碩士 / 國立陽明大學 / 生物醫學影像暨放射科學系 / 103 / Cisd2 is proposed to be a fundamentally important regulator of lifespan. The deficiency of Cisd2 causes not only the defect of mitochondria-mediated and premature aging in mammals, but also neural degeneration diseases relevant to aging (e.g. memory loss) with a significant influence on the substructures of brain tissues. In this study, we used the diffusion MRI technology to construct the super-resolution track density image (TDI) of different genotypes of Cisd2 mice, and contoured the hippocampus referring to brain selections of mice to investigate the effect of Cisd2 on the relevance between the hippocampal volumetric variation and neuron cells.
Six categories of mouse brains were collected: (a) wild-type (WT); (b) Cisd2 gene transgenic (Cisd2-TG); (c) Cisd2-deficient knockout (Cisd2-KO) (d) Alzheimer’s disease (AD) (e) AD combine with Cisd2-KO; (f) AD combine with Cisd2-TG. Diffusion-weighted (DW) imaging datasets of mouse brains were acquired on a 9.4 Tesla Bruker (Ettlingen, Germany) spectrometer. The fiber orientation distribution (FOD) using constrained spherical hamornic deconvolution was estimated. The whole brain fiber track were reconstructed and resampled to construct the high resolution TDI (voxel = 20μm3). The mouse hippocampus was contoured manually using the TDI, and the volume fraction (VF, hippocampus volume to whole brain volume ratio) followed by analysis of variance (ANOVA) among the mouse groups. In addition, in order to observe the tissue cell patterns and neuron state in hippocampus, the paraffin slices selection combined with H&;E and Nissel staining were performed as well. For the histological result, the neuron density was defined as the nucleus number divided by area.
There is no difference between WT and Cisd2-TG groups in VF; Both of the WT and Cisd2-TG groups had significantly larger VF than both of the Cisd2-KO and AD groups, and AD groups had smallest VF. However, the AD;Cisd2-KO group had significantly larger VF than both of AD group and Cisd2-KO group. The histological results demonstrated that AD;Cisd2-KO exhibited the lowest cell density, indicating the high reliability of the results from TDI. We inferred that the hippocampal volume increase in AD;Cisd2-KO mouse might result from the enhancement of the number of microglia, however, further immunostaining study is needed to confirm in the future.
Compared with traditional T1 weighted image, it is beneficial to use TDI as reference images with good contour and edge for hippocampus extraction, which reduced partial volume effects. Our results indicated that Cisd2 deficiency causes hippocampal volume decline, and the effect could be retarded through the enhancement of the Cisd2 expression level. The histological results inferred that the rise of hippocampus volume in AD;Cisd2-KO group might causes by the incensement of the number of microgila, which could be verified by immunostaining. According to the high reliability of TDI for brain tissue detection, TDI might be helpful to exam the human brain structures with different genotypes or clinical diseases in the future.
Keyword: Cisd2 gene, hippocampal atrophy, diffusion microstructure, alzheimer's disease, constrained spherical hamornic deconvolution, track density imaging
| Identifer | oai:union.ndltd.org:TW/103YM005605023 |
| Date | January 2015 |
| Creators | Shen-Pei Lin, 林昇霈 |
| Contributors | Ching-Po Lin, 林慶波 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 65 |
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