穩定長期使用功能性磁振造影與正子斷層攝影術探討大鼠腦部深層腦刺激的反應

功能性磁振造影(fMRI)是腦功能研究中甚佳的檢驗工具，其優越性在於闡明大腦中神經活動的空間分布。在囓齒動物的fMRI研究中，為避免動物不必要的壓力及掙扎，適當的麻醉是必須的。α-氯醛糖(α-chloralose)為動物fMRI中最常用的麻藥，因為這種麻藥可以很好的保留大腦中神經與血管間的耦合反應。然而，α-chloralose對於動物有害，因此並不建議用於長期追蹤研究。最近有人提出以A2-腎上腺素受體的刺激劑medetomidine作為鎮定劑來進行動物fMRI，並在五天的間隔中經由周邊刺激獲得穩定的血氧濃度變化。在本實驗中，我們更進一步的結合這個方法與長期埋入MRI相容的刺激電極，試圖長期追蹤鼠腦中的視丘皮質迴路。利用medetomidine進行麻醉，我們得以在長達幾週之間重複掃描直接電刺激腹外側視丘。我們在同側的初級感覺皮質獲得可重現的刺激強度與頻率依賴性血氧濃度反應，伴隨著高度保守性表現在其反應強度(兩次測試階段間的correlation coefficient = 0.8677, P < 0.001)、反應區域的大小(第二次測試階段為第一次的92.41-96.99%)以及位置(61.3-80.02% 的重疊率)。該反應的分布模式與在α-chloralose麻醉下所獲得的反應近乎相同，但反應強度較小。我們也利用正子造影在S1發現了刺激強度依賴性的葡萄糖代謝變化。其S1中葡萄糖代謝變化量與血氧濃度反應強度呈現高度相關(correlation coefficient = 0.9001, P < 0.001)。這個新的方法將促使我們得以利用動物fMRI和PET來研究特定腦神經迴路於正常運作或疾病狀態下的長期可塑性變化。

關鍵字

功能性磁振造影；正子斷層攝影；深層腦刺激；血氧濃度；氟-18去氧葡萄糖

並列摘要

Functional magnetic resonance imaging (fMRI) provides an excellent tool for the examination of brain function, especially for revealing the global spatial activation pattern in the brain. For rodent fMRI, to prevent the undesired stress and motion artifacts, suitable anesthesia is needed. Alpha-chloralose is the most commonly used anesthetic in rodent fMRI, since it preserve well the neurovascular coupling response in the brain. However, α-chloralose is very harmful to the animal, and is not recommended for longitudinal study. Recently, a noninvasive rat fMRI protocol using the A2-adrenoreceptor agonist medetomidine as sedative has been proposed, and the peripheral evoked BOLD response was observed reproducibly over 5 days. In the current study, we further combine this protocol with chronic implantation of MRI compatible stimulation electrode, and seek to longitudinally trace the thalamocortical circuit in the rat brain. By using medetomidine anesthesia, we were able to repetitively scan direct ventroposterior (VP) thalamus electrical stimulation over weeks. We found reproducible stimulus frequency and amplitude dependent BOLD response within ipsilateral S1, with highly conserved in amplitude (the correlation coefficient between two sessions = 0.8677, P < 0.001), area size (the second session was 92.41-96.99% to the first session) and location (61.3-80.02% overlapping). The pattern of the response was comparable to that under α-chloralose anesthesia, but the response amplitude was weaker. We also found stimulus amplitude dependent change of glucose consumption (CMRglu) in S1 by Positron Emission Tomography (PET). The change of CMRglu was highly correlated with the amplitude of BOLD response in S1, with the correlation coefficient of 0.9001 (P < 0.001). Thus this new protocol will enable us to study long-term plasticity of specific circuitry of the brain in normal function and in disease states by rodent fMRI and PET.

並列關鍵字

BOLD ； fMRI ； FDG ； PET ； DBS ； deep brain stimulation ； longitudinal

參考文獻

Angenstein, F., E. Kammerer, et al. (2007). "Frequency-dependent activation pattern in the rat hippocampus, a simultaneous electrophysiological and fMRI study." NeuroImage 38(1): 150-163.

Antognini, J. F., X. W. Wang, et al. (1999). "Quantitative and qualitative effects of isoflurane on movement occurring after noxious stimulation." Anesthesiology 91(4): 1064.

Austin, V., A. Blamire, et al. (2003). "Differences in the BOLD fMRI response to direct and indirect cortical stimulation in the rat." Magnetic Resonance in Medicine 49(5): 838-847.

Bandettini, P. A., E. C. Wong, et al. (1992). "Time course EPI of human brain function during task activation." Magnetic Resonance in Medicine 25(2): 390-397.

Bock, C., H. Krep, et al. (1998). "Brainmapping of α-chloralose anesthetized rats with T2*-weighted imaging: distinction between the representation of the forepaw and hindpaw in the somatosensory cortex." NMR in Biomedicine 11(3): 115-119.

國際替代計量

穩定長期使用功能性磁振造影與正子斷層攝影術探討大鼠腦部深層腦刺激的反應

全文下載

主題瀏覽