Preziosa Paolo, Pagani Elisabetta, Meani Alessandro, Marchesi Olga, Conti Lorenzo, Falini Andrea, Rocca Maria A, Filippi Massimo
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Neurol. 2023 Feb;270(2):810-823. doi: 10.1007/s00415-022-11415-1. Epub 2022 Oct 6.
Pathologically specific MRI measures may elucidate in-vivo the heterogeneous processes contributing to cognitive impairment in multiple sclerosis (MS).
Using diffusion tensor and neurite orientation dispersion and density imaging (NODDI), we explored the contribution of focal lesions and normal-appearing (NA) tissue microstructural abnormalities to cognitive impairment in MS.
One hundred and fifty-two MS patients underwent 3 T brain MRI and a neuropsychological evaluation. Forty-eight healthy controls (HC) were also scanned. Fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (ICV_f) and orientation dispersion index (ODI) were assessed in cortical and white matter (WM) lesions, thalamus, NA cortex and NAWM. Predictors of cognitive impairment were identified using random forest.
Fifty-two MS patients were cognitively impaired. Compared to cognitively preserved, impaired MS patients had higher WM lesion volume (LV), lower normalized brain volume (NBV), cortical volume (NCV), thalamic volume (NTV), and WM volume (p ≤ 0.021). They also showed lower NAWM FA, higher NAWM, NA cortex and thalamic MD, lower NAWM ICV_f, lower WM lesion ODI, and higher NAWM ODI (false discovery rate-p ≤ 0.026). Cortical lesion number and microstructural abnormalities were not significantly different. The best MRI predictors of cognitive impairment (relative importance) (out-of-bag area under the curve = 0.727) were NAWM FA (100%), NTV (96.0%), NBV (84.7%), thalamic MD (43.4%), NCV (40.6%), NA cortex MD (26.0%), WM LV (23.2%) and WM lesion ODI (17.9%).
Our multiparametric MRI study including NODDI measures suggested that neuro-axonal damage and loss of microarchitecture integrity in focal WM lesions, NAWM, and GM contribute to cognitive impairment in MS.
病理特异性MRI测量可能在体内阐明导致多发性硬化症（MS）认知障碍的异质性过程。
利用扩散张量和神经突方向离散度与密度成像（NODDI），我们探讨了局灶性病变和正常外观（NA）组织微观结构异常对MS认知障碍的影响。
152例MS患者接受了3T脑MRI检查和神经心理学评估。还对48名健康对照者（HC）进行了扫描。评估了皮质和白质（WM）病变、丘脑、NA皮质和NAWM中的分数各向异性（FA）、平均扩散率（MD）、细胞内体积分数（ICV_f）和方向离散度指数（ODI）。使用随机森林确定认知障碍的预测因素。
52例MS患者存在认知障碍。与认知功能保留的患者相比，认知障碍的MS患者有更高的WM病变体积（LV）、更低的标准化脑体积（NBV）、皮质体积（NCV）、丘脑体积（NTV）和WM体积（p≤0.021）。他们还表现出更低的NAWM FA、更高的NAWM、NA皮质和丘脑MD、更低的NAWM ICV_f、更低的WM病变ODI以及更高的NAWM ODI（错误发现率-p≤0.026）。皮质病变数量和微观结构异常无显著差异。认知障碍的最佳MRI预测因素（相对重要性）（袋外曲线下面积=0.727）为NAWM FA（100%）、NTV（96.0%）、NBV（84.7%）、丘脑MD（43.4%）、NCV（40.6%）、NA皮质MD（26.0%）、WM LV（23.2%）和WM病变ODI（17.9%）。
我们包括NODDI测量的多参数MRI研究表明，局灶性WM病变、NAWM和GM中的神经轴突损伤和微结构完整性丧失导致了MS的认知障碍。
