Microbubble Axial Localization Errors in Ultrasound Super-Resolution Imaging

Acoustic super-resolution imaging has allowed visualization of microvascular structure and flow beyond the diffraction limit using standard clinical ultrasound systems through the localization of many spatially isolated microbubble signals. The determination of each microbubble position is typically performed by calculating the centroid, finding a local maximum, or finding the peak of a 2-D Gaussian function fit to the signal. However, the backscattered signal from a microbubble depends not only on diffraction characteristics of the waveform, but also on the microbubble behavior in the acoustic field. Here, we propose a new axial localization method by identifying the onset of the backscattered signal. We compare the accuracy of localization methods using in vitro experiments performed at 7 cm depth and 2.3 MHz center frequency. We corroborate these findings with simulated results based on the Marmottant model. We show experimentally and in simulations that detecting the onset of the returning signal provides considerably increased accuracy for super-resolution. Resulting experimental cross-sectional profiles in super-resolution images demonstrate at least 5.8 times improvement in contrast ratio and more than 1.8 reduction in spatial spread (provided by 90% of the localizations) for the onset method over centroiding, peak detection and 2D Gaussian fitting methods. Simulations estimate that these latter methods could create errors in relative bubble positions as high as 900 μ m at these experimental settings, while the onset method reduced the interquartile range of these errors by a factor of over 2.2. Detecting the signal onset is therefore expected to considerably improve the accuracy of super-resolution

Two-stage motion correction for super-resolution ultrasound imaging in human lower limb

The structure of microvasculature cannot be resolved using conventional ultrasound imaging due to the fundamental diffraction limit at clinical ultrasound frequencies. It is possible to overcome this resolution limitation by localizing individual microbubbles through multiple frames and forming a super-resolved image, which usually requires seconds to minutes of acquisition. Over this time interval, motion is inevitable and tissue movement is typically a combination of large and small scale tissue translation and deformation. Therefore, super-resolution imaging is prone to motion artefacts as other imaging modalities based on multiple acquisitions are. This study investigates the feasibility of a two-stage motion estimation method, which is a combination of affine and non-rigid estimation, for super-resolution ultrasound imaging. Firstly, the motion correction accuracy of the proposed method is evaluated using simulations with increasing complexity of motion. A mean absolute error of 12.2 μm was achieved in simulations for the worst case scenario. The motion correction algorithm was then applied to a clinical dataset to demonstrate its potential to enable in vivo super-resolution ultrasound imaging in the presence of patient motion. The size of the identified microvessels from the clinical super-resolution images were measured to assess the feasibility of the two-stage motion correction method, which reduced the width of the motion blurred microvessels approximately 1.5-fold

Physics in the Real Universe: Time and Spacetime

The Block Universe idea, representing spacetime as a fixed whole, suggests the flow of time is an illusion: the entire universe just is, with no special meaning attached to the present time. This view is however based on time-reversible microphysical laws and does not represent macro-physical behaviour and the development of emergent complex systems, including life, which do indeed exist in the real universe. When these are taken into account, the unchanging block universe view of spacetime is best replaced by an evolving block universe which extends as time evolves, with the potential of the future continually becoming the certainty of the past. However this time evolution is not related to any preferred surfaces in spacetime; rather it is associated with the evolution of proper time along families of world linesComment: 28 pages, including 9 Figures. Major revision in response to referee comment

Light propagation in statistically homogeneous and isotropic universes with general matter content

We derive the relationship of the redshift and the angular diameter distance to the average expansion rate for universes which are statistically homogeneous and isotropic and where the distribution evolves slowly, but which have otherwise arbitrary geometry and matter content. The relevant average expansion rate is selected by the observable redshift and the assumed symmetry properties of the spacetime. We show why light deflection and shear remain small. We write down the evolution equations for the average expansion rate and discuss the validity of the dust approximation.Comment: 42 pages, no figures. v2: Corrected one detail about the angular diameter distance and two typos. No change in result

Light propagation in statistically homogeneous and isotropic dust universes

We derive the redshift and the angular diameter distance in rotationless dust universes which are statistically homogeneous and isotropic, but have otherwise arbitrary geometry. The calculation from first principles shows that the Dyer-Roeder approximation does not correctly describe the effect of clumping. Instead, the redshift and the distance are determined by the average expansion rate, the matter density today and the null geodesic shear. In particular, the position of the CMB peaks is consistent with significant spatial curvature provided the expansion history is sufficiently close to the spatially flat LambdaCDM model.Comment: 33 pages. v2: Published version. Corrected typo