Despite advances in diagnosis and management, cardiovascular diseases (CVDs) remain 22 the leading cause of death in the US. Atherosclerosis is the most common form of CVD and the 23 vulnerability of atherosclerotic plaques to rupture is a primary determinant for risk of catastrophic 24 ischemic events. Current imaging of atherosclerotic disease focuses on assessing plaque size and 25 the degree of luminal stenosis, which are not good predictors of plaque stability. Functional 26 methods to identify biomarkers of inflammation in plaques could facilitate assessment of plaque 27instability to allow early intervention. In this study, we validate the use of a purpose-built, 28 magnetic resonance imaging (MRI)-compatible positron emission tomography (PET) insert for 29 multimodal, molecular imaging of vulnerable plaques in mice. We illustrate the application of PET 30 to screen for inflamed regions to guide the application of MRI. Molecular MRI visualizes regions 31 of vascular inflammation and is coupled with anatomical MRI to generate detailed maps of the 32 inflammatory marker within the context of an individual vessel. As a testbed for this imaging 33 methodology, we developed a multimodal, iron oxide nanoparticle (NP) targeting vascular cell 34 adhesion molecule-1 (VCAM-1) for simultaneous PET/MRI of vascular inflammation performed 35 on a mouse carotid ligation model. In vitro cell studies confirmed that the NPs are not cytotoxic to 36 liver cells. In vivo simultaneous PET/MRI imaging identified regions of inflammation.37 Three-dimensional rendering of the MRI data facilitated high-resolution visualization of patterns 38 of inflammation along the injured vessel. Histology validated the co-localization of the NPs with 39 VCAM-1 expression at sites of induced inflammation. The results of this work validate the utility 40 of the simultaneous PET/MR insert as a research tool for small animals and lays groundwork to 41 further advance the potential clinical utility of integrated imaging systems.42 43 vulnerable plaque; cardiovascular imaging; vessel wall; VCAM. 44 45 1. Introduction localized inflammatory response can lead to the development of "vulnerable" plaques that are 51 prone to rupture and cause downstream vascular occlusion.[3] Imaging can play a role in 52 identifying patients with vascular lesions susceptible to acute cardiovascular events, who may be 53 amenable to treatment with anti-inflammatories or interventional procedures. Recent literature has 54 shown that plaque lesion composition, particularly the presence of inflammatory markers and 55 immune cells, as opposed to the degree of vessel stenosis, is a better predictor of patient mortality 56 and morbidity; and assessment of plaque inflammation is an excellent target for noninvasive 57 imaging.[4] However, current clinical imaging techniques seldom provide specific information 58 about inflammation.59 Current clinical imaging techniques such as coronary angiography, vascular ultrasound and 60 computed tomography focus on identifying stenotic diseas...