MICA: Non-invasive quantitative ventilation imaging by MRI of fluorocarbon gases
Lead Research Organisation:
Newcastle University
Department Name: Translational and Clinical Res Institute
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.
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.
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.
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.
Organisations
- Newcastle University (Lead Research Organisation)
- University of Sheffield (Collaboration)
- MANCHESTER UNIVERSITY NHS FOUNDATION TRUST (Collaboration)
- The Hospital for Sick Children (SickKids) (Collaboration)
- Philips Medical Systems UK Ltd (Collaboration)
- Monash University (Collaboration)
- Philips (United Kingdom) (Project Partner)
Publications
Neal MA
(2020)
Dynamic susceptibility contrast 19 F-MRI of inhaled perfluoropropane: a novel approach to combined pulmonary ventilation and perfusion imaging.
in Magnetic resonance in medicine
Pippard BJ
(2021)
Reproducibility of 19 F-MR ventilation imaging in healthy volunteers.
in Magnetic resonance in medicine
Maunder A
(2021)
MR properties of 19 F C3 F8 gas in the lungs of healthy volunteers: T 2 * and apparent diffusion coefficient at 1.5T and T 2 * at 3T.
in Magnetic resonance in medicine
Neal MA
(2019)
Optimized and accelerated 19 F-MRI of inhaled perfluoropropane to assess regional pulmonary ventilation.
in Magnetic resonance in medicine
Cooke F
(2022)
Fluorine labelling of therapeutic human tolerogenic dendritic cells for 19F-magnetic resonance imaging.
in Frontiers in immunology
Description | CiC - Using lung ventilation imaging to optimise lung cancer radiotherapy plans |
Amount | £118,517 (GBP) |
Funding ID | NU-016399 |
Organisation | Newcastle University |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2023 |
End | 12/2024 |
Description | Invited Research Award |
Amount | £1,106,921 (GBP) |
Funding ID | 21811 |
Organisation | Versus Arthritis |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2022 |
Description | MRC Confidence in Concept: A novel MRI method for quantitation of lung perfusion properties |
Amount | £18,399 (GBP) |
Organisation | Newcastle University |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2017 |
End | 01/2018 |
Description | MRC Confidence in Concept: New tools to image pulmonary embolism without exposure to ionising radiation |
Amount | £68,878 (GBP) |
Funding ID | NU-000756 |
Organisation | Newcastle University |
Sector | Academic/University |
Country | United Kingdom |
Start | 02/2020 |
End | 02/2021 |
Description | Non-invasive quantitative ventilation imaging by MRI: pathway to clinical use |
Amount | £184,467 (GBP) |
Funding ID | PGL22 100063 |
Organisation | Rosetrees Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2023 |
End | 02/2026 |
Title | Quantitative imaging measurement of lung ventilation properties |
Description | We have developed imaging measurements of lung ventilation properties, and demonstrated their ability to visualise and quantify ventilation defects. We image the distribution of an inert, inhalable, MRI-visible gas, perfluoropropane. |
Type Of Material | Physiological assessment or outcome measure |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | We have measured reproducibility of these lung MRI measurements in healthy volunteers, and shown ability to quantify locations and extent of ventilation defects in patients with asthma and in patients with chronic obstructive lung disease. We have demonstrated that these scan methods can quantify improvement in lung function with treatment. |
Description | Hospital for Sick Kids, Toronto |
Organisation | The Hospital for Sick Children (SickKids) |
Country | Canada |
Sector | Hospitals |
PI Contribution | Provided advice and input into the setup of scan protocols for MRI in inhaled perfluoropropane to measure ventilation properties in healthy volunteers and patients with a respiratory disease. Provided technical expertise based on similar studies performed on the same type of MRI scanner as used by the team in Toronto with the aim of accelerating progress towards delivery of lung function MRI scan capabilities for use in respiratory clinical research and clinical trials. |
Collaborator Contribution | No direct contribution to this project. |
Impact | No outputs yet reported |
Start Year | 2021 |
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 | Wythenshawe Hospital |
Organisation | Manchester University NHS Foundation Trust |
Department | Respiratory Clinical Research Centre, Wythenshawe |
Country | United Kingdom |
Sector | Public |
PI Contribution | Established collaboration between Newcastle University, The Wythenshawe Hospital in Manchester UK, and The Royal Children's Hospital in Melbourne Australia to grow the network of sites capable of performing 19F-MRI to assess lung ventilation properties. Newcastle University have arranged loan of hardware from Melbourne to The Wythenshawe to enable their participation in the project as a study site. |
Collaborator Contribution | Creation of lung 19F-MRI scan protocols for quantitation of lung ventilation properties on a Siemens Vida 3T MRI scanner, and associated preparations to become a study site for recruitment and MRI scanning of patients with Chronic Obstructive Pulmonary Disease. |
Impact | No outputs yet: collaboration established and preparations for study participation are underway, with patient recruitment to the study planned to start in spring 2022. |
Start Year | 2022 |
Title | Quantitative lung ventilation imaging by MRI of inhaled perfluoropropane |
Description | Methodology for 3D imaging of lung ventilation properties by MRI of an inhaled MR-visible inert gas. We have demonstrated the ability measure lung ventilation properties in patients with respiratory disease, providing quantitative metrics of disease impact and change in lung function in response to therapy. We are currently assessing the ability to incorporate these measurements into clinical workflows for radiotherapy treatment of lung cancer (MRC Impact Accelerator Account funding), to be followed by studies that determine whether the incorporation of lung function imaging into lung cancer radiotherapy planning can deliver improved radiotherapy outcomes. |
Type | Diagnostic Tool - Imaging |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2024 |
Development Status | Under active development/distribution |
Impact | Under active development towards patient impact. |
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 |