醫用超音波諧波影像常受限於其較低的訊雜比(SNR)以及不足的微氣泡顯影劑與背景組織之間對比度(CTR)，三倍頻發射相位法可藉由發射基頻與可改變相位的三倍頻信號來產生頻率和與頻率差成分來抑制或增強組織諧波信號以改善諧波影像的品質，本研究中我們進一步探討三倍頻發射相位法與Golay編碼波型結合的設計方式與對諧波影像的影響。
Golay編碼應用在一般線性影像上是藉由發射兩組由+1與1位元波形構成的脈衝序列，並將接收信號經由匹配濾波器做脈衝壓縮以加強聲束主瓣(Mainlobe)的強度來提升訊雜比，並消去軸向旁瓣(Range Sidelobe)的干擾。而在諧波成像中為達到Golay編碼效果，基頻與三倍頻發射信號的相位將必須分別往前與往後調整90∘以產生1位元波形的諧波信號編碼。本研究利用組織與顯影劑的諧波模擬來驗證該Golay編碼設計並以實驗量測對應的諧波信號與影像。
研究結果顯示Golay編碼配合三倍頻相位法依其編碼長度不同能有效的改善訊雜比到8~14 dB，並提升影像之顯影劑對組織對比度達14~16 dB，但因微氣泡特殊的非線性振盪導致顯影劑區域仍殘留明顯的軸向旁瓣，因此對顯影劑諧波影像品質造成一定的劣化。

Ultrasonic harmonic image is limited by low signal-to-noise ratio (SNR) and insufficient contrast-to-tissue ratio (CTR). The method of 3f0 transmit phasing utilizes an additional 3f0 transmit signal to provide mutual cancellation between the frequency-sum component and frequency-difference component of tissue harmonic signal to improve image quality. This paper presents a technique that uses Golay code in third harmonic (3f0) transmit phasing for harmonic imaging with ultrasound.
In linear imaging, Golay coded transmission is achieved by transmitting two coded sequences comprising of +1 and -1 pulses. The echoes from the two coded transmissions are processed with matched filter and are summed to increase mainlobe SNR. The complementary range sidelobes are also cancelled in the sum. To produce the -1 pulse of the Golay code for the harmonic signal in 3f0 transmit phasing, the phase shift of 90 degrees is added into the fundamental transmit phase and subtracted from the 3f0 transmit phase, respectively. Both simulations and experiments are performed to validate the Golay-encoded transmit waveform for the 3f0 transmit phasing.
Our results show that, depending on the code length, the Golay code in combination with the 3f0 transmit phasing can enhance SNR by 8~14 dB together with the CTR improvement of 14~16 dB. Nevertheless, due to unique nonlinear oscillation of the microbubbles, the residual range sidelobes remain in the contrast region and thus lead to image degradation.

Keywords: 3f0 transmit phasing, Golay code, contrast harmonic image, SNR, Contrast-to-tissue ratio (CTR)

