Ultrafast ultrasonic imaging is a rapidly developing field based on the unfocused transmission of plane or diverging ultrasound waves. This recent approach to ultrasound imaging leads to a large increase in raw ultrasound data available per acquisition. Bigger synchronous ultrasound imaging datasets can be exploited in order to strongly improve the discrimination between tissue and blood motion in the field of Doppler imaging. Here we propose a spatiotemporal singular value decomposition clutter rejection of ultrasonic data acquired at ultrafast frame rate. The singular value decomposition (SVD) takes benefits of the different features of tissue and blood motion in terms of spatiotemporal coherence and strongly outperforms conventional clutter rejection filters based on high pass temporal filtering. Whereas classical clutter filters operate on the temporal dimension only, SVD clutter filtering provides up to a four-dimensional approach (3D in space and 1D in time). We demonstrate the performance of SVD clutter filtering with a flow phantom study that showed an increased performance compared to other classical filters (better contrast to noise ratio with tissue motion between 1 and 10mm/s and axial blood flow as low as 2.6 mm/s). SVD clutter filtering revealed previously undetected blood flows such as microvascular networks or blood flows corrupted by significant tissue or probe motion artifacts. We report in vivo applications including small animal fUltrasound brain imaging (blood flow detection limit of 0.5 mm/s) and several clinical imaging cases, such as neonate brain imaging, liver or kidney Doppler imaging.

Spatiotemporal Clutter Filtering of Ultrafast Ultrasound Data Highly Increases Doppler and fUltrasound Sensitivity

The majority of exchanges of oxygen and nutrients are performed around vessels smaller than 100 μm, allowing cells to thrive everywhere in the body. Pathologies such as cancer, diabetes and arteriosclerosis can profoundly alter the microvasculature. Unfortunately, medical imaging modalities only provide indirect observation at this scale. Inspired by optical microscopy, ultrasound localization microscopy has bypassed the classic compromise between penetration and resolution in ultrasonic imaging. By localization of individual injected microbubbles and tracking of their displacement with a subwavelength resolution, vascular and velocity maps can be produced at the scale of the micrometer. Super-resolution ultrasound has also been performed through signal fluctuations with the same type of contrast agents, or through switching on and off nano-sized phase-change contrast agents. These techniques are now being applied pre-clinically and clinically for imaging of the microvasculature of the brain, kidney, skin, tumors and lymph nodes.

/pdf/super-resolution-ultrasound-imaging-4hezs821zu.pdf

Super-resolution Ultrasound Imaging.

All cells sense and integrate mechanical and biochemical cues from their environment to orchestrate organismal development and maintain tissue homeostasis. Mechanotransduction is the evolutionarily conserved process whereby mechanical force is translated into biochemical signals that can influence cell differentiation, survival, proliferation and migration to change tissue behavior. Not surprisingly, disease develops if these mechanical cues are abnormal or are misinterpreted by the cells - for example, when interstitial pressure or compression force aberrantly increases, or the extracellular matrix (ECM) abnormally stiffens. Disease might also develop if the ability of cells to regulate their contractility becomes corrupted. Consistently, disease states, such as cardiovascular disease, fibrosis and cancer, are characterized by dramatic changes in cell and tissue mechanics, and dysregulation of forces at the cell and tissue level can activate mechanosignaling to compromise tissue integrity and function, and promote disease progression. In this Commentary, we discuss the impact of cell and tissue mechanics on tissue homeostasis and disease, focusing on their role in brain development, homeostasis and neural degeneration, as well as in brain cancer.

/pdf/tissue-mechanics-regulate-brain-development-homeostasis-and-2550hmlmo5.pdf

Tissue mechanics regulate brain development, homeostasis and disease

Estimation of individual muscle force remains one of the main challenges in biomechanics. This review presents a series of experiments that used ultrasound shear wave elastography to support the hypothesis that muscle stiffness is linearly related to both active and passive muscle forces. Examples of studies that used measurement of muscle stiffness to estimate changes in muscle force are presented.

Elastography for Muscle Biomechanics: Toward the Estimation of Individual Muscle Force.

Because it drives the compromise between resolution and penetration, the diffraction limit has long represented an unreachable summit to conquer in ultrasound imaging. Within a few years after the introduction of optical localization microscopy, we proposed its acoustic alter ego that exploits the micrometric localization of microbubble contrast agents to reconstruct the finest vessels in the body in-depth. Various groups now working on the subject are optimizing the localization precision, microbubble separation, acquisition time, tracking, and velocimetry to improve the capacity of ultrasound localization microscopy (ULM) to detect and distinguish vessels much smaller than the wavelength. It has since been used in vivo in the brain, the kidney, and tumors. In the clinic, ULM is bound to improve drastically our vision of the microvasculature, which could revolutionize the diagnosis of cancer, arteriosclerosis, stroke, and diabetes.

https://hal.archives-ouvertes.fr/hal-02344318/document

Ultrasound Localization Microscopy and Super-Resolution: A State of the Art

Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra—and inter-observer variability.

https://iopscience.iop.org/article/10.1088/0031-9155/59/19/L1/pdf

3D ultrafast ultrasound imaging in vivo.

