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

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).

Study Overview

• Status: Recruiting
• Conditions: Aortic Diseases; Aortic Dissection
• Intervention / Treatment: Diagnostic test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)

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).

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Andrea Salzano, MD; Phone Number: +44 (0) 1162583041; Email: andrea.salzano@leicester.ac.uk
• Study Contact Backup: Name: Toru Suzuki, MD, PhD; Phone Number: +44 (0)116 204 4741; Email: tsuzuki@leicester.ac.uk

Study Locations

• United Kingdom
  • Leicester, United Kingdom
    • Recruiting
    • University Hospitals of Leicester NHS Trust
    • Contact: Prof Suzuki
  • Leicester, United Kingdom, LE3 9QP
    • Not yet recruiting
    • University of Leicester
    • Contact: Andrea Salzano, MD; Email: andrea.salzano@leicester.ac.uk
    • Contact: Toru Suzuki, PhD; Email: tsuzuki@leicester.ac.uk
    • Sub-Investigator: Gerry P McCann, MD
    • Sub-Investigator: Anvesha Singh, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Acute patients will be identified in cardiologic inward, after that patients have been discharged from the coronary care unit at Glenfield Hospital, Leicester. Chronic patients will be identified from the aortic outpatient clinic at Glenfield Hospital.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute aortic dissection; stable patients with confirmed diagnosis of acute AD.	Diagnostic test: Magnetic 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.
Chronic aortic dissection; 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); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Leicester
• Investigators: Study Chair: Toru Suzuki, MD, PhD, University of Leicester

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2019
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 14, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Aneurysm; Inflammation; Aneurysm, Dissecting; Aortic Diseases
• Other Study ID Numbers: 0688

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No