高頻超音波血流成像

High Frequency Ultrasonic Flow Imaging

李承翰(Chen-Han Li)

指導教授 ： 李百祺

國立臺灣大學/電機資訊學院/電機工程學研究所/碩士(2005年)

https://doi.org/10.6342/NTU.2005.02428

摘要

在人類疾病研究、基因體研究、藥物發展等生物醫學研究上，常使用以老鼠或是其他小動物的動物模型，因此若能有一套高解析度、高靈敏度以及非侵入式小動物成像系統，可提供上述研究領域很大的幫助，並減少對實驗動物的犧牲與傷害。高頻超音波成像系統（>20MHz）由於有較高的空間解析度以及流速解析度，使我們能即時觀察小動物體內微細的組織與血流情況。在高頻超音波血流成像方面，偵測緩慢血流時會遇到一些問題。目前高頻超音波掃描的方式，是將單一固定聚焦的探頭以馬達帶動來做機械式的掃瞄，此種掃掠式掃瞄方式容易造成緩慢血流信號與組織信號發生混疊的情況，進而造成彩色都卜勒成像中血流流速估計的誤差。此外，由於微細血管內血流的超音波散射信號十分微弱，因此在血流成像上難以獲得較高的訊雜比。本研究的目標在於進一步改進小動物血流成像，期望提升系統偵測緩慢血流速度的能力，以及提高偵測微小血管的靈敏度。為了提升彩色都卜勒成像對於微細緩慢血流的偵測能力，我們針對掃描方式以及信號處理方面來做探討。掃掠式掃瞄可分為「分段掃掠式掃描」與「連續掃掠式掃描」兩種方式，為了能有效區分緩慢血流信號與組織信號，以利緩慢血流流速的估計，我們最後選擇使用低掃描速度（2mm/sec）的連續掃掠式掃描，使我們能在彩色都卜勒影像上偵測到流速5mm/sec 以下的微血管。在對比劑成像方面，使用對比劑可增加血流成像的訊雜比，對比劑非線性成像技術可進ㄧ步提升偵測血流的靈敏度。我們採用自製的微脂體來當作高頻對比劑，此對比劑可由製程控制微氣泡的尺寸大小，使微氣泡的共振頻率接近高頻超音波的頻率範圍( 20MHz~50MHz )。此外，利用微氣泡對正、負聲壓的非線性響應，我們使用脈衝反相基頻成像技術來壓制組織信號而留下微氣泡信號，以提升血流與組織在影像上的對比度以及增加偵測血流的靈敏度。體外的仿體實驗結果顯示，氣泡直徑大小1μm 的微脂體在高頻超音波(25~50MHz)下可有效增強流體信號。使用脈衝反相基頻成像技術可成功壓制組織信號，與傳統的基頻成像比較，當發射信號為頻率範圍25~50MHz 的十個週期正弦波時，脈衝反相基頻成像可提升流體與組織的對比度7~18 dB，隨著發射信號週期數的提升，其對比度提升效果越佳。在活體實驗部份，我們發現微脂體微氣泡在血液中會發生破裂的現象，無法有效增強血流散射信號，微氣泡在血液中球殼內外部的滲透壓不等可能是造成微氣泡破裂的原因之一，針對此問題我們必須改變微氣泡內部的滲透壓，期望能將對比劑成功應用在小動物血流成像上，以達到提升血流偵測靈敏度的目的。

關鍵字

高頻超音波 ； 小動物影像 ； 都卜勒超音波 ； 掃掠式掃描 ； 對比劑成像 ； 微脂體 ； 脈衝反相基頻成像

並列摘要

Small animal models have been used extensively in disease research, genomics research, drug development, and developmental biology. A non-invasive, small animal imaging system with high spatial resolution and high sensitivity is beneficial to the above-mentioned research. With such a system, the need to sacrifice animals can be reduced. The high frequency ultrasound imaging system (>20MHz) is ideal for such applications. However, one of the major limitations is the ability to detect slow and weak flows. A mechanical swept-scan technique is adopted in
our study, but the continuous movement of the transducer during data acquisition also potentially causes ambiguities in the Doppler spectrum. In addition, it is difficult to obtain high signal-to-noise ratio in this case
due to weak backscattering in micro circulation. Therefore, the main goal of this study is to improve the high frequency ultrasonic flow imaging on small animals in both areas. First, the scanning technique and signal
processing on color Doppler imaging for improvement of slow flow estimation is discussed. The swept-scan technique includes “block swept-scan” and “continuous swept-scan”. Continuous swept-scan with slow scanning velocity (2mm/sec) is found to be desired for slow flow
slower than 5mm/sec. On the other hand, contrast agents are used to enhance the signal-to-noise ratio and develop non-linear imaging methods. Liposome micro-bubbles are made in-house as the high frequency ultrasonic contrast agent. Based on in vitro results, it is shown that liposome bubbles can enhance the back-scattering signals in flow region at high frequencies (20~50MHz). The pulse-inversion based fundamental imaging technique is also tested to improve the contrast-to-tissue ratio. Compared to fundamental imaging, the contrast-to-tissue ratio can be
improved by 7~18dB. For the in-vivo experiments, on the other hand, the liposome bubble appears to break in the blood. So the contrast imaging of small animal is not as effective. The osmosis pressure is considered to be the major problem, and improving the effectiveness for in vivo flow imaging will be the primary future work of this research.

並列關鍵字

High frequency ultrasound ； Small animal imaging ； Doppler ultrasound ； Swept-scan ； Contrast imaging ； Liposome ； Pulse-inversion based fundamental imaging

參考文獻

[2] D. A. Knapik, B. Starkoski, C. J. Palvin, and F. S. Foster, ”A 100-200 MHz Ultrasound Biomicroscope”, IEEE Trans. on Ultrasonics, Ferroelectrics, and Frequency Control, Vol. 47, No. 6, pp.1540-1549, Nov. 2000.

[4] W. F. Cheng, C. A. Chen, C. N. Lee, T. M. Chen, F. J. Hsieh, and C. Y. Hsieh, “Vascular Endothelial Growth Factor in Cervical Carcinoma”, Obstet Gynecol, Vol. 93, pp. 761-765, 1999.

[5] C. A. Chen, W. F. Cheng, C. N. Lee, T. M. Chen, C. C. Kung, F. J. Hsieh, and C. Y. Hsieh, “Serum Vascular Endothelial Growth Factor in Epithelial Ovarian Neoplasms: Correlation with Patient Survival”, Gynecol Oncol, Vol. 74, No. 2, pp. 235-240, 1999.

[6] T. Nakamura, Y. Mochizuki, H. Kanetake, and S. Kanda, “Signals via FGF Receptor 2 Regulate Migration of Endothelial Cells”, Biochem Biophys Res Commun, Vol. 289, No.4, pp. 801-806, 2001.

[9] C. K. L. Phoon, O. Aristizabal, and D. H. Turnbull, “40 MHz Doppler Characterization of Umbilical and Dorsal Aortic Blood Flow in the Early Mouse Embryo“, Ultrasound in Medical & Biology, Vol. 26, No. 8, pp. 1275-1283, Oct. 2000.