Prediction and suppression of HIFU-induced vessel rupture using passive cavitation detection in an ex vivo model

Journal of Therapeutic Ultrasound

T Douglas Mast¹  Mario Zuccarello¹  Mark T Burgess¹  Joseph C Serrone¹  Cameron L Hoerig¹ 

[1] University of Cincinnati, Cincinnati, OH 45267-0586, USA

关键词: Rupture suppression;    Passive cavitation detection;    Vessel occlusion;    High-intensity focused ultrasound;   

Others  :  1132955
DOI  :  10.1186/2050-5736-2-14

 received in 2014-01-26, accepted in 2014-07-15,  发布年份 2014

【 摘 要 】

Background

Occlusion of blood vessels using high-intensity focused ultrasound (HIFU) is a potential treatment for arteriovenous malformations and other neurovascular disorders. However, attempting HIFU-induced vessel occlusion can also cause vessel rupture, resulting in hemorrhage. Possible rupture mechanisms include mechanical effects of acoustic cavitation and heating of the vessel wall.

Methods

HIFU exposures were performed on 18 ex vivo porcine femoral arteries with simultaneous passive cavitation detection. Vessels were insonified by a 3.3-MHz focused source with spatial-peak, temporal-peak focal intensity of 15,690–24,430 W/cm² (peak negative-pressure range 10.92–12.52 MPa) and a 50% duty cycle for durations up to 5 min. Time-dependent acoustic emissions were recorded by an unfocused passive cavitation detector and quantified within low-frequency (10–30 kHz), broadband (0.3–1.1 MHz), and subharmonic (1.65 MHz) bands. Vessel rupture was detected by inline metering of saline flow, recorded throughout each treatment. Recorded emissions were grouped into ‘pre-rupture’ (0–10 s prior to measured point of vessel rupture) and ‘intact-vessel’ (>10 s prior to measured point of vessel rupture) emissions. Receiver operating characteristic curve analysis was used to assess the ability of emissions within each frequency band to predict vessel rupture.

Based on these measurements associating acoustic emissions with vessel rupture, a real-time feedback control module was implemented to monitor acoustic emissions during HIFU treatment and adjust the ultrasound intensity, with the goal of maximizing acoustic power delivered to the vessel while avoiding rupture. This feedback control approach was tested on 10 paired HIFU exposures of porcine femoral and subclavian arteries, in which the focal intensity was stepwise increased from 9,117 W/cm² spatial-peak temporal-peak (SPTP) to a maximum of 21,980 W/cm², with power modulated based on the measured subharmonic emission amplitude. Time to rupture was compared between these feedback-controlled trials and paired controller-inactive trials using a paired Wilcoxon signed-rank test.

Results

Subharmonic emissions were found to be the most predictive of vessel rupture (areas under the receiver operating characteristic curve (AUROC) = 0.757, p < 10^-16) compared to low-frequency (AUROC = 0.657, p < 10^-11) and broadband (AUROC = 0.729, p < 10^-16) emissions. An independent-sample t test comparing pre-rupture to intact-vessel emissions revealed a statistically significant difference between the two groups for broadband and subharmonic emissions (p < 10^-3), but not for low-frequency emissions (p = 0.058).

In a one-sided paired Wilcoxon signed-rank test, activation of the control module was shown to increase the time to vessel rupture (T_- = 8, p = 0.0244, N = 10). In one-sided paired t tests, activation of the control module was shown to cause no significant difference in time-averaged focal intensity (t = 0.362, p = 0.363, N = 10), but was shown to cause delivery of significantly greater total acoustic energy (t = 2.037, p = 0.0361, N = 10).

Conclusions

These results suggest that acoustic cavitation plays an important role in HIFU-induced vessel rupture. In HIFU treatments for vessel occlusion, passive monitoring of acoustic emissions may be useful in avoiding hemorrhage due to vessel rupture, as shown in the rupture suppression experiments.

