Werring D J, Brassat D, Droogan A G, Clark C A, Symms M R, Barker G J, MacManus D G, Thompson A J, Miller D H
NMR Research Unit, Queen Square, London, UK.
Brain. 2000 Aug;123 ( Pt 8):1667-76. doi: 10.1093/brain/123.8.1667.
The idea that the initiating event in the formation of all new multiple sclerosis lesions is a focal blood-brain barrier (BBB) leakage associated with perivascular inflammation has been challenged recently by the observation of subtle abnormalities in some quantitative magnetic resonance (MR) parameters (including the magnetization transfer ratio) prior to lesion enhancement. MR diffusion imaging can non-invasively quantify the average apparent diffusion coefficient (ADC(av)), a measure of water molecule random motion that is sensitive to pathological change in multiple sclerosis lesions and to abnormalities in the normal-appearing white matter (NAWM). We therefore used MR diffusion imaging to investigate the dynamic evolution of water diffusion measurements in new enhancing multiple sclerosis lesions, in the NAWM from which they arise, and in anatomically matched contralateral NAWM regions from which no visible lesions develop. Gadolinium diethylenetriaminepentaacetic acid (Gd)-enhanced MRI and MR diffusion studies were performed monthly for 1 year in five multiple sclerosis patients with clinically and radiologically active disease. The ADC(av) was calculated at each time point of the study (before, during and after lesion appearance on Gd-enhanced scans) for each new enhancing lesion, and for regions matched for size and position in the contralateral NAWM. A steady and moderate increase in ADC(av) in prelesion NAWM was observed, which was followed by a rapid and marked increase at the time of Gd enhancement and a slower decay after the cessation of enhancement. In matched contralateral NAWM regions there was a significant but milder increase in ADC(av) at the time of the first noted lesion enhancement. These findings indicate that new focal lesions associated with frank BBB leakage are preceded by subtle, progressive alterations in tissue integrity beyond the resolution of conventional MRI. The increases in ADC(av) in anatomically matched contralateral regions after lesions have appeared supports the concept that structural damage in lesions causes damage or dysfunction in connected areas of NAWM.
所有新的多发性硬化症病灶形成的起始事件是与血管周围炎症相关的局灶性血脑屏障（BBB）渗漏，这一观点最近受到了挑战，因为在病灶强化之前观察到一些定量磁共振（MR）参数（包括磁化传递率）存在细微异常。MR扩散成像可以非侵入性地量化平均表观扩散系数（ADC(av)），这是一种水分子随机运动的测量指标，对多发性硬化症病灶的病理变化以及正常外观白质（NAWM）的异常敏感。因此，我们使用MR扩散成像来研究新出现的强化性多发性硬化症病灶、病灶起源的NAWM以及未出现可见病灶的解剖学匹配对侧NAWM区域中水分子扩散测量的动态演变。对5例临床和放射学表现活跃的多发性硬化症患者进行了为期1年的每月一次钆喷酸葡胺（Gd）增强MRI和MR扩散研究。在研究的每个时间点（Gd增强扫描上病灶出现之前、期间和之后），计算每个新出现的强化病灶以及对侧NAWM中大小和位置匹配区域的ADC(av)。观察到病灶前NAWM中的ADC(av)稳定且适度增加，随后在Gd增强时迅速且显著增加，增强停止后下降较慢。在首次发现病灶增强时，匹配的对侧NAWM区域中的ADC(av)有显著但较轻的增加。这些发现表明，与明显的BBB渗漏相关的新局灶性病灶之前，组织完整性存在细微的、渐进性的改变，超出了传统MRI的分辨率。病灶出现后，解剖学匹配的对侧区域中ADC(av)的增加支持了病灶中的结构损伤会导致NAWM相连区域损伤或功能障碍的概念。
