Publications by authors named "Gail ter Haar"

An improvement in the reliability and comparability of tissue characterization results is crucial for enabling further progress in cancer detection and the assessment of therapeutic effects. This can only be achieved by integrating quantitative methods into well-established qualitative characterization routines. This case study presents a hybrid metrological approach for tissue characterisation including vibrational Fourier Transform InfraRed (FTIR) spectroscopy and traceable reference-free X-Ray Fluorescence analysis (XRF).

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High intensity focused ultrasound (HIFU) can destroy tissue by thermal ablation which may be accompanied by acoustic cavitation and/or tissue water boiling, but the biological and histological effects of these treatments have not been fully documented. Here, detailed histological analysis over time using well characterized HIFU exposures in rat livers is described. Exposures used invoked either (i) thermal, with acoustic cavitation and/or tissue water boiling or (ii) predominantly thermal damage.

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A toroidal high-intensity focused ultrasound (HIFU) transducer was used to expose normal bladder wall tissues non-invasively in vivo in a porcine model in order to investigate the potential to treat bladder tumors. The transducer was divided into 32 concentric rings with equal surface areas, operating at 2.5 MHz.

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Hyperthermia is currently used to treat cancer due to its ability to radio- and chemo-sensitize and to stimulate the immune response. While ultrasound is non-ionizing and can induce hyperthermia deep within the body non-invasively, achieving uniform and volumetric hyperthermia is challenging. This work presents a novel focused ultrasound hyperthermia system based on 3D-printed acoustic holograms combined with a high-intensity focused ultrasound (HIFU) transducer to produce a uniform iso-thermal dose in multiple targets.

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High-intensity focused ultrasound can ablate a target permanently, leaving tissues through which it passes thermally unaffected. When delivered under magnetic resonance (MR) imaging guidance, the change in tissue relaxivity on heating is used to monitor the temperatures achieved. Different tissue types in the pre-focal beam path result in energy loss defined by their individual attenuation coefficients.

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These recommendations are intended to provide guidance and to encourage best practice in reporting therapeutic ultrasound treatment parameters. Detailed uniform reporting will allow testing of therapy ultrasound systems and protocols, cross-comparison of studies between different teams using different systems and validation of therapeutic bio-effects. These recommendations have been divided into two sets, one for clinical and one for preclinical studies, each with stratified reporting categories, to account for the disparities in expertise and access to equipment between sites.

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The thermal and mechanical effects induced in tissue by ultrasound can be exploited for therapeutic applications. Tissue-mimicking materials (TMMs), reflecting different soft tissue properties, are required for experimental evaluation of therapeutic potential. In the study described here, poly(vinyl alcohol) (PVA) hydrogels were characterized.

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Traditional oncological interventions have failed to improve survival for pancreatic cancer patients significantly. Novel treatment modalities able to release cancer-specific antigens, render immunologically "cold" pancreatic tumours "hot" and disrupt or reprogram the pancreatic tumour microenvironment are thus urgently needed. Therapeutic focused ultrasound exerts thermal and mechanical effects on tissue, killing cancer cells and inducing an anti-cancer immune response.

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Thermal ablation is a form of hyperthermia in which oncologic control can be achieved by briefly inducing elevated temperatures, typically in the range 50-80°C, within a target tissue. Ablation modalities include high intensity focused ultrasound, radiofrequency ablation, microwave ablation, and laser interstitial thermal therapy which are all capable of generating confined zones of tissue destruction, resulting in fewer complications than conventional cancer therapies. Oncologic control is contingent upon achieving predefined coagulation zones; therefore, intraoperative assessment of treatment progress is highly desirable.

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This review provides an introduction to high-intensity focused ultrasound (HIFU) and reviews its historical and current use in urological surgery. Current and historical literature (1927-2020), including that describing trials and review articles in the medical and ultrasonic literature, has been reviewed, using Pub Med and Cochrane search engines. HIFU is currently one of a number of treatments for prostate cancer, both as a primary treatment that can be repeated, and as a salvage treatment post-radiotherapy.

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Background: Sub-ablative heat induces pleiotropic biological effects in cancer cells, activating programmed cell death or survival processes. These processes decide the fate of the heated cell. This study investigates these and assesses whether heat, in combination with HSP90 inhibition, augments cell death and induces a pro-immune phenotype in these cells.

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Ultrasound safety is of particular importance in fetal and neonatal scanning. Fetal tissues are vulnerable and often still developing, the scanning depth may be low, and potential biological effects have been insufficiently investigated. On the other hand, the clinical benefit may be considerable.

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Background: Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) therapy of pelvic tumors is currently assessed by visual estimation of the proportion of tumor that can be reached by the device's focus (coverage). Since it is important to assess whether enough energy reaches the tumor to achieve ablation, a methodology for estimating the proportion of the tumor that can be ablated (treatability) was developed. Predicted treatability was compared against clinically achieved thermal ablation.

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Pulsed high-intensity focused ultrasound (pHIFU) uses acoustic pressure to physically disrupt tumours. The aim of this study was to investigate whether pHIFU can be used in combination with immune checkpoint inhibitors (ICIs) to enhance survival of tumour-bearing animals. Murine orthotopic pancreatic KPC tumours were exposed both to a grid of pHIFU lesions (peak negative pressure = 17 MPa, frequency = 1.

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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.

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Introduction: The quantification of heating effects during exposure to ultrasound is usually based on laboratory experiments in water and is assessed using extrapolated parameters such as the thermal index. In our study, we have measured the temperature increase directly in a simulator of the maternal-fetal environment, the 'ISUOG Phantom', using clinically relevant ultrasound scanners, transducers and exposure conditions.

Methods: The study was carried out using an instrumented phantom designed to represent the pregnant maternal abdomen and which enabled temperature recordings at positions in tissue mimics which represented the skin surface, sub-surface, amniotic fluid and fetal bone interface.

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Objective: To document longitudinal symptom, quality-of-life and imaging response in patients with recurrent gynecological tumors treated with magnetic resonance guided high intensity focused ultrasound (MRgHIFU), and compare changes in patients with intra- versus extra-pelvic lesions.

Methods: Eleven symptomatic patients with painful recurrent gynecological tumors were treated with MRgHIFU (Profound Sonalleve) in a prospective single center study (NCT02714621). Pain scores, analgesic intake and quality-of-life metrics, whole tumor volume, and perfused tumor volume from Gadolinium-enhanced T1W imaging documented before and up to 90 days after treatment were compared between patients with intra- and extra-pelvic tumors.

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The safe and effective delivery of anticancer agents to diseased tissues is one of the significant challenges in cancer therapy. Conventional anticancer agents are generally cytotoxins with poor pharmacokinetics and bioavailability. Nanocarriers are nanosized particles designed for the selectivity of anticancer drugs and gene transport to tumors.

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Temperature estimation is a fundamental step in assessment of the efficacy of thermal therapy. A thermochromic material sensitive within the temperature range 52.5°C-75°C has been developed.

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Background: Patient suitability for magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) ablation of pelvic tumors is initially evaluated clinically for treatment feasibility using referral images, acquired using standard supine diagnostic imaging, followed by MR screening of potential patients lying on the MRgHIFU couch in a 'best-guess' treatment position. Existing evaluation methods result in ≥40% of referred patients being screened out because of tumor non-targetability. We hypothesize that this process could be improved by development of a novel algorithm for predicting tumor coverage from referral imaging.

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The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e.

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Current in vitro sonication experiments show immense variability in experimental set-ups and methods used. As a result, there is uncertainty in the ultrasound field parameters experienced by sonicated samples, poor reproducibility of these experiments and thus reduced scientific value of the results obtained. The scope of this narrative review is to briefly describe mechanisms of action of ultrasound, list the most frequently used experimental set-ups and focus on a description of factors influencing the outcomes and reproducibility of these experiments.

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For multimodality therapies such as the combination of hyperthermia and radiation, quantification of biological effects is key for dose prescription and response prediction. Tumour spheroids have a microenvironment that more closely resembles that of tumours in vivo and may thus be a superior in vitro cancer model than monolayer cultures. Here, the response of tumour spheroids formed from two established human cancer cell lines (HCT116 and CAL27) to single and combination treatments of radiation (0-20 Gy), and hyperthermia at 47 °C (0-780 CEM) has been evaluated.

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