Publications by authors named "Gail R Ter Haar"

12 Publications

  • Page 1 of 1

Inertial Cavitation Behaviors Induced by Nonlinear Focused Ultrasound Pulses.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 27;68(9):2884-2895. Epub 2021 Aug 27.

Inertial cavitation induced by pulsed high-intensity focused ultrasound (pHIFU) has previously been shown to successfully permeabilize tumor tissue and enhance chemotherapeutic drug uptake. In addition to HIFU frequency, peak rarefactional pressure ( p ), and pulse duration, the threshold for cavitation-induced bioeffects has recently been correlated with asymmetric distortion caused by nonlinear propagation, diffraction and formation of shocks in the focal waveform, and therefore with the transducer F -number. To connect previously observed bioeffects with bubble dynamics and their attendant physical mechanisms, the dependence of inertial cavitation behavior on shock formation was investigated in transparent agarose gel phantoms using high-speed photography and passive cavitation detection (PCD). Agarose phantoms with concentrations ranging from 1.5% to 5% were exposed to 1-ms pulses using three transducers of the same aperture but different focal distances ( F -numbers of 0.77, 1.02, and 1.52). Pulses had central frequencies of 1, 1.5, or 1.9 MHz and a range of p at the focus varying within 1-18 MPa. Three distinct categories of bubble behavior were observed as the acoustic power increased: stationary near-spherical oscillation of individual bubbles, proliferation of multiple bubbles along the pHIFU beam axis, and fanned-out proliferation toward the transducer. Proliferating bubbles were only observed under strongly nonlinear or shock-forming conditions regardless of frequency, and only where the bubbles reached a certain threshold size range. In stiffer gels with higher agarose concentrations, the same pattern of cavitation behavior was observed, but the dimensions of proliferating clouds were smaller. These observations suggest mechanisms that may be involved in bubble proliferation: enhanced growth of bubbles under shock-forming conditions, subsequent shock scattering from the gel-bubble interface, causing an increase in the repetitive tension created by the acoustic wave, and the appearance of a new growing bubble in the proximal direction. Different behaviors corresponded to specific spectral characteristics in the PCD signals: broadband noise in all cases, narrow peaks of backscattered harmonics in the case of stationary bubbles, and broadened, shifted harmonic peaks in the case of proliferating bubbles. The shift in harmonic peaks can be interpreted as a Doppler shift from targets moving at speeds of up to 2 m/s, which correspond to the observed bubble proliferation speeds.
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http://dx.doi.org/10.1109/TUFFC.2021.3073347DOI Listing
September 2021

Comparison of Imaging Changes and Pain Responses in Patients with Intra- or Extraosseous Bone Metastases Treated Palliatively with Magnetic Resonance-Guided High-Intensity-Focused Ultrasound.

J Vasc Interv Radiol 2019 Sep 14;30(9):1351-1360.e1. Epub 2019 May 14.

Cancer Research UK Cancer Imaging Centre, Magnetic Resonance Imaging Unit, The Royal Marsden Hospital, Sutton, Surrey SM2 5PT, United Kingdom.

Purpose: This study compared changes in imaging and in pain relief between patients with intraosseous, as opposed to extraosseous bone metastases. Both groups were treated palliatively with magnetic resonance-guided high-intensity-focused ultrasound (MRgHIFU).

Materials And Methods: A total of 21 patients were treated prospectively with MRgHIFU at 3 centers. Intraprocedural thermal changes measured using proton resonance frequency shift (PRFS) thermometry and gadolinium-enhanced T1-weighted (Gd-T1W) image appearances after treatment were compared for intra- and extraosseous metastases. Pain scores and use of analgesic therapy documented before and up to 90 days after treatment were used to classify responses and were compared between the intra- and extraosseous groups. Gd-T1W changes were compared between responders and nonresponders in each group.