【 授权许可】

   
2014 Hoerig et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

【 参考文献 】

• [1]ter Haar G, Coussios C: High intensity focused ultrasound: past, present, and future. Int J Hyperthermia. 2007, 23:85-7.
• [2]Kennedy JE, ter Haar GR, Cranston D: High intensity focused ultrasound: surgery of the future? Br J Radiol. 2003, 76:590-9.
• [3]Fry WJ, Mosberg WH, Barnard JW, Fry FJ: Production of focal destructive lesions in the central nervous system with ultrasound. J Neurosurg. 1954, 11:471-8.
• [4]Fry WJ, Fry FJ: Fundamental neurological research and human neurosurgery using intense ultrasound. IRE Trans Med Electron. 1960, ME-7:166-81.
• [5]Delon-Martin C, Vogt C, Guers C, Chapelon JY, Cathignol D: Venous thrombosis generation by means of high-intensity focused ultrasound. Ultrasound Med Biol. 1995, 21:113-9.
• [6]Hynynen K, Chung AH, Colucci V, Jolesz FA: Potential adverse effects of high-intensity focused ultrasound exposure on blood vessels in vivo. Ultrasound Med Biol. 1996, 22:193-201.
• [7]Hynynen K, Colucci V, Chung A, Jolesz F: Noninvasive arterial occlusion using MRI-guided focused ultrasound. Ultrasound Med Biol. 1996, 22:1071-7.
• [8]Rivens IH, Rowland IJ, Denbow M, Fisk NM, ter Haar GR, Leach MO: Vascular occlusion using focused ultrasound surgery for use in fetal medicine. Eur J Ultrasound. 1999, 9:89-97.
• [9]Denbow ML, Rivens IH, Rowland IJ, Leach MO, Fisk NM, ter Haar GR: Preclinical development of noninvasive vascular occlusion with focused ultrasonic surgery for fetal therapy. Am J Obstet Gynecol. 2000, 182:387-92.
• [10]Mahoney K, Martin H, Hynynen K: Focused ultrasound effects on blood vessels in vivo–limits for vascular intervention. Proc IEEE Ultrasonics Symposium. 2000, 2:1405-8.
• [11]Fujiwara R, Sasaki K, Ishikawa T, Suzuki M, Umemura S, Kushima M, Okai T: Arterial blood flow occlusion by high intensity focused ultrasound and histologic evaluation of its effect on arteries and surrounding tissues. J Med Ultrason. 2002, 29:85-90.
• [12]Ishikawa T, Okai T, Sasaki K, Umemura S, Fujiwara R, Kushima M, Ichihara M, Ichizuka K: Functional and histological changes in rat femoral arteries by HIFU exposure. Ultrasound Med Biol. 2003, 29:1471-7.
• [13]Ichizuka K, Ando S, Ichihara M, Ishikawa T, Uchiyama N, Sasaki K, Kushima M: Application of HIFU for umbilical artery occlusion in a rabbit model. Ultrasound Obstet Gynecol. 2007, 30:47-51.
• [14]Ichihara M, Sasaki K, Umemura SI, Kushima M, Okai T: Blood flow occlusion via ultrasound image-guided high-intensity focused ultrasound and its effect on tissue perfusion. Ultrasound Med Biol. 2007, 33:452-9.
• [15]Hwang JH, Zhou Y, Warren C, Brayman AA, Crum LA: Targeted venous occlusion using pulsed high-intensity focused ultrasound. IEEE Trans Biomed Eng 2010, 57(1):37-40.
• [16]Serrone JC, Kocaeli H, Mast TD, Burgess M, Zuccarello M: The potential applications of high-intensity focused ultrasound (HIFU) in vascular neurosurgery. J Clin Neurosci 2012, 19(2):214-21.
• [17]Fallon JT, Stehbens WE, Eggleton RC: Effect of ultrasound on arteries. Arch Pathol. 1972, 94:380-8.
• [18]Schultz-Haakh H, Li JKJ, Welkowitz W, Rosenberg N: Ultrasonic treatment of varicose veins. Angiology. 1989, 40:129-37.
• [19]Yang R, Griffith SL, Rescoria FJ, Galliani CA, Ehrman KO, Fry FJ, Wessling SM, Grosfeld JL: Feasibility of using high intensity focused ultrasound for the treatment of unresectable retroperitoneal malignancies. J Ultrasound Med. 1992, 11:S37.
• [20]Nizard J, Pessel M, De Keersmaecker B, Barbet JP, Ville Y: High-intensity focused ultrasound in the treatment of postpartum hemorrhage: an animal model. Ultrasound Obstet Gynecol. 2004, 23:262-6.
• [21]Daffertshofer M, Gass A, Ringleb P, Sitzer M, Sliwka U, Els T, Sedlaczek O, Koroshetz WJ, Hennerici MG: Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: Increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator—Results of a phase II clinical trial. Stroke 2005, 36:1441-1446.
• [22]Liu HL, Wai YY, Chen WS, Chen JC, Hsu PH, Wu XY, Huang WC, Yen TC, Wang JJ: Hemorrhage detection during focused-ultrasound induced blood–brain-barrier opening by using susceptibility-weighted magnetic resonance imaging. Ultrasound Med Biol. 2008, 34:598-606.
• [23]Martinot VL, Mordon SR, Mitchell VA, Pellerin PN, Brunetaud JM: Determination of efficient parameters for argon laser-assisted anastomoses in rats: macroscopic, thermal, and histological evaluation. Lasers Surg Med 1994, 15(2):168-75.
• [24]Khokhlova TD, Canney MS, Khokhlova VA, Sapozhnikov OA, Crum LA, Bailey MR: Controlled tissue emulsification produced by high intensity focused ultrasound shock waves and millisecond boiling. J Acoust Soc Am. 2011, 130:3498-510.
• [25]Mast TD, Salgaonkar VA, Karunakaran C, Besse JA, Datta S, Holland CK: Acoustic emissions during 3.1 MHz ultrasound bulk ablation in vitro. Ultrasound Med Biol. 2008, 34(9):1434-48.
• [26]Osborne MFM, Holland FH: The acoustical concomitants of cavitation and boiling, produced by a hot wire. J Acoust Soc Am. 1947, 19:13-29.
• [27]Anand A, Kaczkowski PJ: Noninvasive determination of in situ heating rate using kHz acoustic emissions and focused ultrasound. Ultrasound Med Biol 2009, 35(10):1662-71.
• [28]Crum LA: Cavitation microjets as a contributory mechanism for renal calculi disintegration in ESWL. J Urol. 1988, 140:1587-90.
• [29]Miller MW, Miller DL, Brayman AA: A review of in vitro bioeffects of inertial ultrasonic cavitation from a mechanistic perspective. Ultrasound Med Biol. 1996, 22:1131-54.
• [30]Roberts WW, Hall TL, Ives K, Wolf JS, Fowlkes JB, Cain CA: Pulsed cavitational ultrasound: a noninvasive technology for controlled tissue ablation (histotripsy) in the rabbit kidney. J Urology. 2006, 175:734-8.
• [31]Parsons JE, Cain CA, Abrams GD, Fowlkes JB: Pulsed cavitational ultrasound therapy for controlled tissue homogenization. Ultrasound Med Biol 2006, 32(1):115-29.
• [32]Maxwell AD, Cain CA, Duryea AP, Yuan L, Gurm HS, Xu Z: Non-invasive thrombolysis using pulsed ultrasound cavitation therapy–histotripsy. Ultrasound Med Biol. 2009, 35:1982-94.
• [33]Xu Z, Owens G, Gordon D, Cain C, Ludomirsky A: Non-invasive creation of an atrial septal defect by histotripsy in a canine model. Circulation. 2010, 1216:742-9.
• [34]Nyborg WL: Biological effects of ultrasound: development of safety guidelines. Part II: general review. Ultrasound Med Biol. 2001, 27:301-33.
• [35]Prokop AF, Soltani A, Roy RA: Cavitational mechanisms in ultrasound-accelerated fibrinolysis. Ultrasound Med Biol. 2007, 33:924-33.
