Contributions
Abstract: EP1521
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: 23 rapidly-progressing MS patients were treated with immunoablation and autologous stem cell transplantation (aHSCT). Despite stoppage of all inflammatory activity indicated by MRI and relapses, high rates of short-term brain volume loss (atrophy) were observed following aHSCT. The EDSS score worsened in 30% of the patients.
Signal mass (SM) is an MRI metric that combines both the tissue volume change and MRI signal intensity change (representative of change in tissue density) to address some of the limitations of brain volume change related to tissue injury and volume loss that is partially replaced by water and reactive processes.
Objectives: To compare SM loss 1) within normal-appearing brain tissue (NABT) versus T2-weighted lesions, and 2) between EDSS worsening versus non-worsening subgroups.
Methods: The patients were followed from 1.5 to 10.5 years (mean 5.5y) on 1.5T scanners. Percent SM changes (PSMC) between baseline and follow-up magnetization transfer ratio (MTR) images were calculated as follows: images were linearly registered to a standard template; brain parenchymal masks were obtained using SPM, and T2-weighted lesions were segmented using locally-developed software and manually corrected; follow-up images were non-linearly registered to the baseline image and Jacobian determinant maps (J), quantifying local volume change at the voxel level, were calculated; maps of MTR SM at baseline and follow-up were computed as SMBL = IBL×vol and SMFU = IFU×vol×J where I is the MTR image intensity and vol is the voxel volume. PSMC for a given tissue type (NABT or T2 lesions) was the % difference between SMBL and SMFU in the corresponding tissue mask.
Data was modelled using non-linear mixed-effects models including an exponential decay term estimating the amount and rate of short-term SM loss. The models tested 1) whether tissue in in lesions exhibited disproportionate SM loss, and 2) whether patients with post-treatment EDSS progression had greater SM loss.
Results: The amount of short-term SM loss was greater in lesions compared to NABT (p=0.0001). Progressing patients showed greater amount of SM loss in NABT (p=0.04), but not in lesions (p=0.7).
Conclusion: A disproportionate amount of rapid brain tissue loss after aHSCT may be due to loss of already damaged tissue in lesions. However, greater tissue injury / loss in NABT (rather than in lesions) is associated with disability progression following treatment.
Disclosure: Hyunwoo Lee: Nothing to disclose.
Robert A. Brown: Consultant fees from NeuroRx Research and Biogen.
Douglas L. Arnold: Consultant fees and/or grants from Acorda, Adelphi,
Alkermes, Biogen, Celgene, Frequency Therapeutics, Genentech, Genzyme,
Hoffman LaRoche, Immune Tolerance Network, Immunotec, MedDay Merck-
Serono, Novartis, Pfizer, Receptos, Roche, Sanofi-Aventis, Canadian Institutes of
Health Research, MS Society of Canada, International Progressive MS Alliance,
and an equity interest in NeuroRx Research.
Harold L. Atkins: Nothing to disclose.
Mark S. Freedman: Research or educational grants from Genzyme Canada; consultation fees from Actelion, BayerHealthcare, BiogenIdec, Chugai, Clene Nanomedicine, EMD Canada, Genzyme, Merck Serono, Novartis, Hoffman La-Roche, Sanofi-Aventis, Teva Canada Innovation; company advisory board for Actelion, BayerHealthcare, BiogenIdec, Clene Nanomedicine, Hoffman La-Roche, Merck Serono, MedDay, Novartis, Sanofi-Aventis; participation in a company sponsored speaker´s bureau for Sanofi-Genzyme.
Sridar Narayanan: Personal fees from NeuroRx Research and a speaker´s honorarium from Novartis Canada, unrelated to the submitted work.
Abstract: EP1521
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: 23 rapidly-progressing MS patients were treated with immunoablation and autologous stem cell transplantation (aHSCT). Despite stoppage of all inflammatory activity indicated by MRI and relapses, high rates of short-term brain volume loss (atrophy) were observed following aHSCT. The EDSS score worsened in 30% of the patients.
Signal mass (SM) is an MRI metric that combines both the tissue volume change and MRI signal intensity change (representative of change in tissue density) to address some of the limitations of brain volume change related to tissue injury and volume loss that is partially replaced by water and reactive processes.
Objectives: To compare SM loss 1) within normal-appearing brain tissue (NABT) versus T2-weighted lesions, and 2) between EDSS worsening versus non-worsening subgroups.
Methods: The patients were followed from 1.5 to 10.5 years (mean 5.5y) on 1.5T scanners. Percent SM changes (PSMC) between baseline and follow-up magnetization transfer ratio (MTR) images were calculated as follows: images were linearly registered to a standard template; brain parenchymal masks were obtained using SPM, and T2-weighted lesions were segmented using locally-developed software and manually corrected; follow-up images were non-linearly registered to the baseline image and Jacobian determinant maps (J), quantifying local volume change at the voxel level, were calculated; maps of MTR SM at baseline and follow-up were computed as SMBL = IBL×vol and SMFU = IFU×vol×J where I is the MTR image intensity and vol is the voxel volume. PSMC for a given tissue type (NABT or T2 lesions) was the % difference between SMBL and SMFU in the corresponding tissue mask.
Data was modelled using non-linear mixed-effects models including an exponential decay term estimating the amount and rate of short-term SM loss. The models tested 1) whether tissue in in lesions exhibited disproportionate SM loss, and 2) whether patients with post-treatment EDSS progression had greater SM loss.
Results: The amount of short-term SM loss was greater in lesions compared to NABT (p=0.0001). Progressing patients showed greater amount of SM loss in NABT (p=0.04), but not in lesions (p=0.7).
Conclusion: A disproportionate amount of rapid brain tissue loss after aHSCT may be due to loss of already damaged tissue in lesions. However, greater tissue injury / loss in NABT (rather than in lesions) is associated with disability progression following treatment.
Disclosure: Hyunwoo Lee: Nothing to disclose.
Robert A. Brown: Consultant fees from NeuroRx Research and Biogen.
Douglas L. Arnold: Consultant fees and/or grants from Acorda, Adelphi,
Alkermes, Biogen, Celgene, Frequency Therapeutics, Genentech, Genzyme,
Hoffman LaRoche, Immune Tolerance Network, Immunotec, MedDay Merck-
Serono, Novartis, Pfizer, Receptos, Roche, Sanofi-Aventis, Canadian Institutes of
Health Research, MS Society of Canada, International Progressive MS Alliance,
and an equity interest in NeuroRx Research.
Harold L. Atkins: Nothing to disclose.
Mark S. Freedman: Research or educational grants from Genzyme Canada; consultation fees from Actelion, BayerHealthcare, BiogenIdec, Chugai, Clene Nanomedicine, EMD Canada, Genzyme, Merck Serono, Novartis, Hoffman La-Roche, Sanofi-Aventis, Teva Canada Innovation; company advisory board for Actelion, BayerHealthcare, BiogenIdec, Clene Nanomedicine, Hoffman La-Roche, Merck Serono, MedDay, Novartis, Sanofi-Aventis; participation in a company sponsored speaker´s bureau for Sanofi-Genzyme.
Sridar Narayanan: Personal fees from NeuroRx Research and a speaker´s honorarium from Novartis Canada, unrelated to the submitted work.