Functional Correlates of Diffusion Tensor Imaging in Spinal Cord Injury

1
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
  University
• 2 Department of Neurosurgery, Medical College of
  Wisconsin

2
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).

3
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
4
Differential Sensitivity of DTI
Axonal 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
5
Spinal Somatosensory Evoked Potentials (SpSEPs)
6
Experimental Spinal Contusion
Impactor
Vertebral Body
7
Spinothalamic Tract (STT) Pain
C-fiber input to LSTT (Valeriani, 2007 Li, 1991
Latash, 1988)
Ad-fiber input to MSTT (Valeriani, 2007 Latash,
1988)
Kandel, 2000, Principles of Neural Science
8
Hypothesis

• Diffusion measurements in the spinothalamic
  tracts (STTs) correlate with specific components
  of the SpSEP during high-intensity sciatic nerve
  stimulation.

9
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)
10
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

11
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
12
Results DTI
T2-w
lADC
13
Results SpSEPs
14
ResultsCorrelation DTI and SpSEPs

• LSTT lADC ? Late component (C-fiber)
• (All animals, R 0.905, P lt 0.001)
• (2 weeks, R 0.817, P lt 0.01)
• (5 weeks, R 0.843, P lt 0.01)
• MSTT lADC ? Very Early Component (Ad-fiber)
• (2 weeks, R 0.812, P lt 0.01)
• (5 weeks, R 0.841, P lt 0.01)
• Dorsal Columns lADC tADC ? Very Early to Early
• lADC VE (2 weeks, R 0.852, P lt 0.01)
• E (5 weeks, R -0.718, P lt 0.05)
• tADC VE (2 weeks, R 0.792, P lt 0.01)
• E (5 weeks, R 0.835, P lt 0.01)

15
Discussion

• LSTT lADC ? Late component (C-fiber)
• MSTT lADC ? Very Early Component (Ad-fiber)
• Dorsal Columns lADC tADC ? Very Early to Early

16
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?

17
Thank you

• Brian 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
• NIH
• Falk Foundation
• Department of Biomedical Engineering, Marquette
  University
• Department of Neurosurgery, Radiology, Biophysics
  at MCW
• VA Medical Center, Milwaukee WI