Reverse time migration and genetic algorithms Combined for Reconstruction in Transluminal Shear Wave Elastography: An In Silico Case Study.

A new reconstruction approach that combines Reverse Time Migration (RTM) and Genetic Algorithms (GAs) is proposed for solving the inverse problem associated with transluminal shear wave elastography. The transurethral identification of the first thermal lesion generated by transrectal High Intensity Focused Ultrasound (HIFU) for the treatment of prostate cancer, was used to preliminarily test in silico the combined reconstruction method. The RTM method was optimised by comparing reconstruction images from several cross-correlation techniques, including a new proposed one, and different device configurations in terms of the number and arrangement of emitters and receivers of the conceptual transurethral probe.

New Developments and Challenges in Liver Transplantation.

Liver disease is increasing in incidence and is the third most common cause of premature death in the United Kingdom and fourth in the United States. Liver disease accounts for 2 million deaths globally each year. Three-quarters of patients with liver disease are diagnosed at a late stage, with liver transplantation as the only definitive treatment.

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

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.

Liver Ultrasound Histotripsy: Novel Analysis of the Histotripsy Site Cell Constituents with Implications for Histotripsy Application in Cell Transplantation and Cancer Therapy.

Allogenic hepatocyte transplantation is an attractive alternative to whole-organ transplantation, particularly for the treatment of metabolic disorders and acute liver failure. However, the shortage of human donor organs for cell isolation, the low cell yield from decellularisation regimes, and low engraftment rates from portal administration of donor cells have restricted its clinical application. Using ultrasound histotripsy to provide a nidus in the liver for direct cell transplantation offers a new approach to overcoming key limitations in current cell therapy.

Mechanisms of nuclei growth in ultrasound bubble nucleation.

This paper interrogates the intersections between bubble dynamics and classical nucleation theory (CNT) towards constructing a model that describes intermediary nucleation events between the extrema of cavitation and boiling. We employ Zeldovich's hydrodynamic approach to obtain a description of bubble nuclei that grow simultaneously via hydrodynamic excitation by the acoustic field and vapour transport. By quantifying the relative dominance of both mechanisms, it is then possible to discern the extent to which viscosity, inertia, surface tension and vapour transport shape the growth of bubble nuclei through non-dimensional numbers that naturally arise within the theory.

Experimental evidence of shear waves in fractional viscoelastic rheological models.

Fractional viscoelastic rheological models, such as the Kelvin Voigt Fractional Derivative model, have been proposed in the literature for modelling shear wave propagation in soft tissue. In this article, our previously developed wave propagation model for transluminal propagation based on a Kelvin Voigt Fractional Derivative wave equation is experimentally validated. The transluminal procedure uses the transmission and detection of shear waves through the luminal wall.

Accelerating frequency-domain numerical methods for weakly nonlinear focused ultrasound using nested meshes.

The numerical simulation of weakly nonlinear ultrasound is important in treatment planning for focused ultrasound (FUS) therapies. However, the large domain sizes and generation of higher harmonics at the focus make these problems extremely computationally demanding. Numerical methods typically employ a uniform mesh fine enough to resolve the highest harmonic present in the problem, leading to a very large number of degrees of freedom.

Modeling the Physics of Bubble Nucleation in Histotripsy.

This work aims to establish a theoretical framework for the modeling of bubble nucleation in histotripsy. A phenomenological version of the classical nucleation theory was parametrized with histotripsy experimental data, fitting a temperature-dependent activity factor that harmonizes theoretical predictions and experimental data for bubble nucleation at both high and low temperatures. Simulations of histotripsy pressure and temperature fields are then used in order to understand spatial and temporal properties of bubble nucleation at varying sonication conditions.

Wave Propagation in a Fractional Viscoelastic Tissue Model: Application to Transluminal Procedures.

In this article, a wave propagation model is presented as the first step in the development of a new type of transluminal procedure for performing elastography. Elastography is a medical imaging modality for mapping the elastic properties of soft tissue. The wave propagation model is based on a Kelvin Voigt Fractional Derivative (KVFD) viscoelastic wave equation, and is numerically solved using a Finite Difference Time Domain (FDTD) method.

