functional correlates of diffusion tensor imaging in spinal cord injury benjamin m. ellingson, ph.d....
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Functional Correlates of Diffusion Tensor Imaging in Spinal Cord Injury
Benjamin M. Ellingson, Ph.D.1,2 Shekar N. Kurpad, M.D., Ph.D.2 Brian D. Schmit, Ph.D.1
1 Department of Biomedical Engineering, Marquette University2 Department of Neurosurgery, Medical College of Wisconsin
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Motivation Traditional MRI is not sensitive to axonal injury
(Falconer, 1994; Kulkarni, 1988)
Traditional MRI is no better than neurological exam (Flanders, 1999; Shepard, 1999; Bondurant, 1990)
Diffusion Tensor Imaging (DTI) is more sensitive to axon injury (Ford, 1994; Schwartz, 2003)
Objective: Determine if DTI is sensitive to quantitative measures of sensory function (i.e. electrophysiology).
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Diffusion Tensor Imaging (DTI)
DTI uses MRI gradients to “tag” diffusing H2O molecules
Apparent Diffusion Coefficient (ADC) is dependent on boundaries to diffusion
lADC
tADC
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Differential Sensitivity of DTIAxonal Damage (Song, 2003; 2002; Nair, 2005; Sun, 2006)
↓ lADC
Myelin Damage (Song, 2003; 2002; Nair, 2005; Sun, 2006)
↑ tADC
Image Source: Ellingson et al., Concepts in Magn Reson Part A, 2008
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Spinal Somatosensory Evoked Potentials (SpSEPs)
NormalIncomplete SCI Complete SCI
Normal SCI
No temporalCoherence
Loss ofAmplitude
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Experimental Spinal Contusion
Impactor
Vertebral Body
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Spinothalamic Tract (STT) & Pain
C-fiber input to LSTT (Valeriani, 2007; Li, 1991; Latash, 1988)A-fiber input to MSTT (Valeriani, 2007; Latash, 1988)
Kandel, 2000, Principles of Neural Science
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Hypothesis
Diffusion measurements in the spinothalamic tracts (STTs) correlate with specific components of the SpSEP during high-intensity sciatic nerve stimulation.
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Methods - Animals
Neurologically intact (n = 8) 2 weeks after SCI (n = 8) 5 weeks after SCI (n = 8)
Spinal Contusion at T8
(Modified from Baker, 2005)
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Methods ~ DTI 9.4-T MR Scanner, Embedded in Agarose Gelatin 24 axial images though spinal cord (~7 cm) 6 directions, 100 um resolution Standard Pulsed Gradient Spin-Echo DTI (PG-SE) b = 500 s/mm2
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Methods ~ SpSEPs
- Animals were anesthetized (Ketamine/Medetomidine IP)-400 V, 10 mA, 3.5 Hz monophasic square wave, pulse duration 500 us-Amplified 20,000x, sampled at 21 kHz, total of 1000 epochs
Image source: Ellingson et al., J Neurotrauma, 2008, Under Review
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Results ~ DTI
T2-w
lADC
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Results ~ SpSEPs
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Results~Correlation DTI and SpSEPsLSTT lADC Late component (C-fiber)
(All animals, R = 0.905, P < 0.001)(2 weeks, R = 0.817, P < 0.01)(5 weeks, R = 0.843, P < 0.01)
MSTT lADC Very Early Component (A-fiber)(2 weeks, R = 0.812, P < 0.01)(5 weeks, R = 0.841, P < 0.01)
Dorsal Columns lADC & tADC Very Early to Early
lADC: VE (2 weeks, R = 0.852, P < 0.01) E (5 weeks, R = -0.718, P < 0.05)
tADC: VE (2 weeks, R = 0.792, P < 0.01) E (5 weeks, R = 0.835, P < 0.01)
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Discussion LSTT lADC Late component (C-fiber)
MSTT lADC Very Early Component (A-fiber)
Dorsal Columns lADC & tADC Very Early to Early
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Future Studies More groups & more specimens
Neural stem cells (C17.2) known to cause allodynia Does lADC & SpSEP amplitude increase beyond control?
Prognostic capabilities of DTI Does DTI predict final neurological outcome?
Motor evoked potentials (MEPs) Is DTI sensitive to motor function deficit?
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Thank youBrian Schmit, Ph.D.Shekar Kurpad, M.D., Ph.D.Carmen Clark, B.S.James Grosek, B.S.Angie Geiger, B.S.Christy Stadig, B.S.Krishnaj Gourab, M.D.
Funding: NIHFalk FoundationDepartment of Biomedical Engineering, Marquette UniversityDepartment of Neurosurgery, Radiology, Biophysics at MCWVA Medical Center, Milwaukee WI