Tracking neuronal fiber pathways in the living human brain.

Functional imaging with positron emission tomography and functional MRI has revolutionized studies of the human brain. Understanding the organization of brain systems, especially those used for cognition, remains limited, however, because no methods currently exist for noninvasive tracking of neuronal connections between functional regions [Crick, F. & Jones, E. (1993) Nature (London) 361, 109-110]. Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects.

[1]  J. Dejerine.  Anatomie des centres nerveux , 1895 .

[2]  Sabrina S Wilson.  Radiology , 1938, Glasgow Medical Journal.

[3]  C. G. Smith.  The Anatomy of the Nervous System , 1952 .

[4]  John Crank,et al.  The Mathematics Of Diffusion , 1956 .

[5]  J. Westwater,et al.  The Mathematics of Diffusion. , 1957 .

[6]  J. E. Tanner,et al.  Spin diffusion measurements : spin echoes in the presence of a time-dependent field gradient , 1965 .

[7]  M. Critchley.  The parietal lobes , 1966 .

[8]  LaVail Jh,et al.  The retrograde transport method. , 1975 .

[9]  P. Mansfield.  Multi-planar image formation using NMR spin echoes , 1977 .

[10]  C. Clayman,et al.  The Human Central Nervous System: A Synopsis and Atlas , 1979 .

[11]  M. Raichle,et al.  Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Thanos,et al.  A study in developing visual systems with a new method of staining neurones and their processes in fixed tissue. , 1987, Development.

[13]  G F Vrensen,et al.  Anterograde tracing in the brain using autoradiography and HRP‐histochemistry. A comparison at the ultrastructural level , 1988, Journal of microscopy.

[14]  F. Wouterlood,et al.  Immunohistochemical localization of monoamines and cyclic nucleotides. Their application in quantitative immunofluorescence studies and tracing monoaminergic neuronal connections. , 1988, Acta histochemica. Supplementband.

[15]  M. G. Honig,et al.  Dil and DiO: versatile fluorescent dyes for neuronal labelling and pathway tracing , 1989, Trends in Neurosciences.

[16]  J. Tsuruda,et al.  Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. , 1990, Radiology.

[17]  C. D. Stern,et al.  The Human Central Nervous System: A Synopsis and Atlas, 3rd edition R. Nieuwenhuys, J. Voogd and C. van Huijzen. ISBN 0-387-13441-7. Price: $49.00. Springer, Berlin, 1988 , 1990, Neurochemistry International.

[18]  J V Hajnal,et al.  Normal and abnormal white matter tracts shown by MR imaging using directional diffusion weighted sequences. , 1990, Journal of computer assisted tomography.

[19]  D. J. Felleman,et al.  Distributed hierarchical processing in the primate cerebral cortex. , 1991, Cerebral cortex.

[20]  R. Turner,et al.  Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[21]  A. Reiner,et al.  Biotinylated dextran amine as an anterograde tracer for single- and double-labeling studies , 1992, Journal of Neuroscience Methods.

[22]  R. S. Hinks,et al.  Time course EPI of human brain function during task activation , 1992, Magnetic resonance in medicine.

[23]  Ravi S. Menon,et al.  Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[24]  F. Crick,et al.  Backwardness of human neuroanatomy , 1993, Nature.

[25]  M E Raichle,et al.  Images of the mind: studies with modern imaging techniques. , 1994, Annual review of psychology.

[26]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[27]  A Yagishita,et al.  Location of the corticospinal tract in the internal capsule at MR imaging. , 1994, Radiology.

[28]  H Burton,et al.  Ipsilateral intracortical connections of physiologically defined cutaneous representations in areas 3b and 1 of macaque monkeys: Projections in the vicinity of the central sulcus , 1995, The Journal of comparative neurology.

[29]  T E Conturo,et al.  Diffusion MRI: Precision, accuracy and flow effects , 1995, NMR in biomedicine.

[30]  P. Basser.  Inferring microstructural features and the physiological state of tissues from diffusion‐weighted images , 1995, NMR in biomedicine.

[31]  Song-Lin Ding,et al.  A modification of biotinylated dextran amine histochemistry for labeling the developing mammalian brain , 1995, Journal of Neuroscience Methods.

[32]  A. Mccarthy.  Development , 1996, Current Opinion in Neurobiology.

[33]  E. Akbudak,et al.  Encoding of anisotropic diffusion with tetrahedral gradients: A general mathematical diffusion formalism and experimental results , 1996, Magnetic resonance in medicine.

[34]  T. L. Davis,et al.  Morphometry of in vivo human white matter association pathways with diffusion‐weighted magnetic resonance imaging , 1997, Annals of neurology.

[35]  S. Petersen,et al.  Human Brain Mapping 6:203–215(1998) � Functional MRI Studies of Word-Stem Completion: Reliability Across Laboratories and Comparison to Blood Flow Imaging With PET , 2022 .

[36]  M. Corbetta,et al.  A Common Network of Functional Areas for Attention and Eye Movements , 1998, Neuron.

[37]  P. V. van Zijl,et al.  Three‐dimensional tracking of axonal projections in the brain by magnetic resonance imaging , 1999, Annals of neurology.

[38]  A. Snyder,et al.  Quantitative diffusion-tensor anisotropy brain MR imaging: normative human data and anatomic analysis. , 1999, Radiology.

[39]  D. Wilkin,et al.  Neuron , 2001, Brain Research.