Lisa Michelle Rohrer MA, Abstract Co-Author: Nothing to Disclose

Soe S Mar, Abstract Co-Author: Nothing to Disclose

Joshua S. Shimony MD, PhD, Abstract Co-Author: Nothing to Disclose

Abraham Z. Snyder PhD, Abstract Co-Author: Nothing to Disclose

Tammie Smith Benzinger MD, PhD, Presenter: Speakers Bureau, Siemens AG Travel support, Siemens AG

The leukodystrophies are CNS diseases that result in abnormal myelin development or maintenance with possible secondary axonal injury. In animal models, axonal injury has been linked to an increase in axial diffusivity (λ||) that is distinct from the increase in radial diffusivity (λ⊥) observed with myelin abnormality on diffusion tensor MRI (DTI). The purpose of this investigation was to evaluate the relation of λ|| and λ⊥ to human leukodystrophy type and severity.

Participants were 7 affected patients or carriers of leukodystrophy and 21 age- and sex-matched normal controls. A standard clinical brain MR protocol was performed at 3 T (Siemens Trio) in addition to a 25-direction DTI protocol with multiple, scaled b-values (bmax 1400). After registration to an age-appropriate atlas, DTI images were subjected to ROI analysis in ImageJ. Composite measures of λ|| and λ⊥ were created by averaging across a set of 9 ROIs leading out from lateral ventricles in each quadrant of the brain (right/left anterior, right/left posterior).

Analysis of λ⊥ and λ|| showed the following: •Alexander Disease (n = 3). Patients had elevated in λ⊥ at all sites and elevated λ|| at anterior sites. Results are consistent with a course involving progressive demyelination with frontal predominance. •Pelizaeus Merzbacher Disease Carriers (n = 2). Carriers had elevated λ⊥ at the right posterior site and normal λ||. Results may help to explain the presence of subtle symptoms in some carriers. •Adrenoleukodystrophy (n = 2). Patients had elevated λ⊥. The patient with autosomal recessive ALD also had elevated λ|| at two sites, whereas the patient with X-linked ALD had reduced λ|| at two sites. The patient with X-linked ALD died within days of the scan; the reduction in λ|| suggests acute axonal injury at the time of the scan.

Measures of MRI directional diffusivity show logical covariation with leukodystrophy type and severity. Further validation of these measures may help to clarify how myelin and axonal injury contribute to leukodystrophy symptoms.

MRI directional diffusivity may be useful in differentiating leukodystrophies and determining prognosis. It may help to identify candidates for new interventions in the pre-clinical leukodystrophy.

Rohrer, L, Mar, S, Shimony, J, Snyder, A, Benzinger, T, Radial and Axial Diffusivity Correlates of Leukodystrophy Type and Severity.  Radiological Society of North America 2010 Scientific Assembly and Annual Meeting, November 28 - December 3, 2010 ,Chicago IL. http://archive.rsna.org/2010/9015841.html