阿尔茨海默病中的脑类淋巴液成像:一项人体MRI和PET研究。

Brain glymphatic fluid mapping in Alzheimer's disease: a human MRI and PET study.

作者信息

Zhou Liangdong, Nguyen Thanh D, Chiang Gloria C, Keil Samantha A, Wang Xiuyuan Hugh, Hu Tsung-Wei, Lan Haoyu, Xi Ke, Costa Ana Paula, Tanzi Emily B, Glodzik Lidia, Wegiel Jarek, Butler Tracy, de Leon Mony J, Li Yi

机构信息

Department of Radiology, Brain Health Imaging Institute (BHII), Weill Cornell Medicine, New York, NY 10065, USA.

Department of Radiology, MRI Research Institute (MRIRI), Weill Cornell Medicine, New York, NY 10065, USA.

出版信息

Brain Commun. 2025 May 23;7(3):fcaf200. doi: 10.1093/braincomms/fcaf200. eCollection 2025.

Abstract

Glymphatic system has been identified as a fluid exchange network in brain parenchymal for removal of toxic metabolites in Alzheimer's disease. However, a clinically feasible, accurate, and non-invasive imaging technique for mapping global glymphatic fluid distribution throughout the entire brain and monitoring its dysfunction in Alzheimer's disease is currently lacking. This cross-sectional retrospective study aims to compare three MRI-based measures of the glymphatic system structural alterations, a novel multi-echo T2 relaxometry-based parenchymal CSF (pCSF) mapping, T2 weighted-based segmented perivascular space burden, and diffusion tensor imaging-based free-water mapping. We evaluated their cross-correlation and investigated their respective association with PET measured beta-amyloid deposition using C-PiB PET. A total of 29 subjects (18 Female, age: 70.07 ± 8.73 years old), among them, 16 were cognitively normal and 13 were mild cognitive impairment or Alzheimer's disease, underwent both MRI and C-PiB PET scans. Parenchymal CSF mapping, diffusion-based free-water mapping and perivascular spaces burden were generated from their respective MRI. Age and sex effects and group differences of these biomarkers were evaluated. The associations among these measures and Aβ deposition on C-PiB PET were analysed and compared. Our analysis demonstrated moderate correlations between pCSF, diffusion-based free-water mapping and perivascular space burden, suggesting these biomarkers capture overlapping yet distinct aspects of glymphatic fluid distribution. Importantly, linear regression analyses revealed that pCSF exhibited a significantly stronger positive association with beta-amyloid deposition (white matter: = 3.536, = 0.002, = 0.446; Alzheimer's disease-related meta regions: = 4.510, < 0.001, = 0.541), compared with diffusion-based free-water mapping in white matter ( = 0.843, = 0.407, = 0.191) and perivascular space burden ( = 0.422, = 0.677, = 0.174), after adjusting for age and sex. This study identifies pCSF mapping, derived from multi-echo T2 data with clinically feasible 5 mins scan FAST-T2 sequence, as a potential non-invasive imaging biomarker for assessing glymphatic dysfunction in Alzheimer's disease. The superior sensitivity of pCSF mapping arises from its direct quantification of glymphatic fluid at the water molecular level based on free CSF-specific T2 relaxation properties. These results suggest that pCSF could be useful in the monitoring of Alzheimer's disease progression as beta-amyloid accumulating and predicting response to anti-amyloid therapies, potentially leading to better diagnostic strategies and therapeutic interventions of Alzheimer's disease.

摘要

类淋巴系统已被确认为脑实质中的一个液体交换网络,用于清除阿尔茨海默病中的有毒代谢产物。然而,目前缺乏一种临床可行、准确且无创的成像技术来绘制全脑的类淋巴液分布并监测其在阿尔茨海默病中的功能障碍。这项横断面回顾性研究旨在比较基于磁共振成像(MRI)的三种类淋巴系统结构改变测量方法,一种基于多回波T2弛豫测量的脑实质脑脊液(pCSF)图谱、基于T2加权的分割血管周围间隙负荷以及基于扩散张量成像的自由水图谱。我们评估了它们的相互相关性,并使用C-PiB正电子发射断层扫描(PET)研究了它们与PET测量的β-淀粉样蛋白沉积的各自关联。共有29名受试者(18名女性,年龄:70.07±8.73岁),其中16名认知正常,13名患有轻度认知障碍或阿尔茨海默病,他们均接受了MRI和C-PiB PET扫描。通过各自的MRI生成脑实质脑脊液图谱、基于扩散的自由水图谱和血管周围间隙负荷。评估了这些生物标志物的年龄和性别效应以及组间差异。分析并比较了这些测量方法与C-PiB PET上Aβ沉积之间的关联。我们的分析表明,pCSF、基于扩散的自由水图谱和血管周围间隙负荷之间存在中度相关性,这表明这些生物标志物捕捉了类淋巴液分布的重叠但不同的方面。重要的是,线性回归分析显示,在调整年龄和性别后,与白质中基于扩散的自由水图谱(β = 0.843,P = 0.407,R² = 0.191)和血管周围间隙负荷(β = 0.422,P = 0.677,R² = 0.174)相比,pCSF与β-淀粉样蛋白沉积表现出显著更强的正相关(白质:β = 3.536,P = 0.002,R² = 0.446;阿尔茨海默病相关元区域:β = 4.510,P < 0.001,R² = 0.541)。本研究确定,使用临床可行的5分钟扫描FAST-T2序列从多回波T2数据得出的pCSF图谱,作为评估阿尔茨海默病中类淋巴功能障碍的一种潜在无创成像生物标志物。pCSF图谱的卓越敏感性源于其基于游离脑脊液特异性T2弛豫特性在水分子水平上对类淋巴液的直接定量。这些结果表明,pCSF在监测阿尔茨海默病进展(随着β-淀粉样蛋白积累)以及预测抗淀粉样蛋白疗法的反应方面可能有用,这可能会带来更好的阿尔茨海默病诊断策略和治疗干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc2/12130685/1e8be76906fc/fcaf200_ga.jpg

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