fMRI study of experimental endotoxemia in humans

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 <18 and >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.

Data acquisition
Experimental design [min]

• -30 -> -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

Human endotoxemia model
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.

MRI data
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)

fMRI data preprocessing
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.

Physiological data
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

Subject information
01    m    25 a    175 cm    70 kg
02    m    44 a    192 cm    84 kg
03    m    27 a    188 cm    85 kg
04    m    19 a    183 cm    99 kg
05    m    20 a    183 cm    90 kg
06    m    26 a    180 cm    78 kg
07    m    21 a    189 cm    80 kg

Missing data

• sub01: functional data during run3 and run4 is shorter

Data structure
data.csv

• Contains blood parameters, symptom ratings, as well as blood pressure measurements for all subjects.

sequences.ods

• MRI sequence parameters

subXX

• 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

templates

• 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

JPreprocessing
Preprocessing pipeline