Super-Resolution Ultrasound Imaging of Renal Vascular Alterations in Zucker Diabetic Fatty Rats during the Development of Diabetic Kidney Disease.

Individuals with diabetes at risk of developing diabetic kidney disease (DKD) are challenging to identify using currently available clinical methods. Prognostic accuracy and initiation of treatment could be improved by a quantification of the renal microvascular rarefaction and the increased vascular tortuosity during the development of DKD. Super-resolution ultrasound (SRUS) imaging is an in vivo technique capable of visualizing blood vessels at sizes below 75 µm. This preclinical study aimed to investigate the alterations in renal blood vessels' density and tortuosity in a type 2 diabetes rat model, Zucker diabetic fatty (ZDF) rats, as a prediction of DKD. Lean age-matched Zucker rats were used as controls. A total of 36 rats were studied, subdivided into ages of 12, 22, and 40 weeks. Measured albuminuria indicated the early stage of DKD, and the SRUS was compared with the ex vivo micro-computed tomography (µCT) of the same kidneys. Assessed using the SRUS imaging, a significantly decreased cortical vascular density was detected in the ZDF rats from 22 weeks of age compared to the healthy controls, concomitant with a significantly increased albuminuria. Already by week 12, a trend towards a decreased cortical vascular density was found prior to the increased albuminuria. The quantified vascular density in µCT corresponded with the in vivo SRUS imaging, presenting a consistently lower vascular density in the ZDF rats. Regarding vessel tortuosity, an overall trend towards an increased tortuosity was present in the ZDF rats. SRUS shows promise for becoming an additional tool for monitoring and prognosing DKD. In the future, large-scale animal studies and human trials are needed for confirmation.

A hybrid approach to full-scale reconstruction of renal arterial network.

The renal vasculature, acting as a resource distribution network, plays an important role in both the physiology and pathophysiology of the kidney. However, no imaging techniques allow an assessment of the structure and function of the renal vasculature due to limited spatial and temporal resolution. To develop realistic computer simulations of renal function, and to develop new image-based diagnostic methods based on artificial intelligence, it is necessary to have a realistic full-scale model of the renal vasculature. We propose a hybrid framework to build subject-specific models of the renal vascular network by using semi-automated segmentation of large arteries and estimation of cortex area from a micro-CT scan as a starting point, and by adopting the Global Constructive Optimization algorithm for generating smaller vessels. Our results show a close agreement between the reconstructed vasculature and existing anatomical data obtained from a rat kidney with respect to morphometric and hemodynamic parameters.

Diagnostic Considerations of Intermetatarsal Bursitis: A Systematic Review.

Intermetatarsal bursitis (IMB) is an inflammation of the intermetatarsal bursas. The condition causes forefoot pain with symptoms similar to those of Morton's neuroma (MN). Some studies suggest that IMB is a contributing factor to the development of MN, while others describe the condition as a differential diagnosis. Among patients with rheumatic diseases, IMB is frequent, but the scope is yet to be understood. The aim of this paper was to investigate the diagnostic considerations of IMB and its role in metatarsalgia by a systematic review approach. We identified studies about IMB by searching the electronic databases Pubmed, Embase, Cochrane Library, and Web of Science in September 2022. Of 1362 titles, 28 met the inclusion criteria. They were subdivided according to topic: anatomical studies (n = 3), studies of patients with metatarsalgia (n = 10), and studies of patients with rheumatic diseases (n = 15). We conclude that IMB should be considered a cause of pain in patients with metatarsalgia and patients with rheumatic diseases. For patients presenting with spreading toes/V-sign, IMB should be a diagnostic consideration. Future diagnostic studies about MN should take care to apply a protocol that is able to differ IMB from MN, to achieve a better understanding of their respective role in forefoot pain.

Super-Resolution Ultrasound Imaging Provides Quantification of the Renal Cortical and Medullary Vasculature in Obese Zucker Rats: A Pilot Study.

