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

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).

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

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

Spinal Somatosensory Evoked Potentials (SpSEPs)

NormalIncomplete SCI Complete SCI

Normal SCI

No temporalCoherence

Loss ofAmplitude

Experimental Spinal Contusion

Impactor

Vertebral Body

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

Hypothesis

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

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)

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

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

Results ~ DTI

T2-w

lADC

Results ~ SpSEPs

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)

Discussion LSTT lADC Late component (C-fiber)

MSTT lADC Very Early Component (A-fiber)

Dorsal Columns lADC & tADC Very Early to Early

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?

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