Taylor Erik N, Huang Nasi, Wisco Jonathan, Wang Yandan, Morgan Kathleen G, Hamilton James A
Department of Radiology, University of New Mexico, Albuquerque, NM, USA.
Department of Physiology & Biophysics, Boston University School of Medicine, Boston, MA, USA.
J Transl Med. 2020 Jul 8;18(1):277. doi: 10.1186/s12967-020-02441-6.
Brain aging is a major risk factor in the progression of cognitive diseases including Alzheimer's disease (AD) and vascular dementia. We investigated a mouse model of brain aging up to 24 months old (mo).
A high field (11.7T) MRI protocol was developed to characterize specific features of brain aging including the presence of cerebral microbleeds (CMBs), morphology of grey and white matter, and tissue diffusion properties. Mice were selected from age categories of either young (3 mo), middle-aged (18 mo), or old (24 mo) and fed normal chow over the duration of the study. Mice were imaged in vivo with multimodal MRI, including conventional T2-weighted (T2W) and T2*-weighted (T2W) imaging, followed by ex vivo diffusion-weighted imaging (DWI) and T2W MR-microscopy to enhance the detection of microstructural features.
Structural changes observed in the mouse brain with aging included reduced cortical grey matter volume and enlargement of the brain ventricles. A remarkable age-related change in the brains was the development of CMBs found starting at 18 mo and increasing in total volume at 24 mo, primarily in the thalamus. CMBs presence was confirmed with high resolution ex vivo MRI and histology. DWI detected further brain tissue changes in the aged mice including reduced fractional anisotropy, increased radial diffusion, increased mean diffusion, and changes in the white matter fibers visualized by color-coded tractography, including around a large cortical CMB.
The mouse is a valuable model of age-related vascular contributions to cognitive impairment and dementia (VCID). In composite, these methods and results reveal brain aging in older mice as a multifactorial process including CMBs and tissue diffusion alterations that can be well characterized by high field MRI.
脑老化是包括阿尔茨海默病（AD）和血管性痴呆在内的认知疾病进展的主要危险因素。我们研究了一个长达24个月龄的脑老化小鼠模型。
开发了一种高场（11.7T）MRI方案，以表征脑老化的特定特征，包括脑微出血（CMB）的存在、灰质和白质的形态以及组织扩散特性。从年轻（3个月）、中年（18个月）或老年（24个月）年龄组中选择小鼠，并在研究期间喂食正常食物。对小鼠进行体内多模态MRI成像，包括传统的T2加权（T2W）和T2加权（T2W）成像，随后进行体外扩散加权成像（DWI）和T2*W MR显微镜检查，以增强对微观结构特征的检测。
随着年龄增长，在小鼠脑中观察到的结构变化包括皮质灰质体积减少和脑室扩大。脑中一个显著的与年龄相关的变化是CMB的出现，从18个月开始发现，并在24个月时总体积增加，主要在丘脑。通过高分辨率体外MRI和组织学证实了CMB的存在。DWI检测到老年小鼠脑组织的进一步变化，包括分数各向异性降低、径向扩散增加、平均扩散增加以及通过彩色编码纤维束成像显示的白质纤维变化，包括围绕一个大的皮质CMB周围。
小鼠是年龄相关的血管对认知障碍和痴呆（VCID）影响的有价值模型。综合来看，这些方法和结果揭示了老年小鼠的脑老化是一个多因素过程，包括CMB和组织扩散改变，这些可以通过高场MRI很好地表征。
