Further characterization of changes in axial strain elastograms due to the presence of slippery tumor boundaries.

Elastography measures tissue strain, which can be interpreted under certain simplifying assumptions to be representative of the underlying stiffness distribution. This is useful in cancer diagnosis where tumors tend to have a different stiffness to healthy tissue and has also shown potential to provide indication of the degree of bonding at tumor-tissue boundaries, which is clinically useful because of its dependence on tumor pathology. We consider the changes in axial strain for the case of a symmetrical model undergoing uniaxial compression, studied by characterizing changes in tumor contrast transfer efficiency (CTE), inclusion to background strain contrast and strain contrast generated by slip motion, as a function of Young's modulus contrast and applied strain. We present results from a finite element simulation and an evaluation of these results using tissue-mimicking phantoms. The simulation results show that a discontinuity in displacement data at the tumor boundary, caused by the surrounding tissue slipping past the tumor, creates a halo of "pseudostrain" across the tumor boundary. Mobile tumors also appear stiffer on elastograms than adhered tumors, to the extent that tumors that have the same Young's modulus as the background may in fact be visible as low-strain regions, or those that are softer than the background may appear to be stiffer than the background. Tumor mobility also causes characteristic strain heterogeneity within the tumor, which exhibits low strain close to the slippery boundary and increasing strain toward the center of the tumor. These results were reproduced in phantom experiments. In addition, phantom experiments demonstrated that when fluid lubrication is present at the boundary, these effects become applied strain-dependent as well as modulus-dependent, in a systematic and characteristic manner. The knowledge generated by this study is expected to aid interpretation of clinical strain elastograms by helping to avoid misinterpretation as well as provide additional diagnostic criteria stated in the paper and stimulate further research into the application of elastography to tumor mobility assessment.

Nano-mechanics of ionic liquids at dielectric and metallic interfaces.

Using a dynamic surface force apparatus, we investigate the nano-mechanics and the nano-rheology of an ionic liquid at dielectric and metallic solid surfaces. On smooth dielectric Pyrex surfaces, we find an ordered interfacial phase extending over less than 3 nm away from the top of the layer, with a compression modulus of 15 MPa extracted from the profile of the oscillatory forces. We discuss the boundary flow of the Newtonian bulk phase on this ordered interfacial layer. On metallic platinum surfaces, our hydrodynamic measurements evidence an interfacial soft solid layer extending up to 20 nm away from the top of the layer. The elastic modulus of this interfacial layer, derived from elasto-hydrodynamic measurements, is similar to the one found on Pyrex surfaces. Both on the dielectric and on the metal surfaces, the thickness of the interfacial phases is not found to change upon approach of the opposite surface, and does not exhibit a capillary-freezing transition.

A micro-nano-rheometer for the mechanics of soft matter at interfaces.

We present a nano-rheometer based on the dynamic drainage flow between a sphere and a plane from bulk regime to highly confined regime. The instrument gives absolute measurements of the viscosity of simple liquids in both regimes. For complex fluids, the measurements involve the viscosity and the elastic modulus. The device operates on distances ranging over four orders of magnitude from 1 nm to 10 µm, bridging rheological properties from the macroscopic to the molecular scale. This allows to measure an hydrodynamic or visco-elastic boundary condition and to explore the causes of the boundary condition at the microscopic level.

4D ultrasound speckle tracking of intra-fraction prostate motion: a phantom-based comparison with x-ray fiducial tracking using CyberKnife.

This study investigates the use of a mechanically-swept 3D ultrasound (3D-US) probe for soft-tissue displacement monitoring during prostate irradiation, with emphasis on quantifying the accuracy relative to CyberKnife® x-ray fiducial tracking. An US phantom, implanted with x-ray fiducial markers was placed on a motion platform and translated in 3D using five real prostate motion traces acquired using the Calypso system. Motion traces were representative of all types of motion as classified by studying Calypso data for 22 patients. The phantom was imaged using a 3D swept linear-array probe (to mimic trans-perineal imaging) and, subsequently, the kV x-ray imaging system on CyberKnife. A 3D cross-correlation block-matching algorithm was used to track speckle in the ultrasound data. Fiducial and US data were each compared with known phantom displacement. Trans-perineal 3D-US imaging could track superior-inferior (SI) and anterior-posterior (AP) motion to ≤0.81 mm root-mean-square error (RMSE) at a 1.7 Hz volume rate. The maximum kV x-ray tracking RMSE was 0.74 mm, however the prostate motion was sampled at a significantly lower imaging rate (mean: 0.04 Hz). Initial elevational (right-left; RL) US displacement estimates showed reduced accuracy but could be improved (RMSE <2.0 mm) using a correlation threshold in the ultrasound tracking code to remove erroneous inter-volume displacement estimates. Mechanically-swept 3D-US can track the major components of intra-fraction prostate motion accurately but exhibits some limitations. The largest US RMSE was for elevational (RL) motion. For the AP and SI axes, accuracy was sub-millimetre. It may be feasible to track prostate motion in 2D only. 3D-US also has the potential to improve high tracking accuracy for all motion types. It would be advisable to use US in conjunction with a small (∼2.0 mm) centre-of-mass displacement threshold in which case it would be possible to take full advantage of the accuracy and high imaging rate capability.

A new method for the acquisition of ultrasonic strain image volumes.

This article presents a new method for acquiring three-dimensional (3-D) volumes of ultrasonic axial strain data. The method uses a mechanically-swept probe to sweep out a single volume while applying a continuously varying axial compression. Acquisition of a volume takes 15-20 s. A strain volume is then calculated by comparing frame pairs throughout the sequence. The method uses strain quality estimates to automatically pick out high quality frame pairs, and so does not require careful control of the axial compression. In a series of in vitro and in vivo experiments, we quantify the image quality of the new method and also assess its ease of use. Results are compared with those for the current best alternative, which calculates strain between two complete volumes. The volume pair approach can produce high quality data, but skillful scanning is required to acquire two volumes with appropriate relative strain. In the new method, the automatic quality-weighted selection of image pairs overcomes this difficulty and the method produces superior quality images with a relatively relaxed scanning technique.

Elastographic contrast generation in optical coherence tomography from a localized shear stress.

A technique for generating contrast in two-dimensional shear strain elastograms from a localized stress is presented. The technique involves generating a non-uniform, localized stress via a magnetically actuated implant. Its effectiveness is demonstrated using finite-element simulations and a phantom study provides experimental verification of this. The method is applied to a superficial cancerous lesion model represented as a stiff inclusion in normal tissue. The lesion was best distinguished from its surroundings using total shear strain elastograms, rather than individual strain components. In experimental phantom studies, the lesion was imaged using optical coherence tomography (OCT) and could still be distinguished in elastograms when not readily identifiable in standard OCT images.