Elsevier

NeuroImage

Volume 80, 15 October 2013, Pages 234-245
NeuroImage

The Human Connectome Project and beyond: Initial applications of 300 mT/m gradients

Highlights

Diffusion spectrum imaging to study traumatic coma recovery

In vivo human axon diameter measurements using 300 mT/m gradients

High-resolution (0.6 mm isotropic) diffusion imaging in whole, fixed human brain

Abstract

The engineering of a 3 T human MRI scanner equipped with 300 mT/m gradients – the strongest gradients ever built for an in vivo human MRI scanner – was a major component of the NIH Blueprint Human Connectome Project (HCP). This effort was motivated by the HCP's goal of mapping, as completely as possible, the macroscopic structural connections of the in vivo healthy, adult human brain using diffusion tractography. Yet, the 300 mT/m gradient system is well suited to many additional types of diffusion measurements. Here, we present three initial applications of the 300 mT/m gradients that fall outside the immediate scope of the HCP. These include: 1) diffusion tractography to study the anatomy of consciousness and the mechanisms of brain recovery following traumatic coma; 2) q-space measurements of axon diameter distributions in the in vivo human brain and 3) postmortem diffusion tractography as an adjunct to standard histopathological analysis. We show that the improved sensitivity and diffusion-resolution provided by the gradients are rapidly enabling human applications of techniques that were previously possible only for in vitro and animal models on small-bore scanners, thereby creating novel opportunities to map the microstructure of the human brain in health and disease.

Keywords

Human connectome
Diffusion MRI
Tractography
Traumatic coma
Consciousness
Axon diameter
Corpus callosum
In vivo
Postmortem
Loading...

