Applying functional MRI to the spinal cord and brainstem.

Functional magnetic resonance imaging of the spinal cord (spinal fMRI) has facilitated the noninvasive visualization of neural activity in the spinal cord (SC) and brainstem of both animals and humans. This technique has yet to gain the widespread usage of brain fMRI, due in part to the intrinsic technical challenges spinal fMRI presents and to the narrower scope of applications it fulfills. Nonetheless, methodological progress has been considerable and rapid. To date, spinal fMRI studies have investigated SC function during sensory or motor task paradigms in spinal cord injury (SCI), multiple sclerosis (MS) and neuropathic pain (NP) patient populations, all of which have yielded consistent and sensitive results. The most recent study in our laboratory has successfully used spinal fMRI to examine cervical SC activity in a SCI patient with a metallic fixation device spanning the C(4) to C(6) vertebrae, a critical step in realizing the clinical utility of the technique. The literature reviewed in this article suggests that spinal fMRI is poised for usage in a wide range of patient populations, as multiple groups have observed intriguing, yet consistent, results using standard, readily available MR systems and hardware. The next step is the implementation of this technique in the clinic to supplement standard qualitative behavioral assessments of SCI. Spinal fMRI may offer insight into the subtleties of function in the injured and diseased SC, and support the development of new methods for treatment and monitoring.

[1]  Patrick W Stroman,et al.  Spinal fMRI investigation of human spinal cord function over a range of innocuous thermal sensory stimuli and study-related emotional influences. , 2009, Magnetic resonance imaging.

[2]  M. Filippi,et al.  Cortical reorganisation in patients with MS , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[3]  P. W. Stroman,et al.  Mapping of Neuronal Function in the Healthy and Injured Human Spinal Cord with Spinal fMRI , 2002, NeuroImage.

[4]  F. Barkhof,et al.  The spinal cord in multiple sclerosis: relationship of high-spatial-resolution quantitative MR imaging findings to histopathologic results. , 2004, Radiology.

[5]  W. Backes,et al.  Functional MRI of the spinal cord: will it solve the puzzle of pain? , 2003, JBR-BTR : organe de la Societe royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie.

[6]  Domenico Caputo,et al.  Tactile-associated recruitment of the cervical cord is altered in patients with multiple sclerosis , 2008, NeuroImage.

[7]  P. W. Stroman,et al.  Spinal fMRI during proprioceptive and tactile tasks in healthy subjects: activity detected using cross-correlation, general linear model and independent component analysis , 2008, Neuroradiology.

[8]  Giovanni Giulietti,et al.  Issues about the fMRI of the human spinal cord. , 2004, Magnetic resonance imaging.

[9]  P W Stroman,et al.  Tactile Sensory and Pain Networks in the Human Spinal Cord and Brain Stem Mapped by Means of Functional MR Imaging , 2010, American Journal of Neuroradiology.

[10]  Richard G. Wise,et al.  Physiological noise modelling for spinal functional magnetic resonance imaging studies , 2008, NeuroImage.

[11]  Daniel P. Ferris,et al.  Muscle activation during unilateral stepping occurs in the nonstepping limb of humans with clinically complete spinal cord injury , 2004, Spinal Cord.

[12]  S. Hunt,et al.  Induction of c-fos-like protein in spinal cord neurons following sensory stimulation , 1987, Nature.

[13]  R. Andrew,et al.  Magnetic resonance imaging of neuronal and glial swelling as an indicator of function in cerebral tissue slices , 2008, Magnetic resonance in medicine.

[14]  P. Batchelor,et al.  International Society for Magnetic Resonance in Medicine , 1997 .

[15]  P. Stroman,et al.  Extravascular proton‐density changes as a non‐BOLD component of contrast in fMRI of the human spinal cord , 2002, Magnetic resonance in medicine.

[16]  Patrick W. Stroman,et al.  Development and validation of retrospective spinal cord motion time-course estimates (RESPITE) for spin-echo spinal fMRI: Improved sensitivity and specificity by means of a motion-compensating general linear model analysis , 2008, NeuroImage.

