Jennings Holck (yogurtweapon4)
The use of animal models to predict the response to new therapies in humans is a vexing issue in nephrology. Unlike patients with chronic kidney disease (CKD), few rodent models develop a progressive decline in glomerular filtration rate (GFR) so that experimental studies frequently report a reduction in proteinuria as the primary efficacy outcome. Moreover, while humans present with established kidney disease that continues to progress, many experimental studies investigate therapies in the prevention rather than in a therapeutic setting. We used the remnant kidney (subtotal nephrectomy [SNX]) rat model that develops a decline in GFR in conjunction with heavy proteinuria and hypertension along with the histological hallmarks of CKD in humans, glomerulosclerosis and tubulointerstitial fibrosis. Using agents that had been shown to improve GFR as well as proteinuria in the prevention setting, angiotensin-converting enzyme (ACE) inhibition with enalapril and SIRT1 activation with SRT3025, treatment was initiated 6 weeks after SNX. While enalapril reduced blood pressure, proteinuria and histological injury, it did not improve GFR, as measured by inulin clearance. SRT3025 improved neither GFR nor structural damage despite a reduction in proteinuria. These findings demonstrate that neither a reduction in proteinuria nor a reversal of structural damage in the kidney will necessarily translate to a restoration of kidney function. These findings demonstrate that neither a reduction in proteinuria nor a reversal of structural damage in the kidney will necessarily translate to a restoration of kidney function. The aim of this work is to shed light on the issue of reproducibility in MR image reconstruction in the context of a challenge. Participants had to recreate the results of "Advances in sensitivity encoding with arbitrary k-space trajectories" by Pruessmann et al. METHODS The task of the challenge was to reconstruct radially acquired multicoil k-space data (brain/heart) following the method in the original paper, reproducing its key figures. Results were compared to consolidated reference implementations created after the challenge, accounting for the two most common programming languages used in the submissions (Matlab/Python). Visually, differences between submissions were small. Pixel-wise differences originated from image orientation, assumed field-of-view, or resolution. The reference implementations were in good agreement, both visually and in terms of image similarity metrics. While the description level of the published algorithm enabled participants to reproduce CG-SENSE in general, details of tt the data lead to further differences, emphasizing the importance of sufficient metadata accompanying open datasets. Defining reproducibility quantitatively turned out to be nontrivial for this image reconstruction challenge, in the absence of ground-truth results. Typical similarity measures like NMSE of SSIM were misled by image intensity scaling and outlier pixels. Thus, to facilitate reproducibility, researchers are encouraged to publish code and data alongside the original paper. Future methodological papers on MR image reconstruction might benefit from the consolidated reference implementations of CG-SENSE presented here, as a benchmark for methods comparison. The purpose of this study was to investigate hyperpolarization and in vivo imaging of [ N]carnitine, a novel endogenous MRI probe with long signal lifetime. L-[ N]carnitine-d was hyperpolarized by the method of dynamic nuclear polarization followed by rapid dissolution. The T signal lifetimes were estimated in aqueous solution and in vivo following intravenous injection in rats, using a custom-built dual-tuned N/ H RF coil at 4.7 T. Tetramisole N chemical shift imaging and N fast spin-echo images of rat abdomen were acquired 3 mi