• [36]Datta S, Coussios CC, Ammi AY, Mast TD, de Courten-Myers GM, Holland CK: Ultrasound-enhanced thrombolysis using Definity as a cavitation nucleation agent. Ultrasound Med Biol. 2008, 34:1421-33.
• [37]Hitchcock KE, Caudell DN, Sutton JT, Klegerman ME, Vela D, Pyne-Geithman GJ, Abruzzo T, Cyr PE, Geng YJ, McPherson DD, Holland CK: Ultrasound-enhanced delivery of targeted echogenic liposomes in a novel ex vivo mouse aorta model. J Controlled Release. 2010, 144:288-95.
• [38]Tung YS, Vlachos F, Choi JJ, Deffieux T, Selert K, Konofagou EE: In vivo transcranial cavitation threshold detection during ultrasound-induced blood–brain barrier opening in mice. Phys Med Biol. 2010, 55:6141-55.
• [39]Lavon I, Grossman N, Kost J, Kimmel E, Enden G: Bubble growth within the skin by rectified diffusion might play a significant role in sonophoresis. J Controlled Release. 2007, 117:246-55.
• [40]Neppiras EA: Acoustic cavitation. Phys Rep. 1980, 61:159-284.
• [41]Leighton TG: The Acoustic Bubble. San Diego: Academic Press; 1994. Chapter 4
• [42]Khokhlova VA, Bailey MR, Reed JA, Cunitz BW, Kaczkowski PJ, Crum LA: Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom. J Acoust Soc Am. 2006, 119:1834-48.
• [43]Coussios CC, Farny CH, ter Haar GR, Roy RA: Role of acoustic cavitation in the delivery and monitoring of cancer treatment by high-intensity focused ultrasound (HIFU). Int J Hyperthermia. 2007, 23:105-20.
• [44]Farny CH, Holt RG, Roy RA: Temporal and spatial detection of HIFU-induced inertial and hot-vapor cavitation with a diagnostic ultrasound system. Ultrasound in Med Biol. 2009, 35:603-15.
• [45]McLaughlan J, Rivens I, Leighton T, Ter Haar G: A study of bubble activity generated in ex vivo tissue by high intensity focused ultrasound. Ultrasound Med Biol. 2010, 36:1327-44.
• [46]O’Reilly MA, Hynynen K: Blood–brain barrier: real-time feedback-controlled focused ultrasound disruption by using an acoustic emissions–based controller. Radiology 2012, 263(1):96-106.
• [47]Shaw CJ, ter Haar GR, Rivens IH, Giussani DA, Lees CC: Pathophysiological mechanisms of high-intensity focused ultrasound-mediated vascular occlusion and relevance to non-invasive fetal surgery. J Royal Soc Interface. 2014, 11:20140029.
• [48]Soneson JE: A user-friendly software package for HIFU simulation. AIP Conf Proc. 2009, 1113:165-9.
• [49]Poliachik SL, Chandler SL, Mourad PD, Ollos RJ, Crum LA: Activation, aggregation, and adhesion of platelets exposed to high-intensity focused ultrasound. Ultrasound Med Biol. 2001, 27:1567-76.
• [50]Salgaonkar VA, Datta S, Holland CK, Mast TD: Passive cavitation imaging with ultrasound arrays. J Acoust Soc Am. 2009, 126:3071-83.
• [51]Gyöngy M, Coussios CC: Passive spatial mapping of inertial cavitation during HIFU exposure. IEEE Trans Biomed Eng. 2010, 57:48-56.
• [52]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, 132:544-53.
• [53]Mast TD, Pucke DP, Subramanian SE, Bowlus WJ, Rudich SM, Buell JF: Ultrasonic monitoring of in vitro radiofrequency ablation by echo decorrelation imaging. J Ultrasound Med. 2008, 27:1685-97.
• [54]Subramanian S, Rudich SM, Karunakaran CP, Rao MB, Mast TD: In vivo thermal ablation monitoring using ultrasound echo decorrelation imaging. Ultras Med Biol. 2014, 40:102-14.