References

Aboitiz et al., 1992
F. Aboitiz, A.B. Scheibel, R.S. Fisher, E. ZaidelFiber composition of the human corpus callosum
Brain Res., 598 (1992), pp. 143-153
Adams et al., 1989
J.H. Adams, D. Doyle, I. Ford, T.A. Gennarelli, D.I. Graham, D.R. McLellanDiffuse axonal injury in head injury: definition, diagnosis and grading
Histopathology, 15 (1989), pp. 49-59
Aggarwal et al., 2013
M. Aggarwal, J. Zhang, O. Pletnikov, B. Crain, J. Troncoso, S. MoriFeasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: a case study at 11.7 T
NeuroImage, 74 (2013), pp. 117-127
Alexander et al., 2010
D.C. Alexander, P.L. Hubbard, M.G. Hall, E.A. Moore, M. Ptito, G.J.M. Parker, T.B. DyrbyOrientationally invariant indices of axon diameter and density from diffusion MRI
NeuroImage, 52 (2010), pp. 1374-1389
Anwander et al., 2010
A. Anwander, A. Pampel, T.R. KnoscheIn vivo measurement of cortical anisotropy by diffusion-weighted imaging correlates with cortex type
Proc. Int. Soc. Magn. Reson. Med., 18 (2010), p. 109
Assaf et al., 2008
Y. Assaf, T. Blumenfeld-Katzir, Y. Yovel, P.J. BasserAxCaliber: a method for measuring axon diameter distribution from diffusion MRI
Magn. Reson. Med., 59 (2008), pp. 1347-1354
Barazany et al., 2009
D. Barazany, P.J. Basser, Y. AssafIn vivo measurement of axon diameter distribution in the corpus callosum of rat brain
Brain, 132 (2009), pp. 1210-1220
Behrens et al., 2003
T.E.J. Behrens, M.W. Woolrich, M. Jenkinson, H. Johansen-Berg, R.G. Nunes, S. Clare, P.M. Matthews, J.M. Brady, S.M. SmithCharacterization and propagation of uncertainty in diffusion-weighted MR imaging
Magn. Reson. Med., 50 (2003), pp. 1077-1088
Bell et al., 2009
R.S. Bell, A.H. Vo, C.J. Neal, J. Tigno, R. Roberts, C. Mossop, J.R. Dunne, R.A. ArmondaMilitary traumatic brain and spinal column injury: a 5-year study of the impact blast and other military grade weaponry on the central nervous system
J. Trauma, 66 (2009), pp. S104-S111
Bodammer et al., 2004
N. Bodammer, J. Kaufmann, M. Kanowski, C. TempelmannEddy current correction in diffusion-weighted imaging using pairs of images acquired with opposite diffusion gradient polarity
Magn. Reson. Med., 51 (2004), pp. 188-193
Bruns and Hauser, 2003
J. Bruns, W.A. HauserThe epidemiology of traumatic brain injury: a review
Epilepsia, 44 (2003), pp. 2-10
Callaghan, 1991
P.T. CallaghanPrinciples of Nuclear Magnetic Resonance Microscopy
Oxford University Press (1991)
Callaghan et al., 1988
P.T. Callaghan, C.D. Eccles, Y. XiaNMR microscopy of dynamic displacements — k-space and q-space imaging
J. Phys. E: Sci. Instrum., 21 (1988), pp. 820-822
Chung et al., 2013
K. Chung, J. Wallace, S.Y. Kim, S. Kalyanasundaram, A.S. Andalman, T.J. Davidson, J.J. Mirzabekov, K.A. Zalocusky, J. Mattis, A.K. Denisin, S. Pak, H. Berstein, C. Ramakrishnan, L. Grosenick, V. Gradinaru, K. DeisserothStructural and molecular interrogation of intact biological systems
Nature (2013), 10.1038/nature12107
Cluskey and Ramsden, 2001
S. Cluskey, D.B. RamsdenMechanisms of neurodegeneration in amyotrophic lateral sclerosis
Mol. Pathol., 54 (2001), pp. 386-392
Cory and Garroway, 1990
D.G. Cory, A.N. GarrowayMeasurement of translational displacement probabilities by NMR—an indicator of compartmentation
Magn. Reson. Med., 14 (1990), pp. 435-444
D'Arceuil et al., 2007
