Non-Invasive Imaging of Atherosclerosis

Atherosclerosis Clinical Trial

Official title:

In Vivo Molecular Imaging (MRI) of Atherothrombotic Lesions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01418313
• Other study ID #: GCO 01-1032
• Secondary ID: R01HL071021
• Status: Completed
• Start date: September 2011
• Est. completion date: March 9, 2020

Study information

• Verified date: July 2020
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to develop and validate novel magnetic resonance imaging (MRI), dynamic contrast enhanced (DCE)-MRI and positron emission tomography (PET)/MR techniques for the detection and risk stratification of patients with atherosclerosis.

Description:

Atherosclerosis is responsible for the majority of disabilities and deaths in developed countries. Previous studies have shown that sudden clinical events correlate highly with plaque composition and the degree of plaque inflammation. These results stress the importance of developing non-invasive surrogate markers of plaque inflammation to detect asymptomatic high-risk plaques in clinical settings. Dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and 18F fluorodeoxyglucose (FDG) positron emission tomography (PET) with combined computed tomography (CT) have shown promise in characterizing and quantifying metabolic activity (i.e., glycolysis/ inflammation) in atherosclerosis, by targeting the presence of neovessels (DCE-MRI) and inflammatory cells such as macrophages (18F-FDG PET) in plaques of both animal and human subjects. However, several challenges need to be overcome prior to translating these imaging approaches to clinical practice. A significant obstacle to adapting conventional DCE-MRI approaches to atherosclerosis includes the necessity to image with high spatial resolution to capture plaque heterogeneity. This can be achieved with longer scan times, but conflicts with need for high temporal resolution required for accurate arterial input function sampling and quantification of contrast agent uptake. In Aim 1, the investigators will develop and validate a novel dual-imaging sequence for DCE-MRI of atherosclerosis where the investigators acquire a high temporal resolution, but low spatial resolution, AIF image and a high spatial resolution/low temporal resolution vessel wall image to allow accurate quantification of contrast agent uptake within plaques. This approach will be compared to conventional approaches in both a rabbit model of atherosclerosis and in human subjects. The limited spatial resolution of conventional PET scanners has an impact on the accuracy of 18F-FDG PET quantification in atherosclerotic plaques because of the partial volume effect (PVE). A posteriori PVE correction methods using high-resolution anatomical images acquired with a different imaging modality can improve quantification, but are challenging since they require accurate co-registration between the another imaging modality and PET. MR is an ideal choice for this second imaging modality as it produces high-resolution anatomical images without the use of ionizing radiation. A combined MR/PET scanner may therefore be better suited for developing novel PVE correction methodologies. As part of Aim 2, the investigators will develop and validate the combined MR-PET(FDG) imaging approach to improve the quantification of atherosclerotic plaque metabolic activity. Attenuation correction based on MR will be compared with CT based attenuation correction. Approaches to improved PVE correction and optimal circulation time for plaque imaging will also be validated in both rabbits and humans. Finally, imaging parameters derived from the improved DCE-MRI and MR- PET(FDG) will be validated in patients undergoing carotid endarterectomy (CEA), with the primary endpoint of establishing the relationship between imaging and histological markers of plaque inflammation. Additionally, the investigators will assess the relationship (if any) with serum biomarkers and, as an exploratory endpoint, the investigators will study by real time PCR the relationship of imaging with the gene expression of markers of plaque vulnerability.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 886
• Est. completion date: March 9, 2020
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Volunteers with carotid artery disease who are MRI and CT compatible.

• All subjects will have either a

• clinical diagnosis of atherosclerosis,

• and/or risk factors

• and/or family history of disease

Exclusion criteria:

• Glomerular filtration rate <30mg/ml (for MRI with contrast)

• Subjects who have any ferromagnetic implants (e.g. aneurysm clip, ICD, pacemaker, etc.) or a condition that may be contraindicated for the MRI procedure (e.g. claustrophobia )

• Pregnant patients will be excluded from the present study.

Related Conditions & MeSH terms

• Atherosclerosis

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), NYU Langone Health

Country where clinical trial is conducted

United States, 

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Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation between imaging and biomarkers of atherosclerosis	R correlation coefficient	5 years
Secondary	DCE-MRI kinetic parameters	Parameters evaluating the uptake of MR contrast agent in atherosclerotic plaques. Kinetic parameters Ktrans (1/min) , ve (a.u.), vp (a.u.), Kep (1/min)	3 years
Secondary	FDG uptake parameters	Parameters evaluating the uptake of FDG in atherosclerotic plaques. Standardized uptake value (SUV) (a.u.); target to background ratio (TBR) (a.u.)	3 years