Uncertainty-weighted Multi-tasking for T1ρ and T2 Mapping in the Liver with Self-supervised Learning.

Multi-parametric mapping of MRI relaxations in liver has the potential of revealing pathological information of the liver. A self-supervised learning based multi-parametric mapping method is proposed to map T1ρ and T2 simultaneously, by utilising the relaxation constraint in the learning process. Data noise of different mapping tasks is utilised to make the model uncertainty-aware, which adaptively weight different mapping tasks during learning. The method was examined on a dataset of 51 patients with non-alcoholic fatter liver disease. Results showed that the proposed method can produce comparable parametric maps to the traditional multi-contrast pixel wise fitting method, with a reduced number of images and less computation time. The uncertainty weighting also improves the model performance. It has the potential of accelerating MRI quantitative imaging.

An uncertainty aided framework for learning based liverT1ρmapping and analysis.

Objective. QuantitativeT1ρimaging has potential for assessment of biochemical alterations of liver pathologies. Deep learning methods have been employed to accelerate quantitativeT1ρimaging. To employ artificial intelligence-based quantitative imaging methods in complicated clinical environment, it is valuable to estimate the uncertainty of the predicatedT1ρvalues to provide the confidence level of the quantification results. The uncertainty should also be utilized to aid the post-hoc quantitative analysis and model learning tasks.Approach. To address this need, we propose a parametric map refinement approach for learning-basedT1ρmapping and train the model in a probabilistic way to model the uncertainty. We also propose to utilize the uncertainty map to spatially weight the training of an improvedT1ρmapping network to further improve the mapping performance and to remove pixels with unreliableT1ρvalues in the region of interest. The framework was tested on a dataset of 51 patients with different liver fibrosis stages.Main results. Our results indicate that the learning-based map refinement method leads to a relative mapping error of less than 3% and provides uncertainty estimation simultaneously. The estimated uncertainty reflects the actual error level, and it can be used to further reduce relativeT1ρmapping error to 2.60% as well as removing unreliable pixels in the region of interest effectively.Significance. Our studies demonstrate the proposed approach has potential to provide a learning-based quantitative MRI system for trustworthyT1ρmapping of the liver.

Uncertainty-aware self-supervised neural network for liverT1ρmapping with relaxation constraint.

Objective.T1ρmapping is a promising quantitative MRI technique for the non-invasive assessment of tissue properties. Learning-based approaches can mapT1ρfrom a reduced number ofT1ρweighted images but requires significant amounts of high-quality training data. Moreover, existing methods do not provide the confidence level of theT1ρestimation. We aim to develop a learning-based liverT1ρmapping approach that can mapT1ρwith a reduced number of images and provide uncertainty estimation.Approach. We proposed a self-supervised neural network that learns aT1ρmapping using the relaxation constraint in the learning process. Epistemic uncertainty and aleatoric uncertainty are modelled for theT1ρquantification network to provide a Bayesian confidence estimation of theT1ρmapping. The uncertainty estimation can also regularize the model to prevent it from learning imperfect data. Main results. We conducted experiments onT1ρdata collected from 52 patients with non-alcoholic fatty liver disease. The results showed that when only collecting twoT1ρ-weighted images, our method outperformed the existing methods forT1ρquantification of the liver. Our uncertainty estimation can further regularize the model to improve the performance of the model and it is consistent with the confidence level of liverT1ρvalues.Significance. Our method demonstrates the potential for accelerating theT1ρmapping of the liver by using a reduced number of images. It simultaneously provides uncertainty ofT1ρquantification which is desirable in clinical applications.

The MicroRNA MiR-29c Alleviates Renal Fibrosis via TPM1-Mediated Suppression of the Wnt/ß-Catenin Pathway.

