title: Quantification of Ultrasonic Scattering Properties of In Vivo Tumor Cell Death in Mouse Models of Breast Cancer.
abstract: BACKGROUND
  Quantitative ultrasound parameters based on form factor models were investigated as potential biomarkers of cell death in breast tumor (MDA-231) xenografts treated with chemotherapy.
  
  
  METHODS
  Ultrasound backscatter radiofrequency data were acquired from MDA-231 breast cancer tumor-bearing mice (n = 20) before and after the administration of chemotherapy drugs at two ultrasound frequencies: 7 MHz and 20 MHz. Radiofrequency spectral analysis involved estimating the backscatter coefficient from regions of interest in the center of the tumor, to which form factor models were fitted, resulting in estimates of average scatterer diameter and average acoustic concentration (AAC).
  
  
  RESULTS
  The ∆AAC parameter extracted from the spherical Gaussian model was found to be the most effective cell death biomarker (at the lower frequency range, r(2) = 0.40). At both frequencies, AAC in the treated tumors increased significantly (P = .026 and .035 at low and high frequencies, respectively) 24 hours after treatment compared with control tumors. Furthermore, stepwise multiple linear regression analysis of the low-frequency data revealed that a multiparameter quantitative ultrasound model was strongly correlated to cell death determined histologically posttreatment (r(2) = 0.74).
  
  
  CONCLUSIONS
  The Gaussian form factor model-based scattering parameters can potentially be used to track the extent of cell death at clinically relevant frequencies (7 MHz). The 20-MHz results agreed with previous findings in which parameters related to the backscatter intensity (i.e., AAC) increased with cell death. The findings suggested that, in addition to the backscatter coefficient parameter ∆AAC, biological features including tumor heterogeneity and initial tumor volume were important factors in the prediction of cell death response.
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Hadi
authors.initials: H
authors.lastname: Tadayyon
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Departments of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Sannachi
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Departments of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Sadeghi-Naini
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: Azza
authors.initials: A
authors.lastname: Al-Mahrouki
authors.affiliation: Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: William T
authors.initials: WT
authors.lastname: Tran
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Physics, Ryerson University, Toronto, ON, Canada.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kolios
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Departments of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: Gregory.Czarnota@sunnybrook.ca.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Czarnota