Therapy Ultrasound Network for Drug Delivery & Ablation Research (ThUNDDAR)

Lead Research Organisation: Institute of Cancer Research
Department Name: Division of Radiotherapy and Imaging

Abstract

Therapeutic ultrasound (ThUS) has enormous potential as a minimally invasive treatment modality with applications ranging from the treatment of cancer and stroke, to fracture healing and neuromodulation. It is uniquely versatile, offering a non-invasive technique with the ability to thermally ablate tissue, to mechanically fragment tissue or to enhance drug delivery, depending on the way in which the acoustic energy is delivered. However, despite highly promising initial trials and its considerable advantages in terms of cost and patient safety, widespread clinical adoption has been hindered by a combination of factors. These include: poor understanding of the mechanisms of action, lack of effective treatment monitoring, absence of standardised treatment protocols and poor communication between basic scientists, engineers and clinicians. The main focus of the Therapeutic Ultrasound for Drug Delivery and Ablation Research (ThUNDDAR) Network is to address these factors by stimulating translational research that will enable the potential of therapeutic ultrasound to be fully realised. The Network brings together engineers, physicists, mathematicians, chemists, biologists, industry and clinicians as well as patient groups and regulatory bodies to identify and break down existing, and future, barriers to the use of therapeutic ultrasound in the UK and throughout the world.
ThUNDDAR's activities will include the organisation of specialist meetings, seed funding for pilot studies that cross disciplinary and institutional boundaries, and the production of web based information about therapy ultrasound for the benefit of industry, clinical users, health commissioners and patient groups.

Planned Impact

There are many beneficiaries of the work of ThUNNDAR. The potential benefits of therapeutic ultrasound as a minimally-invasive treatment for many types of cancer, neurological disorders, hypertension and cardiovascular disease could have a huge impact on the lives of thousands of people every year. The economic benefits will follow due to a healthier workforce. One of the main objectives of ThUNDDAR is to establish and maintain a leading role for the UK research community in therapeutic ultrasound and to see much shortened timelines to first-in-man trials for the resulting research outputs. Additionally the Network will actively seek ways of increasing the revenue of UK industry in this area by creating a viable lab-to-product pipeline. The Network will engage with MHRA and NICE at the outset to identify any bottlenecks in the regulatory approval pathway for academic-led therapeutic ultrasound projects. Early clinical application of outcomes leading to more efficacious treatments could produce significant cost-savings for the NHS. Through the portfolio of collaborative, interdisciplinary projects, the Network will aim to increase the international profile of the UK research community. By fostering old and new collaborations and generating novel and exciting research ThUNNDAR will strengthen the knowledge base of the UK community in both the applications and the underlying mechanisms involved in therapeutic ultrasound. Senior clinicians will be involved with the Network from the outset to ensure their direct input into defining a UK-wide strategy for research, translation of the outputs and identification of resources for follow-on activities such as clinical trials. The research strategies developed by the Network will also be expected to impact on research investment policies in the UK. ThUNDDAR will encourage the involvement of early career researchers in networking activities who will be thus exposed to a wide community of academic, clinical and industrial contacts. ThUNDDAR will also aim to increase the public awareness of advances with this exciting new therapeutic tool for many life-threatening and debilitating diseases. The Network boasts some of the best science communicators in UK academia today with experience of engaging with the public via routes such as The Royal Society Summer Exhibition, radio and TV, YouTube, school visits etc. ThUNDDAR website will be professionally designed with a section for explaining the science and applications of therapeutic ultrasound in easy to digest language for the general public. The Network Newsletter will also keep the public informed about the latest progress within the community.

Publications

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Adams C (2018) HIFU Drive System Miniaturization Using Harmonic Reduced Pulsewidth Modulation. in IEEE transactions on ultrasonics, ferroelectrics, and frequency control

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Betcke T (2019) Boundary Element Methods with Weakly Imposed Boundary Conditions in SIAM Journal on Scientific Computing

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Brüningk SC (2018) Response to comment by G. Borasi. in International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

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Burman E (2020) A finite element data assimilation method for the wave equation in Mathematics of Computation

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Burman E (2019) Cut topology optimization for linear elasticity with coupling to parametric nondesign domain regions in Computer Methods in Applied Mechanics and Engineering

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Burman E (2019) Hybridized CutFEM for Elliptic Interface Problems in SIAM Journal on Scientific Computing

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Burman E (2018) Primal-Dual Mixed Finite Element Methods for the Elliptic Cauchy Problem in SIAM Journal on Numerical Analysis

 
Title A week in the mountains - Therapy Ultrasound Under Scrutiny 
Description Film maker Martin Freeth follows delegates attending the ThUNDDAR network sponsored winter school through a series of interviews. This week long event was designed as an introduction to the wide ranging field of ultrasound therapy, accessible to students of any discipline. 
Type Of Art Film/Video/Animation 
Year Produced 2017 
Impact The interviews have received over 300 views on youtube 
URL https://thunddar.org/video-resources/
 
