Non-Invasive Imaging of Atherosclerosis

July 30, 2020 updated by: Zahi Fayad, Icahn School of Medicine at Mount Sinai

In Vivo Molecular Imaging (MRI) of Atherothrombotic Lesions

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.

Study Overview

Status

Completed

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Actual)

886

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects in the New York area referred by primary care physician, or recruited through Lifeline Screening or ResearchMatch.org, or Mount Sinai Broadcast emails and flyers.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
DCE-MRI
Magnetic resonance imaging (MRI) with and without FDA approved contrast agents: MRI is a non invasive imaging technique used to visualize the internal structure of the body in detail. The MRI machine is an oversized magnet that is always on. It will be used in this study to provide anatomical and functional (MRI with contrast) information about atherosclerotic plaques.
PET/CT and PET/MR
Positron emission tomography (PET)/ computer tomography (CT): PET is a nuclear medicine imaging technique, which produces images of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. Nowadays PET imaging is most useful in combination with anatomical imaging, such as CT scanners, thereby PET scanners are now available with integrated high-end multi-detector row CT scanners. Because the two scans can be performed in immediate sequence during the same session and with the patient not changing position between the two scans, areas of abnormality on PET images can be directly correlated with anatomy on the CT images.
PET/MR
Positron emission tomography (PET)/MRI: PET is a nuclear medicine imaging technique, which produces images of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. To avoid the additional radiation deriving from the CT scan during PET/CT imaging, nowadays PET imaging can be paired with MR anatomical images.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between imaging and biomarkers of atherosclerosis
Time Frame: 5 years
R correlation coefficient
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DCE-MRI kinetic parameters
Time Frame: 3 years
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
FDG uptake parameters
Time Frame: 3 years
Parameters evaluating the uptake of FDG in atherosclerotic plaques. Standardized uptake value (SUV) (a.u.); target to background ratio (TBR) (a.u.)
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Icahn School of Medicine at Mount Sinai

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
NYU Langone Health
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Zahi A Fayad, PhD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (ACTUAL)

March 9, 2020

Study Completion (ACTUAL)

March 9, 2020

Study Registration Dates

First Submitted

August 5, 2011

First Submitted That Met QC Criteria

August 15, 2011

First Posted (ESTIMATE)

August 17, 2011

Study Record Updates

Last Update Posted (ACTUAL)

August 3, 2020

Last Update Submitted That Met QC Criteria

July 30, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 01-1032
  • R01HL071021 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Atherosclerosis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tunisia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe