Project: Research project

Project Details


Clinical manifestations (functional deficit) of spinal cord diseases
such as multiple sclerosis or traumatic cord injury are thought to be
closely related to the degree of axonal disruption and/or demyelination-
the ability of spinal cord axons to conduct nerve impulses is dependent
on the fidelity of the myelin sheaths. Conventional magnetic resonance
(MR) images do not provide information regarding axonal integrity.
However, MR-based measurement of apparent diffusion coefficients (ADC)
can exploit the intrinsic anisotropy of white matter-the myelin sheaths
restrict water diffusion perpendicular to the uninjured axons, but do
not affect diffusion parallel to the axons. Thus ADC measured
longitudinally (lADC) and transverse (tADC) to the axon fiber axis may
be used to detect and characterize white matter damage by quantitating
the loss of normal white matter diffusion anisotropy. However, ADC is
also sensitive to changes in the relative intracellular/extracellular
water content; therefore, the combined effects of axonal swelling,
extracellular edema, and demyelination in spinal cord disease complicate
the interpretation of MRI-based measurements of ADC.

The primary objective is to utilize a computer model to determine the
dependence of MRI-based measurements of tADC and 1ADC in spinal cord
white matter on axonal morphology (distribution of axons, cellular
volume fraction) and axonal integrity (permeability). A computer
simulation of diffusion among axons has been developed that uses
microscopic images of white matter as input; thus no assumptions are
made concerning the axonal arrangement, cellular volume, or myelin
sheath thicknesses. Preliminary results exhibit excellent agreement
between the computer calculations and ADC measured in spinal cord.
Computer simulations indicate that the competing affects of axonal
swelling and demyelination can be deconvolved, without making explicit
assumptions for the values of the intrinsic intracellular and
extracellular diffusion coefficients. The model will be validated by
comparing computer predictions to measured ADC in animal models of
multiple sclerosis (EAE in rats and mice) and traumatic cord injury
(weight-drop injury in rats). The remainder of the research effort is
directed at determining the sensitivity of ADC to pathology in an animal
model of early multiple sclerosis.

A reliable model for white matter diffusion, which can relate measured
ADC values to underlying pathologic changes at the cellular level, would
one day allow the radiologist to infer axonal integrity, and thus
enhance prognostic capability of MRI in spinal cord disease.
Effective start/end date9/15/989/30/98


  • National Institute of Neurological Disorders and Stroke


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