1. Brain and cord myelin water imaging: a progressive multiple sclerosis biomarker
- Author
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Peter Brex, Shannon H. Kolind, Anthony Traboulsee, Bretta Russell-Schulz, Anna J.E. Combes, Gareth J. Barker, Sean C.L. Deoni, Vignan Yogendrakumar, Roger Tam, Steven Williams, Arshia Seddigh, and Naomi Sibtain
- Subjects
Male ,SSFP, steady state free precession ,Pathology ,MSFC, Multiple Sclerosis Functional Composite ,RR, relapsing remitting ,CSF, cerebrospinal fluid ,FOV, field of view ,lcsh:RC346-429 ,030218 nuclear medicine & medical imaging ,vCSF, ventricular cerebrospinal fluid ,Disability Evaluation ,Myelin ,Primary progressive multiple sclerosis ,0302 clinical medicine ,Image Processing, Computer-Assisted ,10. No inequality ,Myelin Sheath ,TE, echo time ,Spinal cord ,medicine.diagnostic_test ,Brain ,Regular Article ,Steady-state free precession imaging ,Middle Aged ,Magnetic Resonance Imaging ,TR, repetition time ,3. Good health ,medicine.anatomical_structure ,Neurology ,PASAT, Paced Auditory Serial Addition Test ,VFM, myelin water volume fraction ,lcsh:R858-859.7 ,Biomarker (medicine) ,Female ,SPGR, spoiled gradient echo ,Adult ,medicine.medical_specialty ,Multiple Sclerosis ,Cord ,9HPT, 9-Hole Peg Test ,Cognitive Neuroscience ,lcsh:Computer applications to medicine. Medical informatics ,Statistics, Nonparametric ,EDSS, Expanded Disability Status Scale ,MR, magnetic resonance ,MS, multiple sclerosis ,03 medical and health sciences ,Atrophy ,Myelin water imaging ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,T25FW, Timed 25-Foot Walk ,lcsh:Neurology. Diseases of the nervous system ,Aged ,business.industry ,Multiple sclerosis ,Water ,CCV, cervical cord volume ,PP, primary progressive ,Magnetic resonance imaging ,medicine.disease ,mcDESPOT, Multi-component driven equilibrium single pulse observation of T1 & T2 ,Neurology (clinical) ,business ,MRI, magnetic resonance imaging ,030217 neurology & neurosurgery - Abstract
Objectives Conventional magnetic resonance imaging (MRI) is used to diagnose and monitor inflammatory disease in relapsing remitting (RR) multiple sclerosis (MS). In the less common primary progressive (PP) form of MS, in which focal inflammation is less evident, biomarkers are still needed to enable evaluation of novel therapies in clinical trials. Our objective was to characterize the association — across the brain and cervical spinal cord — between clinical disability measures in PPMS and two potential biomarkers (one for myelin, and one for atrophy, both resulting from the same imaging technique). Methods Multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) MRI of the brain and cervical spinal cord were obtained for 15 PPMS patients and 11 matched controls. Data were analysed to estimate the signal related to myelin water (VFM), as well as volume measurements. MS disability was assessed using the Multiple Sclerosis Functional Composite score, which includes measures of cognitive processing (Paced Auditory Serial Addition Test), manual dexterity (9-Hole Peg Test) and ambulatory function (Timed 25-Foot Walk); and the Expanded Disability Status Scale. Results Brain and spinal cord volumes were different in PPMS compared to controls, particularly ventricular (+ 46%, p = 0.0006) and cervical spinal cord volume (− 16%, p = 0.0001). Brain and spinal cord myelin (VFM) were also reduced in PPMS (brain: − 11%, p = 0.01; spine: − 19%, p = 0.000004). Cognitive processing correlated with brain ventricular volume (p = 0.009). Manual dexterity correlated with brain ventricular volume (p = 0.007), and both brain and spinal cord VFM (p = 0.01 and 0.06, respectively). Ambulation correlated with spinal cord volume (p = 0.04) and spinal cord VFM (p = 0.04). Interpretation In this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability., Highlights • A biomarker is needed to evaluate therapies for primary progressive MS (PPMS). • We used novel MRI providing both general atrophy and specific myelin measures. • We studied brain and cervical spinal cord in PPMS and healthy controls. • Brain and spinal cord volume and myelin measures were reduced in PPMS vs controls. • MRI measures described cognitive, fine motor and ambulatory disability scores.
- Published
- 2015