PURPOSE: This study aimed to evaluate the mechanism by which miR-29c expression in fibroblasts regulates renal interstitial fibrosis. METHODS: We stimulated NRK-49F cells with TGF-ß1 to mimic the effects of fibrosis in vitro, while unilateral ureteral obstruction (UUO) was performed to obstruct the mid-ureter in mice. MiR-29c mimic or miR-29c inhibitor was used to mediate genes expressions in vitro. The recombinant adeno associated virus (rAAV) vectors carrying a FSP1 promoter that encodes miR-29c precursor or miR-29c inhibitor was used to mediate genes expressions in vivo, and a flank incision was made to expose the left kidney of each animal. RESULTS: In the present study, TGF-ß1 was demonstrated to regulate miR-29c expression through Wnt/ß-catenin signaling. In contrast, miR-29c appears to inhibit the Wnt/ß-catenin pathway by suppressing TPM1 expression. As suggested by this feedback mechanism, miR-29c may be a key fibrosis-related microRNA expressed by fibroblasts in TGF-ß1/Wnt/ß-catenin-driven renal fibrosis, and manipulation of miR-29c action may accordingly offer a potential therapeutic pathway for renal fibrosis treatment. CONCLUSION: MiR-29c expression was downregulated in UUO mouse kidneys as well as TGF-ß1-treated NRK-49F cells, which thus inhibits myofibroblast formation via targeting of TPM1. Additionally, the production of extracellular matrix (ECM) in renal fibroblasts appears to be controlled by the reciprocal regulation of miR-29c action and the Wnt/ß-catenin pathway.

A nationwide cross-sectional survey on prevalence, management and pharmacoepidemiology patterns on hypertension in Chinese patients with chronic kidney disease.

Limited data are available on epidemiology and drug use in Chinese hypertensive patients with chronic kidney disease (CKD). We determined the prevalence; awareness, treatment, and control rates of hypertension; anti-hypertensive use, expenditure pattern; and factors associated with hypertension prevalence and control in Chinese patients with CKD. This was one of the largest cross-sectional surveys that enrolled 6079 CKD participants (mean age, 51.0 ± 16.37 years) with or without hypertension from 22 centres across China. The prevalence, awareness, and treatment rates were 71.2%, 95.4%, and 93.7%, respectively. Control rates 1 and 2 (Blood pressure, BP <140/90 and <130/80 mmHg) were 41.1% and 15.0%, respectively. Patients were treated mostly with monotherapy (37.7%) or 2-drug anti-hypertensive combination (38.7%). Factors associated with prevalence of hypertension included age; smoking; body mass index; physical exercise; family history of hypertension; hyperuricaemia; and CKD. Control rate was associated with CKD stage, BP monitoring at home, and use of drug combinations. Despite high rates of awareness and treatment, the control rates are low. CKD stages 4 and 5 adversely affect the control rate. The results suggest the immediate need of comprehensive controlling measures to improve the control of hypertension in Chinese patients with CKD.

Establishment of a rat autogenous arteriovenous fistula model following 5/6 nephrectomy.

The aim of this study was to establish a stable rat model of autogenous arteriovenous fistula (AVF) with chronic renal function insufficiency. Forty Sprague-Dawley rats were randomly divided into an experimental group (n=20) and sham surgery group (n=20) and a 5/6 nephrectomy model was established in the rats. One week later, in the experimental group, the ipsilateral caroid artery was inserted into the external jugular vein by a cuff technique to establish a carotid arteriovenous fistula; in the sham group, the external jugular vein and carotid artery were dissociated. At 7 and 28 days following the establishment of the AVF, the renal functions of the two groups were measured. Hematoxylin and eosin staining and double collagen and elastin staining were conducted to evaluate the area of intimal hyperplasia in the external jugular vein, and the expression of α-smooth muscle actin in the vein was investigated by immunohistochemistry. The creatinine and urea nitrogen levels in the experimental group at each time-point were significantly higher than those in the sham surgery group (P<0.05). The intimal hyperplasia of the external jugular vein of the experimental group was increased significantly compared with that in the sham group at each time-point (P<0.05). The model, which is easy to establish and simple to master, provides a new and feasible experimental method for the study of intimal hyperplasia associated with autogenous AVF in chronic renal insufficiency, and is worthy of wider use.

A microrna screen to identify regulators of peritoneal fibrosis in a rat model of peritoneal dialysis.

BACKGROUND: Peritoneal fibrosis is a common complication in patients treated with long-term peritoneal dialysis. The aim of this study was to identify the microRNAs (miRNAs) involved in regulation of peritoneal fibrosis in a rat model of peritoneal dialysis. METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly allocated into three groups: (i) Control group (Cg, n = 8); (ii) Saline group (Sg, n = 8): daily intraperitoneal injection with 0.9% normal saline; (iii) Hypertonic dialysate group (HDg, n = 8): daily intraperitoneal injection with 4.25% peritoneal dialysis solution. Rats were sacrificed after four weeks for histological evaluation of peritoneal membrane and the expression of α-SMA and COL-1. A miRNA screen was performed using microarray analysis to identify differentially expressed miRNAs, which were then validated by real-time PCR. RESULTS: Compared with the control and the saline groups, hypertonic dialysate group showed impaired peritoneal function accompanied by a spectrum of morphological changes including thicker peritoneal membrane, higher collagen deposition, infiltration of mononuclear cells and neovascularization in the peritoneum. Increased mRNA and protein levels of α-SMA and COL-1 were observed in hypertonic dialysate group, indicating the progression of peritoneal fibrosis. The miRNA screen identified 8 significantly down-regulated miRNAs (miR-31, miR-93, miR-100, miR-152, miR-497, miR-192, miR-194 and miR-200b) and one highly up-regulated miRNA (miR-122) in the hypertonic dialysate group. The results were confirmed by real-time PCR. CONCLUSIONS: Altered miRNA expression in peritoneum was found in the rat model of peritoneal fibrosis, indicating that these miRNAs may be associated with pathogenesis of peritoneal fibrosis.

