Yan Shaozhen, Zheng Chaojie, Cui Bixiao, Qi Zhigang, Zhao Zhilian, An Yanhong, Qiao Liyan, Han Ying, Zhou Yun, Lu Jie
Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 Kingshighway Blvd., St. Louis, MO, USA.
Eur J Nucl Med Mol Imaging. 2020 Sep;47(10):2440-2452. doi: 10.1007/s00259-020-04752-8. Epub 2020 Mar 10.
The objective of this study is to investigate the hippocampal neurodegeneration and its associated aberrant functions in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients using simultaneous PET/MRI.
Forty-two cognitively normal controls (NC), 38 MCI, and 22 AD patients were enrolled in this study. All subjects underwent F-FDG PET/functional MRI (fMRI) and high-resolution T1-weighted MRI scans on a hybrid GE Signa PET/MRI scanner. Neurodegeneration in hippocampus and its subregions was quantified by regional gray matter volume and F-FDG standardized uptake value ratio (SUVR) relative to cerebellum. An iterative reblurred Van Cittert iteration method was used for voxelwise partial volume correction on F-FDG PET images. Regional gray matter volume was estimated from voxel-based morphometric analysis with MRI. fMRI data were analyzed after slice time correction and head motion correction using statistical parametric mapping (SPM12) with DPARSF toolbox. The regions of interest including hippocampus, cornu ammonis (CA1), CA2/3/dentate gyrus (DG), and subiculum were defined in the standard MNI space.
Patient groups had reduced SUVR, gray matter volume, and functional connectivity compared to NC in CA1, CA2/3/DG, and subiculum (AD < MCI < NC). There was a linear correlation between the left CA2/3DG gray matter volume and F-FDG SUVR in AD patients (P < 0.001, r = 0.737). Significant correlation was also found between left CA2/3/DG-superior medial frontal gyrus functional connectivity and left CA2/3/DG hypometabolism in patients with AD. The functional connectivity of right CA1-precuneus in patients with MCI and right subiculum-superior frontal gyrus in patients with AD was positively correlated with mini mental status examination scores (P < 0.05).
Our findings demonstrate that the associations existed at subregional hippocampal level between the functional connectivity measured by fMRI and neurodegeneration measured by structural MRI and F-FDG PET. Our results may provide a basis for precision neuroimaging of hippocampus in AD.
本研究的目的是使用同步PET/MRI研究轻度认知障碍（MCI）和阿尔茨海默病（AD）患者的海马神经退行性变及其相关的异常功能。
本研究纳入了42名认知正常对照（NC）、38名MCI患者和22名AD患者。所有受试者均在GE Signa混合型PET/MRI扫描仪上接受了F-FDG PET/功能MRI（fMRI）和高分辨率T1加权MRI扫描。通过相对于小脑的区域灰质体积和F-FDG标准化摄取值比率（SUVR）对海马及其亚区域的神经退行性变进行量化。使用迭代再模糊范西特迭代方法对F-FDG PET图像进行体素级部分容积校正。通过基于体素的形态学分析利用MRI估计区域灰质体积。使用带有DPARSF工具箱的统计参数映射（SPM12）在切片时间校正和头部运动校正后分析fMRI数据。在标准MNI空间中定义感兴趣区域，包括海马、海马角（CA1）、CA2/3/齿状回（DG）和下托。
与NC相比，患者组在CA1、CA2/3/DG和下托中的SUVR、灰质体积和功能连接性降低（AD＜MCI＜NC）。AD患者左侧CA2/3DG灰质体积与F-FDG SUVR之间存在线性相关性（P＜0.001，r = 0.737）。在AD患者中，左侧CA2/3/DG-额上内侧回功能连接性与左侧CA2/3/DG代谢减低之间也发现了显著相关性。MCI患者右侧CA1-楔前叶和AD患者右侧下托-额上回的功能连接性与简易精神状态检查评分呈正相关（P＜0.05）。
我们的研究结果表明，通过fMRI测量的功能连接性与通过结构MRI和F-FDG PET测量的神经退行性变在海马亚区域水平上存在关联。我们的结果可能为AD中海马的精准神经成像提供依据。
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