光聲造影跟現有的血氧飽和濃度量測技術相比有著高解析度、高對比及非侵入性等優勢。本論文主要的工作是開發一套以光聲造影技術為基礎的血氧飽和濃度定量技術並使用電腦模擬和仿體實驗驗證其是否有效達到定量血氧飽和濃度量測的目的。在本論文中我們基於最小平方法之反矩陣運算推算出血氧飽和濃度，首先最佳化了雷射波長的選擇使得光聲訊號的訊雜比和矩陣運算容忍系統雜訊能力的最佳化，並依據該波長的雷射光在血液中的穿透深度適當選擇超音波探頭的頻寬，使得量測到的光聲訊號峰值和血液的光吸收係數成正比，以進行定量血氧飽和濃度量測；此外在活體應用中，目標血管的能量密度會隨雷射光的波長改變，因此我們提出一個數學模型，並利用最佳化演算得到能量密度的補償係數，使光聲造影技術在活體應用中也能夠定量量測血氧飽和濃度。電腦模擬結果證實超音波探頭量測到的光聲訊號峰值會隨著光吸收係數不斷提高而發生飽和效應且頻寬越低的超音波探頭會越快發生，以及在雷射光波長為最佳化的情況下，使用頻寬較寬的超音波探頭其量測結果比較貼近原本預設的血氧飽和濃度；接著在仿體實驗部分我們用二種具不同吸收光譜的墨水來模擬帶氧和不帶氧血紅素，兩墨水透過不同濃度比例的混合模擬不同血氧飽和濃度的血液，實驗結果證實在雷射波長為最佳化的情況下，使用頻寬較寬的超音波探頭其量測結果比較貼近原本預設的濃度比例，與模擬結果一致，並和體外血液實驗結果做比較，證實了本論文所提出的光聲定量血氧飽和濃度量測技術擁有對單一血管進行定量血氧飽和濃度監控之可行性。最後的模擬驗證中，我們利用蒙地卡羅法來模擬能量密度在目標組織中隨波長改變之情形，透過我們提出的數學模型並利用最佳化演算，可運算出有效的補償係數去補償不同波長下目標組織不同的能量密度，使得計算出來的血氧飽和濃度能夠更接近預設值，這證明了此數學模型有潛力能夠有效地幫助我們在活體應用中利用光聲造影達到定量血氧飽和濃度量測的目的。

Non-invasive photoacoustic imaging has the advantages of good ultrasonic resolution and high optical absorption contrast when compared with other blood-oxygen-saturation measurement techniques. The purpose of this study is to develop a photoacoustic-imaging-based quantitative measurement technique for the determination of blood oxygen saturation and verify its feasibility by computer simulation and phantom experiments. To perform the robust measurement, an optimized wavelengths set of exciting laser was chosen to improve the signal-to -noise ratio of photoacoustic signals and the stability of matrix inversion based on least-square method which was used to calculate blood oxygen saturation first. According to the penetration depth of photons at each wavelength in the set, a proper bandwidth of ultrasonic transducer was selected to retain the proportionality between the optical absorption coefficient of the interrogating blood and its corresponding photoacoustic signal amplitude. Furthermore, we proposed a mathematical model to get fluence-compensation coefficients with optimization algorithm to compensate its changes depending on different wavelengths. Simulation results indicated the saturation effect, which describes the violation of the linearity between the measured photoacoustic signal amplitude and the target object’s optical absorption coefficient, would happen with optical absorption coefficient increasing in target tissue. We also confirmed that transducers with larger bandwidth could provide more accurate estimation for blood oxygenation saturation when using the selected wavelength set. In the phantom experiments, two kinds of ink with distinct absorption spectra were used to mimic oxy-hemoglobin and deoxy-hemoglobin. The experimental results showed that transducers with larger bandwidth offered better estimation for the mixing ratio between the two kinds of ink with the selected wavelength set, which agreed with the simulation result and experimental result of ex vivo blood data. It demonstrated that the proposed photoacoustic measurement technique is capable of quantitative blood-oxygen-saturation measurement in single blood vessel. In addition, the differences of fluence at the interrogating blood under the selected wavelength set were simulated by Monte Carlo method. The distorted photoacoustic signal amplitude affected by differences of fluence was substituted into our mathematical model with optimization algorithm to get fluence-compensation coefficients. The result showed that our mathematical model with fluence-compensation coefficients provides a better estimation for blood oxygenation saturation compared with the original method. It demonstrated that our mathematical model has the potential to do quantitative blood-oxygen-saturation measurement for in vivo application.

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