Optimising patient specific treatment plans for ultrasound ablative therapies in the abdomen (OptimUS)

Lead Research Organisation: University College London
Department Name: Mechanical Engineering

Abstract

Surgical and ablative technologies are the most effective local therapies for solid malignancies. The significant side effects associated with surgical interventions have led to an ongoing quest for safer, more efficient, and better tolerated alternatives. In recent years, there has been a notable shift away from open surgery towards less invasive procedures such as laparoscopic and robotic surgery, and from there to other methods for in situ tumour destruction, often involving energy based destruction. These include embolisation, radiofrequency, microwave and laser ablation, cryoablation and HIFU. HIFU is a procedure which uses high-amplitude ultrasound to thermally ablate a localised region of tissue. For abdominal applications, the ultrasound is typically generated by a focused transducer located extracorporealy. As the ultrasound propagates through tissue and at high acoustic intensities, absorption of the energy can induce targeted tissue necrosis within a well-defined volume without damaging the overlying tissue.

The aim of OptimUS is to develop a novel mathematical and treatment planning framework for tumours of the abdomen which are to be ablated using HIFU. This new framework will be purpose built for a CE marked commercially available MR-guided & monitored HIFU system, which includes a multi-element transducer. It will make use of high-performance computing capabilities which will deliver optimal treatment plans both accurately and fast. This framework will greatly extend and reinforce the role of HIFU as a completely non-invasive ablative modality, and radically improve the treatment of kidney, pancreas and liver tumours, of uterine fibroids and renal sympathetic denervation (RSD).

World-leading investigators and partners have been assembled to collaborate on this project, from University College London, University of Cambridge, the Institute of Cancer Research UK and Oxford HIFU Unit. All bring unique yet complementary expertise in the fields of mathematics, engineering, physics, oncology and computing to solve a series of complex challenges, which will lead to a significant increase in the quality of life and life expectancy of patients. In addition, the development of HIFU treatment planning methods will lead to more cost-effective cancer treatment protocols, saving the NHS time, resources and money.

Planned Impact

Secondary liver cancer is estimated to affect more than 30,000 patients in the UK each year alone. Hepatocellular carcinoma, the most common form of primary liver cancer, is the fastest growing cancer in the UK. Liver cancer accounts for 3% of UK cancer deaths. Most cases of liver cancer are inoperable and the sufferer has an average life expectancy of less than one year. Cancers of the pancreas are often so far advanced at the time of diagnosis that patients are usually considered to be unsuitable for a surgical procedure. As for liver cancer, surgery is a lengthy procedure and its risks render it unsuitable for the majority of patients. For the treatment of liver and pancreatic cancer, targeted non-invasive surgical methods such as high-intensity focused ultrasound (HIFU) will lead to a significant increase in the quality of life and life expectancy of patients.

Kidney cancer is the fifth most common cancer in the UK, and its incidence is rising. 50% of people affected by renal cancer in England and Wales do not survive beyond 10 or more years and almost 6 in 10 kidney cancer patients receive major surgical resection as part of their cancer treatment. Kidney cancer surgery can be risky and is associated with complications in more than 20% of cases. Through optimal treatment planning, challenges of treating tumours of the kidney will be overcome.
Fibroids are common, with around 1 in 3 women developing them at some point in their life in the UK. They most often occur in women aged 30-50. Improvements in HIFU treatment planning methods for uterine fibroids through advanced treatment planning using numerical simulations will extend the patient base which could benefit from this modality and thus add more leverage towards NICE approval and clinical translation.

It is estimated that 1 billion individuals worldwide suffer from hypertension, and hypertension-related complications are recognised as the major cause of morbidity and mortality. Renal sympathetic denervation (RSD) is a procedure which has been shown to be of benefit for diseases associated with sympathetic overactivity, such as insulin resistance, arrhythmia, and heart failure. It is traditionally a catheter based intervention and can lead to complications. The prospect of carrying out this procedure non-invasively through a rigorous HIFU treatment planning protocol, would represent significant progress.
The development and experimental validation of a full wave treatment planning software for completely non-invasive ablative therapies of the abdomen using HIFU, and which can integrate seamlessly into a clinical system, will thus bear considerable impact. Mathematical and physical sciences research required to develop precise, non-invasive physical interventions to remove diseased tissue, via interventions such as HIFU will lead to more cost-effective cancer treatment protocols, saving the NHS time, resources and money.

Through our recently funded EPSRC-funded ThUNDDAR Network, we will engage with clinicians from different fields of oncology, radiologists, medical physicists and engineers to disseminate and discuss our findings. We will do this through 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.
Throughout the duration of the project, opportunities for patenting relevant innovations will arise which will benefit academia and UK plc. This will include (1) novel designs of HIFU array transducers, (2) novel treatment planning protocols and (3) specific tissue mimicking phantoms. Furthermore, the development of improved numerical schemes will enhance the open-source BEM++ and FEniCS software.

Publications

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

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Burman E (2018) Unique continuation for the Helmholtz equation using stabilized finite element methods in Journal de Mathématiques Pures et Appliquées

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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

 
Description Discussion of a joint proposal on treatment planning for trans-cranial HIFU 
Organisation Durham University
Department School of Engineering and Computing Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution The team at UCL is writing a joint proposal to the EPSRC for a large grant in collaboration with Durham.
Collaborator Contribution The team at UCL is writing a joint proposal to the EPSRC for a large grant in collaboration with Durham.
Impact None yet
Start Year 2018
 
Description Optimus 
Organisation University of Cambridge
Department Department of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution UCL will bring to this partnership the following: Therapeutic ultrasound expertise, experience in treatment planning development, a large-scale open-source boundary element library and expertise in FEM-BEM coupling.
Collaborator Contribution Garth Wells (university of Cambridge) is one of the main developers of the FEniCS project (http://fenicsproject.org/). The FEniCS project is an open source software library for the automated solution of partial differential equations using the finite element method. FEniCS has an excellent user interface and employs latest software technologies including code generation to provide the user with a flexible and efficient way of solving partial differential equations.
Impact This project started in April 2017, hence it is early days.
Start Year 2017