[1] C. A. Cain, “Ultrasonic reflection mode imaging of the nonlinear parameter B/A: I. A theoretical basis,” J. Acoust. Soc. Amer., vol. 80, no. 1, pp. 28-32, July 1986.
[2] R. T. Beyer and S. V. Letcher, Nonlinear acoustics. New York: Academic, 1969, pp. 202-230.
[3] M. E. Haran and B. D. Cook, “Distortion of finite amplitude ultrasound in lossy media,” J. Acoust. Soc. Amer., vol. 73, no. 3, pp. 774-779, March 1983.
[4] P. H. Chang, K. K. Shung, S. J. Wu et al., “Second harmonic imaging and harmonic Doppler measurements with Albunex,” IEEE Trans. Ultrason., Ferroelect., Freq. Contr., vol. 42, no. 6, pp. 1020–1027, Nov. 1995.
[5] N. de Jong, “Improvements in ultrasound contrast agents,” IEEE Eng. Med. Biol., vol. 15, no. 6, pp. 72–82, 1996.
[6] W. T. Shi and F. Forsberg, “Ultrasonic characterization of the nonlinear properties of contrast microbubbles,” Ultrasound Med. Biol., vol.26, no. 1, pp. 93–104, 2000.
[7] F. Tranquart, N. Grenier, V. Eder and L. Pourcelot, “Clinical use of ultrasound tissue harmonic imaging,” Ultrasound in Med. & Biol., vol.25, no. 6, pp. 889–894, 1999.
[8] Bruce M, Averkiou M., Tiemann K, Lohmaier S,Powers J,Bearch K ‘’Vascular flow and perfusion imaging with ultrasound contrast agents,” Ultrasound in Med. & Bio.l, vol. 30, no. 6, pp. 735–743, 2004.
[9] A. Bouakaz. S. Frigstad, F.J. Ten Cate ans N. de Jong,‘’Superharmonic imaging:A new imaging technique for improved contrast detection” Ultrasound in Med. & Bio.l, vol. 28, no. 1, pp. 59-68, 2002.
[10] D. E. Goertz, M. E. Frijlink, D. Tempel, V. Bhagwandas, A. Gisolf, R. Krams, N. de Jong and A. F. W. van der Steen, “Subharmonic contrast intravascular ultrasound for vasa vasorum imaging, ” Ultrasound Med. Biol., vol. 33, no. 12, pp. 1859-1872, 2007.
[11] C. C. Shen and P. C. Li, “Harmonic leakage and image quality degradation in tissue harmonic imaging,” IEEE Trans. Ultrason., Ferroelect., Freq. Contr., vol. 48, no. 3, pp. 728–736, May 2001.
[12] R. J. Eckersley, C. T. Chin, and P. N. Burns, “Optimising phase and amplitude modulation schemes for imaging microbubble contrast agents at low acoustic power,” Ultrasound Med. Biol.,vol. 2, pp. 213–219, 2005.
[13] Borsboom JM, Bouakaz A, de Jong N ‘’Pulse subtraction time delay imaging method for ultrasound contrast agent detection,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control, vol. 56, no. 6, pp. 1151–1158, 2009.
[14] O. Couture, J. F. Aubry, G. Montaldo, M. Tanter and M. Fink, “Suppression of tissue harmonics for pulse-inversion contrast imaging using time reversal,” Phys. Med. Biol., vol.53, pp. 5469–5480, 2008.
[15] Sun Y, Kruse DE, Ferrara KW.‘’Contrast imaging with chirped excitation.,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control, vol. 54, no. 3, pp. 520–529, 2007
[16] Shen CC, Chiu YY.,“Design of chirp excitation waveform for dual-frequency harmonic contrast detection.,” IEEE Trans. Aerosp. Electron. Syst., vol. 56, no. 10, pp.2198–2206, Oct 2009.
[17] A . W. Rihaczek and R. M. Golden,“Range sidelobe suppression for Barker codes,” IEEE Trans. Aerosp. Electron. Syst., vol. 7, no. 6, pp.1087–1092, May 1971.
[18] Leavens C, Williams R, Foster FS, Burns PN, Sherar MD.‘’Golay pulse encoding for microbubble contrast imaging in ultrasound.,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control, vol. 54, no. 10, pp. 2082–2090, 2007.
[19] Y. Li and J. A. Zagzebski, “A Frequency Domain Model for Generating B-Mode Images with Array Transducers,” IEEE Trans. Ultrason., Ferroelect., Freq. Contr., vol. 46, no. 3, pp. 690-698, May. 1999.
[20] P. C. Li, C. C. Shen and S. W. Huang, “Waveform design for ultrasonic pulse-inversion fundamental imaging,” Ultrason Imaging, vol. 29, pp. 73-86, 2007.
[21] K. Chetty, J. V. Hajnal and R. J. Eckersley, “Investigating the nonlinear microbubble response to chirp encoded, multipulse sequences,” Ultrasound in Med. & Bio.l, vol. 32, no. 12, pp. 1887–1895, 2006.
[22] S. van der Meer, M. Versluis, D. Lohse, C.T. Chin, A. Bouakaz, and N. de Jong, “The resonance frequency of SonoVue™ as observed by high-speed optical imaging,” Proc. IEEE Ultrason. Symp., pp. 343–345, 2004.