Correspondence of mean apparent propagator MRI metrics with phosphorylated tau and astrogliosis in chronic traumatic encephalopathy.
Correspondence of mean apparent propagator MRI metrics with phosphorylated tau and astrogliosis in chronic traumatic encephalopathy.
复制标题
慢性创伤性脑病中平均表观传播 MRI 指标与磷酸化 tau 蛋白和星形胶质细胞增生的对应关系。
DOI：
10.1093/braincomms/fcad253
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发表时间：
2023
影响因子：
4.8
通讯作者：
Basser,PeterJ
中科院分区：
文献类型：
--
作者：
Gangolli,Mihika;Pajevic,Sinisa;Kim,JoongHee;Hutchinson,ElizabethB;Benjamini,Dan;Basser,PeterJ
慢性创伤性脑病是一种神经退行性疾病，其诊断和分期基于磷酸化tau病理的定位和程度。虽然其鉴定仍然是区分慢性创伤性脑病与其他tau蛋白病的主要诊断标准，但在皮质灰质和血管周围区域的神经元缠结中积累的过度磷酸化tau蛋白通常伴有伴随的病理学，如星形胶质细胞增生。平均表观传播子MRI是一种临床上可行的扩散MRI方法，适用于对复杂生物介质的微结构进行有效和全面的表征。我们在0.25 mm各向同性体素下对10例患有“高慢性创伤性脑病”的活体人类组织标本进行了横断面研究，在传播指标与潜在的磷酸化tau蛋白和星形胶质细胞病理学之间进行了定量相关性。 感兴趣区域的线性混合效应分析显示，磷酸化tau蛋白与皮质灰质中传播因子估计的非高斯性（P= 0.002）以及星形胶质细胞增生与皮质表面白色物质中传播因子各向异性（P= 0.0009）存在显著关系。使用线性回归发现磷酸化tau蛋白和非高斯性之间的正相关性是适度的，但具有显著性（R2= 0.44，P = 6.0 × 10−5）。我们开发了一种无监督的聚类算法与非高斯性和传播各向异性作为输入，这是能够识别体素在表层皮质白色物质，对应于星形胶质细胞积累在灰色-白色物质界面。我们的研究结果表明，在高空间分辨率的平均表观传播MRI提供了一种手段，不仅确定磷酸化tau病理，但也检测区域与星形胶质细胞病理，因此可能证明在诊断价值的评估伴随病理皮质组织与复杂的微观结构。
Chronic traumatic encephalopathy is a neurodegenerative disease that is diagnosed and staged based on the localization and extent of phosphorylated tau pathology. Although its identification remains the primary diagnostic criteria to distinguish chronic traumatic encephalopathy from other tauopathies, the hyperphosphorylated tau that accumulates in neurofibrillary tangles in cortical grey matter and perivascular regions is often accompanied by concomitant pathology such as astrogliosis. Mean apparent propagator MRI is a clinically feasible diffusion MRI method that is suitable to characterize microstructure of complex biological media efficiently and comprehensively. We performed quantitative correlations between propagator metrics and underlying phosphorylated tau and astroglial pathology in a cross-sectional study of 10ex vivohuman tissue specimens with ‘high chronic traumatic encephalopathy’ at 0.25 mm isotropic voxels. Linear mixed effects analysis of regions of interest showed significant relationships of phosphorylated tau with propagator-estimated non-Gaussianity in cortical grey matter (P= 0.002) and of astrogliosis with propagator anisotropy in superficial cortical white matter (P= 0.0009). The positive correlation between phosphorylated tau and non-Gaussianity was found to be modest but significant (R2= 0.44,P= 6.0 × 10−5) using linear regression. We developed an unsupervised clustering algorithm with non-Gaussianity and propagator anisotropy as inputs, which was able to identify voxels in superficial cortical white matter that corresponded to astrocytes that were accumulated at the grey–white matter interface. Our results suggest that mean apparent propagator MRI at high spatial resolution provides a means to not only identify phosphorylated tau pathology but also detect regions with astrocytic pathology and may therefore prove diagnostically valuable in the evaluation of concomitant pathology in cortical tissue with complex microstructure.