Localisation of Multiple Non-Isolated Microbubbles with Frequency Decomposition in Super-Resolution Imaging

—Sub-diffraction imaging, also known as ultrasound localization microscopy, is a novel method that can overcome the fundamental diffraction limit by localizing spatially isolated microbubbles. This method requires the use of a low concentration of microbubbles to ensure that they are spatially isolated. For in vivo microvascular imaging, especially for cancer tissue with high microvascular density, spatial isolation cannot be always achieved, since vessels are close to each other and the speed of flow is slow. This study proposes a frequency decomposition method that uses the polydisperse nature of commercial contrast agents to separate spatially non-isolated microbubbles with different acoustic signatures. Zero-phase filters were applied to ensure that there is no relative phase delay between decomposed signals.Results showed that a super-resolution image after frequency decomposition can be generated with 1.4 times lower number of acquisitions

Two Stage Sub-Wavelength Motion Correction in Human Microvasculature for CEUS Imaging

The structure of microvasculature cannot be resolved using clinical B-mode or contrast-enhanced ultrasound (CEUS) 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. However, ultrasound super-resolution creates its unique problems since the structures to be imaged are on the order of 10s of μm. Tissue movement much larger than 10 μm is common in clinical imaging, which can significantly reduce the accuracy of super-resolution images created from microbubble locations gathered through hundreds of frames. This study investigated an existing motion estimation algorithm from magnetic resonance imaging for ultrasound super-resolution imaging. Its correction accuracy is evaluated using simulations with increasing complexity of motion. Feasibility of the method for ultrasound super-resolution in vivo is demonstrated on clinical ultrasound images. For a chosen microvessel, the super-resolution image without motion correction achieved a sub-wavelength resolution; however after the application of proposed two-stage motion correction method the size of the vessel was reduced to half

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

3-D Motion Correction for Volumetric Super-Resolution Ultrasound Imaging

© 2018 IEEE. Motion during image acquisition can cause image degradation in all medical imaging modalities. This is particularly relevant in 2-D ultrasound imaging, since out-of-plane motion can only be compensated for movements smaller than elevational beamwidth of the transducer. Localization based super-resolution imaging creates even a more challenging motion correction task due to the requirement of a high number of acquisitions to form a single super-resolved frame. In this study, an extension of two-stage motion correction method is proposed for 3-D motion correction. Motion estimation was performed on high volumetric rate ultrasound acquisitions with a handheld probe. The capability of the proposed method was demonstrated with a 3-D microvascular flow simulation to compensate for handheld probe motion. Results showed that two-stage motion correction method reduced the average localization error from 136 to 18 μm

Poisson Statistical Model of Ultrasound Super-Resolution Imaging Acquisition Time

A number of acoustic super-resolution techniques have recently been developed to visualize microvascular structure and flow beyond the diffraction limit. A crucial aspect of all ultrasound super-resolution (SR) methods using single microbubble localization is time-efficient detection of individual bubble signals. Due to the need for bubbles to circulate through the vasculature during acquisition, slow flows associated with the microcirculation limit the minimum acquisition time needed to obtain adequate spatial information. Here, a model is developed to investigate the combined effects of imaging parameters, bubble signal density, and vascular flow on SR image acquisition time. We find that the estimated minimum time needed for SR increases for slower blood velocities and greater resolution improvement. To improve SR from a resolution of λ10 to λ20 while imaging the microvasculature structure modelled here, the estimated minimum acquisition time increases by a factor of 14. The maximum useful imaging frame rate to provide new spatial information in each image is set by the bubble velocity at low blood flows (< 150 mm/s for a depth of 5 cm) and by the acoustic wave velocity at higher bubble velocities. Furthermore, the image acquisition procedure, transmit frequency, localization precision, and desired super-resolved image contrast, together determine the optimal acquisition time achievable for a fixed flow velocity. Exploring the effects of both system parameters and details of the target vasculature can allow a better choice of acquisition settings and provide improved understanding of the completeness of SR information. © 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works

3-D super-resolution ultrasound (SR-US) imaging using a 2-D sparse array with high volumetric imaging rate

Super-resolution ultrasound imaging has been so far achieved in 3-D by mechanically scanning a volume with a linear probe, by co-aligning multiple linear probes, by using multiplexed 3-D clinical ultrasound systems, or by using 3- D ultrasound research systems. In this study, a 2-D sparse array was designed with 512 elements according to a density- tapered 2-D spiral layout and optimized to reduce the sidelobes of the transmitted beam profile. High frame rate volumetric imaging with compounded plane waves was performed using two synchronized ULA-OP256 systems. Localization-based 3-D super-resolution images of two touching sub-wavelength tubes were generated from a 120 second acquisition

3-D Super-Resolution Ultrasound Imaging with a 2-D Sparse Array

High frame rate 3-D ultrasound imaging technology combined with super-resolution processing method can visualize 3-D microvascular structures by overcoming the diffraction limited resolution in every spatial direction. However, 3-D super-resolution ultrasound imaging using a full 2-D array requires a system with large number of independent channels, the design of which might be impractical due to the high cost, complexity, and volume of data produced. In this study, a 2-D sparse array was designed and fabricated with 512 elements chosen from a density-tapered 2-D spiral layout. High frame rate volumetric imaging was performed using two synchronized ULA-OP 256 research scanners. Volumetric images were constructed by coherently compounding 9-angle plane waves acquired at a pulse repetition frequency of 4500 Hz. Localization-based 3-D super-resolution images of two touching sub-wavelength tubes were generated from 6000 volumes acquired in 12 seconds. In conclusion, this work demonstrates the feasibility of 3-D super-resolution imaging and super-resolved velocity mapping using a customized 2-D sparse array transducer

Temperature dependent behavior of ultrasound contrast agents

Recent interest in ultrasound contrast agents (UCAs) as tools for quantitative imaging and therapy has increased the need for accurate characterization. Laboratory investigations are frequently undertaken in a water bath at room temperature; however, implications for in vivo applications are not presented. Acoustic investigation of a bulk suspension of SonoVue (Bracco Research, Geneva, Switzerland) was made in a water bath at temperatures of 20–45 °C. UCA characteristics were significantly affected by temperature, particularly between 20 and 40 °C, leading to an increase in attenuation from 1.7–2.5 dB, respectively (p = 0.002) and a 2-dB increase in scattered signal over the same range (p = 0.05) at an insonation pressure of 100 kPa. Optical data supported the hypothesis that a temperature-mediated increase in diameter was the dominant cause, and revealed a decrease in bubble stability. In conclusion, measurements made at room temperature require careful interpretation with regard to behavior in vivo