Ultrasound localization microscopy of the human kidney allograft on a clinical ultrasound scanner.

Chronic kidney disease is a major medical problem, causing more than a million deaths each year worldwide. Peripheral kidney microvascular damage characterizes most chronic kidney diseases, yet noninvasive and quantitative diagnostic tools to measure this are lacking. Ultrasound Localization Microscopy (ULM) can assess tissue microvasculature with unprecedented resolution. Here, we optimized methods on 35 kidney transplants and studied the feasibility of ULM in seven human kidney allografts with a standard low frame rate ultrasound scanner to access microvascular damage. Interlobar, arcuate, cortical radial vessels, and part of the medullary organization were visible on ULM density maps. The medullary vasa recta can be seen but are not as clear as the cortical vessels. Acquisition parameters were derived from Contrast-Enhanced Ultrasound examinations by increasing the duration of the recorded clip at the same plane. ULM images were compared with Color Doppler, Advanced Dynamic Flow, and Superb Microvascular Imaging with a contrast agent. Despite some additional limitations due to movement and saturation artifacts, ULM identified vessels two to four times thinner compared with Doppler modes. The mean ULM smallest analyzable vessel cross section was 0.3 ± 0.2 mm in the seven patients. Additionally, ULM was able to provide quantitative information on blood velocities in the cortical area. Thus, this proof-of-concept study has shown ULM to be a promising imaging technique for qualitative and quantitative microvascular assessment. Imaging native kidneys in patients with kidney diseases will be needed to identify their ULM biomarkers.

Implementation of interprofessional learning activities in a professional practicum: The emerging role of technology.

To prepare future healthcare professionals to collaborate effectively, many universities have developed interprofessional education programs (IPE). Till date, these programs have been mostly courses or clinical simulation experiences. Few attempts have been made to pursue IPE in healthcare clinical settings. This article presents the results of a pilot project in which interprofessional learning activities (ILAs) were implemented during students' professional practicum and discusses the actual and potential use of informatics in the ILA implementation. We conducted a pilot study in four healthcare settings. Our analysis is based on focus group interviews with trainees, clinical supervisors, ILA coordinators, and education managers. Overall, ILAs led to better clarification of roles and understanding of each professional's specific expertise. Informatics was helpful for developing a common language about IPE between trainees and healthcare professionals; opportunities for future application of informatics were noted. Our results support the relevance of ILAs and the value of promoting professional exchanges between students of different professions, both in academia and in the clinical setting. Informatics appears to offer opportunities for networking among students from different professions and for team members' professional development. The use of technology facilitated communication among the participants.

Volumetric ultrasound localization microscopy with diverging cylindrical waves.

Transcranial ultrasound plays a limited role in neuroradiology due to its lack of resolution, planar imaging, and user-dependency. By breaching the diffraction limit using injected microbubbles, volumetric ultrasound localization microscopy (ULM) could help alleviate those issues. However, performing 3D ultrasound imaging at a high frame rate with sufficient signal-to-noise ratio to track individual microbubbles through the skull remains a challenge, especially with a portable scanner. In this study, we describe a ULM sequence suitable for volumetric transcranial imaging exploiting cylindrical emissions on multiplexed matrix probes, through simulations, hydrophone measurements, and flow phantoms. This geometry leads to a doubling of the peak acoustic pressure, up to 400 kPa, with respect to spherical emission and improved volume rate, up to 180 Hz. Cylindrical emissions also improve ULM saturation rate by 60% through a skull phantom. The assessment of microbubble velocity was also improved from 33% error in the average flow measured with spherical waves to a 5% error with cylindrical waves. Conversely, we demonstrate the detrimental impacts of cylindrical waves toward the field of view and isotropic sensitivity. Nevertheless, due to its enhanced signal-to-noise ratio and 3D nature, such a cylindrical volumetric sequence could be beneficial for ULM as a diagnostic tool in humans, especially when portability is a necessity.

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..

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.

Sensing ultrasound localization microscopy for the visualization of glomeruli in living rats and humans.

BACKGROUND: Estimation of glomerular function is necessary to diagnose kidney diseases. However, the study of glomeruli in the clinic is currently done indirectly through urine and blood tests. A recent imaging technique called Ultrasound Localization Microscopy (ULM) has appeared. It is based on the ability to record continuous movements of individual microbubbles in the bloodstream. Although ULM improved the resolution of vascular imaging up to tenfold, the imaging of the smallest vessels had yet to be reported. METHODS: We acquired ultrasound sequences from living humans and rats and then applied filters to divide the data set into slow-moving and fast-moving microbubbles. We performed a double tracking to highlight and characterize populations of microbubbles with singular behaviors. We decided to call this technique "sensing ULM" (sULM). We used post-mortem micro-CT for side-by-side confirmation in rats. FINDINGS: In this study, we report the observation of microbubbles flowing in the glomeruli in living humans and rats. We present a set of analysis tools to extract quantitative information from individual microbubbles, such as remanence time or normalized distance. INTERPRETATION: As glomeruli play a key role in kidney function, it would be possible that their observation yields a deeper understanding of the kidney. It could also be a tool to diagnose kidney diseases in patients. More generally, it will bring imaging capabilities closer to the functional units of organs, which is a key to understand most diseases, such as cancer, diabetes, or kidney failures. FUNDING: This study was funded by the European Research Council under the European Union Horizon H2020 program (ERC Consolidator grant agreement No 772786-ResolveStroke).