Hepatic steatosis is a common condition, the prevalence of which is increasing along with non-alcoholic fatty liver disease (NAFLD). Currently, the most accurate noninvasive imaging method for diagnosing and quantifying hepatic steatosis is MRI, which estimates the proton-density fat fraction (PDFF) as a measure of fractional fat content. However, MRI suffers several limitations including cost, contra-indications and poor availability. Although conventional ultrasound is widely used by radiologists for hepatic steatosis assessment, it remains qualitative and operator dependent. Interestingly, the speed of sound within soft tissues is known to vary slightly from muscle (1.575 mm · µs-1) to fat (1.450 mm · µs-1). Building upon this fact, steatosis could affect liver sound speed when the fat content increases. The main objectives of this study are to propose a robust method for sound speed estimation (SSE) locally in the liver and to assess its accuracy for steatosis detection and staging. This technique was first validated on two phantoms and SSE was assessed with a precision of 0.006 and 0.003 mm · µs-1 respectively for the two phantoms. Then a preliminary clinical trial (N  =  17 patients) was performed. SSE results was found to be highly correlated with MRI proton density fat fraction (R 2  =  0.69) and biopsy (AUROC  =  0.952) results. This new method based on the assessment of spatio-temporal properties of the local speckle noise for SSE provides an efficient way to diagnose and stage hepatic steatosis.

https://iopscience.iop.org/article/10.1088/1361-6560/aa6226/pdf

Robust sound speed estimation for ultrasound-based hepatic steatosis assessment.

Purpose: Objective 
Shear wave elastography (SWE) enabled living tissue assessment of stiffness. This is routinely used for breast, thyroid and liver diseases, but there is currently no data for the brain. We aim to characterize elasticity of normal brain parenchyma and brain tumors using SWE.
 Materials and Methods: Patients with scheduled brain tumor removal were included in this study. In addition to standard ultrasonography, intraoperative SWE using an ultrafast ultrasonic device was used to measure the elasticity of each tumor and its surrounding normal brain. Data were collected by an investigator blinded to the diagnosis. Descriptive statistics, box plot analysis as well as intraoperator and interoperator reproducibility analysis were also performed. Results: 63 patients were included and classified into four main types of tumor: meningiomas, low-grade gliomas, high-grade gliomas and metastasis. Young’s Modulus measured by SWE has given new insight to differentiate brain tumors: 33.1 ± 5.9 kPa, 23.7 ± 4.9 kPa, 11.4 ± 3.6 kPa and 16.7 ± 2.5 kPa, respectively, for the four subgroups. Normal brain tissue has been characterized by a reproducible mean stiffness of 7.3 ± 2.1 kPa. Moreover, low-grade glioma stiffness is different from high-grade glioma stiffness (p = 0.01) and normal brain stiffness is very different from low-grade gliomas stiffness (p  Conclusion: This study demonstrates that there are significant differences in elasticity among the most common types of brain tumors. With intraoperative SWE, neurosurgeons may have innovative information to predict diagnosis and guide their resection.

/pdf/in-vivo-measurement-of-brain-tumor-elasticity-using-4uwqr92g41.pdf

In Vivo Measurement of Brain Tumor Elasticity Using Intraoperative Shear Wave Elastography.

Over the last ten years, shear wave elastography (SWE) has seen considerable development and is now routinely used in clinics to provide mechanical characterization of tissues to improve diagnosis. The most advanced technique relies on the use of an ultrafast scanner to generate and image shear waves in real time in a 2-D plane at several thousands of frames per second. We have recently introduced 3-D ultrafast ultrasound imaging to acquire with matrix probes the 3-D propagation of shear waves generated by a dedicated radiation pressure transducer in a single acquisition. In this study, we demonstrate 3-D SWE based on ultrafast volumetric imaging in a clinically applicable configuration. A 32 × 32 matrix phased array driven by a customized, programmable, 1024-channel ultrasound system was designed to perform 4-D shear-wave imaging. A matrix phased array was used to generate and control in 3-D the shear waves inside the medium using the acoustic radiation force. The same matrix array was used with 3-D coherent plane wave compounding to perform high-quality ultrafast imaging of the shear wave propagation. Volumetric ultrafast acquisitions were then beamformed in 3-D using a delay-and-sum algorithm. 3-D volumetric maps of the shear modulus were reconstructed using a time-of-flight algorithm based on local multiscale cross-correlation of shear wave profiles in the three main directions using directional filters. Results are first presented in an isotropic homogeneous and elastic breast phantom. Then, a full 3-D stiffness reconstruction of the breast was performed in vivo on healthy volunteers. This new full 3-D ultrafast ultrasound system paves the way toward real-time 3-D SWE.

4-D ultrafast shear-wave imaging

The functional mapping of brain activity is essential to perform optimal glioma surgery and to minimize the risk of postoperative deficits. We introduce a new, portable neuroimaging modality of the human brain based on functional ultrasound (fUS) for deep functional cortical mapping. Using plane-wave transmissions at an ultrafast frame rate (1 kHz), fUS is performed during surgery to measure transient changes in cerebral blood volume with a high spatiotemporal resolution (250 µm, 1 ms). fUS identifies, maps and differentiates regions of brain activation during task-evoked cortical responses within the depth of a sulcus in both awake and anaesthetized patients.

/pdf/intraoperative-functional-ultrasound-imaging-of-human-brain-3tfomiyaqh.pdf

Marion Imbault

Papers

3D ultrafast ultrasound imaging in vivo.

Robust sound speed estimation for ultrasound-based hepatic steatosis assessment.

In Vivo Measurement of Brain Tumor Elasticity Using Intraoperative Shear Wave Elastography.

4-D ultrafast shear-wave imaging

Intraoperative Functional Ultrasound Imaging of Human Brain Activity.