即時光聲影像系統及雙波長光聲血氧濃度量測

Abstract

在本研究中我們探討利用雙波長雷射光的光聲效應，配合脈衝重複頻率(pulse repetition frequency, PRF)高達數千Hz的脈衝雷射，即時計算血液中血氧濃度之可行性。血氧濃度是重要生理參數，目前常用的檢測方法為侵入式的抽血檢驗或是非侵入式的脈衝血氧計(pulse oximeter)，然而脈衝血氧計也有其侷限。利用光聲效應量測的優點是非侵入式，不僅得到局部血氧資訊，同時能夠搭配B-Mode影像作比較。本論文之研究目標即為發展一套訊號分析方法，利用不帶氧血紅蛋白(Hb)與帶氧血紅蛋白(HbO2)在不同雷射波長下吸收度不同的性質，把雙波長光聲訊號量化成血氧濃度，驗證此方法之可行性，並在高頻超音波系統上實現。在實驗架構方面，即時光聲影像利用染料雷射，可以以frame rate 5Hz成像。在雙波長計算濃度方面，以532nm Nd:YAG雷射驅動，搭配Ti-Sapphire可調波長雷射，選擇雙波長雷射光照射血液，同時以中心插入光纖的超音波探頭，以背向模式進行光聲訊號量測。目前即時光聲影像只能以單一波長722nm成像，可用來凸顯高光學吸收度的區域。在雙波長計算濃度的部分，測得的光聲訊號經過能量正規化修正後，擷取峰值或特定波段進行血氧濃度計算。由於血液取得不易，在血液實驗之前先進行紅藍墨水以及金奈米實驗，做雙波長計算濃度的驗證。結果顯示，當紅藍墨水以不同比例混合時，用光聲訊號計算出的濃度與已知濃度呈高度正相關，平均誤差為-24%，誤差標準差為32%。而金奈米實驗的結果也呈高度正相關，平均誤差為3.43%，誤差標準差為14.5%。血液實驗方面，先確認血液能維持血氧濃度>95%長達一小時以上，再利用光聲訊號比較打入空氣血液與未打入空氣血液的血氧濃度。結果顯示，對於打入空氣的血液與未打入空氣的血液來說，計算出的血氧濃度都在85%以上，但未打入空氣血液血氧濃度較高。而在波長的選擇方面，選用720nm左右搭配超過800nm的雙波長雷射光，能得到比較合理的結果。

In this study we discuss the feasibility of using dual-wavelength photoacoustic imaging, along with a high pulse repetition frequency laser for real-time measurements of blood oxygen level. Blood oxygen level is an important physiological parameter. Conventionally, there are two ways to measure the blood oxygen level. One is direct blood analysis and the other is using a pulse oximeter. The direct method, which draws blood from patients invasively, is the current gold standard for blood oxygen level measurement. Pulse oximeter, on the other hand, is a non-invasive and thus more convenient method. But the accuracy is inferior. The hypothesis of this research is that by combining photoacoustic imaging with blood oxygen level measurements, 2D functional imaging can be achieved. To this end, the goal of this research is to develop and implement a signal processing method, utilizing absorption spectrum difference between oxyhemoglobin and deoxyhemoglobin, to measure the blood oxygen level distribution in real time. In our experimental setup, a high PRF pulsed dye laser is used to achieve a frame rate up to 5 frames/sec. On the other hand, a Ti-Sapphire tunable laser, pumped by a 532nm Nd:YAG laser, is used for dual wavelength measurements. Due to system limitations, currently real-time imaging only with a single wavelength (722nm) is achieved. Various samples, including blue/red ink and gold nano-particles, were used to test our methods. Results show that the measured concentration of blue ink had a mean error of -24%, and a standard deviation of 32%. For gold nanoparticles, the mean error was -3.43%, and the standard deviation was 14.5%. For human blood, the calculated blood oxygen level for both gas-filled blood and no gas-filled blood was above 85%, but the oxygen level was higher for no gas-filled blood. It is suggested that 720nm and 800nm should be the two wavelengths used for future investigation.