Results: Thermal dose volumes were significantly larger in the extraosseous group (P = 0.039). Tumor diameter did not change after treatment in either group. At day 30, Gd-T1W images showed focal nonenhancement in 7 of 9 patients with intraosseous tumors; in patients with extraosseous tumors, changes were heterogeneous. Cohort reductions in worst-pain scores were seen for both groups, but differences from baseline at days 14, 30, 60, and 90 were only significant for the intraosseous group (P = 0.027, P = 0.013, P = 0.012, and P = 0.027, respectively). By day 30, 67% of patients (6 of 9) with intraosseous tumors were classified as responders, and the rate was 33% (4 of 12) for patients with extraosseous tumors. In neither group was pain response indicated by nonenhancement on Gd-T1W.

Conclusions: Intraosseous tumors showed focal nonenhancement by day 30, and patients had better pain response to MRgHIFU than those with extraosseous tumors. In this small cohort, post-treatment imaging was not informative of treatment efficacy.
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http://dx.doi.org/10.1016/j.jvir.2019.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715806PMC
September 2019

MR guided high intensity focused ultrasound (MRgHIFU) for treating recurrent gynaecological tumours: a pilot feasibility study.

Br J Radiol 2019 Jun 14;92(1098):20181037. Epub 2019 May 14.

1 The CRUK Cancer Imaging Centre, The Institute of Cancer Research and The Royal Marsden Hospital , London , United Kingdom.

Objective: To assess the feasibility of targeting recurrent gynaecological tumours with MR guided high intensity focused ultrasound (MRgHIFU).

Methods: 20 patients with recurrent gynaecological tumours were prospectively scanned on a Philips/Profound 3 T Achieva MR/ Sonalleve HIFU system. Gross tumour volume (GTV) and planning target volume (PTV) were delineated on W and diffusion-weighted imaging (DWI). Achievable treatment volumes that (i) assumed bowel and/or urogenital tract preparation could be used to reduce risk of damage to organs-at-risk (TV), or (ii) assumed no preparations were possible (TV) were compared with PTV on virtual treatment plans. Patients were considered treatable if TV ≥ 50 % PTV.

Results: 11/20 patients (55%) were treatable if preparation strategies were used: nine had central pelvic recurrences, two had tumours in metastatic locations. Treatable volume ranged from 3.4 to 90.3 ml, representing 70 ± 17 % of PTVs. Without preparation, 6/20 (30%) patients were treatable (four central recurrences, two metastatic lesions). Limiting factors were disease beyond reach of the HIFU transducer, and bone obstructing tumour access. DWI assisted tumour outlining, but differences from W imaging in GTV size (16.9 ± 23.0%) and PTV location (3.8 ± 2.8 mm in phase-encode direction) limited its use for treatment planning.

Conclusions: Despite variation in size and location within the pelvis, ≥ 50 % of tumour volumes were considered targetable in 55 % patients while avoiding adjacent critical structures. A prospective treatment study will assess safety and symptom relief in a second patient cohort.

Advances In Knowledge: Target size, location and access make MRgHIFU a viable treatment modality for treating symptomatic recurrent gynaecological tumours within the pelvis.
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http://dx.doi.org/10.1259/bjr.20181037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592075PMC
June 2019

Value of diffusion-weighted imaging for monitoring tissue change during magnetic resonance-guided high-intensity focused ultrasound therapy in bone applications: an study.

Eur Radiol Exp 2018 10;2(1):10. Epub 2018 May 10.

2Cancer Research UK Cancer Imaging Centre, Division of Imaging and Radiotherapy, The Institute of Cancer Research, London, UK.

Background: Magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) can palliate metastatic bone pain by periosteal neurolysis. We investigated the value of diffusion-weighted imaging (DWI) for monitoring soft tissue changes adjacent to bone during MR-guided HIFU. We evaluated the repeatability of the apparent diffusion coefficient (ADC) measurement, the temporal evolution of ADC change after sonication, and its relationship with thermal parameters.

