: Aortopathies, such as aortic aneurysm and dissection (AAD), are associated with enhanced aortic wall permeability and endothelial dysfunction. We previously demonstrated that nanoparticle contrast-enhanced computed tomography (nCECT), which detects enhanced aortic wall permeability, could enable non-invasive detection of early AAD before its progresses to fatal aortic rupture. This study investigated the effect of nanoparticle contrast agent (NPCA) size and dose on detection of aortopathy by nCECT. studies were performed in a mouse model of sporadic AAD induced by challenging animals with high fat diet (5 weeks) and angiotensin II infusion (last one week). The effects of NPCA size (80, 150, and 240 nm) and NPCA dose (300, 600, and 1200 mg I/kg) on detection of aortopathy were studied. To examine temporal changes in aortic wall NPCA signal at sites of AAD, mice underwent longitudinal CT. To investigate changes in aortic wall integrity, mice underwent follow-up nCECT at 6 months after initial challenge. Imaging findings were compared with gross and histologic examination of the aorta. Fluorescence microscopy was used to confirm presence or absence of intramural NPCA. : nCECT using all three sizes of NPCAs demonstrated significantly higher sensitivity (p< 0.05) for the detection of aortopathy compared to gross examination. Histologic analysis showed excellent correlation between the nCECT finding of intramural signal and the presence of aortopathy. The absolute improvements in detection rates were 16%, 20%, and 17% for 80 nm, 150 nm, 250 nm NPCA respectively. Sensitivity of nCECT for detection of aortic injury improved with increasing NPCA dose compared to gross exam (-17% at 300 mg I/kg to 14% at 1200 mg I/kg). Temporal analysis of aortic wall NPCA signal at sites of AAD demonstrated a peak in aortic wall CT attenuation at day 3-5 post-contrast followed by gradual return to baseline by day 120. Follow-up nCECT at 6 months demonstrated absence of wall signal enhancement compared to baseline, suggesting resolution of the altered aortic wall permeability and injury. Histologic analysis demonstrated remodeling and healing of the aortic wall. : Nanoparticle contrast-enhanced CT using all three studied nanoparticle sizes demonstrated higher sensitivity than gross examination for the detection of aortopathy. A dose-dependent effect on sensitivity was observed with only high NPCA dose (1200 mg I/kg) demonstrating superior performance compared to gross examination for detecting early stages of aortic injury. Nanoparticle contrast-enhanced CT enabled interrogation of changes in aortic wall integrity.