Brachial artery vasodilatory response and wall shear rate determined by multi-gate Doppler in a healthy young cohort

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.Wall shear rate (WSR) is an important stimulus for the brachial artery flow-mediated dilation (FMD) response. However, WSR estimation near the arterial wall by conventional Doppler is inherently difficult. To overcome this limitation, we utilised multi-gate Doppler to accurately determine the WSR stimulus near the vessel wall simultaneously with the FMD response using an integrated FMD system [Ultrasound Advanced Open Platform (ULA-OP)]. Using the system, we aimed to perform a detailed analysis of WSR-FMD response and establish novel WSR parameters in a healthy young population. Data from 33 young healthy individuals (27.5±4.9yrs, 19F) were analysed. FMD was assessed with reactive hyperemia using ULA-OP. All acquired raw data were post-processed using custom-designed software to obtain WSR and diameter parameters. The acquired velocity data revealed that non-parabolic flow-profiles within the cardiac cycle and under different flow-states, with heterogeneity between participants. We also identified seven WSR magnitude and four WSR time-course parameters. Among them, WSR area under the curve until its return to baseline was the strongest predictor of the absolute (R2 =0.25) and percentage (R2 =0.31) diameter changes in response to reactive hyperemia. For the first time, we identified mono- and biphasic WSR stimulus patterns within our cohort that produced different magnitudes of FMD response [absolute diameter change: 0.24±0.10mm (monophasic) vs 0.17±0.09mm (biphasic), p<0.05]. We concluded that accurate and detailed measurement of the WSR stimulus is important to comprehensively understand the FMD response and that this advance in current FMD technology could be important to better understand vascular physiology and pathology.This study was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013) for the Innovative Medicine Initiative under grant agreement number IMI/115006 (the SUMMIT consortium), in part by the National Institute of Health Research (NIHR) Exeter Clinical Research Facility, and by the Italian Ministry of University and Research (MIUR, Project PRIN 2010-2011)

High Frame Rate Volumetric Imaging of Microbubbles Using a Sparse Array and Spatial Coherence Beamforming

Volumetric ultrasound imaging of blood flow with microbubbles enables a more complete visualization of the microvasculature. Sparse arrays are ideal candidates to perform volumetric imaging at reduced manufacturing complexity and cable count. However, due to the small number of transducer elements, sparse arrays often come with high clutter levels, especially when wide beams are transmitted to increase the frame rate. In this study, we demonstrate with a prototype sparse array probe and a diverging wave transmission strategy, that a uniform transmission field can be achieved. With the implementation of a spatial coherence beamformer, the background clutter signal can be effectively suppressed, leading to a signal to background ratio improvement of 25 dB. With this approach, we demonstrate the volumetric visualization of single microbubbles in a tissue-mimicking phantom as well as vasculature mapping in a live chicken embryo chorioallantoic membrane

3-D Super-Resolution Ultrasound Imaging with a 2-D Sparse Array

High frame rate 3-D ultrasound imaging technology combined with super-resolution processing method can visualize 3-D microvascular structures by overcoming the diffraction limited resolution in every spatial direction. However, 3-D super-resolution ultrasound imaging using a full 2-D array requires a system with large number of independent channels, the design of which might be impractical due to the high cost, complexity, and volume of data produced. In this study, a 2-D sparse array was designed and fabricated with 512 elements chosen from a density-tapered 2-D spiral layout. High frame rate volumetric imaging was performed using two synchronized ULA-OP 256 research scanners. Volumetric images were constructed by coherently compounding 9-angle plane waves acquired at a pulse repetition frequency of 4500 Hz. Localization-based 3-D super-resolution images of two touching sub-wavelength tubes were generated from 6000 volumes acquired in 12 seconds. In conclusion, this work demonstrates the feasibility of 3-D super-resolution imaging and super-resolved velocity mapping using a customized 2-D sparse array transducer

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe