Magnetic Resonance Imaging (MRI) for Aortic Dissection to Visualise Inflammation

Study Overview
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Brief Summary
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The study is a single-centre, prospective, observational cross-sectional imaging study aimed to determine if macrophage-mediated inflammation can be visualised in the aorta of patients with aortic dissection (AD) using ultrasmall super paramagnetic iron oxides (USPIO)-enhanced magnetic resonance imaging (MRI).

Detailed Description
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Aortic dissection (AD) is a condition in which a disruption of the medial layer (in most cases provoked by a tear or an ulcer in the intima) results in separation of the aortic wall layers, with concomitant 'false lumen' formation and malperfusion of end organs. The underlying mechanism of the condition has, until recently, remained unclear. The Pi of the present sutdy has shed light on a mechanism that shows that inflammation underlies the condition. The PI of the present study has showed that inflammation in the aorta is triggered by macrophage infiltration into the aortic wall in both pre-clinical models using animal models of the condition (murine) and in patient tissue samples obtained at time of surgery. Macrophage infiltration into the aortic wall, as a result of activation of the cytokine, granulocyte-macrophage colony stimulating factor (GM-CSF), is the trigger for an inflammatory cascade that is presently understood to underlie the pathogenic mechanism of the condition Non-invasive assessment of macrophage infiltration would prove that this pathogenic mechanism exists (proof-of-concept). Macrophage infiltration has been shown to be feasible by contrast-enhanced Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs). The hypothesis of the present study is that macrophage-mediated inflammation can be visualised in the aorta of patients with AD using the USPIO-enhanced MRI technique, and use the present study to confirm this (proof-of-concept).

Official Title
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Magnetic Resonance Imaging (MRI) for Aortic Dissection to Visualise Inflammation

Conditions
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Aortic Dissection, Aortic Diseases

Intervention / Treatment
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* Diagnostic Test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of acute or chronic aortic dissection (>2 week after initial intimal injury) Able and willing to comply with all study requirements. Age > 40 years (Patients under the age of 40 years will not be included as they may have a connective tissue disorder accounting for their condition) Able and willing to give informed consent An adequate understanding of written and verbal English Exclusion Criteria: Past history of systemic iron overload or haemochromatosis Renal failure (estimated glomerular filtration rate < 30ml/min) Contraindication to MRI Known allergy to iron-containing compounds Participants who have participated in another research study involving an investigational product in the past 12 weeks. Female participants who are pregnant or lactating. Unwilling or unable to give informed consent

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acute aortic dissection<br>stable patients with confirmed diagnosis of acute AD. | Diagnostic Test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)<br>* All patients will undergo two MRI scans (one MRI scan pre-USPIO administration, and one MRI scan 24-36 hours following USPIO administration) and blood samples will be taken for future biomarker analysis.<br>|
| Chronic aortic dissection<br>patients with diagnosis of chronic AD, being followed up in outpatient aortic clinic. | Diagnostic Test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)<br>* All patients will undergo two MRI scans (one MRI scan pre-USPIO administration, and one MRI scan 24-36 hours following USPIO administration) and blood samples will be taken for future biomarker analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visualisation of inflammation | To determine if macrophage-mediated inflammation can be visualised in the aorta of patients with aortic dissection using USPIO-enhanced MRI | Up to 36 hours | 
| Feasibility | To establish the feasibility of imaging macrophage-mediated inflammation in the aorta of patients with aortic dissection, using USPIO-enhanced MRI. | Up to 36 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timing | To determine the timing of macrophage infiltration in aortic dissection (acute or chronic phase) | Up to 36 hours | 
| Localisation | To assess if macrophage mediated inflammation is localised to the site of dissection and the surrounding aorta or more widespread in the vasculature. | Up to 36 hours |