A Metric and Method for Calculating EnergyPreserving Spatiotemporal Cavitation Dose: Cavitational Radiated Energy Density (CRED).

Unlabelled: Passive Acoustic Mapping (PAM) is rapidly emerging as a ubiquitous tool for real-time localization and monitoring of therapeutic ultrasound treatments involving cavitation in the context of safety or efficacy. The ability of PAM to spatially quantify and resolve cavitation activity offers a unique opportunity to correlate the energy of cavitation phenomena with locally observed bioeffects.

Objective: We aim to develop methods of measuring and reporting spatio-temporally varying cavitation energies that are energy-preserving, device-independent, and adequately normalized to the volume of tissue being affected by the reported cavitation activity.

Ultrafast optical and passive acoustic mapping characterization of nanoscale cavitation nuclei based on gas vesicle proteins.

Genetically encodable gas-filled particles, known as gas vesicles (GVs), have shown promise as a biomolecular contrast agent for ultrasound imaging and have the potential to be used as cavitation nuclei for ultrasound therapy. In this study, we used passive acoustic mapping techniques to characterize GV-seeded cavitation, utilizing 0.5 and 1.

Characterisation of Gas Vesicles as Cavitation Nuclei for Ultrasound Therapy using Passive Acoustic Mapping.

Genetically encodable gas filled particles known as gas vesicles (GVs) have shown promise as a biomolecular contrast agent for ultrasound imaging and have the potential to be used as cavitation nuclei for ultrasound therapy. In this study, we used passive acoustic mapping techniques to characterize GV-seeded cavitation, utilizing 0.5 and 1.

Quantitative evaluation of anti-biofilm cavitation activity seeded from microbubbles or protein cavitation nuclei by passive acoustic mapping.

Bacterial biofilms represent a major challenge for effective antibiotic therapy as they confer physical and functional changes that protect bacteria from their surrounding environment. In this work, focused ultrasound in combination with cavitation nuclei was used to disrupt biofilms of Staphylococcus aureus and Pseudomonas aeruginosa, both of which are on the World Health Organization's priority list for new antimicrobial research. Approach: Single species biofilms were exposed to ultrasound (0.

Sound speed and attenuation of human pancreas and pancreatic tumors and their influence on focused ultrasound thermal and mechanical therapies.

Background: There is increasing interest in using ultrasound for thermal ablation, histotripsy, and thermal or cavitational enhancement of drug delivery for the treatment of pancreatic cancer. Ultrasonic and thermal modelling conducted as part of the treatment planning process requires acoustic property values for all constituent tissues, but the literature contains no data for the human pancreas.

Purpose: This study presents the first acoustic property measurements of human pancreatic samples and provides examples of how these properties impact a broad range of ultrasound therapies.

PAX (Passive-Active Crossing) Method for Sub-Millimeter Coregistration of Passive Acoustic Mapping and B-Mode Images.

Nonlinear ultrasonic emissions produced during a therapeutic ultrasound procedure can be detected, localized, and quantified through a class of methods that can be referred to as passive acoustic mapping (PAM). While a variety of PAM beamforming algorithms may be employed, they share a common limitation that a single sound speed is specified for both phase steering of array elements and for calculation of source power or energy. The specified value may be inadequate whether derived from B-mode-based metrics or literature values for constituent materials.

Hemodynamics and Metabolic Parameters in Normothermic Kidney Preservation Are Linked With Donor Factors, Perfusate Cells, and Cytokines.

Kidney transplantation is the best renal-replacement option for most patients with end-stage renal disease. Normothermic machine preservation (NMP) of the kidney has been studied extensively during the last two decades and implemented in clinical trials. Biomarker research led to success in identifying molecules with diagnostic, predictive and therapeutic properties in chronic kidney disease.

Noninvasive assessment of steatosis and viability of cold-stored human liver grafts by MRI.

Purpose: A shortage of suitable donor livers is driving increased use of higher risk livers for transplantation. However, current biomarkers are not sensitive and specific enough to predict posttransplant liver function. This is limiting the expansion of the donor pool.

Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device.

Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically.

Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis-a proteomics study.

We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n = 8 donors after brain death [DBD], n = 8 donors after circulatory death [DCD]) and three with UR (n = 2 DBD, n = 1 DCD), followed by quantitative analysis by mass spectrometry. Damage-associated molecular patterns (DAMPs) were decreased in kidney tissue after 6 hours NMP with URC, suggesting reduced inflammation.

Dual-Array Passive Acoustic Mapping for Cavitation Imaging With Enhanced 2-D Resolution.

Passive acoustic mapping (PAM) techniques have been developed for the purposes of detecting, localizing, and quantifying cavitation activity during therapeutic ultrasound procedures. Implementation with conventional diagnostic ultrasound arrays has allowed planar mapping of bubble acoustic emissions to be overlaid with B-mode anatomical images, with a variety of beamforming approaches providing enhanced resolution at the cost of extended computation times. However, no passive signal processing techniques implemented to date have overcome the fundamental physical limitation of the conventional diagnostic array aperture that results in point spread functions with axial/lateral beamwidth ratios of nearly an order of magnitude.

Urine Recirculation Improves Hemodynamics and Enhances Function in Normothermic Kidney Perfusion.

Unlabelled: The study compares urine recirculation (URC) to urine replacement (UR) with Ringer's lactate in a porcine normothermic kidney machine perfusion (NMP) model using a preclinical prototype device.

Methods: Kidney pairs were recovered uninjured (as live-donor nephrectomy) and perfused consecutively. Pig kidneys (n = 10) were allocated to either NMP with URC (n = 5) or NMP with volume replacement (n = 5).

Spatiotemporal Assessment of the Cellular Safety of Cavitation-Based Therapies by Passive Acoustic Mapping.

Many useful therapeutic bio-effects can be generated using ultrasound-induced cavitation. However, cavitation is also capable of causing unwanted cellular and vascular damage, which should be monitored to ensure treatment safety. In this work, the unique opportunity provided by passive acoustic mapping (PAM) to quantify cavitation dose across an entire volume of interest during therapy is utilised to provide setup-independent measures of spatially localised cavitation dose.

Compensation of array lens effects for improved co-registration of passive acoustic mapping and B-mode images for cavitation monitoring.

Passive acoustic mapping (PAM) techniques offer a simple means of spatio-temporal cavitation monitoring during therapeutic ultrasound procedures. Implementation with a conventional diagnostic ultrasound system allows natural integration of PAM with B-mode imaging. However, the refracting properties of diagnostic array lenses may introduce PAM image registration errors that could lead to inaccuracies in treatment monitoring and guidance.

Transient Cold Storage Prior to Normothermic Liver Perfusion May Facilitate Adoption of a Novel Technology.

Clinical adoption of normothermic machine perfusion (NMP) may be facilitated by simplifying logistics and reducing costs. This can be achieved by cold storage of livers for transportation to recipient centers before commencing NMP. The purpose of this study was to assess the safety and feasibility of post-static cold storage normothermic machine perfusion (pSCS-NMP) in liver transplantation.

Sonothrombolysis with Magnetically Targeted Microbubbles.

Microbubble-enhanced sonothrombolysis is a promising approach to increasing the tolerability and efficacy of current pharmacological treatments for ischemic stroke. Maintaining therapeutic concentrations of microbubbles and drugs at the clot site, however, poses a challenge. The objective of this study was to investigate the effect of magnetic microbubble targeting upon clot lysis rates in vitro.

Microbubbles, Nanodroplets and Gas-Stabilizing Solid Particles for Ultrasound-Mediated Extravasation of Unencapsulated Drugs: An Exposure Parameter Optimization Study.