Obesity is a risk factor of chronic kidney disease (CKD), leading to alterations in the renal vascular structure. This study tested if renal vascular density and tortuosity was quantifiable in vivo in obese rats using microbubble-based super-resolution ultrasound imaging. The kidneys of two 11-week-old and two 20-week-old male obese Zucker rats were compared with age-matched male lean Zucker rats. The super-resolution ultrasound images were manually divided into inner medulla, outer medulla, and cortex, and each area was subdivided into arteries and veins. We quantified vascular density and tortuosity, number of detected microbubbles, and generated tracks. For comparison, we assessed glomerular filtration rate, albumin/creatinine ratio, and renal histology to evaluate CKD. The number of detected microbubbles and generated tracks varied between animals and significantly affected quantification of vessel density. In areas with a comparable number of tracks, density increased in the obese animals, concomitant with a decrease in glomerular filtration rate and an increase in albumin/creatinine ratio, but without any pathology in the histological staining. The results indicate that super-resolution ultrasound imaging can be used to quantify structural alterations in the renal vasculature. Techniques to generate more comparable number of microbubble tracks and confirmation of the findings in larger-scale studies are needed.

Super-Resolution Ultrasound Imaging Can Quantify Alterations in Microbubble Velocities in the Renal Vasculature of Rats.

Super-resolution ultrasound imaging, based on the localization and tracking of single intravascular microbubbles, makes it possible to map vessels below 100 µm. Microbubble velocities can be estimated as a surrogate for blood velocity, but their clinical potential is unclear. We investigated if a decrease in microbubble velocity in the arterial and venous beds of the renal cortex, outer medulla, and inner medulla was detectable after intravenous administration of the α1-adrenoceptor antagonist prazosin. The left kidneys of seven rats were scanned with super-resolution ultrasound for 10 min before, during, and after prazosin administration using a bk5000 ultrasound scanner and hockey-stick probe. The super-resolution images were manually segmented, separating cortex, outer medulla, and inner medulla. Microbubble tracks from arteries/arterioles were separated from vein/venule tracks using the arterial blood flow direction. The mean microbubble velocities from each scan were compared. This showed a significant prazosin-induced velocity decrease only in the cortical arteries/arterioles (from 1.59 ± 0.38 to 1.14 ± 0.31 to 1.18 ± 0.33 mm/s, p = 0.013) and outer medulla descending vasa recta (from 0.70 ± 0.05 to 0.66 ± 0.04 to 0.69 ± 0.06 mm/s, p = 0.026). Conclusively, super-resolution ultrasound imaging makes it possible to detect and differentiate microbubble velocity responses to prazosin simultaneously in the renal cortical and medullary vascular beds.

Evaluation of 2D super-resolution ultrasound imaging of the rat renal vasculature using ex vivo micro-computed tomography.

Super-resolution ultrasound imaging (SRUS) enables in vivo microvascular imaging of deeper-lying tissues and organs, such as the kidneys or liver. The technique allows new insights into microvascular anatomy and physiology and the development of disease-related microvascular abnormalities. However, the microvascular anatomy is intricate and challenging to depict with the currently available imaging techniques, and validation of the microvascular structures of deeper-lying organs obtained with SRUS remains difficult. Our study aimed to directly compare the vascular anatomy in two in vivo 2D SRUS images of a Sprague-Dawley rat kidney with ex vivo µCT of the same kidney. Co-registering the SRUS images to the µCT volume revealed visually very similar vascular features of vessels ranging from ~ 100 to 1300 µm in diameter and illustrated a high level of vessel branching complexity captured in the 2D SRUS images. Additionally, it was shown that it is difficult to use µCT data of a whole rat kidney specimen to validate the super-resolution capability of our ultrasound scans, i.e., validating the actual microvasculature of the rat kidney. Lastly, by comparing the two imaging modalities, fundamental challenges for 2D SRUS were demonstrated, including the complexity of projecting a 3D vessel network into 2D. These challenges should be considered when interpreting clinical or preclinical SRUS data in future studies.

