Laurent Didier, Wasvary James, O'Byrne Elizabeth, Rudin Markus
Novartis Institute for Biomedical Research, East Hanover, New Jersey 07936, USA.
Magn Reson Med. 2003 Sep;50(3):541-9. doi: 10.1002/mrm.10566.
Proteoglycan (PG) loss and disruption of the collagen framework in cartilage are early events associated with osteoarthritis (OA). The feasibility of in vivo high-resolution MRI assessments probing both macromolecules was explored in articular cartilage of the rabbit knee. One-millimeter thick coronal images were obtained at 3 T with a 97 x 97 microm(2) pixel size. A 22% decrease in the magnetization transfer (MT) exchange rate along with an approximately 2-fold greater Gd(DTPA)(2-)-induced decrease in T(1) relaxation time were measured in response to papain injection 1 day prior to the MRI session, indicative of an alteration of collagen integrity and PG depletion, respectively. A two-point method was tested as an alternative to the more time-consuming multipoint method typically used to measure T(1) changes. Kinetics of Gd(DTPA)(2-) uptake were observed with a 10-min time resolution. The diffusive transport of Gd(DTPA)(2-) was characterized by a T(1) decrease approximately 2-fold faster in papain-treated knees. These data suggest that kinetics of tracer diffusion may be used as an informative marker of PG loss, in addition to the amplitude of T(1) variations. When applied to a relevant OA model, the combination of MT and Gd(DTPA)(2-)-MRI may help in identifying new active compounds during efficacy studies on cartilage protection.
蛋白聚糖（PG）丢失和软骨中胶原框架破坏是与骨关节炎（OA）相关的早期事件。本研究探讨了在兔膝关节软骨中进行体内高分辨率MRI评估以探测这两种大分子的可行性。在3 T场强下获得1毫米厚的冠状位图像，像素大小为97×97微米²。在MRI扫描前1天注射木瓜蛋白酶后，测量到磁化传递（MT）交换率下降22%，同时钆喷酸葡胺（Gd（DTPA）²⁻）诱导的T1弛豫时间下降约2倍，分别表明胶原完整性改变和PG耗竭。测试了一种两点法作为通常用于测量T1变化的更耗时的多点法的替代方法。以10分钟的时间分辨率观察Gd（DTPA）²⁻的摄取动力学。在木瓜蛋白酶处理的膝关节中，Gd（DTPA）²⁻的扩散转运表现为T1下降速度快约2倍。这些数据表明，除了T1变化幅度外，示踪剂扩散动力学可用作PG丢失的信息性标志物。当应用于相关OA模型时，MT和Gd（DTPA）²⁻-MRI的联合应用可能有助于在软骨保护功效研究中识别新的活性化合物。
