Thanh Nguyen, Ph.D., has been awarded a National Institutes of Health (NIH) R01 grant for a sophisticated new plan to expose, more precisely than ever before, the unstable atherosclerotic carotid plaque behind one of our biggest “silent killers”: strokes.
Called “Quantitative susceptibility mapping for stroke risk prediction of vulnerable carotid plaques,” Dr. Nguyen’s project involves refining a pioneering approach developed at the Magnetic Resonance Imaging Research Institute (MRIRI).
Quantitative susceptibility mapping (QSM) is a highly effective MRI technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It has been rapidly accepted as a reliable MRI tool since its introduction over a decade ago. Dr. Nguyen’s team, which includes principal investigators Ajay Gupta, professor of radiology, and Hooman Kamel, associate professor of neurology, is now modifying the hailed approach to characterize and provide data for risk evaluation of the unstable carotid atherosclerotic plaque that can rupture and cause ischemic stroke. (Ischemic stroke is caused by blocked blood flow to the brain.)
Dr. Nguyen’s team expects this grant to result in a long-awaited, highly reliable, noninvasive imaging tool for stroke prevention and vascular disease research.
“Our key objective: to use QSM to establish accurate and robust MRI for identification and risk stratification of unstable carotid atherosclerotic plaques, letting clinicians prescribe preventive therapies earlier, so warding off more cases of stroke,” says Dr. Nguyen. “Intraplaque hemorrhage (IPH) and calcification each exerts significant and opposite effects on stroke risk, which cannot be accurately resolved by conventional MRI. We have shown that QSM can reliably differentiate paramagnetic IPH from diamagnetic calcification. We are now developing a fast image acquisition method to combine traditional multi-contrast MRI (mcMRI) with QSM (mcQSM), which enables carotid plaque characterization with higher accuracy and reproducibility in the clinical setting. Our ultimate goal is to give clinicians a better tool for predicting stroke risk in patients with carotid artery disease.”
Currently, decisions using carotid revascularization to prevent stroke, like carotid endarterectomy or artery stenting, are based on significant stenosis (50-99% luminal narrowing). However, this approach does not consider pathological features of the atherosclerotic plaques within the vessel wall, which can help predict the risk of plaque rupture and the ensuing stroke.
Improvement in risk prediction can occur by looking for IPH, a major feature in rupture-prone plaques. IPH is caused by microvascular blood leakage, and by red blood-cell age changes associated with transitions from hemoglobin to methemoglobin and hemosiderin. The ensuing oxidative stress, proteolytic activity, and inflammation lead to cell damage and plaque destabilization. The Nguyen team and others found IPH linked to a four-to-six-fold stroke risk surge. Indeed, recent population studies have suggested that IPH is a more accurate stroke predictor than all other clinical risk factors.
Conventionally, IPH is detected as a hyperintense region on the T1-weighted image acquired as part of the mcMRI vessel wall imaging protocol. But this hyperintensity relates only to the methemoglobin phase of the hemorrhage, when mobile paramagnetic methemoglobin causes T1 enhancement similar to a contrast agent. Hemosiderin has more magnetic susceptibility than methemoglobin, resulting in hypointensity due to field inhomogeneity-induced signal loss. This hypointensity can be mistaken for calcification, resulting in stroke-risk underestimation, as calcification in carotid plaque is linked to a 50% lower risk.
As noted, the MRIRI has pioneered the creation of QSM, which measures tissue magnetic susceptibility and can resolve T1-weighted hypointensity based on the unique magnetic susceptibility properties of hemosiderin (superparamagnetic, >150 ppm) and calcification (highly diamagnetic, -2.3 ppm). Using in vivo imaging referenced to computed tomography, and ex vivo imaging referenced to histology, Dr. Nguyen’s team aims to demonstrate the ability of QSM to distinguish IPH from calcification in carotid plaque. The team believes QSM will allow more precise identification and treatment of high-risk patients who would benefit from invasive revascularization, versus those with lower risk who would benefit from noninvasive medical therapy.
“We propose our mcQSM approach will enable full characterization of carotid plaque,” concludes Dr. Nguyen. “We hope to 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.”
Research reported in this article was supported by the National Institute of Neurological Disorders And Stroke of the NIH under award number R01NS123576. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.