Title Haifu: The Patients' Story 
Description Film maker Martin Freeth documents a medical team in Chong Qing successfully treating thousands of women for Utirine fibroids. They are collaborating with medics in Oxford to bring this treatment to the UK. 
Type Of Art Film/Video/Animation 
Year Produced 2020 
Impact This video has received 47 views so far via the ThUNDDAR website 
URL https://vimeo.com/347696439
 
Title The case of the disappearing essential tremor 
Description Film maker Martin Freeth has created a series of films on therapeutic ultrasound. In this film Professor Wady Gedroyc and his colleagues at St Mary's Hospital cure Dinesh Kotecha's debilitating tremor 
Type Of Art Film/Video/Animation 
Year Produced 2017 
Impact This video has been watched 45,171 times since 2017 according to YouTube 
URL https://thunddar.org/video-resources/
 
Title Ultrasound Therapy: The Basics 
Description Professor Gail ter Haar and animator Anne Marie Walsh team up to provide an engaging basic explanation of how focused ultrasound can be used both for treatment and to target drug therapy. 
Type Of Art Film/Video/Animation 
Year Produced 2017 
Impact This video has received 2431 views on youtube since it's initial posting. 
URL https://www.youtube.com/watch?v=L8F24Y_tOg4
 
Description This grant funds a Network that is informing both the public, and professionals about the potential of therapy ultrasound. We are doing this by awarding funding projects and by running workshops.
Exploitation Route It is hoped that clinicians will recognise the potential applications of these techniques.
Sectors Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://thunddar.org/
 
Description ThUNDDAR has sponsored 4 (lay) films targeted at potential therapy ultrasound patients. The film on essential tremor has been viewed 45,171 times since 2017 according to YouTube, and that explaining therapy ultrasound more than 350 times.
First Year Of Impact 2017
Sector Healthcare
Impact Types Societal,Policy & public services

 
Description AAPM Group on characterisation of MRgHIFU
Geographic Reach North America 
Policy Influence Type Membership of a guideline committee
Impact Better characterisation of MR guided HIFU treatments will lead to more effective and safer treatments. A document describing this is in Press
 
Description Executive committee of Centre for Convergent Science
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
 
Description CRCE (Joint ICR/Imperial College fund)
Amount £20,000 (GBP)
Organisation Institute of Cancer Research UK 
Sector Academic/University
Country United Kingdom
Start 07/2018 
End 12/2018
 
Description Optimising patient specific treatment plans for ultrasound ablative therapies in the abdomen (OptimUS)
Amount £706,803 (GBP)
Funding ID EP/P012434/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2017 
End 08/2020
 
Description Semi-autonomous non-invasive surgery: The "outside in" of molecular-targeted theranostics for cancer
Amount £666,643 (GBP)
Funding ID EP/S001069/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 06/2018 
End 06/2021
 
Description The Cure Starts Now / The DIPG Collective
Amount $100,000 (USD)
Organisation DIPG Collaborative 
Sector Charity/Non Profit
Country United States
Start 12/2018 
End 12/2019
 
Description Ultrasound guided high intensity focused ultrasound for non-invasive cancer treatments
Amount £79,800 (GBP)
Funding ID POC 000129 
Organisation Grow MedTech 
Sector Academic/University
Country United Kingdom
Start  
 
Title Fibre optic hydrophones for cavitation detection 
Description It is necessary to monitor acoustic cavitation during clinical HIFU exposures. The use of an implanted fibre optic hydrophone has allowed this. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact We routinely use fibre optic hydrophones now for cavitation monitoring, and other groups are also beginning to do so following publication of our paper on the subject 
 
Description BMUS 
Organisation British Medical Ultrasound Society
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution ThUNDDAR decides the final programme for one day meetings as a part of BMUS AGM
Collaborator Contribution ThUNDDAR holds a one day meeting at the BMUS annual general meeting, thus exposing a wider audience to the potential of therapy ultrasound. BMUS organizes meeting registration and facilities
Impact Annual meetings attended by up to 50 meetings.
Start Year 2017
 
Description CRCE 
Organisation Imperial College London
Department Department of Bioengineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Study of nanodroplet enhanced histotrispy to provide pilot data for grant funding
Collaborator Contribution Collaborators facilitated and participated in studies
Impact Pilot data which is being used in grant applications currently being drafted
Start Year 2018
 
Description CRCE ICR/Imperial Joint studentship 
Organisation Imperial College London
Department Faculty of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Development of project, application for funding, supervision of student
Collaborator Contribution Development of project, application for funding, supervision of student
Impact PhD studentship
Start Year 2017
 
