Filter and export

Publications

What is a Publication?
377 Publications visible to you, out of a total of 377
PK-DB: PharmacoKinetics DataBase for Individualized and Stratified Computational Modeling

Abstract (Expand)

A multitude of pharmacokinetics studies have been published. However, due to the lack of an open database, pharmacokinetics data, as well as the corresponding meta-information, have been difficult to … access. We present PK-DB (https://pk-db.com), an open database for pharmacokinetics information from clinical trials including pre-clinical research. PK-DB provides curated information on (i) characteristics of studied patient cohorts and subjects (e.g. age, bodyweight, smoking status); (ii) applied interventions (e.g. dosing, substance, route of application); (iii) measured pharmacokinetic time-courses; (iv) pharmacokinetic parameters (e.g. clearance, half-life, area under the curve). Key features are the representation of experimental errors, the normalization of measurement units, annotation of information to biological ontologies, calculation of pharmacokinetic parameters from concentration-time profiles, a workflow for collaborative data curation, strong validation rules on the data, computational access via a REST API as well as human access via a web interface. PK-DB enables meta-analysis based on data from multiple studies and data integration with computational models. A special focus lies on meta-data relevant for individualized and stratified computational modeling with methods like physiologically based pharmacokinetic (PBPK), pharmacokinetic/pharmacodynamic (PK/DB), or population pharmacokinetic (pop PK) modeling.

Authors: Jan Grzegorzewski, Janosch Brandhorst, Dimitra Eleftheriadou, Kathleen Green, Matthias König

Date Published: 9th Sep 2019

Publication Type: Unpublished

Transfer of regulatory knowledge from human to mouse for functional genomics analysis

Abstract (Expand)

Transcriptome profiling followed by differential gene expression analysis often leads to lists of genes that are hard to analyze and interpret. Functional genomics tools are powerful approaches for … downstream analysis, as they summarize the large and noisy gene expression space into a smaller number of biological meaningful features. In particular, methods that estimate the activity of processes by mapping transcripts level to process members are popular. However, footprints of either a pathway or transcription factor (TF) on gene expression show superior performance over mapping-based gene sets. These footprints are largely developed for humans and their usability in the broadly-used model organism Mus musculus is uncertain. Evolutionary conservation of the gene regulatory system suggests that footprints of human pathways and TFs can functionally characterize mice data. In this paper we analyze this hypothesis. We perform a comprehensive benchmark study exploiting two state-of-the-art footprint methods, DoRothEA and an extended version of PROGENy. These methods infer TF and pathway activity, respectively. Our results show that both can recover mouse perturbations, confirming our hypothesis that footprints are conserved between mice and humans. Subsequently, we illustrate the usability of PROGENy and DoRothEA by recovering pathway/TF-disease associations from newly generated disease sets. Additionally, we provide pathway and TF activity scores for a large collection of human and mouse perturbation and disease experiments (2374). We believe that this resource, available for interactive exploration and download (https://saezlab.shinyapps.io/footprint_scores/), can have broad applications including the study of diseases and therapeutics.

Authors: Christian H. Holland, Bence Szalai, Julio Saez-Rodriguez

Date Published: 1st Sep 2019

Publication Type: Not specified

Prediction of Multiple 3D Tissue Structures Based on Single-Marker Images Using Convolutional Neural Networks

Abstract (Expand)

A quantitative understanding of complex biological systems such as tissues requires reconstructing the structure of the different components of the system. Fluorescence microscopy provides the means … to visualize simultaneously several tissue components. However, it can be time consuming and is limited by the number of fluorescent markers that can be used. In this study, we describe a toolbox of algorithms based on convolutional neural networks for the prediction of 3D tissue structures by learning features embedded within single-marker images. As proof of principle, we aimed to predict the network of bile canaliculi (BC) in liver tissue using images of the cortical actin mesh as input. The actin meshwork has a characteristic organization in specific cellular domains, such as BC. However, the use of manually selected features from images of actin is not sufficient to properly reconstruct BC structure. Our deep learning framework showed a remarkable accuracy for the prediction of BC network and was successfully adapted (i.e. transfer learning) to predict the sinusoidal network. This approach allows for a complete reconstruction of tissue microarchitecture using a single fluorescent marker.

