| Objective:Based on the RA rabbit model and ultrasound guided biopsy procedure, the first part of this study aims to discuss the scores of ultrasonic synovitis, the manifestation of synovial pathological in vivo,compare the correlation of synovial pathological changes between the serum biomarkers and ultrasonic scores as well. The second part aims to discuss whether contrast-enhanced ultrasound can reflect synovial pathology better than conventional ultrasound and whether contrast-enhanced ultrasound can estimate the severity of the synovitis quantitatively.Methods:(1) 30 male 6 months New Zealand white rabbits were randomized into antigen-induced arthritis model(AIA) group(25) and control group(5). Antigen induced arthritis(AIA) model was made by ovalbumin(OVA)immunization and intra-articular injection. After last intra-articular injection, pathological changes of knee joints were evaluated by ultrasound and serum CRP、TNF-a and IL-1 were determined by Enzyme linked immuosorbent assay(ELISA). Ultrasound observation included articular fluid thickness, synovial membrane thickness, synovial blood flow signal,the lesion on surface of cartilage and bone. Synovial hyperplasia degree and synovial blood flow signal scoring were evaluated using a 4-grade scale from 0 to 3. After eight weeks of general ultrasound, contrast enhanced ultrasound was performed, by using Sono Vue, and analyzed the data qualitatively after image acquisition, including flow classification(according to IACUS blood flow classification st andard), contrast arrival time, enhancement duration, contrast fading time, the presence of perfusion defects.Analyzing time intensity curve, obtaining parameters of contrast enhanced ultrasound perfusion, recording peak intensity(PI), area under curve(AUC), wash in slope(WS), etc, by using the portable software.(4) Pathological samples were acquired by ultrasound guided biopsy in week 8.(5) The correlation of synovial pathology between serum biomarkers, conventional ultrasound and contrast-enhanced ultrasound were compared.Results: A total of 23 rabbits in AIA group and 5 in control group completed this study.(1) According to the result of grey-scale ultrasound, synovitis and blood flow were graded from 0 to 3. Synovial lesion can be detected before week 4, however, serum biomarkers increased slowly until week 5 and 6(p<0.05). There was significant difference between different grade of synovitis in ultrasound imaging(synovial thickness, grade of blood flow and resistant index, P < 0.05). Meanwhile,there was also significant difference between serum biomarkers level(CRP,IL-1 and TNF-a, P < 0.05). Although the data above were correlative with synovitis scoring, the highest correlation indexes were synovial thickness and grade of blood flow. The correlation index between synovial thickness and pathology grade was significant( r>0.75).(2)According to IACUS blood flow classification standard, synovial blood effusion can be graded from 0 to 2. According to the manifestation of grey-scale and contrast-enhanced ultrasound, the area of synovium in both method could be limited or nearly none, or the area in grey scale larger than that of contrast-enhanced ultrasound. According to the blood flow in Power Doppler and contrast-enhanced ultrasound, the manifestation could be none in both, weak signal in Power Doppler but strong signal in contrast-enhanced ultrasound and strong signal in both. Time intensity curve could be enhancement in synovium, enhancement in synovium lower than surrounding tissue, no enhancement in surrounding tissue and no enhancement or filling defect in synovium. The synovial thickness in grey-scale was thicker than that of in contrast-enhanced ultrasound.Contrast-enhanced ultrasound can show synovium blood flow more effectively than Power Doppler. Synovium blood flow grade in Contrast-enhanced ultrasound was with more closely relationship with pathology grade. There was weak correlation between AUC and synovial pathology(p<0.05). There was no correlation between PI, WS and synovial pathology.Conclusion: Antigen-induced arthritis in rabbits as a stable animal model can simulate human RA disease process. US-guided biopsy is an effective method for pathology study. Ultrasound can reflect early stage of synovial pathology change accurately. To be combined with serum biomarkers, ultrasound can improve the diagnosis and treatment.pathological sections acquired by US guided biopsy can reveal“clinical-pathological separation” and “ biomarker-pathology non-synchronization”. Contrast-enhanced ultrasound can accurately reflect synovial blood flow and membrane thickness; also can locate the biopsy inlet. Contrast-enhanced ultrasound is more sensitive to show the RA synovial blood flow and estimates RA synovial pathological change accurately. Quantitative standard of contrast-enhanced ultrasound was with poor relationship with the severity of RA. |
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