DX63
Myelin Water Fraction As a Potential Marker of Progression in Primary Progressive Multiple Sclerosis
In addition to focal lesions, progressive multiple sclerosis pathology includes diffuse damage in normal-appearing white matter (NAWM), which is difficult to detect with conventional MRI. Thus biologically-specific advanced MRI markers that are sensitive to progressive NAWM damage are needed.
Objectives:
To study myelin water fraction (MWF, related to myelin content) variability and natural history in primary progressive multiple sclerosis (PPMS) patients compared to healthy controls.
Methods:
Data was collected as part of a substudy for the double-blinded, placebo-controlled clinical trial with ocrelizumab in PPMS (ORATORIO; NCT01194570); only baseline and placebo PPMS cases were analysed in this pilot study. At baseline, 41 healthy controls and seven PPMS patients were scanned. Two PPMS patients on placebo were also scanned at months 6, 12, and 24, and one patient at month 48. MRI included multi-component driven equilibrium single pulse observation of T1/T2 (mcDESPOT) to calculate MWF. Voxel-wise MWF Z-score maps (MWFZ) were calculated as: MWFZ = (patient MWF – mean of controls’ MWF)/(standard deviation of controls’ MWF). Severe damage compared to healthy controls was calculated as percentage of white matter voxels with MWFZ < -4, excluding damaged regions smaller than 25 voxels.
Results:
Baseline (n=7): The volume of severe damage in PPMS NAWM varied widely between PPMS patients, and was not correlated with Expanded Disability Status Scale (EDSS) in this small cohort. Areas of severe damage (MWFZ < -4) extended through NAWM far beyond focal lesions. Two patients had more than 8% of white matter volume severely affected. The other five patients had small (<80 voxels), isolated patches of severe damage affecting less than 0.25% of the white matter volume.
Longitudinal (n=2): Patient 1 had no areas of severe damage at baseline (EDSS 2.5), increasing to 0.09% of the white matter volume at month 24 (EDSS 3.5). Patient 2 had extensive severely damaged tissue at baseline, affecting 8.9% of the white matter volume (EDSS 6.5), increasing to 12.6% at month 48 (EDSS 6.5).
Conclusions:
Creating a myelin atlas from a relatively large group of healthy controls allowed for assessment of individual PPMS patients against control values, detecting areas of significant damage that varied widely in size and location between patients. Thus MWFZ may detect progressive damage at the individual patient level, making it a candidate for a biomarker in personalized medicine.