Katsumi Yuta, Brickhouse Michael, Hanford Lindsay C, Nielsen Jared A, Elliott Maxwell L, Mair Ross W, Touroutoglou Alexandra, Eldaief Mark C, Buckner Randy L, Dickerson Bradford C
Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Department of Psychology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
medRxiv. 2025 Mar 17:2025.03.14.25323769. doi: 10.1101/2025.03.14.25323769.
Regional brain atrophy estimated from structural magnetic resonance imaging (MRI) is a widely used measure of neurodegeneration in Alzheimer's disease (AD), Frontotemporal Lobar Degeneration (FTLD), and other dementias. Yet, traditional MRI-derived morphometric estimates are susceptible to measurement errors, posing a challenge for reliably detecting longitudinal atrophy, particularly over short intervals. Here, we examined the utility of multiple MRI scans acquired in rapid succession (i.e., ) for detecting longitudinal cortical atrophy over 3- and 6-month intervals within individual patients. Four individuals with mild cognitive impairment or mild dementia likely due to AD or FTLD participated in this study. At baseline, 3 months, and 6 months, structural MRI data were collected on a 3 Tesla scanner using a fast 1.2-mm T1-weighted multi-echo magnetization-prepared rapid gradient echo (MEMPRAGE) sequence (acquisition time = 2'23"). At each timepoint, participants underwent up to 32 MEMPRAGE scans acquired in four separate sessions over two days. Using linear mixed-effects models, phenotypically vulnerable cortical ("core atrophy") regions exhibited statistically significant longitudinal atrophy in all participants (i.e., decreased cortical thickness) by 3 months and further demonstrated preferential vulnerability compared to control regions in three of the participants over at least one of the 3-month intervals. These findings provide proof-of-concept evidence that pooling multiple morphometric estimates derived from cluster scanning can detect longitudinal cortical atrophy over short intervals in individual patients with neurodegenerative dementias.
通过结构磁共振成像（MRI）估计的局部脑萎缩是阿尔茨海默病（AD）、额颞叶变性（FTLD）和其他痴呆症中广泛使用的神经退行性变测量指标。然而，传统的MRI衍生形态学估计容易受到测量误差的影响，这对可靠地检测纵向萎缩构成了挑战，尤其是在短时间间隔内。在此，我们研究了在个体患者中连续快速采集的多次MRI扫描（即）在检测3个月和6个月间隔内纵向皮质萎缩方面的效用。四名可能因AD或FTLD导致轻度认知障碍或轻度痴呆的个体参与了本研究。在基线、3个月和6个月时，使用快速1.2毫米T1加权多回波磁化准备快速梯度回波（MEMPRAGE）序列（采集时间 = 2分23秒）在3特斯拉扫描仪上收集结构MRI数据。在每个时间点，参与者在两天内分四个单独的时段接受了多达32次MEMPRAGE扫描。使用线性混合效应模型，表型易损皮质（“核心萎缩”）区域在所有参与者中在3个月时均表现出统计学上显著的纵向萎缩（即皮质厚度降低），并且在至少一个3个月间隔内，三名参与者的这些区域与对照区域相比表现出更明显的易损性。这些发现提供了概念验证证据，即汇总从簇扫描获得的多个形态学估计可以在患有神经退行性痴呆的个体患者中短时间间隔内检测到纵向皮质萎缩。
