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Principal Investigator: Ajay Gupta
Organization: WEILL MEDICAL COLL OF CORNELL UNIV
Fiscal Year: 2024
Award: $661,408
Funding agency: National Institute of Neurological Disorders and Stroke
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.
Terms: <Accuracy of Diagnosis><Algorithms><Apoplexy><Area><Arterial Fatty Streak><Arterial Fatty Streaks><Atheroma><Atheromatous><Atheromatous degeneration><Atheromatous plaque><Bleeding><Blood><Blood Reticuloendothelial System><Blood Vessels><Blood erythrocyte><Body Tissues><Brain Vascular Accident><CAT scan><CT X Ray><CT Xray><CT imaging><CT scan><Calcified><Carotid Artery Narrowing><Carotid Artery Plaque><Carotid Artery Plaques><Carotid Artery Stenosis><Carotid Endarterectomy><Carotid Stenosis><Carotid stent><Cellular injury><Cephalic><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Clinical><Cognitive Discrimination><Computed Tomography><Contrast Agent><Contrast Drugs><Contrast Media><Cranial><Data><Detection><Development><Diagnosis><Discrimination><Embolism><Embolus><Erythrocytes><Erythrocytic><Evaluation><Extravasation><Fe element><Ferrihemoglobin><Fingerprint><Hemoglobin><Hemorrhage><Hemosiderin><Histology><Histopathology><Image><Imaging Device><Imaging Instrument><Imaging Tool><Individual><Inflammation><Ipsilateral><Iron><Ischemic Stroke><Lead><Leakage><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Magnetism><Maps><Marrow erythrocyte><Measures><Medical><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Methemoglobin><Motion><NMR Imaging><NMR Tomography><Noise><Nuclear Magnetic Resonance Imaging><Outcome><Outcomes Research><Oxidative Stress><Pathologic Constriction><Pathological Constriction><Patients><Pb element><Phase><Physiologic pulse><Predicting Risk><Predisposition><Property><Protocol><Protocols documentation><Pulse><ROC Analyses><ROC Curve><Radiopaque Media><Red Blood Cells><Red Cell><Reproducibility><Research><Risk><Risk Factors><Rupture><Sampling><Scanning><Schedule><Signal Induction><Spillage><Stenosis><Stroke><Stroke prevention><Susceptibility><Testing><Thrombus><Time><Tissues><Tomodensitometry><Vascular Diseases><Vascular Disorder><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><Zeugmatography><age associated alterations><age associated changes><age correlated alterations><age correlated changes><age dependent alterations><age dependent changes><age related alterations><age related changes><age specific alterations><age specific changes><alterations with age><atherosclerosis plaque><atherosclerotic lesions><atherosclerotic plaque><blood corpuscles><blood loss><blood vessel disorder><brain attack><calcification><carotid artery stent><carotid plaque><carotid stenting><catscan><cell damage><cell injury><cellular damage><cerebral vascular accident><cerebrovascular accident><changes with age><clinical imaging><clinical risk><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><damage to cells><determine efficacy><developmental><diagnostic accuracy><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><ex vivo imaging><examine efficacy><experience><forecasting risk><heavy metal Pb><heavy metal lead><high risk><image construction><image generation><image reconstruction><image-based method><imaging><imaging in vivo><imaging method><imaging modality><improved><in vivo imaging><injury to cells><magnetic><met-hemoglobins><new approaches><non-contrast CT><non-invasive imaging><noncontrast CT><noncontrast computed tomography><noninvasive imaging><novel approaches><novel strategies><novel strategy><patient stratification><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><predict risk><predict risks><predicted risk><predicted risks><predicting risks><predictive risk><predicts risk><prevent stroke><receiver operating characteristic analyses><receiver operating characteristic curve><reconstruction><revascularization><risk for stroke><risk of stroke><risk prediction><risk predictions><risk stratification><secondary outcome><stratified patient><stratify risk><stroke risk><stroked><strokes><superparamagnetic><superparamagnetism><thromboembolic stroke><vascular><vascular dysfunction><vasculopathy><vulnerable plaque>