Aortic Diseases, Aortic Dissection
Conditions
Brief summary
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
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).
Interventions
DIAGNOSTIC_TESTMagnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)
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.
Sponsors
University of Leicester
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visualisation of inflammation | Up to 36 hours | To determine if macrophage-mediated inflammation can be visualised in the aorta of patients with aortic dissection using USPIO-enhanced MRI |
| Feasibility | Up to 36 hours | To establish the feasibility of imaging macrophage-mediated inflammation in the aorta of patients with aortic dissection, using USPIO-enhanced MRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Timing | Up to 36 hours | To determine the timing of macrophage infiltration in aortic dissection (acute or chronic phase) |
| Localisation | Up to 36 hours | To assess if macrophage mediated inflammation is localised to the site of dissection and the surrounding aorta or more widespread in the vasculature. |
Countries
United Kingdom
Contacts
Primary ContactAndrea Salzano, MD
Backup ContactToru Suzuki, MD, PhD
Outcome results
None listed