Histotripsy methods in non-invasive ultrasound surgery
Histotripsy is a recently proposed method of mechanical disintegration (liquefication) of target tissue volumes (e.g., tumors) in the human body using short pulses of focused ultrasound (FUS) [1, 2].
Currently, several histotripsy types have been proposed, differing in:
• pulse duration (from microseconds to several milliseconds),
• nonlinearly distorted ultrasound waveform,
• amplitude of shock fronts at the focal point,
• physical mechanisms underlying the tissue disintegration process.
Nethertheless, all histotripsytypes are based on initiation of intense bubble activity and acoustic microstreams at the focus of an ultrasound beam, leading to tissue fragmentation into subcellular components.
Boiling histotripsy method
One of the histotripsy methods termed “boiling histotripsy“ is being actively developed in our laboratory LIMU at Moscow State University.
The method involves transcutaneous focusing of short (1—10 ms) rarely repeating powerful ultrasound pulses on target tissues in the human body. Nonlinear distortion of the initially harmonic waveform in each pulse as it propagates leads to the formation of high-amplitude shock fronts in the focal zone. Rapid tissue heating due to the absorption of the wave energy at the shock fronts leads to localized tissue boiling at the focal point during each pulse. The interaction of subsequent shock fronts with the resulting millimeter-sized vapor cavity leads to surface cavitation, tissue atomization, and formation of microjets, disintegrating the target tissue down to subcellular fragments.
Histotripsy methods have important clinical advantages over thermal ablation methods using high-intensity focused ultrasound (HIFU or FUS):
- possibility of real-time visualization via conventional, more accessible than MRI, diagnostic ultrasound imaging:
- vapor bubbles formed during histotripsy strongly scatter ultrasound and appear hyperechoic (bright) on ultrasound;
- the resulting liquefied tissue lacks ultrasound scatterers and appears hypoechoic (dark) on ultrasound;
- significant localization of the effect due to minimization of heat diffusion;
- no scar formation at the treated site;
- rapid resorption of liquefied tissue by immune system.
Currently, various new clinical applications of histotripsy methods are rapidly developing, such as local disintagration of tumors, targeted drug delivery without artificial administration of contrast agents, liquefaction of blood clots and large hematomas, enhanced release of specific biomarkers for non-invasive cancer diagnostics, treatment of abscesses, combination immunotherapy, etc.
Research at LIMU
- development of complex methods for planning HIFU exposure in clinical settings;
- transducer design, including phased arrays, to achieve the target amplitudes of shock fronts at the focus;
- studies of cavitation effects in tissue and physical mechanisms affecting tissue exposed to shock-wave HIFU;
- investigation of the effect of tissue acoustic properties on nonlinear focusing and field parameters in situ;
- investigation of acoustic and MRI visualization of the treated area;
- analysis of morphological and ultrastructural changes in tissue induced by ultrasound.
At LIMU Laboratory, boiling histotripsy is being developed for various clinical indications such as:
• prostate cancer;
• breast cancer;
• uterine tumors;
• neurosurgery;
• large hematomas.
LIMU tasks
- Development of new shock-wave HIFU regimes
- Investigation of susceptibility of varied tissues and tumors to histotripsy
- Development of a threshold dose concept for histotripsy of varies target tissues and tumors
- Verification experiments on tissue phantoms
- Design of specialized transducers for specific clinical applications
Activity types
- experiments on tissues and tissue phantoms
- numerical modeling
- design of transducers and phased arrays
Contacts
Details
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