Boiling histotripsy lesion characterization on a clinical magnetic resonance imaging-guided high intensity focused ultrasound system

Abstract

PurposeHigh 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.MethodsThe 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.ResultsSignificant 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.ConclusionOur 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.

Assessment of histotripsy-induced liquefaction with diagnostic ultrasound and magnetic resonance imaging in vitro and ex vivo

“…Insonation of liver tissue samples in this study resulted in more pronounced and uniform changes in T 1 , T 2 , and diffusion compared with RBC phantoms. Uniform increases in T 2 and ADC and both uniform increases and decreases in T 1 have been observed previously following boiling histotripsy ablation in ex vivo tissue (Eranki et al 2017, Partanen et al 2014. Allen et al (2017) reported uniform increases in T 1 , T 2 and ADC in similar 16% RBC phantoms and ex vivo tissue samples following histotripsy liquefaction, but utilized 2-cycle pulses from a 400 kHz transducer with a 10 Hz PRF.…”

“…Successful clinical implementation of histotripsy requires accurate and reliable image guidance to assess the treatment progress and efficacy. The presence of histotripsy-induced bubble activity and the resulting tis sue homogenization has been monitored with diagnostic ultrasound and magnetic resonance (MR) imaging (Hall et al 2005, Wang et al 2009, Kim et al 2013, 2014, Allen et al 2017, Eranki et al 2017, Haworth et al 2017, Bader et al 2018a. Bubble clouds appear hyperechoic on B-mode imaging, and the strength of bubble cloud emissions can be mapped spatially with passive cavitation imaging (PCI) (Salgaonkar et al 2009, Gyöngy and Coussios 2010, Arvanitis and McDannold 2013, Arvanitis et al 2017, Haworth et al 2017.…”

A convenient, reliable, and fast acoustic pressure field measurement method for magnetic resonance-guided high-intensity focused ultrasound systems with phased array transducers

“…The standard pieces of hydrophone equipment are bulky and not designed to be MR compatible, thus preventing acoustic characterization of an MR-HIFU system inside the magnet bore. Therefore, all previously reported hydrophone measurements of MR-HIFU systems were performed outside the magnet fringe field [ 9 – 11 ]. However, the complicated procedure involved in this process has prevented many clinical MR-HIFU sites from performing the measurements.…”

“…Particularly, hydrophone-based characterization of a clinical phased array HIFU transducer is associated with two technical challenges: standard laboratory hydrophone equipment is not MRI-compatible, and the bore of a clinical MRI scanner has limited space to fit those pieces of equipment. Owing to these challenges, in previous studies the HIFU patient table was moved outside the magnet fringe field, and a heavy, high-precision, 3D positioning stage was placed on the table for pressure measurements [ 9 – 11 ]. That procedure is complicated and requires a 3D positioning stage, which is neither feasible nor economical for most clinical MR-HIFU facilities.…”

Feasibility of targeting canine soft tissue sarcoma with MR-guided high-intensity focused ultrasound

“…The technology precisely focuses ultrasound energy within the tumour with local bioeffects ranging from a change in vascular permeability to tissue thermal ablation and/or liquefaction, to immunomodulatory effects and enhancement of drug treatments [5]. By varying sonication parameters, it is possible to customise the therapeutic action within this range of bioeffects [6][7][8][9]. Precise spatio-temporal control of treatment effects may allow MR-HIFU to offer a non-invasive alternative to both surgery and radiation therapy without the sequelae of either of these conventional therapies.…”