Measuring demyelination and remyelination in acute multiple sclerosis lesion voxels.

OBJECTIVE To validate the use of the magnetization transfer ratio (MTR) as a practical imaging marker of demyelination and remyelination in acute multiple sclerosis lesions. DESIGN Case study. SETTING University hospital multiple sclerosis clinic. Patients Six patients with relapsing-remitting multiple sclerosis and acute gadolinium-enhancing lesions were studied serially using a quantitative magnetization transfer examination. MAIN OUTCOME MEASURES Changes in the water content and macromolecular content, a marker of myelin content that, unlike MTR, is not affected by changes in water content (edema) associated with acute inflammation, and changes in MTR of lesions. RESULTS Both the macromolecular content and MTR were lower than normal in acute lesions and recovered over several months. The decrease in macromolecular content relative to contralateral normal-appearing white matter was greater than the decrease in MTR (0.46 vs 0.75 at the time of gadolinium enhancement), likely because edema in the acute lesion increased the T1 relaxation time of water and attenuated the decrease in MTR. Nevertheless, there was still a strong correlation between changes in the relative MTR and macromolecular content (R(2) = 0.70; P < .001). CONCLUSION Our data support the use of MTR as a practical marker of demyelination and remyelination, even in acute lesions where decreases in MTR are attenuated because of the effects of edema.

[1]  Bruce D. Trapp,et al.  Pathogenesis of axonal and neuronal damage in multiple sclerosis , 2007, Neurology.

[2]  R. Henkelman,et al.  Magnetization transfer in MRI: a review , 2001, NMR in biomedicine.

[3]  David H. Miller,et al.  Quantitative magnetization transfer imaging in postmortem multiple sclerosis brain , 2007, Journal of magnetic resonance imaging : JMRI.

[4]  Frederik Barkhof,et al.  Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. , 2003, Archives of neurology.

[5]  Massimo Filippi,et al.  MRI techniques to monitor MS evolution: The present and the future , 2002, Neurology.

[6]  C. Morrison,et al.  A Model for Magnetization Transfer in Tissues , 1995, Magnetic resonance in medicine.

[7]  Rajiv Midha,et al.  MR properties of excised neural tissue following experimentally induced inflammation , 2004, Magnetic resonance in medicine.

[8]  B Quesson,et al.  In vivo evaluation of remyelination in rat brain by magnetization transfer imaging , 2000, Journal of the Neurological Sciences.

[9]  G. B. Pike,et al.  Quantitative imaging of magnetization transfer exchange and relaxation properties in vivo using MRI , 2001, Magnetic resonance in medicine.

[10]  R. Balaban,et al.  Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo , 1989, Magnetic resonance in medicine.

[11]  R I Grossman,et al.  Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging. , 1992, Radiology.

[12]  A J Thompson,et al.  Correlations between changes in disability and T2‐weighted brain MRI activity in multiple sclerosis , 1995, Neurology.

[13]  E. Samulski,et al.  The measurement of cross-relaxation effects in the proton NMR spin-lattice relaxation of water in biological systems: Hydrated collagen and muscle☆ , 1978 .

[14]  D. Louis Collins,et al.  Voxel-based analysis of the evolution of magnetization transfer ratio to quantify remyelination and demyelination with histopathological validation in a multiple sclerosis lesion , 2007, NeuroImage.

[15]  G. Pike,et al.  Correction for B1 and B0 variations in quantitative T2 measurements using MRI , 2000, Magnetic resonance in medicine.

[16]  David H. Miller,et al.  Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain , 2004, Annals of neurology.

[17]  I Levesque,et al.  Regional variations in normal brain shown by quantitative magnetization transfer imaging , 2004, Magnetic resonance in medicine.

[18]  R M Henkelman,et al.  Quantitative interpretation of magnetization transfer , 1993, Magnetic resonance in medicine.

[19]  Christian Enzinger,et al.  Method for quantitative imaging of the macromolecular 1H fraction in tissues , 2003, Magnetic resonance in medicine.

[20]  G. Barker,et al.  Precise estimate of fundamental in-vivo MT parameters in human brain in clinically feasible times. , 2002, Magnetic resonance imaging.

[21]  G. Pike,et al.  Quantitative interpretation of magnetization transfer in spoiled gradient echo MRI sequences. , 2000, Journal of magnetic resonance.

[22]  R M Henkelman,et al.  Relaxivity and magnetization transfer of white matter lipids at MR imaging: importance of cerebrosides and pH. , 1994, Radiology.

[23]  Estimation of magnetization transfer rates from PACE experiments with pulsed RF saturation , 2000, Journal of magnetic resonance imaging : JMRI.

[24]  Sridar Narayanan,et al.  The role of edema and demyelination in chronic T1 black holes: A quantitative magnetization transfer study , 2005, Journal of magnetic resonance imaging : JMRI.

[25]  D. Arnold.  Evidence for neuroprotection and remyelination using imaging techniques , 2007, Neurology.

[26]  B K Rutt,et al.  Magnetization transfer and multicomponent T2 relaxation measurements with histopathologic correlation in an experimental model of MS , 2000, Journal of magnetic resonance imaging : JMRI.

[27]  G. B. Pike,et al.  Multiple sclerosis: magnetization transfer MR imaging of white matter before lesion appearance on T2-weighted images. , 2000, Radiology.

[28]  D. Arnold,et al.  Magnetic resonance techniques for the in vivo assessment of multiple sclerosis pathology: Consensus report of the white matter study group , 2005, Journal of magnetic resonance imaging : JMRI.

[29]  Correction for B(1) and B(0) variations in quantitative T(2) measurements using MRI. , 2000 .

[30]  John C Gore,et al.  Quantitative magnetization transfer imaging via selective inversion recovery with short repetition times , 2007, Magnetic resonance in medicine.

[31]  C. S. Poon,et al.  Practical T2 quantitation for clinical applications , 1992, Journal of magnetic resonance imaging : JMRI.

[32]  P L Carson,et al.  Experimental analysis of T1 imaging with a single‐scan, multiple‐point, inversion‐recovery technique , 1992, Magnetic resonance in medicine.

[33]  Vasily L Yarnykh,et al.  Pulsed Z‐spectroscopic imaging of cross‐relaxation parameters in tissues for human MRI: Theory and clinical applications , 2002, Magnetic resonance in medicine.

[34]  J L Ostuni,et al.  Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis , 2001, Multiple sclerosis.