Sevelamer carbonate lowers serum phosphorus effectively in haemodialysis patients: a randomized, double-blind, placebo-controlled, dose-titration study.

BACKGROUND: Hyperphosphataemia in patients with advanced chronic kidney disease (CKD) is associated with adverse outcomes, including vascular calcification and higher mortality rates. While phosphate lowering is an integral aspect of CKD management, the efficacy and safety of phosphate binders in a contemporary cohort of Chinese haemodialysis patients (who have different genetics and dietary patterns than other populations) has not been previously described. Moreover, sparse data are available on strategies for optimal dose titration when transitioning from a calcium-based to a polymer-based phosphate binder. METHODS: This randomized, double-blind, dose-titration study compared sevelamer carbonate (starting dose 800 mg three times daily) with placebo over 8 weeks' duration in Chinese CKD patients on haemodialysis. Patients were required to be using calcium-based binders prior to study start. RESULTS: In all, 205 patients were randomized (sevelamer, n = 135; placebo, n = 70); mean age was 48.6 years, 61% were male and the mean time on dialysis was 4.4 years. The mean serum phosphorus decreased significantly in patients treated with sevelamer carbonate [change -0.69 ± 0.64 mmol/L (-2.14 ± 1.98 mg/dL)] but remained persistently elevated with placebo [change -0.06 ± 0.57 mmol/L (-0.19 ± 1.76 mg/dL)] (P < 0.0001). When compared with placebo, sevelamer carbonate treatment resulted in statistically significant greater mean reductions from baseline in serum total (-17.1 versus -3.3%) and low-density lipoprotein cholesterol (-33.5 versus-7.6%) (P < 0.0001 for both). Sevelamer carbonate was well tolerated with 96% adherence compared with 97% adherence in the placebo arm. Overall, adverse events experienced by patients in the sevelamer carbonate and placebo treatment groups were similar and consistent with their underlying renal disease. CONCLUSIONS: This study demonstrated that hyperphosphataemia developed quickly following the cessation of phosphate binders and remained persistently elevated in end-stage CKD in the placebo-treated group. Gradually titrating up sevelamer carbonate from an initial dose of 2.4 g/day to an average daily dose of 7.1 ± 2.5 g/day was well tolerated, safe and efficacious in contemporary Chinese haemodialysis patients.

Concise semiquantitative histological scoring system for immunoglobulin A nephropathy.

AIM: Immunoglobulin A nephropathy (IgAN) is a common and progressive glomerulonephritis. Histological lesions of IgAN are variable and considered as a risk factor for renal outcome. Establishing a relatively concise histological semiquantitative scoring system would be valuable in clinical practice. METHODS: Renal biopsy sections of 293 patients with primary IgAN from two centres in China were reviewed. A histological scoring system was established based on multivariate survival analysis of semiquantitative histological indices, using end-stage renal disease (ESRD) as the end-point event. RESULTS: Four indices--extracapillary glomerular activity index (exGAI), mesangial proliferation index (MsI), glomerular chronicity index (GCI) and tubulointerstitial chronicity index (TCI)--independently correlated with ESRD (relative risk (RR) = 1.16, 2.27, 1.29 and 1.80, respectively). The four indices and the sum of their scores (Total I) constituted the scoring system. Patients with exGAI of 4 or more, GCI of 4 or more, MsI of 2 or more and TCI of 2 or more were considered as having a higher risk for progression (P < 0.05). A score of 4 or more on the exGAI index could identify the patients who should be treated with immunosuppressive drugs, which showed a lower incidence of ESRD than that without (24.3% vs 52.4%, P = 0.031). CONCLUSION: It suggested that the present concise scoring system could serve as prognostic and therapeutic indications.