Model-Based Treatment Planning for Focused Ultrasound Surgery

Lead Research Organisation: University College London
Department Name: Medical Physics and Biomedical Eng

Abstract

Cancer is one of the most prevalent diseases in the UK. Each year it accounts for nearly 1 in 3 of all deaths. For patients with late-stage cancer, the cancer cells often spread to other parts of the body. This process is called metastasis, and the secondary tumours that form are called metastases. One of the most common sites for metastases to develop is bones. Around 2 in 3 patients with late-stage breast and prostate cancer, and 1 in 3 with late-stage lung, thyroid, and kidney cancer will develop bone metastases. This can cause debilitating pain, which has a significant impact on patients' quality of life. The most common treatment for reducing pain from bone metastases is external beam radiation therapy. This is aimed at relieving symptoms and controlling the growth of the cancer to improve quality of life, rather than trying to cure the patient (this is known as palliative care). However, as many as 1 in 3 patients treated with radiation therapy do not experience adequate pain relief, and the treatment cannot be repeated due to the toxicity of radiation to healthy tissue inside the body.

A very promising alternative therapy for pain palliation is focused ultrasound surgery, also known as high-intensity focused ultrasound or HIFU. This technique works by sending a tightly focused beam of ultrasound into the tissue. At the focus, the ultrasound energy is sufficient to heat the tissue and cause cell death in a very localised region, while the surrounding tissue is not harmed. This is akin to focusing sunlight through a magnifying glass, where only in the focus is the energy high enough to singe an object. Focused ultrasound surgery can be used to alleviate the pain from bone metastases by treating the layer of nerves and connective tissue that surrounds the bone. The major challenge is to ensure the focus is accurately placed at the desired target within the body. This is difficult because bones and other organs can significantly distort the path of the ultrasound beam.

The aim of this fellowship is to develop, validate, and apply new computer models to simulate how sound waves travel inside the human body. These models will be based on innovative advances in theoretical acoustics and numerical methods, and will use state-of-the-art computing facilities that have only recently become available. The computer models will allow the position of the focus and the heating of bones during focused ultrasound surgery to be accurately predicted for the first time. This will allow physicians to carefully plan and optimise the treatment parameters to eliminate the pain arising from bone metastases. This is expected to increase the effectiveness of focused ultrasound surgery, reduce the time it takes to treat patients, and extend the range and location of cancers that are eligible for treatment. As part of the fellowship, the models will be rigorously validated using patient data from previous clinical treatments, along with carefully planned laboratory experiments using phantom materials designed to mimic human tissue.

Planned Impact

The direct beneficiaries of this project are cancer patients with metastatic bone disease. These patients often experience excruciating and unrelenting pain. This can have a significant impact on quality of life, including causing functional impairment, physical debilitation, and psychological distress. The number of people affected by pain from bone metastases in the UK is continuing to grow due to the rising incidence of cancer. This is directly related to the ageing population, with the number of people in the UK over 65 expected to rise to 1 in 4 by 2050. Critically, nearly two-thirds of all new cancers are diagnosed in people in this age group. Moreover, two of the most common cancers in the elderly, prostate cancer and breast cancer, are also the most likely to lead to bone metastases.

Coupled with the appropriate treatment planning tools, focused ultrasound surgery offers the potential to deliver pain palliation to these patients with significantly less side effects than existing radiotherapy treatments. The therapy is completely non-invasive, delivered as a day procedure, and can be repeated if necessary without the dose tolerance and toxicity limits associated with radiation. It is hypothesised that the model-based treatment planning tools proposed in this fellowship will significantly accelerate the application of this technology for the treatment of skeletal lesions. In particular, these tools will provide detailed insight into the delivered ultrasound dose under different treatment conditions; increase the targeting accuracy by allowing the delivery parameters to be optimised; and extend the range of skeletal metastases that are eligible for treatment (the skull and the majority of the spine are currently excluded from clinical trials). In the context of delivering value-based healthcare, these tools could also play a significant role in decreasing procedural costs and optimising clinical outcomes.