Authors: Hernan Morales-Navarrete, Fabian Segovia-Miranda, Marino Zerial, Yannis Kalaidzidis

Date Published: 1st Sep 2019

Publication Type: InProceedings

Transient elastography for screening of liver fibrosis: Cost-effectiveness analysis from six prospective cohorts in Europe and Asia.

Abstract (Expand)

BACKGROUND & AIMS: Non-alcoholic fatty liver disease and alcohol-related liver disease pose an important challenge to current clinical healthcare pathways because of the large number of at-risk … patients. Therefore, we aimed to explore the cost-effectiveness of transient elastography (TE) as a screening method to detect liver fibrosis in a primary care pathway. METHODS: Cost-effectiveness analysis was performed using real-life individual patient data from 6 independent prospective cohorts (5 from Europe and 1 from Asia). A diagnostic algorithm with conditional inference trees was developed to explore the relationships between liver stiffness, socio-demographics, comorbidities, and hepatic fibrosis, the latter assessed by fibrosis scores (FIB-4, NFS) and liver biopsies in a subset of 352 patients. We compared the incremental cost-effectiveness of a screening strategy against standard of care alongside the numbers needed to screen to diagnose a patient with fibrosis stage >/=F2. RESULTS: The data set encompassed 6,295 participants (mean age 55+/-12years, BMI 27+/-5kg/m(2), liver stiffness 5.6+/-5.0kPa). A 9.1kPa TE cut-off provided the best accuracy for the diagnosis of significant fibrosis (>/=F2) in general population settings, whereas a threshold of 9.5kPa was optimal for populations at-risk of alcohol-related liver disease. TE with the proposed cut-offs outperformed fibrosis scores in terms of accuracy. Screening with TE was cost-effective with mean incremental cost-effectiveness ratios ranging from 2,570 euro/QALY (95% CI 2,456-2,683) for a population at-risk of alcohol-related liver disease (age >/=45years) to 6,217 euro/QALY (95% CI 5,832-6,601) in the general population. Overall, there was a 12% chance of TE screening being cost saving across countries and populations. CONCLUSIONS: Screening for liver fibrosis with TE in primary care is a cost-effective intervention for European and Asian populations and may even be cost saving. LAY SUMMARY: The lack of optimized public health screening strategies for the detection of liver fibrosis in adults without known liver disease presents a major healthcare challenge. Analyses from 6 independent international cohorts, with transient elastography measurements, show that a community-based risk-stratification strategy for alcohol-related and non-alcoholic fatty liver diseases is cost-effective and potentially cost saving for our healthcare systems, as it leads to earlier identification of patients.

Authors: M. Serra-Burriel, I. Graupera, P. Toran, M. Thiele, D. Roulot, V. Wai-Sun Wong, I. Neil Guha, N. Fabrellas, A. Arslanow, C. Exposito, R. Hernandez, G. Lai-Hung Wong, D. Harman, S. Darwish Murad, A. Krag, G. Pera, P. Angeli, P. Galle, G. P. Aithal, L. Caballeria, L. Castera, P. Gines, F. Lammert

Date Published: 31st Aug 2019

Publication Type: Not specified

Tomoelastography for non-invasive detection and treatment monitoring in acute appendicitis.

Abstract (Expand)

Acute appendicitis is the most common cause of the acute abdomen syndrome and can be treated either surgically or conservatively with antibiotics. This case demonstrates the first time use of mechanics … based MRI by tomoelastography with generation of quantitative maps of tissue stiffness (shear wave speed in m/s) and tissue fluidity (shear modulus loss angle, in rad) in a case of uncomplicated acute appendicitis with antibiotic treatment at (i) baseline, (ii) the end of treatment (EOT) and (iii) the 10 day follow-up after EOT. Baseline maps of stiffness and fluidity revealed to the naked eye the extent of intestinal inflammation by markedly increased values of stiffness and fluidity (2.56+/-0.12 m/s, 1.37+/-0.24 rad) compared with normal values, indicating the immediate response to antibiotic treatment at EOT (1.47+/-0.28 m/s, 0.80+/-0.11 rad) and persistent normalisation at follow-up (1.54+/-0.22 m/s, 0.92+/-0.22 rad). Tomoelastography is a non-invasive, quantitative imaging method for mechanics based characterisation and follow-up of acute appendicitis.

