O'Byrne Elizabeth, Pellas Theodore, Laurent Didier
Department of Arthritis Biology, Novartis Institute for Biomedical Research, 556 Morris Avenue, Summit, NJ 07901-1398, USA.
Novartis Found Symp. 2003;249:190-8; discussion 198-202, 234-8, 239-41.
The molecular organization and biochemical composition that give cartilage the viscoelasticity necessary for load distribution also convey unique magnetic resonance (MR) properties. In that context, MR imaging has the potential to detect cartilage degeneration and regeneration. Magnetization transfer (MT) imaging probes the exchange of magnetization between the bulk water pool and the water pool bound to macromolecules such as collagen and hence MT may be applied for evaluation of collagen integrity. In addition, Gd(DTPA)(2-)-induced T1 changes have been proposed as a surrogate marker of proteoglycan (PG) loss based on the principle that the paramagnetic agent Gd(DTPA)2- penetrates cartilage to an equilibrium concentration inversely proportional to the negative charge density (i.e. the PG concentration). Results obtained in vivo from MT and Gd(DTPA)(2-)-enhanced MRI acquisitions on the goat knee showed early signs of biochemical changes in response to a papain injection. A dose-dependent effect of papain was observed with both approaches over a wide range of PG depletion (i.e. T1 measurement) and collagen damage (i.e. MT measurement) as confirmed with post-mortem biochemistry and histology. Development of MRI protocols for non-invasive assessment of cartilage will facilitate diagnosis and monitoring of treatment efficacy in the clinic.
赋予软骨负荷分布所需黏弹性的分子结构和生化组成也赋予了其独特的磁共振(MR)特性。在这种情况下,MR成像有潜力检测软骨退变和再生。磁化传递(MT)成像探测本体水池与结合在诸如胶原蛋白等大分子上的水池之间的磁化交换,因此MT可用于评估胶原蛋白的完整性。此外,基于顺磁性剂钆喷酸葡胺(Gd(DTPA)2-)穿透软骨达到与负电荷密度(即蛋白聚糖(PG)浓度)成反比的平衡浓度这一原理,钆喷酸葡胺(Gd(DTPA)2-)诱导的T1变化已被提议作为PG丢失的替代标志物。在山羊膝关节上进行MT和Gd(DTPA)2-增强MRI采集的体内研究结果显示,木瓜蛋白酶注射后出现了生化变化的早期迹象。两种方法均观察到木瓜蛋白酶在广泛的PG消耗范围(即T1测量)和胶原蛋白损伤范围(即MT测量)内呈现剂量依赖性效应,这一点通过死后生化和组织学得以证实。开发用于软骨无创评估的MRI方案将有助于临床诊断和治疗效果监测。