Elastin is a primary component of the vessel wall and is present in all elastic vessels such as the aorta and carotid arteries. Elastogenesis begins with the synthesis and secretion of the soluble precursor tropoelastin that becomes cross-linked into insoluble elastin in the presence of lysyl oxidase. Under normal conditions cross-linked elastin is the only form of the molecule present in the vessel wall whereas tropoelastin is absent. Conversely, under pathological conditions including atherosclerosis and aortic aneurysms, elastogenesis resumes and tropoelastin molecules accumulate in the vessel wall. We developed a novel tropoelastin-binding MRI contrast-agent that specifically binds to tropoelastin but not to cross-linked mature elastin, and thus, minimizes non-specific signal from endogenously present mature elastin and maximizes detection of pathologic elastogenesis that occurs in atherosclerosis. Two tropoelastin-binding probes (Gd-DOTA)-VVGSPSAQDEASPLS (VVGS) and K(Gd-DOTA)YPDHVQYTHY (YPDH) were investigated. In vitro binding studies were performed using the Europium-labeled analogues and a DELFIA method. In vivo MRI of the aortic root, aortic arch and brachiocephalic arteries was performed in atherosclerotic ApoE-/- and control mice using a 3T Philips Achieva scanner and a single loop microscopy surface coil. 8 week-old ApoE-/- mice were switched to a HFD containing 21% fat from lard, and 0.15% (wt/wt) cholesterol. Three groups of ApoE-/- mice were imaged at 4, 8, and 12 weeks post commencement of the HFD (n=8 per group). In the treatment group, ApoE-/- mice received pravastatin (40mg/kg/day) administered in the drinking water simultaneously with the HFD and for 12 weeks (n=8). Wild-type mice were fed a normal chow diet for 12 weeks (n=8). Images were acquired for up to 1h after intravenous administration of 0.2 mmol/kg tropoelastin-binding agent. 3D gradient-echo late gadolinium enhancement (LGE)-MRI images were acquired with FOV=30x8x30mm, matrix=300, resolution=0.1x0.1mm, slice thickness=0.25mm, TR/TE=27/8ms, TR between subsequent IR pulses=1000ms, and flip angle=30°. T1 mapping was performed using a 3D modified Lock-Locker sequence FOV=22x8x36, matrix=180x171, resolution=0.2x0.2, slice thickness=0.5mm, TR/TE= 9.2/4.7ms, flip angle=10°. T1 values were computed on a pixel-by-pixel basis using a 2-parameter fit with an in-house Matlab algorithm.In vitro binding assays showed high selectivity of the compounds towards tropoelastin compared to other proteins and particularly mature elastin (Fig 1). The VVGS probe achieved maximum discrimination between tropoelastin and mature elastin (64±7 % vs 1±0%). Serial LGE-MRI studies using the VVGS probe showed progressive enhancement of the brachiocephalic artery because of the deposition of tropoelastin during atherosclerosis development (Fig. 2A1-2-D1-2). Importantly, there was no uptake in control (2A1-2) or reduced uptake in statin-treated animals (Fig. 2E1-2) where tropoelastin is absent or less, respectively. Quantitative analysis of the vessel wall R1 showed increasingly higher R1 values during disease progression using the VVGS based probe (Fig. 2A3-E3 & Figure 3). These data are in agreement with our previous studies that showed increased tropoelastin content during atherosclerosis progression and reduction of tropoelastin in statin-treated mice by western blotting [2].We were able to quantify plaque burden in the vasculature of ApoE-/- mice using a newly developed gadolinium-based tropoelastin-binding contrast agent. This agent allows molecular imaging of impaired elastogenesis and accumulation of de novo synthesized tropoelastin molecules that accompany plaque development but are absent in the vessel wall under normal conditions.