Description Edinburgh/Leeds 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR funded pilot study 'Investigation of the ability of gas-filled nano-bubbles to deliver hydrophobic and hydrophilic com-pounds to the brain by disruption of the blood brain barrier (BBB) using focused ultrasound' to establish collaboration
Collaborator Contribution ThUNDDAR funded pilot study 'Investigation of the ability of gas-filled nano-bubbles to deliver hydrophobic and hydrophilic com-pounds to the brain by disruption of the blood brain barrier (BBB) using focused ultrasound' to establish collaboration
Impact Results presented at British Medical Ultrasound Society's Annual Scientific Meeting 2017, BNA Festival of Neursocience 2017
Start Year 2018
 
Description Edinburgh/Leeds 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR funded pilot study 'Investigation of the ability of gas-filled nano-bubbles to deliver hydrophobic and hydrophilic com-pounds to the brain by disruption of the blood brain barrier (BBB) using focused ultrasound' to establish collaboration
Collaborator Contribution ThUNDDAR funded pilot study 'Investigation of the ability of gas-filled nano-bubbles to deliver hydrophobic and hydrophilic com-pounds to the brain by disruption of the blood brain barrier (BBB) using focused ultrasound' to establish collaboration
Impact Results presented at British Medical Ultrasound Society's Annual Scientific Meeting 2017, BNA Festival of Neursocience 2017
Start Year 2018
 
Description Imperial 
Organisation Imperial College London
Department Faculty of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution co-director of Network
Collaborator Contribution co-director of network
Impact We have held workshops and training schools. Multidisciplinary network, involving physicists, engineers, biologists, clinicians, vets, industry and others
Start Year 2016
 
Description Imperial College 
Organisation Imperial College London
Department Department of Chemical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution We co-supervise a student working on the effects of acoustic streaming set up by single bubbles on blood vessel walls. Much of the experimental work is carried out at ICR
Collaborator Contribution Imperial College is funding the research, and leading the theoretical aspects of this work
Impact presentations at informal seminars
Start Year 2017
 
Description King's College London 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Added to network
Collaborator Contribution network participation
Impact Participation in network events
Start Year 2017
 
Description Leeds 
Organisation University of Leeds
Department School of Electronic and Electrical Engineering Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution co-director of Network
Collaborator Contribution co-director of Network
Impact We have held workshops and training schools. Multidisciplinary network, involving physicists, engineers, biologists, clinicians, vets, industry and others
Start Year 2016
 
