The Digital Brain Bank, an open access platform for post-mortem imaging datasets

  1. Benjamin C Tendler  Is a corresponding author
  2. Taylor Hanayik
  3. Olaf Ansorge
  4. Sarah Bangerter-Christensen
  5. Gregory S Berns
  6. Mads F Bertelsen
  7. Katherine L Bryant
  8. Sean Foxley
  9. Martijn P van den Heuvel
  10. Amy FD Howard
  11. Istvan N Huszar
  12. Alexandre A Khrapitchev
  13. Anna Leonte
  14. Paul R Manger
  15. Ricarda AL Menke
  16. Jeroen Mollink
  17. Duncan Mortimer
  18. Menuka Pallebage-Gamarallage
  19. Lea Roumazeilles
  20. Jerome Sallet
  21. Lianne H Scholtens
  22. Connor Scott
  23. Adele Smart
  24. Martin R Turner
  25. Chaoyue Wang
  26. Saad Jbabdi
  27. Rogier B Mars
  28. Karla L Miller  Is a corresponding author
  1. Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom
  2. Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom
  3. Psychology Department, Emory University, United States
  4. Centre for Zoo and Wild Animal Health, Copenhagen Zoo, Denmark
  5. Department of Radiology, University of Chicago, United States
  6. Department of Complex Trait Genetics, Centre for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Netherlands
  7. Department of Child Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Netherlands
  8. Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, United Kingdom
  9. School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, South Africa
  10. Wellcome Centre for Integrative Neuroimaging, Department of Experimental Psychology, University of Oxford, United Kingdom
  11. Stem Cell and Brain Research Institute, Université Lyon 1, INSERM, France
  12. Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Netherlands
6 figures, 7 tables and 2 additional files

Figures

The Digital Anatomist.

(a) Whole-brain diffusion MRI data available in the Human High-Resolution Diffusion MRI-PLI dataset reveals the wealth of information provided at increased spatial scales, one of the key aims of the …

The Digital Brain Zoo.

(a) The first release of the Digital Brain Zoo provides whole-brain MRI datasets spanning multiple species and taxonomic ranks. Notably, we provide whole-brain diffusion MRI datasets from 14 …

The Digital Pathologist.

One of the key aims of the Digital Pathologist is the examination of neuropathological spread in neurological disease. The Human ALS MRI-Histology dataset (a) facilitates these investigations, …

Appendix 3—figure 1
Post-mortem human brain holder.

The brain holder ensures consistent placement during scanning. Here, the custom holder tightly seals the brain in place, whilst the 3D printed shell (provided by Dr Alard Roebroeck, Maastricht …

Appendix 3—figure 2
Post-mortem cylindrical brain holder.

The brain holder used for scanning large nonhuman brains which fit inside the 28 channel QED knee coil. This consisted of a cylindrical container, with plastic gauze (black) used to secure samples …

Appendix 4—figure 1
Structural MRI.

Example structural MRI dataset acquired using a bSSFP sequence in the European wolf (Canis lupus) at a resolution of 220 μm (isotropic). bSSFP Structural MRI datasets display excellent gray-white …

Tables

Table 1
Description of all datasets provided in the first release to the Digital Brain Bank.

All Structural MRI datasets in the first release were acquired using a balanced SSFP (bSSFP) or T2-weighted sequence, which yields strong gray-white matter contrast in formalin-fixed post-mortem …

CategoryNameContents: MRIResolution (MRI)Contents: MicroscopyRelevant publications
Digital AnatomistHuman High-Resolution Diffusion MRI-PLIWhole-brain diffusion MRI, structural MRI, quantitative T1 and T2 maps:
– Control human brain: 1×
Diffusion MRI: (500 μm, 1 and 2 mm iso.)
Structural MRI: 312.5×312.5×500 μm3
T1 map: (0.75×0.75×1.6 mm3)
T2 map: (0.75×0.75×1.6 mm3)
Polarised light imaging (4 μm in-plane) in the anterior commissure, corpus callosum, pons, thalamus, and visual cortex (same brain)Dataset described in this publication (Methodology in Appendix 1), Diffusion MRI processing described in Tendler et al., 2020b, T2 mapping described in Tendler et al., 2021
Digital AnatomistHuman Callosum MRI-PLI-HistologyCorpus callosum diffusion MRI:
– Excised control human corpus callosum samples: 3×
Diffusion MRI: (400 μm iso.)Polarised light imaging (4 μm in-plane), bright-field microscopy images of immunohistochemistry stains (0.25 μm in-plane) for PLP (myelin) and GFAP (astrocyte) (same human corpus callosum samples)Mollink et al., 2017
Whole-brain diffusion MRI and structural MRI (available in brains marked with a *):
  • Bushbaby (Galago senegalensis): 1×

