Contributions
Abstract: P1122
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Objective: To compare the myelin water fraction from normal appearing white matter (NAWM) and diffusely abnormal white matter (DAWM) in different MS subtypes.
Background: DAWM is found in the brain of some MS and clinically isolated syndrome (CIS) subjects. DAWM has poorly defined boundaries, with signal intensity higher on proton density and T2-weighted MRI images than NAWM but not as high as lesions. Histologically, DAWM shows blood-brain barrier breakdown, as well as myelin changes and axonal loss. Using MRI, myelin can be quantified by measuring the signal from water trapped within myelin bilayers known as the myelin water fraction (MWF). MWF is reduced in NAWM and lesions compared to healthy white matter.
Methods: Sixty MS participants (6 CIS, 29 RRMS, 17 SPMS, 8 PPMS) underwent 3T MRI. Participants with DAWM (DAWM+) and without DAWM (DAWM-) were identified. DAWM and similarly located NAWM areas in the DAWM- subjects were delineated. Mean (±standard deviation) MWF was determined for whole brain white matter as well as the DAWM/matching-NAWM regions. Comparisons of MWF between DAWM+ and DAWM- as well as MS subtypes were done using ANOVA and unpaired t-tests.
Results: Whole brain white matter mean MWF was different between CIS and SPMS (p=0.05) (CIS=0.108±0.022, RRMS=0.098±0.014, SPMS=0.095±0.010, PPMS=0.099±0.014). Thirty-three participants were identified as DAWM+ (2 CIS, 19 RRMS, 8 SPMS, 4 PPMS). MWF was lower in DAWM regions in subjects with DAWM compared to corresponding NAWM regions in DAWM- subjects (DAWM+ vs DAWM-: all subjects=0.089±0.016 vs. 0.097±0.021, p=0.10; CIS=0.088±0.004 vs. 0.114±0.037, p=0.42; RRMS=0.087±0.016 vs. 0.093±0.016, p=0.33; SPMS=0.090±0.018 vs. 0.093±0.018, p=0.75; PPMS=0.097±0.014 vs. 0.099±0.017, p=0.90).
Discussion: As expected, progressive stages of MS showed less myelin than RRMS and CIS, even in NAWM. MWF in areas of DAWM was lower for all MS subtypes compared to NAWM although the differences did not reach significance. Due to improved signal to noise ratio and resolution, DAWM identified at 3T likely includes mildly diffuse abnormalities that would not be visible at 1.5T and would have formerly been classified as NAWM. Thus, 3T DAWM+ regions include less severe abnormalities, suggesting that larger sample sizes may be needed to detect differences between DAWM+ and DAWM- groups.
Disclosure: Funded by Multiple Sclerosis Society of Canada. IM Vavasour: nothing to disclose. DKB Li: Research funding from the Canadian Institute of Health Research and MS Society of Canada. 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. 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. Given lectures which have been supported by non-restricted education grants from Academy of Health Care Learning, Biogen-Idec, Consortium of MS Centers, Novartis, Sanofi-Genzyme and Teva. A. Traboulsee: Research funding from Chugai, Roche, Novartis, Genzyme, Biogen. Consultancy honoraria from Genzyme, Roche, Teva, Biogen, Serono. R. Carruthers: Site Investigator for studies funded by Novartis, MedImmune, and Roche and receives research support from Teva Innovation Canada, Roche Canada and Vancouver Coastal Health Research Institute. He has done consulting work and has received honoraria from Roche, EMD Serono, Sanofi, Biogen, Novartis, and Teva. GRW Moore: Received a grant-in-aid of research from Berlex Canda, acted as a consultant for Schering, and received honoraria from Teva for teaching. He is a member of the Medical Advisory Committee of the Multiple Sclerosis Society of Canada. S.H. Kolind: Research funding from F. Hoffmann La Roche, Sanofi Genzyme, MS society of Canada and NSERC. C. Laule: Research funding from MS society of Canada and NSERC.
Abstract: P1122
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Objective: To compare the myelin water fraction from normal appearing white matter (NAWM) and diffusely abnormal white matter (DAWM) in different MS subtypes.
Background: DAWM is found in the brain of some MS and clinically isolated syndrome (CIS) subjects. DAWM has poorly defined boundaries, with signal intensity higher on proton density and T2-weighted MRI images than NAWM but not as high as lesions. Histologically, DAWM shows blood-brain barrier breakdown, as well as myelin changes and axonal loss. Using MRI, myelin can be quantified by measuring the signal from water trapped within myelin bilayers known as the myelin water fraction (MWF). MWF is reduced in NAWM and lesions compared to healthy white matter.
Methods: Sixty MS participants (6 CIS, 29 RRMS, 17 SPMS, 8 PPMS) underwent 3T MRI. Participants with DAWM (DAWM+) and without DAWM (DAWM-) were identified. DAWM and similarly located NAWM areas in the DAWM- subjects were delineated. Mean (±standard deviation) MWF was determined for whole brain white matter as well as the DAWM/matching-NAWM regions. Comparisons of MWF between DAWM+ and DAWM- as well as MS subtypes were done using ANOVA and unpaired t-tests.
Results: Whole brain white matter mean MWF was different between CIS and SPMS (p=0.05) (CIS=0.108±0.022, RRMS=0.098±0.014, SPMS=0.095±0.010, PPMS=0.099±0.014). Thirty-three participants were identified as DAWM+ (2 CIS, 19 RRMS, 8 SPMS, 4 PPMS). MWF was lower in DAWM regions in subjects with DAWM compared to corresponding NAWM regions in DAWM- subjects (DAWM+ vs DAWM-: all subjects=0.089±0.016 vs. 0.097±0.021, p=0.10; CIS=0.088±0.004 vs. 0.114±0.037, p=0.42; RRMS=0.087±0.016 vs. 0.093±0.016, p=0.33; SPMS=0.090±0.018 vs. 0.093±0.018, p=0.75; PPMS=0.097±0.014 vs. 0.099±0.017, p=0.90).
Discussion: As expected, progressive stages of MS showed less myelin than RRMS and CIS, even in NAWM. MWF in areas of DAWM was lower for all MS subtypes compared to NAWM although the differences did not reach significance. Due to improved signal to noise ratio and resolution, DAWM identified at 3T likely includes mildly diffuse abnormalities that would not be visible at 1.5T and would have formerly been classified as NAWM. Thus, 3T DAWM+ regions include less severe abnormalities, suggesting that larger sample sizes may be needed to detect differences between DAWM+ and DAWM- groups.
Disclosure: Funded by Multiple Sclerosis Society of Canada. IM Vavasour: nothing to disclose. DKB Li: Research funding from the Canadian Institute of Health Research and MS Society of Canada. 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. 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. Given lectures which have been supported by non-restricted education grants from Academy of Health Care Learning, Biogen-Idec, Consortium of MS Centers, Novartis, Sanofi-Genzyme and Teva. A. Traboulsee: Research funding from Chugai, Roche, Novartis, Genzyme, Biogen. Consultancy honoraria from Genzyme, Roche, Teva, Biogen, Serono. R. Carruthers: Site Investigator for studies funded by Novartis, MedImmune, and Roche and receives research support from Teva Innovation Canada, Roche Canada and Vancouver Coastal Health Research Institute. He has done consulting work and has received honoraria from Roche, EMD Serono, Sanofi, Biogen, Novartis, and Teva. GRW Moore: Received a grant-in-aid of research from Berlex Canda, acted as a consultant for Schering, and received honoraria from Teva for teaching. He is a member of the Medical Advisory Committee of the Multiple Sclerosis Society of Canada. S.H. Kolind: Research funding from F. Hoffmann La Roche, Sanofi Genzyme, MS society of Canada and NSERC. C. Laule: Research funding from MS society of Canada and NSERC.