Description Leeds/Glasgow pilot 
Organisation University of Glasgow
Department School of Engineering Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR pilot study: A mechanistic study of acoustic emissions from controlled microbubble populations exposed to focused ultrasound
Collaborator Contribution ThUNDDAR pilot study: A mechanistic study of acoustic emissions from controlled microbubble populations exposed to focused ultrasound Project Aim: This collaborative project between the ultrasound groups based and the Universities of Glasgow and Leeds, was aiming to combine the use of high speed optical imaging with passive acoustic mapping (PAM) in order to investigate the behaviour of microbubble clusters under exposure from 692 kHz high intensity focused ultrasound (HIFU). Outcome Summary: A BK medical high frequency (8-40 MHz) linear ultrasound array, was integrated with the ultrasound array research platform (UARP). This involved the manufacture of a new connector plate (Figure 1a) to ensure each element of the array was connected to the correct system channel, enabling the saving of the raw RF data generated during HIFU exposures. A contact at BK medical was able to provide a pin-out diagram for this specific model of transducer to achieve this. The unavailability of this information for the originally stated Visualsonics probe was why the BK medical probe was used in this study. The UARP was transported and installed in the ultrasound lab at the University of Glasgow for a period of a month. It was integrated in the experimental setup shown in Figure 1b, for studying the interaction of bubble clusters in a 500 µm capillary tube exposed to HIFU. A TTL timing circuit was used to ensure correct synchronisation, allowing for time of flight, between the HIFU transducer, UARP and high speed optical cameras and illumination source. Low concentrations of SonoVue and Sonozoid microbubbles were used to ensure that single microbubbles were present in the imaging region. The acoustic emissions were detected using both a needle hydrophone (Figure 1c) and the UARP (Figure 1d), in conjunction with high speed optical imaging (Figure 1e). This approach was repeated approximately 100 times with varying peak negative pressures, ranging from 0.38 - 1.14 MPa. Both optical and needle hydrophone detection demonstrated the presences of periodic shockwaves, specifically those with subharmonic component (Figure 1c). However, the PAM algorithms used were not sufficient to identify this temporal behaviour. Nevertheless, it was able to spatially locate the presence of these bubble clusters in the capillary tube.
Impact Outputs related to award: Abou-Saleh, R.H., McLaughlan, J.R., Bushby, R.J., Johnson, B.R., Freear, S., Evans, S.D. and Thomson, N.H., 2019. Molecular Effects of Glycerol on Lipid Monolayers at the Gas-Liquid Interface: Impact on Microbubble Physical and Mechanical Properties. Langmuir, 35(31), pp.1009710105. S. Cleve, C. Inserra, P. Prentice, Contrast agent microbubble jetting during initial interaction with 200-kHz focused ultrasound. Ultrasound in Medicine and Biology 45(11) 3075-3080 (2019) J. H. Song, A. Moldovan, P. Prentice, Non-linear acoustic emissions from therapeutically driven contrast agent microbubbles. Ultrasound in Medicine and Biology 45(8) 2188-2204 (2019) Adams, C., Carpenter, T.M., Cowell, D., Freear, S. and McLaughlan, J.R., 2018. Hifu drive system miniaturization using harmonic reduced pulsewidth modulation. IEEE transactions on ultrasonics, ferroelectrics, and frequency control, 65(12), pp.2407-2417. Nie, L., McLaughlan, J.R., Cowell, D.M., Carpenter, T.M. and Freear, S., 2018, October. Subharmonic Plane Wave Imaging of Liposome-Loaded Microbubbles. In 2018 IEEE International Ultrasonics Symposium (IUS) (pp. 1-4). IEEE. Nie, L., Harput, S., Cowell, D.M., Carpenter, T.M., McLaughlan, J.R. and Freear, S., 2018. Combining acoustic trapping with plane wave imaging for localized microbubble accumulation in large vessels. IEEE transactions on ultrasonics, ferroelectrics, and frequency control, 65(7), pp.1193-1204. Dissemination Activities: Oral presentation: IEEE International Ultrasonics Symposium (IUS), 'Modified passive acoustic mapping with diagnostic-array angular response for cavitation monitoring during HIFU ablation in ex vivo tissue'. SUBMITTED 2020 Invited presentation: ASA (special session on polydisperse scatterers); Contrast agent microbubble response to sub-resonant ultrasonic driving. May 2020 Oral presentation: British Medical Ultrasound Society, 'Interleaving passive acoustic mapping with compounded diverging-wave imaging for HIFU treatment monitoring'. New technologies for clinical and clinical research into ultrasound therapy and imaging. December 2019. Oral presentation: IEEE International Ultrasonics Symposium (IUS), 'Volumetric Thermal HIFU Therapy Using Continuous Phase Modulation'. Tumor Therapy and Drug Delivery. October 2019. Poster presentation: IEEE International Ultrasonics Symposium (IUS), 'Spectral peak suppression in the acoustic emissions from multiple microbubbles cavitating in focused ultrasound'. October 2019. Poster presentation: IEEE International Ultrasonics Symposium (IUS), 'The influence of bubblebubble interactions on contrast agent microbubble-jetting during initial exposure to 200 kHz focused ultrasound'. October 2019. Oral presentation: British Medical Ultrasound Society, 'Non-linear acoustic emissions from therapeutically driven contrast microbubbles'. New technologies for clinical and clinical research into ultrasound therapy and imaging. December 2018. Further funding related to award: 2020 'Characterising tissue disruption and inflammatory response to resolved microbubble cavitation' EPSRC with council - decision pending £720,000 2019 'Ultrasound guided high intensity focused ultrasound for non-invasive cancer treatments' Grow MedTech (Research England), POC 000129, £79,800. 2018 'Semi-autonomous non-invasive surgery: The "outside in" of molecular-targeted theranostics for cancer', EPSRC UKRI Innovation Fellowship, EP/S001069/1, £850,000.
Start Year 2018
 
Description Leeds/Glasgow pilot 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR pilot study: A mechanistic study of acoustic emissions from controlled microbubble populations exposed to focused ultrasound
Collaborator Contribution ThUNDDAR pilot study: A mechanistic study of acoustic emissions from controlled microbubble populations exposed to focused ultrasound Project Aim: This collaborative project between the ultrasound groups based and the Universities of Glasgow and Leeds, was aiming to combine the use of high speed optical imaging with passive acoustic mapping (PAM) in order to investigate the behaviour of microbubble clusters under exposure from 692 kHz high intensity focused ultrasound (HIFU). Outcome Summary: A BK medical high frequency (8-40 MHz) linear ultrasound array, was integrated with the ultrasound array research platform (UARP). This involved the manufacture of a new connector plate (Figure 1a) to ensure each element of the array was connected to the correct system channel, enabling the saving of the raw RF data generated during HIFU exposures. A contact at BK medical was able to provide a pin-out diagram for this specific model of transducer to achieve this. The unavailability of this information for the originally stated Visualsonics probe was why the BK medical probe was used in this study. The UARP was transported and installed in the ultrasound lab at the University of Glasgow for a period of a month. It was integrated in the experimental setup shown in Figure 1b, for studying the interaction of bubble clusters in a 500 µm capillary tube exposed to HIFU. A TTL timing circuit was used to ensure correct synchronisation, allowing for time of flight, between the HIFU transducer, UARP and high speed optical cameras and illumination source. Low concentrations of SonoVue and Sonozoid microbubbles were used to ensure that single microbubbles were present in the imaging region. The acoustic emissions were detected using both a needle hydrophone (Figure 1c) and the UARP (Figure 1d), in conjunction with high speed optical imaging (Figure 1e). This approach was repeated approximately 100 times with varying peak negative pressures, ranging from 0.38 - 1.14 MPa. Both optical and needle hydrophone detection demonstrated the presences of periodic shockwaves, specifically those with subharmonic component (Figure 1c). However, the PAM algorithms used were not sufficient to identify this temporal behaviour. Nevertheless, it was able to spatially locate the presence of these bubble clusters in the capillary tube.
Impact Outputs related to award: Abou-Saleh, R.H., McLaughlan, J.R., Bushby, R.J., Johnson, B.R., Freear, S., Evans, S.D. and Thomson, N.H., 2019. Molecular Effects of Glycerol on Lipid Monolayers at the Gas-Liquid Interface: Impact on Microbubble Physical and Mechanical Properties. Langmuir, 35(31), pp.1009710105. S. Cleve, C. Inserra, P. Prentice, Contrast agent microbubble jetting during initial interaction with 200-kHz focused ultrasound. Ultrasound in Medicine and Biology 45(11) 3075-3080 (2019) J. H. Song, A. Moldovan, P. Prentice, Non-linear acoustic emissions from therapeutically driven contrast agent microbubbles. Ultrasound in Medicine and Biology 45(8) 2188-2204 (2019) Adams, C., Carpenter, T.M., Cowell, D., Freear, S. and McLaughlan, J.R., 2018. Hifu drive system miniaturization using harmonic reduced pulsewidth modulation. IEEE transactions on ultrasonics, ferroelectrics, and frequency control, 65(12), pp.2407-2417. Nie, L., McLaughlan, J.R., Cowell, D.M., Carpenter, T.M. and Freear, S., 2018, October. Subharmonic Plane Wave Imaging of Liposome-Loaded Microbubbles. In 2018 IEEE International Ultrasonics Symposium (IUS) (pp. 1-4). IEEE. Nie, L., Harput, S., Cowell, D.M., Carpenter, T.M., McLaughlan, J.R. and Freear, S., 2018. Combining acoustic trapping with plane wave imaging for localized microbubble accumulation in large vessels. IEEE transactions on ultrasonics, ferroelectrics, and frequency control, 65(7), pp.1193-1204. Dissemination Activities: Oral presentation: IEEE International Ultrasonics Symposium (IUS), 'Modified passive acoustic mapping with diagnostic-array angular response for cavitation monitoring during HIFU ablation in ex vivo tissue'. SUBMITTED 2020 Invited presentation: ASA (special session on polydisperse scatterers); Contrast agent microbubble response to sub-resonant ultrasonic driving. May 2020 Oral presentation: British Medical Ultrasound Society, 'Interleaving passive acoustic mapping with compounded diverging-wave imaging for HIFU treatment monitoring'. New technologies for clinical and clinical research into ultrasound therapy and imaging. December 2019. Oral presentation: IEEE International Ultrasonics Symposium (IUS), 'Volumetric Thermal HIFU Therapy Using Continuous Phase Modulation'. Tumor Therapy and Drug Delivery. October 2019. Poster presentation: IEEE International Ultrasonics Symposium (IUS), 'Spectral peak suppression in the acoustic emissions from multiple microbubbles cavitating in focused ultrasound'. October 2019. Poster presentation: IEEE International Ultrasonics Symposium (IUS), 'The influence of bubblebubble interactions on contrast agent microbubble-jetting during initial exposure to 200 kHz focused ultrasound'. October 2019. Oral presentation: British Medical Ultrasound Society, 'Non-linear acoustic emissions from therapeutically driven contrast microbubbles'. New technologies for clinical and clinical research into ultrasound therapy and imaging. December 2018. Further funding related to award: 2020 'Characterising tissue disruption and inflammatory response to resolved microbubble cavitation' EPSRC with council - decision pending £720,000 2019 'Ultrasound guided high intensity focused ultrasound for non-invasive cancer treatments' Grow MedTech (Research England), POC 000129, £79,800. 2018 'Semi-autonomous non-invasive surgery: The "outside in" of molecular-targeted theranostics for cancer', EPSRC UKRI Innovation Fellowship, EP/S001069/1, £850,000.
Start Year 2018
 
Description MRC grant Christoph Lees 
Organisation Imperial College London
Department Faculty of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Grant writing, physics/engineering research
Collaborator Contribution Grant writing, medical/pre-clinical research
Impact Several papers Follow on MRC grant funding Commercial collaboration with Canon (previously Toshiba) medical imaging
Start Year 2014
 
Description NPL 
Organisation National Physical Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution We carried out the major part of this project, developing measurement methods
Collaborator Contribution NPL contributed advice and expertise to help develop measurement methods
Impact Papers, conference presentations
Start Year 2007
 