Ultrasound-induced cavitation has been proposed as a strategy to tackle the challenge of inadequate extravasation, penetration and distribution of therapeutics into tumours. Here, the ability of microbubbles, droplets and solid gas-trapping particles to facilitate mass transport and extravasation of a model therapeutic agent following ultrasound-induced cavitation is investigated. Significant extravasation and penetration depths on the order of millimetres are achieved with all three agents, including the range of pressures and frequencies achievable with existing clinical ultrasound systems.

Focused Ultrasound Hyperthermia for Targeted Drug Release from Thermosensitive Liposomes: Results from a Phase I Trial.

Purpose To demonstrate the feasibility and safety of using focused ultrasound planning models to determine the treatment parameters needed to deliver volumetric mild hyperthermia for targeted drug delivery without real-time thermometry. Materials and Methods This study was part of the Targeted Doxorubicin, or TARDOX, phase I prospective trial of focused ultrasound-mediated, hyperthermia-triggered drug delivery to solid liver tumors ( ClinicalTrials.gov identifier NCT02181075).

Normothermic Machine Perfusion (NMP) Inhibits Proinflammatory Responses in the Liver and Promotes Regeneration.

Liver transplantation (LT) is a successful treatment for patients with liver failure. However, organ shortage results in over 11% of patients losing their chance of a transplant attributed to liver decompensation (LD) and death. Ischemia/reperfusion injury (IRI) following conventional cold storage (CS) is a major cause of injury leading to graft loss after LT.

Long-term radiological and histological outcomes following selective internal radiation therapy to liver metastases from breast cancer.

Liver metastasis from breast cancer is associated with poor prognosis and is a major cause of early morbidity and mortality. When liver resection is not feasible, minimally invasive directed therapies are considered to attempt to prolong survival. Selective internal radiation therapy (SIRT) with yttrium-90 microspheres is a liver-directed therapy that can improve local control of liver metastases from colorectal cancer.

Broadband Ultrasonic Attenuation Estimation and Compensation With Passive Acoustic Mapping.

Several active and passive techniques have been developed to detect, localize, and quantify cavitation activity during therapeutic ultrasound procedures. Much of the prior cavitation monitoring research has been conducted using lossless in vitro systems or small animal models in which path attenuation effects were minimal. However, the performance of these techniques may be substantially degraded by attenuation between the internal therapeutic target and the external monitoring system.

Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial.

Background: Previous preclinical research has shown that extracorporeal devices can be used to enhance the delivery and distribution of systemically administered anticancer drugs, resulting in increased intratumoural concentrations. We aimed to assess the safety and feasibility of targeted release and enhanced delivery of doxorubicin to solid tumours from thermosensitive liposomes triggered by mild hyperthermia, induced non-invasively by focused ultrasound.

Methods: We did an open-label, single-centre, phase 1 trial in a single UK hospital.

Passive Acoustic Mapping Using Data-Adaptive Beamforming Based on Higher Order Statistics.

Sources of nonlinear acoustic emissions, particularly those associated with cavitation activity, play a key role in the safety and efficacy of current and emerging therapeutic ultrasound applications, such as oncological drug delivery, blood-brain barrier opening, and histotripsy. Passive acoustic mapping (PAM) is the first technique to enable real-time and non-invasive imaging of cavitation activity during therapeutic ultrasound exposure, through the recording and passive beamforming of broadband acoustic emissions using an array of ultrasound detectors. Initial limitations in PAM spatial resolution led to the adoption of optimal data-adaptive beamforming algorithms, such as the robust capon beamformer (RCB), that provide improved interference suppression and calibration error mitigation compared to non-adaptive beamformers.

Twenty-four-hour normothermic perfusion of discarded human kidneys with urine recirculation.

Transportable normothermic kidney perfusion for 24 hours or longer could enable viability assessment of marginal grafts, increased organ use, and improved transplant logistics. Eleven clinically declined kidneys were perfused normothermically, with 6 being from donors after brain death (median cold ischemia time 33 ± 36.9 hours) and 5 being from donors after circulatory death (36.

A randomized trial of normothermic preservation in liver transplantation.

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing.