磁化率影像於大腦之研究與應用：定量靜脈血氧濃度與鐵沉積

Abstract

近幾年來，個人化及精準化醫學已經成為二十一世紀最重要的課題之一。藉由專屬之治療方式來提高療效，降低副作用。定量醫學影像之技術可用以評估病灶的發展與治療的反應就成為重要之方法。利用磁振造影為基礎之磁化率權重影像來觀察大腦出血或是中風，已經成為目前臨床診斷的必要方法。相較於傳統的磁化率權重影像技術，磁化率影像技術能夠提供量化資訊，進而幫助個人化醫學影像的發展。然而，此方法於神經科學與臨床應用的可行性仍需要進一步之驗證。 因此，本論文的主要目的為增進磁化率影像技術於臨床應用的可行性，並且可分為下列四部分。第一為利用數值模擬與仿體實驗來驗證磁化率影像技術；第二為利用定量探討高氧狀態下，大鼠顱內的靜脈血氧變化；第三為長期地定量監測大鼠中風後的血氧變化；第四為系統性最佳化人大腦之重建參數與其於臨床上之可行性。 在數值模擬的研究中，我們驗證了磁化率影像演算法有99%的準確率，仿體的實驗也呈現了磁化率數值與鐵離子濃度為線性相關 (R2 = 0.98)。在大鼠的高氧研究中，我們發現到磁化率的變化主要來自於靜脈血管；此外，相較於常氧狀態下，靜脈的血氧上升約10%。在大鼠中風的研究中，我們發現了靜脈的血氧濃度會於七天後恢復至與正常側無顯著差異(p > 0.05)。最後，我們將此方法應用於臨床的定量鐵沉積、出血與鈣化研究中，利用定量磁化率影像可分辨兩病灶於一次磁振造影掃描中。 總結而言，我們呈現了磁化率影像技術於神經科學與臨床上進一步應用之潛力。此外，我們也建立一套最佳化磁化率影像之方法，並針對鼠腦與人腦探討其最適當參數之選擇。本論文成功地建立定量磁化率影像技術由動物研究轉移至臨床上的可行性與最佳化之方法，相信對未來神經科學的研究或是臨床診斷都有極大的助益。

Since last few years, personalised or precise medicine has been a crucial issue in 21st century. With exclusive way to improve the outcome of treatment, the side effect could be reduced. For this purpose, a quantitative medical imaging is essential to evaluate the disease progress and the response to treatment. At present, using susceptibility weighted imaging (SWI) based on magnetic resonance imaging (MRI) to observe haemorrhage and stroke has become an essential methodology for clinical diagnosis. Compared to the conventional SWI, quantitative susceptibility mapping (QSM) technique can offer quantitative information to approach to the personalised medicine. However, the capability of QSM technique on neuroscience researches and clinical applications has not been well demonstrated yet. Therefore, the overall objective of this dissertation is fourfold and targeted to facilitate the QSM technique for clinical use. First, we start from verifying the capability of the QSM technique using numerical simulation and phantom experiment. Second, we investigate the hyperoxic effect in rat brain using the QSM technique. Third, we applied the QSM technique to longitudinally monitor the venous oxygen saturation (SvO2) after stroke. Forth, we optimised the parameters of QSM technique for human brain and tested its potential on cerebral disorders such as haemorrhage, microbleeds, and calcification. In our results, accuracy of the QSM technique was 99% in numerical simulation, and a linear correlation (R2 = 0.98) was found between estimated susceptibility and iron concentration in the phantom experiment. For hyperoxia study, we found the susceptibility change were mainly from veins and venules. A 10% shift of SvO2 was estimated relative to normoxia. For stroke study, there was no significant difference (p > 0.05) of SvO2 between contralateral and ipsilateral cortex after reperfusion at 7- days. Finally, the QSM technique to quantify iron deposition and differentiate haemorrhage/microbleeds and calcification was demonstrated in one MRI scan. In summary, we successfully demonstrated the feasibility of QSM technique on neuroscience researches and clinical applications. Additionally, we optimised the QSM technique for rat and human brain. Conclusively, our proposed methods can further advance the translation of QSM technique from animal to clinical applications, which will be potentially useful to facilitate the neuroscience research and clinical applications.