Assessment of hepatic transporter function in rats using dynamic gadoxetate-enhanced MRI: a reproducibility study.

Objective: Previous studies have revealed a substantial between-centre variability in DCE-MRI biomarkers of hepatocellular function in rats. This study aims to identify the main sources of variability by comparing data measured at different centres and field strengths, at different days in the same subjects, and over the course of several months in the same centre.

Materials And Methods: 13 substudies were conducted across three facilities on two 4.

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic.

Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats.

Gadoxetate, a magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 and multidrug resistance-associated protein 2. Six drugs, with varying degrees of transporter inhibition, were used to assess gadoxetate dynamic contrast enhanced MRI biomarkers for transporter inhibition in rats. Prospective prediction of changes in gadoxetate systemic and liver AUC (AUCR), resulting from transporter modulation, were performed by physiologically-based pharmacokinetic (PBPK) modelling.

Multiparametric magnetic resonance imaging allows non-invasive functional and structural evaluation of diabetic kidney disease.

Background: We sought to develop a novel non-contrast multiparametric MRI (mpMRI) protocol employing several complementary techniques in a single scan session for a comprehensive functional and structural evaluation of diabetic kidney disease (DKD).

Methods: In the cross-sectional part of this prospective observational study, 38 subjects ages 18‒79 years with type 2 diabetes and DKD [estimated glomerular filtration rate (eGFR) 15‒60 mL/min/1.73 m] and 20 age- and gender-matched healthy volunteers (HVs) underwent mpMRI.

Fatty acids in multiple circulating lipid fractions reflects the composition of liver triglycerides in humans.

Background And Aims: Fatty acids (e.g. 16:1n-7) and desaturase indices (e.

Hepatic Unsaturated Fatty Acids Are Linked to Lower Degree of Fibrosis in Non-alcoholic Fatty Liver Disease.

The hepatic lipidome of patients with early stages of non-alcoholic fatty liver disease (NAFLD) has been fairly well-explored. However, studies on more progressive forms of NAFLD, i.e.

The Combination of MR Elastography and Proton Density Fat Fraction Improves Diagnosis of Nonalcoholic Steatohepatitis.

Background: Nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is subdivided into nonalcoholic fatty liver (NAFL) and the more aggressive form, nonalcoholic steatohepatitis (NASH), which carries a higher risk of developing fibrosis and cirrhosis. There is currently no reliable non-invasive method for differentiating NASH from NAFL.

Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging.

Background: Glucagon-like peptide-1 receptor agonists may be a treatment option in patients with non-alcoholic fatty liver disease (NAFLD).

Aims: To investigate the effects of semaglutide on liver stiffness and liver fat in subjects with NAFLD using non-invasive magnetic resonance imaging (MRI) methods.

Methods: This randomised, double-blind, placebo-controlled trial enrolled subjects with liver stiffness 2.

Long-term effects of dapagliflozin plus saxagliptin versus glimepiride on a background of metformin in patients with type 2 diabetes: Results of a 104-week extension to a 52-week randomized, phase 3 study and liver fat MRI substudy.

Aim: To report the results of a 104-week extension to a 52-week study in which dapagliflozin plus saxagliptin (DAPA+SAXA) improved glycaemic control, liver fat and metabolic variables compared with glimepiride (GLIM) in participants with type 2 diabetes (T2D) receiving background metformin.

Materials And Methods: This extension to a 52-week global, multicentre, parallel-group, active-controlled, double-blind study (NCT02419612) continued randomized participants (1:1) on DAPA+SAXA (10/5 mg) plus placebo, or GLIM (1-6 mg) plus placebo, once daily. Eligible participants were aged ≥18 years, had T2D (glycated haemoglobin [HbA1c] 58.

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI.

Background: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool.

Clinical Characteristics of a Non-Alcoholic Fatty Liver Disease Population Across the Fibrosis Spectrum Measured by Magnetic Resonance Elastography: Analysis of Screening Data.

Introduction: Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is associated with liver-related complications and metabolic comorbidities. The phenotype is wide, ranging from simple steatosis to non-alcoholic steatohepatitis with advanced fibrosis. In this analysis of a phase 1 trial, clinical characteristics of screened subjects with NAFLD were studied according to the extent of fibrosis assessed using magnetic resonance elastography (MRE).

HEROIC: a 5-year observational cohort study aimed at identifying novel factors that drive diabetic kidney disease: rationale and study protocol.

Introduction: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments.

Dapagliflozin plus saxagliptin add-on to metformin reduces liver fat and adipose tissue volume in patients with type 2 diabetes.

Aim: To assess the effects of dapagliflozin plus saxagliptin plus metformin versus glimepiride plus metformin on liver fat (proton density fat fraction) and visceral and subcutaneous adipose tissue volumes over 52 weeks of treatment.

Materials And Methods: This was a magnetic resonance imaging substudy of a 52-week, multicentre, randomized, double-blind, parallel-group trial that evaluated the efficacy and safety of dapagliflozin 10 mg/day plus saxagliptin 5 mg/day versus titrated glimepiride 1-6 mg (1, 2, 3, 4 or 6 mg) in 82 patients with type 2 diabetes (HbA1c 7.5%-10.

Drug-induced myocardial dysfunction - recommendations for assessment in clinical and pre-clinical studies.

: Drug-induced myocardial dysfunction is an important safety concern during drug development. Oncology compounds can cause myocardial dysfunction, leading to decreased left ventricular ejection fraction and heart failure via several mechanisms. Cardiovascular imaging has a major role in the early detection and monitoring of cardiotoxicity.

Consensus-based technical recommendations for clinical translation of renal T1 and T2 mapping MRI.

To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method.

Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA.

Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification.

A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function.

Unlabelled: Drug-induced liver injury (DILI) is a leading cause of acute liver failure and transplantation. DILI can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats.

Variable flip angle 3D ultrashort echo time (UTE) T mapping of mouse lung: A repeatability assessment.

Background: Lung T is a potential translational biomarker of lung disease. The precision and repeatability of variable flip angle (VFA) T mapping using modern 3D ultrashort echo time (UTE) imaging of the whole lung needs to be established before it can be used to assess response to disease and therapy.

Purpose: To evaluate the feasibility of regional lung T quantification with VFA 3D-UTE and to investigate long- and short-term T repeatability in the lungs of naive mice.

Imaging atherosclerosis in rheumatoid arthritis: evidence for increased prevalence, altered phenotype and a link between systemic and localised plaque inflammation.

In rheumatoid arthritis (RA), chronic inflammation is thought to drive increased cardiovascular risk through accelerated atherosclerosis. It may also lead to a more high-risk plaque phenotype. We sought to investigate carotid plaque phenotype in RA patients using Dynamic Contrast-Enhanced MRI (DCE-MRI) and Fludeoxyglucose Positron Emission Tomography(FDG-PET).

In Vivo Measurements of T2 Relaxation Time of Mouse Lungs during Inspiration and Expiration.

Purpose: The interest in measurements of magnetic resonance imaging relaxation times, T1, T2, T2*, with intention to characterize healthy and diseased lungs has increased recently. Animal studies play an important role in this context providing models for understanding and linking the measured relaxation time changes to the underlying physiology or disease. The aim of this work was to study how the measured transversal relaxation time (T2) in healthy lungs is affected by normal respiration in mouse.