MICA: Non-invasive quantitative ventilation imaging by MRI of fluorocarbon gases

Lead Research Organisation: Newcastle University
Department Name: Institute of Cellular Medicine

Abstract

Respiratory diseases are among the leading causes of death worldwide. New treatments for respiratory diseases are increasingly emerging, and tests to determine response to treatments are vital for management of a patient's respiratory disease. Unfortunately, existing measures of assessing lung function and structure have limitations. For example, spirometry cannot provide information on regional change within the lungs, so early localised changes in ventilation properties may pass undetected. Computed tomography (CT) scanning provides images of lung structure, but uses ionising radiation (x-rays) to generate these images and the associated radiation dose means that regular scanning to monitor disease progression or response to therapy is typically impossible. There is therefore a pressing need for new techniques that can perform safe, objective, repeatable and accurate measurement of lung ventilation properties, to better understand how respiratory diseases progress over time and to assess how they respond to therapy strategies.

We are developing non-invasive and radiation-free imaging of lung ventilated volume, using new MRI technologies. MRI is a safe and repeatable medical imaging technology that uses strong magnetic fields to generate images of the body. We are using MRI to visualise a gas that can be safely inhaled, allowing us to generate images of the lungs that show areas that are (and that are not) well ventilated. We aim to show that we can measure the differences in lung ventilation properties between people with healthy lungs and those with a respiratory disease, and measure the change in ventilation properties when patients with a respiratory disease take a bronchodilator (a common treatment for asthma).

This work is significant because at present there is no imaging measurement with such capabilities in widespread clinical practice. Our overall aim is to develop this technology so that it can be introduced to clinical practice, delivering new measurements to help clinicians care for patients with respiratory disease.

In this study we will perform a proof of concept study that tests the reproducibility of our MRI scan methods in a group of healthy volunteers. We will then recruit patients with asthma and patients with chronic obstructive pulmonary disease (COPD) and demonstrate that our MRI scan methods can characterise the impaired ventilation properties associated with these conditions. We will also perform MRI scans before and after these patients receive a bronchodilator, to test whether we can detect a change in ventilation properties due to drug treatment. The study is a clinical trial of an investigational medicinal product, and will be performed with appropriate regulatory approval and oversight.

Once we have performed these studies we will be well positioned to further develop our MRI techniques to assess lung ventilation properties. We intend to follow this current project with larger multi-site studies that demonstrate the utility of perfluoropropane MRI in the management of patients with a respiratory disease, and then to further develop the technology such that it is ready for adoption by the NHS and other healthcare providers.

This project will be performed at two sites, Newcastle and Sheffield, and is a collaborative project between Newcastle University, The University of Sheffield, the Newcastle upon Tyne Hospitals NHS Foundation Trust, and the Sheffield Teaching Hospitals NHS Foundation Trust.

Technical Summary

We are developing non-invasive and radiation-free methods for imaging lung ventilation properties, using new Magnetic Resonance Imaging (MRI) technologies. Our methods provide quantitative measures with potential for translation to clinical practice.
Respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma have a major impact on health. Existing techniques to objectively measure lung ventilation properties have significant limitations. For example, spirometry gives no anatomical information and CT scans incur an ionising radiation dose. There is a pressing need for techniques allowing safe, objective, repeatable and quantifiable measurements of ventilation properties.
A recently described technique employs a fluorocarbon gas (perfluoropropane) as an inert, inhalable tracer that can be imaged by MRI. Critically, this approach does not involve gas hyperpolarisation, so can be implemented on clinical MRI scanners with minimal additional hardware.
Our study seeks to develop 19F-MRI of perfluoropropane by testing its ability to quantify ventilation defects, representing a step towards the ultimate goal of implementation in clinical practice. Specifically, we will determine the reproducibility of the methods in healthy volunteers, use the methods to quantify the degree of airway disease in asthma and COPD patient cohorts, and benchmark performance of 19F-MRI against established hyperpolarised MRI methods. Studies will be performed at two sites (Newcastle and Sheffield), laying the groundwork for future multisite clinical trials.
Our study team brings together MR physicists and clinical academics with longstanding experience of respiratory conditions, MR technical approaches, and translational research. Our preliminary studies have confirmed feasibility and safety in healthy volunteers. 19F-MRI of inhaled perfluoropropane represents a nascent field that we are well positioned to develop and apply, and to exploit its clinical potential.

Planned Impact

Chronic obstructive pulmonary disease (COPD) and asthma are obstructive airway diseases with a major impact on health. COPD is projected to rank fifth worldwide in burden of disease by 2020 (GOLD initiative), and is the fifth biggest killer in the UK (Department of Health, UK). Asthma affects over 5 million patients in the UK (Asthma UK). Respiratory diseases are a major cause of productivity loss in the work place, associated poor quality of life and place a considerable burden on the NHS. The direct healthcare costs of respiratory disease in the EU is over 55 billion Euro per annum, and 1 in 8 deaths in the EU from respiratory diseases (European Lung White Book).
For a patient with respiratory disease, pulmonary function impairment and associated symptoms can significantly impact well-being and undertaking normal daily activities, and also affect the lives of family members providing care for patients.

