Olm Christopher A, Peterson Claire S, Irwin David J, Lee Edward B, Trojanowski John Q, Massimo Lauren, Detre John A, McMillan Corey T, Gee James C, Grossman Murray
Penn Frontotemporal Degeneration Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Penn Image Computing & Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Imaging Neurosci (Camb). 2024 Mar 22;2. doi: 10.1162/imag_a_00118. eCollection 2024.
Regional cerebral blood flow (CBF) changes quantified using arterial spin labeling (ASL) are altered in neurodegenerative disorders such as frontotemporal lobar degeneration due to tau (FTLD-tau), but the relationship between ASL CBF and pathologic burden has not been assessed. Our objective was to determine whether regional ASL CBF acquired antemortem in patients with FTLD-tau is related to pathologic burden measured at autopsy in those same regions in the same patients to directly test the imaging-pathology relationship. In this case-control study, data were acquired between 3/4/2010 and 12/16/2018. Data processing and analysis were completed in 2023. Twenty-one participants with autopsy-confirmed FTLD-tau (N = 10 women, mean[SD] age 67.9[7.56] years) along with 25 control participants (N = 15 women, age 64.7[7.53]) were recruited through the cognitive neurology clinic at the University of Pennsylvania. All participants had ASL and T1-weighted images collected antemortem. ASL images were processed to estimate CBF and T1-weighted images were processed to estimate gray matter (GM) volumes in regions corresponding to regions sampled postmortem. Digital quantification of pathologic burden was performed to find the percent area occupied (%AO) of pathologic FTLD-tau at autopsy. Regional CBF and GM volumes were both related to pathologic burden in the same regions from the same participants. Strengths of model fits of imaging measures to pathologic burden were compared. CBF in FTLD-tau and controls were compared, with results considered significant at p < 0.05 after Bonferroni correction. We found that relative to controls, FTLD-tau displayed hypoperfusion in anterior cingulate, orbitofrontal, middle frontal, and superior temporal regions, as well as angular gyrus. For patients with FTLD-tau regional CBF was significantly associated with pathologic burden (beta = -1.07, t = -4.80, p < 0.005). Models including both GM volume and CBF provided significantly better fits to pathologic burden data than single modality models (p < 0.05, Bonferroni-corrected). Our results indicate that reduced CBF measured using ASL MRI is associated with increased pathologic burden in FTLD-tau and adds complementary predictive value of pathologic burden to structural MRI.
使用动脉自旋标记（ASL）定量的局部脑血流量（CBF）变化在诸如因tau蛋白导致的额颞叶痴呆（FTLD-tau）等神经退行性疾病中会发生改变，但ASL CBF与病理负担之间的关系尚未得到评估。我们的目标是确定FTLD-tau患者生前获得的局部ASL CBF是否与同一患者尸检时在相同区域测量的病理负担相关，以直接检验影像学与病理学之间的关系。在这项病例对照研究中，数据采集于2010年3月4日至2018年12月16日之间。数据处理和分析于2023年完成。通过宾夕法尼亚大学认知神经科门诊招募了21名经尸检确诊为FTLD-tau的参与者（10名女性，平均[标准差]年龄67.9[7.56]岁）以及25名对照参与者（15名女性，年龄64.7[7.53]岁）。所有参与者生前均采集了ASL和T1加权图像。对ASL图像进行处理以估计CBF，对T1加权图像进行处理以估计与死后采样区域相对应区域的灰质（GM）体积。对病理负担进行数字量化以确定尸检时病理性FTLD-tau的所占面积百分比（%AO）。同一参与者相同区域的局部CBF和GM体积均与病理负担相关。比较了影像学测量指标与病理负担的模型拟合强度。比较了FTLD-tau组和对照组的CBF，经Bonferroni校正后，p<0.05的结果被认为具有显著性。我们发现，相对于对照组，FTLD-tau在前扣带回、眶额、额中回、颞上回以及角回区域表现为灌注不足。对于FTLD-tau患者，局部CBF与病理负担显著相关（β=-1.07，t=-4.80，p<0.005）。与单模态模型相比，同时包含GM体积和CBF的模型对病理负担数据具有显著更好的拟合度（p<0.05，经Bonferroni校正）。我们的结果表明，使用ASL MRI测量的CBF降低与FTLD-tau中病理负担增加相关，并为结构MRI增加了病理负担的补充预测价值。
