Nanomechanics of biocompatible hollow thin-shell polymer microspheres.

The nanomechanical properties of biocompatible thin-shell hollow polymer microspheres with approximately constant ratio of shell thickness to microsphere diameter were measured by nanocompression tests in aqueous conditions. These microspheres encapsulate an inert gas and are used as ultrasound contrast agents by releasing free microbubbles in the presence of an ultrasound field as a result of free gas leakage from the shell. The tests were performed using an atomic force microscope (AFM) employing the force-distance curve technique. An optical microscope, on which the AFM was mounted, was used to guide the positioning of tipless cantilevers on top of individual microspheres. We performed a systematic study using several cantilevers with spring constants varying from 0.08 to 2.3 N/m on a population of microspheres with diameters from about 2 to 6 microm. The use of several cantilevers with various spring constants allowed a systematic study of the mechanical properties of the microsphere thin shell at different regimes of force and deformation. Using thin-shell mechanics theory for small deformations, the Young's modulus of the thin wall material was estimated and was shown to exhibit a strong size effect: it increased as the shell became thinner. The Young's modulus of thicker microsphere shells converged to the expected value for the macroscopic bulk material. For high applied forces, the force-deformation profiles showed a reversible and/or irreversible nonlinear behavior including "steps" and "jumps" which were attributed to mechanical instabilities such as buckling events.

Factors affecting the arterial distension waveform derived from tissue Doppler imaging (TDI): an in vitro study on precision.

An investigation was made into the effect of acquisition parameters on the distension waveform estimated from tissue Doppler imaging (TDI). Physiological distension waveforms were generated using a compliant wall phantom. Distensions derived over a range of scanning geometries and transducer pressures were compared with those obtained in optimised scanning conditions. The estimated maximum distension decreased with scanning depth by 7% between 20 mm and 44 mm below the phantom surface, with an increase in transducer-vessel angle (by 22% from 0 degrees to 24 degrees ) and with a decrease in scan plane-vessel coincidence (by 34% from coincidence to 2 mm from the vessel central axis). An increase with transducer pressure was observed (by 20% from contact to high exerted pressure).

Error analysis of ultrasonic tissue doppler velocity estimation techniques for quantification of velocity and strain.

Recent work in the field of Doppler tissue imaging has focused mainly on the quantification of results involving the use of techniques of strain and strain-rate imaging. These results are based on measuring a velocity gradient between two points, a known distance apart, in the region-of-interest. Although many recent publications have demonstrated the potential of this technique in clinical terms, the method still suffers from low repeatability. The work presented here demonstrates, through the use of a rotating phantom arrangement and a custom developed single element ultrasound system, that this is a consequence of the fundamental accuracy of the technique used to estimate the original velocities. Results are presented comparing the performance of the conventional Kasai autocorrelation velocity estimator with those obtained using time domain cross-correlation and the complex cross-correlation model based estimator. The results demonstrate that the complex cross-correlation model based technique is able to offer lower standard deviations of the velocity gradient estimations compared with the Kasai algorithm.

An anthropomorphic tissue-mimicking phantom of the oesophagus for endoscopic ultrasound.

This study details the design and construct of an anthropomorphic phantom of the oesophagus suitable for use with endoscopic ultrasound (EUS) and 3-D volume measurements. The phantom was constructed using agar-based tissue-mimicking material (TMM) of different acoustical properties to simulate various anatomical and pathologic features. The acoustical properties were measured with a scanning acoustical macroscope. An Olympus GF-UM200 echo-endoscope and digital position measurement arm were used to scan the phantom at 7.5 and 12 MHz. Comparative dimensional measurements were performed on the phantom via 2-D and 3-D EUS. TMM attenuation varied between 0.1 and 0.5 dB/cm.MHz. Backscatter power, relative to normal TMM, was from 0 to -12.2 dB, with an average speed of sound of 1537 +/- 1.9 m/s. Measurements of objects within the phantom by 2-D and 3-D EUS had mean errors of 8% and 2.2%, respectively. The construction of the anthropomorphic EUS phantom facilitated EUS training and research and development studies.

B-mode compound imaging in mice.

Cross-sectional B-mode images were obtained from a dead mouse for a 360 degrees scan around the mouse using a 12-MHz linear array. For each cross-section, a set of aligned images was obtained after rotation about the isocenter, which were added to produce a single compound image. The compound images demonstrated a substantial improvement over single B-mode images, with uniform image quality, low noise and improved visualization of structures. This technique may be of interest in forming the basis for a new 3-D in vivo technique in the abdomen and pelvic regions, providing high-quality ultrasound images that are not dependent on operator skill. A further development worth pursuing for improved spatial resolution is reconstruction-based tomography.

Laser Doppler anemometry measurements of the shear stresses on ultrasonic contrast agent microbubbles attached to agar.

Ultrasonic contrast agents are currently being developed to target and bind to specific areas of interest such as atheromous plaque. A microbubble has been developed in-house which can be targeted to attach to specific cell-lines. To assess the feasibility of using the microbubble in vivo, the shear stresses which the bound microbubbles can withstand need to be known. A flow chamber was developed for use with intravascular ultrasound (IVUS) and laser Doppler anemometry (LDA). Biotin was incorporated into the microbubble shells and streptavidin was used to attach them to agar. IVUS at 40 MHz was then used to image the attached microbubbles under steady flow at a range of flow rates from 75 to 480 mL min(-1) through a flow area of 9 mm(2). LDA was employed to find high resolution velocity profiles of the flow in the chamber at a selection of these flow rates and the shear stresses on the bubbles were calculated. The bubbles were found to remain attached to the agar for shear stresses of up to 3.4 Pa. This compares with mean physiological arterial shear stresses of less than 1.5 Pa for pulsatile flow.

Doppler colour flow imaging and flow quantification with a novel forward-viewing intravascular ultrasound system.

The aim of this work was to investigate the potential of a novel forward-viewing intravascular ultrasound (IVUS) system for flow quantification and colour flow imaging combined with B-mode imaging. A stiff 3.8-mm diameter catheter was used to scan a 72 degrees sector ahead of its tip. Operating at 30 MHz, the catheter was integrated with an IVUS scanner and a radiofrequency (RF) data-acquisition system. RF data were software processed for producing B-mode images and deriving velocity estimates. Steady flow in the range of 45 to 146 mL/min toward the catheter, was used in wall-less tissue-mimicking phantoms simulating healthy lumen (8-mm diameter), 30% diameter symmetrical stenosis and 37% diameter eccentric stenosis. The system provided colour flow images and good estimation of peak velocity and volumetric flows (within 1% to 9% and 16% to 48%, respectively, of calculated values) at 5 to 7 mm distal to the catheter. A sector forward-viewing IVUS imaging/Doppler system is suitable for combined anatomical and functional assessment of stenosed vessels.

Tissue Doppler Echocardiography: Historical Perspective and Technological Considerations.

Tissue Doppler echocardiography is a new ultrasonographic approach to the quantification of myocardial function. It is based on the interrogation of the high amplitude, low velocity reflected ultrasound signals from the myocardium. Velocity data can be obtained during pulsed- or color Doppler methodologies. Color Doppler data can be processed to determine regional acceleration, strain, strain rate, delay, and amplitude of motion. Color myocardial Doppler frame rates of up to 200 s(-1) can be implemented by parallel processing of the data, thus overcoming the early temporal resolution limitations of the technique.