年齡、性別與第二型糖尿病對大腦白質完整性的影響

Abstract

大腦白質(white matter, WM)與大腦灰質，在人類大腦功能與運作上占有相同重要的角色。大腦白質結構主要由神經纖維所構成，負責腦部不同功能區之間的互相連結與協調。過去對大腦白質的影像學研究，著重在白質體積的變化與白質影像信號強度的改變(所謂的白質影像訊號增強，white matter hyperintensity, WMH)，以此二者代表白質病變的標記。然而，此二種指標，非但對病變的偵測均不敏感，且對病變解剖構造名稱無法提供詳細資料。新近發展的磁振擴散張量造影技術(Diffusion tensor imaging, DTI)，一方面可提供較精確的病變構造名稱，於定位上比起之前的技術更精進，另一方面可提供白質微細構造更多的資料。本研究利用磁振擴散張量造影技術，探討年齡、性別與心血管危險因子，對大腦白質微細構造完整性的影響。 首先於論文第一部份整理了老化與心血管危險因子對大腦白質的影響，從白質構造的萎縮與白質影像訊號增強均有文獻的回顧，另外也簡短說明磁振擴散張量造影的技術與應用。 於第二部份整理了有關年齡、性別與第二型糖尿病對白質微細構造影響的三篇研究論文。 1. 第四章使用線性迴歸模型分析年齡與性別對大腦白質微細構造完整性的影響，本研究發現前扣帶迴與前後內囊的白質完整性會隨年齡增加而改變，另外女性在右側顳葉的白質在隨年齡的變化上與男性的變化趨勢也有不同。 2. 第五章使用高階多項式迴歸模型分析全腦白質的磁振擴散張量造影指標與年齡變化的關連，本研究發現除了年齡與fractional anisotropy (FA)在與全腦的平均值上呈一階線性關連外，mean diffusivity (MD)則與年齡呈現二項式的關連，其最低的MD約出現在44歲。另外不同腦區與年齡增加的關連性也有不同，代表無法單獨使用一階線性迴歸方式來模擬不同腦區與年齡增加的變化，其生理上的意義便是指年齡增加對不同腦部白質的微細構造變化可能以次方的方式加重其影響。 3. 第六章探討糖尿病對大腦白質微細構造的影響。本研究發現即使在傳統磁振造影無法明顯看到病變的糖尿病病人，其大腦白質完整性仍是隨糖尿病的病程增加而被影響。 總結而言，磁振擴散張量造影提供了一個工具用來探討白質與疾病的關連性，它更能建構腦部不同區域的連結圖，值得我們儘量多加應用。

Cerebral white matter (WM) stands the same important role as well as the gray matter (GM) in the cerebral function. Cerebral WM is constructed by the neuronal fiber bundles which connent with various brain regions and modulate the different functions. In the past, image study for cerebral WM was focused on the volumetric changes (e.g. tissue loss) or intensity changes (e.g. white matter hyperintensity, WMH). However, these two indexes neither sensitive to the lesion detection nor loss the detail anatomic structural labeling. Recently developed magnetic resonance (MR) diffusion tensor imaging (DTI) technique could provide the more dedicate anatomical fiber bundle labeling, which could help the researcher in accurate anatomical localization. It also could provide more detail micro-structural information then previously conventional MR technique in WM. In this study, we use the DTI to study the effects of age, gender and vascular risk factors in cerebral WM. In the first part of thesis, we summarized the effect of age, gender and vascular risk factors in cerebral WM based on the volumetric studies and WMH from literatures. Then, a brief description of DTI technique and application was followed. In the second part of thesis, we present three papers regarding age, gender and type 2 DM and cerebral WM. 1. In chapter 4, we used the linear regression model to study the age and gender effect on WM microsturcture. Our study found that microsturctural integrity base on the DTI parameters in the anterior cingulate gyrus and the anterior/posterior limbs of internal capsule correlated with the aging change. We also found the WM integrity in the right side temporal lobes has the gender difference. 2. In chapter 5, a high-order polynominal regression model to analyze the aging effect on various brain regions. Traditional linear regression model assumed the aging effect could be linear correlate with the variable and the various brain regions. In this study, we found the fractional anisotrophy (FA) index showed a linear decreased with aging change, but the mean diffusivity (MD) showed a quadratic change with aging process. The lowest level of MD value was found at age 44, which could not be found by the linear regression model. The biological interpretation could be that WM integrity could present as accerate changes with age in different brain regions. 3. In chapter 6, we discuss the type 2 DM and WM integrity. Our study found that even the conventional MR showed no significant changes in WM, the type 2DM patient still could have the microsturctural integrity changes based on the DTI findings. Moreover, this change was associated with disease duration. In summary, DTI provided a useful tool to explore the WM integrity and its relationship with the disease. It also could provide the structural connentivity map for different brain regions. These adventage help researchers to reconstruct a more sophicate brain-function relationship.