Contributions
Abstract: P1066
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: It has been suggested that an aberrant iron metabolism and an abnormal iron deposition in the brain may be relevant to multiple sclerosis (MS). Using MRI, it was found that in iron excessively accumulates in the brain´s deep gray matter (DGM), mainly in the basal ganglia. On the other hand, brain volume loss has been reported to accompany the disease from very early stages on and has been correlated with disability progression and cognitive impairment in MS. In this work we focus on the influence that the simultaneously occurring shrinkage of the DGM can have on MR-based iron measurements (R2*).
Methods: 39 patients with MS (age:[32-69] yrs., EDSS: [0-6.5], disease duration: [3-41] yrs.,) and 30 healthy controls (HC; age: [30-69] yrs) were recruited. A 3T Philips Achieva was used for acquire the data. DTI: 2.2x2.2x2.2mm3 and 0.83x0.83x2.2mm3 rec., b=1000, 16 dir. R2*: flow compensated GRE with 5 echoes, vxl size 0.9x1x1.6mm3 acquired and 0.8x0.8x0.8mm3 rec. R2*were obtained by fitting of a mono-exponential. DGM ROIs were obtained from the MNI space manually corrected by two blinded operators. Volumes were normalized to the brain volume and average R2* values were computed for each structure. Finally, average R2* were corrected for the DGM volumes (R2* mass: R2*m=R2*×Volume). Significance between groups was tested using ANOVA and Kruskal-Wallis.
Results: We found volume (normalized and non-normalized) reductions of all DGM structures in the MS group compared to the HC group, significant in caudate and pallidus. The R2* values in the MS group were higher than in the HC group with significant differences in the pallidus. The R2* were correlated to the volume of the structures, being most pronounced for the caudate. R2* mass (R2*m) were smaller in all the MS brain DGM structures compared to HC, with exception of the putamen. Particularly, the caudate showed a significant reduction in R2*m.
Conclusions: R2* values are inversely related to the volumes of the structures. If the relationship between R2* and volume, particularly in the MS, is not accounted for, could lead to misinterpretation of the results. Reduced R2*m measurements, suggest that iron accumulation may not be a common feature of MS, but a redistribution/reduction of the iron. Our observations agree well with the reported high prevalence in the caudate, and the subsequent iron and myelin loss expected in these regions of tissue damage, which both reduce R2*.
Disclosure: Data acquisition funded by the MS Society of Canada.
Enedino Hernández-Torres has nothing to disclose.
Vanessa Wiggermann is supported by a Graduate Student Award from the MS Society of Canada.
David Li has received research funding from the Canadian Institute of Health Research and Multiple Sclerosis Society of Canada. He is the Emeritus Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Novartis, Perceptives, Roche and Sanofi-Aventis. The UBC MS/MRI Research Group has also received grant support for investigator-initiated independent studies from Genzyme, Merck-Serono, Novartis and Roche. He has acted as a consultant to Vertex Pharmaceuticals and served on the Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Celgene, Novartis and Roche. He has also given lectures which have been supported by non-restricted education grants from Teva, Novartis and Biogen.
Lindsay Machan is a member of the Research Steering Committee for Cook Inc and Medical Advisory Board for Boston Scientific Corp.
Dessa Sadovnick has received personal compensation for activities with Biogen Idec, Merck Serono, Teva Neuroscience, and Bayer Pharmaceuticals Corp as a speaker.
Anthony Traboulsee received research support from Biogen, Chugai, CIHR, Roche, Michael Smith Foundation, MS Society of Canada and consulted for Biogen, Roche, EMD Serono, Teva Pharmaceuticals.
Simon Hametner has nothing to disclose.
Alexander Rauscher received research support NSERC and National MS Society.
Abstract: P1066
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: It has been suggested that an aberrant iron metabolism and an abnormal iron deposition in the brain may be relevant to multiple sclerosis (MS). Using MRI, it was found that in iron excessively accumulates in the brain´s deep gray matter (DGM), mainly in the basal ganglia. On the other hand, brain volume loss has been reported to accompany the disease from very early stages on and has been correlated with disability progression and cognitive impairment in MS. In this work we focus on the influence that the simultaneously occurring shrinkage of the DGM can have on MR-based iron measurements (R2*).
Methods: 39 patients with MS (age:[32-69] yrs., EDSS: [0-6.5], disease duration: [3-41] yrs.,) and 30 healthy controls (HC; age: [30-69] yrs) were recruited. A 3T Philips Achieva was used for acquire the data. DTI: 2.2x2.2x2.2mm3 and 0.83x0.83x2.2mm3 rec., b=1000, 16 dir. R2*: flow compensated GRE with 5 echoes, vxl size 0.9x1x1.6mm3 acquired and 0.8x0.8x0.8mm3 rec. R2*were obtained by fitting of a mono-exponential. DGM ROIs were obtained from the MNI space manually corrected by two blinded operators. Volumes were normalized to the brain volume and average R2* values were computed for each structure. Finally, average R2* were corrected for the DGM volumes (R2* mass: R2*m=R2*×Volume). Significance between groups was tested using ANOVA and Kruskal-Wallis.
Results: We found volume (normalized and non-normalized) reductions of all DGM structures in the MS group compared to the HC group, significant in caudate and pallidus. The R2* values in the MS group were higher than in the HC group with significant differences in the pallidus. The R2* were correlated to the volume of the structures, being most pronounced for the caudate. R2* mass (R2*m) were smaller in all the MS brain DGM structures compared to HC, with exception of the putamen. Particularly, the caudate showed a significant reduction in R2*m.
Conclusions: R2* values are inversely related to the volumes of the structures. If the relationship between R2* and volume, particularly in the MS, is not accounted for, could lead to misinterpretation of the results. Reduced R2*m measurements, suggest that iron accumulation may not be a common feature of MS, but a redistribution/reduction of the iron. Our observations agree well with the reported high prevalence in the caudate, and the subsequent iron and myelin loss expected in these regions of tissue damage, which both reduce R2*.
Disclosure: Data acquisition funded by the MS Society of Canada.
Enedino Hernández-Torres has nothing to disclose.
Vanessa Wiggermann is supported by a Graduate Student Award from the MS Society of Canada.
David Li has received research funding from the Canadian Institute of Health Research and Multiple Sclerosis Society of Canada. He is the Emeritus Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Novartis, Perceptives, Roche and Sanofi-Aventis. The UBC MS/MRI Research Group has also received grant support for investigator-initiated independent studies from Genzyme, Merck-Serono, Novartis and Roche. He has acted as a consultant to Vertex Pharmaceuticals and served on the Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Celgene, Novartis and Roche. He has also given lectures which have been supported by non-restricted education grants from Teva, Novartis and Biogen.
Lindsay Machan is a member of the Research Steering Committee for Cook Inc and Medical Advisory Board for Boston Scientific Corp.
Dessa Sadovnick has received personal compensation for activities with Biogen Idec, Merck Serono, Teva Neuroscience, and Bayer Pharmaceuticals Corp as a speaker.
Anthony Traboulsee received research support from Biogen, Chugai, CIHR, Roche, Michael Smith Foundation, MS Society of Canada and consulted for Biogen, Roche, EMD Serono, Teva Pharmaceuticals.
Simon Hametner has nothing to disclose.
Alexander Rauscher received research support NSERC and National MS Society.