以擴散張量成像技術研究輕度認知障礙和阿茲海默氏症病人之皮質下區域異常

Investigating subcortical abnormalities in mild cognitive impairment and Alzheimer’s disease using diffusion tensor imaging

王承元(Chen-Yuan Wang)

指導教授 ： 蔡炳煇

中山醫學大學/醫學科技學院/醫學影像暨放射科學系/碩士(2021年)

https://doi.org/10.6834/csmu202100166

摘要

研究背景：阿茲海默氏症(Alzheimer’s disease, AD)是一種進行性神經退行性疾病，是老年人中最常見的癡呆類型。輕度認知障礙(Mild cognitive impairment, MCI)是發展成AD的高風險階段。 對於疾病的早期診斷和進展監測而言，可靠的生物標記很重要的。隨著MR(Magnetic resonance)技術的發展，MR成像能檢視由神經原纖維纏結、突觸和神經元在疾病發展過程中引起的神經病理學改變，AD和MCI病人的認知能力下降可能與皮層下區域的微結構改變有關。 在這項研究中，我們旨在使用具有高角度分辨率的擴散張量成像(Diffusion tensor imaging, DTI)來檢查AD和MCI病人包括基底核和其周圍區域之皮質下灰質區域的微結構異常。
材料與方法：從Alzheimer's Dementia Neuroimaging Initiative(ADNI)第三期數據庫納入16名認知正常(Cognitive normal, CN)受試者，13名MCI和11名AD病人，所有受試者均接受3T MRI檢查，包括常規MR成像和高角度分辨率擴散成像。此外也蒐集了神經心理學評估結果以進行分析。影像前處理、皮層下分割和擴散張量分析均在DSI studio中進行，而皮層下區域測量結果的統計分析全部使用SPSS進行，比較三組受試者的DTI指標和體積測量結果。為了確定與臨床評估分數相關的皮層下區域結構變化，我們使用偏相關分析(Partial correlation analysis)評估了三組之間的體積和DTI參數差異。
結果：在統計結果中，MCI和AD病人的大腦兩側皮層下灰質的體積均無明顯異常。與健康受試者相比，MCI組右側杏仁核的FA值明顯降低。在AD階段，MD、AxD和RD在海馬迴和杏仁核中均顯著增加。與MCI相比，AD病人的右側杏仁核的MD和AxD值以及左側海馬迴的AxD值均顯著增加。而與臨床評估分數的相關性，在體積測量和DTI指標中發現了顯著的相關性。調整年齡和性別差異後，杏仁核兩側的體積以及左側視丘和杏仁核的FA與MMSE得分呈正相關。海馬迴和杏仁核兩側的MD，AxD和RD值與MMSE評分呈負相關。體積和CDR得分之間無顯著相關性，而視丘和海馬迴兩側的FA值與CDR得分呈負相關。此外，視丘、尾狀、海馬和杏仁核兩側的MD、AxD和RD值與CDR得分呈正相關。
結論：本研究表明AD和MCI病人的皮質下區域的微結構變化與神經心理下降之間的關係，這可能被用於監測疾病的進展。

關鍵字

阿茲海默氏症 ； 擴散張量成像 ； 皮質下區域

並列摘要

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia in the elderly. Mild cognitive impairment (MCI) is a stage that has a high risk of developing into AD. A reliable biomarker for early diagnosis and progression monitoring of the disease is important. With the development of MR technology, MR imaging could potentially reveal the information of neuropathological changes caused by neurofibrillary tangles, loss of synapses and neurons during disease progression. According to previous studies, the cognitive ability declines of AD and MCI patients can be associated with the microstructural changes in the subcortical regions. In this study, we aims to use diffusion tensor imaging (DTI) with high angular resolution to examine the microstructural abnormalities in the subcortical gray matter areas of AD and MCI patients, including the basal ganglia and surrounding areas.
Methods: 16 cognitive normal (CN) subjects, 13 MCI and 11 AD patients were included from the phase Alzheimer's Dementia Neuroimaging Initiative (ADNI) 3 database, all participants had underwent MRI examinations, including conventional MR imaging and high angular resolution diffusion imaging, at a 3T Siemens system.Standard neuropsychological assessments including a measure of functioning by mini–mental state examination (MMSE) and a clinical dementia rating (CDR) examination were obtained from the ADNI3 database for the following analysis.
Image preprocessing, subcortical segmentation and diffusion tensor analysis were all processed in DSI studio. At first, corrections for eddy-current distortion and head motion were performed. After deriving the diffusion tensor related information, the subcortical regions were selected from the altlas list provided by DSI Studio. These specified regions were segmented by FreeSurfer image analysis suite and registered to the HCP1021 template. Then, the non-linear alignment and calculation of DTI values can carry out automatically in the DSI studio.
The statistical analyses for measurements in subcortical regions were all performed using Statistical Package for Social Sciences (SPSS). DTI metrics and volume measurements were compared across three groups using Analysis of Variance (ANOVA). And Scheffe method were used in post-hoc multiple comparisons. To identify subcortical region structural changes related to the clinical assessment scores, we assessed volumemetric and DTI metric differences between three groups using partial correlation analysis. Age and gender were also entered as covariates. P value<0.05 was considered as statistically significant.
Results: In the statistical results, MCI and AD patients had no significant abnormalities in the volume of the subcortical gray matter on both sides of the brain. Compared with healthy subjects, FA values were found to be significantly decrease in the right amygdala of MCI group. At the AD stage, MD AxD and RD has a significant increase in both hippocampus and amygdala. The MD and AxD values of the right amygdala and the AxD values of the left hippocampus both increase significantly in AD patients compared with MCI.
With respect to correlation with clinical assessment score, significant correlations were found in volume measurements and DTI metrics. After adjusting for age and gender, the volumes of the both sides of amygdala and the FA of the left thalamus and amygdala were positively correlated with the MMSE scores. The MD, AxD and RD values of the both sides of hippocampus and amygdala were negatively correlated with the MMSE scores. There were no significant correlation between volume and CDR score. While, the FA values of the both sides of the thalamus and hippocampus were negatively correlated with the CDR scores. Furthermore, the MD, AxD and RD values of the both sides of thalamus, caudate, hippocampus and amygdala were positively correlated with the CDR scores.
Conclusion: This study indicated the relationship between microstructural changes of the subcortical regions and neuropsychological declines in AD and MCI patients, which may potentially be used to monitor the disease progression.

並列關鍵字

Alzheimer’s disease ； diffusion tensor imaging ； subcortical

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