通用擴散波數取樣磁振造影評估化療對乳癌患者大腦結構聯結體與神經心理學之影響

癌症是台灣人十大死因之首，癌症中，乳腺癌的罹病人數多，藉由適當的治療，使乳腺癌病患存活率提高，然而，此族群接受治療後，身心變化獲得重視。除了患者本身罹病的身心壓力之外，治療方式亦會造成患者的身心變化，包括大腦結構的改變或認知功能與情緒的影響，甚至嚴重影響患者的生活品質。化學治療藥物的直接或間接神經毒性可能造成認知變化，以前的研究集中在化療對患者大腦結構的晚期作用；而本研究對化療於患者大腦結構的早期作用感興趣。此外，我們嘗試使用通用擴散波數取樣影像(Generalized q-sampling imaging, GQI)來取代擴散張量影像(Diffusion tensor imaging, DTI)做擴散影像分析，以得知乳腺癌已化療患者或乳腺癌未化療患者的大腦結構是否有損傷。本研究為橫向式研究(Cross-sectional study)，於台中榮民總醫院及嘉義長庚紀念醫院收案，分別招募三組受試者：乳腺癌化療組、乳腺癌未化療組及健康控制組。所有受試者皆接受擴散磁振造影檢查及神經心理學測試。本研究影像分析分為三大部分，分別是基於體素之統計分析(Voxel-based statistical analysis)、圖論分析(Graph theoretical analysis)與多元回歸分析(Multiple regression analysis)。分析結果顯示乳腺癌化療組部分腦區之Generalized fractional anisotropy (GFA)與Normalized quantitative anisotropy (NQA)顯著降低，如：Left superior corona radiata、Left middle temporal gyrus，提供創傷後壓力症候群(Post-traumatic stress disorder, PTSD)及化學治療後，腦損傷的進一步證據。藉由連結GQI擴散指標與認知功能量表，顯示化療確實會影響大腦白質完整性及造成認知表現下降。此外，亦發現乳腺癌化療組之特徵路徑長度(Characteristic path length)變長，表示其大腦網路整合能力較差。乳腺癌患者化療後，大腦結構之GFA或NQA下降，或拓樸網路特性的變化，未來或許能成為監測化療藥物引起神經毒性(Neurotoxicity)的一個神經病理學生物指標。

Breast neoplasms cases are the most common cancer in women in Taiwan. Advances in cancer treatments have resulted in significantly improved survival rates but are often associated with side effects, such as cognitive decline, that may reduce the quality of life. Cognitive deficits were most pronounced in executive function and verbal memory domains. Both direct and indirect neurotoxicity from cytotoxic agents may underlie the cognitive changes.The previous studies focused on the late effect of the brain by chemotherapy in the last decade. Our study interested in the early effect of the brain by chemotherapy. Since diffusion tensor imaging (DTI) is associated with restrictions in the resolution of crossing fibers, we tried to use generalized q-sampling imaging (GQI) that can overcome these difficulties and is advantageous over DTI for the tractography of the fiber bundle.This cross-sectional study included three groups: breast cancer survivors who had completed their chemotherapy, breast cancer patient who didn’t received chemotherapy and healthy control group. All participants underwent diffusion MRI exam and neuropsychologic assessments. We have three parts of our image analysis, which are voxel-based statistical analysis, graph theoretical analysis, multiple regression analysis.Compared to the control group, results from voxel-based analysis showed significantly lower GFA and NQA in the breast cancer group (p < 0.05). Differences of brain regions included left superior corona radiata and left middle temporal gyrus. This study provides further evidence of brain injury results from chemotherapy and post-traumatic stress disorder. We have shown changes in cerebral white matter of patients after chemotherapy by linking GQI indices with decreased cognitive functioning. In addition, it has also been found that the characteristic path length of the breast cancer chemotherapy group increases, indicating that the brain network integration gets worse. Changes in GFA, NQA and network topological properties may therefore serve as a neuropathologic biomarker for treatment-induced neurotoxicity.