Microbubble Track-based Functional Ultrasound Localization Microscopy in Awake Mice.

Functional neuroimaging with ultrafast ultrasound is an emerging neuroimaging tool for studying neural activities in the rodent brain. Existing methods, however, are challenged by the compromise between functional imaging sensitivity (i.e.

High-Volume Acquisition Rate Nonlinear Imaging Enables Robust 3-D Ultrasound Localization Microscopy.

3-D ultrasound localization microscopy (ULM) enables comprehensive mapping of microvascular networks by providing micrometer-scale spatial resolution while avoiding projection errors inherent to 2-D ULM imaging. Current 3-D ULM techniques are based on linear pulse sequences combined with spatiotemporal filtering to distinguish microbubble flow from tissue signals. However, singular-value decomposition (SVD)-based filtering demonstrates poor performance in highly mobile organs, suppressing small vessels with slow blood flow along with tissue signals.

Deep-tissue high-sensitivity multimodal imaging and optogenetic manipulation enabled by biliverdin reductase knockout.

Performance of near-infrared probes and optogenetic tools derived from bacterial phytochromes is limited by availability of their biliverdin chromophore. To address this, we use a biliverdin reductase-A knock-out mouse model (Blvra), which elevates endogenous biliverdin levels. We show that Blvra⁻/⁻ significantly enhances function of bacterial phytochrome-based systems.

Super-Resolution Ultrasound: From Data Acquisition and Motion Correction to Localization, Tracking, and Evaluation.

Super-resolution ultrasound (SRUS) imaging through localizing and tracking microbubbles (MBs), also known as ultrasound localization microscopy (ULM), has achieved unprecedented resolution in deep tissue in vivo. In this review, we will focus on the key technical steps of ULM, including data acquisition and tissue clutter removal, motion correction, localization, tracking, and final image visualization, as well as offering the authors' perspectives of the techniques. In each of the technical steps, we review what has been done and the state of the art and describe the key factors and parameters that influence each step, existing issues, and considerations when choosing the parameters.

Improved Microbubble Tracking for Super-Resolution Ultrasound Localization Microscopy using a Bi-Directional Long Short-term Memory Neural Network.

Ultrasound localization microscopy (ULM) enabled high-accuracy measurements of microvessel flow beyond the resolution limit of conventional ultrasound imaging by utilizing contrast microbubbles (MBs) as point targets. Robust tracking of MBs is an essential task for fast and high-quality ULM image reconstruction. Existing MB tracking methods suffer from challenging imaging scenarios such as high-density MB distributions, fast blood flow, and complex flow dynamics.

Combined Nanodrops Imaging and Ultrasound Localization Microscopy for Detecting Intracerebral Hemorrhage.

Objective: Advanced imaging methods are crucial for understanding stroke mechanisms and discovering effective treatments to reduce bleeding and enhance recovery. In pre-clinical in vivo stroke imaging, MRI, CT and optical imaging are commonly used to evaluate stroke outcomes in rodent models. However, MRI and CT have limited spatial resolution for rodent brains, and optical imaging is hindered by limited imaging depth of penetration.

Advanced deep-tissue imaging and manipulation enabled by biliverdin reductase knockout.

We developed near-infrared (NIR) photoacoustic and fluorescence probes, as well as optogenetic tools from bacteriophytochromes, and enhanced their performance using biliverdin reductase-A knock-out model (Blvra-/-). Blvra-/- elevates endogenous heme-derived biliverdin chromophore for bacteriophytochrome-derived NIR constructs. Consequently, light-controlled transcription with IsPadC-based optogenetic tool improved up to 25-fold compared to wild-type cells, with 100-fold activation in Blvra-/- neurons.

Capillary-scale Microvessel Imaging with High-frequency Ultrasound Localization Microscopy in Mouse Brain.

