Acoustic Emission as a non-invasive biomarker for quantitative dynamic assessment of knee joint repair in clinical trials and stratified medicine

Lead Research Organisation: Lancaster University
Department Name: Medicine

Abstract

Knee osteoarthritis remains a common cause of pain and disability worldwide because there have been very few advances in the treatment of this condition. However, increased research in recent years has started to produce several promising new treatments. These might either improve the condition or reduce the rate at which deterioration occurs.

In order to decide whether new treatments really work, and if so which patients they work best for, it is important to have better techniques to measure whether the joint is getting better or worse. Such techniques should be safe, convenient, and widely available to doctors and other health professionals working in general practices or in hospitals.

Over the past few years we have been researching a new and very distinctive technique for measuring the severity of knee osteoarthritis. This is done by capturing and analysing high-frequency sounds coming from moving knee joints to find out how severely the joint is affected by age and osteoarthritis, and to assess whether the joint is improving or deteriorating.

We have put together a team of experts from the NHS, universities and industry, with a wide range of expertise in medicine, health, science and engineering, to work together on this project. We are using an advanced sound wave sensing technology that is highly sensitive to sound inaudible to the human ear. The equipment was developed originally by engineers for testing and checking for faults in moving parts and in complex structures, such as aircraft.

We attach a small microphone-like sensor to the skin over the knee and collect high-frequency sounds which are produced during sit-to-stand movements. We also attach a small flexible sensor to measure the knee angle, which enables us to know exactly where in the movement cycle each 'sound' is generated. We analyse the amount of 'sound' produced, and also the features of the many different 'sound' waveforms. Our results so far show very clear differences between the 'sounds' from knees of people with and without knee osteoarthritis, and suggest that 'joint sounds' change with age. These very interesting results suggest that it will eventually be possible to use this technology in clinical practice.

We want now to find out whether this technique could be used to provide a better and more convenient way of testing whether or not new treatments work, and of identifying which patients get the most benefit. This work could potentially revolutionise clinical trials in knee osteoarthritis by providing a safe, convenient, portable tool which is widely-available in hospitals and general practices. This would make it possible to do large clinical trials, involving many centres across the world, which would provide better and faster ways of testing urgently-needed new treatments for this condition.

Technical Summary

We are the first to investigate high-frequency acoustic emission (AE) as a non-invasive, quantitative biomarker of the integrity of interactions between knee joint components during weight bearing movement (1-4). Our portable system uses wide-band AE sensors to detect sound waves with frequencies up to 200 kHz emitted from knees during sit-stand-sit movement. Similar principles are utilised in non-destructive testing and condition monitoring of engineering structures for early detection of damage and material defects. We are investigating various AE applications in clinical practice and research, and are progressing this work towards prototype development (see Project Plan).
In this study we shall undertake technical validation of AE as a biomarker for enhancing the ability of clinical trials to provide relevant, robust evaluation of the growing array of new interventions aimed at improving or reducing deterioration in joint condition in knee OA. This study will enable us to investigate AE's utility to provide definition of patient subgroups for inclusion in clinical trials, and to inform stratified medicine approaches for optimising the use of such treatments in clinical practice.
AE sensors are piezoelectric transducers which are attached to knee surfaces, using defined anatomical landmarks, to record short bursts of acoustic energy generated by stress upon, and friction between, joint components during weight-bearing movement. An electrogoniometer is attached to enable each acquired AE waveform to be linked to knee angle. A range of signal processing, analysis and visualisation methods has been developed based on AE waveform features in both time and frequency domains, AE statistics in different joint movement phases, and AE classification by principal component analysis. Our published results demonstrate that AE can distinguish not only between healthy and osteoarthritic knees, but also between knees in different age groups and differences in joint condition

Planned Impact

The study will address four core impact objectives, which will be met both during and beyond the project's lifetime:

1. Establishing AE biomarkers as distinctive new tools for clinical trials in knee OA
Establishing AE biomarkers for use in clinical trials in knee OA would have a major impact on primary and secondary healthcare as well as benefit for the biopharmaceutical and health technology sectors. There is currently a paucity of biomarkers for knee OA, and all current techniques have important limitations in terms either of their objectivity, their utility and/or their convenience.
The use of simple, non-invasive, portable and easily-accessible equipment, providing an objective measurement, would enable more frequent and comprehensive patient assessment, better definition of patient subgroups, and better targeting and monitoring of treatments. Furthermore, the need for some other assessments, particularly X-rays, should be reduced, thus conserving resources and minimising radiation exposure.
Availability of AE biomarkers would also stimulate increased interest in developing new treatments and interventions for knee OA, and in undertaking large multicentre clinical trials to evaluate their efficacy, whilst also opening up new approaches for improving longer term outcomes. In principle, this may lead to substantial health and economic benefits, not only in terms of improved musculoskeletal health of the population, but also in terms of improved health and performance of the workforce and reduced costs of medical and surgical healthcare.

