Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 217D Traylor Building, 720 Rutland Avenue, Baltimore, MD, 21205, USA.
Neuroradiology. 2013 Aug;55(8):1027-1038. doi: 10.1007/s00234-013-1195-0. Epub 2013 May 5.
Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model.
VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy.
Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p < 0.05, corrected). The average kappa value between manual and atlas-based structure delineation was approximately 0.8, and there was no significant difference between APP/PS1 and WT mice (p > 0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen.
This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the feasibility of applying whole-brain analysis methods to the investigation of an AD mouse model.
扩散张量成像（DTI）已被应用于在 AD 小鼠模型中描述病理特征，尽管对于这些特征是否具有结构特异性知之甚少。体素基分析（VBA）和图谱基分析（ABA）是全脑 DTI 分析的良好补充工具。本研究的目的是确定 AD 小鼠模型中与疾病相关的病理学的空间定位。
使用 VBA 和 ABA 对 9 只 APP/PS1 小鼠和野生型（WT）对照的全脑 DTI 进行定量分析。研究了多种标量测量，包括各向异性分数（FA）、轨迹、轴向弥散度（DA）和径向弥散度（DR），以捕捉各种类型的病理学。通过比较手动和图谱基结构描绘的kappa 统计数据评估图像转换应用的准确性。在 MR 检查后，对动物的大脑进行显微镜分析。
与 WT 小鼠相比，APP/PS1 小鼠的灰质区域（新皮质、海马体、尾状核、丘脑、下丘脑、屏状核、杏仁核和梨状皮层）和白质区域（胼胝体/外囊、扣带回、隔核、内囊、终纹和视束）中都发现了广泛的解剖学改变，表现为 FA 或 DA 增加，或两者兼而有之（p < 0.05，校正）。手动和图谱基结构描绘之间的平均 kappa 值约为 0.8，APP/PS1 和 WT 小鼠之间无显著差异（p > 0.05）。通过显微镜研究证实了灰质区域的组织病理学变化。然而，DTI 确实显示了白质区域的显著变化，而通过单个切片组织学标本的定性观察，这种差异并不明显。
本研究表明 APP/PS1 小鼠的病理变化具有结构特异性，也表明了应用全脑分析方法研究 AD 小鼠模型的可行性。
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