光聲顯微術於小動物大腦功能性造影之應用

Abstract

了解大腦血液動力學之變化是一個相當重要之研究議題，並且與多種醫學應用息息相關，例如監控與治療多種神經生理學上之疾病。老鼠大腦中之總含氧濃度(total hemoglobin concentration; HbT)、大腦血容積(cerebral blood volume; CBV)和血氧濃度(hemoglobin oxygen saturation; SO2)是近幾年被大量擷取用於研究之生理資訊。於老鼠左前肢進行功能性電刺激於文獻中已驗證能有效激發足夠鼠腦血液動力學之特定變化。本論文透過功能性光聲顯微影像技術(fPAM)來研究老鼠大腦單一血管中血液之總含氧濃度、大腦血容積和血氧濃度在功能性電刺激下於特殊腦區域之變化。本論文主要包含三大研究議題: (1)使用25-MHz之功能性光聲造影系統研究功能性腦血氧濃度與腦血容積於特殊腦區域之變化可行性；(2) 於單一血管中利用50-MHz功能性光聲造影系統探討功能性總含氧濃度、大腦血容積和血氧濃度之變化；(3) 建構穿腦顱50-MHz光聲造影系統來研究單一血管中之老鼠大腦血液動力學之變化規則。我們證實了此光聲系統透過其專一光學吸收對比之特性，將可以可靠地來研究大腦血液動力學。本論文闡述之技術將有潛力可以進一步讓我們了解腦神經血管耦合下血液動力學之變化於老鼠大腦上之研究上。

Understanding the cerebral hemodynamic changes is a crucial issue, which is related to a broad range of medical applications, such as monitoring the therapeutic interventions of the physiological basis of neurological diseases. Assessing the functional changes in cerebral-blood-volume (CBV), hemoglobin oxygen saturation (SO2) and total hemoglobin concentration (HbT) are the most measured parameters in small animals’ brain. In this dissertation, a functional photoacoustic microscopy (fPAM) system was established that was able to assess functional changes in HbT, SO2 and CBV corresponding to specific brain activation. Electrical forepaw stimulation was employed to activate the contralateral primary somatosensory cortex. There are three important neuroscience cases studied in thisdissertation: 1) studying of the functional changes in SO2 and CBV in specific brain region using the 25-MHz fPAM system, 2) studying of the functional changes in HbT, SO2 and CBV in specific cerebral vessels using the 50-MHz fPAM system and 3) transcranial imaging of functional changes in HbT, SO2 and CBV in specific cerebral vessels with skull intact using the 50-MHz fPAM system. Novel functional imaging analysis methods using fPAM system for imaging HbT, SO2 and CBV changes have been also proposed. We showed that the current fPAM can robustly and transcranially probe cerebral hemodynamic changes in HbT, SO2 and CBV by using intrinsic optical-absorption contrast. The technique presented here has potential in advancing our understanding of brain-neurovascular coupling, as well as in monitoring brain disease progression in small animal models.