應用於動物腦血流時變分析之高速雷射光斑對比顯像儀

雷射散斑對比成像是一種因應腦血流觀察需要而開發的免掃描全景光學技術。本研究發展一套了以雷射散斑對比成像為基礎的多用途腦血流動力分析系統，可用於觀察功能性刺激實驗的腦血流相對流速變化和血流脈波信號，並以脈波信號計算血管硬度指標。此系統的硬體包含高速CMOS相機、同調性光源、顯微鏡以及個人電腦，相機由個人電腦上的Labview軟體控制。其精簡的硬體需求十分符合生醫實驗的使用。在微流道實驗中，此一系統的流速指標與流道中懸浮液體流速呈現一線性關係，此實驗中所得得決定係數r^2皆高於0.96 (使用75μs相機曝光時間)。這結果將鼓勵雷射散斑對比成像的採樣頻率提升高過於常見的200Hz，若以75μs為曝光時間，採樣頻率甚至可高達13000Hz。在此研究中，兩次的功能性刺激實驗用以驗證所開發的血流觀測儀。12%缺氧功能性刺激實驗結果顯示，此系統所量測出的血流對時間的變化與主動脈波速呈現正相關。去氧腎上腺素功能性刺激實驗結果顯示此系統所量測出的血流對時間變化與過去文獻中單點多普勒的腦血流對時間變化呈現正相關。為系統的應用提供腦血流脈波研究展示範例，此研究以兩條鄰近的小動脈和小靜脈進行腦脈波流分析。以1869Hz擷取頻率採集結果顯示:兩脈波的最低點間無明顯相位延遲。在上升時間上，小動脈脈波較小靜脈脈波短13毫秒。在下降時間上，小動脈脈波較小靜脈脈波長6毫秒。透過使用二次微分脈波流分析指標，血管硬度程度可被評斷，其中血管硬度上升指標與血管硬度成正比，而血管硬度衰減指標與血管硬度成反比。結果顯示，在血管硬度上升指標上，小動脈為0.95和小靜脈為0.74，而在血管硬度衰減指標上，小動脈為0.125和小靜脈為0.35。兩個二次微分脈波流分析指標皆指向小動脈血管硬度高於小靜脈。此研究所開發的多用途雷射散斑系統不僅能觀察功能性刺激實驗的平均相對血流變化，同時可以觀測血管脈波流和提供血管硬度分析指數。此方法終將幫助中風研究，了解中風前後腦血管健康的變化及其前因後果，可望提升腦中風發生時的即時診治手段並使傷害降到最小。

關鍵字

腦血流；血流脈波分析；雷射散斑顯像儀；血管硬度指數；高速雷射散斑顯像儀

並列摘要

Laser Speckle Contrast Imaging (LSCI) is a non-scanning wide field-of-view optical imaging technique specifically developed for cerebral blood flow monitoring. In this project a versatile Laser speckle contrast imaging system has been proposed to monitor hemodynamics changes in functional activation experiment and pulsatile blood flow to examine the vasculature physical properties. The hardware of the system consists of a high speed CMOS camera, a coherent source, a Trinocular microscope, and a PC that does camera controlling and data storage. The simplicity of its hardware system is suitable for biological experiments. Under experimental setting, the proposed system shows a linear relationship between the blood flow index (ICT) and controlled flow rate of the microchannel. This linear relationship has a minimum coefficient of determination〖 r〗^2= 0.96 with camera exposure time setting of 75μs. This permitted LSCI can be used in the enhanced sample rate setting and allow sample rate up to 13000 Hz which will be bounded by camera capacity. The proposed LSCI system has applied in two experiments of functional activation in rat, a 12 % hypoxia event and a Phenylephrine injection event. The 12% hypoxia results show blood flow time trace produced from proposed system shows positive correlation with the aortic pulse wave velocity. The Phenylephrine injection results show the hemodynamic response measured from proposed LSCI correlate well with the results found in the literature. To exemplify the instantaneous pulsatility flow study acquired with high sample rate, a pulsatile cerebral blood flow analysis has been conducted on two vessels, an arteriole and a venule. The pulsatile waveform results captured under 1869Hz sample rate shows there is no phase delay between the foot of the pulsatile flow of the arteriole and the venule. The pulse of the arteriole rise 13ms faster than the pulse of the venule, and it takes 6ms longer for the pulse of the arteriole to fall below the lower fall-time boundary. By using second order derivative (accelerated) blood flow index the vascular stiffness can be evaluated, the results shows the arteriole and the venule have increased vascular stiffness index (b/a amplitude ratio) of 0.95 and 0.74. On the other side, the arteriole and the venule have the decreased vascular stiffness index (c/a amplitude ratio) of 0.125 and 0.35. Both accelerated blood blow index suggested the arteriole has higher stiffness than the venule. The proposed LSCI system can monitor not only the mean blood flow over function activation experiment but also pulsatile flow which provided vascular stiffness metrics for estimating the stroke preliminary symptom and may provide insight of the casualness of the stroke and support the development of instantaneous cure to minimize the damage to the brain.

並列關鍵字

Cerebral Blood Flow Monitoring ； Blood Flow Pulse Wave Analysis ； High Speed Laser Speckle Contrast Imaging ； Vascular Stiffness Index ； LSCI

參考文獻

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應用於動物腦血流時變分析之高速雷射光斑對比顯像儀

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