Evaluation of Scatterer Parameters From Ultrasound Scattering Models Taking Into Account Scattering From Nuclei and Cells of Cell-Pellet Biophantoms and Ex Vivo Tumors.

The Quantitative Ultrasound backscatter coefficient provides the capability to evaluate tissue microstructure parameters. Tissue-based scatterer parameters are extracted using ultrasound scattering models. It is challenging to correlate ultrasound scatterer parameters of tissue structures from optical-measured histology, possibly because of inappropriate scattering models or the presence of multiple scatterers. The objective of this study is to pursue the quantification of pertinent scatterer parameters with scattering models that consider ultrasound scattering from nuclei and cells. The concentric sphere model (CSM) and the structure factor model adapted for two types of scatterers (SFM2) are evaluated for cell-pellet biophantoms and ex vivo tumors of four cell lines: 4T1, JC, LMTK, and MAT. The structure factor model (SFM) was used for comparison. CSM and SFM2 provided scatterer parameters closer to histology (lower relative errors) for nucleus and cell radii and volume fractions than SFM but were not always accompanied by lower dispersion of the scatterer distribution (lower coefficient of variation). CSM and SFM2 quantified cell and nucleus radius and volume fraction parameters with lower relative error compared to SFM. For tumors, CSM provided better results than SFM2.

Cancer characterization using light backscattering spectroscopy and quantitative ultrasound: an ex vivo study on sarcoma subtypes.

Histological analysis is the gold standard method for cancer diagnosis. However, it is prone to subjectivity and sampling bias. In response to these limitations, we introduce a quantitative bimodal approach that aims to provide non-invasive guidance towards suspicious regions. Light backscattering spectroscopy and quantitative ultrasound techniques were combined to characterize two different bone tumor types from animal models: chondrosarcomas and osteosarcomas. Two different cell lines were used to induce osteosarcoma growth. Histological analyses were conducted to serve as references. Three ultrasound parameters and intensities of the light reflectance profiles showed significant differences between chondrosarcomas and osteosarcomas at the 5% level. Likewise, variations in the same biomarkers were reported for the two types of osteosarcoma, despite their similar morphology observed in the histological examinations. These observations show the sensitivity of our techniques in probing fine tissue properties. Secondly, the ultrasound spectral-based technique identified the mean size of chondrosarcoma cells and nuclei with relative errors of about 22% and 9% respectively. The optical equivalent technique correctly extracted scatterer size distributions that encompass nuclei and cells for chondrosarcomas and osteosarcomas ([Formula: see text] and [Formula: see text] respectively). The optical scattering contributions of nuclei were estimated at 52% for the chondrosarcomas and 69% for the osteosarcomas, probably indicating the abundant and the absent extracellular matrix respectively. Thus, the ultrasound and the optical methods brought complementary parameters. They successfully estimated morphological parameters at the cellular and the nuclear scales, making our bimodal technique promising for tumor characterization.

Ultrasound Scattering From Cell-Pellet Biophantoms and Ex Vivo Tumors Provides Insight Into the Cellular Structure Involved in Scattering.

The histologically identifiable cellular structure(s) involved in ultrasonic scattering is(are) yet to be uniquely identified. The study quantifies six possible cellular scattering parameters, namely, cell and nucleus radii and their respective cell and nucleus volume fractions as well as a combination of cell and nucleus radii and their volume fraction. The six cellular parameters are each derived from four cell lines (4T1, JC, LMTK, and MAT) and two tissue types (cell-pellet biophantom and ex vivo tumor). Optical histology and quantitative ultrasound (QUS), both independent approaches, are used to yield these cellular parameters. QUS scatterer parameters are experimentally determined using two ultrasonic scattering models: the spherical Gaussian model (GM) and the structure factor model (SFM) to yield insight about scattering from nuclei only and cells only. GM is a classical ultrasonic scattering model to evaluate QUS parameters and is well adapted for diluted media. SFM is adapted for dense media to estimate reasonably well scatterer parameters of cellular structures from ex vivo tissue. Nucleus and cell radii and volume fractions are measured optically from histology. They were used as inputs to calculate BSC for scattering from cells, nuclei, and both cells and nuclei. The QUS-derived scatterers (radii and volume fractions) distributions were then compared to the optical histology scatterer parameters derived from these calculated BSCs. The results suggest scattering from cells only (LMTK and MAT) or both cells and nuclei (4T1 and JC) for cell-pellet biophantoms and scattering from nuclei only for tumors.

Nonlinear ultrasound parameter to monitor cell death in cancer cell samples.

A scaling subtraction method was proposed to analyze the radio frequency data from cancer cell samples exposed to an anti-cancer drug and to estimate a nonlinear parameter. The nonlinear parameter was found to be well correlated (R2 = 0.62) to the percentage of dead cells in apoptosis and necrosis. The origin of the nonlinearity may be related to a change in contacts between cells, since the nonlinear parameter was well correlated to the average total coordination number of binary packings (R2 ≥ 0.77). These results suggest that the scaling subtraction method may be used to early quantify chemotherapeutic treatment efficiency.

Ultrasound Localization Microscopy and Super-Resolution: A State of the Art.

Because it drives the compromise between resolution and penetration, the diffraction limit has long represented an unreachable summit to conquer in ultrasound imaging. Within a few years after the introduction of optical localization microscopy, we proposed its acoustic alter ego that exploits the micrometric localization of microbubble contrast agents to reconstruct the finest vessels in the body in-depth. Various groups now working on the subject are optimizing the localization precision, microbubble separation, acquisition time, tracking, and velocimetry to improve the capacity of ultrasound localization microscopy (ULM) to detect and distinguish vessels much smaller than the wavelength. It has since been used in vivo in the brain, the kidney, and tumors. In the clinic, ULM is bound to improve drastically our vision of the microvasculature, which could revolutionize the diagnosis of cancer, arteriosclerosis, stroke, and diabetes.

High-Frequency Quantitative Ultrasound Spectroscopy of Excised Canine Livers and Mouse Tumors Using the Structure Factor Model.

Three scattering models were examined for characterizing ex vivo canine livers and HT29 mouse tumors in the 10-38- and the 15-42-MHz frequency bandwidth, respectively. The spherical Gaussian model (SGM) and the fluid sphere model (FSM) that were examined are suitable for dealing with sparse media, whereas the structure factor model (SFM) is adapted for characterizing concentrated media. For the canine livers, the scatterer radius and the acoustic concentration estimated with the three models were similar and matched well the nuclear structures obtained from histological analysis (with relative errors less than 7%). These results show that the livers could be considered as a diluted medium and that the nuclei in liver could be a dominant source of scattering. For the homogeneous mouse tumors, containing mostly viable HT29 cells, scatterer radius and volume fraction estimated with the SFM showed good agreement with the whole cell structures obtained from histological analysis (with relative errors less than 15%), whereas the sparse models (the SGM and the FSM) gave no consistent quantitative ultrasound parameters. This suggests that the viable HT29 cell areas have densely packed cellular content and that the whole HT29 cell could be responsible for scattering. For the heterogeneous tumors, the hyperechogenic zones observed in the B-mode images were linked to the presence of small necrotic areas surrounded by viable HT29 cells. Comparison between sparse and concentrated models shows that these hyperechogenic zones could be considered as a concentrated medium.