Search

Glomeruli are the filtration units of the kidney and their function relies heavily on their microcirculation. Despite its obvious diagnostic importance, an accurate estimation of blood flow in the capillary bundle within glomeruli defies the resolution of conventional imaging modalities. Ultrasound Localization Microscopy (ULM) has demonstrated its ability to image in-vivo deep organs in the body. Recently, the concept of sensing ULM or sULM was introduced to classify individual microbubble behavior based on the expected physiological conditions at the micrometric scale. In the kidney of both rats and humans, it revealed glomerular structures in 2D but was severely limited by planar projection. In this work, we aim to extend sULM in 3D to image the whole organ and in order to perform an accurate characterization of the entire kidney structure. The extension of sULM into the 3D domain allows better localization and more robust tracking. The 3D metrics of velocity and pathway angular shift made glomerular mask possible. This approach facilitated the quantification of glomerular physiological parameter such as an interior traveled distance of approximately 7.5 ±0.6 microns within the glomerulus. This study introduces a technique that characterize the kidney physiology which can serve as a method to facilite pathology assessment. Furthermore, its potential for clinical relevance could serve as a bridge between research and practical application, leading to innovative diagnostics and improved patient care.

Super-resolution ultrasound (SRUS) has evolved significantly with the advent of Ultrasound Localization Microscopy (ULM). This technique enables sub-wavelength resolution imaging using microbubble contrast agents. Initially confined to 2D imaging, ULM has progressed towards volumetric approaches, allowing for comprehensive three-dimensional visualization of microvascular networks. This review explores the technological advancements and challenges associated with volumetric ULM, focusing on key aspects such as transducer design, acquisition speed, data processing algorithms, or integration into clinical practice. We discuss the limitations of traditional 2D ULM, including dependency on precise imaging plane selection and compromised resolution in microvasculature quantification. In contrast, volumetric ULM offers enhanced spatial resolution and allowed motion correction in all direction, promising transformative insights into microvascular pathophysiology. By examining current research and future directions, this review highlights the potential of volumetric ULM to contribute significantly to diagnostic across various medical conditions, including cancers, arteriosclerosis, strokes, diabetes, and neurodegenerative diseases.

In Ultrasound Localization Microscopy (ULM), achieving high-resolution images relies on the precise localization of contrast agent particles across a series of beamformed frames. However, our study uncovers an enormous potential: The process of delay-and-sum beamforming leads to an irreversible reduction of Radio-Frequency (RF) channel data, while its implications for localization remain largely unexplored. The rich contextual information embedded within RF wavefronts, including their hyperbolic shape and phase, offers great promise for guiding Deep Neural Networks (DNNs) in challenging localization scenarios. To fully exploit this data, we propose to directly localize scatterers in RF channel data. Our approach involves a custom super-resolution DNN using learned feature channel shuffling, non-maximum suppression, and a semi-global convolutional block for reliable and accurate wavefront localization. Additionally, we introduce a geometric point transformation that facilitates seamless mapping to the B-mode coordinate space. To understand the impact of beamforming on ULM, we validate the effectiveness of our method by conducting an extensive comparison with State-Of-The-Art (SOTA) techniques. We present the inaugural in vivo results from a wavefront-localizing DNN, highlighting its real-world practicality. Our findings show that RF-ULM bridges the domain shift between synthetic and real datasets, offering a considerable advantage in terms of precision and complexity. To enable the broader research community to benefit from our findings, our code and the associated SOTA methods are made available at https://github.com/hahnec/rf-ulm.

Systemic injection of thrombolytic drugs is the gold standard treatment for non-invasive blood clot resolution. The most serious risks associated with the intravenous injection of tissue plasminogen activator-like proteins are the bleeding complication and the dose related neurotoxicity. Indeed, the drug has to be injected in high concentrations due to its short half-life, the presence of its natural blood inhibitor (PAI-1) and the fast hepatic clearance (0.9 mg/kg in humans, 10 mg/kg in mouse models). Overall, there is a serious need for a dose-reduced targeted treatment to overcome these issues. We present in this article a new acoustic cavitation-based method for polymer MBs synthesis, three times faster than current hydrodynamic-cavitation method. The generated MBs are ultrasound responsive, stable and biocompatible. Their functionalization enabled the efficient and targeted treatment of stroke, without side effects. The stabilizing shell of the MBs is composed of Poly-Isobutyl Cyanoacrylate (PIBCA), copolymerized with fucoidan. Widely studied for its targeting properties, fucoidan exhibit a nanomolar affinity for activated endothelium and activated platelets (P-selectins). Secondly, the thrombolytic agent (rtPA) was loaded onto microbubbles (MBs) with a simple adsorption protocol. Hence, the present study validated the in vivo efficiency of rtPA-loaded Fuco MBs to be over 50 % more efficient than regular free rtPA injection for stroke resolution. In addition, the relative injected rtPA grafted onto targeting MBs was 1/10th of the standard effective dose (1 mg/kg in mouse). As a result, no hemorrhagic event, BBB leakage nor unexpected tissue distribution were observed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cedric CHAUVIERRE reports financial support was provided by French National Research Agency. Olivier COUTURE reports a relationship with Resolve Stroke company that includes: board membership. Cedric CHAUVIERRE has patent pending to INSERM Transfert. Louise FOURNIER has patent pending to INSERM Transfert., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We introduce a model that describes spherical oscillations of encapsulated microbubbles in an unbounded surrounding fluid. A Rayleigh-Plesset-like equation is derived by coupling the Navier-Stokes equation that describes fluid dynamics with the Navier equation that describes solid dynamics via the internal/external boundary conditions. While previous models were restricted to incompressible isotropic shells, the solid shell is modeled here as a compressible viscoelastic isotropic material and then generalized to an anisotropic material. The exact value of the resonance frequency is calculated analytically, and the damping constant is computed in the approximation of weak damping. A correction of the widely used Church model for incompressible shells is evidenced, and the effects of shell compressibility and anisotropy are discussed.