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.

Ultrasound super-resolution imaging with a hierarchical Kalman tracker.

Microbubble (MB) tracking plays an important role in ultrasound super-resolution imaging (SRI) by enabling velocity estimation and improving image quality. This work presents a new hierarchical Kalman (HK) tracker to achieve better performance at scenarios with high concentrations of MBs and high localization uncertainty. The method attempts to follow MBs with different velocity ranges using different Kalman filters. An extended simulation framework for evaluating trackers is also presented and used for comparison of the proposed HK tracker with the nearest-neighbor (NN) and Kalman (K) trackers. The HK tracks were most similar to the ground truth with the highest Jaccard similarity coefficient in 79% of the scenarios and the lowest root-mean-square error in 72% of the scenarios. The HK tracker reconstructed vessels with a more accurate diameter. In a scenario with an uncertainty of 51.2µm in MB localization, a vessel diameter of 250µm was estimated as 257µm by HK tracker, compared with 329µm and 389µm for the K and NN trackers. In the same scenario, the HK tracker estimated MB velocities with a relative bias down to 1.7% and a relative standard deviation down to 8.3%. Finally, the different tracking techniques were applied to in vivo data from rat kidneys, and trends similar to the simulations were observed. Conclusively, the results showed an improvement in tracking performance, when the HK tracker was employed in comparison with the NN and K trackers.

In Vivo Motion Correction in Super-Resolution Imaging of Rat Kidneys.

Super-resolution (SR) imaging has the potential of visualizing the microvasculature down to the 10- [Formula: see text] level, but motion induced by breathing, heartbeats, and muscle contractions are often significantly above this level. This article, therefore, introduces a method for estimating tissue motion and compensating for this. The processing pipeline is described and validated using Field II simulations of an artificial kidney. In vivo measurements were conducted using a modified bk5000 research scanner (BK Medical, Herlev, Denmark) with a BK 9009 linear array probe employing a pulse amplitude modulation scheme. The left kidney of ten Sprague-Dawley rats was scanned during open laparotomy. A 1:10 diluted SonoVue contrast agent (Bracco, Milan, Italy) was injected through a jugular vein catheter at 100 [Formula: see text]/min. Motion was estimated using speckle tracking and decomposed into contributions from the heartbeats, breathing, and residual motion. The estimated peak motions and their precisions were: heart: axial- [Formula: see text] and lateral- [Formula: see text], breathing: axial- [Formula: see text] and lateral- [Formula: see text], and residual: axial-30 [Formula: see text] and lateral-90 [Formula: see text]. The motion corrected microbubble tracks yielded SR images of both bubble density and blood vector velocity. The estimation was, thus, sufficiently precise to correct shifts down to the 10- [Formula: see text] capillary level. Similar results were found in the other kidney measurements with a restoration of resolution for the small vessels demonstrating that motion correction in 2-D can enhance SR imaging quality.

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.

Accuracy and Precision of a Plane Wave Vector Flow Imaging Method in the Healthy Carotid Artery.

The objective of the study described here was to investigate the accuracy and precision of a plane wave 2-D vector flow imaging (VFI) method in laminar and complex blood flow conditions in the healthy carotid artery. The approach was to study (i) the accuracy for complex flow by comparing the velocity field from a computational fluid dynamics (CFD) simulation to VFI estimates obtained from the scan of an anthropomorphic flow phantom and from an in vivo scan; (ii) the accuracy for laminar unidirectional flow in vivo by comparing peak systolic velocities from VFI with magnetic resonance angiography (MRA); (iii) the precision of VFI estimation in vivo at several evaluation points in the vessels. The carotid artery at the bifurcation was scanned using both fast plane wave ultrasound and MRA in 10 healthy volunteers. The MRA geometry acquired from one of the volunteers was used to fabricate an anthropomorphic flow phantom, which was also scanned using the fast plane wave sequence. The same geometry was used in a CFD simulation to calculate the velocity field. Results indicated that similar flow patterns and vortices were estimated with CFD and VFI in the phantom for the carotid bifurcation. The root-mean-square difference between CFD and VFI was within 0.12 m/s for velocity estimates in the common carotid artery and the internal branch. The root-mean-square difference was 0.17 m/s in the external branch. For the 10 volunteers, the mean difference between VFI and MRA was -0.17 m/s for peak systolic velocities of laminar flow in vivo. The precision in vivo was calculated as the mean standard deviation (SD) of estimates aligned to the heart cycle and was highest in the center of the common carotid artery (SD = 3.6% for velocity magnitudes and 4.5° for angles) and lowest in the external branch and for vortices (SD = 10.2% for velocity magnitudes and 39° for angles). The results indicate that plane wave VFI measures flow precisely and that estimates are in good agreement with a CFD simulation and MRA.

Safety Assessment of Advanced Imaging Sequences I: Measurements.

A method for rapid measurement of intensities (I(spta)), mechanical index (MI), and probe surface temperature for any ultrasound scanning sequence is presented. It uses the scanner's sampling capability to give an accurate measurement of the whole imaging sequence for all emissions to yield the true distributions. The method is several orders of magnitude faster than approaches using an oscilloscope, and it also facilitates validating the emitted pressure field and the scanner's emission sequence software. It has been implemented using the experimental synthetic aperture real-time ultrasound system (SARUS) scanner and the Onda AIMS III intensity measurement system (Onda Corporation, Sunnyvale, CA, USA). Four different sequences have been measured: a fixed focus emission, a duplex sequence containing B-mode and flow emissions, a vector flow sequence with B-mode and flow emissions in 17 directions, and finally a SA duplex flow sequence. A BK8820e (BK Medical, Herlev, Denmark) convex array probe is used for the first three sequences and a BK8670 linear array probe for the SA sequence. The method is shown to give the same intensity values within 0.24% of the AIMS III Soniq 5.0 (Onda Corporation, Sunnyvale, CA, USA) commercial intensity measurement program. The approach can measure and store data for a full imaging sequence in 3.8-8.2 s per spatial position. Based on I(spta), MI, and probe surface temperature, the method gives the ability to determine whether a sequence is within U.S. FDA limits, or alternatively indicate how to scale it to be within limits.