Department of Neurology, RWTH Aachen University, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen University, Aachen, Germany.
NeuroSpin, CEA, CNRS UMR9027, Paris-Saclay University, Gif-sur-Yvette, France.
Neuroimage Clin. 2022;36:103274. doi: 10.1016/j.nicl.2022.103274. Epub 2022 Nov 21.
Application of MRI in clinical routine mainly addresses structural alterations. However, pathological changes at a cellular level are expected to precede the occurrence of brain atrophy clusters and of clinical symptoms. In this context, Na-MRI examines sodium changes in the brain as a potential metabolic parameter. Recently, we have shown that Na-MRI at ultra-high-field (7 T) was able to detect increased tissue sodium concentration (TSC) in Alzheimer's disease (AD). In this work, we aimed at assessing AD-pathology with Na-MRI in a larger cohort and on a clinical 3T MR scanner.
We used a multimodal MRI protocol on 52 prodromal to mild AD patients and 34 cognitively healthy control subjects on a clinical 3T MR scanner. We examined the TSC, brain volume, and cortical thickness in association with clinical parameters. We further compared TSC with intra-individual normalized TSC for the reduction of inter-individual TSC variability resulting from physiological as well as experimental conditions. Normalized TSC maps were created by normalizing each voxel to the mean TSC inside the brain stem.
We found increased normalized TSC in the AD cohort compared to elderly control subjects both on global as well as on a region-of-interest-based level. We further confirmed a significant association of local brain volume as well as age with TSC. TSC increase in the left temporal lobe was further associated with the cognitive state, evaluated via the Montreal cognitive assessment (MoCA) screening test. An increase of normalized TSC depending on disease stage reflected by the Clinical Dementia Rating (CDR) was found in our AD patients in temporal lobe regions. In comparison to classical brain volume and cortical thickness assessments, normalized TSC had a higher discriminative power between controls and prodromal AD patients in several regions of the temporal lobe.
We confirm the feasibility of Na-MRI at 3T and report an increase of TSC in AD in several regions of the brain, particularly in brain regions of the temporal lobe. Furthermore, to reduce inter-subject variability caused by physiological factors such as circadian rhythms and experimental conditions, we introduced normalized TSC maps. This showed a higher discriminative potential between different clinical groups in comparison to the classical TSC analysis. In conclusion, Na-MRI represents a potential translational imaging marker applicable e.g.for diagnostics and the assessment of intervention outcomes in AD even under clinically available field strengths such as 3T. Implication of Na-MRI in association with other metabolic imaging marker needs to be further elucidated.
磁共振成像（MRI）在临床常规中的应用主要针对结构改变。然而，细胞水平的病理变化预计会先于脑萎缩簇和临床症状的发生。在这方面，Na-MRI 检查大脑中的钠变化作为潜在的代谢参数。最近，我们已经证明，超高场（7T）的 Na-MRI 能够检测到阿尔茨海默病（AD）中组织钠浓度（TSC）的增加。在这项工作中，我们旨在使用更大的队列和临床 3T MRI 扫描仪评估 Na-MRI 对 AD 病理学的影响。
我们使用多模态 MRI 方案对 52 名前驱期至轻度 AD 患者和 34 名认知健康对照者进行检查，在临床 3T MRI 扫描仪上进行。我们检查了 TSC、脑容量和皮质厚度与临床参数的关系。我们还将 TSC 与个体内标准化 TSC 进行了比较，以减少因生理和实验条件引起的个体间 TSC 变异性。通过将每个体素归一化为脑干内的平均 TSC，创建了标准化 TSC 图谱。
我们发现 AD 队列的标准化 TSC 高于老年对照组，无论是在全局还是在基于感兴趣区域的水平上。我们进一步证实了局部脑容量和年龄与 TSC 的显著相关性。左颞叶的 TSC 增加与认知状态进一步相关，通过蒙特利尔认知评估（MoCA）筛选测试进行评估。我们发现，在我们的 AD 患者中，根据临床痴呆评定量表（CDR）反映的疾病阶段，标准化 TSC 会随着时间的推移而增加。与经典的脑容量和皮质厚度评估相比，在颞叶的几个区域，标准化 TSC 在对照组和前驱期 AD 患者之间具有更高的区分能力。
我们证实了 3T 时 Na-MRI 的可行性，并报告了 AD 患者大脑中多个区域 TSC 的增加，特别是在颞叶区域。此外，为了减少因生理因素（如昼夜节律和实验条件）引起的个体间变异性，我们引入了标准化 TSC 图谱。与经典的 TSC 分析相比，这显示了在不同临床组之间更高的区分能力。总之，Na-MRI 是一种潜在的转化成像标志物，即使在临床可用的场强（如 3T）下，也可用于 AD 的诊断和干预效果的评估。需要进一步阐明 Na-MRI 与其他代谢成像标志物的关联。