[17]  P. London Injury , 1969, Definitions.

[18]  H. Fields,et al.  Pain and the Placebo: What We Have Learned , 2005, Perspectives in biology and medicine.

[19]  R Pórszász,et al.  Signal changes in the spinal cord of the rat after injection of formalin into the hindpaw: characterization using functional magnetic resonance imaging. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Wu,et al.  Functional MR Imaging of the Cervical Spinal cord by Use of 20Hz Functional Electrical Stimulation to Median Nerve , 2007, 2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[21]  Geng Li,et al.  Proton-density-weighted spinal fMRI with sensorimotor stimulation at 0.2 T , 2006, NeuroImage.

[22]  Patrick W. Stroman,et al.  Spatial normalization, bulk motion correction and coregistration for functional magnetic resonance imaging of the human cervical spinal cord and brainstem. , 2008, Magnetic resonance imaging.

[23]  M D O'Brien,et al.  Spinal Cord Injury: Progress, Promise and Priorities , 2006 .

[24]  Maria Fitzgerald,et al.  C-fos can be induced in the neonatal rat spinal cord by both noxious and innocuous peripheral stimulation , 1996, Pain.

[25]  Noritaka Kawashima,et al.  Alternate leg movement amplifies locomotor-like muscle activity in spinal cord injured persons. , 2005, Journal of neurophysiology.

[26]  Patrick W Stroman,et al.  Functional imaging of the rat cervical spinal cord , 2002, Journal of magnetic resonance imaging : JMRI.

[27]  Patrick W Stroman,et al.  In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change. , 2010, Magnetic resonance imaging.

[28]  Johan Michiels,et al.  Functional MRI of the cervical spinal cord on 1.5 T with fingertapping: to what extent is it feasible? , 2006, Neuroradiology.

[29]  Laurel O. Sillerud,et al.  Functional Magnetic Resonance Imaging of Motor Activation in the Human Cervical Spinal Cord , 1996, NeuroImage.

[30]  E. Jankowska,et al.  How Can Corticospinal Tract Neurons Contribute to Ipsilateral Movements? A Question With Implications for Recovery of Motor Functions , 2006, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[31]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Yeyu Xiao,et al.  Functional MR Imaging of the Cervical Spinal Cord by Use of Electrical Stimulation at LI4 (Hegu) , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[33]  M. Filippi,et al.  Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosis , 2008, Magnetic resonance in medicine.

[34]  J. Brooks,et al.  A role for the brainstem in central sensitisation in humans. Evidence from functional magnetic resonance imaging , 2005, Pain.

[35]  J Nissanov,et al.  Functional MR imaging of the human cervical spinal cord. , 2001, AJNR. American journal of neuroradiology.

[36]  James Lowe,et al.  Spinal cord atrophy in multiple sclerosis caused by white matter volume loss. , 2005, Archives of neurology.

[37]  G. Gebhart,et al.  Descending modulation of pain , 2004, Neuroscience & Biobehavioral Reviews.

[38]  R. Edelman,et al.  Magnetic resonance imaging (2) , 1993, The New England journal of medicine.

[39]  P W Stroman,et al.  BOLD MRI of the human cervical spinal cord at 3 tesla , 1999, Magnetic resonance in medicine.

[40]  Jonathan C. W. Brooks,et al.  Noninvasive brain imaging: Functional magnetic resonance imaging (fMRI) of the spinal cord : a methodological study , 2004 .

[41]  Edward S Yang,et al.  Spinal effects of acupuncture stimulation assessed by proton density-weighted functional magnetic resonance imaging at 0.2 T. , 2005, Magnetic resonance imaging.

[42]  P W Stroman,et al.  Detection of the neuronal activity occurring caudal to the site of spinal cord injury that is elicited during lower limb movement tasks , 2007, Spinal Cord.

[43]  G H Glover,et al.  Image‐based method for retrospective correction of physiological motion effects in fMRI: RETROICOR , 2000, Magnetic resonance in medicine.

