Measurements of Aneurysm Morphology Determined by 3-D Micro-Ultrasound Imaging as Potential Quantitative Biomarkers in a Mouse Aneurysm Model

Aneurysms remain a significant medical problem and our current understanding of aneurysm formation and developmental stages remains incomplete. Noninvasive 3-D micro-ultrasound (3-D micro-US) imaging technologies designed for noninvasive evaluation of small laboratory animals diminish risks associated with invasive examination and provide in-situ (live) analysis of vascular morphological changes, which enables quantitative measurements of live biological specimens. We demonstrate here that aneurysm morphology can be quantified using 3-D micro-US, and we validate this methodology through comparison of geometric measures with those obtained from 3-D serial histologic records in a mouse model of accelerated aneurysm formation. Aneurysms were induced in Balb/C mice after C57Bl/6 mouse aortic transplant with injections of a pro-inflammatory viral serpin with a mutated reactive site. Aortic transplant segments were imaged 28 days after transplant using 3-D micro-US. Upon sacrifice, the aortas were excised and histology sections (5-μm thick) were digitized, co-registered using mutual information and stacked to form 3-D images. Surfaces of the mouse aorta and aneurysm were manually segmented from the 3-D micro-US and histology images. Comparisons with 3-D histology images demonstrated that 3-D micro-US allowed in-vivo analysis of aneurysm morphology, including total aneurysm area, plaque growth and lumen size. Linear regression of 3-D US-derived aneurysm and plaque volumes vs. 3-D histology-derived volumes resulted in slopes of 1.30 (R2 = 0.96) and 1.20 (R2 = 0.98), respectively, demonstrating that 3-D micro-US measurements can be used to track aneurysm growth in a mouse aortic transplant model. (E-mail: afenster@imaging.robarts.ca)