Highlights of the development in ultrasound during the last 70 years: A historical review.

This review looks at highlights of the development in ultrasound, ranging from interventional ultrasound and Doppler to the newest techniques like contrast-enhanced ultrasound and elastography, and gives reference to some of the valuable articles in Acta Radiologica. Ultrasound equipment is now available in any size and for any purpose, ranging from handheld devices to high-end devices, and the scientific societies include ultrasound professionals of all disciplines publishing guidelines and recommendations. Interventional ultrasound is expanding the field of use of ultrasound-guided interventions into nearly all specialties of medicine, from ultrasound guidance in minimally invasive robotic procedures to simple ultrasound-guided punctures performed by general practitioners. Each medical specialty is urged to define minimum requirements for equipment, education, training, and maintenance of skills, also for medical students. The clinical application of contrast-enhanced ultrasound and elastography is a topic often seen in current research settings.

Cardiac magnetic resonance imaging with standard imaging planes for mitral valve scallop pathology: interrater agreement and comparison with echocardiography.

Magnetic resonance imaging (CMR) is applied in mitral valve regurgitation (MR) to quantify regurgitation volume/fraction and cardiac volumes, but individual scallop pathology is evaluated by echocardiography. To evaluate CMR for determination of individual scallop pathology, interrater variability on evaluation of scallop pathology from echocardiography and a standard clinical CMR protocol including a transversal stack was compared. 318 mitral scallops from 53 patients with primary MR were evaluated by two cardiologists evaluating echocardiography scans and two other cardiologists evaluating CMR scans (blinded). Inter-rater variability was determined with percentage agreement and Cohen's kappa. In evaluable scallops, interrater agreement on the diagnosis of a prolapsing and/or flail scallop was 77-87% and kappa values of 0.27-0.67, irrespective of physician or modality. Important differences between modalities were primarily related to CMR-evaluators judging the A3 and the P3 to be normal when echocardiography demonstrated prolapsing or even flail scallops; poor imaging of calcification; and flailed scallops occasionally being undetected with CMR since the flow-voids may mask the scallop. Inter-rater agreement for scallop pathology in primary MR is comparable for echocardiography and standard magnetic resonance imaging scans, but CMR has important pitfalls relating to evaluation of A3 and P3 scallops, and suffers from poor visualization of calcification and lower spatial resolution than echo. CMR with standard planes cannot replace CMR with longitudinal planes or echo for the evaluation of specific scallop pathology in severe primary MR.

Super-Resolution Imaging with Ultrasound for Visualization of the Renal Microvasculature in Rats Before and After Renal Ischemia: A Pilot Study.

In vivo monitoring of the microvasculature is relevant since diseases such as diabetes, ischemia, or cancer cause microvascular impairment. Super-resolution ultrasound imaging allows in vivo examination of the microvasculature by detecting and tracking sparsely distributed intravascular microbubbles over a minute-long period. The ability to create detailed images of the renal vasculature of Sprague-Dawley rats using a modified clinical ultrasound platform was investigated in this study. Additionally, we hypothesized that early ischemic damage to the renal microcirculation could be visualized. After a baseline scan of the exposed kidney, 10 rats underwent clamping of the renal vein (n = 5) or artery (n = 5) for 45 min. The kidneys were rescanned at the onset of clamp release and after 60 min of reperfusion. Using a processing pipeline for tissue motion compensation and microbubble tracking, super-resolution images with a very high level of detail were constructed. Image filtration allowed further characterization of the vasculature by isolating specific vessels such as the ascending vasa recta with a 15-20 µm diameter. Using the super-resolution images alone, it was only possible for six assessors to consistently distinguish the healthy renal microvasculature from the microvasculature at the onset of vein clamp release. Future studies will aim at attaining quantitative estimations of alterations in the renal microvascular blood flow using super-resolution ultrasound imaging.