Authors: S. R. Marticorena Garcia, B. Hamm, I. Sack

Date Published: 26th Aug 2019

Publication Type: Not specified

Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin.

Abstract (Expand)

PURPOSE: Evaluation of [(68)Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity. PROCEDURES: Tracer specificity … of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [(68)Ga]NODAGA-duramycin. In vivo data were validated by immunohistology and blood parameters. RESULTS: In vitro experiments confirmed specific binding of [(68)Ga]NODAGA-duramycin. Organ toxicities were detected successfully using [(68)Ga]NODAGA-duramycin PET/X-ray computed tomography (CT) and confirmed by immunohistochemistry and blood parameter analysis. Organ toxicities in livers and kidneys showed similar trends in PET/CT and immunohistology. Busulfan and cisplatin-related organ toxicities in heart, liver, and lungs were detected earlier by PET/CT than by blood parameters and immunohistology. CONCLUSION: [(68)Ga]NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice. It, therefore, represents a promising alternative to standard toxicological analyses with a high translational potential.

Authors: A. Rix, N. I. Drude, A. Mrugalla, F. Baskaya, K. Y. Pak, B. Gray, H. J. Kaiser, R. H. Tolba, E. Fiegle, W. Lederle, F. M. Mottaghy, F. Kiessling

Date Published: 8th Aug 2019

Publication Type: Not specified

Benchmark and integration of resources for the estimation of human transcription factor activities

Abstract (Expand)

The prediction of transcription factor (TF) activities from the gene expression of their targets (i.e., TF regulon) is becoming a widely used approach to characterize the functional status of transcriptional … regulatory circuits. Several strategies and data sets have been proposed to link the target genes likely regulated by a TF, each one providing a different level of evidence. The most established ones are (1) manually curated repositories, (2) interactions derived from ChIP-seq binding data, (3) in silico prediction of TF binding on gene promoters, and (4) reverse-engineered regulons from large gene expression data sets. However, it is not known how these different sources of regulons affect the TF activity estimations and, thereby, downstream analysis and interpretation. Here we compared the accuracy and biases of these strategies to define human TF regulons by means of their ability to predict changes in TF activities in three reference benchmark data sets. We assembled a collection of TF–target interactions for 1541 human TFs and evaluated how different molecular and regulatory properties of the TFs, such as the DNA-binding domain, specificities, or mode of interaction with the chromatin, affect the predictions of TF activity. We assessed their coverage and found little overlap on the regulons derived from each strategy and better performance by literature-curated information followed by ChIP-seq data. We provide an integrated resource of all TF–target interactions derived through these strategies, with confidence scores, as a resource for enhanced prediction of TF activities.

Authors: Luz Garcia-Alonso, Christian H. Holland, Mahmoud M. Ibrahim, Denes Turei, Julio Saez-Rodriguez

Date Published: 1st Aug 2019

Publication Type: Not specified

Genetic Variants in the Promoter Region of the Macrophage Migration Inhibitory Factor are Associated with the Severity of Hepatitis C Virus-Induced Liver Fibrosis.

Abstract (Expand)

