Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis

TY - JOUR

T1 - Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis

AU - Nadel, James

AU - Wang, Xiaoying

AU - Saha, Prakash

AU - Bongers, André

AU - Tumanov, Sergey

AU - Giannotti, Nicola

AU - Chen, Weiyu

AU - Vigder, Niv

AU - Chowdhury, Mohammed

AU - Lima da Cruz,, Gastao

AU - Velasco Jimeno, Carlos

AU - Prieto Vasquez, Claudia

AU - Jabbour, Andrew

AU - Botnar, René

AU - Stocker, Roland

AU - Phinikaridou, Alkystis

PY - 2024/1

Y1 - 2024/1

N2 - Aims Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma. Methods and results Plaque MPO activity was assessed in vivo in rabbits (n = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis. Excised plaques were used to confirm MPO activity by liquid chromatography–tandem mass spectrometry (LC–MSMS) and to determine MPO distribution by histology. MPO activity was higher in plaques that caused post-trigger atherothrombosis than plaques that did not. Among the in vivo MRI metrics, the plaques’ R1 relaxation rate after administration of MPO-Gd was the best predictor of atherothrombosis. MPO activity measured in human carotid endarterectomy specimens (n = 30) by MPO-Gd–enhanced MRI was correlated with in vivo patient MRI and histological plaque phenotyping, as well as LC–MSMS. MPO-Gd retention measured as the change in R1 relaxation from baseline was significantly greater in histologic and MRI-graded American Heart Association (AHA) type VI than type III–V plaques. This association was confirmed by comparing AHA grade to MPO activity determined by LC–MSMS. Conclusion We show that elevated intraplaque MPO activity detected by molecular MRI employing MPO-Gd predicts future atherothrombosis in a rabbit model and detects ruptured human atheroma, strengthening the translational potential of this approach to prospectively detect high-risk atherosclerosis.

AB - Aims Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma. Methods and results Plaque MPO activity was assessed in vivo in rabbits (n = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis. Excised plaques were used to confirm MPO activity by liquid chromatography–tandem mass spectrometry (LC–MSMS) and to determine MPO distribution by histology. MPO activity was higher in plaques that caused post-trigger atherothrombosis than plaques that did not. Among the in vivo MRI metrics, the plaques’ R1 relaxation rate after administration of MPO-Gd was the best predictor of atherothrombosis. MPO activity measured in human carotid endarterectomy specimens (n = 30) by MPO-Gd–enhanced MRI was correlated with in vivo patient MRI and histological plaque phenotyping, as well as LC–MSMS. MPO-Gd retention measured as the change in R1 relaxation from baseline was significantly greater in histologic and MRI-graded American Heart Association (AHA) type VI than type III–V plaques. This association was confirmed by comparing AHA grade to MPO activity determined by LC–MSMS. Conclusion We show that elevated intraplaque MPO activity detected by molecular MRI employing MPO-Gd predicts future atherothrombosis in a rabbit model and detects ruptured human atheroma, strengthening the translational potential of this approach to prospectively detect high-risk atherosclerosis.

KW - Atherosclerosis, atherothrombosis, carotid endarterectomy, molecular magnetic resonance imaging, myeloperoxidase, plaque disruption

U2 - 10.1093/ehjimp/qyae004

DO - 10.1093/ehjimp/qyae004

M3 - Article

VL - 2

JO - European Heart Journal – Imaging Methods and Practice

JF - European Heart Journal – Imaging Methods and Practice

IS - 1

M1 - qyae004

ER -