高角鑑別率擴散磁振造影技術於神經纖維結構之研究

Abstract

近幾年來，運用磁振造影技術來探討不同大腦功能區之間的複雜神經連結性，為神經科學研究以及臨床神經性或是精神性疾病應用中相當重要的一個方法。擴散磁振造影由於具有非侵入式偵測神經纖維方向的優點，更是廣泛地被應用於解構複雜的神經連結。相較於傳統的擴散磁振造影技術，高角鑑別率擴散磁振造影技術能夠更精準地解析複雜的交叉神經結構。然而，此方法與解剖結構的相關性以及臨床應用的可行性仍需要作進一步之驗證。 因此，本論文的主要目的為增進高角鑑別率擴散磁振造影技術於臨床上應用的可行性，並且可分為下列三部份。第一為驗證擴散譜磁振造影技術與鼠癲癇模型中病灶的相關性。第二為發展一套系統性最佳化的方法來探討擴散譜磁振造影與Q球磁振造影技術於臨床上的可行性。最後，我們運用高溫超導射頻線圈來增進擴散張量磁振造影之信噪比，進而提升神經追蹤之準確度。 於癲癇鼠疾病模型之研究中，我們發現到擴散譜磁振造影之量化指標與病灶評估指標之間有存在顯著的相關性。平均擴散度與病灶評估指標在海馬迴中CA3處為正相關(r = 0.62; p = 0.0174)。至於非等向性指標在海馬迴中dentate gyrus處與病灶評估指標呈正相關(r = 0.71; p = 0.0047)，而在CA3處中呈負相關(r = -0.63; p = 0.0151)。在臨床最佳化的研究中，我們發現到信噪比及角度解析度均為影響高角鑑別率擴散磁振造影技術最佳擴散敏感度之重要因素。此外，減少取樣法也能夠得到與正常取樣法接近之準確度。最後，我們驗證了在現有的系統中，運用高溫超導線圈能夠提升擴散張量磁振造影平均約為三倍之信噪比增益，更可將差異角度之標準差由40.11度縮小為34.88度，也同時增進了神經追蹤之準確度。 總結而言，我們驗證了擴散譜磁振造影與病灶評估間的相關性，也建立此技術於臨床上進一步應用之潛力。此外，我們也建立了一套最佳化高角鑑別率擴散磁振造影技術之方法，並且探討其最適當參數在臨床上之可行性。最後，在高溫超導射頻線圈的研究中，我們率先將其應用於擴散張量磁振造影的技術中，並且驗證了此方法於神經追蹤準確度上之增益。本論文成功地建立了高角鑑別率擴散磁振造影技術由動物研究轉移至臨床上的可行性以及最佳化之方法，相信對未來神經科學的基礎研究或是臨床診斷都有極大的助益。

Since last few years, magnetic resonance imaging (MRI) has become an important approach to map the complex neural connectivity between different functional areas for neuroscience research and clinical applications. With the ability of mapping fiber orientations non-invasively, diffusion MRI provides a novel aspect of depicting the structural connectivity of brain. Compared with conventional diffusion MRI techniques, high angular resolution diffusion MRI (HARDI) techniques have the capability of resolving complex neural fiber architectures. However, the histological correspondence of HARDI and its potential on clinical applications have not been well demonstrated yet. Therefore, the overall objective of this dissertation is threefold and targeted to facilitate HARDI techniques for clinical use. First, we demonstrated the histological correspondence of one of the HARDI techniques, diffusion spectrum imaging (DSI), on a rat epilepsy model. Second, we developed a systematic approach to investigate two HARDI techniques, DSI and q-ball imaging (QBI), on a clinical 3T MRI system. Finally, we verified the capability of high-temperature superconducting (HTS) radiofrequency (RF) coil on diffusion tensor imaging (DTI) and investigated the association between signal-to-noise ratio (SNR) and accuracy of neural fiber tractography. In our results, significant subregion-dependent correlations were found between DSI indices and histological evaluation, namely Timm’s score. For mean diffusivity, positive correlation was found in cornu ammonis (CA3), r = 0.62; p = 0.0174. The correlation between diffusion anisotropy and Timm’s score showed positive correlation in dentate gyrus (DG), r = 0.71; p = 0.0047, and negative correlation in CA3, r = -0.63; p = 0.0151. For optimization study, our results indicated that the optimum maximum b-value (bmax) was a trade-off between SNR and angular resolution. At their own optimum bmax, the reduced sampling schemes yielded angular precision and accuracy comparable to the high sampling schemes. Finally, our results showed that HTS coil provided an average SNR gain of approximately three folds on our 3T MRI system, the standard deviation of deviation angles was significantly reduced from 40.11° to 34.88°, which also significantly improved the connectivity of fiber tracking. In summary, we successfully demonstrated the histological correspondence of our proposed DSI indices and their potential use on clinical applications. Additionally, we verified the clinical feasibility of HARDI techniques, DSI and QBI, and found the optimum sequence parameters for their reduced sampling schemes. Finally, we demonstrated the capability of HTS coil on improving neural fiber tractography inferred from DTI data. Conclusively, our proposed methods can further advance the translation of HARDI techniques from laboratory to clinical setting, which will be potentially useful to facilitate the neuroscience research and clinical applications.