Ultrasound localization microscopy is a super-resolution vascular imaging technique which has garnered substantial interest as a tool for small animal neuroimaging, neuroscience research, and the characterization of vascular pathologies. In the pursuit of increasingly high-fidelity reconstructions of microvasculature, there remains several outstanding questions concerning this sub-diffraction imaging technology, including the accurate reconstruction of microvessels approaching the capillary scale and the pragmatic challenges associated with long data acquisition times. In the context of small animal neurovascular imaging, we posit that increasing the ultrasound imaging frequency is a straightforward approach to enable higher concentrations of microbubble contrast agents, thus increasing the likelihood of microvascular/capillary mapping and decreasing the imaging duration.

ULTRA-SR Challenge: Assessment of Ultrasound Localization and TRacking Algorithms for Super-Resolution Imaging.

With the widespread interest and uptake of super-resolution ultrasound (SRUS) through localization and tracking of microbubbles, also known as ultrasound localization microscopy (ULM), many localization and tracking algorithms have been developed. ULM can image many centimeters into tissue in-vivo and track microvascular flow non-invasively with sub-diffraction resolution. In a significant community effort, we organized a challenge, Ultrasound Localization and TRacking Algorithms for Super-Resolution (ULTRA-SR).

High-Resolution Power Doppler Using Null Subtraction Imaging.

To improve the spatial resolution of power Doppler (PD) imaging, we explored null subtraction imaging (NSI) as an alternative beamforming technique to delay-and-sum (DAS). NSI is a nonlinear beamforming approach that uses three different apodizations on receive and incoherently sums the beamformed envelopes. NSI uses a null in the beam pattern to improve the lateral resolution, which we apply here for improving PD spatial resolution both with and without contrast microbubbles.

Three-Dimensional Shear Wave Elastography Using Acoustic Radiation Force and a 2-D Row-Column Addressing (RCA) Array.

Acoustic radiation force (ARF)-based shear wave elastography (SWE) is a clinically available ultrasound imaging mode that noninvasively and quantitatively measures tissue stiffness. Current implementations of ARF-SWE are largely limited to 2-D imaging, which does not provide a robust estimation of heterogeneous tissue mechanical properties. Existing 3-D ARF-SWE solutions that are clinically available are based on wobbler probes, which cannot provide true 3-D shear wave motion detection.

Super-Resolution Ultrasound Reveals Cerebrovascular Impairment in a Mouse Model of Alzheimer's Disease.

Increasing evidence has suggested a link between cerebrovascular disease and the cognitive impairment associated with Alzheimer's disease. However, detailed descriptions of microvascular changes across brain regions and how they relate to other more traditional pathology have been lacking. Additionally, the efforts to elucidate the interplay between cerebral microvascular function and Alzheimer's disease progression are complicated by the necessity of probing deep-brain structures since early-stage Alzheimer's disease typically involves hippocampal pathology.

Longitudinal Awake Imaging of Mouse Deep Brain Microvasculature with Super-resolution Ultrasound Localization Microscopy.

Ultrasound localization microscopy (ULM) is an emerging imaging modality that resolves microvasculature in deep tissues with high spatial resolution. However, existing preclinical ULM applications are largely constrained to anesthetized animals, introducing confounding vascular effects such as vasodilation and altered hemodynamics. As such, ULM quantifications (e.

Contrast-Free Super-Resolution Power Doppler (CS-PD) Based on Deep Neural Networks.

Super-resolution ultrasound microvessel imaging based on ultrasound localization microscopy (ULM) is an emerging imaging modality that is capable of resolving micrometer-scaled vessels deep into tissue. In practice, ULM is limited by the need for contrast injection, long data acquisition, and computationally expensive postprocessing times. In this study, we present a contrast-free super-resolution power Doppler (CS-PD) technique that uses deep networks to achieve super-resolution with short data acquisition.

High-Volume-Rate 3-D Ultrasound Imaging Using Fast-Tilting and Redirecting Reflectors.

Three-dimensional ultrasound imaging has many advantages over 2-D imaging such as more comprehensive tissue evaluation and less operator dependence. However, developing a low-cost and accessible 3-D ultrasound solution with high volume rate and imaging quality remains a challenging task. Recently, we proposed a 3-D ultrasound imaging technique: fast acoustic steering via tilting electromechanical reflectors (FASTER), which uses a fast-tilting acoustic reflector to steer ultrafast plane waves elevationally to achieve high-volume-rate 3-D imaging with conventional 1-D transducers.

