Mechanical decellularization of tissue volumes using boiling histotripsy

Area of Science:

• Medical Physics
• Biomedical Engineering
• Acoustic Medicine

Background:

• High intensity focused ultrasound (HIFU) offers non-invasive thermal ablation for pathological tissues.
• Boiling histotripsy (BH), a novel HIFU modality, induces mechanical fractionation of tissue into subcellular fragments.
• Previous studies on BH tissue selectivity were limited to single lesions, not large volumes.

Purpose of the Study:

• To investigate tissue decellularization effects in large, clinically relevant liquefied volumes using BH.
• To evaluate the accumulated thermal effects within volumetric BH lesions under varying exposure parameters.
• To explore the potential of BH for tailored treatments in biofabrication and tissue ablation.

Main Methods:

• Utilized a clinical magnetic resonance imaging-guided HIFU (MR-HIFU) system with a 256-element 1.2 MHz array.
• Generated volumetric BH lesions in ex vivo bovine liver using pulse durations of 1-10 ms and shock amplitudes of 75-100 MPa.
• Employed pulse repetition frequencies (PRFs) from 1-10 Hz to achieve effects ranging from mechanical homogenization to thermal ablation.
• Conducted multimodal analysis including histology, electron microscopy, and biochemistry to characterize lesions.

Main Results:

• Demonstrated a spectrum of tissue effects in large BH lesions, including varying degrees of tissue selectivity.
• Quantified a range of accumulated thermal effects within the volumetric lesions.
• Observed that tissue response varied based on exposure parameters, indicating tunable outcomes.
• Confirmed tissue selectivity, with cellular structures being more sensitive than collagenous tissues.

Conclusions:

• BH can induce significant mechanical tissue fractionation and decellularization in large volumes.
• The thermal effects associated with BH are tunable and depend on exposure parameters.
• BH shows promise for applications requiring precise tissue ablation or decellularization while potentially sparing critical structures.
• This research supports the development of BH for diverse clinical applications, from biofabrication to targeted cancer therapy.