Description NPL/ICR/UCL 
Organisation Institute of Cancer Research UK
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR funded pilot study 'Machine learning for cavitation detection' to enable collaboration
Collaborator Contribution ThUNDDAR funded pilot study 'Machine learning for cavitation detection' to enable collaboration
Impact Internal report
Start Year 2018
 
Description NPL/ICR/UCL 
Organisation National Physical Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR funded pilot study 'Machine learning for cavitation detection' to enable collaboration
Collaborator Contribution ThUNDDAR funded pilot study 'Machine learning for cavitation detection' to enable collaboration
Impact Internal report
Start Year 2018
 
Description National Physical Laboratories Studentship Gomis 
Organisation National Physical Laboratory
Department Acoustics Group
Country United Kingdom 
Sector Public 
PI Contribution Joint supervision of a CASE studentship, ICR being the primary host/supervisors
Collaborator Contribution Expertise on radiotherapy, measurement standards
Impact Conference presentations
Start Year 2018
 
Description National Physical Laboratories Studentship Gomis 
Organisation University College London
Department Department of Medical Physics and Biomedical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Joint supervision of a CASE studentship, ICR being the primary host/supervisors
Collaborator Contribution Expertise on radiotherapy, measurement standards
Impact Conference presentations
Start Year 2018
 
Description Oxford University 
Organisation University of Oxford
Department Institute of Biomedical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution co-director of the Network
Collaborator Contribution co-director of the Network
Impact We have held workshops and training schools. Multidisciplinary network, involving physicists, engineers, biologists, clinicians, vets, industry and others
Start Year 2016
 
Description Precision Acoustics 
Organisation Precision Acoustics Ltd
Country United Kingdom 
Sector Private 
PI Contribution Member of the ThUNDDAR network
Collaborator Contribution collaboration within Network
Impact Collaboration in pilot studies, especially with UCL
Start Year 2016
 
Description Royal Marsden Hospital 
Organisation Royal Marsden Hospital
Country United Kingdom 
Sector Hospitals 
Start Year 2004
 
Description St Thomas' Hospital 
Organisation St Thomas' Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution added to the ThUNDDAR network
Collaborator Contribution network members
Impact Participation in network events
Start Year 2016
 
Description UCL/ICR pilot study 
Organisation Institute of Cancer Research UK
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR pilot funding: Treatment of Age-related Macular Degeneration by Ultrasound
Collaborator Contribution ThUNDDAR pilot funding: Treatment of Age-related Macular Degeneration by Ultrasound. ICR is providing the biological expertise needed for this project - UCL is providing the engineering
Impact none yet
Start Year 2020
 
Description UCL/ICR pilot study 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR pilot funding: Treatment of Age-related Macular Degeneration by Ultrasound
Collaborator Contribution ThUNDDAR pilot funding: Treatment of Age-related Macular Degeneration by Ultrasound. ICR is providing the biological expertise needed for this project - UCL is providing the engineering
Impact none yet
Start Year 2020
 
Description UCL/Imperial College/Precision Acoustics 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR Pilot study: Quantifying the effects of standing waves within the skull for ultrasound-mediated opening of the blood-brain barrier
Collaborator Contribution ThUNDDAR Pilot study: Frequency optimisation for opening the blood-brain-barrier
Impact Final report submitted. In this pilot project, a novel large diameter 1-3 piezocomposite transducer was designed, constructed, and characterised. The final transducer had a broad bandwidth and reasonable beam characteristics. Experimental and numerical simulations were conducted to assess the importance of standing waves within the skull when using low frequencies for the targeting opening of the BBB. The standing waves effects were clearly visible in both the experiments and simulations. However, in general, the distortions to the main focal lobe were small, and any secondary side lobes or hot spots were much smaller in amplitude. It is known from previous work that the effects of standing waves are reduced when using larger aperture diameter transducers (i.e., smaller f-numbers) [Song2011]. This is because the focal gain depends on waves arriving from a wider range of angles, so is less sensitive to perturbations. Thus, the large-aperture realised in this pilot project can be considered to strike a good balance between construction feasibility and cost, and the presence of standing waves. Regarding pulse length, the presence of standing waves in the field increased with the duration of the pulse. However, these effects were relatively small, and overall there was not a significant difference in the beam stability for the locations within the skull that were tested. The transducer design and construction process has increased the technology readiness level of Precision Acoustics for this type of piezocomposite design, and established a new and ongoing collaboration between the project partners. The preliminary data will form the basis of grant application between the project partners related to opening the BBB in humans. The data will also be used as part of future publications
Start Year 2019
 
