| Abstract: | 近年來醫療對癌症的診斷以及治療進步顯著，使患者生存率大大的提升。而伴隨著癌症治療的存活率上升，對於癌症治療的副作用越來越受到關注。許多的癌症病患指出在進行化療前後會有認知功能上的變化產生。有研究顯示，約20％〜30％的乳腺癌患者在開始化學治療前會有認知功能障礙。並且也有研究證實了乳癌患者化療藥物的使用劑量與認知功能障礙之間有相關性的假說。隨著對乳癌患者化療前後與認知功能障礙之間關聯的研究越來越多，功能性磁振造影做為觀察罹癌前後或化療前後之間的大腦功能性影像差異的工具而被廣泛的運用。然而絕大多數對於這方面的功能性磁振造影研究都是使用血氧濃度依賴(blood oxygen-level dependent, BOLD)的任務刺激型功能性磁振造影，在本研究中我們所使用的是動脈自迴旋標記(arterial spin labeling, ASL)的靜息態功能性磁振造影來觀察正常組、乳癌患者化療前與乳癌患者化療後三組的差異。 本篇研究總共造影了31位健康受試者、31位化療前乳癌患者與31位化療後乳癌患者，經過影像前處理後進行區域同質性(regional homogeneity, ReHo)及低頻振幅(amplitude of low frequency fluctuations, ALFF)分析，最後，進行t-test比較組間差異與multiple regression觀察影像結果與各個量表參數之間的關聯性，包含醫院之焦慮與憂鬱量表(Hospital Anxiety and Depression Scale, HADS)、事件影響測量表修訂版(Impact of Event Scale – Revised, IES-R)、簡易心智量表(Mini-mental state examination, MMSE)、認知與情緒正念量表修訂版(Cognitive and Affective Mindfulness Scale- Revised, CAMS-R)、癌症治療認知功能評估表(Functional Assessment of Cancer Therapy-Cognitive Function, FACT-Cog)。 在我們的結果中主要發現在ALFF分析中，在化療後病人組相較於化療前病人組有多處腦區自發性神經活度下降，包含temporal、frontal等腦區，而在化療後相較於化療前病人之間組間比較也觀察到了多處腦區自發性神經活度下降，包含frontal、hippocampus，最後，化療後病人組與正常人組相比，主要在frontal有神經活度降低的情況。 另外ReHo分析中，化療後病人組相較於化療前病人組在lingual、inferior orbito-frontal、middle temporal等腦區的區域神經訊號的一致性有差異，在化療後相較於化療前病人之間組間比較中看到middle temporal、superior temporal、inferior temporal、hippocampus等腦區的區域神經訊號的一致性降低，化療後病人組與正常人組相比在superior temporal、precuneus、inferior frontal、precuneus等腦區的區域神經訊號的一致性降低。 本研究是第一個使用ASL技術fmri的方法來進行乳癌與化療所造成之腦功能變化影響的靜息態磁振造影影像學研究，藉由ASL 的技術，提供空間定位及敏感性更佳、更多可能的腦區變化的資訊，能夠幫助我們更深入的理解罹患乳癌所造成的心理及生理影響與化學治療對我們的大腦功能性方面的改變，未來研究中如果能真正理解出化療對癌症病人大腦的影響，對於發展針對化療相關的認知障礙的預防或康復方式以及治療定能有莫大的幫助。Recent advances in the diagnosis and treatment of cancers are allowing more patients to achieve complete physical recovery. However, with these advances in cancer treatment, there is a growing concern about the side-effects. It has been reported that patients have experienced cognitive changes after chemotherapy. Previous study has shown that there is cognitive dysfunction in about 20% to 30% of breast cancer patients who underwent chemotherapy. There are many studies on the association between cognitive impairment and chemotherapy in patients with breast cancer who underwent chemotherapy. Functional magnetic resonance imaging has been widely used as a tool for observing the differences in functional brain imaging caused by chemotherapy-related cognitive impairments. In this study, Arterial Spin Labeling (ASL) fMRI was used to observe the differences in brain activity among the normal control group, the pre-treatment group, and the post-treatment group. The Brain images of women with breast cancer treated with chemotherapy (N = 31), those without chemotherapy (N = 31) and matched healthy controls (N = 31) were scanned by using pulsed arterial spin labeling MRI. After image preprocessing, regional homogeneity (ReHo) analysis and amplitude of low-frequency fluctuations (ALFF) analysis were then applied. Finally, t-test and multiple regression were used for statistical analysis. Comparison of the data analyzed, showed less activation in the temporal, the middle frontal in the patients that were in the pre-chemotherapy group than those patients in the control group. In addition, there were also changes in brain activation from pre- to post-chemotherapy in patients. Post-chemotherapy, patients had less activation in the frontal , the hippocampus. Finally, patients also showed significantly less activation when compared to the control group. Brain regions analyzed included: the lingual, the fusiform, the middle occipital, the precentral, the inferior orbito-frontal, the postcentral, the middle frontal. This new method of using of ASL-base fMRI in this cohort study of breast cancer patients provide a high sensitivity tool to analyze the effects of chemotherapy on brain activity. High spatial resolution fMRI can help us to better understand the mechanisms of chemotherapy-induced cognitive impairments. |