2. Stimulating development within the health and commercial sectors of new treatments and interventions for knee OA, and consequently increased clinical trials activity in this field.
If the results of this study support the principle, benefits and utility of AE for use in clinical trials, the next stage would be to design and develop prototype equipment tailored for use by clinical researchers and research practitioners, together with associated software, for wider use in future studies. We envisage that it would be feasible to reach such a stage within two years of completion of this project.

3. Achieving effective interdisciplinary, cross-sectoral working
This project depends and draws upon a unique mix of skills and expertise within the project team, which spans musculoskeletal science, medical imaging, signal processing and biostatistics, and upon successful cross-sectoral working. As such, it provides an excellent environment for staff to acquire valuable and stimulating experience of interdisciplinary, cross-sectoral research collaboration, and opportunities for professional development in this context.

4. Stimulating interest in the health and medical devices sector in exploring AE applications for other musculoskeletal and medical conditions.
This work will not only consolidate our leading position in AE applications for knee OA but also provide a foundation for investigating AE in other joint conditions and areas of medicine. By stimulating the development of new devices for acoustic applications in health it offers potential for the UK to take an internationally-leading role in this field.
 
Description MRC Proximity to Discovery funding
Amount £10,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2018 
End 06/2019
 
Description MRC Proximity to Discovery funding
Amount £9,320 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2019 
End 08/2019
 
Title Developmental dataset 
Description Method for using developmental dataset to identify candidate biomarkers for testing in larger dataset. 
Type Of Material Improvements to research infrastructure 
Year Produced 2016 
Provided To Others? No  
Impact Analysis of the study data. 
 
Title Data handling and sharing protocol 
Description This process is in development to ensure a fair and robust process for other research teams to access the database as well as existing team members to consider utilising the data for purposes other than those outlined in the original study. It takes into account ethical considerations and formal documentation of approvals and data sharing. 
Type Of Material Data handling & control 
Provided To Others? No  
Impact None yet 
 
Title Database 
Description Clinical, imaging and acoustic emission data from the study have been collated into a database, which will be the data source for future requests and collaborations. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact This database streamlines requests from the team to answer research questions in the study. It ensures that high quality data is available for analysis within the team and provides the basis for a data handling and control system to share with other research groups as appropriate 
 
Description Accoustic Emission in Knee Osteoarthritis - phase 2 - equipment development 
Organisation Lancaster University
Department Department of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution The Principle Investigator has brought into the team Dr David Cheneler in the Engineering Department at Lancaster University with specialist expertise in microengineering and experience in application of new technologies in medicine. Professor Goodacre and a number of colleagues in the orinigal study team have developed an MRC funding application for the next phase following on from the completion of this study, and are planning further projects based on this work.
Collaborator Contribution Dr Cheneler led the MRC DFPS funding application. Unfortuntely this was unsuccessful, the team is awaiting feedback from this application to inform the next steps.
Impact An MRC DFPS funding application was submitted, and engagement has been established with colleagues at Imperial College London who are working in the field of acoustic emission.
Start Year 2017
 
Description Acoustic emissions in biomechanics & sports science 
Organisation Lancaster University
Department Faculty of Health and Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution The equipment used in the Noisy Knees study has the potenital to be transferred to other academic disciplines and real world applications. Colleagues in Sports Science (Dr Chris Gaffney and Dr Theo Bampourus) were keen to understand the development of equipment and understanding of data as applied to knee osteoarthritis and could see a range of options in terms of application in sports science. One of the JAAS machines used in the Noisy Knees study have been passed to this team for future research.
Collaborator Contribution Dr Theo Bampourus has led an MRC Proximity to Discovery application to use the equipment pre and post run with athletes. This application was successful and the study starts in May 2019.
Impact One of the lead academics in biomechanics has been successful in bidding for ~£10,000 from the MRC Proximity to Discovery funding to work with a local GP and Industry partner to test the acoustic emission equipment from the Noisy Knees study before and after athletes run.
Start Year 2019
 
