title: Compound speckle model detects anti-angiogenic tumor response in preclinical nonlinear contrast-enhanced ultrasonography.
abstract: OBJECTIVE
  This paper proposes a method for analyzing the first-order speckle statistics of nonlinear contrast-enhanced ultrasound images from tumors.
  
  
  METHODS
  Contrast signal intensity is modeled as a compound distribution of exponential probability density functions with a gamma weighting function. The gamma probability weighting function serves as an approximation for log-normally distributed flow velocities in a vascular network. The model was applied to sub-harmonic bolus-injection images acquired from a mouse breast cancer xenograft model treated with murine version bevacizumab.
  
  
  RESULTS
  The area under curve produced using the compound statistical model could more accurately discriminate anti-VEGF-treated tumors from untreated tumors than conventional contrast-enhanced ultrasound image processing. This result was validated with gold standard histological measures of microvascular density. Fractal vessel geometry was estimated using the gamma weighting function and tested against micro-CT perfusion casting. Treated tumors had a significantly lower vascular fractal dimension than control tumors. Vascular complexity estimated using the ultrasound compound statistical model performed similarly to micro-CT fractal dimension for discriminating treated from control tumors.
  
  
  CONCLUSIONS
  The proposed technique can quantify tumor perfusion and provide an index of vascular complexity, making it a potentially useful addition for clinical detection of vascular normalization in anti-angiogenic trials.
authors.affiliation: Department of Medical Biophysics, Western University, London, ON, N6A 3K7, Canada.|Robarts Research Institute, Western University, London, ON, N6A 5B7, Canada.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lowerison
authors.affiliation: Department of Medical Biophysics, Western University, London, ON, N6A 3K7, Canada.|Robarts Research Institute, Western University, London, ON, N6A 5B7, Canada.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Tse
authors.affiliation: London Regional Cancer Program, London Health Sciences Centre, London, ON, N6A 4L6, Canada.
authors.forename: M Nicole
authors.initials: MN
authors.lastname: Hague
authors.affiliation: London Regional Cancer Program, London Health Sciences Centre, London, ON, N6A 4L6, Canada.|Departments of Oncology and Medical Biophysics, Western University, London, ON, N6A 3K7, Canada.
authors.forename: Ann F
authors.initials: AF
authors.lastname: Chambers
authors.affiliation: Robarts Research Institute, Western University, London, ON, N6A 5B7, Canada.|Departments of Surgery, and Medical Biophysics, Western University, London, ON, N6A 3K7, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Holdsworth
authors.affiliation: Robarts Research Institute, Western University, London, ON, N6A 5B7, Canada.|Departments of Electrical and Computer Engineering, and Medical Biophysics, Western University, London, ON, N6A 3K7, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Lacefield
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000068258:Bevacizumab / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003287:Contrast Media; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D017711:Nonlinear Dynamics; D014463:Ultrasonography; D055114:X-Ray Microtomography; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D000068258:Bevacizumab
keywords: anti-angiogenesis; contrast-enhanced ultrasound; high-frequency ultrasound; perfusion imaging; speckle statistics; tumor heterogeneity