高頻超音波都卜勒血流估計一般以掃掠式掃描法(swept-scan)來擷取流速資訊，而超音波探頭的橫向移動會造成時變的組織反射信號，進而造成slow-time方向上組織訊號頻譜加寬(spectral broadening)的效應，所以當使用雜波高通濾波器(wall filter)來濾除組織信號的時候，必須把wall filter的截止頻率提高，因此造成低流速的血流信號被濾除，導致所偵測出來的血流資訊也會不正確。為了抑制使用掃掠式掃描法時所產生的組織頻譜加寬效應，本研究採用對比劑非線性成像方法來達到組織抑制效果。三倍頻發射相位法利用外加的三倍頻發射信號搭配一適當的相位與振幅大小以有效地抑制組織諧波信號，基頻脈衝反相都卜勒(pulse inversion Doppler, PID)法則將組織線性信號與微氣泡特殊非線性信號在都卜勒頻譜上區分開來以減少組織干擾，此時wall filter設計便能調整以保留較低流速的血流信號，進而提升都卜勒偵測能力。結果顯示在三倍頻發射相位法的部分，有組織抑制經過1/4倍濾波截止頻率的wall filter和沒有組織抑制經過1倍濾波截止頻率的wall filter所得到之signal to clutter ratio (SCR)有0.5 dB(p<0.27)的提升，而其color pixel density (CPD)有2.3 %(p<0.3)的提升。在基頻脈衝反相技術的部分，使用PID在馬達移動速度為8 mm/s的情形，SCR有3.2 dB(p<0.03)的提升，而CPD則有31 %(p<0.007)的提升。

High-frequency ultrasound Doppler estimation generally uses swept-scan mode to acquire the flow information. In swept-scan mode, the lateral scanning of ultrasonic transducer results in tissue spectral broadening in the Doppler spectrum. To remove the tissue signal, the cut-off frequency of wall filtering has to increase, leading to the loss of low-velocity blood signal and thus incorrect blood flow detection. To alleviate the effect of wall filtering on low-velocity blood signal, the suppression of tissue Doppler signal can be helpful. With the method of 3f0 transmit phasing, the tissue harmonic intensity is effectively suppressed by including additional 3f0 transmit signal with proper phase and amplitude. With the method of fundamental pulse-inversion Doppler (PID), the bubble signal can be isolated from the tissue signal in the Doppler domain to avoid clutter interference. In this study, results indicate that the nonlinear tissue suppression helps to retain the low-velocity blood flow signal in power Doppler imaging and thus improves the efficacy of blood flow detection. Results indicate that, the method of 3f0 transmit phasing has already improved the signal-to-clutter ratio (SCR) by 0.5 dB(p<0.27) and a color pixel density (CPD) by 2.3 %(p<0.3). With the PID method, the SCR increases by 3.2 dB(p<0.03) and the CPD increases by 31 %(p<0.007) in the case of 8-mm/s motor lateral velocity.

[1] Lockwood, G.R., Ryan, L.K., Hunt, J.W., Foster, F.S., “High
frequency ultrasound vascular tissue characterization”, Ultrasonics Symposium Proceedings 3, pp. 1409-1412, 1990.
[2] Harland, C.C., Bamber, J.C., Gusterson, B.A., Mortimer, P.S., “High
frequency, high resolution B-scan ultrasound in the assessment of
skin tumours”, British Journal of Dermatology 128 (5), pp. 525-532,
1993.
[3] Szymańska, E., Nowicki, A., Mlosek, K., Litniewski, J.,
Lewandowski, M., Secomski, W., Tymkiewicz, R., “Skin imaging
with high frequency ultrasound - Preliminary results”, European
Journal of Ultrasound 12 (1), pp. 9-16, 2000.
[4] Passmann, C., Ermert, H., “Adaptive 150 MHz ultrasound imaging
of the skin and the eye using an optimal combination of short
pulse mode and pulse compression mode”, Proceedings of the
IEEE Ultrasonics Symposium 2, pp. 1291-1294, 1995.
[5] Vogt, M., Ermert, H., “Application of high frequency broadband
ultrasound for high resolution blood flow measurement”,
Proceedings of the IEEE Ultrasonics Symposium 2, pp. 1243-1246,
1997.
[6] Rasmussen, K., “Methodological problems related to measurement
of quantitative blood flow with the ultrasound Doppler
technique”, Scandinavian Journal of Clinical and Laboratory
Investigation 47 (4), pp. 303-309, 1987.
[7] Rasmussen, K., “Non-invasive quantitative measurement of blood
flow and estimation of vascular resistance by the Doppler
ultrasound method. Methodological studies and clinical
application on the fetus and the transplanted kidney allograft.”,
Danish medical bulletin 39 (1), pp. 1-14, 1992.
[8] Kruse, D.E., Silverman, R.H., Fornaris, R.J., Jackson Coleman, D.,
Ferrara, K.W., “A swept-scanning mode for estimation of blood
velocity in the microvasculature”, IEEE Transactions on
Ultrasonics, Ferroelectrics, and Frequency Control 45 (6), pp.
1437-1440, 1998.
[9] Newhouse, V.L., Reid, J.M., “Invariance of Doppler bandwidth
with flow axis displacement”, Ultrasonics Symposium Proceedings 3
, pp. 1533-1536, 1990.
[10] Rajaonah, Jean-Claude, Dousse, Bruno, Meister, Jean-Jacques,
“Compensation of the bias caused by the wall filter on the mean
Doppler frequency”, IEEE Transactions on Ultrasonics,
Ferroelectrics, and Frequency Control 41 (6), pp. 812-819, 1994.
