the selections of clinical treatment and evaluating the prognosis.更多还原