以功能性磁振造影追蹤產前內分泌干擾物暴露對青少年腦功能之影響

The Impact of Prenatal Endocrine-Disrupting-Chemical Exposure on Brain Function in Teenagers – Rules of fMRI

洪子揚(Chi-Ieong Hong)

指導教授 ： 陳拓榮 ； 翁駿程

中山醫學大學/醫學科技學院/醫學影像暨放射科學系碩士班/碩士(2018年)

摘要

許多研究指出婦女在懷孕期間暴露在內分泌干擾物(endocrine disrupting chemicals, EDCs)造成日後出生的小孩認知功能障礙和行為發展異常。本研究目的是探討懷孕期間內分泌干擾物暴露對後代大腦的影響。
　　我們在台灣中部收集了59位第三孕期懷孕婦女的血清和尿液樣本，分別對樣本中的重金屬、塑化劑代謝物、全氟化合物進行濃度檢驗。並在其後代13-14歲時為他們進行靜息態功能性磁振造影(resting-state functional magnetic resonance imaging, rs-fMRI)，利用分率低頻振幅波動 (fractional amplitude of low-frequency fluctuation, fALFF)和區域同質性(regional homogeneity, ReHo)進行多元迴歸分析來尋找懷孕期間母親體內內分泌干擾物的濃度和日後小孩大腦功能發育之間的關聯，並通過T-分數(以0-5的數值代表之)來表示相關性的強弱。
　　我們觀察到MBP濃度與額上回和額中回的負相關性(T-score=2.01，p<0.025，T-Score為0-5判定相關性大小的數據，越大表示相關性越高)，與顳中回和顳下回的正相關性(T-score=2.24，p<0.015)；另外我們觀察到MBzP濃度與前扣帶回(T-score=2.21，p<0.02)和島葉(T-score=1.86，p<0.04)有負相關性，並只在女生組觀察到這樣的情況。我們觀察到PFOS濃度在男女混合組中與島葉和殼核有負相關性(T-score=2.24，p<0.015)，男生組中與蒼白球和殼核有負相關性(T-score=2.50，p<0.01)；另外我們觀察到PFNA濃度在男女混合組中與尾狀核和殼核有負相關性(T-score=2.78，p<0.004)，男生組中與尾狀核和殼核有負相關性(T-score=2.56，p<0.009)。在重金屬的結果中，我們觀察到鉛濃度與楔狀葉有正相關性(T-score=2.56，p<0.007)；另外我們觀察到甲基汞濃度與顳上回有正相關(T-score=2.11，p<0.025)，而與尾狀核和殼核有負相關性(T-score=2.20，p<0.021)。在男女混合組和男生組的PFOS結果中，以塑化劑或重金屬作為共變數後，依然可以觀察到PFOS與右腦殼核的負相關關係(T-score=2.22-2.35，p<0.0125-0.02)。而在男女混合組和男生組的PFNA結果中，以其他EDCs作為共變數後，依然可觀察到PFNA與左右腦殼核及左腦尾狀核的負相關關係(T-score=2.28-2.71，p<0.005-0.017)。
　　我們觀察到孕期間EDCs濃度與青少年後代大腦在靜息態下的關連，EDCs對不同性別下所影響的腦區也略有不同。

關鍵字

內分泌干擾物 ； 塑化劑 ； 氟化物 ； 重金屬 ； 靜息態功能性磁振造影

並列摘要

Many studies reported prenatal exposure to Endocrine-Disrupting-Chemicals (EDCs) could cause adverse behavioral effect or cognitive dysfunction in children. This study aimed to find the relationship between prenatal EDCs’ concentrations and teenager’s brain function.
59 mother-child pairs were recruited during third trimester of pregnancy. Collected and examined EDCs concentrations in maternal urine/serum such as heavy metal, phthalate and perfluoroalkyl substances (PFASs). Teenage resting-state functional magnetic resonance imaging (rs-fMRI) data were collected at 13 to 14 years of age. Fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) were performed to find the association between the maternal EDCs concentrations and the teenage brain functional development by using multiple regression. Results were transform into T-score (a value between 0 and 5) to represent the strength of correlation.
We observed MBP concentration have a negative correlation with superior frontal gyrus and middle frontal gyrus (T-score=2.01, p<0.025, T-score is a 0-5 value to determine correlation, which increase with value). A negative correlation with middle temporal gyrus and inferior temporal gyrus (T-score=2.24, p<0.015). We also observed a negative correlation between MBzP concentration and anterior cingulum gyrus (T-score=2.21, p<0.02), insula (T-score=1.86, p<0.04) in girls group. We observed PFOS concentration have a negative correlation with putamen and insula in boys and girls combined group (T-score=2.24, p<0.015), a negative correlation with putamen and pallidum in boys group (T-score=2.50, p<0.01). We also observed PFNA concentration have a negative correlation with caudate nucleus and putamen in boys and girls combined group (T-score=2.78, p<0.004), a negative correlation with caudate nucleus and putamen in boys group (T-score=2.56, p<0.009). We observed a positive correlation between lead concentration and cuneus (T-score=2.56, p<0.007). We also observed a positive correlation between MeHg concentration and superior temporal gyrus (T-score=2.11, p<0.025), a positive correlation with caudate nucleus and putamen (T-score=2.20, p<0.021). PFOS results showed the negative relationship with right putamen in boys and girls combined group/boys group after applied phthalate or heavy metal as covariates (T-score=2.22-2.35, p<0.0125-0.02). PFNA results showed the negative relationship with left/right putamen, left caudate nucleus in boys and girls combined group/boys group after applied phthalate, heavy metal or PFOS as covariates (T-score=2.28-2.71, p<0.005-0.017).
We reported the correlation between maternal EDCs concentration and neurodevelopment of teenage brain, and the impacts on teenage brain were slightly different in different gender.

並列關鍵字

Endocrine disrupting chemicals (EDCs) ； phthalate ； perfluoroalkyl substances (PFASs) ； heavy metal ； brain function ； resting-state fMRI

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