Two polymorphisms in the promoter region of macrophage migration inhibitory factor (MIF) - rs755622 and rs5844572 - exhibit prognostic relevance in inflammatory diseases. The aim of this study was to … investigate a correlation between these MIF promoter polymorphisms and the severity of hepatitis C virus (HCV)-induced liver fibrosis. Our analysis included two independent patient cohorts with HCV-induced liver fibrosis (504 and 443 patients, respectively). The genotype of the single nucleotide polymorphism (SNP) -173 G/C and the repeat number of the microsatellite polymorphism -794 CATT5-8 were determined in DNA samples and correlated with fibrosis severity. In the first cohort, homozygous carriers of the C allele in the rs755622 had lower fibrosis stages compared to heterozygous carriers or wild types (1.25 vs. 2.0 vs. 2.0; p = 0.03). Additionally, >/=7 microsatellite repeats were associated with lower fibrosis stages (<F2) (p = 0.04). Comparable tendencies were observed in the second independent cohort, where fibrosis was assessed using transient elastography. However, once cirrhosis had been established, the C/C genotype and higher microsatellite repeats correlated with impaired liver function and a higher prevalence of hepatocellular carcinoma. Our study demonstrates that specific MIF polymorphisms are associated with disease severity and complications of HCV-induced fibrosis in a stage- and context-dependent manner.

Authors: T. H. Wirtz, P. Fischer, C. Backhaus, I. Bergmann, E. F. Brandt, D. Heinrichs, M. T. Koenen, K. M. Schneider, T. Eggermann, I. Kurth, C. Stoppe, J. Bernhagen, T. Bruns, J. Fischer, T. Berg, C. Trautwein, M. L. Berres

Date Published: 31st Jul 2019

Publication Type: Journal

Genetic Variants in the Promoter Region of the Macrophage Migration Inhibitory Factor are Associated with the Severity of Hepatitis C Virus-Induced Liver Fibrosis.

Abstract (Expand)

Two polymorphisms in the promoter region of macrophage migration inhibitory factor (MIF) - rs755622 and rs5844572 - exhibit prognostic relevance in inflammatory diseases. The aim of this study was to … investigate a correlation between these MIF promoter polymorphisms and the severity of hepatitis C virus (HCV)-induced liver fibrosis. Our analysis included two independent patient cohorts with HCV-induced liver fibrosis (504 and 443 patients, respectively). The genotype of the single nucleotide polymorphism (SNP) -173 G/C and the repeat number of the microsatellite polymorphism -794 CATT5-8 were determined in DNA samples and correlated with fibrosis severity. In the first cohort, homozygous carriers of the C allele in the rs755622 had lower fibrosis stages compared to heterozygous carriers or wild types (1.25 vs. 2.0 vs. 2.0; p = 0.03). Additionally, >/=7 microsatellite repeats were associated with lower fibrosis stages (<F2) (p = 0.04). Comparable tendencies were observed in the second independent cohort, where fibrosis was assessed using transient elastography. However, once cirrhosis had been established, the C/C genotype and higher microsatellite repeats correlated with impaired liver function and a higher prevalence of hepatocellular carcinoma. Our study demonstrates that specific MIF polymorphisms are associated with disease severity and complications of HCV-induced fibrosis in a stage- and context-dependent manner.

Authors: T. H. Wirtz, P. Fischer, C. Backhaus, I. Bergmann, E. F. Brandt, D. Heinrichs, M. T. Koenen, K. M. Schneider, T. Eggermann, I. Kurth, C. Stoppe, J. Bernhagen, T. Bruns, J. Fischer, T. Berg, C. Trautwein, M. L. Berres

Date Published: 31st Jul 2019

Publication Type: Journal

Cooperative and distinct functions of MK2 and MK3 in the regulation of the macrophage transcriptional response to lipopolysaccharide.

Abstract (Expand)

The p38(MAPK) downstream targets MAPKAP kinases (MK) 2 and 3 are critical for the regulation of the macrophage response to LPS. The extents to which these two kinases act cooperatively and distinctly … in regulating LPS-induced inflammatory cytokine expression are still unclear. To address this uncertainty, whole transcriptome analyses were performed using bone marrow-derived macrophages (BMDM) generated from MK2(-/-) or MK2/3(-/-) animals and their wild-type littermates. The results suggest that in BMDM, MK2 and MK3 not only cooperatively regulate the transcript expression of signaling intermediates, including IL-10, IL-19, CXCL2 and the IL-4 receptor (IL-4R)alpha subunit, they also exert distinct regulatory effects on the expression of specific transcripts. Based on the differential regulation of gene expression by MK2 and MK3, at least six regulatory patterns were identified. Importantly, we confirmed our previous finding, which showed that in the absence of MK2, MK3 negatively regulates IFN-beta. Moreover, this genome-wide analysis identified the regulation of Cr1A, NOD1 and Serpina3f as similar to that of IFN-beta. In the absence of MK2, MK3 also delayed the nuclear translocation of NFkappaB by delaying the ubiquitination and subsequent degradation of IkappaBbeta, reflecting the substantial plasticity of the response of BMDM to LPS.

