應用化學位移影像於偵測大鼠神經膠質瘤之代謝物變化

Abstract

分子影像在未來個人化醫療扮演診斷的重要角色，而核磁共振中之化學位移影像正提供非侵入式的方法來獲取代謝物在不同組織上之分佈與含量，在大腦疾病上之應用可提供不同代謝物與疾病之間的訊息，對於發病機制及治療成效評估是舉足輕重的一項工具。 多形性神經膠母細胞瘤(GlioBlastoma Multiforme，GBM)在腦癌中為侵襲性高以及成長快速之癌細胞，也因此是高度惡性的腦癌，並且也是腦瘤中的最大宗。治療計畫與療效評估與其癌細胞的生理特性、機制以及狀態有緊密的關係，化學位移影像提供各種代謝物在大腦中的分布，此技術可用以觀察組織生理特性與狀態，進一步得到關鍵的訊息。 本論文目的為建立化學位移影像之實驗標準化流程，並且將之應用在多形性神經膠母細胞瘤之動物模型。將C6神經膠質瘤植入大鼠鼠腦紋狀體，利用化學位移影像以及活體磁振頻譜觀察神經膠質瘤與其正常對側組織之代謝物，並且比較其之間生理狀態之差異。從實驗結果可以得知，在C6神經膠質瘤可以觀察到正常神經元細胞死亡，腫瘤細胞快速生長及代謝活性增加，腫瘤中心區域缺氧。 總結本實驗所建立起之CSI可以將代謝物分佈影像化，從結果可得知化學位移影像具有定量腫瘤組織代謝物組成之潛力，但惟其冗長掃描時間以及其低空間解析度仍有相當大的改進空間，所以未來將針對上述兩者的問題，將在脈衝序列以及後處理的方面上改善化學位移影像技術。

Molecular imaging shall play an important role in the diagnosis for the personalized medicine in the future. Chemical shift imaging (CSI), one of molecular imaging techniques, provides us an opportunity to non-invasively assess the distribution and concentration of the metabolites of interest in different living tissues. In the case of brain diseases, CSI provides insight into the relationship between disease progress and metabolic changes. Therefore, CSI is an invaluable tool to reveal the mechanisms underlying the brain diseases and helpful in conducting the treatment plan. Glioblastoma multiforme is an aggressive and fast-growing tumor cell in brain cancers, so it is a highly malignant brain cancer. And it is the major of all brain cancer population. The treatment planning and the therapeutic evaluation have close relationship with the physiological characteristics, mechanism, and state of tumor cell. CSI provides the distributions of variable metabolites in the brain, and it can be used to observe physiological characteristics and state of the tissue to get key information. The aim of this thesis is to establish the experimental standard procedure of the CSI. We’ve applied it to the rat model of glioblastoma multiforme. After the implantation of C6 glioma cells into the rat striatum, the metabolic changes and physiological status in the growing tumor and the contralateral normal tissue were observed by CSI. Our results showed neuronal loss in the tumor-implanted striatum with rapid growth and increased metabolic activity in C6 tumor, and hypoxia in the core of tumor. Conclusively, our results demonstrate that CSI can be applied to detect the distribution of metabolites. From the results, it shows the potential of the quantification for the composition of tumor tissues. But there are still great room for improvements of the prolonged scan time and the low spatial resolution. For the above two problems, we’ll improve CSI technique on the pulse sequence and post-processing in the future.