以功能性造影研究大鼠腦部之傷害性反應

Abstract

近年來，以功能性造影方法研究小動物疼痛反應有相當迅速的發展。動物模型的建立不僅可用於模擬人體可能的神經生理反應，更可提供新型藥物及治療方法的測試與評估。然而，由於疼痛訊號在腦部的處理相當錯綜複雜，欲了解不同腦部區域對於疼痛機制的表現便需要同時取得神經反應的空間分部及其隨時間的變化。功能性磁振造影與正子電腦斷層造影由於可在非侵入式的情況下量測活體腦部血液動力參數及分子層面的訊息，因此是常被用於攝取腦神經活動的技術。本論文即以血氧對比磁振造影、腦血量權重磁振造影、及氟-18去氧葡萄糖正子電腦斷層造影觀察小動物腦部對於疼痛的反應。為求實驗結果的精確，本論文亦發展了一套影像後處理及分析平台。在後基因體世代中，藉由生醫影像技術研究小動物腦部對疼痛之反應，將可協助探討臨床上的疼痛問題，進而升醫療品質，並在生物醫學研究中扮演相當重要的角色。

Assessing nociception in small animals using imaging techniques has drastically increased in the last decade. The development of animal models mimics the potential neurophysical effects in humans and undertakes the evaluation of new drugs and therapeutic strategies in the preclinical stages. However, owing to the complexity of the pain processing in brain, understanding the mechanisms within different brain areas raises a need for simultaneously detecting the spatiotemporal patterns of neuronal activities. Functional magnetic resonance imaging and positron emission tomography are the most commonly used techniques providing non-invasive, in vivo measurement of the cerebral hemodynamics as well as molecular processes. This thesis encompasses a range of widely used functional brain imaging techniques, including blood-oxygenation-level-dependent fMRI, cerebral blood volume weighted fMRI, and 18F-fluorodeoxyglucose microPET to capture nociception induced hemodynamic responses and metabolic features in the rodent brain. To better improve the quality of the results, the development of a novel image analysis platform is also incorporated. The study of nociception in small animal, along with continued expansion of advanced biomedical imaging techniques in the post-genomic era nowadays, have been crucial in the drive toward healthcare optimization that allows linking preclinical pain studies and clinical issues within living subjects.