BOLD與錳離子增強磁振造影於大鼠初級觸覺皮質區之功能研究

Abstract

大鼠初級觸覺皮層桶狀區的神經拓撲分佈，是研究神經功能與可塑性的最佳模型，然而以高空間解析度與精準空間定位方法，非侵入式地造影大腦功能與可塑性仍具有很高的挑戰性。本論文的目標為發展新的造影方法來偵測大腦功能的進行，包括解剖、神經活化、以及神經可塑性。我們嘗試以錳離子增強磁振造影術，建立了大鼠於鬍鬚刺激下，造影大腦皮質之適宜的工作平台；我們也嘗試以功能性磁振造影術，建立了大鼠於手指刺激下，造影出大腦手指初級觸覺皮質區，並應用至斷指大鼠大腦可塑性之研究。我們發展及改良了功能性磁振造影與錳離子增強磁振造影二個技術，能以最低侵入限度來研究大腦功能，此外這個研究使我們更加理解對所發展的大腦功能造影術的應用範圍。 我們以錳離子增強磁振造影術所造影大鼠大腦鬍鬚皮質區，證實了大腦中錳離子增強皮質區域與鬍鬚觸覺誘發神經活化間的關係，在大腦皮質反應區，鬍鬚刺激組的大鼠之影像強度(1.72 ± 0.22)與R1值(1.12 ± 0.16)皆比控制組的值高(1.27 ± 0.14, p<0.05; 0.83 ± 0.21, p<0.05)。我們也證實了在11.7 T的高場下，以功能性磁振造影術可以造影出單一手指觸覺皮質區，及斷指大鼠的大腦皮質可塑性。二根手指反應區質心的距離由控制組的1.45 ± 0.29 mm下降至斷指組的0.90 ± 0.21 mm (p<0.01)。這個技術對於研究大鼠的神經可塑性有很大的幫助。 總結而言，我們成功的使用錳離子增強磁振造影的策略，以非侵入性的方式及技術，造影出大鼠大腦神經活化；並且配合被我們完整建立的全腦功能性磁振造影，我們以非侵入性的方式得到更多過去必須以侵入性的組織切片或耗時的電生理量測所取得的資訊。據我們的瞭解，這是世界上首次以功能性磁振造影術來研究大腦皮質神經桶的可塑性。未來這些發展於大鼠上的磁振造影術將可以推展至人的研究與應用上，而這些新造影術的發展將有助於正常大腦以及因為學習、可塑性、藥物或基因調控而變化大腦的研究。

The topographic organization of cortical barrel in layer IV of rat primary somatosensory cortex is a good model for studying neural function and plasticity. However, mapping brain function and plasticity with high spatial resolution and accurate spatial localization methods non-invasively remained challenges. The overall objectives of this dissertation were to develop novel imaging techniques to monitor functional processes of the brain, including anatomy, neural activity, and neural plasticity. We sought to establish a feasible working protocol of applying manganese- enhanced magnetic resonance imaging (MEMRI) to map the cortical barrels of the rat following whisker stimulation. We’d also like to test the feasibility of using functional MRI (fMRI) to map the forepaw digit representations in the primary somatosensory cortex of the rat and to apply to the study of cortical plasticity after digit amputation. The development of these technologies provided two techniques, i.e. fMRI and MEMRI, that can be used to study brain function in minimally invasive ways. In addition, the study allowed us to better understand the range of applicability of new brain functional imaging techniques that were developed. In our results, we have mapped rat whisker barrels using the MEMRI method and have shown a clear relationship between manganese-enhanced cortical regions and whisker tactile-sense-evoked activity. In the right cortical barrels, the enhancement ratios (1.72 ± 0.22) and R1 values (1.12 ± 0.16) in the whisker stimulation group were significantly higher than those (1.27 ± 0.14, p<0.05; 0.83 ± 0.21, p<0.05) in the control group. We have also demonstrated that forepaw barrel subfields of single digits can be reliably mapped using fMRI at 11.7T. The alteration of the digit representation after digit amputation was also detected. The distance between the centers of mass of two digits representations decreased from 1.45 ± 0.29 mm in the control group to 0.90 ± 0.21 mm (p<0.01) in the amputated group. The method will be useful to study neural plasticity in rat brains after surgical or genetic manipulation. In conclusions, exciting MEMRI strategies showed great promise for enabling non-invasive techniques to map neuronal activity throughout the rat brain non-invasively. Combined with established whole brain fMRI techniques, it became possible to get an increasing range of information non-invasively that in the past required invasive histology or time consuming electrophysiology. To the best of out knowledge this is the first fMRI demonstration of plasticity in cortical columns by fMRI. In the future, these MRI techniques developed in rats can often be extended for use in humans. The development of these new imaging techniques will be used to study the normal rodent brain and changes in the brain that occur during learning and plasticity or due to specific genetic changes.