In vivo microcartography and subcellular imaging of tumor angiogenesis: A novel platform for translational angiogenesis research

Mark P S Dunphy, David R. Entenberg, Ricardo Toledo-Crow, Steven M. Larson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: To eliminate the variable of tumor heterogeneity from a novel in vivo model of tumor angiogenesis. Experimental design: We developed a method to navigate tumor neovasculature in a living tissue microenvironment, enabling relocation of a cell- or microregion-of-interest, for serial in vivo imaging. Orthotopic melanoma was grown, in immunocompetent Tie2GFP mice. Intravital multiphoton fluorescence and confocal reflectance imaging was performed, on a custom microscope with motorized stage and coordinate navigation software. A point within a Tie2GFP+ microvessel was selected for relocation. Custom software predicted target coordinates based upon reference points (tissue-embedded polystyrene beads) and baseline target coordinates. Mice were removed from the stage to make previously-obtained target coordinates invalid in subsequent imaging. Results: Coordinate predictions always relocated target points, in vivo, to within 10-200 μm (within a single 40× field-of-view). The model system provided a virtual living histology of tumor neovascularization and microenvironment, with subcellular spatial resolution and hemodynamic information. Conclusions: The navigation procedure, termed in vivo microcartography, permits control of tissue heterogeneity, as a variable. Tie2 may be the best reporter gene identified, to-date, for intravital microscopy of tumor angiogenesis. This novel model system should strengthen intravital microscopy in its historical role as a vital tool in oncology, angiogenesis research, and angiotherapeutic drug development.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalMicrovascular Research
Volume78
Issue number1
DOIs
StatePublished - Jun 2009

Fingerprint

Translational Medical Research
Tumors
Imaging techniques
Relocation
Neoplasms
Tissue
Software
Navigation
Tumor Microenvironment
Polystyrenes
Microvessels
Reporter Genes
Histology
Oncology
Hemodynamics
Melanoma
Research Design
Fluorescence
Design of experiments
Microscopes

Keywords

  • Angiogenesis
  • Angiogenesis inhibitors
  • Animals
  • Confocal microscopy
  • Green fluorescent proteins
  • Intravital microscopy
  • Luminescent proteins
  • Mice
  • Microscopy
  • Molecular imaging
  • Neoplasms
  • Neovascularization
  • Receptor
  • Reflectance
  • Tie2
  • Transgenic
  • Vascular disrupting agents
  • Vasculopathy

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

In vivo microcartography and subcellular imaging of tumor angiogenesis : A novel platform for translational angiogenesis research. / Dunphy, Mark P S; Entenberg, David R.; Toledo-Crow, Ricardo; Larson, Steven M.

In: Microvascular Research, Vol. 78, No. 1, 06.2009, p. 51-56.

Research output: Contribution to journalArticle

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abstract = "Purpose: To eliminate the variable of tumor heterogeneity from a novel in vivo model of tumor angiogenesis. Experimental design: We developed a method to navigate tumor neovasculature in a living tissue microenvironment, enabling relocation of a cell- or microregion-of-interest, for serial in vivo imaging. Orthotopic melanoma was grown, in immunocompetent Tie2GFP mice. Intravital multiphoton fluorescence and confocal reflectance imaging was performed, on a custom microscope with motorized stage and coordinate navigation software. A point within a Tie2GFP+ microvessel was selected for relocation. Custom software predicted target coordinates based upon reference points (tissue-embedded polystyrene beads) and baseline target coordinates. Mice were removed from the stage to make previously-obtained target coordinates invalid in subsequent imaging. Results: Coordinate predictions always relocated target points, in vivo, to within 10-200 μm (within a single 40× field-of-view). The model system provided a virtual living histology of tumor neovascularization and microenvironment, with subcellular spatial resolution and hemodynamic information. Conclusions: The navigation procedure, termed in vivo microcartography, permits control of tissue heterogeneity, as a variable. Tie2 may be the best reporter gene identified, to-date, for intravital microscopy of tumor angiogenesis. This novel model system should strengthen intravital microscopy in its historical role as a vital tool in oncology, angiogenesis research, and angiotherapeutic drug development.",
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