Role of ultrasonic shear rate estimation errors in assessing inflammatory response and vascular risk.

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 noninvasive 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 to 1.9 Pa) within a flow chamber. A 13-bit optimal code (Opt) was found to be most effective in reducing bias and standard deviation in WSS estimates down to approximately 10% and approximately 8%. The measurement errors slowly increased with input WSS for all imaging pulses. The expression of endothelial cellular adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) was investigated over a similar shear range (0 to 1.6 Pa) 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 two-dimensional in vivo shear imaging is also presented to provide information about the spatial heterogeneity in arterial WSS distribution.

Modeling and phantom studies of ultrasonic wall shear rate measurements using coded pulse excitation.

Wall shear rate (WSR) is the derivative of blood velocity with respect to vessel radius at the endothelial cell (EC) surface. The product of WSR and blood viscosity is the wall shear stress (WSS) that has been identified as an important factor for atherosclerosis development. High echo signal-to-noise ratio (eSNR) and high spatial resolution are crucial for minimizing the errors in WSR estimates. By transmitting coded pulses with time-bandwidth product greater than one, high eSNR from weak blood scatter can be achieved without increasing instantaneous power or sacrificing spatial resolution. This paper summarizes a series of measurements in a straight tube (5-mm diameter), constant velocity flow phantom using a 10 MHz transducer (60% bandwidth, f/1.5) imaged with a 72 degrees Doppler angle, 125 MHz sampling frequency and 1 kHz pulse repetition frequency. Measurements were made using a frequency-modulated (FM) code, phase-modulated (PM) codes, and uncoded broadband and narrow band pulse transmissions. Both simulation and experimental results show that coded-pulse excitation increases accuracy and precision in WSR estimation for laminar flow over a broad range of peak velocity values when compared to standard pulsing techniques in noise-limited conditions (eSNR < 30 dB). The code sequence and its length are selected to balance range lobe suppression with eSNR and echo coherence enhancements to minimize WSR errors. In our study, the combination of an eight bit Optimal coded pulse with a Wiener compression filter yielded the highest WSR estimation performance.

Ultrasonic viscoelasticity imaging of nonpalpable breast tumors: preliminary results.

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: Twenty-one patients with nonpalpable, pathology-confirmed Breast Imaging Reporting and Data System (BIRADS) 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, T(1), provided the best discrimination between malignant and benign tumors (P < .01). T(1) measures the time required for tissues to fully deform (strain) once compressed; 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 T(1) values, whereas benign lesions have higher T(1) 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, T(1).

Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress.

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-alpha and simultaneously exposed to a linear gradient of shear stress that increased from 0 to 16 dyne/cm2. Cell adhesion molecule expression and activation of NFkappa B 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/cm2 (6 and 4-fold, respectively) and above 8 dyne/cm2 expression was suppressed below that of untreated endothelial cells. In contrast, ICAM-1 expression and NFkappa B nuclear translocation increased with shear stress up to a maximum at 9 dyne/cm2. 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/cm2 over a length of approximately 10 cells, regulating the level of protein transcription, cellular adhesion molecule expression, and leukocyte recruitment during inflammation.