Our current clinical targets are Hypoplastic Left Heart Syndrome (HLHS) and several other cardiac applications including cardiac ablation for treatment of arrhythmias. 

HLHS is a congenital heart disease characterized by an underdeveloped or absent left ventricle, which is unable to pump enough oxygenated blood to meet the body’s needs. In utero, placental transport and the right ventricle provide the fetus with oxygenation and blood circulation. After birth, the condition is universally fatal with 95% of babies dying within the first month of life [1]. Other than a heart transplant, the only successful treatment for HLHS is reconstructive heart surgery performed throughout the first 2-4 years of life [2]. To extend patients’ survival until the reconstructive surgery, a blood flow channel between the two atria is required, which can be achieved though one or more perforations in the atrial septum. All current procedures to produce an atrial septal perforation involve catheter-based septostomy [3-5]. They are all invasive and have high mortality rate (~50%) [3, 6, 7]. The goal of this proposal is to develop a noninvasive ultrasound procedure to perforate the atrial septum using image guided high intensity ultrasound (histotripsy). This is an opportunity to save the 50% of current HLHS patients who do not survive catheter based attempts to maintain blood flow between the two atria. We have conducted extensive successful in vitro tissue erosion and perforation studies using histotripsy [8-11]. In addition, in our recent in vivo canine experiments, we successfully generated atrial septal perforation in the canine atrial septum.

[1] A. G. Stuart, C. Wren, and P. M. Shaples, “Hypoplastic left heart syndrome: more potential transplant recipients than suitable donors,” Lancet, vol. 337, pp. 957-9, 1991. 
[2] W. I. Norwood, Jr., “Hypoplastic left heart syndrome,” Annals of Thoracic Surgery, vol. 52, pp. 688-95, 1991. 
[3] A. M. Atz, J. A. Feinstein, R. A. Jonas, S. B. Perry, and D. L. Wessel, “Preoperative management of pulmonary venous hypertension in hypoplastic left heart syndrome with restrictive atrial septal defect,” American Journal of Cardiology, vol. 83, pp. 1224-8, 1999. 
[4] J. Rychik, J. J. Rome, M. H. Collins, W. M. DeCampli, and T. L. Spray, “The hypoplastic left heart syndrome with intact atrial septum: atrial morphology, pulmonary vascular histopathology and outcome,” Journal of the American College of Cardiology, vol. 34, pp. 554-60, 1999. 
[5] J. P. Cheatham, “Intervention in the critically ill neonate and infant with hypoplastic left heart syndrome and intact atrial septum,” Journal of Interventional Cardiology, vol. 14, pp. 357-66, 2001. 
[6] R. Andrews and R. Tulloh, “Hypoplastic left heart syndrome: diagnosis and management,” Hospital Medicine, vol. 63, pp. 24-7, 2002. 
[7] A. P. Vlahos, J. E. Lock, D. B. McElhinney, and M. E. van der Velde, “Hypoplastic left heart syndrome with intact or highly restrictive atrial septum: outcome after neonatal transcatheter atrial septostomy,” Circulation, vol. 109, pp. 2326-30, 2004. 
[8] Xu Z, Ludomirsky A, Eun LY, Hall TL, Tran BC, Fowlkes JB, Cain CA, “Controlled ultrasound tissue erosion,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 51, 726-736 (2004). 
[9] Xu Z, Fowlkes JB, Ludomirsky A, Cain CA, “Investigation of intensity threshold for ultrasound tissue erosion,” Ultrasound Med. Biol. 31, 1673-1682 (2005). 
[10] Xu Z, Fowlkes JB, Rothman ED, Levin AM, Cain CA, “Controlled ultrasound tissue erosion: the role of dynamic interaction between insonation and microbubble activity,” J. Acoust. Soc. Am. 117, 424-435 (2005). 
[11] Xu Z, Fowlkes JB, Cain CA, “A new strategy to enhance cavitational tissue erosion by using a high intensity initiating sequence,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 53, 1412-1424 (2006).