Contributions
Abstract: EP1534
Type: ePoster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: The three major pathologies of multiple sclerosis (MS) are inflammatory demyelination, neurodegeneration, and remyelination failure. Conventional magnetic resonance imaging (MRI) modalities were only able to depict the former two pathologies. For the detection of remyelination or its failure, more specific MRI modalities such as diffusion tensor imaging (DTI) were required. In addition, we have recently succeeded in developing a novel q-space imaging-based modality producing "myelin map (MM)" (Fujiyoshi et al., J Neurosci (2016)), which could be obtained within 10 minutes using a 3 T scanner. We have previously shown that MM is more sensitive and myelin-specific compared to various DTI maps in experimental animals.
Objective: To compare the sensitivity of MM and various DTI maps (i.e. fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) maps) for the visualization of remyelination in MS patients.
Methods: We have previously shown that MM-supported remyelination was observed in a subset of MS patients with fingolimod (FTY) treatment (Nakahara et al., ECTRIMS (2015)). In the current study, five MS patients with FTY treatment were sequentially followed with both MM and DTI maps, and total of five MM-supported remyelination activities were identified. The signal intensity of each lesion was evaluated by 8-bit gray scale (GS; 0-255). The relative contrast of demyelinated lesion was calculated by dividing the GS difference between the lesion and normal-appearing white matter (NAWM) by 255. The relative contrast of remyelination activity was calculated by dividing the GS difference between demyelinated and remyelinated lesions by 255. Statistical analysis was performed using the Mann-Whitney U test and p< 0.05 was considered to be significant.
Results: The relative contrast of demyelinated lesion was significantly higher in MM (0.21±0.08; average ± standard deviation) compared to T2-weighted images (T2WI; 0.02±0.03) or AD map (0.08±0.05) whereas FA map (0.15±0.05) was similarly sensitive. The relative contrast of remyelination activity was significantly higher in MM (0.13±0.05) compared to T2WI (0.01±0.02) or all DTI measures (0.06±0.03, 0.03±0.03, 0.06±0.05, 0.06±0.05 in FA, AD, RD, and MD maps, respectively).
Conclusions: MM and FA maps were similarly sensitive in detecting demyelinated lesions, whereas MM was superior to all DTI measures in depicting remyelination activity in MS.
Disclosure:
Jin Nakahara: received honoraria from Bayer, Biogen, Mitsubishi Tanabe, Novartis, and Takeda and served as a paid scientific advisor to Biogen and Takeda.
Mariko Tanikawa: nothing to disclose.
Junichi Hata: nothing to disclose.
Kanehiro Fujiyoshi: nothing to disclose.
Shigeaki Suzuki: nothing to disclose.
Hirokazu Fujiwara: nothing to disclose.
Suketaka Momoshima: nothing to disclose.
Masahiro Jinzaki: nothing to disclose.
Masaya Nakamura: nothing to disclose.
Hideyuki Okano: Served as a paid member of scientific advisory board of SanBio Co. Ltd.
Shinichi Takahashi: nothing to disclose.
Norihiro Suzuki: nothing to disclose.
This study was supported by a Grant-in-Aid for Scientific Research (#25670424) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan to Jin Nakahara and by Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from MEXT and the Japan Agency for Medical Research and Development (AMED) to Hideyuki Okano.
Abstract: EP1534
Type: ePoster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: The three major pathologies of multiple sclerosis (MS) are inflammatory demyelination, neurodegeneration, and remyelination failure. Conventional magnetic resonance imaging (MRI) modalities were only able to depict the former two pathologies. For the detection of remyelination or its failure, more specific MRI modalities such as diffusion tensor imaging (DTI) were required. In addition, we have recently succeeded in developing a novel q-space imaging-based modality producing "myelin map (MM)" (Fujiyoshi et al., J Neurosci (2016)), which could be obtained within 10 minutes using a 3 T scanner. We have previously shown that MM is more sensitive and myelin-specific compared to various DTI maps in experimental animals.
Objective: To compare the sensitivity of MM and various DTI maps (i.e. fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) maps) for the visualization of remyelination in MS patients.
Methods: We have previously shown that MM-supported remyelination was observed in a subset of MS patients with fingolimod (FTY) treatment (Nakahara et al., ECTRIMS (2015)). In the current study, five MS patients with FTY treatment were sequentially followed with both MM and DTI maps, and total of five MM-supported remyelination activities were identified. The signal intensity of each lesion was evaluated by 8-bit gray scale (GS; 0-255). The relative contrast of demyelinated lesion was calculated by dividing the GS difference between the lesion and normal-appearing white matter (NAWM) by 255. The relative contrast of remyelination activity was calculated by dividing the GS difference between demyelinated and remyelinated lesions by 255. Statistical analysis was performed using the Mann-Whitney U test and p< 0.05 was considered to be significant.
Results: The relative contrast of demyelinated lesion was significantly higher in MM (0.21±0.08; average ± standard deviation) compared to T2-weighted images (T2WI; 0.02±0.03) or AD map (0.08±0.05) whereas FA map (0.15±0.05) was similarly sensitive. The relative contrast of remyelination activity was significantly higher in MM (0.13±0.05) compared to T2WI (0.01±0.02) or all DTI measures (0.06±0.03, 0.03±0.03, 0.06±0.05, 0.06±0.05 in FA, AD, RD, and MD maps, respectively).
Conclusions: MM and FA maps were similarly sensitive in detecting demyelinated lesions, whereas MM was superior to all DTI measures in depicting remyelination activity in MS.
Disclosure:
Jin Nakahara: received honoraria from Bayer, Biogen, Mitsubishi Tanabe, Novartis, and Takeda and served as a paid scientific advisor to Biogen and Takeda.
Mariko Tanikawa: nothing to disclose.
Junichi Hata: nothing to disclose.
Kanehiro Fujiyoshi: nothing to disclose.
Shigeaki Suzuki: nothing to disclose.
Hirokazu Fujiwara: nothing to disclose.
Suketaka Momoshima: nothing to disclose.
Masahiro Jinzaki: nothing to disclose.
Masaya Nakamura: nothing to disclose.
Hideyuki Okano: Served as a paid member of scientific advisory board of SanBio Co. Ltd.
Shinichi Takahashi: nothing to disclose.
Norihiro Suzuki: nothing to disclose.
This study was supported by a Grant-in-Aid for Scientific Research (#25670424) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan to Jin Nakahara and by Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from MEXT and the Japan Agency for Medical Research and Development (AMED) to Hideyuki Okano.