DIAGNOSIS AND MONITORING, AND TREATMENT: Magnetic resonance imaging (MRI) provides a non-invasive way to view structure and function of tissues within the human body. Objective and reliable measures of lung ventilation properties such as MRI-based methods to image inhaled tracer gases will enable better characterisation of respiratory diseases, their progression over time, and the effects of treatment. As new treatment options are increasingly emerging, such improved monitoring would allow more effective and economical prescribing at the individual level, as well as providing better endpoints in clinical trials.

Our methods to image ventilation properties with MRI have significant advantages over the existing lung function measures used in clinical practice, and thus have significant potential for clinical impact. Spirometry and whole-body plethysmography do not provide regional functional information. CT scan and gamma-camera methodologies are imaging-based, but incur cumulative radiation doses with consequent risk to the patient. MRI provides spatially-resolved quantitative measures of structure and function without exposure to ionising radiation, and our methods employ an inert tracer gas that can be safely inhaled. Thus we are developing a safe and repeatable radiological tool.

HEALTH AND WELLBEING, AND THE NHS: Perfluoropropane MRI is a new tool for stratified medicine, aiding decision-making by respiratory clinicians with higher quality, spatially resolved diagnostic information. It thus has potential to impact patient outcome by providing better metrics of disease impact and provision of a safely repeatable measure. Improved clinical care has consequent societal and economic benefits, both to the NHS (via reduction of overall treatment costs) and to patients (in terms of quality of life, health and wellbeing and employment prospects).

CAPACITY BUILDING: Newcastle and Sheffield Universities are well placed to exploit MRI of inhaled fluorocarbon gases, and to lead imaging technology advances with consequent impact for patients and the healthcare industry. The project represents capacity building in a nascent field, with consequent strengthening of the UK MR physics community and with strong potential for NHS benefit and how health care is provided.

INDUSTRY: Improved endpoints for clinical trials benefit pharma and bioscience companies developing novel respiratory therapeutics. Radiation-free measurements benefit participants in trials, and enable repeated measurements and thus collection of better data to assess response to therapy. Accurate imaging-based endpoints represent an advance over conventional measurements such as spirometry.

Publications

10 25 50
 
Description Invited Research Award
Amount £1,106,921 (GBP)
Funding ID 21811 
Organisation Arthritis Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2018 
End 03/2022
 
Description MRC Confidence in Concept
Amount £18,399 (GBP)
Organisation Newcastle University 
Sector Academic/University
Country United Kingdom
Start 07/2017 
End 01/2018
 
Description Monash University 
Organisation Monash University
Department Faculty of Science
Country Australia 
Sector Academic/University 
PI Contribution Expertise and experimental methods for MRI of inhaled tracer gases.
Collaborator Contribution Organisation of a research study to assess ability of 19F-MRI of inhaled fluorocarbon tracer gases to report on lung ventilation properties
Impact -
Start Year 2016
 
Description Philips 
Organisation Philips Medical Systems UK Ltd
Country United Kingdom 
Sector Private 
PI Contribution Access to advanced MRI scanner tools, technologies and capabilities for the development of novel MRI scan methods and their application to clinical research.
Collaborator Contribution - Provision of a suite of MRI scanner pulse programming tools and access to the MRI scanner source code to allow modification of existing MRI scanner functionality and creation of novel MRI scan methodologies. - Provision of the ability to interface RF coils (MRI scanner sensors) from third party suppliers, and in-house RF coils, to the MRI scanners for use in research studies - Provision of multinuclear MR spectroscopy and imaging capabilities for use in research studies.
Impact No outputs to date
Start Year 2016
 
Description Sheffield University 
Organisation University of Sheffield
Department School of Health and Related Research (ScHARR)
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-investigators in the development and application of novel MRI methods to assess lung ventilation properties
Collaborator Contribution Development of novel technologies for 19F-MRI of inhaled fluorocarbon tracer gases for visualisation of lung structure and function, including input on scanner hardware and image analysis software.
Impact No outputs yet.
Start Year 2016
 
Description Patient and participant input regarding lung MRI studies (preparation for ethics submission) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Discussions were held with a group of patients with respiratory disease, and with a group of members of the general public. The purpose of the discussions was to gain input on study objectives and design, and to gain input on documentation provided to study participants as part of study recruitment and consent processes (eg. participant information sheets and consent forms).
Findings from the discussions were used to revise and refine study documents prior to submission as part of the study ethical approval process.
Year(s) Of Engagement Activity 2016