Histotripsy Group
    Biomedical Engineering Department, University of Michigan



Treatement of:

Cardiac Tissue

Prostate Tissue

Kidney Tissue



Research -> Histotripsy Acute Bioeffects

Histotripsy Acute Bioeffects


At a fluid-tissue interface, histotripsy results in localized tissue removal with sharp boundaries, which we use to remove cardiac tissue in treatment of congenital heart disease. In bulk tissue, histotripsy produces mechanical fragmentation of tissue resulting in a liquefied cored with very sharply demarcated boundaries. Histology demonstrates treated tissue within the lesion is fragmented to subcelluar level surrounded by an almost imperceptibly narrow margin of cellular injury. Histotripsy has vast clinical applications where non-invasive precise tissue ablation and removal are needed (e.g., tumor treatment).




Treatment of Cardiac Tissue


Perforation of the atrial septum (the membrane between the two atria) in treatment of a congenital heart disease called Hypoplastic Left Heart Syndrome (HLHS).

Histotripsy generated tissue erosion in porcine atrial wall tissue. a). Gross picture of perforations generated in the porcine atrial wall using histotrispy. b). Histology of histotripsy induced tissue erosion in porcine atrial wall. Erosion was purposely stopped before perforation. c). Expanded view of the erosion boundary.

References:
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).
Xu Z, Fowlkes JB, Ludomirsky A, Cain CA, "Investigation of intensity threshold for ultrasound tissue erosion," Ultrasound Med. Biol. 31, 1673-1682 (2005).



Cardiac ablation

Lesions produced using high-intensity ultrasound in porcine myocardium. (A) Uniform tissue homogenate produced using pulsed cavitational ultrasound therapy. The tissue has been mechanically disintegrated and ceases to be anchored in the surrounding tissue bed. (B) Void remaining after homogenate evident in (A) has been irrigated out of the lesion volume, leaving an empty cavity with regular borders. (C) Histology at the lesion boundary. Within the lesion, tissue was fragmented to acelluar debris. The boundary is very sharp, with half of the myocyte cut and the other half intact.

References:
Parsons JE, Cain CA, Abrams GD, Fowlkes JB, "Pulsed cavitational ultrasound therapy for controlled tissue homogenization," Ultrasound Med. Biol. 32, 115-129 (2006).




Treatment of Prostate Tissue


In vivo canine prostate ablation for treatment of prostate cancer and BPH

A. H&E slides of the ablated canine prostate tissue. Within the ablated region, no cellular structures remained.
B. Expanded view of the tissue damage boundary, indicating a sharp transition zone of about 100 μm.

References:
Hall TL, Kieran K, Fowlkes JB, Cain CA, Roberts WW, "Temporal trends in the histology of the rabbit kidney after cavitational tissue ablation," 6th International Symposium on Therapeutic Ultrasound, S07 (2006).




Treatment of Kidney Tissue


In vivo rabbit kidney Ablation for treatment of renal cancer

Spectrum of damage found in representative lesions created with 10, 100, 1,000 and 10,000 pulses (left to right). Lesions created by 10 or 100 pulses had scattered areas of focal hemorrhage and cellular debris surrounded by narrow band of cellular injury in 3 × 10 mm focal zone. Lesions created by 1,000 or 10,000 pulses had cavity with sharp boundaries and liquefied core. Histologically this material consisted of confluent areas of hemorrhage and cellular debris with thin surrounding margin of cellular injury. Reduced from × 5 (top) and × 100 (bottom).

References:
Roberts WW, Hall TJ, Ives K, Wolf JJS, Fowlkes JB, Cain CA, "Pulsed cavitational ultrasound : a noninvasive technology for controlled tissue ablation (histotripsy) in the rabbit kidney," Journal of Urology 175, 734-738 (2006).