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HRP research project zeros in on stroke, heart attack triggers

Best Practice
Yuan, Chun, Ph.D. Seattle, University of Washington USA

Recognizing the importance of atherosclerotic plaque in worldwide morbidity and death, Philips is joining with a group of companies to study vulnerable plaque (HRP). The HRP initiative will set the groundwork for development, registration and commercialization of diagnostic tests and therapeutic interventions to manage vulnerable plaque.


One of HRP's six roadmap tracks that will entail studies of up to 6,000 high-risk volunteers, will include carotid artery MRI on a mobile Achieva 3.0T system. The carotid protocol is an histology-validated technique designed to enable full plaque characterization, according to Chun Yuan, Ph.D., a University of Washington (Seattle, WA USA) radiology professor and cardiovascular imaging specialist.

 Chun Yuan, Ph.D.
Chun Yuan, Ph.D.

Full plaque characterization sought

According to the World Health Organization (WHO), one-third of all deaths globally are caused by cardiovascular events in the heart and brain. Plaque rupture is estimated to cause 75 percent of these deaths. These high-risk, vulnerable plaques are the focus of the HRP research initiative, a group of companies that is joining forces to make vulnerable plaque managed disease through an intensive outcomes-based study.


To fully evaluate vulnerable plaque, six parallel tracks will be implemented:

  1. Biomarker discovery and validation.
  2. Animal HRP model development for drug discovery.
  3. Anatomical and functional imaging, in which MRI, CTA, and ultrasound studies will be performed for carotid, aorta and coronary arteries.
  4. Molecular imaging.
  5. Regulatory framework.
  6. Economic.


The project will involve as many as 6,000 participants diagnosed as having risk factors for developing vulnerable plaque (e.g., high BP, family history, obesity, blood serum biomarkers).

The HRP Alliance

The HRP group of companies and entities includes AstraZeneca, Merck, Philips Medical Systems, Humana, and others. BG Medicine's CEO, Pieter Muntendam, M.D., will lead the HRP research project. "The HRP alliance is the strongest effort to date to try to identify those at highest risk of stroke or heart attack due to vulnerable plaque," Dr. Muntendam says.
"Through a wide range of complementary modalities, this research will increase our understanding of how to best find those at highest risk and what modalities are most suitable to monitor development and progression of vulnerable plaque. Once we can reliably identify the individuals who have this condition it will open exciting new avenues for prevention and treatment with potentially a marked impact on cardiovascular morbidity and mortality."

Carotid MRI studies on mobile Achieva 3.0T

Chun Yuan, Ph.D.,  Professor of Radiology and Bioengineering and cardiovascular imaging specialist at the University of Washington, and his colleagues, have contributed the carotid/aorta MRI protocol that will be used on all eligible participants in the project. The studies will be performed on a mobile Achieva 3.0T system.

"Pathology originating in the carotid is directly linked with stroke, so early detection of vulnerable plaques will help prevent future strokes. The main goal of the carotid MRI studies is a comprehensive characterization of atherosclerosis in the carotids," Dr. Yuan says. "These studies will be complemented by MRI studies of the aorta and coronary arteries."


The carotid MR protocol that the HRP project will employ is an established University of Washington protocol that was validated based on histology, he notes. Patients scheduled for carotid endarterectomy had an MR scan just before their surgery, after which the plaque specimen was retrieved and subjected to comprehensive histology. "Histological validation of the protocol makes it ideal for the HRP initiative," Dr. Yuan adds.

Protocol examines morphology, tissue composition and plaque inflammation

The carotid protocol consists of seven different sequences, including time-of-flight, black blood sequences with flow suppression (especially T1, T2), dynamic contrast sequences and post-contrast T1. Bilateral carotid artery images will be obtained and the orientations are lateral and cross-sectional (i.e. axial). A 4- or 8-channel (optional) non-standard carotid phased array coil is used.

3.0T carotid protocol images from a patient with intermediate left carotid atherosclerosis. There is a calcification (white arrow) in the artery wall, which shows hypointense signal on all five matched cross-sectional images (3D TOF, T1WI, CE T1WI, PDWI, and T2WI) of the left internal carotid artery. The spatial resolution of the cross-sectional images is 0.6 x 0.6 x 2 mm³ . The proton density weighted, oblique image (OBL) demonstrates a longitudinal view of the left carotid artery. A hyperintense region on the OBL highlights the plaque distribution from common into the internal carotid artery (red arrow).


"With this protocol we want to measure vessel morphology - wall thickness, volume and plaque burden," Dr. Yuan notes. "Second, we want to analyze tissue composition and plaque inflammation, as these are closely linked with plaque stability. Assisted by the imaging processing tool, CASCADE, developed by the University of Washington group, we want to measure a series of quantitative parameters, such as normalized wall index, lipid-rich necrotic core size, fibrous cap thickness and inflammation status, and determine whether these parameters or a combination are better predictors of vulnerable plaques as compared with luminal narrowing (as measured by angiographic techniques).


Plaques that are likely to rupture are designated unstable or vulnerable, and through imaging, clinicians hope to identify those at high risk for a heart attack or stroke, he explains.


"Imaging can conceivably provide both qualitative and quantitative information for this determination - I don't think just looking at luminal narrowing is enough," Dr. Yuan says. "The quantitative information we obtain through the HRP project might be able to assist us in predicting future events."

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Feb 7, 2008

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Best Practice
Achieva 3.0T
Release 1, Release 2
Quasar, Quasar Dual
3T, Carotid, Vascular

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