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-microm 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 (R(2) = 0.96) and 1.20 (R(2) = 0.98), respectively, demonstrating that 3-D micro-US measurements can be used to track aneurysm growth in a mouse aortic transplant model.
Goldberg
Alyse
A
Robarts Research Institute, London, Ontario, Canada.
Pakkiri
Pria
P
Dai
Erbin
E
Lucas
Alexandra
A
Fenster
Aaron
A
D000818:Animals; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging* / Q000473:pathology / Q000637:transplantation; D001014:Aortic Aneurysm / Q000000981:diagnostic imaging* / Q000473:pathology; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000473:pathology; D021621:Imaging, Three-Dimensional; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D009154:Mutation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D013194:Staining and Labeling; D014184:Transplantation, Homologous; D018608:Ultrasonography, Doppler
D008565:Membrane Proteins; D017395:Plasminogen Activator Inhibitor 1; C511174:Serp1 protein, mouse