Super-resolution ultrasound microvascular imaging: Is it ready for clinical use?

The field of super-resolution ultrasound microvascular imaging has been rapidly growing over the past decade. By leveraging contrast microbubbles as point targets for localization and tracking, super-resolution ultrasound pinpoints the location of microvessels and measures their blood flow velocity. Super-resolution ultrasound is the first in vivo imaging modality that can image micron-scale vessels at a clinically relevant imaging depth without tissue destruction.

High-Level Synthesis Design of Scalable Ultrafast Ultrasound Beamformer With Single FPGA.

Ultrafast ultrasound imaging is essential for advanced ultrasound imaging techniques such as ultrasound localization microscopy (ULM) and functional ultrasound (fUS). Current ultrafast ultrasound imaging is challenged by the ultrahigh data bandwidth associated with the radio frequency (RF) signal, and by the latency of the computationally expensive beamforming process. As such, continuous ultrafast data acquisition and beamforming remain elusive with existing software beamformers based on CPUs or GPUs.

Localization Free Super-Resolution Microbubble Velocimetry Using a Long Short-Term Memory Neural Network.

Ultrasound localization microscopy is a super-resolution imaging technique that exploits the unique characteristics of contrast microbubbles to side-step the fundamental trade-off between imaging resolution and penetration depth. However, the conventional reconstruction technique is confined to low microbubble concentrations to avoid localization and tracking errors. Several research groups have introduced sparsity- and deep learning-based approaches to overcome this constraint to extract useful vascular structural information from overlapping microbubble signals, but these solutions have not been demonstrated to produce blood flow velocity maps of the microcirculation.

High Volume Rate 3-D Ultrasound Imaging Using Fast-Tilting and Redirecting Reflectors.

3-D ultrasound imaging has many advantages over 2-D imaging such as more comprehensive tissue evaluation and less operator dependence. Although many 3-D ultrasound imaging techniques have been developed in the last several decades, a low-cost and accessible solution with high imaging volume rate and imaging quality remains elusive. Recently we proposed a new, high volume rate 3-D ultrasound imaging technique: Fast Acoustic Steering via Tilting Electromechanical Reflectors (FASTER), which uses a water-immersible and fast-tilting acoustic reflector to steer ultrafast plane waves in the elevational direction to achieve high volume rate 3-D ultrasound imaging with conventional 1-D array transducers.

Three-Dimensional Shear Wave Elastography Using a 2D Row Column Addressing (RCA) Array.

. To develop a 3D shear wave elastography (SWE) technique using a 2D row column addressing (RCA) array, with either external vibration or acoustic radiation force (ARF) as the shear wave source. .

Curvelet Transform-Based Sparsity Promoting Algorithm for Fast Ultrasound Localization Microscopy.

Ultrasound localization microscopy (ULM) based on microbubble (MB) localization was recently introduced to overcome the resolution limit of conventional ultrasound. However, ULM is currently challenged by the requirement for long data acquisition times to accumulate adequate MB events to fully reconstruct vasculature. In this study, we present a curvelet transform-based sparsity promoting (CTSP) algorithm that improves ULM imaging speed by recovering missing MB localization signal from data with very short acquisition times.

Deep Learning-Based Microbubble Localization for Ultrasound Localization Microscopy.

Ultrasound localization microscopy (ULM) is an emerging vascular imaging technique that overcomes the resolution-penetration compromise of ultrasound imaging. Accurate and robust microbubble (MB) localization is essential for successful ULM. In this study, we present a deep learning (DL)-based localization technique that uses both Field-II simulation and in vivo chicken embryo chorioallantoic membrane (CAM) data for training.

A Review of Clinical Applications for Super-resolution Ultrasound Localization Microscopy.

Microvascular structure and hemodynamics are important indicators for the diagnosis and assessment of many diseases and pathologies. The structural and functional imaging of tissue microvasculature in vivo is a clinically significant objective for the development of many imaging modalities. Contrast-enhanced ultrasound (CEUS) is a popular clinical tool for characterizing tissue microvasculature, due to the moderate cost, wide accessibility, and absence of ionizing radiation of ultrasound.