Absinta Martina, Sati Pascal, Schindler Matthew, Leibovitch Emily C, Ohayon Joan, Wu Tianxia, Meani Alessandro, Filippi Massimo, Jacobson Steven, Cortese Irene C M, Reich Daniel S
J Clin Invest. 2016 Jul 1;126(7):2597-609. doi: 10.1172/JCI86198. Epub 2016 Jun 6.
In some active multiple sclerosis (MS) lesions, a strong immune reaction at the lesion edge may contain growth and thereby isolate the lesion from the surrounding parenchyma. Our previous studies suggest that this process involves opening of the blood-brain barrier in capillaries at the lesion edge, seen on MRI as centripetal contrast enhancement and a colocalized phase rim. We hypothesized that using these features to characterize early lesion evolution will allow in vivo tracking of tissue degeneration and/or repair, thus improving the evaluation of potential therapies for chronic active lesions.
Centripetally and centrifugally enhancing lesions were studied in 17 patients with MS using 7-tesla MRI. High-resolution, susceptibility-weighted, T1-weighted (before/after gadolinium), and dynamic contrast-enhanced scans were acquired at baseline and months 1, 3, 6, and 12. For each lesion, time evolution of the phase rim, lesion volume, and T1 hypointensity were assessed. In autopsies of 3 progressive MS cases, the histopathology of the phase rim was determined.
In centripetal lesions, a phase rim colocalized with initial contrast enhancement. In 12 of 22, this phase rim persisted after enhancement resolved. Compared with centripetal lesions with transient rim, those with persistent rim had less volume shrinkage and became more T1 hypointense between months 3 and 12. No centrifugal lesions developed phase rims at any time point. Pathologically, persistent rims corresponded to an iron-laden inflammatory myeloid cell population at the edge of chronic demyelinated lesions.
In early lesion evolution, a persistent phase rim in lesions that shrink least and become more T1 hypointense over time suggests that the rim might mark failure of early lesion repair and/or irreversible tissue damage. In later stages of MS, phase rim lesions continue to smolder, exerting detrimental effects on affected brain tissue.
NCT00001248.
The Intramural Research Program of NINDS supported this study.
在一些活动性多发性硬化（MS）病灶中，病灶边缘强烈的免疫反应可能会抑制生长，从而使病灶与周围实质组织隔离。我们之前的研究表明，这一过程涉及病灶边缘毛细血管血脑屏障的开放，在磁共振成像（MRI）上表现为向心性对比增强和共定位的相位边缘。我们假设利用这些特征来表征早期病灶演变将能够在体内追踪组织变性和/或修复情况，从而改善对慢性活动性病灶潜在治疗方法的评估。
使用7特斯拉MRI对17例MS患者的向心性和离心性强化病灶进行研究。在基线以及第1、3、6和12个月时进行高分辨率、磁敏感加权、T1加权（钆剂注射前后）和动态对比增强扫描。对每个病灶评估相位边缘、病灶体积和T1低信号强度随时间的变化。在3例进行性MS病例的尸检中，确定相位边缘的组织病理学情况。
在向心性病灶中，相位边缘与初始对比增强共定位。在22个病灶中的12个中，这种相位边缘在增强消退后持续存在。与具有短暂边缘的向心性病灶相比，具有持续边缘的病灶在第3至12个月间体积缩小较少，且T1低信号更强。在任何时间点，离心性病灶均未出现相位边缘。病理上，持续的边缘对应于慢性脱髓鞘病灶边缘富含铁的炎性髓样细胞群。
在早期病灶演变过程中，随着时间推移体积缩小最少且T1低信号更强的病灶中持续存在的相位边缘表明，该边缘可能标志着早期病灶修复失败和/或不可逆的组织损伤。在MS的后期，相位边缘病灶持续存在，对受影响的脑组织产生有害影响。
NCT00001248。
美国国立神经疾病和中风研究所的内部研究项目资助了本研究。
