Objective: Early detection of aortic degeneration is critical for improving outcomes in patients with aortic aneurysm and dissection. We investigated nanoparticle contrast-enhanced computed tomography for the early detection of aortic injury. Approach and Results: In a mouse model of sporadic aortic aneurysm and dissection, C57BL/6J mice were challenged with a high-fat diet and Ang II (angiotensin II) infusion (n=20). Unchallenged control mice received a standard laboratory diet and saline infusion (n=19). Computed tomography angiography (CTA) was performed to evaluate aortic enlargement, and delayed nanoparticle contrast-enhanced computed tomography (CTD) imaging was performed to detect wall signal enhancement indicative of aortic wall degeneration. Aortic segments that exhibited CTD findings but appeared normal on CTA were termed preclinical aortic disease. Aortic aneurysm and dissection development was determined upon the gross examination of excised aortas. Aortic degeneration and inflammation were examined by performing histological and immunofluorescence analyses. Leakage of Evans blue dye into the aortic wall was used to validate changes in vascular permeability. In challenged mice, gross findings of aortic disease were found in 41% of aortic segments. CTA findings of mild disease (dilatation) and advanced disease (aortic aneurysm and dissection with the presence of false lumen) were seen in 33% of aortic segments. CTD findings of wall signal enhancement were seen in 63% of aortic segments. Of those, 48% appeared normal on CTA. Aortic segments with CTD findings showed aortic wall degeneration and inflammation on histological and immunofluorescence analyses. Immunofluorescence analysis and Evans blue dye uptake suggested passive leakage of nanoparticle contrast agent due to endothelial injury as a potential mechanism underlying the detection of aortic disease on CTD. Conclusions: In mice, CTD imaging exhibits high sensitivity for detecting aortic wall degeneration and inflammation before vessel enlargement becomes evident on CTA.