In Vivo Molecular Imaging (MRI) of Atherothrombotic Lesions

Non-Invasive Imaging of Atherosclerosis

Sponsors

Lead sponsor: Icahn School of Medicine at Mount Sinai

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

Source Icahn School of Medicine at Mount Sinai
Brief 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.

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.

Overall Status Recruiting
Start Date September 2011
Completion Date April 2020
Primary Completion Date April 2020
Study Type Observational
Primary Outcome
Measure Time Frame
Correlation between imaging and biomarkers of atherosclerosis 5 years
Secondary Outcome
Measure Time Frame
DCE-MRI kinetic parameters 3 years
FDG uptake parameters 3 years
Enrollment 159
Condition
Eligibility

Sampling method: Non-Probability Sample

Criteria:

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.

Gender: All

Minimum age: 20 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Zahi A Fayad, PhD Principal Investigator Icahn School of Medicine at Mount Sinai
Overall Contact

Last name: Juan G Aguinaldo, MD

Phone: 212-824-8459

Email: [email protected]

Location
facility status contact contact_backup investigator Icahn School of Medicine at Mount Sinai Zahi Fayad, PhD [email protected] Venkatesh Mani, PhD Sub-Investigator Zahi A Fayad, PhD Principal Investigator
Location Countries

United States

Verification Date

February 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Arm group label: DCE-MRI

Description: 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.

Arm group label: PET/CT and PET/MR

Description: 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.

Arm group label: PET/MR

Description: 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.

Study Design Info

Observational model: Cohort

Time perspective: Cross-Sectional

Source: ClinicalTrials.gov