[44]  P. Stroman,et al.  Discrimination of errors from neuronal activity in functional MRI of the human spinal cord by means of general linear model analysis , 2006, Magnetic resonance in medicine.

[45]  R. Neptune,et al.  Does unilateral pedaling activate a rhythmic locomotor pattern in the nonpedaling leg in post-stroke hemiparesis? , 2006, Journal of neurophysiology.

[46]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[47]  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.

[48]  P. Stroman,et al.  Investigation of human cervical and upper thoracic spinal cord motion: Implications for imaging spinal cord structure and function , 2007, Magnetic resonance in medicine.

[49]  P. Huttenlocher Neurological Anatomy in Relation to Clinical Medicine , 1970, The Yale Journal of Biology and Medicine.

[50]  P W Stroman,et al.  fMRI of the lumbar spinal cord during a lower limb motor task , 2004, Magnetic resonance in medicine.

[51]  W. Backes,et al.  Functional MR imaging of the cervical spinal cord by use of median nerve stimulation and fist clenching. , 2001, AJNR. American journal of neuroradiology.

[52]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[53]  Patrick W Stroman,et al.  Magnetic resonance imaging of neuronal function in the spinal cord: spinal FMRI. , 2005, Clinical medicine & research.

[54]  Walter H. Backes,et al.  Spinal cord functional MRI at 3 T: Gradient echo echo-planar imaging versus turbo spin echo , 2008, NeuroImage.

[56]  H. Gray Gray's Anatomy , 1858 .

[57]  M. Filippi,et al.  Associations between cervical cord gray matter damage and disability in patients with multiple sclerosis. , 2007, Archives of neurology.

[58]  W. Donovan,et al.  International Standards For Neurological Classification Of Spinal Cord Injury , 2003, The journal of spinal cord medicine.

[59]  James Lowe,et al.  Spinal Cord Gray Matter Demyelination in Multiple Sclerosis—A Novel Pattern of Residual Plaque Morphology , 2006, Brain pathology.

[60]  Patrick W Stroman,et al.  Correlation of functional activation in the rat spinal cord with neuronal activation detected by immunohistochemistry , 2004, NeuroImage.

[61]  D. Tank,et al.  Functional Brain Mapping Using Magnetic Resonance Imaging: Signal Changes Accompanying Visual Stimulation , 1992, Investigative radiology.

[62]  P. Stroman,et al.  Noninvasive assessment of the injured human spinal cord by means of functional magnetic resonance imaging , 2004, Spinal Cord.

[63]  P W Stroman,et al.  Functional magnetic resonance imaging of the human cervical spinal cord with stimulation of different sensory dermatomes. , 2002, Magnetic resonance imaging.

[64]  W. S. Monkhouse,et al.  GRAY'S ANATOMY , 1947 .

[65]  J. W. Belliveau,et al.  Functional Brain Mapping Using Magnetic Resonance Imaging , 1991, Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society Volume 13: 1991.

[66]  Boguslaw Tomanek,et al.  Functional magnetic resonance imaging within the rat spinal cord following peripheral nerve injury , 2007, NeuroImage.

[67]  Laszlo Zaborszky,et al.  Functional localization of brainstem and cervical spinal cord nuclei in humans with fMRI. , 2002, AJNR. American journal of neuroradiology.

[68]  T. Herdegen,et al.  Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins , 1998, Brain Research Reviews.

[69]  Toshiki Endo,et al.  Blood Oxygenation Level-Dependent Visualization of Synaptic Relay Stations of Sensory Pathways along the Neuroaxis in Response to Graded Sensory Stimulation of a Limb , 2006, The Journal of Neuroscience.

[70]  Gian Domenico Iannetti,et al.  Behavioral/systems/cognitive Functional Responses in the Human Spinal Cord during Willed Motor Actions: Evidence for Side-and Rate-dependent Activity , 2022 .

[71]  F. Barkhof,et al.  Post-mortem high-resolution MRI of the spinal cord in multiple sclerosis: a correlative study with conventional MRI, histopathology and clinical phenotype. , 2001, Brain : a journal of neurology.