Methods: experiments in lamb legs ( = 8) were performed on a Sonalleve MR-guided HIFU system. Baseline proton resonance frequency shift (PRFS) thermometry evaluated the accuracy of temperature measurements and tissue cooling times after exposure. PRFS acquired during sonication ( = 27) was used to estimate thermal dose volume and temperature. After repeat baseline measurements, DWI was assessed longitudinally and relative ADC changes were derived for heated regions.

Results: Baseline PRFS was accurate to 1 °C and showed that tissues regained baseline temperatures within 5 min. Before sonication, coefficient of variation for repeat ADC measurements was 0.8%. After sonication, ADC increased in the muscle adjacent to the exposed periosteum, it was maximal 1-5 min after sonication, and it significantly differed between samples with persistent versus non-persistent ADC changes beyond 20 min. ADC increases at 20 min were stable for 2 h and correlated significantly with thermal parameters (ADC versus applied acoustic energy at 16-20 min: = 0.77, < 0.001). A 20% ADC increase resulted in clear macroscopic tissue damage.

Conclusions: Our preliminary results suggest that DWI can detect intra-procedural changes in ex-vivo muscle overlying the periosteum. This could be useful for studying the safety and efficacy of clinical MR-guided HIFU bone treatments.
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http://dx.doi.org/10.1186/s41747-018-0041-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945713PMC
May 2018

Development of a hybrid magnetic resonance and ultrasound imaging system.

Biomed Res Int 2014 7;2014:914347. Epub 2014 Aug 7.

Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London SW7 3RP, UK.

A system which allows magnetic resonance (MR) and ultrasound (US) image data to be acquired simultaneously has been developed. B-mode and Doppler US were performed inside the bore of a clinical 1.5 T MRI scanner using a clinical 1-4 MHz US transducer with an 8-metre cable. Susceptibility artefacts and RF noise were introduced into MR images by the US imaging system. RF noise was minimised by using aluminium foil to shield the transducer. A study of MR and B-mode US image signal-to-noise ratio (SNR) as a function of transducer-phantom separation was performed using a gel phantom. This revealed that a 4 cm separation between the phantom surface and the transducer was sufficient to minimise the effect of the susceptibility artefact in MR images. MR-US imaging was demonstrated in vivo with the aid of a 2 mm VeroWhite 3D-printed spherical target placed over the thigh muscle of a rat. The target allowed single-point registration of MR and US images in the axial plane to be performed. The system was subsequently demonstrated as a tool for the targeting and visualisation of high intensity focused ultrasound exposure in the rat thigh muscle.
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http://dx.doi.org/10.1155/2014/914347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142177PMC
May 2015

Do we need to restrict the use of Doppler ultrasound in the first trimester of pregnancy?

Ultrasound Med Biol 2013 Mar 16;39(3):374-80. Epub 2013 Jan 16.

Joint Department of Physics, Division of Radiotherapy and Imaging, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK.

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http://dx.doi.org/10.1016/j.ultrasmedbio.2012.11.024DOI Listing
March 2013

Telling it like it is.

J Ther Ultrasound 2013 25;1. Epub 2013 Apr 25.

Joint Department of Physics, Institute of Cancer Research, Sutton, SM2 5NG, UK.

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http://dx.doi.org/10.1186/2050-5736-1-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988612PMC
April 2014

Design and development of a prototype endocavitary probe for high-intensity focused ultrasound delivery with integrated magnetic resonance imaging.

J Magn Reson Imaging 2007 Mar;25(3):548-56

Therapeutic Ultrasound, Joint Department of Physics, The Institute of Cancer Research, Sutton, Surrey, UK.

Purpose: To integrate a high intensity focused ultrasound (HIFU) transducer with an MR receiver coil for endocavitary MR-guided thermal ablation of localized pelvic lesions.