Description Knee acoustic emission collaboration 
Organisation Imperial College London
Department MSk Lab
Country United Kingdom 
Sector Academic/University 
PI Contribution Discussions initiated by us are in progress to explore the mutual interests and methodologies for analysing acoustic emissions in the knee, involving myself and other colleagues in our research team (Signal Processing,Engineering, and Imaging expertise) and colleagues in the Musculoskeletal Laboratory at Imperial College London. An NDA has been developed to facilitate in depth discussions about the teams' current research in this field, and to explore potential for future collaboration. Lancaster University hosted a meeting with colleagues from Imperial and UCLAN in November 2017 to discuss past work and explore areas of interest. We have set up teleconferences and regular emails are developing the detail on joint projects and funding applications in the near future. Engaged in this work from the original team are Professor John Goodacre, Associate Dean for Engagement and Innovation, Lancaster Univeristy; Professor Lik-Kwan Shark, Head of ADMT and ADSIP, UCLan; Dr Wei Quan, Senior Lecturer, UCLan, Dr Daniella Schluter, Senior Research Associate, Lancaster University and Jane Huddleston, Operations Officer, Lancaster University. In addition, Dr David Cheneler from the Engineering Department, Lancaster University has joined the team recently to add expertise in relation to equipment and materials development.
Collaborator Contribution Early discussions have taken place between the Senior Clinical Scientist in Translational Musculoskeletal Science and Technology and Research Associate from Faculty of Medicine, Department of Surgery & Cancer, and our research team. An NDA has been developed to enable and support further discussions. A Team from Imperial College London visited Lancaster Univeristy to attend a meeting in November 2017 with the following attendees: Professor Catherine Dan der Straeten; Edouard Auvinet, Research Associate; Rhiannon Lambkin, Research Associate. Professor Van Der Straeten has since resumed her substantive post at Ghent University but retains an honorary position at Imperial College London to continue the work with the team there.
Impact An NDA is in place. Discussions around shared research interests are underway with plans to identify and apply for funding in the next 6-12 months, including H2020 as a potential call to work towards. The main disciplines involved are clinical science, signal processing, imaging, engineering and biomechanics.
Start Year 2017
 
Description Knee acoustic emission research study collaboration 
Organisation Imorphics
Country United Kingdom 
Sector Private 
PI Contribution The Lancaster University research team led the study, including the set up of the collaboration agreement, ethical approval, data collection and data archiving. This included project management skills and meetings infrastructure, which ensured a high level of communication and information sharing within the collaboration throughout the project.
Collaborator Contribution Mistras were funded to provided the bespoke acoustic emission data collection systems and provided on going engagement, maintenance and expertise Imorphics were funded to provide expert analysis of the MR images and ongoing engagement and expertise Wellcome Trust CRF facility were funded to collect MR images from participants in line with the study protocol
Impact This collaboration includes expertise from clinical, imaging, manufacturing and engineering Software production for data processing, Database creation, Collaboration outside the original team, Conference prentations (IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2016 and British Society for Rheumatology Annual Conference in May 2018), Further papers in development, first paper submitted was rejected.
Start Year 2014
 
Description Knee acoustic emission research study collaboration 
Organisation Mistras Group Ltd
Country United Kingdom 
Sector Private 
PI Contribution The Lancaster University research team led the study, including the set up of the collaboration agreement, ethical approval, data collection and data archiving. This included project management skills and meetings infrastructure, which ensured a high level of communication and information sharing within the collaboration throughout the project.
Collaborator Contribution Mistras were funded to provided the bespoke acoustic emission data collection systems and provided on going engagement, maintenance and expertise Imorphics were funded to provide expert analysis of the MR images and ongoing engagement and expertise Wellcome Trust CRF facility were funded to collect MR images from participants in line with the study protocol
Impact This collaboration includes expertise from clinical, imaging, manufacturing and engineering Software production for data processing, Database creation, Collaboration outside the original team, Conference prentations (IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2016 and British Society for Rheumatology Annual Conference in May 2018), Further papers in development, first paper submitted was rejected.
Start Year 2014
 
Description Knee acoustic emission research study collaboration 
Organisation National Institute for Health Research
Department NIHR Biomedical Research Centre Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution The Lancaster University research team led the study, including the set up of the collaboration agreement, ethical approval, data collection and data archiving. This included project management skills and meetings infrastructure, which ensured a high level of communication and information sharing within the collaboration throughout the project.
Collaborator Contribution Mistras were funded to provided the bespoke acoustic emission data collection systems and provided on going engagement, maintenance and expertise Imorphics were funded to provide expert analysis of the MR images and ongoing engagement and expertise Wellcome Trust CRF facility were funded to collect MR images from participants in line with the study protocol
Impact This collaboration includes expertise from clinical, imaging, manufacturing and engineering Software production for data processing, Database creation, Collaboration outside the original team, Conference prentations (IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2016 and British Society for Rheumatology Annual Conference in May 2018), Further papers in development, first paper submitted was rejected.
Start Year 2014
 
Title JAAS system 
Description Undergoing clinical evaluation, funded by MRC. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact None as yet 
URL http://www.lancaster.ac.uk/shm/research/projects/noisy-knees/
 