H.E. D'Arceuil, S. Westmoreland, A.J. de CrespignyAn approach to high resolution diffusion tensor imaging in fixed primate brain
NeuroImage, 35 (2007), pp. 553-565
DuBose et al., 2011
J.J. DuBose, G. Barmparas, K. Inaba, D.M. Stein, T. Scalea, L.C. Cancio, J. Cole, B. Eastridge, L. BlackbouneIsolated severe traumatic brain injuries sustained during combat operations: demographics, mortality outcomes, and lessons to be learned from contrasts to civilian counterparts
J. Trauma, 70 (2011), pp. 11-16
Dyrby et al., 2012
T.B. Dyrby, L.V. Sogaard, M.G. Hall, M. Ptito, D.C. AlexanderContrast and stability of the axon diameter index from microstructure imaging with diffusion MRI
Magn. Reson. Med. (2012), 10.1002/mrm.24501
Edlow et al., 2012
B. Edlow, E. Takahashi, O. Wu, T. Benner, G. Dai, L. Bu, P.E. Grant, D.M. Greer, S.M. Greenberg, H.C. Kinney, R.D. FolkerthNeuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders
J. Neuropathol. Exp. Neurol., 71 (2012), pp. 531-546
Edlow et al.,2013
B.L. Edlow, R.L. Haynes, E. Takahashi, J.P. Klein, P. Cummings, T. Benner, D.M. Greer, S.M. Greenberg, O. Wu, H.C. Kinney, R.D. FolkerthDisconnection of the ascending arousal system in traumatic coma
J. Neuropathol. Exp. Neurol., 72 (2013), pp. 505-523
Faul et al., 2010
M. Faul, L. Xu, M.M. Wald, V.G. CoronadoTraumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations, and Deaths
Center for Disease Control and Prevention, National Center for Injury Prevention and Control (2010)
Fernandez-Espejo et al., 2012
D. Fernandez-Espejo, A. Soddu, D. Cruse, E.M. Palacios, C. Junque, Vanhaudenhuyse, E. Rivas, V. Newcombe, D.K. Menon, J.D. Pickard, S. Laureys, A.M. OwenA role for the default mode network in the bases of disorders of consciousness
Ann. Neurol., 72 (2012), pp. 335-343
Fuller et al., 2011
P. Fuller, D. Sherman, N.P. Pedersen, C.B. Saper, L, JReassessment of the structural basis of the ascending arousal system
J. Comp. Neurol., 519 (2011), pp. 933-956
Gennarelli et al., 1982
T.A. Gennarelli, L.E. Thibault, J.H. Adams, D.I. Graham, C.J. Thompson, R.P. MarcincinDiffuse axonal injury and traumatic coma in the primate
Ann. Neurol., 12 (1982), pp. 564-574
Geschwind, 1965
N. GeschwindDisconnexion syndromes in animals and man. I
Brain, 88 (1965), pp. 237-294
Giacino et al., 2012
J.T. Giacino, J. Whyte, E. Bagiella, K. Kalmar, N. Childs, A. Khademi, B. Eifert, D. Long, D.I. Katz, S. Cho, S.A. Yablon, M. Luther, F.M. Hammond, A. Nordenbo, P. Novak, W. Mercer, P. Maurer-Karattup, M. ShererPlacebo-controlled trial of amantadine for severe traumatic brain injury
N. Engl. J. Med., 366 (2012), pp. 819-826
Heads et al., 1991
T. Heads, M. Pollock, A. Robertson, W.H. Sutherland, S. AllpressSensory nerve pathology in amyotrophic lateral sclerosis
Acta Neuropathol. Berl., 82 (1991), pp. 316-320
Heidemann et al., 2010
R.M. Heidemann, D.A. Porter, A. Anwander, T. Feiweier, K. Heberlein, T.R. Knösche, R. TurnerDiffusion imaging in humans at 7 T using readout-segmented EPI and GRAPPA
Magn. Reson. Med., 64 (2010), pp. 9-14
Hess et al., 2006
C.P. Hess, P. Muherjee, E.T. Han, D. Xu, D.B. VigneronQ-ball reconstruction of multimodal fiber orientations using the spherical harmonic basis
Magn. Reson. Med., 56 (2006), pp. 104-117
Hoffmeister et al., 1991
B. Hoffmeister, W. Janig, S.J. LisneyA proposed relationship between circumference and conduction velocity of unmyelinated axons from normal and regenerated cat hindlimb cutaneous nerves
