使用定量超音波參數偵測血液凝固與血塊形成

Detection of Blood Coagulation and Clot Formation Using Quantitative Ultrasonic Parameters

黃執中(Chih-Chung Huang)

指導教授 ： 王士豪

中原大學/工學院/醫學工程研究所/博士(2007年)

https://doi.org/10.6840/cycu200700162

摘要

血液凝固是種極為複雜的過程。不正常的凝血會導致一些嚴重的併發症，例如增加出血的機率、造成血栓的形成或栓塞於人體循環系統。因此，發展有效的技術以應用於偵測早期血液凝固對於臨床診斷極為重要。由於超音波具有非侵入性與即時監控等能力，使得超音波組織特化技術提供達到此目標的可能方案。
本研究使用定量化超音波參數包含積體逆散射 (integrated backscatter)、衰減係數與聲速，同時偵測靜態血液凝固與血塊形成的過程。為提高偵測的靈敏性與準確性，我們使用5至50 MHz的超音波頻率偵測血容比介於25至55 %豬隻血液的凝固過程。誘發血液凝固機制是於24毫升的血液中添加12毫升(0.2 M)的氯化鈣溶液。實驗結果指出積體逆散射、衰減係數與聲速皆能清楚判別不同時期的凝血過程並對應於不同時期的物理與化學變化，其中包含紅血球的聚集效應，血容比的稀釋、血液的凝固與血塊的形成。超音波逆散射與衰減係數的量測結果也證實血容比於凝血機制中是一重要的實質因子，其可影響血液的黏度與超音波的逆散射特性。另外，高頻超音波展現較高的靈敏度於凝血的偵測。
本研究進一步完成動態的凝血偵測。使用10 MHz 脈衝式Doppler系統量測Doppler功率與Doppler流速的變化於攪動中的血液於凝血過程。Doppler功率與Doppler流速在凝血過程中分別呈現上升與下降的趨勢。造成Doppler功率上升的主要原因為血塊體積的增大與擾流的發生；而Doppler流速下降則是由於血液黏度的上升導致流體阻力的增加。為進一步探討流動狀態之血液凝固，使用超音波逆散射係數偵測流動中血液於血管仿體內之凝固過程，並將血流保持於層流狀態且控制剪速率為10 至 100 s–1。實驗結果顯示：較高的剪速率有礙於血液的凝固，並且降低血塊的生成率。當凝血機制啟動後，由流管內超音波逆散射訊號的空間變化發現血液由層流轉變為擾流的流動狀態。最後，超音波逆散射訊號之Nakagami統計模型被應用於動態血液凝固的偵測；結果顯示，Nakagami參數於流動中之血液為0.75±0.1，當血液發生凝固時，Nakagami參數上升到最大將近2.6±0.5。實驗證明超音波統計參數可偵測動態凝血的特性，提供未來應用於臨床偵測的可行性。

關鍵字

定量超音波參數 ； 血塊形成 ； 血液凝固 ； 血流 ； Doppler超音波

並列摘要

The coagulation of blood is a complex process during which solid clots are formed consequently. Disorders of blood coagulation however could lead to such complications as the increasing hemorrhage, thrombosis, and embolism in the circulation system. Therefore, it is crucial to develop techniques for early detecting the formation of vessel embolisms and assessing blood coagulation in clinical diagnoses. Ultrasonic tissue characterization techniques provide potential methods for achieving this goal due to its noninvasive and real-time capability.
The quantitative ultrasonic parameters including integrated backscatter, attenuation, and sound velocity were applied simultaneously to the detection of blood coagulation and clot formation in a static condition. With the aim of improving the sensitivity and accuracy when using ultrasound techniques to detect blood coagulation and clot formation, measurements were performed on porcine blood with hematocrits range from 25 to 55% using ultrasonic transducers frequencies from 5 to 50 MHz. A 24 ml aliquot of blood was placed in a container and 12 ml of 0.2 M CaCl2 solution was added to induce clot formation. Results indicated that the integrated backscatter, attenuation, and sound velocity can be divided into different stages, including red cells aggregation, reduction in hematocrit, blood coagulation, and clot formation corresponding to variations in the physical and chemical properties of the blood. In addition, this study demonstrates that blood hematocrit is a substantial factor affecting viscosity and backscattering properties of blood during coagulation capable of being discerned by ultrasonic backscattering and attenuation. In particular, measurements using high frequency ultrasound tended to exhibits a better sensitivity to detect the blood coagulation. Furthermore, the dynamic blood coagulation was studied by Doppler ultrasound and ultrasonic integrated backscatter. A 10 MHz pulsed Doppler ultrasound was applied to measure both Doppler power and Doppler velocity from stirred porcine blood of various hematocrits during clotting. During the period of blood coagulation and clot formation, the mean Doppler power and Doppler velocity, corresponding to variations in blood properties, were respectively demonstrated to be increasing and decreasing. The increase in Doppler power may be attributable to the combined effect of the increase in turbulent flow and scatterer size; the decrease in Doppler velocity is primarily due to the increase in flow resistance with increasing blood viscosity. To better elucidate blood clotting under a flow condition, ultrasonic backscattering were measured from the coagulating porcine blood circulated in a mock flow loop with various steady laminar flows at mean shear rates from 10 to 100 s–1. The results consistently demonstrate that higher shear rate tends to prolong the duration for blood to be coagulated and to decrease the rate of clot growth. Moreover, the blood flow was changed from laminar to turbulent during blood clotting discerned by spatial variations of ultrasound backscattering in the conduit. Finally, a Nakagami statistical model was used to detect blood coagulation as well. The Nakagami parameter was approximately 0.75±0.1 for flowing blood during the initial stage of blood coagulation, and increased rapidly to its highest level of 2.6±0.5 during clotting. These experimental results demonstrate the feasibility of using the ultrasonic statistical parameter for detecting blood coagulation from flowing blood and provide a novel method for further monitor the progress of clotting and thrombosis research in vivo.

並列關鍵字

clot formation ； Blood coagulation ； Doppler ultrasound ； blood flow ； quantitative ultrasonic parameters

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