In this prospective study, approved by the Comité de Ética en Investigación Clínica de Cantabria, human aneurysmal specimens from ascending thoracic aorta were collected during cardiovascular surgery (Bentall, Wheat) of aorta replacement, isolated into a phosphate buffered saline (PBS) and refrigerated until the OCT measurement was performed. Each aorta sample was divided into different regions of interest (ROIs) of average size . Different orientations were considered for each ROI: along and across the direction of blood flow. Fiducial markers with India ink delimit the area of each ROI to facilitate coregistration with the histopathological examination. During the image acquisition procedure, tissue was continuously rehydrated with PBS. After the OCT measurement, the examined tissue was placed in 10% buffered formalin solution for the histopathological analysis. Four different histological stains were analyzed: hematoxylin and eosin (H&E), Verhoeff’s Van Gieson (EVG) to check the atrophy of elastic tissue and the thinning and loss of elastic fibers, Alcian Blue (AB) at pH 2.5 to determine acidic polysaccharides, and some types of mucopolysaccharides, and Alpha-smooth muscle actin () used as a marker of vascular SMC. Healthy ascending thoracic aortas, i.e., control specimens, come from donors for heart transplantations. Donors were selected following standard cardiac donation criteria. Patients with previous cardiac history or other heart diseases were excluded, gender was not an exclusion criterion and donors older than 55 years of age were excluded. In this study, 36 ROIs from 14 patients have been analyzed: 28 ROIs are extracted from ascending thoracic aorta with aneurysm (average diameter 55 mm; max. 70 mm; min. 46 mm) and 8 from controls with average diameters of 40 mm. As histopathological diagnosis becomes the gold standard for the OCT image interpretation, all samples were stained with H&E, EVG, AB, and stains. Two experienced pathologists, blinded to the clinical data, graded the aortic specimens. A semiquantitative grading scheme that accounts for fibrosis, medionecrosis, cystic medial change, SMC orientation, and elastic fiber fragmentation24 was applied. Each indicator was graded from 0 (no change) to 3 (most severe change). The aortic wall score for each individual patient (from 0 to 15) arises from the sum of the results of all variables. The global aortic wall score in control specimens varies from 0 to 1 [Figs. 1(a), 1(b), and 1(c)], whereas in aneurysmal samples, it reaches scores of 12. High scores are due to changes in the SMC orientation [Fig. 1(d)], focal fragmentation of elastic lamellae in the media [Fig. 1(e)], and mucoid material accumulation [Fig. 1(f)].