Experimental Evidence of Generation and Reception by a Transluminal Axisymmetric Shear Wave Elastography Prototype.

Experimental evidence on testing a non-ultrasonic-based probe for a new approach in transluminal elastography was presented. The proposed modality generated shear waves by inducing oscillatory rotation on the lumen wall. Detection of the propagated waves was achieved at a set of receivers in mechanical contact with the lumen wall.

The interaction of shockwaves with a vapour bubble in boiling histotripsy: The shock scattering effect.

Boiling histotripsy is a High Intensity Focused Ultrasound (HIFU) technique which uses a number of short pulses with high acoustic pressures at the HIFU focus to induce mechanical tissue fractionation. In boiling histotripsy, two different types of acoustic cavitation contribute towards mechanical tissue destruction: a boiling vapour bubble and cavitation clouds. An understanding of the mechanisms underpinning these phenomena and their dynamics is therefore paramount to predicting and controlling the overall size of a lesion produced for a given boiling histotripsy exposure condition.

Systematic review of the role of high intensity focused ultrasound (HIFU) in treating malignant lesions of the hepatobiliary system.

Background: High Intensity Focused Ultrasound (HIFU) is an emerging non-invasive, targeted treatment of malignancy. The aim of this review was to assess the efficacy, safety and optimal technical parameters of HIFU to treat malignant lesions of the hepatobiliary system.

Methods: A systematic search of the English literature was performed until March 2020, interrogating Pubmed, Embase and Cochrane Library databases.

The effects of ultrasound pressure and temperature fields in millisecond bubble nucleation.

A phenomenological implementation of Classical Nucleation Theory (CNT) is employed to investigate the connection between high intensity focused ultrasound (HIFU) pressure and temperature fields with the energetic requirements of bubble nucleation. As a case study, boiling histotripsy in tissue-mimicking phantoms is modelled. The physics of key components in the implementation of CNT in HIFU conditions such as the derivation of nucleation pressure thresholds and approximations regarding the surface tension of the liquid are reviewed and discussed.

Mechanical damage induced by the appearance of rectified bubble growth in a viscoelastic medium during boiling histotripsy exposure.

In boiling histotripsy, the presence of a boiling vapour bubble and understanding of its dynamic behaviour are crucially important for the initiation of the tissue fractionation process and for the control of the size of a lesion produced. Whilst many in vivo studies have shown the feasibility of using boiling histotripsy in mechanical fractionation of solid tumours, not much is known about the evolution of a boiling vapour bubble in soft tissue induced by boiling histotripsy. The main objective of this present study is therefore to investigate the formation and dynamic behaviour of a boiling vapour bubble which occurs under boiling histotripsy insonation.

Bubble dynamics in boiling histotripsy.

Boiling histotripsy is a non-invasive, cavitation-based ultrasonic technique which uses a number of millisecond pulses to mechanically fractionate tissue. Though a number of studies have demonstrated the efficacy of boiling histotripsy for fractionation of solid tumours, treatment monitoring by cavitation measurement is not well studied because of the limited understanding of the dynamics of bubbles induced by boiling histotripsy. The main objectives of this work are to (a) extract qualitative and quantitative features of bubbles excited by shockwaves and (b) distinguish between the different types of cavitation activity for either a thermally or a mechanically induced lesion in the liver.

Numerical and Experimental Study of Mechanisms Involved in Boiling Histotripsy.

The aim of boiling histotripsy is to mechanically fractionate tissue as an alternative to thermal ablation for therapeutic applications. In general, the shape of a lesion produced by boiling histotripsy is tadpole like, consisting of a head and a tail. Although many studies have demonstrated the efficacy of boiling histotripsy for fractionating solid tumors, the exact mechanisms underpinning this phenomenon are not yet well understood, particularly the interaction of a boiling vapor bubble with incoming incident shockwaves.

Unmyelinated Peripheral Nerves Can Be Stimulated in Vitro Using Pulsed Ultrasound.

