Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 - 3, 68167 Mannheim, Germany.
VGMorph GmbH, Waterloostr. 32, 45472 Mülheim an der Ruhr, Germany; Neurocentrum, Am Ziegelkamp 1f, 41515 Grevenbroich, Germany.
Mult Scler Relat Disord. 2022 Jan;57:103340. doi: 10.1016/j.msard.2021.103340. Epub 2021 Oct 18.
Several studies have pointed out that seemingly chronic multiple sclerosis (MS) lesions may also be in inflammatory states. In pathological studies, up to 40% of chronic MS lesions are characterized as "chronic active" or "smoldering" lesions that are characterized by a rim of iron-laden proinflammatory macrophages/microglial cells at the lesion edge with low-grade continuous myelin breakdown. In vivo, these lesions can be visualized as "iron rim lesions" (IRLs) on susceptibility-weighted imaging (SWI). The aim of this study was to investigate the long-term dynamics of IRLs in vivo for a more detailed evolution of dynamic lesion volume changes occurring over time.
We retrospectively identified patients with MS who were followed for at least 36 months (up to 72 months) and underwent at least an annual MRI on the same 3 Tsystem. Using Voxel-Guided Morphometry (VGM) we investigated regional volume changes within lesions and correlated these findings with SWI for the presence of a characteristic hypointense lesion rim. To estimate tissue damage, apparent diffusion coefficient (ADC) values for every lesion at baseline and follow-up MRIs were determined.
Forty-three patients were included in the study. Overall, we identified 302 supratentorial non-confluent MS lesions (52 persistent IRLs, nine transient IRLs, 228 non-IRLs and 13 acute contrast-enhancing lesions). During follow-up, persistent IRLs significantly enlarged, whereas non-IRLs showed a tendency to shrink. At baseline MRI, ADC values were significantly higher in persistent IRLs (1.23 × 10 mm/s) compared to non-IRLs (1.01 × 10 mm/s; p < 0.001), but not compared to transient IRLs (1.06 × 10 mm/s; p = 0.15) and contrast-enhancing lesions (1.15 × 10 mm/s; p = 1.0). During follow-up, ADC values significantly increased more often in persistent IRLs compared to all other lesion types (p < 0.0001).
Our long-term data demonstrate that persistent IRLs enlarge during disease duration, whereas non-IRLs show a tendency to shrink. Furthermore, IRLs are associated with sustained tissue damage, supporting the notion that IRLs could represent a new imaging biomarker in MS.
多项研究指出，看似慢性的多发性硬化症（MS）病灶也可能处于炎症状态。在病理学研究中，高达 40%的慢性 MS 病灶表现为“慢性活动”或“闷烧”病灶，其特征是病灶边缘有一圈含铁的促炎巨噬细胞/小胶质细胞，伴有低级别、持续的髓鞘破坏。在体内，这些病灶在磁化率加权成像（SWI）上可以被视为“铁环病灶”（IRLs）。本研究旨在探讨体内 IRL 的长期动态变化，以更详细地了解随时间推移发生的动态病灶体积变化的演变。
我们回顾性地确定了至少接受 36 个月（最长 72 个月）随访且在同一 3T 系统上至少每年进行一次 MRI 的 MS 患者。使用体素导向形态计量学（VGM），我们研究了病灶内的区域体积变化，并将这些发现与 SWI 相关联，以确定特征性的低信号病灶边缘。为了估计组织损伤，我们在基线和随访 MRI 上确定了每个病灶的表观扩散系数（ADC）值。
本研究纳入了 43 名患者。总体而言，我们共确定了 302 个幕上非融合性 MS 病灶（52 个持续性 IRL、9 个短暂性 IRL、228 个非 IRL 和 13 个急性对比增强病灶）。在随访期间，持续性 IRL 明显增大，而非 IRL 则有缩小的趋势。在基线 MRI 上，持续性 IRL 的 ADC 值明显高于非 IRL（1.23×10mm/s 比 1.01×10mm/s；p<0.001），但与短暂性 IRL（1.06×10mm/s；p=0.15）和对比增强病灶（1.15×10mm/s；p=1.0）无差异。在随访期间，持续性 IRL 的 ADC 值较其他所有病灶类型的升高更为显著（p<0.0001）。
我们的长期数据表明，持续性 IRL 在疾病过程中会增大，而非 IRL 则有缩小的趋势。此外，IRLs 与持续的组织损伤相关，支持 IRLs 可能成为 MS 的一种新的影像学生物标志物的观点。