The enhanced computational performance, unprecedented levels of physical accuracy, extensive validation, and clinician-led translation of the modelling tools developed in this fellowship will provide a significant competitive edge over the simulation packages currently used in academia and in industry. These advances will make the software commercially attractive to the manufacturers of focused ultrasound devices, one of whom is already directly engaged with the project through the expert advisory panel. It is expected the generated IP will lead to licensing agreements or the development of new start-ups, with the UK becoming a base for future international investment into treatment planning technology. The developed software tools will also act as a platform technology for other research areas that require large-scale acoustic models, including seismology, architectural acoustics, and sonar.
 
Description The primary objective of this fellowship is to develop, validate, and apply new computer models to simulate how sound waves travel inside the human body. These models will be used for model-based treatment planning in focused ultrasound surgery, particularly for the neuromodulation of deep brain structures. The project is now in its fifth year, and significant progress has been made towards these objectives. First, new models coupling elastic wave propagation and heating have been developed to allow the study of bone heating under different sonication conditions. These results give new insights into the mechanisms of heating for different types of ultrasound transducer and different bone geometries. Second, new numerical methods based on novel domain-decomposition approaches have allowed these models to be parallelised on clusters containing large numbers of graphical processing units (GPUs). This has allowed predictions with unprecedented scale and realism. Third, new techniques for measuring high-intensity ultrasound waves have been developed to allow these models to be validated. In particular, we have developed a system that can map the pressure fields from ultrasound therapy devices at clinical levels at unprecedented speeds and signal-to-noise ratios. This will allow the models to be tested under clinical conditions, a critical step towards their translation into the clinical workflow. Finally, we have conducted a series of careful validation experiments to ensure that the acoustic outputs produced by the software are correct.
Exploitation Route The developed modelling and measurement tools are likely to generate impact both on the targeted delivery of ultrasound therapy, as well as academics working to understand wave physics and ultrasound metrology. This impact is likely to come about through our open-source software and dataset releases, as well as the development of new measurement and modelling approaches that can be applied in many other fields.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare

 
Description The acoustic models being developed as part of this fellowship are being used by ultrasound and acoustic companies in the private sector, including for transducer design, image reconstruction, and ultrasound dose calculations.
First Year Of Impact 2015
Sector Digital/Communication/Information Technologies (including Software),Education,Healthcare,Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Description ThUNDDAR Network Pilot Funding
Amount £49,298 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 09/2018 
End 02/2019
 
Description UCL Knowledge Exchange and Innovation Fund
Amount £28,163 (GBP)
Organisation UCL Business 
Sector Private
Country United Kingdom
Start 03/2018 
End 09/2018
 
Title k-Wave Acoustics Toolbox 
Description k-Wave is an open source MATLAB toolbox designed for the time-domain simulation of propagating acoustic waves in 1D, 2D, or 3D. The toolbox has a wide range of functionality, but at its heart is an advanced numerical model that can account for both linear and nonlinear wave propagation, an arbitrary distribution of heterogeneous material parameters, and power law acoustic absorption. The numerical model is based on the solution of three coupled first-order partial differential equations which are equivalent to a generalised form of the Westervelt equation. The equations are solved using a k-space pseudospectral method, where spatial gradients are calculated using a Fourier collocation scheme, and temporal gradients are calculated using a k-space corrected finite-difference scheme. The temporal scheme is exact in the limit of linear wave propagation in a homogeneous and lossless medium, and significantly reduces numerical dispersion in the more general case. Power law acoustic absorption is accounted for using a linear integro-differential operator based on the fractional Laplacian. A split-field perfectly matched layer (PML) is used to absorb the waves at the edges of the computational domain. The main advantage of the numerical model used in k-Wave compared to models based on finite-difference time domain (FDTD) schemes is that fewer spatial and temporal grid points are needed for accurate simulations. This means the models run faster and use less memory. A detailed description of the model is given in the k-Wave User Manual and the references below. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact The toolbox is widely used in academia and industry, and has been used for research into transcranial ultrasound, ultrasound therapy, the development of novel ultrasound sources, photoacoustic imaging, and many other applications. There have been ten releases of the toolbox. It currently has more than 11,000 registered users in 70 countries. A 2010 paper describing the first release of the toolbox has >650 citations, and the active online user forum has >3000 posts.