Whole organ volumetric sensing Ultrasound Localization Microscopy for characterization of kidney structure.

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..

RF-ULM: Ultrasound Localization Microscopy Learned from Radio-Frequency Wavefronts.

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.

Visualization of Renal Glomeruli in Human Native Kidneys With Sensing Ultrasound Localization Microscopy.

OBJECTIVES: Kidney diseases significantly impact individuals' quality of life and strongly reduce life expectancy. Glomeruli play a crucial role in kidney function. Current imaging techniques cannot visualize them due to their small size. Sensing ultrasound localization microscopy (sULM) has shown promising results for visualizing in vivo the glomeruli of human kidney grafts. This study aimed to evaluate the ability of sULM to visualize glomeruli in vivo in native human kidneys despite their depth and a shorter duration of ultrasound acquisition limited by the period of the patient's apnea. Sensing ultrasound localization microscopy parameters in native kidneys and kidney grafts and their consequence regarding glomeruli detection were also compared. MATERIALS AND METHODS: Exploration by sULM was conducted in 15 patients with native kidneys and 5 with kidney allografts. Glomeruli were counted using a normalized distance metric projected onto sULM density maps. The difference in the acquisition time, the kidney depth, and the frame rate between native kidneys and kidney grafts and their consequence regarding glomeruli detection were assessed. RESULTS: Glomerular visualization was achieved in 12 of 15 patients with native kidneys. It failed due to impossible breath-holding for 2 patients and a too-deep kidney for 1 patient. Sensing ultrasound localization microscopy found 16 glomeruli per square centimeter in the native kidneys (6-31) and 33 glomeruli per square centimeter in kidney transplant patients (18-55). CONCLUSIONS: This study demonstrated that sULM can visualize glomeruli in native human kidneys in vivo. The proposed method may have many hypothetical applications, including biomarker development, assisting biopsy, or potentially avoiding it. It establishes a framework for improving the detection of local microstructural pathology, influencing the evaluation of allografts, and facilitating disease monitoring in the native kidney.

rtPA-loaded fucoidan polymer microbubbles for the targeted treatment of stroke.

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.

Buckling of lipidic ultrasound contrast agents under quasi-static load.

Collapse of lipidic ultrasound contrast agents under high-frequency compressive load has been historically interpreted by the vanishing of surface tension. By contrast, buckling of elastic shells is known to occur when costly compressible stress is released through bending. Through quasi-static compression experiments on lipidic shells, we analyse the buckling events in the framework of classical elastic buckling theory and deduce the mechanical characteristics of these shells. They are then compared with that obtained through acoustic characterization. This article is part of the theme issue 'Probing and dynamics of shock sensitive shells'.

Spherical oscillations of encapsulated microbubbles: Effect of shell compressibility and anisotropy.

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.