Multi-centre MRI study of the heart microstructure in healthy volunteers
| ISRCTN | ISRCTN46174869 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN46174869 |
| IRAS number | 343837 |
- Submission date
- 30/04/2025
- Registration date
- 12/05/2025
- Last edited
- 20/06/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Cardiac diffusion tensor imaging (cDTI) is an emerging magnetic resonance imaging (MRI) based technique for examining the microstructure of the heart. The cardiac function and microstructure are highly interconnected. The adult heart comprises more than a billion heart muscle cells that are intricately connected and that contract in a highly coordinated manner to support the beating of the heart. Changes to the heart microstructure are an important feature in conditions such as heart attack or myocardial infarction (MI) and hypertrophic cardiomyopathy (HCM), where the heart muscle wall thickens. For example, an increase in collagen and scar following changes in microstructure following MI, and cell disarray in HCM, which can be assessed with cDTI. The microscopic displacement of water molecules due to diffusion is heavily influenced by the presence of cells and by the properties of these cells such as size, shape, orientation, integrity and so forth. Thus, by encoding the water diffusion information in the MRI image, one can evaluate the cardiac microstructure. In cDTI, several diffusion directions are encoded and then diffusion tensors (a mathematical model that can be pictured in 3D as an American football in shape) are fitted. From the diffusion tensor, several quantitative values can be derived such as the mean diffusivity (MD) that describes the average apparent diffusion, the fractional anisotropy (FA) that describes how pointed the tensor is, and the helix angle (HA) and sheetlet angle (E2A) that reflect the orientations of the heart muscle cells and their arrangement in sheetlets.
The links between the diffusion tensor and cardiac microstructure have been verified in numerous preclinical ex vivo and in vivo studies. Early clinical studies have reported diffusion parameters in the pathologic heart. In particular, higher myocardial MD and lower FA have been reported in pathologies such as MI, HCM and aortic stenosis (AS). Similarly, differences in HA and E2A angles have been reported in conditions such as MI, HCM, AS and dilated cardiomyopathy (DCM). This is thought to be related to the underlying changes in the cardiac microstructure.
The field of cardiac diffusion MRI remains technologically challenging due to a number of factors such as motion from the heart beating and breathing, distorted images and long scan times. Nonetheless, the field has been rapidly expanding over the past years, with publications in cDTI more than doubling over the decade up to 2020, and whole-heart cDTI within clinically feasible scan times looks increasingly likely to be achievable within the foreseeable future.
The study aims to:
1. Evaluate variation in cDTI data due to differences in (i) site/operator/scanner, (ii) subject, (iii) acquisition and (iv) post-processing methods.
2. Identify the greatest sources of variation and inform strategies for optimisation, standardisation and harmonisation of cDTI.
3. Inform power calculations and data interpretation in future larger studies, in particular, where different sites/methods are used.
Who can participate?
Healthy volunteers aged 18 to 65 years old with a body mass index (BMI) of 18.5 to 29.9 kg/m2. For the travelling volunteer study: Ability to travel independently between sites and to have all scans done within 2 months from first scan; possession of valid documentation (e.g. passport and visa) to travel between sites with validity extending to at least 8 months following first MRI scan, and with a passport no older than 10 years at the time of the last scan.
What does the study involve?
Non-travelling healthy volunteers will be identified, approached and recruited by non-travelling volunteer sites in accordance with site-specific ethics for sites outside the UK. Non-travelling volunteers will only be consented under the respective site-specific ethics. These are non-NHS sites and non-HRA-relevant.
Travelling volunteers will be recruited and consented by the study team at Royal Brompton Hospital to travel to multiple sites for a single MRI scan at each site. Potential volunteers who express interest in participating will be sent the participant information sheet (PIS) and research volunteer checklist. Before consent/scan, volunteers who wish to participate in the study will be asked to complete and return the research volunteer checklist for the study team to assess eligibility. Participants who meet eligibility requirements and are interested in participation will be invited to provide written consent. Consent will also be sought for the sharing and storing of personal information for study oversight, scan scheduling, safety monitoring, booking travel and reimbursement.
Volunteers will be invited to undergo a single MRI examination at each site. Before each scan, the participant’s height and weight will be measured. A site-specific MRI screening questionnaire shall be completed to help ensure safety in the MRI scanner. The MRI scan will typically last between 60 to 90 minutes. Surface electrodes (stickers) will be placed on the chest to monitor heart beat during the scan.
What are the possible benefits and risks of participating?
This study is done solely for research purposes and participants will not benefit from taking part. Their participation may, however, benefit future care. The scans will be for research purposes only and cannot be used for clinical diagnosis.
MRI is safe and no ionising radiation (energy that can potentially cause damage to cells) is used for this scan. There are no known risks from the technique. Some people may experience claustrophobia (fear of confined spaces). The MRI staff will do all that they can to make participants feel comfortable during the scan. Participants may withdraw from the study at any time. For travelling volunteers, there is a small risk associated with travel. Participants are asked to highlight any concerns they may have about such travel. Travel and accommodation will be arranged through reputable vendors, and participants will be kept updated on any travel advisories at the time.
Where is the study run from?
This is an international multi-centre initiative, initiated by the Society of Cardiovascular Magnetic Resonance Cardiac Diffusion Special Interest Group. The Project Management Committee responsible for taking decisions on the study has members based in Switzerland, the UK and the USA.
When is the study starting and how long is it expected to run for?
July 2024 to August 2029
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Dr Irvin Teh, i.teh@leeds.ac.uk
Contact information
Scientific, Principal Investigator
University of Leeds
Leeds
LS2 9JT
United Kingdom
 ORCID ID |
0000-0002-6705-3129 |
|---|---|
| Phone | +44 (0)1133438306 |
| i.teh@leeds.ac.uk |
Public
University of Leeds
Leeds
LS2 9JT
United Kingdom
| Phone | +44 (0)1133928250 |
|---|---|
| k.h.richards@leeds.ac.uk |
Study information
| Study design | Multi-centre prospective observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital, University/medical school/dental school |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Multi-centre investigation of cardiac diffusion tensor imaging (DTI) in healthy volunteers by SCMR Cardiac Diffusion Special Interest Group NETwork |
| Study acronym | SIGNET |
| Study objectives | There exists a wide range of reported diffusion tensor imaging (DTI) metrics in the literature, including reports that are potentially artifactual, which have been previously highlighted. This will be influenced by the subject cohort, e.g. health vs disease. Other potential sources of variation include differences in sites/operators/scanners, acquisition and post-processing methods. This variation needs to be better understood to support clinical validation of the technique. Early work has evaluated reproducibility in a ten-site study in isotropic phantoms and in a two-site study in healthy volunteers. In this study, we propose a broad multi-centre collaborative effort to evaluate inter-site variation due to differences in (i) site/operator/scanner, (ii) acquisition and (iii) post-processing methods. The results will guide the interpretation of the cardiac diffusion MRI literature, and help to refine strategies for standardisation and harmonisation of protocols. We propose in the first instance to study healthy volunteers to establish a baseline of variation due to technical (non-pathology related) factors. |
| Ethics approval(s) |
Approved 31/07/2024, University of Leeds School of Medicine Research Ethics Committee (SoMREC) (Worsley Building, University of Leeds, Leeds, LS2 9JT, United Kingdom; -; FMHUniEthics@leeds.ac.uk), ref: MREC 23-027 |
| Health condition(s) or problem(s) studied | Evaluation of cardiac microstructure with cardiac DTI |
| Intervention | Single MRI scan for non-travelling volunteers Single MRI scan for travelling volunteers at each site, over multiple sites Non-travelling healthy volunteers will be identified, approached and recruited by non-travelling volunteer sites in accordance with site-specific ethics for sites outside the UK. Non-travelling volunteers will only be consented under the respective site-specific ethics. These are non-NHS sites and non-HRA-relevant. Travelling volunteers will be recruited and consented by the study team at Royal Brompton Hospital to travel to multiple sites for a single MRI scan at each site. Potential volunteers who express interest in participating will be sent the participant information sheet (PIS) and research volunteer checklist. Prior to consent/scan, volunteers who wish to participate in the study will be asked to complete and return the research volunteer checklist for the study team to assess eligibility. Participants who meet eligibility requirements and are interested in participation will be invited to provide written consent. Consent will also be sought for the sharing and storing of personal information for study oversight, scan scheduling, safety monitoring, booking travel and reimbursement. Volunteers will be invited to undergo a single MRI examination at each site. Prior to each scan, participants’ height and weight will be measured. A site-specific MRI screening questionnaire shall be completed to help ensure safety in the MRI scanner. The MRI scan will typically last between 60 to 90 minutes. Surface electrodes (stickers) will be placed on the chest to monitor heartbeat during the scan. |
