Maharjan Surendra, Tsai Andy P, Lin Peter B, Ingraham Cynthia, Jewett Megan R, Landreth Gary E, Oblak Adrian L, Wang Nian
Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, United States.
Stark Neurosciences Research Institute, Indiana University, Indianapolis, IN, United States.
Front Neurosci. 2022 Aug 17;16:964654. doi: 10.3389/fnins.2022.964654. eCollection 2022.
To evaluate the age-dependent microstructure changes in 5xFAD mice using high-resolution diffusion tensor imaging (DTI).
The 5xFAD mice at 4, 7.5, and 12 months and the wild-type controls at 4 months were scanned at 9.4T using a 3D echo-planar imaging (EPI) pulse sequence with the isotropic spatial resolution of 100 μm. The -value was 3000 s/mm for all the diffusion MRI scans. The samples were also acquired with a gradient echo pulse sequence at 50 μm isotropic resolution. The microstructure changes were quantified with DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD). The conventional histology was performed to validate with MRI findings.
The FA values ( = 0.028) showed significant differences in the cortex between wild-type (WT) and 5xFAD mice at 4 months, while hippocampus, anterior commissure, corpus callosum, and fornix showed no significant differences for either FA and MD. FA values of 5xFAD mice gradually decreased in cortex (0.140 ± 0.007 at 4 months, 0.132 ± 0.008 at 7.5 months, 0.126 ± 0.013 at 12 months) and fornix (0.140 ± 0.007 at 4 months, 0.132 ± 0.008 at 7.5 months, 0.126 ± 0.013 at 12 months) with aging. Both FA ( = 0.029) and MD ( = 0.037) demonstrated significant differences in corpus callosum between 4 and 12 months age old. FA and MD were not significantly different in the hippocampus or anterior commissure. The age-dependent microstructure alterations were better captured by FA when compared to MD.
FA showed higher sensitivity to monitor amyloid deposition in 5xFAD mice. DTI may be utilized as a sensitive biomarker to monitor beta-amyloid progression for preclinical studies.
使用高分辨率扩散张量成像（DTI）评估5xFAD小鼠中随年龄变化的微观结构改变。
对4个月、7.5个月和12个月大的5xFAD小鼠以及4个月大的野生型对照小鼠在9.4T磁场下使用三维回波平面成像（EPI）脉冲序列进行扫描，各向同性空间分辨率为100μm。所有扩散磁共振成像扫描的(T_2^*)值为3000s/mm。还使用梯度回波脉冲序列以50μm各向同性分辨率采集样本。用DTI指标对微观结构改变进行量化，包括分数各向异性（FA）和平均扩散率（MD）。进行传统组织学检查以验证磁共振成像结果。
4个月大时，野生型（WT）和5xFAD小鼠皮质的FA值（(P = 0.028)）存在显著差异，而海马体、前连合、胼胝体和穹窿的FA和MD均无显著差异。5xFAD小鼠皮质（4个月时为0.140±0.007，7.5个月时为0.132±0.008，12个月时为0.126±0.013）和穹窿（4个月时为0.140±0.007，7.5个月时为0.132±0.008，12个月时为0.126±0.013）的FA值随年龄增长逐渐降低。4个月和12个月大时，胼胝体的FA（(P = 0.029)）和MD（(P = 0.037)）均存在显著差异。海马体或前连合中的FA和MD无显著差异。与MD相比，FA能更好地捕捉随年龄变化的微观结构改变。
FA在监测5xFAD小鼠淀粉样蛋白沉积方面表现出更高的敏感性。DTI可作为一种敏感的生物标志物，用于临床前研究中监测β淀粉样蛋白的进展。
