title: Quantitative evaluation of cell death response in vitro and in vivo using conventional-frequency ultrasound.
abstract: Previous studies using high-frequency ultrasound have suggested that radiofrequency (RF) spectral analysis can be used to quantify changes in cell morphology to detect cell death response to therapy non-invasively. The study here investigated this at conventional-frequencies, frequently used in clinical settings. Spectral analysis was performed using ultrasound RF data collected with a clinical ultrasound platform. Acute myeloid leukemia (AML-5) cells were exposed to cisplatinum for 0-72 hours in vitro and prepared for ultrasound data collection. Preclinical in vivo experiments were also performed on AML-5 tumour-bearing mice receiving chemotherapy. The mid-band fit (MBF) spectral parameter demonstrated an increase of 4.4 ± 1.5 dBr for in vitro samples assessed 48 hours after treatment, a statistically significant change (p < 0.05) compared to control. Further, in vitro concentration-based analysis of a mixture of apoptotic and untreated cells indicated a mean change of 10.9 ± 2.4 dBr in MBF between 0% and 40% apoptotic cell mixtures. Similar effects were reproduced in vivo with an increase of 4.6 ± 0.3 dBr in MBF compared to control, for tumours with considerable apoptotic areas within histological samples. The alterations in the size of cells and nuclei corresponded well with changes measured in the quantitative ultrasound (QUS) parameters.
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 ; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada ; Department 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.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zhou
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 ; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada ; Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Mehrdad J
authors.initials: MJ
authors.lastname: Gangeh
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: Zahra
authors.initials: Z
authors.lastname: Jahedmotlagh
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 ; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada ; Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Omar
authors.initials: O
authors.lastname: Falou
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: Shawn
authors.initials: S
authors.lastname: Ranieri
authors.affiliation: Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Azrif
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: Anoja
authors.initials: A
authors.lastname: Giles
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 ; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada ; Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Czarnota
keywords: apoptosis; cancer therapy; personalized medicine; quantitative ultrasound; treatment response monitoring