title: Effect of chromatin structure on quantitative ultrasound parameters.
abstract: High-frequency ultrasound (~20 MHz) techniques were investigated using in vitro and ex vivo models to determine whether alterations in chromatin structure are responsible for ultrasound backscatter changes in biological samples. Acute myeloid leukemia (AML) cells and their isolated nuclei were exposed to various chromatin altering treatments. These included 10 different ionic environments, DNA cleaving and unfolding agents, as well as DNA condensing agents. Raw radiofrequency (RF) data was used to generate quantitative ultrasound parameters from spectral and form factor analyses. Chromatin structure was evaluated using electron microscopy. Results indicated that trends in quantitative ultrasound parameters mirrored trends in biophysical chromatin structure parameters. In general, higher ordered states of chromatin compaction resulted in increases to ultrasound paramaters of midband fit, spectral intercept, and estimated scatterer concentration, while samples with decondensed forms of chromatin followed an opposite trend. Experiments with isolated nuclei demonstrated that chromatin changes alone were sufficient to account for these observations. Experiments with ex vivo samples indicated similar effects of chromatin structure changes. The results obtained in this research provide a mechanistic explanation for ultrasound investigations studying scattering from cells and tissues undergoing biological processes affecting chromatin.
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.|Department of Physics, Ryerson University, Toronto, Canada.
authors.forename: Maurice
authors.initials: M
authors.lastname: Pasternak
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, Canada.
authors.forename: Lilian
authors.initials: L
authors.lastname: Doss
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Golnaz
authors.initials: G
authors.lastname: Farhat
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, Canada.
authors.forename: Azza
authors.initials: A
authors.lastname: Al-Mahrouki
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, Canada.
authors.forename: Christina Hyunjung
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Physics, Ryerson University, Toronto, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Kolios
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.|Department of Radiation Oncology, University of Toronto, Toronto, Canada.
authors.forename: William Tyler
authors.initials: WT
authors.lastname: Tran
authors.affiliation: Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.|Department of Radiation Oncology, University of Toronto, Toronto, Canada.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Czarnota
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000648:ultrastructure; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D046529:Microscopy, Electron, Transmission; D014463:Ultrasonography / Q000379:methods*
chemical_list: D002843:Chromatin
keywords: chromatin; electron microscopy; form-factor analysis; spectral analysis; ultrasound