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

  • Alyse Goldberg
    Affiliations
    Robarts Research Institute, London, Ontario, Canada

    Department of Biophysics, University of Western Ontario, London, Ontario, Canada
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  • Pria Pakkiri
    Affiliations
    Robarts Research Institute, London, Ontario, Canada

    Department of Biophysics, University of Western Ontario, London, Ontario, Canada
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  • Erbin Dai
    Affiliations
    Robarts Research Institute, London, Ontario, Canada
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  • Alexandra Lucas
    Affiliations
    Robarts Research Institute, London, Ontario, Canada

    Department of Biophysics, University of Western Ontario, London, Ontario, Canada

    Departments of Medicine and Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada

    Department of Medicine, University of Florida, Gainesville, FL
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  • Aaron Fenster
    Correspondence
    Address correspondence to: Aaron Fenster, Imaging Research Laboratories, Robarts Research Institute, P.O Box 5015, 100 Perth Drive, London, Ontario, N6A 5K8, CANADA.
    Affiliations
    Robarts Research Institute, London, Ontario, Canada

    Department of Biophysics, University of Western Ontario, London, Ontario, Canada
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      Abstract

      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: [email protected] )

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