Contributions
Abstract: P492
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: The lack of established in vivo methods for monitoring de- and remyelination is well recognized in multiple sclerosis (MS). High angular resolution diffusion imaging (HARDI) and texture alignment measures have shown promise in probing subtle structural changes following brain white matter injury.
Aim: To investigate the sensitivity and power of high-resolution diffusion MRI and texture analysis methods for tracking de- and remyelination induced in mouse brain.
Methods: Sequential brain MRI was acquired using a 9.4T scanner from 5 C57BL/6 male mice before and after being fed with 0.2% cuprizone (Cu). Imaging protocols included 2-shell HARDI (b1/b2=1000/2000; 15 and 30 directions) and T2-weighted MRI (TR/TE=4000/48 ms; pixel size=0.05×0.05 mm2; and slice thickness=0.5 mm), at 4 and 6 weeks on Cu (demyelinating), and at 1 and 3 weeks of normal diet after stopping Cu (remyelinating). A control mouse was also scanned at 2,7, and 12 weeks for comparison. The diffusion MRI was first analyzed to obtain the orientation dispersion index (ODI), and neurite density index (NDI) using a software (NODDI toolbox, UCL, UK) and then processed to get the fractional anisotropy (FA). Image analysis focused on the corpus callosum at select slices of genu, body, and splenium. The T2 MRI was used to evaluate texture alignment complexity using an in-house program (genu only). Diffusion images were co-registered to the T2 MRI within a time point, and then between T2s over time to ensure position alignment. All metrics were normalized using intra-slice values of 3rd ventricle. Data analysis used two-way ANOVA; p≤.05 as significance.
Results: All normalized diffusion and texture metrics showed significant changes over time (p≤.05). There was a 29% increase in ODI (p≤.0001) and 49% in angular entropy from 4 to 6 weeks on Cu diet, and a 17% recovery in FA (p=0.03), and 6% in NDI (p≤.0005) from 1 to 3 weeks of normal diet. Control mice week 2 FA (10.6±2.4), ODI (-.89±.05), and NDI (-.39±.03) compared to the average of all mice week 6 on Cu FA (3.74±.19), ODI (-.29±.18), and NDI (-.59±.04) also showed significant changes (p≤.0001).
Conclusion: The Cu mouse model is well understood featuring a progressive de- and remyelination course before and after ceasing the toxic diet. Corresponding changes in MRI suggest that high angular resolution diffusion and texture alignment analyses may be promising methods for monitoring de- and remyelination that occurs frequently in MS patients.
Disclosure: Md. Shahnewaz Hossain: nothing to disclose.
Olayinka Oladosu: nothing to disclose.
Tim Luo: nothing to disclose.
Shrushrita Sharma: nothing to disclose.
Yunyan Zhang: nothing to disclose.
Abstract: P492
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: The lack of established in vivo methods for monitoring de- and remyelination is well recognized in multiple sclerosis (MS). High angular resolution diffusion imaging (HARDI) and texture alignment measures have shown promise in probing subtle structural changes following brain white matter injury.
Aim: To investigate the sensitivity and power of high-resolution diffusion MRI and texture analysis methods for tracking de- and remyelination induced in mouse brain.
Methods: Sequential brain MRI was acquired using a 9.4T scanner from 5 C57BL/6 male mice before and after being fed with 0.2% cuprizone (Cu). Imaging protocols included 2-shell HARDI (b1/b2=1000/2000; 15 and 30 directions) and T2-weighted MRI (TR/TE=4000/48 ms; pixel size=0.05×0.05 mm2; and slice thickness=0.5 mm), at 4 and 6 weeks on Cu (demyelinating), and at 1 and 3 weeks of normal diet after stopping Cu (remyelinating). A control mouse was also scanned at 2,7, and 12 weeks for comparison. The diffusion MRI was first analyzed to obtain the orientation dispersion index (ODI), and neurite density index (NDI) using a software (NODDI toolbox, UCL, UK) and then processed to get the fractional anisotropy (FA). Image analysis focused on the corpus callosum at select slices of genu, body, and splenium. The T2 MRI was used to evaluate texture alignment complexity using an in-house program (genu only). Diffusion images were co-registered to the T2 MRI within a time point, and then between T2s over time to ensure position alignment. All metrics were normalized using intra-slice values of 3rd ventricle. Data analysis used two-way ANOVA; p≤.05 as significance.
Results: All normalized diffusion and texture metrics showed significant changes over time (p≤.05). There was a 29% increase in ODI (p≤.0001) and 49% in angular entropy from 4 to 6 weeks on Cu diet, and a 17% recovery in FA (p=0.03), and 6% in NDI (p≤.0005) from 1 to 3 weeks of normal diet. Control mice week 2 FA (10.6±2.4), ODI (-.89±.05), and NDI (-.39±.03) compared to the average of all mice week 6 on Cu FA (3.74±.19), ODI (-.29±.18), and NDI (-.59±.04) also showed significant changes (p≤.0001).
Conclusion: The Cu mouse model is well understood featuring a progressive de- and remyelination course before and after ceasing the toxic diet. Corresponding changes in MRI suggest that high angular resolution diffusion and texture alignment analyses may be promising methods for monitoring de- and remyelination that occurs frequently in MS patients.
Disclosure: Md. Shahnewaz Hossain: nothing to disclose.
Olayinka Oladosu: nothing to disclose.
Tim Luo: nothing to disclose.
Shrushrita Sharma: nothing to disclose.
Yunyan Zhang: nothing to disclose.