Orthopaedic Research Center, C. Wayne McIlwraith Translational Medicine Institute, Colorado State University, Fort Collins, Colorado, USA.
Harvard Medical School, Beth Israel Deaconess Medical Center, Center for Advanced Orthopaedic Studies, Boston, Massachusetts, USA.
J Orthop Res. 2024 Oct;42(10):2264-2276. doi: 10.1002/jor.25869. Epub 2024 May 8.
Cationic contrast-enhanced computed tomography (CECT) capitalizes on increased contrast agent affinity to the charged proteoglycans in articular cartilage matrix to provide quantitative assessment of proteoglycan content with enhanced images. While high resolution microCT has demonstrated success, we investigate cationic CECT use in longitudinal in vivo imaging at clinical resolution. We hypothesize that repeated administration of CA4+ will have no adverse side effects or complications, and that sequential in vivo imaging assessments will distinguish articular cartilage repair tissue from early degenerative and healthy cartilage in critically sized chondral defects. In an established equine translational preclinical model, lameness and synovial effusion scores are similar to controls after repeated injections of CA4+ (eight injections over 16 weeks) compared to controls. Synovial fluid total protein, leukocyte concentration, and sGAG and PGE concentrations and articular cartilage and synovial membrane scores are also equivalent to controls. Longitudinal in vivo cationic CECT attenuation in repair tissue is significantly lower than peripheral to (adjacent) and distantly from defects (remote sites) by 4 weeks (p < 0.001), and this difference persists until 16 weeks. At the 6- and 8-week time points, the adjacent locations exhibit significantly lower cationic CECT attenuation compared with the remote sites, reflecting peri-defect degeneration (p < 0.01). Cationic CECT attenuation at clinical resolution significantly correlates with cationic CECT (microCT) (r = 0.69, p < 0.0001), sGAG (r = 0.48, p < 0.0001), and ICRS II histology score (r = 0.63, p < 0.0001). In vivo cationic CECT imaging at clinical resolution distinguishes fibrous repair tissue from degenerative and healthy hyaline cartilage and correlates with molecular tissue properties of articular cartilage.
阳离子对比增强计算机断层扫描（CECT）利用造影剂对关节软骨基质中带电荷的蛋白聚糖的亲和力，提供对蛋白聚糖含量的定量评估，并增强图像。虽然高分辨率 microCT 已经取得了成功，但我们研究了阳离子 CECT 在临床分辨率的活体纵向成像中的应用。我们假设重复给予 CA4+不会产生不良反应或并发症，并且连续的活体成像评估将区分关节软骨修复组织与临界大小软骨缺损中的早期退行性和健康软骨。在已建立的马转化临床前模型中，与对照组相比，在重复注射 CA4+（16 周内注射 8 次）后，跛行和滑膜炎评分相似。滑液总蛋白、白细胞浓度、sGAG 和 PGE 浓度以及关节软骨和滑膜评分也与对照组相当。修复组织的纵向活体阳离子 CECT 衰减在第 4 周时明显低于缺损周围（相邻）和远处（远程部位）（p < 0.001），并且这种差异一直持续到 16 周。在 6 周和 8 周的时间点，相邻部位的阳离子 CECT 衰减明显低于远程部位，反映了缺陷周围的退行性变（p < 0.01）。临床分辨率下的阳离子 CECT 衰减与阳离子 CECT（microCT）（r = 0.69，p < 0.0001）、sGAG（r = 0.48，p < 0.0001）和 ICRS II 组织学评分（r = 0.63，p < 0.0001）显著相关。临床分辨率下的活体阳离子 CECT 成像可区分纤维修复组织与退行性和健康透明软骨，并与关节软骨的分子组织特性相关。
