Quantitative pre-clinical screening of therapeutics for joint diseases using contrast enhanced micro-computed tomography.
Quantitative pre-clinical screening of therapeutics for joint diseases using contrast enhanced micro-computed tomography.
复制标题
使用对比增强微计算机断层扫描对关节疾病的治疗方法进行定量临床前筛选。
DOI：
10.1016/j.joca.2016.04.021
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发表时间：
2016
影响因子：
7
通讯作者：
Kamath,RV
中科院分区：
文献类型：
--
作者：
Willett,NJ;Thote,T;Hart,M;Moran,S;Guldberg,RE;Kamath,RV
ObjectiveThe development of effective therapies for cartilage protection has been limited by a lack of efficient quantitative cartilage imaging modalities in pre-clinicalin vivomodels. Our objectives were two-fold: first, to validate a new contrast-enhanced 3D imaging analysis technique, equilibrium partitioning of an ionic contrast agent-micro computed tomography (EPIC-μCT), in a rat medial meniscal transection (MMT) osteoarthritis (OA) model; and second, to quantitatively assess the sensitivity of EPIC-μCT to detect the effects of matrix metalloproteinase inhibitor (MMPi) therapy on cartilage degeneration.MethodsRats underwent MMT surgery and tissues were harvested at 1, 2, and 3 weeks post-surgery or rats received an MMPi or vehicle treatment and tissues harvested 3 weeks post-surgery. Parameters of disease progression were evaluated using histopathology and EPIC-μCT. Correlations and power analyses were performed to compare the techniques.ResultsEPIC-μCT was shown to provide simultaneous 3D quantification of multiple parameters, including cartilage degeneration and osteophyte formation. In MMT animals treated with MMPi, OA progression was attenuated, as measured by 3D parameters such as lesion volume and osteophyte size. Apost-hocpower analysis showed that 3D parameters for EPIC-μCT were more sensitive than 2D parameters requiring fewer animals to detect a therapeutic effect of MMPi. 2D parameters were comparable between EPIC-μCT and histopathology.ConclusionThis study demonstrated that EPIC-μCT has high sensitivity to provide 3D structural and compositional measurements of cartilage and bone in the joint. EPIC-μCT can be used in combination with histology to provide a comprehensive analysis to screen new potential therapies.
