Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland.
Department of Neurology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
Sci Rep. 2024 Apr 29;14(1):9848. doi: 10.1038/s41598-024-60497-6.
Pathological data showed focal inflammation and regions of diffuse neuronal loss in the cortex of people with multiple sclerosis (MS). In this work, we applied a novel model ("soma and neurite density imaging (SANDI)") to multishell diffusion-weighted MRI data acquired in healthy subjects and people with multiple sclerosis (pwMS), in order to investigate inflammation and degeneration-related changes in the cortical tissue of pwMS. We aimed to (i) establish whether SANDI is applicable in vivo clinical data; (ii) investigate inflammatory and degenerative changes using SANDI soma fraction (f)-a marker of cellularity-in both cortical lesions and in the normal-appearing-cortex and (iii) correlate SANDI f with clinical and biological measures in pwMS. We applied a simplified version of SANDI to a clinical scanners. We then provided evidence that pwMS exhibited an overall decrease in cortical SANDI f compared to healthy subjects, suggesting global degenerative processes compatible with neuronal loss. On the other hand, we have found that progressive pwMS showed a higher SANDI f in the outer part of the cortex compared to relapsing-remitting pwMS, possibly supporting current pathological knowledge of increased innate inflammatory cells in these regions. A similar finding was obtained in subpial lesions in relapsing-remitting patients, reflecting existing pathological data in these lesion types. A significant correlation was found between SANDI f and serum neurofilament light chain-a biomarker of inflammatory axonal damage-suggesting a relationship between SANDI soma fraction and inflammatory processes in pwMS again. Overall, our data show that SANDI f is a promising biomarker to monitor changes in cellularity compatible with neurodegeneration and neuroinflammation in the cortex of MS patients.
病理数据显示，多发性硬化症 (MS) 患者的大脑皮层存在局灶性炎症和弥漫性神经元丢失区域。在这项工作中，我们应用了一种新的模型（“神经元胞体和突起密度成像（SANDI）”）来分析健康受试者和多发性硬化症患者（pwMS）的多壳层弥散加权 MRI 数据，以研究 pwMS 大脑皮层组织中的炎症和退行性变化。我们旨在：(i) 确定 SANDI 是否适用于体内临床数据；(ii) 使用 SANDI 胞体分数（f）——细胞数量的标志物——来研究皮质病变和正常外观皮层中的炎症和退行性变化；(iii) 将 SANDI f 与 pwMS 的临床和生物学指标相关联。我们应用了 SANDI 的简化版本来分析临床扫描仪数据。然后，我们提供了证据表明，与健康受试者相比，pwMS 的大脑皮层 SANDI f 整体下降，表明存在与神经元丢失一致的全脑退行性过程。另一方面，我们发现进展性 pwMS 比缓解-复发型 pwMS 在外层大脑皮层中具有更高的 SANDI f，这可能支持这些区域中固有炎症细胞增加的当前病理知识。在缓解-复发型患者的软脑膜下病变中也得到了类似的发现，反映了这些病变类型的现有病理数据。SANDI f 与血清神经丝轻链（一种炎症性轴突损伤的生物标志物）之间存在显著相关性，这再次表明 SANDI 胞体分数与 pwMS 中的炎症过程之间存在关系。总的来说，我们的数据表明，SANDI f 是一种很有前途的生物标志物，可以监测与大脑皮层神经退行性变和神经炎症相一致的细胞数量变化。
