Morphological and Functional Changes of Alzheimer’s Disease Animal Model Using MRI Techniques

• Main Authors: Ming-Shiuan Chiue, 闕洺軒
• Other Authors: Chung-Ming Chen
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/62219455060406886445

碩士 === 國立臺灣大學 === 醫學工程學研究所 === 101 === ABSTRACT Towards increasing aging population in the modern society, the treatment of Alzheimer''s disease (AD) patient is getting more important. Patients suffering from Alzheimer''s disease will gradually lose memory capability and have language emotional barriers. This situation will cause a huge burden in both ones family or society. The only medical care one can apply is to use drugs to defer AD patient’s conditions due to the lack of understanding on its fundamental mechanism. The situation in the Alzheimer''s disease that gradually lost intellectual deterioration is known as dementia. Studies indicated that in this process of the brain of a patient would be the deposition of beta-amyloid plaques and neurofibrillary Tangles of NFTs phenomenon. More and more evidences have shown that the recession of the brain microvascular circulation might be one of main factors causing Alzheimer''s disease [1]. This study is to provide more valuable information taking advantage of various MRI techniques for vascular changes in the brain. In the brains of Alzheimer''s patients, past research pointed out that there will be abnormal protein deposition, and the metabolic state of the brains are also accompanied by change in the blood supply to the brain [2]. In a variety of physiological observation instruments, MRI is a major modality in the study of this disease to obtain physiological parameters with high-resolution anatomical images. So far, there is little information discussing the variation of cerebral vasculature of the Alzheimer''s disease in the literature. This thesis is to use the newly developed MRI 3D-ΔR2-MRA angiography to present the overall high-resolution images of the vascular nature of the whole brain. In addition to it, TOF-MRA(time-of-flight MR angiography), CBF(cerebral blood flow) and MRS(MR spectroscopy) are also employed to reveal the blood vessel structures, blood perfusion and associated metabolites change in the brain. Aricept, the most commonly used drugs for Alzheimer’s disease, are applied to explore the relationship between Alzheimer''s disease, vascular brain metabolite changes. The results show that, in the AD rat model with no treatment, that blood flow to the brain is decreased by about 40 ~ 50% (P <0.05), and is 15~20%(P <0.05) in the Aricept treatment group. Notably, there is no significant difference in the brain volume at the three groups. This shows that the variations of the brain blood flow might occur before the anatomy changes. Neuronal activity indicators N-acetylaspartate (NAA) in the magnetic resonance spectrum decreased by 10 ~ 20% (P <0.05) in AD rats   iii compared with normal rats. The Aricept treatment will raise NAA slightly, but insignificantly. Similar results are also shown in the TOF-MRA. In the normal rats, the intensity of the overall vascular were higher than that of AD. For Aricept treated rats, the blood vessels signal also shows higher compared to AD rats. Finally, 3D-ΔR2-MRA angiography can visualize the relatively sparse distribution of small vessels hence the overall density of the brain cortex in the AD animals, with brain cortex vascular density of 4.95% for the normal group, 2.1% for the AD rats, and 2.9% for the drug treatment group. Spreads of amyloid plaques in the brain parenchyma can also be seen in the final brain stained sections. In Summary, brain structure and functional change of the blood vessels can be studied for AD rats using various MRI technologies. Our result suggests that MRI could provide more valuable information for clinical diagnosis as well as treatment strategies in the near future.