Diffusion tensor imaging detects axonal injury and demyelination in the spinal cord and cranial nerves of a murine model of globoid cell leukodystrophy.
NMR Biomed
; 22(10): 1100-6, 2009 Dec.
Article
en En
| MEDLINE
| ID: mdl-19650072
ABSTRACT
Globoid cell leukodystrophy is an inherited neurodegenerative disorder caused by a deficiency of the lysosomal enzyme galactosylceramidase. In both human patients and the authentic murine Twitcher model, pathological findings include demyelination as well as axonal damage in both the central and peripheral nervous system. Diffusion tensor imaging (DTI) has emerged as a powerful noninvasive technique that is sensitive to these white matter disease processes. Increases in radial diffusivity (lambda perpendicular) and decreases in axial diffusivity (lambda parallel) correlate with histopathological evidence of demyelination and axonal damage, respectively. Compared to age-matched, normal littermates, DTI of optic nerve and trigeminal nerve in end-stage Twitcher mice displayed a statistically significant increase in lambda perpendicular and decrease in lambda parallel, consistent with previously characterized demyelination and axonal damage in these regions. In the Twitcher spinal cord, a statistically significant decrease in lambda parallel was identified in both the dorsal and ventrolateral white matter, relative to normal controls. These results were consistent with immunofluorescence evidence of axonal damage in these areas as detected by staining for nonphosphorylated neurofilaments (SMI32). Increase in lambda perpendicular in Twitcher spinal cord white matter relative to normal controls reached statistical significance in the dorsal columns and approached statistical significance in the ventrolateral region. Correlative reduced levels of myelin basic protein were detected by immunofluorescent staining in both these white matter regions in the Twitcher spinal cord. Fractional anisotropy, a nonspecific but sensitive indicator of white matter disease, was significantly reduced in the optic nerve, trigeminal nerve, and throughout the spinal cord white matter of Twitcher mice, relative to normal controls. This first reported application of spinal cord DTI in the setting of GLD holds potential as a noninvasive, quantitative assay of therapeutic efficacy in future treatment studies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Médula Espinal
/
Axones
/
Enfermedades Desmielinizantes
/
Nervios Craneales
/
Imagen de Difusión Tensora
/
Leucodistrofia de Células Globoides
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
NMR Biomed
Asunto de la revista:
DIAGNOSTICO POR IMAGEM
/
MEDICINA NUCLEAR
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos