Journal
EXPERIMENTAL NEUROLOGY
Volume 201, Issue 2, Pages 293-300Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2006.04.007
Keywords
apparent diffusion coefficient; ADC; magnetic resonance imaging; progression markers; T-2 mapping
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Magnetic resonance imaging (MRI) has provided important information in characterizing amyotrophic lateral sclerosis (ALS) in humans and in animal models. A frequently used animal model to study mechanisms of pathogenesis and the efficacy of drugs in ALS is a transgenic mouse over-expressing the human mutated G93A-superoxide dismutase I (G93A-SOD1). In our study, we applied MRI to find suitable progression markers, which can be used to monitor the development of ALS and to evaluate therapeutic approaches at early stages of the disease. Therefore, we generated parameter maps of the spin-spin relaxation time (T-2) and the apparent diffusion coefficient (ADC) starting at day 70 after birth, i.e., before motor scores decline around day 90. Depending on the progression of the disease, G93A-SOD1 mice showed significantly increased values of T-2 in the brain stein motor nuclei Nc. V (trigeminal nucleus), VII (facial nucleus), and XII (hypoglossal nucleus), and spinal cord compared to non-transgenic wild-type mice and transgenic mice over-expressing the non-mutated wild-type human SOD1 (tg-SOD1). Similar effects in these motor nuclei were revealed by ADC mapping. Furthermore, in the upper spinal cord, a dorsal-ventral difference with significantly higher T-2 values in the ventral part was demonstrated by T-2 mapping. While both T-2 and ADC might prove useful as progression markers and enable the longitudinal non-invasive evaluation of ALS in G93A-SOD1 mice, the potential is limited by age-dependent effects in case of ADC mapping. (c) 2006 Elsevier Inc. All rights reserved.
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