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

• Published in: Neurobiology of disease 2007-06, Vol.26 (3), p.590-596
• Main Authors: Boska, Michael D, Hasan, Khader M, Kibuule, Danette, Banerjee, Rebecca, McIntyre, Erin, Nelson, Jay A, Hahn, Theresa, Gendelman, Howard E, Mosley, R. Lee
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Anisotropy; Brain Mapping - methods; Cell Count; Corpus Striatum - metabolism; Corpus Striatum - pathology; Corpus Striatum - physiopathology; Diffusion; Diffusion Magnetic Resonance Imaging - methods; Diffusion tensor imaging; Disease Models, Animal; Dopamine - metabolism; Dopaminergic neurons; Male; Mice; Mice, Inbred C57BL; MPTP; Nerve Degeneration - diagnosis; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Myelinated - pathology; Neural Pathways - metabolism; Neural Pathways - pathology; Neural Pathways - physiopathology; Neurology; Neurons - metabolism; Neurons - pathology; Parkinsonian Disorders - diagnosis; Parkinsonian Disorders - pathology; Parkinsonian Disorders - physiopathology; Parkinson’s disease; Striatum; Substantia nigra; Substantia Nigra - metabolism; Substantia Nigra - pathology; Substantia Nigra - physiopathology
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2007.02.010

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 ≤ 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.