Neuroscience, 42 (1991), pp. 603-611
Horowitz et al., 2012
A. Horowitz, D. Barazany, G. Yovel, Y. AssafInter hemispheric transfer time and axon diameter properties of the corpus callosum
Proc. Int. Soc. Magn. Reson. Med. (2012), p. 3619
Hursh, 1939
J.B. HurshThe properties of growing nerve fibers
Am. J. Physiol., 127 (1939), pp. 29-35
Jbabdi et al., 2012
S. Jbabdi, S.N. Sotiropoulos, A.M. Savio, M. Grana, T.E.J. BehrensModel-based analysis of multishell diffusion MR data for tractography: how to get over fitting problems
Magn. Reson. Med., 68 (2012), pp. 1846-1855
Jones et al., 2013
D.K. Jones, T.R. Knösche, R. TurnerWhite matter integrity, fiber count, and other fallacies: the do's and don'ts of diffusion MRI
Magn. Reson. Med., 73 (2013), pp. 239-254
Kaufman and Rosenquist, 1985
E.S. Kaufman, A.C. RosenquistAfferent connections of the thalamic intralaminar nuclei in the cat
Brain Res., 335 (1985), pp. 281-296
Keil et al., 2012
B. Keil, J.N. Blau, S. Biber, P. Hoecht, V. Tountcheva, K. Setsompop, C. Triantafyllou, L.L. WaldA 64-channel 3 T array coil for accelerated brain MRI
Magn. Reson. Med. (2012), 10.1002/mrm.24427
Kinney and Samuels, 1994
H.C. Kinney, M.A. SamuelsNeuropathology of the persistent vegetative state. A review
J. Neuropathol. Exp. Neurol., 53 (1994), pp. 548-558
Kinomura et al., 1996
S. Kinomura, J. Larsson, B. Gulyas, P.E. RolandActivation by attention of the human reticular formation and thalamic intralaminar nuclei
Science, 271 (1996), pp. 512-515
Leuze et al., 2012
C.W. Leuze, A. Anwander, P.L. Bazin, C. Stüber, K. Reimann, S. Geyer, R. TurnerLayer-specific intracortical connectivity revealed with diffusion MRI
Cereb. Cortex (2012), 10.1093/cercor/bhs311
Lindsley et al., 1949
D.B. Lindsley, J.W. Bowden, H.W. MagounEffect upon the EEG of acute injury to the brain stem activating system
Electroencephalogr. Clin. Neurophysiol., 1 (1949), pp. 475-486
Mai et al., 2008
J.K. Mai, G. Paxinos, T. VossAtlas of the Human Brain
Elsevier (2008)
Marner et al., 2003
L. Marner, J.R. Nyengaard, Y. Tang, B. PakkenbergMarked loss of myelinated nerve fibers in the human brain with age
J. Comp. Neurol., 462 (2003), pp. 144-152
McNab et al., 2009
J.A. McNab, S. Jbabdi, S.C.L. Deoni, G. Douaud, T.E.J. Behrens, K.L. MillerHigh resolution diffusion weighted imaging in fixed human brain using diffusion weighted steady state free precession
NeuroImage, 46 (2009), pp. 775-785
McNab et al., 2013
J.A. McNab, J.R. Polimeni, R. Wang, J.C. Augustinack, K. Fujimoto, A. Stevens, T. Janssens, R. Farivar, R.D. Folkerth, W. Vanduffel, L.L. WaldSurface based analysis of diffusion orientation for identifying architectonic domains in the in vivo human cortex
NeuroImage, 69 (2013), pp. 87-100
Miller et al., 2011
K.L. Miller, C.J. Stagg, G. Douaud, S. Jbabdi, S.M. Smith, T.E.J. Behrens, M. Jenkinson, S.A. Chance, M.M. Esiri, N.L. Voets, N. Jenkinson, T.Z. Aziz, M.R. Turner, H. Johansen-Berg, J.A. McNabDiffusion imaging of whole, post-mortem human brains on a clinical MRI scanner
NeuroImage, 57 (2011), pp. 167-181
Morel et al., 1997
A. Morel, M. Magnin, D. JeanmonodMultiarchitectonic and stereotactic atlas of the human thalamus
J. Comp. Neurol., 387 (1997), pp. 588-630
Moruzzi and Magoun, 1949