Authors: C. Ehlting, J. Rex, U. Albrecht, R. Deenen, C. Tiedje, K. Kohrer, O. Sawodny, M. Gaestel, D. Haussinger, J. G. Bode

Date Published: 30th Jul 2019

Publication Type: Not specified

ECM1 Prevents Activation of Transforming Growth Factor beta, Hepatic Stellate Cells, and Fibrogenesis in Mice.

Abstract (Expand)

BACKGROUND & AIMS: Activation of transforming growth factor beta (TGFB) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanism of TGFB activation are not clear. We … investigated the role of extracellular matrix protein 1 (ECM1), which interacts with extracellular and structural proteins, in TGFB activation in livers of mice. METHODS: We performed studies with e C57BL/6J mice (controls), ECM1-knockout (ECM1-KO) mice, and mice with hepatocyte-specific knockout of EMC1 (ECM1Deltahep). ECM1 or soluble TGFB receptor 2 (TGFBR2) were expressed in livers of mice following injection of an adeno-associated virus vector. Liver fibrosis was induced by carbon tetrachloride (CCl4) administration. Livers were collected from mice and analyzed by histology, immunohistochemistry, in situ hybridization, and immunofluorescence analyses. Hepatocytes and HSCs were isolated from livers of mice and incubated with ECM1; production of cytokines and activation of reporter genes were quantified. Liver tissues from patients with viral or alcohol-induced hepatitis (with different stages of fibrosis) and individuals with healthy liver were analyzed by immunohistochemistry and in situ hybridization. RESULTS: ECM1-KO mice spontaneously developed liver fibrosis and died by 2 months of age without significant hepatocyte damage or inflammation. In liver tissues of mice, we found that ECM1 stabilized extracellular matrix-deposited TGFB in its inactive form by interacting with alphav integrins to prevent activation of HSCs. In liver tissues from patients and in mice with CCl4-induced liver fibrosis, we found an inverse correlation between level of ECM1 and severity of fibrosis. CCl4-induced liver fibrosis was accelerated in ECM1Deltahep mice compared with control mice. Hepatocytes produced the highest levels of ECM1 in livers of mice. Ectopic expression of ECM1 or soluble TGFBR2 in liver prevented fibrogenesis in ECM1-KO mice and prolonged their survival. Ectopic expression of ECM1 in liver also reduced the severity of CCl4-induced fibrosis in mice. CONCLUSIONS: ECM1, produced by hepatocytes, inhibits activation of TGFB and its activation of HSCs to prevent fibrogenesis in mouse liver. Strategies to increase levels of ECM1 in liver might be developed for treatment of fibrosis.

Authors: W. Fan, T. Liu, W. Chen, S. Hammad, T. Longerich, Y. Fu, N. Li, Y. He, C. Liu, Y. Zhang, Q. Lian, X. Zhao, C. Yan, L. Li, C. Yi, Z. Ling, L. Ma, X. Zhao, H. Xu, P. Wang, M. Cong, H. You, Z. Liu, Y. Wang, J. Chen, D. Li, L. Hui, S. Dooley, J. Hou, J. Jia, B. Sun

Date Published: 27th Jul 2019

Publication Type: Not specified

Adenovirusmediated overexpression of bone morphogenetic protein9 promotes methionine choline deficiencyinduced nonalcoholic steatohepatitis in nonobese mice.