  • Capuchin monkey (Sepajus apella): 1×

  • Chimpanzee* (Pan troglodytes): 2×

  • Colobus monkey (Colobus guereza): 1×

  • Cotton-Top tamarin (Saguinus oedipus): 1×

  • Golden Lion tamarin (Leontopithecus rosalia): 1×

  • Hamadryas baboon* (Papio hamadryas): 1×

  • Macaque monkey (Macaca mulatta): 3×

  • Mangabey (Lophocebus albigena): 1×

  • Night monkey, (Aotus lemurinus): 1×

  • Ring-tailed lemur (Lemur catta): 3×

  • Saki monkey (Pithecia pithecia): 1×

  • Western Lowland gorilla* (Gorilla gorilla): 1×

  • Woolly monkey (Lagothrix lagotricha): 1×

Diffusion MRI:
300 μm iso.: Bushbaby, Cotton-Top tamarin & Golden Lion Tamarin
400 μm iso: Night monkey
500 μm iso: Ring-tailed lemur and Saki monkey
600 μm iso: Capuchin monkey, Chimpanzee, Colobus monkey, Hamadryas baboon, Macaque monkey, Mangabey, Western Lowland Gorilla and Woolly Monkey
Structural MRI
200 μm iso: Western Lowland Gorilla
220 μm iso: Hamadryas Baboon
0.22×0.22×0.19 mm3: 1× Chimpanzee
0.375×0.375×0.40 mm3: 1× Chimpanzee
None1× Western Lowland gorilla and 1× Chimpanzee described in Roumazeilles et al., 2020, 3× Macaque monkey and 3× Ring-Tailed Lemur described in Roumazeilles et al., 2021. Hamadryas baboon, Cotton-Top tamarin and Golden Lion tamarin datasets described in this publication (Methodology in Appendix 1). All other datasets described in Bryant et al., 2021
Digital Brain ZooMarsupialsWhole-brain diffusion MRI and structural MRI:
  • Tasmanian devil (Sarcophilus harrisii): 2×

  • Thylacine (Thylacinus cynocephalus): 2×

Diffusion MRI:
1 mm iso: 1× Tasmanian devil
1.5 mm iso: 1× Tasmanian devil
1.1 mm iso: 1× Thylacine
1.0×1.1×0.8 mm3: 1× Thylacine
Structural MRI
330 μm iso: 1× Tasmanian devil and 1× Thylacine
330×330×300 μm3: 1× Tasmanian devil
500 μm iso: 1× Thylacine
NoneBerns and Ashwell, 2017
Digital Brain ZooCetaceansWhole-brain diffusion MRI and structural MRI
  • Common dolphin (Delphinus delphis): 1×

  • Pantropical dolphin (Stenella attenuata): 1×

Diffusion MRI: (1.3 mm iso.)
Structural MRI: (640×640×500 μm3)
NoneBerns et al., 2015
Digital Brain ZooCarnivoraWhole-brain diffusion MRI and structural MRI:
– European wolf (Canis lupus): 1×
Diffusion MRI: (600 μm iso.)
Structural MRI: (220 μm iso.)
NoneDataset described in this publication (Methodology in Appendix 1)
Digital PathologistHuman ALS MRI-HistologyWhole-brain diffusion MRI, structural MRI, quantitative T1, T2, and T2* maps, magnetic susceptibility maps (selected brains†):
  • Amyotrophic lateral sclerosis (ALS) human brains: 12×

