Monitoring Blood-Brain Barrier Opening in Rats with a Preclinical Focused Ultrasound System.

The brain has a highly selective semipermeable blood barrier, termed the blood-brain barrier (BBB), which prevents the delivery of therapeutic macromolecular agents to the brain. The integration of MR-guided low-intensity pulsed focused ultrasound (FUS) with microbubble pre-injection is a promising technique for non-invasive and non-toxic BBB modulation. MRI can offer superior soft-tissue contrast and various quantitative assessments, such as vascular permeability, perfusion, and the spatial-temporal distribution of MRI contrast agents.

Treatment Planning Strategies for Interstitial Ultrasound Ablation of Prostate Cancer.

Purpose: To develop patient-specific 3D models using Finite-Difference Time-Domain (FDTD) simulations and pre-treatment planning tools for the selective thermal ablation of prostate cancer with interstitial ultrasound. This involves the integration with a FDA 510(k) cleared catheter-based ultrasound interstitial applicators and delivery system.

Methods: A 3D generalized "prostate" model was developed to generate temperature and thermal dose profiles for different applicator operating parameters and anticipated perfusion ranges.

Volumetric hyperthermia delivery using the ExAblate Body MR-guided focused ultrasound system.

Objectives: To investigate image-guided volumetric hyperthermia strategies using the ExAblate Body MR-guided focused ultrasound ablation system, involving mechanical transducer movement and sector-vortex beamforming.

Materials And Methods: Acoustic and thermal simulations were performed to investigate volumetric hyperthermia using mechanical transducer movement combined with sector-vortex beamforming, specifically for the ExAblate Body transducer. The system control in the ExAblate Body system was modified to achieve fast transducer movement and MR thermometry-based hyperthermia control, mechanical transducer movements and electronic sector-vortex beamforming were combined to optimize hyperthermia delivery.

Motion-robust, multi-slice, real-time MR thermometry for MR-guided thermal therapy in abdominal organs.

Purpose: To develop an effective and practical reconstruction pipeline to achieve motion-robust, multi-slice, real-time MR thermometry for monitoring thermal therapy in abdominal organs.

Methods: The application includes a fast spiral magnetic resonance imaging (MRI) pulse sequence and a real-time reconstruction pipeline based on multi-baseline proton resonance frequency shift (PRFS) method with visualization of temperature imaging. The pipeline supports multi-slice acquisition with minimal reconstruction lag.

An endoluminal cylindrical sectored-ring ultrasound phased-array applicator for minimally-invasive therapeutic ultrasound.

Background: The size of catheter-based ultrasound devices for delivering ultrasound energy to deep-seated tumors is constrained by the access pathway which limits their therapeutic capabilities.

Purpose: To devise and investigate a deployable applicator suitable for minimally-invasive delivery of therapeutic ultrasound, consisting of a 2D cylindrical sectored-ring ultrasound phased array, integrated within an expandable paraboloid-shaped balloon-based reflector. The balloon can be collapsed for compact delivery and expanded close to the target position to mimic a larger-diameter concentric-ring sector-vortex array for enhanced dynamic control of focal depth and volume.

Technical note: Low-cost MR-compatible pneumatic respiratory organ motion simulator for the development of MR-guided thermal therapy.

Background: In magnetic resonance (MR)-guided thermal therapy, respiratory motion can cause a significant temperature error in MR thermometry and reduce the efficiency of the treatment. A respiratory motion simulator is necessary for the development of new MR imaging (MRI) and motion compensation techniques.

Purpose: The purpose of this study is to develop a low-cost and simple MR-compatible respiratory motion simulator to support proof-of-concept studies of MR monitoring approaches with respiratory-induced abdominal organ motion.

Sonication strategies toward volumetric ultrasound hyperthermia treatment using the ExAblate body MRgFUS system.

Purpose: The ExAblate body MRgFUS system requires advanced beamforming strategies for volumetric hyperthermia. This study aims to develop and evaluate electronic beam steering, multi-focal patterns, and sector vortex beamforming approaches in conjunction with partial array activation using an acoustic and biothermal simulation framework along with phantom experiments.

Methods: The simulation framework was developed to calculate the 3D acoustic intensity and temperature distribution resulting from various beamforming and scanning strategies.

Deployable ultrasound applicators for endoluminal delivery of volumetric hyperthermia.

Purpose: To investigate the design of an endoluminal deployable ultrasound applicator for delivering volumetric hyperthermia to deep tissue sites as a possible adjunct to radiation and chemotherapy.

Method: This study considers an ultrasound applicator consisting of two tubular transducers situated at the end of a catheter assembly, encased within a distensible conical shaped balloon-based reflector that redirects acoustic energy distally into the tissue. The applicator assembly can be inserted endoluminally or laparoscopically in a compact form and expanded after delivery to the target site.

AAPM Task Group 241: A medical physicist's guide to MRI-guided focused ultrasound body systems.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a completely non-invasive technology that has been approved by FDA to treat several diseases. This report, prepared by the American Association of Physicist in Medicine (AAPM) Task Group 241, provides background on MRgFUS technology with a focus on clinical body MRgFUS systems. The report addresses the issues of interest to the medical physics community, specific to the body MRgFUS system configuration, and provides recommendations on how to successfully implement and maintain a clinical MRgFUS program.

High Contrast Ultrasonic Method With Multi-Spatiotemporal Compounding for Monitoring Catheter-Based Ultrasound Thermal Therapy: Development and Ex Vivo Evaluations.

Objective: Changes in ultrasound backscatter energy (CBE) imaging can monitor thermal therapy. Catheter-based ultrasound (CBUS) can treat deep tumors with precise spatial control of energy deposition and ablation zones, of which CBE estimation can be limited by low contrast and robustness due to small or inconsistent changes in ultrasound data. This study develops a multi-spatiotemporal compounding CBE (MST-CBE) imaging approach for monitoring specific to CBUS thermal therapy.

Anatomic thermochromic tissue-mimicking phantom of the lumbar spine for pre-clinical evaluation of MR-guided focused ultrasound (MRgFUS) ablation of the facet joint.

Objective: To develop a thermochromic tissue-mimicking phantom (TTMP) with an embedded 3D-printed bone mimic of the lumbar spine to evaluate MRgFUS ablation of the facet joint and medial branch nerve.

Materials And Methods: Multiple 3D-printed materials were selected and characterized by measurements of speed of sound and linear acoustic attenuation coefficient using a through-transmission technique. A 3D model of the lumbar spine was segmented from a de-identified CT scan, and 3D printed.

LIPUS far-field exposimetry system for uniform stimulation of tissues in-vitro: development and validation with bovine intervertebral disc cells.

Therapeutic Low-intensity Pulsed Ultrasound (LIPUS) has been applied clinically for bone fracture healing and has been shown to stimulate extracellular matrix (ECM) metabolism in numerous soft tissues including intervertebral disc (IVD). In-vitro LIPUS testing systems have been developed and typically include polystyrene cell culture plates (CCP) placed directly on top of the ultrasound transducer in the acoustic near-field (NF). This configuration introduces several undesirable acoustic artifacts, making the establishment of dose-response relationships difficult, and is not relevant for targeting deep tissues such as the IVD, which may require far-field (FF) exposure from low frequency sources.

Microbubble-Facilitated Ultrasound Catheter Ablation Causes Microvascular Damage and Fibrosis.

High-intensity ultrasound (US) ablation produces deeper myocardial lesions than radiofrequency ablation. The presence of intravascular microbubble (MB) contrast agents enhances pulsed-wave US ablation via cavitation-related histotripsy, potentially facilitating ablation in persistently perfused/conducting myocardium. US ablation catheters were developed and tested in the presence of MBs using ex vivo and in vivo models.

In vivo Nakagami-m parametric imaging of microbubble-enhanced ultrasound regulated by RF and VF processing techniques.

Purpose: Application of the Nakagami statistical model and associated m parameter has the potential to suppress artifacts from adjustable system parameters and operator selections typical in echo amplitude-coded microbubble-enhanced ultrasound (MEUS). However, the feasibility of applying m estimation and determination of the associated Nakagami distribution features for in vivo MEUS remain to be investigated. Sensitivity and discriminability of m-coded MEUS are often limited since raw envelopes are regulated by complex radiofrequency (RF) and video-frequency (VF) processing.

In silico feasibility assessment of extracorporeal delivery of low-intensity pulsed ultrasound to intervertebral discs within the lumbar spine.

Low intensity pulsed ultrasound (LIPUS) may have utility for non-invasive treatment of discogenic lower back pain through stimulating, remodeling and accelerating healing of injured or degenerated intervertebral disc (IVD) tissues. This study investigates the feasibility of delivering LIPUS to lumbar IVDs between L2 and S1 spine vertebra using a planar extracorporeal phased array (8 × 8 cm, 1024 elements, 500 kHz). Three 3D anatomical models with heterogenous tissues were generated from patient CT image sets and used in the simulation-based analysis.

Dual-sectored transurethral ultrasound for thermal treatment of stress urinary incontinence: in silico studies in 3D anatomical models.

The purpose of this study is to investigate the feasibility and performance of a stationary, non-focused dual-sectored tubular transurethral ultrasound applicator for thermal exposure of tissue regions adjacent to the urethra for treatment of stress urinary incontinence (SUI) through acoustic and biothermal simulations on 3D anatomical models. Parametric studies in a generalized tissue model over dual-sectored ultrasound applicator configurations (acoustic surface intensities, lateral active acoustic output sector angles, and durations) were performed. Selected configurations and delivery strategies were applied on 3D pelvic anatomical models.

Endobronchial high-intensity ultrasound for thermal therapy of pulmonary malignancies: simulations with patient-specific lung models.

This study investigates the feasibility of endobronchial ultrasound applicators for thermal ablation of lung tumors using acoustic and biothermal simulations. Endobronchial ultrasound applicators with planar (10 mm width) or tubular transducers (6 mm outer diameter (OD)) encapsulated by expandable coupling balloons (10 mm OD) are considered for treating tumors from within major airways; smaller catheter-based applicators with tubular transducers (1.7-4 mm OD) and coupling balloons (2.

Deployable cylindrical phased-array applicator mimicking a concentric-ring configuration for minimally-invasive delivery of therapeutic ultrasound.

A novel design for a deployable catheter-based ultrasound applicator for endoluminal and laparoscopic intervention is introduced. By combining a 1D cylindrical ring phased array with an expandable paraboloid or conical-shaped balloon-based reflector, the applicator can be controllably collapsed for compact delivery and deployed to mimic a forward-firing larger diameter concentric ring array with tight focusing and electronic steering capabilities in depth. Comprehensive acoustic and biothermal parametric studies were employed to characterize the capabilities of the applicator design as a function of transducer dimensions, phased array configuration, and balloon reflector geometry.

Noninvasive, Targeted Creation of Neuromyelitis Optica Pathology in AQP4-IgG Seropositive Rats by Pulsed Focused Ultrasound.

Neuromyelitis optica spectrum disorders (herein called NMO) is an autoimmune disease of the CNS characterized by astrocyte injury, inflammation, and demyelination. In seropositive NMO, immunoglobulin G autoantibodies against aquaporin-4 (AQP4-IgG) cause primary astrocyte injury. A passive transfer model of NMO was developed in which spatially targeted access of AQP4-IgG into the CNS of seropositive rats was accomplished by pulsed focused ultrasound through intact skin.

880 kHz ultrasound treatment for drug delivery to the vitreous humor.

Clinical management of many chronic ophthalmological disorders requires direct delivery of drugs into the vitreous. There is an important need to investigate novel needle-less alternatives to deliver drugs to the vitreous. The purpose of this study is to assess the effects of a needle-less system using ultrasound to enhance vitreal delivery of small molecules through the sclera in an model and to evaluate whether changes in permeability are mainly due to the heat generated by sonication.

MR thermometry-guided ultrasound hyperthermia of user-defined regions using the ExAblate prostate ablation array.

Background: Hyperthermia therapy (HT) has shown to be an effective adjuvant to radiation, chemotherapy, and immunotherapy. In order to be safe and effective, delivery of HT requires maintenance of target tissue temperature within a narrow range (40-44 °C) for 30-60 min, which necessitates conformal heat delivery and accurate temperature monitoring. The goal of this project was to develop an MR thermometry-guided hyperthermia delivery platform based upon the ExAblate prostate array that would achieve uniform stable heating over large volumes within the prostate, while allowing the user to precisely control the power deposition patterns and shape of the region of treatment (ROT).

Assessing high-intensity focused ultrasound treatment of prostate cancer with hyperpolarized C dual-agent imaging of metabolism and perfusion.

The goal of the study was to establish early hyperpolarized (HP) C MRI metabolic and perfusion changes that predict effective high-intensity focused ultrasound (HIFU) ablation and lead to improved adjuvant treatment of partially treated regions. To accomplish this a combined HP dual-agent ( C pyruvate and C urea) C MRI/multiparametric H MRI approach was used to measure prostate cancer metabolism and perfusion 3-4 h, 1 d, and 5 d after exposure to ablative and sub-lethal doses of HIFU within adenocarcinoma of mouse prostate tumors using a focused ultrasound applicator designed for murine studies. Pathologic and immunohistochemical analysis of the ablated tumor demonstrated fragmented, non-viable cells and vasculature consistent with coagulative necrosis, and a mixture of destroyed tissue and highly proliferative, poorly differentiated tumor cells in tumor tissues exposed to sub-lethal heat doses in the ablative margin.

Transurethral high-intensity ultrasound for treatment of stress urinary incontinence (SUI): simulation studies with patient-specific models.

Background: Stress urinary incontinence (SUI) is prevalent in adult women, attributed to weakened endopelvic supporting tissues, and typically treated using drugs and invasive surgical procedures. The objective of this in silico study is to explore transurethral high-intensity ultrasound for delivery of precise thermal therapy to the endopelvic tissues adjacent to the mid-urethra, to induce thermal remodeling as a potential minimally invasive treatment alternative.

Methods: 3D acoustic (Rayleigh-Sommerfeld) and biothermal (Pennes bioheat) models of the ultrasound applicator and surrounding tissues were devised.

A minimally invasive catheter-based ultrasound technology for therapeutic interventions in brain: initial preclinical studies.

OBJECTIVE Minimally invasive procedures may allow surgeons to avoid conventional open surgical procedures for certain neurological disorders. This paper describes the iterative process for development of a catheter-based ultrasound thermal therapy applicator. METHODS Using an ultrasound applicator with an array of longitudinally stacked and angularly sectored tubular transducers within a catheter, the authors conducted experimental studies in porcine liver, in vivo and ex vivo, in order to characterize the device performance and lesion patterns.

Low intensity pulsed ultrasound (LIPUS) for the treatment of intervertebral disc degeneration.

Discogenic back pain presents a major public health issue, with current therapeutic interventions limited to short-term symptom relief without providing regenerative remedies for diseased intervertebral discs (IVD). Many of these interventions are invasive and can diminish the biomechanical integrity of the IVDs. Low intensity pulsed ultrasound (LIPUS) is a potential treatment option that is both non-invasive and regenerative.