高強度聚焦超音波所產生的空蝕作用可以人體內引發多種生物效應，該機制已知可被用於多種疾病的治療，諸如血栓塞溶解、腫瘤消蝕或是開啟血腦屏障以利人體吸收治療藥物等等，也因此，空蝕氣泡在體內的活動情形，牽涉到HIFU的治療功效。
在臨床的治療上，會以被動空蝕成像法監測空蝕氣泡的活動情形，藉此確保治療時的安全性及準確性，該方法係透過被動地接收空蝕氣泡所產生的信號來重建出空蝕氣泡能量在空間當中的分布，在所有的被動成像方法中，最為傳統方法為TEA-PCM，該方法透過延遲加總累加法來重建出空間當中空蝕能量分布的情形，因此又被稱為DSAI成像。雖然基於TEA的PCM是一種相當簡便的成像方法，然而該方法卻會使得被動空蝕圖像上出現X形狀假影而增加HIFU治療時監測空蝕作用的難度，此外，也受限於接收孔徑的尺寸，TEA-PCM有著較差的影像解析度，故該方法並不能非常精確地在HIFU治療中定位出空蝕信號產生的位置。
為了克服前述方法的缺點，本研究中提出了DMAS-VA被動成像法，該方法係一種結合BB-DMAS技術以及虛擬孔徑擴大(Virtual augmentation of aperture)的PCM成像方式，透過倍乘每個接收通道的相角以獲致將孔徑虛擬放大的效果，再搭配DMAS技術中自相關運算抑制旁瓣信號以及雜訊，以提升PCM影像解析度以及抑制X形狀假影。
透過模擬與實驗的結果，驗證了提出的方法相較於傳統的TEA-PCM有著更好的影像解析度及SNR，經由被動成像所成像之空蝕信號的軸向寬度在模擬及實驗當中分別從降至原本TEA波束成形器的26.18%和23%，而橫向寬度則分別降至成原本的19.80%及9.68%，SNR則分別提升了15.44dB和15.96dB，除此之外，該方法也能夠更準確地定位出空蝕信號的位置。同時，在空間當中含有多個空蝕氣泡的情況下，提出的DMAS-VA也能夠將多個氣泡的位置區別並定位出來。基於上述的優勢，我們所提出的方法具有在臨床的HIFU治療當中，可以更進一步的提升手術安全性以及準確性的潛力。

The acoustic cavitation induced by HIFU exposure can trigger a variety of bioeffects. This mechanism is known to be used in the treatment of various diseases, such as thrombolysis, tumor ablation and blood-brain barrier opening. Therefore, the activity of cavitation bubbles in the body is related to the therapeutic effect of HIFU therapy.
In clinical HIFU treatment, passive cavitation mapping (PCM) is widely used to monitor the activity of cavitation bubbles to ensure the safety and precision of treatment. PCM image shows the distribution of cavitation bubble energy in space, it is reconstructed by cavitation signal passively received by an acoustic array.
PCM based on TEA is the most common method to monitor cavitation activity during HIFU treatment, PCM-TEA reconstruct energy distribution through delay-sum and integral, it is also called DSAI.
TEA-PCM can be easily implement, however, this method causes X-shaped artifacts on image, which increases the difficulty of monitoring cavitation during HIFU treatment. Besides, TEA-PCM has poor image resolution, it is caused by the limited size of receiving aperture. Based on these reasons, TEA-PCM is a less precision method to monitor cavitation activity during HIFU treatment.
To overcome the mentioned problem, in this study, a novel adaptive beamformer, DMAS-VA, is proposed, which combines BB-DMAS technology and virtual augmentation of aperture.

The DMAS-VA beamformer virtually enlarge the size of receiving aperture by multiplying the phase angle of each receiving channel, and combine with the autocorrelation operation in DMAS technology to suppress side lobe signals and noise. By using DMAS-VA beamformer, the PCM image has better image quality, the X-shaped artifacts on PCM is also suppressed.
According to the simulation and experimental results, the proposed method is verified that can provide better image resolution and SNR than the conventional TEA-PCM. In the simulation, the axial width and lateral width is reduced to 26.18 % of TEA and 19.80 % of TEA, respectively. And the SNR increase 15.44dB. In the in vitro experiment, the axial width and lateral width is reduced to 23 % of TEA and 9.68 % of TEA, respectively. And the SNR increase 15.96 dB. The proposed method not only improve the image quality of PCM, also improve the accuracy of cavitation source localization. Meanwhile, DMAS-VA has the ability to distinguish different cavitation bubbles, even these bubbles are very close.
Based on this, our proposed method has the potential to further improve the safety and precision of surgery in clinical HIFU treatment.

[1] J. E. Kennedy. High-intensity focused ultrasound in the treatment of solid tumours. Nature Reviews Cancer, 5(4):321–327, 2005.
[2] McLaughlan, James Ross. (2008). An investigation into the use of cavitation for the optimisation of high intensity focused ultrasound (HIFU) treatments.
[3] Kennedy, J. E. et al. High-intensity focused ultrasound for the treatment of liver tumours. Ultrasonics 42, 931–935 (2004).
[4] Wu, F. et al. Preliminary experience using high intensity focused ultrasound for the treatment of patients with advanced stage renal malignancy. J. Urol. 170, 2237–2240 (2003).
[5] Gianfelice, D., Khiat, A., Boulanger, Y., Amara, M. & Belblidia, A. Feasibility of magnetic resonance imagingguided focused ultrasound surgery as an adjunct to tamoxifen therapy in high-risk surgical patients with breast carcinoma. J. Vasc. Interv. Radiol. 14, 1275–1282 (2003).
[6] C. A. Speed. Therapeutic ultrasound in soft tissue lesions. Rheumatology, 40(12):1331–1336, 2001.
[7] T. Watson. Ultrasound in contemporary physiotherapy practice. Ultrasonics, 48:321–329, 2008.
[8] van der Zee J. Heating the patient: a promising approach? Ann Oncol. 2002 Aug;13(8):1173-84. doi: 10.1093/annonc/mdf280. PMID: 12181239.
[9] Zhang HG, Mehta K, Cohen P, Guha C. Hyperthermia on immune regulation: a temperature's story. Cancer Lett. 2008 Nov 28;271(2):191-204. doi: 10.1016/j.canlet.2008.05.026. Epub 2008 Jul 1. PMID: 18597930.
[10] C. C. Coussios and R. A. Roy. Applications of acoustics and cavitation to noninvasive therapy and drug delivery. Annual Review of Fluid Mechanics, 40:395–420, 2008.
[11] Speed CA. Therapeutic ultrasound in soft tissue lesions. Rheumatology (Oxford). 2001 Dec;40(12):1331-6. doi: 10.1093/rheumatology/40.12.1331. PMID: 11752501.
[12] S. Datta, C. C. Coussios, L. E. McAdory, J. Tan, T. Porter, G. D. Courten-Myers, and C. K. Holland. Correlation of cavitation with ultrasound enhancement of thrombolysis. Ultrasound in Medicine & Biology, 32(8):1257–1267, 2006.
[13] N. McDannold, N. Vykhodtseva, and K. Hynynen. Targeted disruption of the blood-brain barrier with focused ultrasound: association with cavitation activity. Physics in Medicine and Biology, 51(4):793–807, 2006.
[14] A. Maxwell, C. Cain, A. P. Duryea, L. Yuan, H. S. Gurm, and Z. Xu. Noninvasive thrombolysis using pulsed ultrasound cavitation therapy – histotripsy. Ult Med Biol, 35(12):1982–1994, 2009.
[15] A. J. Coleman and J. E. Saunders. A review of the physical properties and biological effects of the high amplitude acoustic fields used in extracorporeal lithotripsy. Ultrasonics, 31(2):75–89, 1993.
[16] Z. Xu, Z. Fan, T. L. Hall, F. Winterroth, J. B. Fowlkes, and C. Cain. Size measurement of tissue debris particles generated from pulse ultrasound cavitational therapy – histotripsy. Ult Med Biol, 35(2):245–255, 2009.
[17] C. D. Ohl, M. Arora, R. Ikink, N. de Jong, M. Versluis, M. Delius, and D. Lohse. Sonoporation from jetting cavitation bubbles. Biophysical Journal, 91(11):4285–4295, 2006.
[18] J. McLaughlan, I. Rivens, T. Leighton, and G. ter Haar, “A study of bubble activity generated in ex vivo tissue by high intensity focused ultrasound,” Ultrasound Med. Biol. 36, 1327–1344 (2010).
[19] Jensen CR, Ritchie RW, Gy€ongy M, Collin JRT, Leslie T, Coussios CC. Spatiotemporal monitoring of high-intensity focused ultrasound therapy with passive acoustic mapping. Radiology. 2012;262:252–261.
[20] M. Gyongy and C. Coussios, "Passive Spatial Mapping of Inertial Cavitation During HIFU Exposure," in IEEE Transactions on Biomedical Engineering, vol. 57, no. 1, pp. 48-56, Jan. 2010, doi: 10.1109/TBME.2009.2026907.
[21] Kamimura HAS, Wu SY, Grondin J, Ji R, Aurup C, Zheng W, Heidmann M, Pouliopoulos AN, Konofagou EE. Real-Time Passive Acoustic Mapping Using Sparse Matrix Multiplication. IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Jan;68(1):164-177. doi: 10.1109/TUFFC.2020.3001848. Epub 2020 Dec 23. PMID: 32746182; PMCID: PMC7770101.
[22] C. C. Coussios, C. H. Farny, G. ter Haar, and R. A. Roy, “Role of acoustic cavitation in the delivery and monitoring of cancer treatment by highintensity focused ultrasound (HIFU),” Int. J. Hyperthermia, vol. 23, pp. 105–120, 2007.
[23] K. J. Haworth, K. B. Bader, K. T. Rich, C. K. Holland and T. D. Mast, "Quantitative Frequency-Domain Passive Cavitation Imaging," in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, vol. 64, no. 1, pp. 177-191, Jan. 2017, doi: 10.1109/TUFFC.2016.2620492.
[24] C. Arvanitis, N. McDannold, and G. Clement, “Fast passive cavitation mapping with angular spectrum approach,” J. Acoust. Soc. Amer., vol. 138, no. 3, p. 1845, Sep. 2015.
[25] M. Polichetti, F. Varray, B. Gilles, J. -C. Béra and B. Nicolas, "Use of the Cross-Spectral Density Matrix for Enhanced Passive Ultrasound Imaging of Cavitation," in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, vol. 68, no. 4, pp. 910-925, April 2021, doi: 10.1109/TUFFC.2020.3032345.
[26] Abadi SH, Haworth KJ, Mercado-Shekhar KP, Dowling DR. Frequency-sum beamforming for passive cavitation imaging. J Acoust Soc Am. 2018 Jul;144(1):198. doi: 10.1121/1.5045328. PMID: 30075672; PMCID: PMC6927771.
[27] Haworth KJ, Mast TD, Radhakrishnan K, Burgess MT, Kopechek JA, Huang SL, McPherson DD, Holland CK. Passive imaging with pulsed ultrasound insonations. J Acoust Soc Am. 2012 Jul;132(1):544-53. doi: 10.1121/1.4728230. PMID: 22779500; PMCID: PMC3407164.
[28] P. Boulos et al., "Weighting the Passive Acoustic Mapping Technique With the Phase Coherence Factor for Passive Ultrasound Imaging of Ultrasound-Induced Cavitation," in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, vol. 65, no. 12, pp. 2301-2310, Dec. 2018, doi: 10.1109/TUFFC.2018.2871983.
[29] J. Capon, "High-resolution frequency-wavenumber spectrum analysis," in Proceedings of the IEEE, vol. 57, no. 8, pp. 1408-1418, Aug. 1969, doi: 10.1109/PROC.1969.7278.
[30] Coviello C, Kozick R, Choi J, Gyöngy M, Jensen C, Smith PP, Coussios CC. Passive acoustic mapping utilizing optimal beamforming in ultrasound therapy monitoring. J Acoust Soc Am. 2015 May;137(5):2573-85. doi: 10.1121/1.4916694. PMID: 25994690.
[31] E. Lyka, C. M. Coviello, C. Paverd, M. D. Gray and C. C. Coussios, "Passive Acoustic Mapping Using Data-Adaptive Beamforming Based on Higher Order Statistics," in IEEE Transactions on Medical Imaging, vol. 37, no. 12, pp. 2582-2592, Dec. 2018, doi: 10.1109/TMI.2018.2843291.
[32] Lu S, Li R, Yu X, Wang D, Wan M. Delay multiply and sum beamforming method applied to enhance linear-array passive acoustic mapping of ultrasound cavitation. Med Phys. 2019 Oct;46(10):4441-4454. doi: 10.1002/mp.13714. Epub 2019 Aug 10. PMID: 31309568.
[33] Matrone G, Savoia AS, Caliano G, Magenes G. The delay multiply ands um beamforming algorithm in ultrasound B-mode medical imaging. IEEE Trans Med Imaging. 2015;34:940–949.
[34] A. Ramalli et al., "High dynamic range ultrasound imaging with real-time filtered-delay multiply and sum beamforming," 2017 IEEE International Ultrasonics Symposium (IUS), 2017, pp. 1-4, doi: 10.1109/ULTSYM.2017.8092339.
 
[35] M. Polichetti, F. Varray, J. Béra, C. Cachard and B. Nicolas, "Advanced Beamforming Techniques for Passive Imaging of Stable and Inertial Cavitation," 2018 IEEE International Ultrasonics Symposium(IUS),2018, pp. 1-4, doi: 10.1109/ULTSYM.2018.8579816.
[36] A. V. Telichko, T. Lee, M. Jakovljevic and J. J. Dahl, "Passive Cavitation Mapping by Cavitation Source Localization From Aperture-Domain Signals—Part I: Theory and Validation Through Simulations," in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, vol. 68, no. 4, pp. 1184-1197, April 2021, doi: 10.1109/TUFFC.2020.3035696.
[37] A. V. Telichko et al., "Passive Cavitation Mapping by Cavitation Source Localization From Aperture-Domain Signals—Part II: Phantom and In Vivo Experiments," in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, vol. 68, no. 4, pp. 1198-1212, April 2021, doi: 10.1109/TUFFC.2020.3035709.
[38] Che-Chou Shen, Pei-Ying Hsieh, Ultrasound Baseband Delay-Multiply-and-Sum(BB-DMAS) nonlinear beamforming, Ultrasonics 96 (2019) 165–174, https://doi.org/10.1016/j.ultras.2019.01.010
[39] 沈哲州，「醫用超音波影像課程講義」，國立臺灣科技大學電機所，民國109年。
[40] Yeh CK, Su SY, Shen CC, Li ML. Dual high-frequency difference excitation for contrast detection. IEEE Trans Ultrason Ferroelectr Freq Control. 2008 Oct;55(10):2164-76. doi: 10.1109/TUFFC.916. PMID:
 
[41] R. Schmidt, "Multiple emitter location and signal parameter estimation," in IEEE Transactions on Antennas and Propagation, vol. 34, no. 3, pp. 276-280, March 1986, doi: 10.1109/TAP.1986.1143830
[42] Seo CH, Yen JT. Sidelobe suppression in ultrasound imaging using dual apodization with cross-correlation. IEEE Trans Ultrason Ferroelectr Freq Control. 2008 Oct;55(10):2198-210. doi: 10.1109/TUFFC.919. PMID: 18986868; PMCID: PMC2905597.
[43] Vokurka K.: Power spectrum of the periodic group pulse process. Kybernetika 16, 5, 462-471, 1980.
[44] K. Vokurka, “ Cavitation noise modeling and analyzing,” in CD-ROM Proceedings of Forum Acousticum 2002, Sevilla, Spain
[45] Burgess MT, Apostolakis I, Konofagou EE. Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles. Phys Med Biol. 2018 Mar 15;63(6):065009. doi: 10.1088/1361-6560/aab05c. PMID: 29457587; PMCID: PMC5881390.
[46] A. N. Pouliopoulos et al., "Doppler Passive Acoustic Mapping," in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, vol. 67, no. 12, pp. 2692-2703, Dec. 2020, doi: 10.1109/TUFFC.2020.3011657.