title: 3-D Ultrasound Localization Microscopy for Identifying Microvascular Morphology Features of Tumor Angiogenesis at a Resolution Beyond the Diffraction Limit of Conventional Ultrasound.
abstract: Angiogenesis has been known as a hallmark of solid tumor cancers for decades, yet ultrasound has been limited in its ability to detect the microvascular changes associated with malignancy. Here, we demonstrate the potential of 'ultrasound localization microscopy' applied volumetrically in combination with quantitative analysis of microvascular morphology, as an approach to overcome this limitation. This pilot study demonstrates our ability to image complex microvascular patterns associated with tumor angiogenesis in-vivo at a resolution of tens of microns - substantially better than the diffraction limit of traditional clinical ultrasound, yet using an 8 MHz clinical ultrasound probe. Furthermore, it is observed that data from healthy and tumor-bearing tissue exhibit significant differences in microvascular pattern and density. Results suggests that with continued development of these novel technologies, ultrasound has the potential to detect biomarkers of cancer based on the microvascular 'fingerprint' of malignant angiogenesis rather than through imaging of blood flow dynamics or the tumor mass itself.
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA.
authors.forename: Fanglue
authors.initials: F
authors.lastname: Lin
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Shelton
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA.
authors.forename: David
authors.initials: D
authors.lastname: Espíndola
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Rojas
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA.
authors.forename: Gianmarco
authors.initials: G
authors.lastname: Pinton
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Dayton
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008853:Microscopy / Q000379:methods*; D055806:Microvessels / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010865:Pilot Projects; D011916:Rats, Inbred F344; D014463:Ultrasonography / Q000379:methods*
keywords: Angiogenesis; acoustic angiography; biomarker.; microbubble contrast agent; super-resolution; ultrasound localization microscopy