Non-Invasive Imaging of Atherosclerosis

This study is currently recruiting participants.
Verified January 2014 by Mount Sinai School of Medicine
Sponsor:
Collaborators:
New York University School of Medicine
Information provided by (Responsible Party):
Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01418313
First received: August 5, 2011
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition
Atherosclerosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: In Vivo Molecular Imaging (MRI) of Atherothrombotic Lesions

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Correlation between imaging and biomarkers of atherosclerosis [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    R correlation coefficient


Secondary Outcome Measures:
  • DCE-MRI kinetic parameters [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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)

  • FDG uptake parameters [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Parameters evaluating the uptake of FDG in atherosclerotic plaques. Standardized uptake value (SUV) (a.u.); target to background ratio (TBR) (a.u.)


Biospecimen Retention:   Samples With DNA

Whole Blood, Endarterectomy Specimens


Estimated Enrollment: 159
Study Start Date: September 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01418313

Contacts
Contact: Juan G Aguinaldo, MD 212-824-8459 gilbert.aguinaldo@mssm.edu

Locations
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Zahi Fayad, PhD       zahi.fayad@mssm.edu   
Contact: Venkatesh Mani, PhD         
Sub-Investigator: Venkatesh Mani, PhD         
Principal Investigator: Zahi A Fayad, PhD         
Sponsors and Collaborators
Mount Sinai School of Medicine
New York University School of Medicine
Investigators
Principal Investigator: Zahi A Fayad, PhD Mount Sinai School of Medicine
  More Information

Publications:
Keereman V, Vandenberghe S, De Deene Y, Luypaert R, Broux T, Lemahieu I. MR-Based attenuation correction for PET using an Ultrashort Echo Time (UTE) sequence Paper presented at: IEEE Nuclear Science Symposium/Medical Imaging Conference 2009; Dresden, Germany

Responsible Party: Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01418313     History of Changes
Other Study ID Numbers: GCO 01-1032, R01HL071021
Study First Received: August 5, 2011
Last Updated: January 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
Atherosclerosis
Non-invasive imaging
Magnetic Resonance Imaging
MRI
Positron Emission Tomography
PET/CT
PET/MRI
Inflammation
Neovascularization

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 23, 2014