Appreciation for the medical and research potential of ultrasound neuromodulation is growing rapidly, with potential applications in non-invasive treatment of neurodegenerative disease and functional brain mapping spurring recent progress. However, little progress has been made in our understanding of the ultrasound-tissue interaction. The current study tackles this issue by measuring compound action potentials (CAPs) from an ex vivo crab walking leg nerve bundle and analysing the acoustic nature of successful stimuli using a passive cavitation detector (PCD).

The Effect of Boundary Conditions on Resonant Ultrasonic Spherical Chains.

The response of a resonant chain of spheres to changes in holder material and precompression is studied at ultrasonic frequencies. The system is found to be very sensitive to these parameters, with the creation of impulsive waveforms from a narrow bandwidth input seen only for certain chain lengths and holder materials. In addition, careful experiments were performed using known amounts of precompression force, using a calibrated stylus arrangement.

A Novel Approach to Ultrasound-Mediated Tissue Decellularization and Intra-Hepatic Cell Delivery in Rats.

Liver transplantation is the mainstay of treatment for end stage liver diseases, including metabolic and congenital liver diseases. The number of suitable donor organs is, however, limited, and a whole-liver transplant requires complex surgery. Cell therapy, such as intra-portal hepatocytes transplantation, has been considered as a bridging therapy to liver transplantation but has shown a mixed clinical outcome with limited success, including low level of engraftment of transplanted hepatocytes.

Forced vibrations of a bubble in a liquid-filled elastic vessel.

There is increasing demand for accurate characterization of the in vivo behavior of microbubble agents used for ultrasound imaging and therapy. This study examines bubble-vessel interaction, in particular the propagation of disturbances along the vessel wall. Finite element simulations of a 3 μm radius microbubble suspended in a viscous liquid and enclosed in a 4 μm radius elastic vessel were performed, and the results compared with existing analytical results for wave propagation in elastic liquid-filled tubes.

Modelling of the acoustic field of a multi-element HIFU array scattered by human ribs.

The efficacy of high-intensity focused ultrasound (HIFU) for the treatment of a range of different cancers, including those of the liver, prostate and breast, has been demonstrated. As a non-invasive focused therapy, HIFU offers considerable advantages over techniques such as chemotherapy and surgical resection in terms of reduced risk of harmful side effects. Despite this, there are a number of significant challenges which currently hinder its widespread clinical application.

The natural frequencies of microbubble oscillation in elastic vessels.

A theoretical model for the dynamics of a bubble in an elastic blood vessel is applied to study numerically the effect of confinement on the free oscillations of a bubble. The vessel wall deformations are described using a lumped-parameter membrane-type model, which is coupled to the Navier-Stokes equations for the fluid motion inside the vessel. It is shown that the bubble oscillations in a finite-length vessel are characterized by a spectrum of frequencies, with distinguishable high-frequency and low-frequency modes.

Ultrasound elastography to determine the layered mechanical properties of articular cartilage and the importance of such structural characteristics under load.

Articular cartilage is an important load bearing surface in joints. Prone to damage and with limited self-repair ability, it is of interest to tissue engineers. Tissue implant design requires full mechanical characterisation of healthy native tissue.

Controlled microchannelling in dense collagen scaffolds by soluble phosphate glass fibers.

A problem with tissue engineering scaffolds is maintaining seeded cell viability and function due to limitations of oxygen and nutrient transfer. An approach to maintain suitable oxygen concentrations throughout the scaffold would be to controllably incorporate microchannelling within these scaffolds. This study investigated the incorporation of unidirectionally aligned soluble phosphate based glass fibers (PGF) into dense collagen scaffolds.

Investigating the significance of multiple scattering in ultrasound contrast agent particle populations.

The majority of the existing models describing the behavior of microbubble ultrasound contrast agents consider single, isolated microbubbles suspended in infinite media. The behavior of a microbubble population is predicted by summing the results for single microbubbles and ignoring multiple scattering effects. The aim of this investigation is to determine the significance of multiple scattering in microbubble populations and establish whether an alternative approach is required.