DOI: 10.5281/zenodo.5084809
title: fMRI study of experimental endotoxemia in humans

description: This dataset was acquired at Hannover Medical School, Hanover, Germany. The study complied with the Declaration of Helsinki, and was approved by the local ethics committee (#7427). All subjects gave written informed consent, and consent to publish their data anonimously. Using high-resolution functional magnetic resonance imaging (fMRI) we recorded brain activity in healthy male subjects undergoing experimental inflammation from intravenous endotoxin. Four fMRI runs covered key phases of the developing inflammation: pre-inflammatory baseline, onset of endotoxemia, onset of proinflammatory cytokinemia, and peak of proinflammatory cytokinemia. We informed the participants that they would either receive an endotoxin or saline injection at some point during the fMRI experiment. However, all subjects received the endotoxin with the start of the second fMRI acquisition. General exclusion criteria included a body mass index of &lt;18 and &gt;30 kg/m², any concurrent medical condition, history of allergies, current use of prescription and non-prescription medications, smoking, and regular high alcohol use. To exclude any inflammatory diseases that may aggravate through the HEM, each subject was interviewed and examined by a physician before being admitted to the study. <br> <strong>Data acquisition</strong><br> <em>Experimental design [min]</em> -30 -&gt; -10: Baseline fMRI -5: Baseline blood levels 0: Endotoxin administration 0-20: Second fMRI 20, 30: Blood sampling 30-50: Third fMRI 50, 60, 70, 80: Blood sampling 80-100: Fourth fMRI 100, 110, 120, 180, 240, 300, 360: Blood sampling <br> <em>Human endotoxemia model</em><br> All subjects received an intravenous bolus injection of endotoxin over one minute through an intravenous catheter in an antecubital forearm vein. GMP-grade lipopolysaccharide from Escherichia coli O:113:H10:K-strain (Lot 94332B1) provided by National Institute of Health Clinical Center, Bethesda, MD, USA was prepared for human use by reconstitution with sterile water for injection, shaking for 15 minutes on a vortex shaker and final dilution. We used a dose of 1ng/kg (0,02 ml/kg) body weight. All endotoxin solutions were administered immediately after their preparation. Subjects were injected between nine and ten o’clock in the morning and discharged six to eight hours later, when their symptoms had receded, all altered physiological parameters had demonstrated consistent reduction toward baseline values, and the physical exam was normal. <br> <em>MRI data</em><br> All MR images were acquired on a Siemens 3T MAGNETOM Skyra using a 64-channel head/neck coil. The scanning protocol consisted of the following sequences (see Sequences.ods): func_i: Functional whole brain gradient-echo echo-planar images (EPI) (TR=1180 ms; TE=32 ms; 2 mm isotropic resolution; simultaneous multi-slice factor=6; partial Fourier=7/8) func_ref: Reference scan for motion correction and template formation; equivalent to func but without multi-band acceleration (TR=6770 ms) SE_pe1_pe2: Reference scans for unwarping: Two spin-echo images matched to func in distortion without multi-band acceleration; one with the same, the other one with inverted phase encoding direction. t1: T1-weighted magnetisation-prepared rapid acquisition gradient-echo image (MPRAGE) (TR=2400 ms; TE=2.13 ms; TI=1000 ms; 1 mm isotropic resolution; in-plane acceleration factor=2) t2: T2-weighted image (TR=3200 ms; TE=564 ms; 1 mm isotropic resolution; in-plane acceleration factor=2) <br> <em>fMRI data preprocessing</em><br> Our preprocessing pipleine (JPreprocessing) is optimised for the brainstem and hypothalamus by avoiding superfluous resampling steps and unnecessary smoothing. On that account, motion correction (MCFLIRT [Jenkinson et al., 2002]) and unwarping (topup [Andersson et al.,2003]) are applied in a single transformation. Afterwards, brain extraction (BET [Smith, 2002]), grand mean scaling and high pass filtering (0.005 Hz) are applied. The data are not smoothed. Two study templates were generated using Advanced Normalization Tools (ANTs [Avants et al., 2008] using antsMultivariateTemplateConstruction2.sh). The first one using the unwarped EPI reference images (func_ref); the second one using the T1-images. <br> <em>Physiological data</em><br> The following physiological measures were acquired with an MR-compatible BIOPAC MP150 system Blood pressure (systolic and dyastolic): Non-invasive continuous blood pressure of the digital artery (pulse decomposition analysis using CareTaker) Electrodermal activity Photoplethysmography Respiration (belt) Electrocardiography <br> <em>Subject information</em><br> 01 m 25 a 175 cm 70 kg<br> 02 m 44 a 192 cm 84 kg<br> 03 m 27 a 188 cm 85 kg<br> 04 m 19 a 183 cm 99 kg<br> 05 m 20 a 183 cm 90 kg<br> 06 m 26 a 180 cm 78 kg<br> 07 m 21 a 189 cm 80 kg <br> <em>Missing data</em> sub01: functional data during run3 and run4 is shorter <strong>Data structure</strong><br> <em>data.csv</em> Contains blood parameters, symptom ratings, as well as blood pressure measurements for all subjects. <br> <em>sequences.ods</em> MRI sequence parameters <br> <em>subXX</em> acqparams.txt: Acquisition parameters needed for topup func_i: raw functional data func_ref: Reference image for motion correction and template generation physio.acq: Physiological measurements Trigger Blood pressure (systolic and dyastolic) Electrodermal activity Photoplethysmogram Respiration Electrocardiogram physio_cuts.txt: time points in the physio data that correspond to fMRI blocks (start-time end-time TR #volumes) SE_pe1_pe2: auxiliary image for unwarping slicetiming_i.txt: Slice timing information in seconds t1: Defaced T1-weighted image (undefaced images were used for template generation) t2: Defaced T1-weighted image <br> <em>templates</em> EPI-template: Generated from unwarped func_ref images Transformations for all subjects (can be applied using antsApplyTransforms) wb_mask EPI-2-T1: Transformation from EPI to T1-template MNI-template: T1-template warped into MNI_152 wb_mask T1-template: Generated from t1 images hyp_mask wb_mask T1-2-MNI: Transformation from T1 to MNI_152-template <br> <em>JPreprocessing</em><br> Preprocessing pipeline