生物組織的黏彈特性通常與其執行特定的功能有關，更是組織生物力學行為模擬時之重要參數，例如義肢殘肢介面壓力之有限元素分析及人工器官之設計。但目前有關組織黏彈特性的量測大多為離體實驗與侵入性的方法為主，故應用於活體組織時，其精確度及信賴度經常被質疑。因此設計及研發一套創新性、非侵入性及無傷害性的量測方法，客觀量化活體軟組織的黏彈特性，對生物工程及醫療診斷領域而言相當重要。近十年來，超音波彈性影像利用都卜勒超音波配合低頻振動量測組織內部位移的振幅及相位梯度來探討組織的彈性模數，為目前相當具有潛力的一種方法。

本研究的目的為設計及發展一套脈波式都卜勒超音波量測系統，客觀量化及探討活體軟組織之黏彈特性；此系統的設計包括儀器設計及數位訊號處理軟體的建立及發展。本研究之理論基礎與原理包括連體力學、黏彈理論、波動理論、通訊及數位訊號處理，利用都卜勒超音波原理量測軟組織之位移振幅與相位變化，並從振幅與相位梯度計算出軟組織之黏彈特性。計劃之特定目標包括：1) 設計一套脈波式都卜勒超音波系統：包括超音波探頭、脈波訊號產生器、功率放大器、隔離電路、低頻振動器與儀器放大器的設計，以及都卜勒訊號解調、訊號處理的軟體；2)系統校準與測試以及都卜勒訊號之模擬與分析；3)利用類軟組織之假體，進行系統化之實驗與統計分析，探討系統之可行性。

在系統硬體校準方面包括每一個組件之校準與測試，以及系統整體訊號雜訊比的量測；數位訊號處理軟體包括都卜勒訊號之解調、內部組織位移與黏彈性之計算、超音波在組織中的傳遞速度及衰減係數的估計。在假體實驗方面，利用中心頻率為3.5MHz之超音波探頭與三種之振動頻率(10、50、100Hz)，量測三種不同硬度(最硬、中硬、軟)之假體的黏彈特性。為了驗證都卜勒超音波系統之可行性，同時利用材料測試機(Rheometer SR5)量測假體組織的黏彈特性，並比較兩系統之結果。

結果顯示:超音波在三種假體組織的波速為1476.2 ± 12.60m/s (軟)、1543.4 ± 2.73m/s(中硬)、1647.3 ± 23.87m/s(最硬)；利用振幅衰減方法所估計之衰減係數為0.3105dB/mm(中硬)、0.3163dB/mm(軟)、0.3562dB/mm(最硬)。利用材料測試機量測之結果顯示:每種假體組織之彈性係數隨頻率增加而增加，但是黏性隨頻率增加而降低；三種假體組織之彈性模數與黏性係數大小順序皆為: 最硬>中硬>軟。利用脈波式都卜勒超音波量測結果顯示:三種假體組織之彈性模數與黏性係數皆隨振動頻率的增加而增加；其中，以最硬的假體組織之彈性模數與黏性係數最大，而中硬與軟的假體組織之彈性模數與黏性係數，兩者無明顯差異。由於超音波在組織中的傳遞速度與組織的彈性模數有關，彈性模數愈大，波速愈快；而超音波的衰減與組織的黏性係數有關，黏性係數愈大，能量衰減愈大，因此本實驗量測之結果符合實際的現象。比較都卜勒超音波系統與材料測試之結果發現:兩種方法所量測的彈性模數皆隨振動頻率之增加而上升，能量的損失也隨頻率的增加而上升；但兩種方法所量測之黏性係數，結果並無一致性。因為利用都卜勒超音波系統所量測之組織黏性與彈性結果，與本研究所使用之線性黏彈理論、平面波原理、超音波在組織中的散射原理、以及材料等向均質性之假設有關，因此都卜勒超音波系統之可行性仍是可以接受的。

目前都卜勒超音波系統最小可量測的大小為1.1mm´6mm´6mm。從本研究之初步結果可提供設計及發展脈波式都卜勒超音波量測系統之規格參考。在未來之研究，仍需要進行大量的假體、離體與活體組織的實驗，及更進一步的訊號處理技術，以提供系統發展與設計的修改與改善。

The viscoelastic properties of biological tissue are critical to specific functional characteristics for each living organ and fundamental in biomechanical modeling of tissue behavior, such as finite element analysis of loadbearing at the prosthesis-stump interface, biomaterials and artificial organs design. Currently invasive methods are frequently used to measure biomechanical properties in vitro, which are deviated widely from those in living status and are difficult to be applied in practice. Therefore, it is important and valuable to design and develop innovatively a cost-effective, non-invasive and in vivo measuring technology for the quantitative investigation on viscoelasticity of living soft tissues. During the last decade, sonoelastic’ quantification has being investigated by the Doppler ultrasonic technology with low frequency tissue vibration. It seems to be prospective in the development of non-invasive, in vivo measuring technology for viscoelasticity.

