Rationale and Objectives Improvements in the diagnosis of early breast cancers depend on a physician’s ability to obtain the information necessary to distinguish nonpalpable malignant and benign tumors. Viscoelastic features that describe mechanical properties of tissues may help to distinguish these types of lesions. Materials and Methods 21 patients with nonpalpable, pathology-confirmed BI-RADS 4 or 5 breast lesions (10 benign, 11 malignant) detected by mammography were studied. Viscoelastic parameters were extracted from a time sequence of ultrasonic strain images and differences in the parameters between malignant and benign tumors were compared. Parametric data were color coded and superimposed on sonograms. Results The strain retardance time parameter, T1, provided the best discrimination between malignant and benign tumors (p<0.01). T1 measures the time required for tissues to fully deform (strain) once compressed, and therefore it describes the time-varying viscous response of tissue to a small deforming force. Compared to the surrounding background tissues, malignant lesions have smaller average T1 values while benign lesions have larger T1 values. This tissue-specific contrast correlates with known changes in the extracellular matrix of breast stroma. Conclusion Characterization of nonpalpable breast lesions is improved by the addition of viscoelastic strain imaging parameters. The differentiation of malignant and benign BI-RADS 4 or 5 tumors is especially evident with the use of the retardation time estimates, T1.
Objective-Atherosclerosis is a focal disease that develops at sites of low and oscillatory shear stress in arteries. This study aimed to understand how endothelial cells sense a gradient of fluid shear stress and transduce signals that regulate membrane expression of cell adhesion molecules and monocyte recruitment.Methods-Human aortic endothelial cells were stimulated with TNF-α and simultaneously exposed to a linear gradient of shear stress that increased from 0 to 16 dyne/cm 2 . Cell adhesion molecule expression and activation of NFκB were quantified by immunofluorescence microscopy with resolution at the level of a single endothelial cell. Monocyte recruitment was imaged using custom microfluidic flow chambers.Results-VCAM-1 and E-selectin upregulation was greatest between 2-4 dyne/cm 2 (6 and 4-fold, respectively) and above 8 dyne/cm 2 expression was suppressed below that of untreated endothelial cells. In contrast, ICAM-1 expression and NFκB nuclear translocation increased with shear stress up to a maximum at 9 dyne/cm 2 . Monocyte recruitment was most efficient in regions where E-selectin and VCAM-1 expression was greatest.Conclusions-We found that the endothelium can sense a change in shear stress on the order of 0.25 dyne/cm 2 over a length of ~10 cells, regulating the level of protein transcription, cellular adhesion molecule expression, and leukocyte recruitment during inflammation.
Atherosclerotic lesions preferentially originate in arterial regions that experience low wall shear stress (WSS) and reversing flow patterns. Therefore, routinely monitoring arterial WSS may help to identify the potential sites of early atherosclerosis. A new non-invasive ultrasonic method implemented with coded excitation techniques was utilized to improve WSS estimation accuracy and precision by providing high spatial and temporal resolution. WSS measurement errors were quantified in a model system by scanning a linearly-varying WSS field (0.3-1.9 Pa) within a flow chamber. A 13-bit Optimal code was found to be most effective in reducing bias and standard deviation in WSS estimates down to ~ 10 % and ~ 8 %. The measurement errors slowly increased with input WSS for all imaging pulses. The expression of endothelial cellular adhesion molecules VCAM-1 and E-selectin was investigated over a similar shear range (0-1.6 Pa) in order to study the impact of relating shear-mediated cellular adhesion molecule (CAM) expression to inaccuracies in WSS measurements. We quantified this influence as the prediction error, which accounts for the ultrasonic measurement errors and the sensitivity of CAM expression within certain shear ranges. The highest prediction errors were observed at WSS < 0.8 Pa, where CAM expression is most responsive to WSS. The results emphasize the importance of minimizing estimation errors, especially within low shear regions. Preliminary 2-D in vivo shear imaging is also presented to provide information about the spatial heterogeneity in arterial WSS distribution.
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