Abstract (Expand)

Liver inflammation and macrophage infiltration are critical steps in the progression of nonalcoholic fatty liver to the development of nonalcoholic steatohepatitis. Bone morphogenetic protein9 is a … cytokine involved in the regulation of chemokines and lipogenesis. However, the function of bone morphogenetic protein9 in nonalcoholic steatohepatitis is still unknown. The present study hypothesized that bone morphogenetic protein9 may contribute to steatohepatitis in mice fed a methionine choline deficiency diet (MCD). C57BL/6 mice overexpressing bone morphogenetic protein9 and control mice were fed the MCD diet for 4 weeks. Liver tissue and serum samples were obtained for subsequent measurements. Bone morphogenetic protein9 overexpression exacerbated steatohepatitis in mice on the MCD diet, as indicated by liver histopathology, increased serum alanine aminotransferase activity, aspartate transaminase activity, hepatic inflammatory gene expression and M1 macrophage recruitment. Although bone morphogenetic protein9 overexpression did not affect the expression of profibrogenic genes, including Collagen I (alpha)1 or matrix metalloproteinase (MMP) 9, it did upregulate the expression of transforming growth factorbeta and plasminogen activator inhibitor 1, and downregulated the expression of MMP2. The above results indicate that bone morphogenetic protein9 exerts a proinflammatory role in MCD dietinduced nonalcoholic steatohepatitis.

Authors: Q. Li, B. Liu, K. Breitkopf-Heinlein, H. Weng, Q. Jiang, P. Dong, S. Dooley, K. Xu, H. Ding

Date Published: 20th Jul 2019

Publication Type: Not specified

US Time-Harmonic Elastography for the Early Detection of Glomerulonephritis.

Abstract (Expand)

Background Glomerulonephritis refers to renal diseases characterized by glomerular and tubulointerstitial fibrosis. Multifrequency US time-harmonic elastography enables the noninvasive quantification … of tissue elasticity. Purpose To assess the diagnostic performance of US time-harmonic elastography for the early detection of glomerulonephritis. Materials and Methods From August 2016 through May 2017, study participants with biopsy-proven glomerulonephritis were prospectively examined with US time-harmonic elastography. Participants were subdivided according to chronic kidney disease (CKD) stage. All participants underwent elastography of both kidneys to generate full-field-of-view maps of renal shear wave speed (SWS). SWS was determined separately for the whole renal parenchyma, cortex, and medulla and was correlated with quantitative B-mode findings such as renal length and parenchymal thickness. Diagnostic performance of renal elastography was assessed with receiver operating characteristic curve analysis. Results Fifty-three participants with glomerulonephritis (mean age +/- standard deviation, 49 years +/- 14) and 30 healthy volunteers (mean age, 37 years +/- 11) were evaluated. Age-adjusted renal SWS was lower in participants with glomerulonephritis than in healthy volunteers in the parenchyma, cortex, and medulla, with mean values of 1.55 m/sec (95% confidence interval [CI]: 1.51 m/sec, 1.59 m/sec) and 1.69 m/sec (95% CI: 1.64 m/sec, 1.74 m/sec; P < .001), respectively, in parenchyma, 1.80 m/sec (95% CI: 1.75 m/sec, 1.84 m/sec) and 2.08 m/sec (95% CI: 2.02 m/sec, 2.13 m/sec; P < .001) in cortex, and 1.25 m/sec (95% CI: 1.21 m/sec, 1.29 m/sec) and 1.33 (95% CI: 1.27 m/sec, 1.38 m/sec; P = .03) in medulla. Age-adjusted renal cortex SWS was lower in participants with glomerulonephritis and stage 1 CKD (preserved renal function) than in healthy volunteers (mean, 1.88 [95% CI: 1.81, 1.96] vs 2.08 [95% CI: 2.02, 2.13]; P < .001). In participants with CKD, renal cortex SWS values showed a positive association with estimated glomerular filtration rate (n = 39; r = 0.56; P < .001). Exploratory diagnostic performance of US time-harmonic elastography (area under the receiver operating characteristic curve [AUC], 0.89; 95% CI: 0.82, 0.97) outperformed that of B-mode parameters such as parenchymal thickness (AUC, 0.64; 95% CI: 0.51, 0.77; P < .001) and renal length (AUC, 0.55; 95% CI: 0.40, 0.68; P < .001) in identifying glomerulonephritis. Conclusion US time-harmonic elastography depicts abnormal renal stiffness in glomerulonephritis, particularly among patients with early disease and preserved renal function. Advanced chronic kidney disease is associated with further cortical softening. Time-harmonic elastography outperforms B-mode-based size quantification. (c) RSNA, 2019 Online supplemental material is available for this article.

Authors: M. Grossmann, H. Tzschatzsch, S. T. Lang, J. Guo, A. Bruns, M. Durr, B. F. Hoyer, U. Grittner, M. Lerchbaumer, M. Nguyen Trong, M. Schultz, B. Hamm, J. Braun, I. Sack, S. R. Marticorena Garcia

Date Published: 10th Jul 2019

Publication Type: Journal

Multiparametric Quantitative MRI for the Detection of IgA Nephropathy Using Tomoelastography, DWI, and BOLD Imaging.

Abstract (Expand)

OBJECTIVES: The aim of this study was to noninvasively evaluate changes in renal stiffness, diffusion, and oxygenation in patients with chronic, advanced stage immunoglobulin A nephropathy (IgAN) by … multiparametric magnetic resonance imaging using tomoelastography, diffusion-weighted imaging (DWI), and blood oxygen level-dependent (BOLD) imaging. MATERIALS AND METHODS: In this prospective study, 32 subjects (16 patients with biopsy-proven IgAN and 16 age- and sex-matched healthy controls) underwent multifrequency magnetic resonance elastography with tomoelastography postprocessing at 4 frequencies from 40 to 70 Hz to generate shear wave speed (meter per second) maps reflecting tissue stiffness. In addition, DWI and BOLD imaging were performed to determine the apparent diffusion coefficient in square millimeter per second and T2* relaxation time in milliseconds, respectively. Regions including the entire renal parenchyma of both kidneys were analyzed. Areas under the receiver operating characteristic (AUCs) curve were calculated to test diagnostic performance. Clinical parameters such as estimated glomerular filtration rate and protein-to-creatinine ratio were determined and correlated with imaging findings. RESULTS: Success rates of tomoelastography, DWI, and BOLD imaging regarding both kidneys were 100%, 91%, and 87%, respectively. Shear wave speed was decreased in IgAN (-21%, P < 0.0001), accompanied by lower apparent diffusion coefficient values (-12%, P = 0.004). BOLD imaging was not sensitive to IgAN (P = 0.12). Tomoelastography detected IgAN with higher diagnostic accuracy than DWI (area under the curve = 0.9 vs 0.8) and positively correlated with estimated glomerular filtration rate (r = 0.66, P = 0.006). CONCLUSIONS: Chronic, advanced stage IgAN is associated with renal softening and restricted water diffusion. Tomoelastography is superior to DWI and BOLD imaging in detecting IgAN.

Authors: S. T. Lang, J. Guo, A. Bruns, M. Durr, J. Braun, B. Hamm, I. Sack, S. R. Marticorena Garcia

Date Published: 2nd Jul 2019

Publication Type: Not specified

Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2019

Abstract (Expand)

This special issue of the Journal of Integrative Bioinformatics presents an overview of COMBINE standards and their latest specifications. The standards cover representation formats for computational … modeling in synthetic and systems biology and include BioPAX, CellML, NeuroML, SBML, SBGN, SBOL and SED-ML. The articles in this issue contain updated specifications of SBGN Process Description Level 1 Version 2, SBML Level 3 Core Version 2 Release 2, SBOL Version 2.3.0, and SBOL Visual Version 2.1.

Authors: Falk Schreiber, Björn Sommer, Gary D. Bader, Padraig Gleeson, Martin Golebiewski, Michael Hucka, Sarah M. Keating, Matthias König, Chris Myers, David Nickerson, Dagmar Waltemath

Date Published: 26th Jun 2019

Publication Type: Not specified

Powered by
 (v.1.14.2)
About FAIRDOM | About LiSyM | Funding and Programmes | Credits | Terms & Conditions | Imprint
Copyright © 2008 - 2023 The University of Manchester and HITS gGmbH