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Sanderson, R. W.

Publications and source records attributed to Sanderson, R. W..

2 recordsLinked to original sources

Visualization of breast cancer using contrast-enhanced optical coherence elastography based on tissue heterogeneity

By mapping the mechanical properties of tissue, elastography can improve identification of breast cancer. On the macro-scale, ultrasound elastography and magnetic resonance elastography have emerged as effective clinical methods for the diagnosis of tumors. On the micro-scale, optical coherence elastography (OCE) shows promise for intraoperative tumor margin assessment during breast-conserving surgery. Whilst several OCE studies have demonstrated strong potential, the mechanical models used require the assumption of uniaxial stress throughout the sample. However, breast tissue is heterogeneous and contains compressible features (e.g., ducts and blood vessels) and collagen-rich fibrotic features (e.g., stroma). This heterogeneity can invalidate the assumption of uniaxial stress and reduce the accuracy of OCE, often making it challenging to interpret images. Here, we demonstrate a new variant of OCE based on mapping the Euler angle, i.e., the angle between the principal compression and the loading axis induced by tissue heterogeneity, which removes the assumption of uniaxial deformation. This is enabled by a hybrid three-dimensional (3-D) displacement estimation method that combines phase-sensitive detection and complex cross-correlation, providing access to the 3-D displacement and 3-D strain tensor on the micro-scale. We demonstrate this new OCE technique through experiments on phantoms and 10 fresh human breast specimens. Through close correspondence with histology, our results show that mapping the Euler angle provides additional contrast to both optical coherence tomography and a current OCE technique in identifying cancer. Mapping the Euler angle in breast tissue may provide a new biomarker for intraoperative tumor margin assessment.

bioengineering↗

Multimodal mechano-microscopy reveals mechanical phenotypes of breast cancer spheroids in three dimensions

Cancer cell invasion relies on an equilibrium between cell deformability and the biophysical constraints imposed by the extracellular matrix (ECM). However, there is little consensus on the nature of the local biomechanical alterations in cancer cell dissemination in the context of three-dimensional (3D) tumor microenvironments (TME). While the shortcomings of two-dimensional (2D) models in replicating in situ cell behavior are well known, 3D TME models remain underutilized because contemporary mechanical quantification tools are limited to surface measurements. Here, we overcome this major challenge by quantifying local mechanics of cancer cell spheroids in 3D TMEs. We achieve this using multimodal mechano-microscopy, integrating optical coherence microscopy-based elasticity imaging with confocal fluorescence microscopy. We observe that non-metastatic cancer spheroids show no invasion while showing increased peripheral cell elasticity in both stiff and soft environments. Metastatic cancer spheroids, however, show ECM-mediated softening in a stiff microenvironment and, in a soft environment, initiate cell invasion with peripheral softening associated with early metastatic dissemination. This exemplar of live-cell 3D mechanotyping supports that invasion increases cell deformability in a 3D context, illustrating the power of multimodal mechano-microscopy for quantitative mechanobiology in situ.

bioengineering↗