The purpose of this research was to design and develop a PW Doppler ultrasonic measuring system for the quantitative investigation and determination of the elasticity and viscosity of living soft tissue. Theories in continuum mechanics, viscoelastic biosolids, wave propagation, Doppler ultrasound, communication and DSP form the basis to provide underlying principles for the development of this research. Instrumentation design and DSP algorithm were developed to establish the Doppler ultrasonic system and to quantitatively determine the amplitude and phase of internal tissue motion displacement through externally low-frequency vibration on the surface of soft tissues. The elasticity and viscosity are then derived and estimated from the amplitude and phase gradients of tissue displacement. More specifically, this research was aimed to 1) to develop a PC-based PW Doppler ultrasound system, including ultrasonic transducer, burst signal generator, power amplifier, isolation limiter, instrumentation amplifier, tissue vibrator, and algorithms of Doppler signal demodulation and estimation of tissue displacement and elasticity and viscosity; 2) to conduct system calibration and analytical simulation on the Doppler signal in response to ultrasonic signal through a vibrated soft tissue medium; and 3) to investigate the feasibility of system on gel phantom.

The PW Doppler Ultrasonic system was calibrated and evaluated to characterize the functional performance of system. The testing and calibration of each individual component were conducted for the performance evaluation. The signal-to-noise ratio of the overall system was evaluated for the correction of estimating Doppler signal. The software of DSP algorithms was developed for Doppler frequency demodulation, estimation of internal tissue displacement for elasticity and viscosity, attenuation coefficient and velocity measurements. The sonoelastic determination of elasticity and viscosity was conducted on three types of hard, middle and soft gel phantoms by the developed PW Doppler ultrasonic system with a 3.5MHz transducer and the low-frequency tissue vibrator. The experimental measurements included: 1) ultrasonic velocity and attenuation coefficient on the gel phantom to determine the target depth for compensating the ultrasonic attenuation; and 2) amplitude and phase of internal displacement on phantom with low-frequency vibration at 10, 50 and 100Hz applied to the surface of gel phantom. Moreover, for the validity of Doppler ultrasonic system, the values of elasticity and viscosity determined from the phantom material testing were compared with these estimated from the PW Doppler ultrasonic system.
The results of ultrasonic speed measurement show that the average speeds with standard deviations are 1476.2 ± 12.60m/s for soft gel, 1543.4 ± 2.73m/s for middle gel and 1647.3 ± 23.87m/s for hard gel. The measurement of attenuation coefficient by using loss of amplitude method is 0.3105 dB/mm for middle gel, 0.3163 dB/mm for soft gel and 0.3562dB/mm for hard gel. The viscoelastic properties of hard gel phantom measured from PW Doppler ultrasonic system show that the elastic modulus and tand are 2.2MPa and 0.01 at 10Hz vibration frequency, 74.92MPa and 0.05 at 50Hz vibration frequency, and 251.38MPa and 0.05 at 100Hz vibration frequency. The middle gel phantom shows that the elastic modulus and tand are 0.1kPa and 0.003 at 10Hz vibration frequency, 0.74kPa and 0.047 at 50Hz vibration frequency, and 73kPa and 0.099 at 100Hz vibration frequency. The soft gel phantom indicates the elastic modulus and tand are 0.5kPa and 0.07 at 10Hz vibration frequency, 0.52kPa and 0.023 at 50Hz vibration frequency, and 9.6kPa and 0.018 at 100Hz vibration frequency. The results from material testing show that the elastic modulus and energy loss for each gel phantom are increasing with an increasing frequency, and the viscosity is decreasing with an increasing frequency. The elastic modulus and viscosity are increasing in the order from soft, middle to hard gel phantoms. The results by PW Doppler ultrasonic measuring show that the elastic modulus and viscosity for each gel phantom are increasing with an increasing frequency, and the energy loss of middle gel phantom is increasing with an increasing frequency. The results from comparing the PW Doppler ultrasonic measuring to material testing indicate that elastic modulus and energy loss for each gel phantom are increasing with an increasing frequency. However, the viscosity resulted from PW Doppler ultrasound is no agreed with that from material testing. Since the sonoelastic method is still in the experimental development stage, the viscoelastic estimation could inaccuracy due to premature sonoelastic measurement. In this research, the estimated elasticity and internal friction resulted from the study are within the reasonable range reported by the literature. Therefore, the PW Doppler ultrasonic measuring system developed in this research is likely to be feasible for the viscoelastic determination of living soft tissue.

The objectives of this innovative research study are to investigate the feasibility of using PW Doppler ultrasonic system to quantitatively measure the viscoelasticity of soft tissues in vivo, also to provide improved system specifications for the design of a useful PW Doppler ultrasonic instrumentation for practical implementation. In this research, the ultrasound transducer with a central frequency of 3.5MHz and beam width of 6mm provides a measuring resolution of 1.1mm ´ 6mm ´ 6mm. This resolution can be improved through an increasing central frequency and decreasing beam width design. The future study work is recommended to stepwisely modify and improve each subsystem or modulus. The outcomes are expected to provide basic data and fundamental information to improve our understanding in biomechanics of in vivo soft tissue and medical sciences, also contribute to useful application in clinical diagnosis and development of bioengineering and biological technology.

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