Title

Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease.

Publication Date

6-1-2007

Journal

Neurobiol Dis. 2007 June; 26(3): 590–596.

Abstract

Early diagnosis of Parkinson's disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect >50% loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p<0.005) and decreased fractional anisotropy (p<0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p < or = 0.002) and correlated with the numbers of SN dopaminergic neurons (r=-0.75, p=0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.

Keywords

Animals, Anisotropy, Brain Mapping, Cell Count, Corpus Striatum, Diffusion, Diffusion Magnetic Resonance Imaging, Disease Models, Animal, Dopamine, Male, Mice, Mice, Inbred C57BL, Nerve Degeneration, Nerve Fibers, Myelinated, Neural Pathways, Neurons, Parkinsonian Disorders, Substantia Nigra