Ultrasound Histotripsy on a Viable Perfused Whole Porcine Liver: Histological Aspects, Including 3D Reconstruction of the Histotripsy Site

Froghi, Saied; Hall, Andrew; Hanafi Bin Jalal, Arif; Andrade, Matheus Oliveira de; Mohammad Hadi, Layla; Rashidi, Hassan; Gélat, Pierre; Saffari, Nader; Davidson, Brian; Quaglia, Alberto

doi:10.3390/bioengineering10030278

Open AccessArticle

Ultrasound Histotripsy on a Viable Perfused Whole Porcine Liver: Histological Aspects, Including 3D Reconstruction of the Histotripsy Site

by

Saied Froghi

^1,2,

Andrew Hall

³,

Arif Hanafi Bin Jalal

⁴

,

Matheus Oliveira de Andrade

⁵

,

Layla Mohammad Hadi

²,

Hassan Rashidi

⁶

,

Pierre Gélat

⁷,

Nader Saffari

⁵,

Brian Davidson

^1,2 and

Alberto Quaglia

^3,*

¹

Department of HPB & Liver Transplantation Surgery, Royal Free London NHS Foundation Trust, Pond Street, Hampstead, London NW3 2QG, UK

²

Centre for Surgical Innovation, Organ Regeneration and Transplantation, UCL Division of Surgery & Interventional Sciences, Royal Free Hospital Campus, Pond Street, Hampstead, London NW3 2QG, UK

³

Department of Cellular Pathology, UCL Cancer Institute Royal Free London NHS Foundation Trust, Pond Street, Hampstead, London NW3 2QG, UK

⁴

UCL Medical School, University College London, 74 Huntley Street, London WC1E 6BT, UK

⁵

Ultrasonics Group, Department of Mechanical Engineering, Roberts Engineering Building, University College London, Torrington Place, London WC1E 7JE, UK

⁶

Developmental Biology and Cancer Program, UCL Great Ormond Street, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK

⁷

Department of Surgical Biotechnology, Division of Surgery and Interventional Science, UCL, Royal Free Hospital Campus, Pond Street, Hampstead, London NW3 2QG, UK

^*

Author to whom correspondence should be addressed.

Bioengineering 2023, 10(3), 278; https://doi.org/10.3390/bioengineering10030278

Submission received: 30 November 2022 / Revised: 26 January 2023 / Accepted: 11 February 2023 / Published: 21 February 2023

(This article belongs to the Special Issue Cell- and Gene-Based Therapeutic Strategies for Liver Disease: Recent Advances and Prospects)

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Abstract

Non-invasive therapeutic-focused ultrasound (US) can be used for the mechanical dissociation of tissue and is described as histotripsy. We have performed US histotripsy in viable perfused ex vivo porcine livers as a step in the development of a novel approach to hepatocyte cell transplantation. The histotripsy nidus was created with a 2 MHz single-element focused US transducer, producing 50 pulses of 10 ms duration, with peak positive and negative pressure values of P+ = 77.7 MPa and P− = –13.7 MPaat focus, respectively, and a duty cycle of 1%. Here, we present the histological analysis, including 3D reconstruction of histotripsy sites. Five whole porcine livers were retrieved fresh from the abattoir using human transplant retrieval and cold static preservation techniques and were then perfused using an organ preservation circuit. Whilst under perfusion, histotripsy was performed to randomly selected sites on the live. Fifteen lesional sites were formalin-fixed and paraffin-embedded. Sections were stained with Haematoxylin and Eosin and picro-Sirius red, and they were also stained for reticulin. Additionally, two lesion sites were used for 3D reconstruction. The core of the typical lesion consisted of eosinophilic material associated with reticulin loss, collagen damage including loss of birefringence to fibrous septa, and perilesional portal tracts, including large portal vein branches, but intact peri-lesional hepatic plates. The 3D reconstruction of two histotripsy sites was successful and confirmed the feasibility of this approach to investigate the effects of histotripsy on tissue in detail.

Keywords: boiling histotripsy; liver; whole organ perfusion system; pig liver; birefringence; necrosis

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MDPI and ACS Style

Froghi, S.; Hall, A.; Hanafi Bin Jalal, A.; Andrade, M.O.d.; Mohammad Hadi, L.; Rashidi, H.; Gélat, P.; Saffari, N.; Davidson, B.; Quaglia, A. Ultrasound Histotripsy on a Viable Perfused Whole Porcine Liver: Histological Aspects, Including 3D Reconstruction of the Histotripsy Site. Bioengineering 2023, 10, 278. https://doi.org/10.3390/bioengineering10030278

AMA Style

Froghi S, Hall A, Hanafi Bin Jalal A, Andrade MOd, Mohammad Hadi L, Rashidi H, Gélat P, Saffari N, Davidson B, Quaglia A. Ultrasound Histotripsy on a Viable Perfused Whole Porcine Liver: Histological Aspects, Including 3D Reconstruction of the Histotripsy Site. Bioengineering. 2023; 10(3):278. https://doi.org/10.3390/bioengineering10030278

Chicago/Turabian Style

Froghi, Saied, Andrew Hall, Arif Hanafi Bin Jalal, Matheus Oliveira de Andrade, Layla Mohammad Hadi, Hassan Rashidi, Pierre Gélat, Nader Saffari, Brian Davidson, and Alberto Quaglia. 2023. "Ultrasound Histotripsy on a Viable Perfused Whole Porcine Liver: Histological Aspects, Including 3D Reconstruction of the Histotripsy Site" Bioengineering 10, no. 3: 278. https://doi.org/10.3390/bioengineering10030278

APA Style

Froghi, S., Hall, A., Hanafi Bin Jalal, A., Andrade, M. O. d., Mohammad Hadi, L., Rashidi, H., Gélat, P., Saffari, N., Davidson, B., & Quaglia, A. (2023). Ultrasound Histotripsy on a Viable Perfused Whole Porcine Liver: Histological Aspects, Including 3D Reconstruction of the Histotripsy Site. Bioengineering, 10(3), 278. https://doi.org/10.3390/bioengineering10030278

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Ultrasound Histotripsy on a Viable Perfused Whole Porcine Liver: Histological Aspects, Including 3D Reconstruction of the Histotripsy Site

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