PROFILE-MI - The FAPI Fibrosis Study

Study Overview
=================
Brief Summary
-----------------
The investigators here propose to investigate the timing and pattern of myocardial fibrosis activity following acute myocardial infarction using hybrid 68Ga-FAPI positron emission tomography and cardiovascular magnetic resonance. The investigators hypothesise that peak fibrosis activity will occur within 2-4 weeks of acute myocardial infarction and will predict subsequent scar formation and cardiac remodelling. Simultaneously, matrix remodelling and fibrosis activity in aortic and coronary atheroma will be assessed enabling the exploration of the presence of unstable atheroma.

Detailed Description
-----------------
Fibrosis is a fundamental process underlying almost all cardiomyopathic conditions. Established fibrosis can be detected by existing imaging techniques including cardiovascular magnetic resonance. However, these techniques are not specific for fibrosis and do not directly measure fibrosis activity or matrix remodelling. This limits the ability to detect early disease and differentiate active from end-stage phenotypes. Fibroblast activation protein is a key factor in fibrogenesis that is expressed in the myocardium following myocardial infarction and in thin-capped fibroatheroma. Radiolabelled fibroblast activation protein inhibitor (68Ga-FAPI) measures in vivo fibrosis activity and matrix remodelling, as supported by preliminary pilot studies. The timing and pattern of myocardial fibrosis activity following acute myocardial infarction will be investigated using hybrid 68Ga-FAPI positron emission tomography. The investigators hypothesise that peak fibrosis activity will occur within 2-4 weeks of acute myocardial infarction and will predict subsequent scar formation and cardiac remodelling. Simultaneously, matrix remodelling and fibrosis activity in aortic and coronary atheroma will also be assessed allowing exploration of the presence of unstable atheroma. This project will enhance understanding of fibrosis activity and matrix remodelling in myocardial infarction and unstable atherosclerotic plaque with potential future application to a broad range of cardiovascular diseases.

Official Title
-----------------
PROline and FapI With Late Gadolinium Enhancement in Myocardial Infarction PROFILE-MI - The FAPI Fibrosis Study

Conditions
-----------------
Myocardial Infarction, Myocardial Fibrosis

Intervention / Treatment
-----------------
* Radiation: 68Gallium FAPI PET/MR scan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: specific to cohort; aged 50 years or older Exclusion Criteria: Claustrophobia Inability to undergo MRI eGFR <30ml/min/1.73^m2

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy volunteers<br>Age- and sex- matched to participants, those aged 50 or over without known heart disease. n=20 | Radiation: 68Gallium FAPI PET/MR scan<br>* 68Gallium FAPI PET/MR scan<br>|
| Acute myocardial infarction - multi-timepoint imaging<br>Those aged 50 or over with recent myocardial infarction who will be imaged using PET/MR at 1,2,4, and 12 weeks post-MI. n=20 | Radiation: 68Gallium FAPI PET/MR scan<br>* 68Gallium FAPI PET/MR scan<br>|
| Acute or chronic myocardial infarction - single timepoint imaging<br>Those aged 50 or over with recent (n=20) or prior established (>24 months, n=20) myocardial infarction who will be imaged at a single timepoint (1,2,4, or 12 weeks post-MI for acute, at the time of enrolement to the study for chronic). | Radiation: 68Gallium FAPI PET/MR scan<br>* 68Gallium FAPI PET/MR scan<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of maximal fibrosis activity following myocardial infarction | SUVmax and TBR of 68Ga-FAPI uptake within the infarct, border zone, and remote myocardium | 12 weeks | 
| Whether fibrosis activity predicts myocardial scar volume and ventricular remodelling | As measured by CMR 12 months following acute MI | 12 months | 
| Fibrosis activity and myocardial remodelling within atherosclerotic plaque in patients with myocardial infarct | SUVmax and TBR of 68Ga-FAPI uptake within areas of atherosclerotic plaque in the aorta and/or carotid arteries | 12 weeks |