| Intervention type | Other |
| Primary outcome measure | Cardiac DTI data including mean diffusivity, fractional anisotropy, helix angle and E2 angle. For non-travelling volunteers, these will be acquired at baseline. For travelling volunteers, these will be acquired at all travelling volunteer sites within 2 months of baseline. |
| Secondary outcome measures | Signal-to-noise ratio and potential non-compliance of scans with the protocol collected during each scan |
| Overall study start date | 31/07/2024 |
| Completion date | 31/08/2029 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | Non-travelling volunteer sites: 12 per site, with provision for up to additional 4 subjects per site as contingency. Travelling volunteer sites: 12 in total, with provision for up to additional 4 subjects in total as contingency. Total final enrolment shall be 12 × (N+1) where N = number of non-travelling volunteer sites, with provision for up to 4 × (N+1) as contingency. Example: Assuming N = 20 non-travelling volunteer sites and 0 volunteers needed for contingency, then total final enrolment will be (20+1)*12 = 252. |
| Key inclusion criteria | 1. Healthy volunteer 2. Male or female; sites shall aim to recruit equal numbers, i.e. male (n = 6) / female (n = 6) 3. Age 18 to 65 years old 4. Body mass index (BMI) 18.5 to 29.9 kg/m2 5. For travelling volunteer study: Ability to travel independently between sites, and to have all scans done within 2 months from first scan; possession of valid documentation (e.g. passport and visa) to travel between sites with validity extending to at least 8 months following first MRI scan, and with passport no older than 10 years at time of last scan. |
| Key exclusion criteria | 1. Safety or clinical concerns precluding participation 2. Any history of health conditions that may affect the heart (e.g. hypertension, diabetes, arrhythmias, angina, myocardial, valve and vessel disease) 3. Pregnancy or breastfeeding, including suspected pregnancy 4. Claustrophobia that limits/prevents participants from remaining in the MRI scanner 5. Inability to lie flat on the scanner table 6. Physical frailty 7. Contraindications to MRI (some pacemakers, intraorbital debris, intraauricular implants, intracranial clips, etc) 8. Those who could be considered to have a particularly dependent relationship with an investigator, e.g. members of staff or students 9. Involvement with the research apart from volunteering 10. Any relevant health conditions precluding safe travel between sites within 2 2-month time frame (For travelling volunteer study) |
| Date of first enrolment | 01/09/2025 |
| Date of final enrolment | 31/05/2026 |
Locations
Countries of recruitment
- Belgium
- Denmark
- England
- France
- Japan
- Poland
- Switzerland
- United Kingdom
- United States of America
- Wales
Study participating centres
8200
Denmark
E1 1BB
United Kingdom
MA 02215
United States of America
MA 02115
United States of America
1090 Jette
Belgium
CF24 4HQ
United Kingdom
OH 44195
United States of America
1172 København
Denmark
69100 Villeurbanne
France
GA 30322
United States of America
8092 Zürich
Switzerland
1205 Genève
Switzerland
060-8648
Japan
TX 77401
United States of America
80-210
Poland
MA 02114
United States of America
MD 20892
United States of America
61-701
Poland
2100 København
Denmark
SW3 6NP
United Kingdom
CA 94305
United States of America
TX 77840
United States of America
33076
France
WC1E 6BT
United Kingdom
LS2 9JT
United Kingdom
OX1 2JD
United Kingdom
2820 Bonheiden
Belgium
Sponsor information
University/education
Research Ethics and Governance Officer
The Secretariat
Woodhouse Lane
Leeds
LS2 9JT
England
United Kingdom
| Phone | +44 (0)113 343 7587 |
|---|---|
| governance-ethics@leeds.ac.uk | |
| Website | https://www.leeds.ac.uk/ |
"ROR" |
https://ror.org/024mrxd33 |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 31/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | Planned publication in peer-reviewed journals and conferences. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a publicly available repository. Anonymised research data will be made available by UoL to the research community for the current study and future research as governed by the Collaboration Agreement. Access to publicly available data by third parties will be governed by an agreement with an End User / Data Sharing Agreement. |
Editorial Notes
20/06/2025: The recruitment start date was changed from 01/06/2025 to 01/09/2025.
01/05/2025: Study's existence confirmed by the HRA.