P. Moruzzi, H.W. MagounBrain stem reticular formation and activation of the EEG
Electroencephalogr. Clin. Neurophysiol., 1 (1949), pp. 455-473
Nauta and Kuypers, 1958
W.J.H. Nauta, H.G.J.M. KuypersSome ascending pathways in the brain stem reticular formation
H.H. Jasper, L.D. Proctor, R.S. Knighton, W.C. Noshay, R.T. Costello (Eds.), Reticular Formation of the Brain, Little, Brown, and Company, Boston, MA (1958), pp. 3-30
Ommaya and Gennarelli, 1974
A.K. Ommaya, T.A. GennarelliCerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observations of blunt head injuries
Brain, 97 (1974), pp. 633-654
Ong and Wehrli, 2010
H.H. Ong, F.W. WehrliQuantifying axon diameter and intra-cellular volume fraction in excised mouse spinal cord with q-space imaging
NeuroImage, 51 (2010), pp. 1360-1366
Parvizi and Damasio, 2001
P.J. Parvizi, A. DamasioConsciousness and the brainstem
Cognition, 79 (2001), pp. 135-160
Parvizi and Damasio, 2003
J. Parvizi, A.R. DamasioNeuroanatomical correlates of brainstem coma
Brain, 126 (2003), pp. 1524-1536
Paxinos et al., 2011
G. Paxinos, H. Xu-Feng, G. Sengul, C. WatsonOrganization of Brainstem Nuclei. The Human Nervous System
Elsevier, Amsterdam (2011)
Piven et al., 1997
J. Piven, J. Bailey, B.J. Ranson, S. ArndtAn MRI study of the corpus callosum in autism
Am. J. Psychiatry, 154 (1997), pp. 1051-1056
Reese et al., 1995
N.B. Reese, E. Garcia-Rill, R.D. SkinnerThe pedunculopontine nucleus—auditory input, arousal and pathophysiology
Prog. Neurobiol., 47 (1995), pp. 105-133
Ringo et al., 1994
J.L. Ringo, R.W. Doty, S. Demeter, P.Y. SimardTime is of the essence: a conjecture th at hemispheric specialization arises from interhemispheric conduction delay
Cereb. Cortex, 4 (1994), pp. 331-343
Schiff and Plum, 2000
N.D. Schiff, F. PlumThe role of arousal and “gating” systems in the neurology of impaired consciousness
J. Clin. Neurophysiol., 17 (2000), pp. 438-452
Schiff et al., 2007
N.D. Schiff, J.T. Giacino, K. Kalmar, J.D. Victor, K. Baker, M. Gerber, B. Fritz, B. Eisenberg, T. Biondi, J. O'Connor, E.J. Kobylarz, S. Farris, A. Machado, C. McCagg, F. Plum, J.J. Fins, A.R. RezaiBehavioural improvements with thalamic stimulation after severe traumatic brain injury
Nature, 448 (2007), pp. 600-603
Schmahmann and Pandya, 2008
J.D. Schmahmann, D.N. PandyaDisconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems
Cortex, 44 (2008), pp. 1037-1066
Setsompop et al., 2013
K. Setsompop, R. Kimmlingen, E. Eberlein, T. Witzel, J. Cohen-Adad, J.A. McNab, B. Keil, M.D. Tisdall, P. Hoecht, P. Dietz, S.F. Cauley, V. Tountcheva, V. Matschl, V.H. Lenz, K. Heberlein, A. Potthast, H. Thein, J. Van Horn, A. Toga, F. Schmitt, D. Lehne, B.R. Rosen, V. Wedeen, L.L. WaldPushing the limits of in vivo diffusion MRI for the Human Connectome Project
Neuroimage, 80 (2013), pp. 220-233
Shute and Lewis, 1963
C.C. Shute, P.R. LewisCholinesterase-containing systems of the brain of the rat
Nature, 199 (1963), pp. 1160-1164
Silva et al., 2010
S. Silva, X. Alacoque, O. Fourcade, K. Samil, P. Marque, R. Woods, J. Mazziotta, F. Chollet, I. LoubinouxWakefulness and loss of awareness: brain and brainstem interaction in the vegetative state
Neurology, 74 (2010), pp. 313-320
Skandsen et al., 2011
T. Skandsen, K.A. Kvistad, O. Solheim, S. Lydersen, I.H. Strand, A. VikPrognostic value of magnetic resonance imaging in moderate and severe head injury: a prospective study of early MRI findings and one-year outcome
