Multimodal Imaging To Identify Pre-signals For Acute Aortic Dissection By Using Marfan Syndrome Model Mouse

Background: Marfan syndrome (MFS) is a genetic disorder caused by mutations in the gene encoding theextracellular matrix Fibrillin-1 (FBN1), resulting in systemic connective tissue abnormalities. The mostcommon life-threatening conditions are aortic rupture and/or dissection. Aortic dissections show a highmortality rate, but the details of molecular triggers are unknown, particularly in acute aortic dissection(AAD). Raman spectroscopy is a technique for analyzing molecular structures from Raman spectra. It hasrecently attracted attention in the biology field because it can non-invasively distinguish between diseaseand non-disease areas. Objectives: This study aimed to identify the signals that induce changes in the aortic wall prior to acuteaortic dissection using genetic analysis and Raman spectroscopy with preservation of positional information. Methods: An acute aortic dissection model was created by using MFS model mice (Fbn1 mgR/mgR ) byadministration of angiotensin II (AngII) via osmotic pump (Fbn1 mgR/mgR -AAD). Aortas from wild-type(WT), Fbn1 mgR/mgR and Fbn1 mgR/mgR -AAD mice were harvested, and frozen sections were prepared. Thevascular wall of each mouse was assessed histologically, followed by spatial transcriptomic analysis andRaman microscopy measurements. Multivariate data analysis was performed on the obtained Ramanspectra. Mass spectrometry (MS) imaging was utilized for lipidome analysis. Results: Label-free imaging of extracellular substrates (collagen fibres, elastic fibres, versican, andaggrecan), lipids, and cells was produced in WT, Fbn1 mgR/mgR and Fbn1 mgR/mgR - AAD aortic tissue. Spatialtranscriptomic analysis identified differentially expressed genes among these aortas. We identified markedlipid accumulations in the acute aortic dissection models with Raman and MS imaging.