[11] Kruse, D.E., Ferrara, K.W., “A new high resolution color flow
system using an eigendecomposition-based adaptive filter for
clutter rejection”, IEEE Transactions on Ultrasonics,
Ferroelectrics, and Frequency Control 49 (10), pp. 1384-1399,
2002.
[12] 李承翰，“高頻超音波血流成像”，國立台灣大學，碩士論文，民
國94 年。
[13] Needles, A., Goertz, D.E., Cheung, A.M., Foster, F.S., “Interframe
Clutter Filtering for High Frequency Flow Imaging”, Ultrasound
in Medicine and Biology 33 (4), pp. 591-600, 2007.
[14] 陳彥甫，“超音波小動物影像之血流計算及應用”，國立台灣大
學，碩士論文，民國92年。
[15] Cherin, E., Poulsen, J.K., Van der Steen, A.F.W., Foster, F.S.,
“Comparison of nonlinear and linear imaging techniques at high
frequency”, Proceedings of the IEEE Ultrasonics Symposium 2, pp.
1639-1644, 2000.
[16] De Jong, N., “Improvements in ultrasound contrast agents”,
IEEE Engineering in Medicine and Biology Magazine 15 (6), pp.
72-82, 1996.
[17] Forsberg, F., Shi, W.T., Goldberg, B.B., “Subharmonic imaging of
contrast agents”, Ultrasonics 38 (1), pp. 93-98, 2000.
[18] Nielsen, M.B., Bang, N., “Contrast enhanced ultrasound in liver
imaging”, European Journal of Radiology 51 (SUPPL.), pp. S3-S8,
2004.
[19] Needles, A., Goertz, D.E., Karshafian, R., Cherin, E., Brown, A.S.,
Burns, P.N., Foster, F.S., “High-Frequency Subharmonic
Pulsed-Wave Doppler and Color Flow Imaging of Microbubble
Contrast Agents”, Ultrasound in Medicine and Biology 34 (7), pp.
1139-1151, 2008.
[20] Christopher, T., “Source prebiasing for improved second
harmonic bubble-response imaging”, IEEE Transactions on
Ultrasonics, Ferroelectrics, and Frequency Control 46 (3), pp.
556-563, 1999.
[21] Eckersley, R.J., Chin, C.T., Burns, P.N., “Optimising phase and
amplitude modulation schemes for imaging microbubble
contrast agents at low acoustic power”, Ultrasound in Medicine
and Biology 31 (2), pp. 213-219, 2005.
[22] Borsboom, J.M.G., Bouakaz, A., De Jong, N., “Pulse subtraction
time delay imaging method for ultrasound contrast agent
detection”, IEEE Transactions on Ultrasonics, Ferroelectrics, and
Frequency Control 56 (6), art. no. 5075098, pp. 1151-1158, 2009.
[23] Simpson, D.H., Chin, C.T., Burns, P.N., “Pulse inversion Doppler:
a new method for detecting nonlinear echoes from microbubble
contrast agents”, IEEE Transactions on Ultrasonics, Ferroelectrics
, and Frequency Control 46 (2), pp. 372-382, 1999.
[24] Mahue, V., Mari, J.M., Eckersley, R.J., Meng-Xing Tang,
“Comparison of pulse subtraction doppler and pulse inversion
doppler”, IEEE Transactions on Ultrasonics, Ferroelectrics, and
Frequency Control 58 (1), pp. 73-81, 2011.
[25] 王裕鈞，“使用三倍頻發射相位法於組織諧波信號分析”，國立台
灣科技大學，碩士論文，民國96年。
[26] Li, C.-H., Liao, A.-H., Ho, J.-A., Li, P.-C., “Ultrasonic
pulse-inversion fundamental imaging with liposome
microbubbles at 25-50 MHz”, Proceedings - IEEE Ultrasonics
Symposium 1, art. no. 1602929, pp. 621-624, 2005.
[27] Frijlink, M.E., Goertz, D.E., De Jong, N., Van Der Steen, A.F.W.,
“Pulse inversion sequences for mechanically scanned
transducers”, IEEE Transactions on Ultrasonics, Ferroelectrics,
and Frequency Control 55 (10), art. no. 4638902, pp. 2154-2163,
2008.
[28] Yoo, Y.M., Managuli, R., Kim, Y., “Adaptive clutter rejection for
ultrasound color Doppler imaging”, Progress in Biomedical Optics
and Imaging - Proceedings of SPIE 5750, art. no. 15, pp. 139-147,
2005.
[29] Pinter, S.Z., Lacefield, J.C., “Understanding quantification of
microvascularity with high-frequency power Doppler
ultrasound”, Progress in Biomedical Optics and Imaging –
Proceedings of SPIE 7265, art. no. 72650U, 2009.
[30] Bruce, M., Averkiou, M., Tiemann, K., Lohmaier, S., Powers, J.,
Beach, K., “Vascular flow and perfusion imaging with ultrasound
contrast agents”, Ultrasound in Medicine and Biology 30 (6), pp.
735-743, 2004.
[31] Kang, S.-T., Yeh, C.-K., “A maleimide-based in-vitro model for
ultrasound targeted imaging”, Ultrasonics Sonochemistry 18 (1),
pp. 327-333, 2011.
[32] Lu, S.-C., Ho, J.-A., Yeh, C.-K., “Echogenic liposomes in
high-frequency ultrasound imaging”, Proceedings - IEEE
Ultrasonics Symposium , art. no. 4410127, pp. 2203-2206, 2007.