Description UCL/Imperial College/Precision Acoustics 
Organisation Precision Acoustics Ltd
Country United Kingdom 
Sector Private 
PI Contribution ThUNDDAR Pilot study: Quantifying the effects of standing waves within the skull for ultrasound-mediated opening of the blood-brain barrier
Collaborator Contribution ThUNDDAR Pilot study: Frequency optimisation for opening the blood-brain-barrier
Impact Final report submitted. In this pilot project, a novel large diameter 1-3 piezocomposite transducer was designed, constructed, and characterised. The final transducer had a broad bandwidth and reasonable beam characteristics. Experimental and numerical simulations were conducted to assess the importance of standing waves within the skull when using low frequencies for the targeting opening of the BBB. The standing waves effects were clearly visible in both the experiments and simulations. However, in general, the distortions to the main focal lobe were small, and any secondary side lobes or hot spots were much smaller in amplitude. It is known from previous work that the effects of standing waves are reduced when using larger aperture diameter transducers (i.e., smaller f-numbers) [Song2011]. This is because the focal gain depends on waves arriving from a wider range of angles, so is less sensitive to perturbations. Thus, the large-aperture realised in this pilot project can be considered to strike a good balance between construction feasibility and cost, and the presence of standing waves. Regarding pulse length, the presence of standing waves in the field increased with the duration of the pulse. However, these effects were relatively small, and overall there was not a significant difference in the beam stability for the locations within the skull that were tested. The transducer design and construction process has increased the technology readiness level of Precision Acoustics for this type of piezocomposite design, and established a new and ongoing collaboration between the project partners. The preliminary data will form the basis of grant application between the project partners related to opening the BBB in humans. The data will also be used as part of future publications
Start Year 2019
 
Description UCL/Imperial College/Precision Acoustics 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution ThUNDDAR Pilot study: Quantifying the effects of standing waves within the skull for ultrasound-mediated opening of the blood-brain barrier
Collaborator Contribution ThUNDDAR Pilot study: Frequency optimisation for opening the blood-brain-barrier
Impact Final report submitted. In this pilot project, a novel large diameter 1-3 piezocomposite transducer was designed, constructed, and characterised. The final transducer had a broad bandwidth and reasonable beam characteristics. Experimental and numerical simulations were conducted to assess the importance of standing waves within the skull when using low frequencies for the targeting opening of the BBB. The standing waves effects were clearly visible in both the experiments and simulations. However, in general, the distortions to the main focal lobe were small, and any secondary side lobes or hot spots were much smaller in amplitude. It is known from previous work that the effects of standing waves are reduced when using larger aperture diameter transducers (i.e., smaller f-numbers) [Song2011]. This is because the focal gain depends on waves arriving from a wider range of angles, so is less sensitive to perturbations. Thus, the large-aperture realised in this pilot project can be considered to strike a good balance between construction feasibility and cost, and the presence of standing waves. Regarding pulse length, the presence of standing waves in the field increased with the duration of the pulse. However, these effects were relatively small, and overall there was not a significant difference in the beam stability for the locations within the skull that were tested. The transducer design and construction process has increased the technology readiness level of Precision Acoustics for this type of piezocomposite design, and established a new and ongoing collaboration between the project partners. The preliminary data will form the basis of grant application between the project partners related to opening the BBB in humans. The data will also be used as part of future publications
Start Year 2019
 
Description UCOM 
Organisation City, University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Grant application, hosting of 2 ESR, collaborative research
Collaborator Contribution Grant application, hosting of 12 ESR, collaborative research
Impact None yet
Start Year 2015
 
Description UCOM 
Organisation Sorbonne Universités
Country France 
Sector Academic/University 
PI Contribution Grant application, hosting of 2 ESR, collaborative research
Collaborator Contribution Grant application, hosting of 12 ESR, collaborative research
Impact None yet
Start Year 2015
 
Description UCOM 
Organisation Swiss Federal Institute of Technology in Lausanne (EPFL)
Country Switzerland 
Sector Public 
PI Contribution Grant application, hosting of 2 ESR, collaborative research
Collaborator Contribution Grant application, hosting of 12 ESR, collaborative research
Impact None yet
Start Year 2015
 
Description UCOM 
Organisation Technical University of Munich
Country Germany 
Sector Academic/University 
PI Contribution Grant application, hosting of 2 ESR, collaborative research
Collaborator Contribution Grant application, hosting of 12 ESR, collaborative research
Impact None yet
Start Year 2015
 
Description UCOM 
Organisation The Otto-von-Guericke University Magdeburg
Country Germany 
Sector Academic/University 
PI Contribution Grant application, hosting of 2 ESR, collaborative research
Collaborator Contribution Grant application, hosting of 12 ESR, collaborative research
Impact None yet
Start Year 2015
 
Description UCOM 
Organisation University of Geneva
Country Switzerland 
Sector Academic/University 
PI Contribution Grant application, hosting of 2 ESR, collaborative research
Collaborator Contribution Grant application, hosting of 12 ESR, collaborative research
Impact None yet
Start Year 2015
 
Description UCOM 
Organisation University of Twente
Country Netherlands 
Sector Academic/University 
PI Contribution Grant application, hosting of 2 ESR, collaborative research
Collaborator Contribution Grant application, hosting of 12 ESR, collaborative research
Impact None yet
Start Year 2015
 
Title "Ultrasound Array Research Platform UARP" 
Description "The Ultrasound Array Research Platform UARP is a fully programmable combined imaging and therapy system. Capable of prototyping next generation image guided therapeutic systems aiding research and translation to the clinic." 
Type Of Technology Systems, Materials & Instrumental Engineering 
Year Produced 2020 
Impact The ThUNDDAR grant has help support the progress of a UK based ultrasonic therapy research platform - Ultrasound Array Research Platform or UARP. The system is being made freely available on a loan to network members 
URL https://eps.leeds.ac.uk/medical-electronics/doc/developing-ultrasound-systems-better-imaging-cancer-...
 