  • Control human brains: 3×

Diffusion MRI: (850 μm iso.)
Structural MRI: (230–250 μm in-plane; 270–500 μm slice)
T1 map: (0.65–1 mm in-plane; 0.90–1.6 mm slice)
T2 map: (0.65–1 mm in-plane; 0.90–1.6 mm slice)
T2*/magnetic susceptibility maps: (0.5 mm in-plane; 1.1–1.3 mm slice)
Bright-field microscopy immunohistochemistry stains (0.50 μm in-plane, exception pTDP43 – 0.25 μm in-plane): pTDP-43, IBA1 (pan microglia), CD68 (activated microglia/macrophages), PLP (myelin), SMI-312 (axonal phosphorylated neurofilaments), and ferritin (iron storage, subset of regions)
Regions: Anterior cingulate cortex, corpus callosum, hippocampus, primary motor cortex, and visual cortex (same brains).
Selected multimodal histology available in two brains (1× ALS and 1× Control), and multiregional PLP (available in 10 out of 12 ALS brains and all control brains, 5–8 regions per brain) in first data release – remaining histology being actively curated.
Pallebage-Gamarallage et al., 2018, Magnetic susceptibility and T2* mapping protocol described in Wang et al., 2020, Diffusion MRI processing described in Tendler et al., 2020b, T2 mapping described in Tendler et al., 2021
Table 2
Acquisition site and MRI scanner associated with all projects in the first release to the Digital Brain Bank.
CategoryDataset(s)Acquisition locationMRI scanner
Digital AnatomistHuman High-Resolution Diffusion MRI-PLIUniversity of OxfordSiemens 7T Magnetom
32-channel receive/1-channel transmit head coil (Nova Medical)
Digital AnatomistHuman Callosum MRI-PLI-HistologyUniversity of Oxford9.4T 160 mm horizontal bore VNMRS preclinical MRI system
100 mm bore gradient insert (Varian Inc)
26 mm ID quadrature birdcage coil (Rapid Biomedical GmbH)
Digital Brain ZooNonHuman PrimatesUniversity of OxfordBaboon, Chimpanzee, Gorilla
Siemens 7T Magnetom
28-channel receive/1 channel transmit knee coil (QED)
All other brains
7T magnet with Agilent Direct-Drive console
72 mm ID quadrature birdcage RF coil (Rapid Biomedical GmbH)
Digital Brain ZooMarsupialsEmory UniversitySiemens 3T Trio
32-channel receive/1-channel transmit head coil
Digital Brain ZooCetaceansEmory University2× Tasmanian devil and 1× Thylacine
Siemens 3T Trio
32-channel receive/1-channel transmit head coil
1× Thylacine
Bruker 9.4T BioSpec preclinical MR system
Digital Brain ZooCarnivoraUniversity of OxfordSiemens 7T Magnetom
28-channel receive/1 channel transmit knee coil (QED)
Digital PathologistHuman ALS MRI-HistologyUniversity of OxfordSiemens 7T Magnetom
32-channel receive/1-channel transmit head coil (Nova Medical)
Appendix 1—table 1
DW-SSFP Acquisition parameters at 0.5, 1.0, and 2.0 mm.
DW-SSFP (0.5 mm)DW-SSFP (1.0 mm)
q-value (cm–1)300q-value (cm–1)300
Diffusion gradient duration (ms)14.10Diffusion gradient duration (ms)14.10
Diffusion gradient strength (mTm–1)50Diffusion gradient strength (mTm–1)50
Flip angles (°)33 and 98Flip angles (°)33 and 98
No. of directions (per flip angle)90No. of directions (per flip angle)60
No. of non-DW (per flip angle)6 (q=20 cm–1)No. of non-DW (per flip angle)5 (q=20 cm–1)
Resolution (μm3)500·500·500Resolution (mm3)1.0·1.0·1.0
TE (ms)21TE (ms)21
TR (ms)30TR (ms)30
EPI factor1EPI factor1
Bandwidth (Hz per pixel)198Bandwidth (Hz per pixel)130
Acquisition time (per direction/non-DW)45 min 03 sNo. of averages1
Acquisition time (total)6 days 0 hr
No. of averages1
DW-SSFP (2.0 mm)
q-value (cm–1)300
Diffusion gradient duration (ms)14.10
Diffusion gradient strength (mTm–1)50
Flip angles (°)33 and 98
No. of directions (per flip angle)221
No. of non-DW (per flip angle)6 (q=20 cm–1)
Resolution (mm3)2.0·2.0·2.0
TE (ms)21
TR (ms)30
EPI factor1
Bandwidth (Hz per pixel)130
No. of averages1
Appendix 1—table 2
Acquisition parameters for the TIR, TSE, structural (TRUFI), and B1-mapping (AFI) sequences.
Turbo inversion-recovery (TIR)True-Fast Imaging with SSFP (TRUFI)
Resolution (mm3)0.75·0.75·1.60Resolution (μm3)312.5·312.5·500
Number of inversions6TE (ms)5.95
TE (ms)12TR (ms)11.9
TR (ms)1000Flip angle (°)35
TIs (ms)31, 62, 125, 250, 500, and 850Bandwidth (Hz per pixel)130
Flip angle (°)180Phase increments (o)0 and 180
Bandwidth (Hz per pixel)199Number of averages (per set of increments)16
Number of averages1
Turbo spin-echo (TSE) – T2Actual flip-angle imaging (AFI) – B1
Resolution (mm3)0.75·0.75·1.60Resolution (mm3)1.50·1.50·1.50
Number of echoes6TE (ms)1.5
TEs (ms)14, 28, 42, 56, 70, and 84TR1/TR2 (ms)6/30
TR (ms)1,000Flip angle (°)60
Flip angle (°)180Bandwidth (Hz per pixel)630
Bandwidth (Hz per pixel)130Number of averages1
Number of averages1
Appendix 1—table 3
Acquisition parameters for the DW-SSFP and structural (TRUFI) sequences.

The only difference between the European wolf and Hamadryas baboon acquisition was the number of non-diffusion weighted directions acquired (13 for wolf and 11 for baboon).

DW-SSFPTrue-Fast Imaging with SSFP (TRUFI)
q-value (cm–1)300Resolution (μm3)217·217·220
Diffusion gradient duration (ms)13.56TE (ms)7.33
Diffusion gradient strength (mTm–1)52TR (ms)14.65
Flip angle (°)39Flip angle (°)30
No. of directions160Bandwidth (Hz per pixel)100
No. of non-DW13/11 (q=20 cm–1)Phase increments (o)0, 45, 90, 135, 180, 225, 270, and 315
Resolution (μm3)600·600·600No. of averages (per set of increments)2
TE (ms)21
TR (ms)29
EPI factor1
Bandwidth (Hz per pixel)100
Acquisition time (per direction/non-DW)16 min 25 s
Acquisition time (total)1 day 20 hr
No. of averages1
Appendix 1—table 4
Acquisition parameters for the DW-SEMS sequence.
DW-SEMS
b-value (s/mm2)4000
δ (ms)7
Δ (ms)13
Diffusion gradient strength (mTm–1)320
No. of directions128
No. of non-DW16
Resolution (μm3)300·300·300
TE (ms)25
TR (s)10
EPI factor1
Bandwidth (kHz)100
Acquisition time (per direction/non-DW)21 min 20 s
Acquisition time (total)2 days 4 hr
No. of averages1
Appendix 2—table 1
p-values associated with differences between the ALS and control cohort for the diffusivity estimates.

Here ‘p’ defines the p-value, and ‘PFWER’ defines the FWER-corrected p-value (*=p<0.05; **=pFWER<0.05). The largest differences between the ALS and control cohort were found in the Body (Pre/Supp …

Body (Sensory)Body (Motor)Body (Pre/Supp Motor)Genu (PreFrontal)
Fractional anisotropy (FA)p=0.34
pFWER=0.70
p=0.042*
pFWER=0.11
p=0.0044* pFWER=0.013**p=0.013*
pFWER=0.037**
Mean diffusivity (MD)p=0.99
pFWER=1.00
p=0.18
pFWER=0.48
p=0.015*
pFWER=0.053
p=0.037*
pFWER=0.12
Axial diffusivity (AD)p=0.53
pFWER=0.92
p=0.58
pFWER=0.95
p=0.084
pFWER=0.27
p=0.11
pFWER=0.32
Radial diffusivity (RD)p=0.66
pFWER=0.97
p=0.073
pFWER=0.23
p=0.0022* pFWER=0.015**p=0.022*
pFWER=0.062

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