The subtleties of ultrasound images of an ensemble of cells: simulation from regular and more random distributions of scatterers

Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo

“…The process of nuclear condensation, which takes place in the early stages of apoptosis (Allera et al, 1997), similar to mitosis, compacts chromosomes from forms which are distributed throughout most of the cell's nucleus to more canonical condensed forms. Other previous studies also support the postulate that the cellular nuclear material is the major scatterer of high frequency ultrasound (Bérubé et al, 1992;Hunt et al, 1995;Czarnota et al, 1997a). Direct evidence providing strong support for this hypothesis is presented in this study, where the induction of DNA condensation and enzymatic degradation of condensed DNA demonstrates such condensation to be sufficient and necessary to obtain an increased ultrasound backscatter.…”

“…This is consistent with the result that cells in early apoptosis, at 6 h after cisplatinum treatment, also scatter ultrasound less than in later stages in which nuclei are fragmented. A plausible reason for such increases is linked to the randomization of scatterer location (Hunt et al, 1995) within the cell, which would occur with apoptotic nuclear condensation and fragmentation. In preliminary simulations, the condensing of the nucleus, its fragmentation and the spatial randomization of these nuclear components increased the backscatter signal intensity by at least five times.…”

Quantitative Ultrasound Characterization of Responses to Radiotherapy in Cancer Mouse Models

“…For example, the darker staining of condensed nuclei suggested changes in the nuclear acoustic impedances, i.e., higher values of 2.00 MRayl for condensed chromatin versus 1.58 to 1.55 Mrayl for cytoplasm have been reported recently (37). The increase in the randomization of nuclei during the sequence of cell death may also contribute to the increase in the UIB as previously indicated by a model of ultrasound scattering (36) and, recently, suggested by experimental observations (31). Because SI is related to the size, concentration, and relative acoustic impedance of scatterers (27,28), the increase in the SI, similar to the increase in the UIB, might result from changes in nuclear properties and increase in the number of nuclear fragments after apoptotic cell death.…”

“…Changes in UIB can be related to a combination of scatterer properties: size, spatial organization, concentration, and relative acoustic impedance (28,36). The regions exhibiting cell death in histology were characterized by an overall decrease in nuclear sizes, a consequence of nuclear condensation and fragmentation during the sequence of apoptotic cell death (Fig.…”

Quantitative Ultrasound Characterization of Cancer Radiotherapy Effects In Vitro

“…In the present study, we also investigated the variance of cell sizes (the squared standard deviation), because it can considerably influence cell and nuclei spatial organization in a sample (24,25). The UIB measured from all cell samples correlated well with the variance of cell sizes, with a Pearson correlation coefficient of r = 0.80 and statistical significance of p < 0.01 (Fig.…”