J. Neurotrauma, 28 (2011), pp. 691-699
Smith et al., 2000
D.H. Smith, M. Nonaka, R. Miller, M. Leoni, X.H. Chen, D. Alsop, D.F. MeaneyImmediate coma following inertial brain injury dependent on axonal damage in the brainstem
J. Neurosurg., 93 (2000), pp. 315-322
Stanisz et al., 1997
G.J. Stanisz, A. Szafer, G.A. Wright, R.M. HenkelmanAn analytical model for restricted diffusion in bovine optic nerve
Magn. Reson. Med., 37 (1997), pp. 103-111
Starzl et al., 1951
T.E. Starzl, C.W. Taylor, H.W. MagounAscending conduction in reticular activating system, with special reference to the diencephalon
J. Neurophysiol., 14 (1951), pp. 461-477
Steriade and Glenn, 1982
M. Steriade, L.L. GlennNeocortical and caudate projections of intralaminar thalamic neurons and their synaptic excitation from midbrain reticular core
J. Neurophysiol., 48 (1982), pp. 352-371
Strich, 1961
S.J. StrichShearing of nerve fibers as a cause of brain damage due to head injury: a pathological study of twenty cases
Lancet, 2 (1961), pp. 443-448
Tournier et al., 2004
J.D. Tournier, F. Calamante, D.G. Gadian, A. ConnellyDirect estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution
NeuroImage, 23 (2004), pp. 1176-1185
Van Essen et al., 2012
D.C. Van Essen, K. Ugurbil, E. Auerbach, D. Barch, T.E. Behrens, R. Bucholz, A. Chang, L. Chen, M. Corbetta, S.W. Curtiss, S. Della Penna, D. Feinberg, M.F. Glasser, N. Harel, A.C. Heath, L. Larson-Prior, D. Marcus, G. Michalareas, S. Moeller, R. Oostenveld, S.E. Petersen, F. Prior, B.L. Schlaggar, S.M. Smith, A.Z. Snyder, u, J, Yacoub, WU–Minn HCP ConsortiumThe human connectome project: a data acquisition perspective
NeuroImage, 62 (2012), pp. 2222-22431
Vanhaudenhuyse et al., 2010
A. Vanhaudenhuyse, Q. Noirhomme, L.J.-F. Tshibanda, M.-A. Bruno, P. Boveroux, C. Schnakers, A. Soddu, V. PerlbargDefault network connectivity reflects the level of consciousness in non-communicative brain-damaged patients
Brain, 133 (2010), pp. 161-171
Vertes and Martin, 1988
R.P. Vertes, G.F. MartinAutoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat
J. Comp. Neurol., 275 (1988), pp. 511-541
Wang et al., 2007
R. Wang, T. Benner, A.G. Sorensen, V.J. WedeenDiffusion toolkit: a software package for diffusion imaging data processing and tractography
Proc. Int. Soc. Magn. Reson. Med., 15 (2007), p. 3720
Wedeen et al., 2005
V. Wedeen, P. Hagmann, W. Tseng, T. Reese, R. WeisskoffMapping complex tissue architecture with diffusion spectrum magnetic resonance imaging
Magn. Reson. Med., 54 (2005), pp. 1377-1386
Wedeen et al., 2008
V.J. Wedeen, R.P. Wang, J.D. Schmahmann, T. Benner, W.Y.I. Tseng, G. Dai, D.N. Pandya, P. Hagmann, H. D'Arceuil, A.J. de CrespignyDiffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers
NeuroImage, 41 (2008), pp. 1267-1277
Whyte and Myers, 2009
J. Whyte, R. MyersIncidence of clinically significant responses to zolpidem among patients with disorders of consciousness
Am. J. Phys. Med. Rehabil., 88 (2009), pp. 410-418
Zhang et al., 2011
H. Zhang, P.L. Hubbard, G.J.M. Parker, D.C. AlexanderAxon diameter mapping in the presence of orientation dispersion with diffusion MRI
NeuroImage, 56 (2011), pp. 1301-1315
1

Jennifer A. McNab and Brian L. Edlow are co-first authors of this manuscript.