Title Data processing software 
Description The software was developed by study team members at UCLAN to process the raw acoustic to collate features or create biomarkers to enable analysis. 
Type Of Technology Software 
Year Produced 2016 
Impact The acoustic emission data was processed to a high standard to enable analysis. A paper detailing the software development was presented at the IEEE BIBM Conference in Shenzhen in December 2016 titled 'Acoustic emission sonification and magnetic resonance imaging-based kinematics for exploratory analysis of knee joints' 
 
Title Visual imaging software 
Description Project titled 'Understanding knee osteoarthritis from angle-and-force based acoustic emission which links visual imaging to acoustic emissions. 
Type Of Technology Software 
Year Produced 2016 
Impact Analysis of study data 
 
Description Acoustic emission research carried out in FHM to assess patients with osteoarthritis in the knee received widespread news coverage by the BBC. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Acoustic emission research carried out in FHM to assess patients with osteoarthritis in the knee received widespread news coverage by the BBC.
https://www.lancaster.ac.uk/news/listening-to-noisy-knees-to-diagnose-osteoarthritis-the-first-human-cohort-study
The research appeared in the i newspaper and also:
BBC News online
https://www.bbc.co.uk/news/health-50071602
BBC One 9 o'clock TV News, BBC TV News Channel, BBC 2, BBC Radio 5Live; BBC Radio 4 Today ;30 BBC Radio Scotland and across almost every BBC local radio station in the UK: Cornwall, Cambridgeshire, Three Counties, Sheffield, Manchester, Norfolk, Northampton, Kent, Oxford, Lancashire, Leicester, Berkshire, Jersey, Hereford and Worcester, York, Leeds, Cumbria, Devon, Stoke, Shetland, Highlands & Islands, Somerset,

Researchers received several emails from companies wishing to collaborate and members of the public wishing to be part of future studies.
Year(s) Of Engagement Activity 2019
URL https://www.lancaster.ac.uk/news/listening-to-noisy-knees-to-diagnose-osteoarthritis-the-first-human...
 
Description Conference poster presentation 
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 Conference poster presentation
Year(s) Of Engagement Activity 2018
URL https://www.immunology.org/events/british-society-for-rheumatology-annual-conference
 
Description Dissemination of noisy knees in oral presentation at Mellanby Centre for Bone Research Annual Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Dissemination of noisy knees in oral presentation at Mellanby Centre for Bone Research Annual Meeting
Title: Acoustic Emissions as a Biomarker for Knee Osteoarthritis
Authors: Lucy Spain, David Cheneler, Daniela K. Schlueter, Lik-kwan Shark, Nicola Platt, Joe Mercer, John C. Waterton, Mike Bowes, Mandy Dixon, Jane Huddleston, John Goodacre
No known impact
Year(s) Of Engagement Activity 2019
URL https://insigneo.org/event/10th-annual-mellanby-centre-research-day-save-the-date/
 
Description Invited speaker at Lancashire Teaching Hospitals NHS Research and Innovation Showcase annual conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact As the Chief Investigator I was invited to one of the participating secondary care site to present about progress with the study. This reached an audience comprising of approximately 80 NHS consultants, nurses, students, industry and other academic institutions who were in attendance.
Year(s) Of Engagement Activity 2016
 
Description Lancaster University Pathway to Health and Wealth event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Demonstrated the research at Lancaster University's 'Pathway to Health and Wealth' conference, which was aimed at Life Sciences businesses. The demonstration attracted the interest of a few companies.

Following the conference, one of the companies has developed a collaboration with the University, though not directly on this project.
Year(s) Of Engagement Activity 2014
URL http://www.lancaster.ac.uk/healthandwealth/exhibition/
 
Description NHS Innovation Expo 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Provided demonstration of the research as part of Lancaster University's exhibit at the NHS Health Innovation Expo event in Manchester.

Generated interest in this new area of health research (acoustic emission).
Year(s) Of Engagement Activity 2014
URL http://www.england.nhs.uk/ourwork/expo/
 
Description News item on BBC North West Tonight 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The news item generated significant interest in the research project. This included over 15 email and telephone enquiries from members of the public who requested further information about the study or who wanted to be involved in the research. It also included an approach from a company who requested further discussions about potential collaboration.

The project team is in discussion with the company mentioned above about a potential future collaboration.
Year(s) Of Engagement Activity 2014
URL http://www.nwcahsn.nhs.uk/news/news-article.php?id=49
 
Description Webinar - Biomedical Acoustics Special Interest Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact We held an online webinar for UK Biomedical Acoustics SIG on Friday 26th June 2020 between 13:00-17:00.
Year(s) Of Engagement Activity 2020
URL https://acoustics.ac.uk/biomedical-acoustics/webinar-biomedical-acoustics-special-interest-group/