Background and Purpose

Multiple Sclerosis (MS) is a progressive, inflammatory, neuro-degenerative disease of the central nervous system (CNS) characterized by a wide range of histopathological features including vascular abnormalities. In this study, an ultra-small superparamagnetic iron oxide (USPIO) contrast agent, Ferumoxytol, was administered to induce an increase in susceptibility for both arteries and veins to help better reveal the cerebral microvasculature. The purpose of this work was to examine the presence of vascular abnormalities and vascular density in MS lesions using high-resolution susceptibility weighted imaging (SWI).

Methods

Six subjects with relapsing remitting MS (RRMS, age = 47.3 ± 11.8 years with 3 females and 3 males) and fourteen age-matched healthy controls were scanned at 3 T with SWI acquired before and after the infusion of Ferumoxytol. Composite data was generated by registering the FLAIR data to the high resolution SWI data in order to highlight the vascular information in MS lesions. Both the central vein sign (CVS) and, a new measure, the multiple vessel sign (MVS) were identified, along with any vascular abnormalities, in the lesions on pre- and post-contrast SWI-FLAIR fusion data. The small vessel density within the periventricular normal-appearing white matter (NAWM) and the periventricular lesions were compared for all subjects.

Results

Averaged across two independent raters, a total of 530 lesions were identified across all patients. The total number of lesions with vascularity on pre- and post-contrast data were 287 and 488, respectively. The lesions with abnormal vascular behavior were broken up into following categories: small lesions appearing only at the vessel boundary; dilated vessels within the lesions; and developmental venous angiomas. These vessel abnormalities observed within lesions increased from 55 on pre-contrast data to 153 on post-contrast data. Finally, across all the patients, the periventricular lesional vessel density was significantly higher (p < 0.05) than that of the periventricular NAWM.

Conclusions

By inducing a super-paramagnetic susceptibility in the blood using Ferumoxytol, the vascular abnormalities in the RRMS patients were revealed and small vessel densities were obtained. This approach has the potential to monitor the venous vasculature present in MS lesions, catalogue their characteristics and compare the vascular structures spatially to the presence of lesions. These enhanced vascular features may provide new insight into the pathophysiology of MS.

中文翻译：

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使用 USPIO 揭示多发性硬化症病变中的血管异常并测量小血管密度

背景和目的

多发性硬化症 (MS) 是一种进行性、炎症性、中枢神经系统 (CNS) 神经退行性疾病，其特征是多种组织病理学特征，包括血管异常。在这项研究中，使用超小型超顺磁性氧化铁 (USPIO) 造影剂 Ferumoxytol 来诱导动脉和静脉敏感性增加，以帮助更好地揭示脑微血管系统。这项工作的目的是使用高分辨率磁敏感加权成像 (SWI) 检查 MS 病变中是否存在血管异常和血管密度。

方法

六名复发缓解型 MS 受试者（RRMS，年龄 = 47.3 ± 11.8 岁，其中 3 名女性和 3 名男性）和 14 名年龄匹配的健康对照者在输注 Ferumoxytol 之前和之后使用 SWI 进行 3 T 扫描。通过将 FLAIR 数据与高分辨率 SWI 数据配准来生成复合数据，以突出 MS 病变中的血管信息。根据对比前和对比后的 SWI-FLAIR 融合数据，在病变中识别出中央静脉征 (CVS) 和新的测量方法多血管征 (MVS)，以及任何血管异常。比较所有受试者的脑室周围正常白质（NAWM）内的小血管密度和脑室周围病变。

结果

对两名独立评估者进行平均，所有患者总共发现 530 个病变。对比前和对比后数据中具有血管分布的病变总数分别为 287 个和 488 个。血管行为异常的病变分为以下几类：仅出现在血管边界的小病变；病变内血管扩张；和发育性静脉血管瘤。病变内观察到的这些血管异常从对比前数据的 55 个增加到对比后数据的 153 个。最后，在所有患者中，脑室周围病变血管密度显着高于 脑室周围 NAWM （ p < 0.05）。

结论

通过使用 Ferumoxytol 在血液中诱导超顺磁磁化率，揭示了 RRMS 患者的血管异常并获得了小血管密度。这种方法有可能监测多发性硬化症病变中存在的静脉脉管系统，对其特征进行分类，并在空间上比较血管结构与病变的存在。这些增强的血管特征可能为多发性硬化症的病理生理学提供新的见解。