Zhang Yifan, Wang Yue, Li Zhaoqing, Wang Zejun, Cheng Juange, Bai Xiaoyan, Hsu Yi-Cheng, Sun Yi, Li Shiping, Shi Jiong, Sui Binbin, Bai Ruiliang
Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.
National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Neuroimage. 2023 Apr 15;270:119951. doi: 10.1016/j.neuroimage.2023.119951. Epub 2023 Feb 18.
Blood-brain barrier (BBB) impairment is an important pathophysiological process in Alzheimer's disease (AD) and a potential biomarker for early diagnosis of AD. However, most current neuroimaging methods assessing BBB function need the injection of exogenous contrast agents (or tracers), which limits the application of these methods in a large population. In this study, we aim to explore the feasibility of vascular water exchange MRI (VEXI), a diffusion-MRI-based method proposed to assess the BBB permeability to water molecules without using a contrast agent, in the detection of the BBB breakdown in AD. We tested VEXI on a 3T MRI scanner on three groups: AD patients (AD group), mild cognitive impairment (MCI) patients due to AD (MCI group), and the age-matched normal cognition subjects (NC group). Interestingly, we find that the apparent water exchange across the BBB (AXR) measured by VEXI shows higher values in MCI compared with NC, and this higher AXR happens specifically in the hippocampus. This increase in AXR value gets larger and extends to more brain regions (medial orbital frontal cortex and thalamus) from MCI group to the AD group. Furthermore, we find that the AXR values of these three regions is correlated significantly with the impairment of respective cognitive domains independent of age, sex and education. These results suggest VEXI is a promising method to assess the BBB breakdown in AD.
血脑屏障（BBB）损伤是阿尔茨海默病（AD）的一个重要病理生理过程，也是AD早期诊断的一个潜在生物标志物。然而，目前大多数评估BBB功能的神经成像方法需要注射外源性造影剂（或示踪剂），这限制了这些方法在大量人群中的应用。在本研究中，我们旨在探索血管水交换磁共振成像（VEXI）的可行性，VEXI是一种基于扩散磁共振成像的方法，旨在在不使用造影剂的情况下评估BBB对水分子的通透性，用于检测AD中的BBB破坏。我们在3T磁共振成像扫描仪上对三组人群进行了VEXI测试：AD患者（AD组）、因AD导致的轻度认知障碍（MCI）患者（MCI组）以及年龄匹配的正常认知受试者（NC组）。有趣的是，我们发现通过VEXI测量的BBB上的表观水交换（AXR）在MCI组中比NC组更高，并且这种更高的AXR特别发生在海马体中。从MCI组到AD组，AXR值的这种增加变得更大并扩展到更多脑区（眶额内侧皮质和丘脑）。此外，我们发现这三个区域的AXR值与各自认知领域的损伤显著相关，且不受年龄、性别和教育程度的影响。这些结果表明VEXI是评估AD中BBB破坏的一种有前景的方法。
