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Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder, characterized by the accumulation of excess fat in the liver, and is a driving factor for various severe liver diseases. These multi -factorial and multi-timescale changes are observed in different clinical studies, but these studies have not been integrated into a uni fied framework. In this study, we aim to present such a uni fied framework in the form of a dynamic mathematical model. Methods: For model training and validation, we collected data for dietary or drug -induced interventions aimed at reducing or increasing liver fat. The model was formulated using ordinary differential equations (ODEs) and the mathematical analysis, model simulation, model formulation and the model parameter estimation were all performed in MATLAB. Results: Our mathematical model describes accumulation of fat in the liver and predicts changes in lipid fluxes induced by both dietary and drug interventions. The model is validated using data from a wide range of drug and dietary intervention studies and can predict both short-term (days) and long-term (weeks) changes in liver fat. Importantly, the model computes the contribution of each individual lipid flux to the total liver fat dynamics. Furthermore, the model can be combined with an established bodyweight model, to simulate even longer scenarios (years), also including the effects of insulin resistance and body weight. To help prepare for corresponding eHealth applications, we also present a way to visualize the simulated changes, using dynamically changing lipid droplets, seen in images of liver biopsies. Conclusion: In conclusion, we believe that the minimal model presented herein might be a useful tool for future applications, and to further integrate and understand data regarding changes in dietary and drug induced changes in ectopic TAG in the liver. With further development and validation, the minimal model could be used as a diseas, Funding Agencies|Swedish Research Council [2018-05418, 2018-03319, 2019-03767]; CENIIT [15.09]; Knut and Alice Wallenberg Foundation [2020.0182]; H2020 project PRECISE4Q [777107]; H-EUROPE project STRATIF-AI [101080875]; Swedish Fund for Research without Animal Experiments [F2019-0010]; ELLIIT [2020-A12]; VINNOVA [2020-04711]; Knowledge Foundation [20200017]; CENIIT; Ake Wibergs Stiftelse; Swedish Fund for Research; [ITM17-0245]

A novel method of high -spatial -resolution, 3D B1 -field distribution measurements is presented. The method is independent of the MR -scanner, and it allows for automated acquisitions of complete maps of all magnetic field vector components for both proton and heteronuclear MR coils of arbitrary geometrical shapes. The advantage of the method proposed here, compared with methods based on measurements with an MR -scanner, is that a complete image of both receive and transmit B1 -fields, including the phase of the B1 -field, can be acquired. The B1 field maps obtained in this manner can be used for absolute quantification of metabolites in MRS experiments, as well as for intensity compensations in imaging experiments, both of which are important concepts in biological and medical MR applications. Another use might be in coil development and testing. A comparison with B1 field magnitude maps obtained with an MR -scanner was included to validate the accuracy of the proposed method., Funding Agencies|University Hospital Research Funds

Objectives This explorative study analyses interrelationships between peripheral compounds in saliva, plasma, and muscles together with body composition variables in healthy subjects and in fibromyalgia patients (FM). There is a need to better understand the extent cytokines and chemokines are associated with body composition and which cytokines and chemokines differentiate FM from healthy controls.Methods Here, 32 female FM patients and 30 age-matched female healthy controls underwent a clinical examination that included blood sample, saliva samples, and pain threshold tests. In addition, the subjects completed a health questionnaire. From these blood and saliva samples, a panel of 68 mainly cytokines and chemokines were determined. Microdialysis of trapezius and erector spinae muscles, phosphorus-31 magnetic resonance spectroscopy of erector spinae muscle, and whole-body magnetic resonance imaging for determination of body composition (BC)-i.e., muscle volume, fat content and infiltration-were also performed.Results After standardizing BC measurements to remove the confounding effect of Body Mass Index, fat infiltration and content are generally increased, and fat-free muscle volume is decreased in FM. Mainly saliva proteins differentiated FM from controls. When including all investigated compounds and BC variables, fat infiltration and content variables were most important, followed by muscle compounds and cytokines and chemokines from saliva and plasma. Various plasma proteins correlated positively with pain intensity in FM and negatively with pain thresholds in all subjects taken together. A mix of increased plasma cytokines and chemokines correlated with an index covering fat infiltration and content in different tissues. When muscle compounds were included in the analysis, several of these were identified as the most important regressors, although many plasma and saliva proteins remained significant.Discussion Peripheral factors were important for group diffe, Funding Agencies|Swedish Research Council

BACKGROUND: Drug induced liver injury (DILI) is a major concern when developing new drugs. A promising biomarker for DILI is the hepatic uptake rate of the contrast agent gadoxetate. This rate can be estimated using a novel approach combining magnetic resonance imaging and mathematical modeling. However, previous work has used different mathematical models to describe liver function in humans or rats, and no comparative study has assessed which model is most optimal to use, or focused on possible translatability between the two species. AIMS: Our aim was therefore to do a comparison and assessment of models for DILI biomarker assessment, and to develop a conceptual basis for a translational framework between the species. METHODS AND RESULTS: We first established which of the available pharmacokinetic models to use by identifying the most simple and identifiable model that can describe data from both human and rats. We then developed an extension of this model for how to estimate the effects of a hepatotoxic drug in rats. Finally, we illustrated how such a framework could be useful for drug dosage selection, and how it potentially can be applied in personalized treatments designed to avoid DILI. CONCLUSION: Our analysis provides clear guidelines of which mathematical model to use for model-based assessment of biomarkers for liver function, and it also suggests a hypothetical path to a translational framework for DILI., Funding: Swedish Research Council: VR/MH [2020-04826, 2020.0182]; County Council; Swedish Research Council: VR/NT [777107]; Center for Industrial Information Technology (CENIIT); Swedish foundation for Strategic Research; SciLifeLab; KAW; H2020 project PRECISE4Q; Swedish Fund for Research without Animal Experiments; Excellence Center at Linkoping -Lund in Information Technology (ELLIIT); [2018-03319]; [2007-2884]; [2018-05418]; [15.09]; [ITM17-0245]