Gadoxetate kinetics measured with MRI

Database 🚀 Summary Signal-time curves, sequence parameters and clinical data measured through the various experiments of the liver workpackage of the TRISTAN consortium. The database is maintained by the open medical imaging biomarkers laboratory (miblab.org). Subjects: Human healthy volunteers, patients and rats. 📚 Background The data are taken from a series of preclinical and clinical studies performed by the TRISTAN project, in the period 2018-2024. The aim of these studies was to test if the effect of drugs on uptake and excretory function of the liver can be measured reliably with dynamic gadoxetate-enhanced MRI. Combined these studies provide proof of concept for a new MRI-based biomarker to predict the risk of liver-mediated drug-drug interactions, and of drug-induced liver injury. The data have been used to support a submission to the FDA's biomarker qualification program (details). 🛠️ Format All data are in dmr format - a folder with three csv files: data.csv: Data dictionary including definitions and units of all parameters rois.csv: ROI curves pars.csv: Parameter values for each subject and visit The data can be read and manipulated interactively with common applications such as excel, or programmatically with the python package pydmr. 📜 Version History Version Description v0.0.8 Harmonized rat database ahead of release of DICOM database v0.0.7 Human data extended to include demographics, liver function tests, blood tests. Corrected errors in some T1 values and one liver volume v0.0.6 Rat data separated out per study in line with the human data v0.0.5 Removed non-kinetic data due to a miblab database restructure. v0.0.4 Added covariates for LDS subjects v0.0.3 Added results for all human data v0.0.2 Removed duplicate human results and combined all controls without treatment in a single file Unique naming of subject ID's by adding a study acronym to the subject number: LDS for Leeds subjects, SHF for Sheffield subjects and GOT for Gothenburg subjects v0.0.1 Combined various formats of previous studies in a coherent dmr format 📦 Datasets tristan_humans_healthy_rifampicin 8 healthy volunteers with dynamic gadoxetate-enhanced MRI, before and after administration of a drug (rifampicin) which is known to inhibit liver function. The assessments were done on two separate visits at least 2 weeks apart. On each visit, the volunteer had two scans each with a separate contrast agent injection of a quarter dose each. See Min et al 2025 for details. tristan_humans_healthy_metformin tristan_humans_healthy_ciclosporin Data from a similar experiment as the rifampicin study in healthy volunteers, but with the drugs metformin and ciclosporin and performed in another center with a different scanner vendor. The study includes 6 volunteers for each drug tristan_humans_healthy_controls Five subjects enrolled in the rifampicin, metformin and ciclosporin studies had their baseline assessment but did not go on to have the the treatment visit, for various reasons. These data are combined together in this file. They can be added to the baseline data of the other studies to form a control cohort. tristan_humans_patients_rifampicin 3 patients with dynamic gadoxetate-enhanced MRI. The study participants take rifampicin as part of their routine clinical workup, with an aim to promote their liver function. For this study, they were taken off rifampicin 3 days before the first scan, and placed back on rifampicin 3 days before the second scan. tristan_rats_study_01_rifampicin_effect_sizetristan_rats_study_02_rifampicin_effect_sizetristan_rats_study_03_rifampicin_effect_sizetristan_rats_study_04_rifampicin_effect_sizetristan_rats_study_05_single_asunaprevirtristan_rats_study_06_single_pioglitazonetristan_rats_study_07_single_ketoconazoletristan_rats_study_08_single_cyclosporinetristan_rats_study_09_single_bosentan_hightristan_rats_study_10_single_bosentantristan_rats_study_11_chronic_bosentan_placebotristan_rats_study_12_single_rifampicintristan_rats_study_13_field_strengthtristan_rats_study_14_chronic_rifampicin_placebotristan_rats_study_15_chronic_cyclosporine_placebo Signal-time curves for a series of preclinical studies providing proof-of-concept before moving into human studies. These include studies with a single dose of a test drug (scanned before and after), chronic dosing studies, as well as studies looking at repeatability. A tabulated overview of all studies can be found in Gunwhy 2024. Results of the single test drugs have been reported in Melillo 2023, and chronic dosing results are reported in Montelius 2021 (manuscript in preparation). References Thazin Min, Marta Tibiletti, Paul D Hockings, Aleksandra Galetin, Ebony Gunwhy, Eve Shalom, J. Gerry Kenna, Nicola Melillo, Geoff JM Parker, Gunnar Schuetz, Daniel Scotcher, John C Waterton, Ian Rowe, Steven Sourbron. Assessing drug-mediated inhibition of liver transporter function with MRI: A first-in-human study. Radiology 2025; 317 (3): https://pubs.rsna.org/doi/10.1148/radiol.251899; https://pubs.rsna.org/doi/10.1148/radiol.251899 Thazin Min, Marta Tibiletti, Paul D Hockings, Aleksandra Galetin, Ebony Gunwhy, Eve Shalom, J. Gerry Kenna, Nicola Melillo, Geoff JM Parker, Gunnar Schuetz, Daniel Scotcher, John C Waterton, Ian Rowe, Steven Sourbron. Assessing drug-mediated inhibition of liver transporter function with MRI: A first-in-human study. medRxiv 2025.06.16.25329670; doi: https://doi.org/10.1101/2025.06.16.25329670 Ebony R. Gunwhy, Catherine D. G. Hines, Claudia Green, Iina Laitinen, Sirisha Tadimalla, Paul D. Hockings, Gunnar Schütz, J. Gerry Kenna, Steven Sourbron, and John C. Waterton. Assessment of hepatic transporter function in rats using dynamic gadoxetate-enhanced MRI: A reproducibility study. MAGMA. 2024 Aug;37(4):697-708. doi: 10.1007/s10334-024-01192-5. Melillo N, Scotcher D, Kenna JG, Green C, Hines CDG, Laitinen I, Hockings PD, Ogungbenro K, Gunwhy ER, Sourbron S, et al. Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug–Drug Interactions in Rats. Pharmaceutics. 2023; 15(3):896. Mikael Montelius, Steven Sourbron, Nicola Melillo, Daniel Scotcher, Aleksandra Galetin, Gunnar Schuetz, Claudia Green, Edvin Johansson, John C. Waterton, and Paul Hockings. Acute and chronic rifampicin effect on gadoxetate uptake in rats using gadoxetate DCE-MRI. Int Soc Mag Reson Med 2021; 2674.