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.
Keywords: 9HPT, 9-Hole Peg Test; Atrophy; CCV, cervical cord volume; CSF, cerebrospinal fluid; EDSS, Expanded Disability Status Scale; FOV, field of view; MR, magnetic resonance; MRI, magnetic resonance imaging; MS, multiple sclerosis; MSFC, Multiple Sclerosis Functional Composite; Myelin; Myelin water imaging; PASAT, Paced Auditory Serial Addition Test; PP, primary progressive; Primary progressive multiple sclerosis; RR, relapsing remitting; SPGR, spoiled gradient echo; SSFP, steady state free precession; Spinal cord; T25FW, Timed 25-Foot Walk; TE, echo time; TR, repetition time; VFM, myelin water volume fraction; mcDESPOT, Multi-component driven equilibrium single pulse observation of T1 & T2; vCSF, ventricular cerebrospinal fluid.