Contributions
Abstract: P1233
Type: Poster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: Diffusion MRI can be used to measure changes in tissue microstructure, and it has not been used to examine the effects of fingolimod, an MS treatment, on myelination. Fingolimod has previously shown a positive effect on myelination, with drug dosage suggested to influence treatment efficacy. Researchers have also assessed diffusion metric changes using the experimental autoimmune encephalomyelitis model, however studies on the effect of fingolimod on MRI diffusion metrics in an MS demyelination model are lacking.
Objective: Assess how at acute and chronic stages of demyelination fingolimod dosage affects diffusion MRI metrics, namely the apparent diffusion coefficient, axial and radial diffusivity and fractional anisotropy.
Methods: Eighty mice were split into normal, cuprizone diet (0.2% by weight), cuprizone plus 0.1mg/kg fingolimod and cuprizone plus 0.3mg/kg fingolimod groups and acute (5 week diet) and chronic cohorts (12 week diet) were formed. Diffusion-weighted images were acquired on a Bruker 9.4T animal scanner: TE/TR = 20/2000 ms, matrix = 64 by 64 and field-of-view = 20 mm by 20 mm. Seven b-values between
0 and 3200 s/mm2 and 30 gradient directions were acquired. MRtrix3 was used to calculate diffusion metrics for the corpus callosum, which was segmented manually for each mouse. Mouse brains were stained for myelin using Luxol Fast Blue.
Results: The cuprizone diet in general resulted in larger radial diffusivities than normal mice. Cuprizone groups exhibited an increase in the apparent diffusion coefficient in comparison to the normal groups.
A significant difference in radial diffusivity was found between 0.1mg/kg and 0.3mg/kg fingolimod treated mice, implying sensitivity to drug dosage. Fractional anisotropy did not show a extensive sensitivity to treatment.
Conclusions: Myelin staining results were in agreement with changes in radial diffusivity, implying radial diffusivity is a potential biomarker of changes in myelination due to fingolimod treatment. Additionally, the apparent diffusion coefficient showed a systematic trend with myelin staining, thereby it is also a potentially useful biomarker for treatment monitoring in MS.
Disclosure: The project was funded by Novartis Pharmaceuticals Pty. Ltd., Australia, as an investigator initiated trial.
Qiang Yu: nothing to disclose
Timothy Le Pers: nothing to disclose
Laura Ziser: nothing to disclose
David Reutens: nothing to disclose
Viktor Vegh: nothing to disclose
Abstract: P1233
Type: Poster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: Diffusion MRI can be used to measure changes in tissue microstructure, and it has not been used to examine the effects of fingolimod, an MS treatment, on myelination. Fingolimod has previously shown a positive effect on myelination, with drug dosage suggested to influence treatment efficacy. Researchers have also assessed diffusion metric changes using the experimental autoimmune encephalomyelitis model, however studies on the effect of fingolimod on MRI diffusion metrics in an MS demyelination model are lacking.
Objective: Assess how at acute and chronic stages of demyelination fingolimod dosage affects diffusion MRI metrics, namely the apparent diffusion coefficient, axial and radial diffusivity and fractional anisotropy.
Methods: Eighty mice were split into normal, cuprizone diet (0.2% by weight), cuprizone plus 0.1mg/kg fingolimod and cuprizone plus 0.3mg/kg fingolimod groups and acute (5 week diet) and chronic cohorts (12 week diet) were formed. Diffusion-weighted images were acquired on a Bruker 9.4T animal scanner: TE/TR = 20/2000 ms, matrix = 64 by 64 and field-of-view = 20 mm by 20 mm. Seven b-values between
0 and 3200 s/mm2 and 30 gradient directions were acquired. MRtrix3 was used to calculate diffusion metrics for the corpus callosum, which was segmented manually for each mouse. Mouse brains were stained for myelin using Luxol Fast Blue.
Results: The cuprizone diet in general resulted in larger radial diffusivities than normal mice. Cuprizone groups exhibited an increase in the apparent diffusion coefficient in comparison to the normal groups.
A significant difference in radial diffusivity was found between 0.1mg/kg and 0.3mg/kg fingolimod treated mice, implying sensitivity to drug dosage. Fractional anisotropy did not show a extensive sensitivity to treatment.
Conclusions: Myelin staining results were in agreement with changes in radial diffusivity, implying radial diffusivity is a potential biomarker of changes in myelination due to fingolimod treatment. Additionally, the apparent diffusion coefficient showed a systematic trend with myelin staining, thereby it is also a potentially useful biomarker for treatment monitoring in MS.
Disclosure: The project was funded by Novartis Pharmaceuticals Pty. Ltd., Australia, as an investigator initiated trial.
Qiang Yu: nothing to disclose
Timothy Le Pers: nothing to disclose
Laura Ziser: nothing to disclose
David Reutens: nothing to disclose
Viktor Vegh: nothing to disclose