Our main objective is to use quantitative susceptibility mapping (QSM) in establishing reliable noninvasive MRI
for identification and risk stratification of unstable carotid atherosclerotic plaques. Currently, decisions about
carotid revascularization to prevent stroke, such as carotid endarterectomy or carotid artery stenting, are based
on whether there is ?50% carotid artery stenosis. However, this strategy uses only one feature of vulnerable
plaque and frequently misclassifies patients. Using imaging to identify other features of rupture-prone carotid
plaques with high risk for thromboembolic stroke, in combination with stenosis assessment, proves to be a
more effective approach for risk evaluation. Of these features, intraplaque hemorrhage (IPH) is associated with
a 4 to 6-fold higher risk of stroke, while calcification is associated with a 50% lower stroke risk. In the
conventional approach, IPH and calcification are defined as hyperintensity and hypointensity, respectively, in a
plaque region on the T1-weighted (T1w) image acquired as part of the multi-contrast MRI (mcMRI) protocol.
However, T1w hyperintensity only captures the transient methemoglobin phase of hemorrhage. In the ensuing
hemosiderin phase, IPH appears hypointense due to the strong susceptibility-induced dephasing effects of the
superparamagnetic hemosiderin (susceptibility>150 ppm), which can be misinterpreted as calcification,
although calcification is strongly diamagnetic (-2.3 ppm). The key scientific premise of this proposal is that
QSM can reliably resolve T1w hypointensity into IPH hemosiderin versus calcification based on their different
magnetic property, and therefore will significantly improve imaging characterization and risk stratification of
patients with atherosclerotic carotid plaques. We have pioneered QSM development and demonstrated the
exquisite sensitivity of QSM for hemorrhage and calcification in carotid plaque. In this project, we will further
improve the utility of carotid plaque QSM for routine clinical imaging by developing a multi-contrast QSM
(mcQSM) approach which can provide not only QSM but also traditional mcMRI contrasts in 5 min scan time.
We will develop a nonlinear QSM reconstruction algorithm which is robust against noise and motion and can
separate co-existing IPH and calcification to improve IPH detection in calcified vessels. We will then establish
the improvement in diagnostic accuracy of mcQSM over mcMRI for detecting IPH and calcification in patients
who are scheduled for carotid endarterectomy. Finally, we will test the hypothesis that mcQSM will provide
significantly higher discrimination for stroke than mcMRI. A successful outcome of this proposal will make
carotid plaque QSM ready for widespread and routine clinical use in the emerging era of personalized
medicine to reduce the individual and societal burden of stroke.