Materials And Methods: A hollow semicylindrical probe (diameter 3.2 cm) with a rectangular upper surface (7.2 cm x 3.2 cm) was designed to house a HIFU transducer and enable acoustic contact with an intraluminal wall. The probe was distally rounded to ease endocavitary insertion and was proximally tapered to a 1.5-cm diameter cylindrical handle through which the irrigation tubes (for transducer cooling) and electrical connections were passed. MR compatibility of piezoceramic and piezocomposite transducers was assessed using gradient-echo (GRE) sequences. The radiofrequency (RF) tuning of identical 6.5 cm x 2.5 cm rectangular receiver coils on the upper surface of the probe was adjusted to compensate for the presence of the conductive components of the HIFU transducers. A T1-weighted (T1-W) sliding window dual-echo GRE sequence monitored phase changes in the focal zone of each transducer. High-intensity (2400 W/cm(-2)), short duration (<1.5 seconds) exposures produced subtherapeutic temperature rises.

Results: For T1-W images, signal-to-noise ratio (SNR) improved by 40% as a result of quartering the conductive surface of the piezoceramic transducer. A piezocomposite transducer showed a further 28% improvement. SNRs for an endocavitary coil in the focal plane of the HIFU trans-ducer (4 cm from its face) were three times greater than from a phased body array coil. Local shimming improved uniformity of phase images. Phase changes were detected at subtherapeutic exposures.

Conclusion: We combined a HIFU transducer with an MR receiver coil in an endocavitary probe. SNRs were improved by quartering the conductive surface of the piezoceramic. Further improvement was achieved with a piezocomposite transducer. A phase change was seen on MR images during both subtherapeutic and therapeutic HIFU exposures.
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http://dx.doi.org/10.1002/jmri.20833DOI Listing
March 2007

Spatial and acoustic pressure dependence of microbubble-mediated gene delivery targeted using focused ultrasound.

J Gene Med 2006 Nov;8(11):1347-57

The Institute of Cancer Research, Gene Therapy Group, Department of Cell and Molecular Biology, 237 Fulham Road, Chelsea, London SW3 6JB, UK.

Background: Ultrasound/microbubble-mediated gene delivery has the potential to be targeted to tissue deep in the body by directing the ultrasound beam following vector administration. Application of this technology would be minimally invasive and benefit from the widespread clinical experience of using ultrasound and microbubble contrast agents. In this study we evaluate the targeting ability and spatial distribution of gene delivery using focused ultrasound.

Methods: Using a custom-built exposure tank, Chinese hamster ovary cells in the presence of SonoVue microbubbles and plasmid encoding beta-galactosidase were exposed to ultrasound in the focal plane of a 1 MHz transducer. Gene delivery and cell viability were subsequently assessed. Characterisation of the acoustic field and high-resolution spatial analysis of transfection were used to examine the relationship between gene delivery efficiency and acoustic pressure.

Results: In contrast to that seen in the homogeneous field close to the transducer face, gene delivery in the focal plane was concentrated on the ultrasound beam axis. Above a minimum peak-to-peak value of 0.1 MPa, transfection efficiency increased as acoustic pressure increased towards the focus, reaching a maximum above 1 MPa. Delivery was microbubble-dependent and cell viability was maintained.

Conclusions: Gene delivery can be targeted using focused ultrasound and microbubbles. Since delivery is dependent on acoustic pressure, the degree of targeting can be determined by appropriate transducer design to modify the ultrasound field. In contrast to other physical gene delivery approaches, the non-invasive targeting ability of ultrasound makes this technology an attractive option for clinical gene therapy.
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http://dx.doi.org/10.1002/jgm.962DOI Listing
November 2006

Physical parameters affecting ultrasound/microbubble-mediated gene delivery efficiency in vitro.

Ultrasound Med Biol 2006 Aug;32(8):1269-79

The Institute of Cancer Research, Gene Therapy Group, Section of Cell and Molecular Biology, London, UK.