Description Article for Pan-European networks 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Article just published. It is hoped it will stimulate pan-European research collaborations

Too early to tell yet
Year(s) Of Engagement Activity 2014
 
Description International Society for Therapeutic Ultrasound - Tutorial Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Over 200 people logged into listen to the lecture which was followed by a live question and answer session and subsequent engagement by email. Excellent feedback was received from the audience including a proposal for a research collaboration.
Year(s) Of Engagement Activity 2021
URL https://istu.org/february-25-2021-webinar/
 
Description Interview for the Economist 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Interview by the Economist and featured in their special feature 'Closing in on Cancer' (September 16th 2017) which covered the importance of radiation therapy research and recent progress.
Year(s) Of Engagement Activity 2017
URL https://www.economist.com/news/leaders/21728893-science-will-win-technical-battle-against-cancer-onl...
 
Description KTN 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Knowledge Transfer meeting. One day meeting designed to introduce Therapy Ultrasound to funders, clinicians and senior people in the NHS
Year(s) Of Engagement Activity 2017
 
Description Les Houches 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Les Houches Therapy Ultrasound Winter School. This was a one week school which covered all topics in therapy Ultrasound. 80 participants. 14 UK students were sponsored to attend by ThUNDDAR. This introduced students and young researchers to the field, and allowed them to interact with the international faculty .
Year(s) Of Engagement Activity 2017
 
Description Les Houches 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Introductory Winter School for those entering the field of Therapy Ultrasound. ThUNDDAR funded 10 UK students to attend.
Year(s) Of Engagement Activity 2019
URL https://thunddar.org/
 
Description NPL meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact One day workshop held at NPL. Young researchers presented their results.
Year(s) Of Engagement Activity 2017
 
Description Sandpit 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A 'sandpit' meeting was organised, the aim of which was to promote therapy ultrasound to a wider audience.
Year(s) Of Engagement Activity 2016
 
Description Speed dating 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 'Speed dating' event in which practitioners with a need presented, and researchers proposed solutions to these needs. These were pitched, and 2 pilot grants were awarded
Year(s) Of Engagement Activity 2018
URL https://thunddar.org/
 
Description THUGs 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Therapy Ultrasound Group one day seminar as a satellite meeting of the British Medical Ultrasound Society annual general meeting.
Year(s) Of Engagement Activity 2017
 
Description THUGs 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact One day seminar held during the annual BMUS meeting, This promulgates the interest in therapy ultrasound to the wider diagnostic ultrasound audience
Year(s) Of Engagement Activity 2017,2018,2019
 
Description ThUNDDAR Live 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact ThUNDDAR Live was set up to provide introductory lectures on key topics in Therapeutic Ultrasound aimed at doctoral students, medical practitioners and other interested groups (including patients and industry representatives). Since its creation in July 2020 the youtube channel has had 3791 views with the lecture breakdown as follows:
Mike Gray - 2 March 2021 Message in a Bubbl 11
Dario Carugo 2 December 2020 Acoustofluidics for Cell Manipulation and Stimulation 128
Robin Cleveland 28 October 2020 Ultrasound Propagation the Fundamentals II 136
Manxing Tang 30 July 2020 Super Resolution Ultrasound 213
Eleanor Stride 22 July 2020 Bubble Basics 172
Robin Cleveland Ultrasound Propagation the Fundamentals 15 July 2020 214
Year(s) Of Engagement Activity 2020,2021
URL https://thunddar.org/thunddar-live/
 
Description ThUNDDAR website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact thUNDDAR website with video descriptions of Therapy Ultrasound
Year(s) Of Engagement Activity 2019
 
Description • Invited presentation: ASA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact • Invited presentation: ASA (special session on polydisperse scatterers); Contrast agent microbubble response to sub-resonant ultrasonic driving - James McLaughlan, recipient of ThUNDDAR pilot study
Year(s) Of Engagement Activity 2020
 
Description • Oral presentation: British Medical Ultrasound Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact • Oral presentation: British Medical Ultrasound Society, 'Non-linear acoustic emissions from therapeutically driven contrast microbubbles'. New technologies for clinical and clinical research into ultrasound therapy and imaging. December 2018. by James Mcaughlan, recipient of ThUNDDAR funding
Year(s) Of Engagement Activity 2018