title: Boiling histotripsy lesion characterization on a clinical magnetic resonance imaging-guided high intensity focused ultrasound system.
abstract: OBJECTIVE
  High intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique that can thermally ablate tumors. Boiling histotripsy (BH) is a HIFU approach that can emulsify tissue in a few milliseconds. Lesion volume and temperature effects for different BH sonication parameters are currently not well characterized. In this work, lesion volume, temperature distribution, and area of lethal thermal dose were characterized for varying BH sonication parameters in tissue-mimicking phantoms (TMP) and demonstrated in ex vivo tissues.
  
  
  METHODS
  The following BH sonication parameters were varied using a clinical MR-HIFU system (Sonalleve V2, Philips, Vantaa, Finland): acoustic power, number of cycles/pulse, total sonication time, and pulse repetition frequency (PRF). A 3×3×3 pattern was sonicated inside TMP's and ex vivo tissues. Post sonication, lesion volumes were quantified using 3D ultrasonography and temperature and thermal dose distributions were analyzed offline. Ex vivo tissues were sectioned and stained with H&E post sonication to assess tissue damage.
  
  
  RESULTS
  Significant increase in lesion volume was observed while increasing the number of cycles/pulse and PRF. Other sonication parameters had no significant effect on lesion volume. Temperature full width at half maximum at the end of sonication increased significantly with all parameters except total sonication time. Positive correlation was also found between lethal thermal dose and lesion volume for all parameters except number of cycles/pulse. Gross pathology of ex vivo tissues post sonication displayed either completely or partially damaged tissue at the focal region. Surrounding tissues presented sharp boundaries, with little or no structural damage to adjacent critical structures such as bile duct and nerves.
  
  
  CONCLUSIONS
  Our characterization of effects of HIFU sonication parameters on the resulting lesion demonstrates the ability to control lesion morphologic and thermal characteristics with a clinical MR-HIFU system in TMP's and ex vivo tissues. We demonstrate that this system can produce spatially precise lesions in both phantoms and ex vivo tissues. The results provide guidance on a preliminary set of BH sonication parameters for this system, with a potential to facilitate BH translation to the clinic.
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington DC, United States of America.|Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Avinash
authors.initials: A
authors.lastname: Eranki
authors.affiliation: Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Navid
authors.initials: N
authors.lastname: Farr
authors.affiliation: Clinical Science MR Therapy, Philips, Andover, Massachusetts, United States of America.
authors.forename: Ari
authors.initials: A
authors.lastname: Partanen
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington DC, United States of America.
authors.forename: Karun
authors.initials: K
authors.lastname: V Sharma
authors.affiliation: Department of Biomedical Engineering, School of Engineering & Applied Science, Washington University, St. Louis, Missouri, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington DC, United States of America.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Rossi
authors.affiliation: Department of Biomedical Engineering, School of Engineering & Applied Science, Washington University, St. Louis, Missouri, United States of America.
authors.forename: Satya V V N
authors.initials: SV
authors.lastname: Kothapalli
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington DC, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Oetgen
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington DC, United States of America.
authors.forename: AeRang
authors.initials: A
authors.lastname: Kim
authors.affiliation: Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Ayele
authors.initials: A
authors.lastname: H Negussie
authors.affiliation: Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Woods
authors.affiliation: Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Bradford
authors.initials: B
authors.lastname: J Wood
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington DC, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: C W Kim
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington DC, United States of America.
authors.forename: Pavel
authors.initials: P
authors.lastname: S Yarmolenko
mesh_terms: D000818:Animals; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009369:Neoplasms / Q000628:therapy; D019047:Phantoms, Imaging; D013552:Swine