Ultrasound (US)/microbubble-mediated gene delivery is a technology with many potential advantages suited to clinical application. Previous studies have demonstrated transfection but many are unsatisfactory in respect to the exposure apparatus, lack of definition of the US field or the limitations on parameters that can be explored using clinical diagnostic US machines. We investigated individual exposure parameters using a system minimising experimental artefacts and allowing control of many parameters of the US field. Using a 1-MHz transducer we systematically varied US parameters, the duration of exposure and the microbubble and DNA concentrations to optimise gene delivery. Delivery was achieved, using lipid microbubbles (SonoVue) and clinically acceptable US exposures, to adherent cells at efficiencies of approximately 4%. The acoustic pressure amplitude (0.25 MPa peak-negative), pulse repetition frequency (1-kHz) and duration of exposure (10 s) were important in optimising gene delivery with minimal impact on cell viability. These findings support the hypothesis that varying the physical parameters of US-mediated gene delivery has an affect on both efficiency and cell viability. These data are the first in terms of their thorough exploration of the US parameter space and will be the basis for more-informed approaches to developing clinical applications of this technology.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2006.04.014DOI Listing
August 2006

Contrast-enhanced ultrasound assessment of tissue response to high-intensity focused ultrasound.

Ultrasound Med Biol 2004 Jun;30(6):851-4

Department of Urology, Churchill Hospital, Oxford, UK.

We report the use of contrast-enhanced ultrasonography as an immediate means of assessing the clinical response to high-intensity focused ultrasound (US) or HIFU treatment of liver tumours. HIFU is a noninvasive transcutaneous technique for the ablation of tumours that has been shown to destroy tumour vasculature, as well as to cause coagulative necrosis of tumour cells. As a dynamic indicator of tissue perfusion, microbubble contrast agents have already been reported to increase the diagnostic sensitivity of ultrasonography in the detection of liver tumours. This report documents the ability of one i.v. microbubble contrast agent (SonoVue, Bracco, Italy) to delineate the extent of HIFU ablation by comparison of pre- and immediately posttreatment perfusion within the target tumour. Observed changes were seen to correlate well with the ablated volume on histologic evaluation of the treated volume. This is the first time that this imaging technique has been reported in this setting.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2004.03.011DOI Listing
June 2004

Imaging of temperature-induced echo strain: preliminary in vitro study to assess feasibility for guiding focused ultrasound surgery.

Ultrasound Med Biol 2004 Mar;30(3):345-56

Joint Department of Physics, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey, UK.

Ultrasonic estimation of heat-induced echo strain has been suggested as a noninvasive technique for guiding focused ultrasound (US) surgery (FUS), that is, for predicting the location of the thermal lesion before it is formed. The proposed strategy is to run the FUS system at a nonablative intensity and to use a diagnostic transducer to image the heat-induced echo strain, which, over a sufficiently small temperature range, is proportional to the temperature rise. The principal aim of this in vitro study was to determine if temperature-induced strain imaging is likely to be able to visualise the small (< 0.5%) strains that one would be restricted to in vivo. Temperature rises ranging from approximately 2 degrees C to 15 degrees C (starting at approximately 25 degrees C) were induced in bovine liver samples using an FUS system. The pre- and post-heated US images were processed to produce images of the apparent axial strain. These images were found to possess excellent spatial and contrast resolution, so that the hot spot remained clearly visible even when the spatial peak strain value was approximately 0.2% (corresponding to temperature rises on the order of 2 to 5 degrees C). Good repeatability in the strain images was observed within and between tissue samples. Artefacts due to thermoacoustic refraction were seen distal to the heated region, but they did not reduce hot spot visibility. The length of the hot spot exceeded that of the subsequent ablation (by approximately 200%), which was to be expected given that temperature imaging depicts the entire area over which the temperature has increased relative to the baseline. We conclude that temperature-induced strain imaging for the guidance of FUS in the liver is likely to be feasible, provided that it will be possible either to neglect or to correct for the additional sources of error (such as cardiac-induced motion) that will arise in vivo.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2003.11.016DOI Listing
March 2004
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