擴散光學造影系統量測人類大腦嗅覺響應之臨床應用

Abstract

嗅覺功能失調或喪失發生在大多數腦部病變或退化性疾病當中，舉凡如：阿茲海默症、帕金森氏症、認知功能障礙、妥瑞氏症…等等。此類疾病的極早期診斷已成為目前醫療的趨勢，而近紅外光譜造影系統或稱擴散光學斷層掃描術提供了快速、及時、非侵入性、對人體低傷害等優點，協助進行臨床潛在生物指標的觀測。由於光打入組織耗散極快，以致無法深入組織內部，因此本研究觀測主要落在大腦前額葉區域，前額葉與大腦內部許多部位有著極高的相關性，嗅覺與眼眶額葉皮質區域會是主要探討的重點。 本研究中採用連續波式多通道近紅外動態血氧量測系統，觀測常人與妥瑞氏症病童於嗅覺刺激下的腦部活化程度的差異以及常人嗅覺記憶相關測試，未來目標包含阿茲海默症及帕金森氏症等腦部退化性疾病。量測點採10-20系統之定位，實驗分三部分，第一為resting state量測，第二為使用不同嗅刺激物做刺激，觀測腦部活化現象，最後為嗅覺記憶部分，測試常人對於同一種味道在每隔一段時間重複嗅聞後，對於此味道產生的記憶與腦部活化程度的關聯。雖然量測結果可能因為受測者大腦主觀意識影響，但整體而言，對於刺激後的活化反應表現仍算顯著。研究結果透過含氧血、缺氧血濃度變化可推測出嗅覺能力可能與前額葉眼眶額葉皮質容積大小有關，這可以映證妥瑞氏症病患的大腦結構性病症。其次，病患發生tics時會造成劇烈性含氧血濃度驟降現象。最後實驗觀測當同一嗅刺激物在短時間內多次嗅聞後，大腦會對該種味道活化程度愈趨低下，可解釋為大腦對該味道產生記憶，未來可應用於阿茲海默症病患做比對，罹病者也會有此現象或否。期待此臨床研究能對大腦疾病之極早期診斷提供客觀的協助診斷指標。

Olfactory dysfunction is one of the earliest clinical features in cerebral disease, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), cognitive impairment, and Tourette Syndromes (TS). Thus, the pathway for the olfactory response may be used as a potential biomarker in early stage of above noted diseases. Near-infrared spectroscopy (NIRS) and also called diffuse optical imaging (DOI) technique is a noninvasive neuroimaging tool used to measure activation induced changes in cerebral hemoglobin concentration. In this feasibility study of first year, the multi-channel (16-channels) DOI system was used to measure the olfactory response of prefrontal cortex. In order to verify the feasibility of the DOI system and the correlation of short-term memory and olfaction, a total of twenty subjects including healthy male and female adults were recruited for this study. In the results, the hemoglobin responses of orbitofrontal cortices are increased significantly during olfactory stimulation; nevertheless, the increasing amplitude would get smaller in every test later when olfactory memory has already been built. Our study shows that the multi-channel DOI system can provide high potential to apply to clinical neuroscience for diagnosis of olfactory disorders. In future studies, the DOI system will continuously be used to measure the olfactory response of healthy and diseased subjects for further evaluation. We hope that the olfactory DOI system can provide the sensitive and objective biomarker for early diagnosis.