Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation

Unfixed and fixed postmortem multiple sclerosis (MS) brain is being used to probe pathology underlying quantitative MR (qMR) changes. Effects of fixation on qMR indices in MS brain are unknown. In 15 postmortem MS brain slices T1, T2, MT ratio (MTR), macromolecular proton fraction (fB), fractional anisotropy (FA), and mean, axial, and radial diffusivity (MD, Dax, and Drad) were assessed in white matter (WM) lesions (WML) and normal appearing WM (NAWM) before and after fixation in formalin. Myelin content, axonal count, and gliosis were quantified histologically. Student's t‐test and regression were used for analysis. T1, T2, MTR, and fB obtained in unfixed MS brain were similar to published values obtained in patients with MS in vivo. Following fixation T1, T2 (NAWM, WML) and MTR (NAWM) dropped, whereas fB (NAWM, WML) increased. Compared to published in vivo data all diffusivity measures were lower in unfixed MS brain, and dropped further following fixation (except for FA). MTR was the best predictor of Tmyelin (inversely related to myelin) in unfixed MS brain (r = −0.83; P < 0.01) whereas postfixation T2 (r = 0.92; P < 0.01), T1 (r = 0.89; P < 0.01), and fB (r = −0.86; P < 0.01) were superior. All diffusivity measures (except for Dax in unfixed tissue) were predictors of myelin content. Magn Reson Med 59:268–277, 2008. © 2008 Wiley‐Liss, Inc.

[1]  P. Valk,et al.  Staging of multiple sclerosis (MS) lesions: pathology of the time frame of MS. , 2000 .

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

[3]  A. Blamire,et al.  Optimising Imaging Parameters for Post Mortem MR Imaging of the Human Brain , 1999, Acta radiologica.

[4]  Mark A. van Buchem,et al.  MT: magnetization transfer , 2003 .

[5]  E P du Boulay,et al.  Histopathology of multiple sclerosis lesions detected by magnetic resonance imaging in unfixed postmortem central nervous system tissue. , 1991, Brain : a journal of neurology.

[6]  T. Inoue,et al.  Formalin fixed brains are useful for magnetic resonance imaging (MRI) study , 1987, Journal of the Neurological Sciences.

[7]  Philip A. Boulby,et al.  T2: The Transverse Relaxation Time , 2004 .

[8]  P. Basser,et al.  A simplified method to measure the diffusion tensor from seven MR images , 1998, Magnetic resonance in medicine.

[9]  A. Mouritzen Dam.  Shrinkage of the brain during histological procedures with fixation in formaldehyde solutions of different concentrations. , 1979, Journal fur Hirnforschung.

[10]  G. Barker,et al.  An interleaved sequence for accurate and reproducible clinical measurement of magnetization transfer ratio. , 1996, Magnetic resonance imaging.

[11]  M. Horsfield,et al.  Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging , 1999, Magnetic resonance in medicine.

[12]  C. Laule,et al.  Myelin water imaging in multiple sclerosis: quantitative correlations with histopathology , 2006, Multiple sclerosis.

[13]  David H. Miller,et al.  A multicenter measurement of magnetization transfer ratio in normal white matter , 1999, Journal of magnetic resonance imaging : JMRI.

[14]  G R Wayne Moore,et al.  MRI-clinical correlations: more than inflammation alone-what can MRI contribute to improve the understanding of pathological processes in MS? , 2003, Journal of the neurological sciences.

[15]  L D Hall,et al.  Magnetic Resonance Imaging of the Common Marmoset Head , 1998, Alternatives to laboratory animals : ATLA.

[16]  P. Basser,et al.  In vivo fiber tractography using DT‐MRI data , 2000, Magnetic resonance in medicine.

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

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

[19]  K. Misulis,et al.  DEMYELINATING diseases. , 1952, Lancet.

[20]  P. Roller,et al.  Formaldehyde fixation. , 1985, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[21]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

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

[23]  Hompson,et al.  A LONGITUDINAL STUDY OF ABNORMALITIES ON MRI AND DISABILITY FROM MULTIPLE SCLEROSIS , 2002 .

[24]  G. Moore.  MRI-clinical correlations: more than inflammation alone-what can MRI contribute to improve the understanding of pathological processes in MS? , 2003, Journal of the Neurological Sciences.

[25]  G. Barker,et al.  Quantification of MRI lesion load in multiple sclerosis: a comparison of three computer-assisted techniques. , 1996, Magnetic resonance imaging.

[26]  M. Maier.  Quantitative MRI of the brain—measuring changes caused by disease , 2004 .

[27]  F. Barkhof,et al.  Post-mortem high-resolution MRI of the spinal cord in multiple sclerosis: a correlative study with conventional MRI, histopathology and clinical phenotype. , 2001, Brain : a journal of neurology.

[28]  I. Vavasour,et al.  A pathology-MRI study of the short-T2 component in formalin-fixed multiple sclerosis brain , 2000, Neurology.

[29]  D.L. Plummer,et al.  DispImage: Un mezzo di analisi e presentazione per iconografia medica , 1992 .

[30]  G J Barker,et al.  Stereotactic co‐registration of magnetic resonance imaging and histopathology in post‐mortem multiple sclerosis brain , 2003, Neuropathology and applied neurobiology.

[31]  J. Bancroft,et al.  Theory and Practice of Histological Techniques , 1990 .

[32]  A. MacKay,et al.  In vivo visualization of myelin water in brain by magnetic resonance , 1994, Magnetic resonance in medicine.

[33]  G Macchi,et al.  An in vivo and post mortem MRI study in multiple sclerosis with pathological correlation. , 1992, Italian journal of neurological sciences.

[34]  F. Barkhof,et al.  The spinal cord in multiple sclerosis: relationship of high-spatial-resolution quantitative MR imaging findings to histopathologic results. , 2004, Radiology.

[35]  A. MouritzenDam.  Shrinkage of the brain during histological procedures with fixation in formaldehyde solutions of different concentrations. , 1979 .

[36]  Andre Obenaus,et al.  Magnetic resonance imaging and mathematical modeling of progressive formalin fixation of the human brain , 2005, Magnetic resonance in medicine.

[37]  M. Solaiyappan,et al.  In vivo three‐dimensional reconstruction of rat brain axonal projections by diffusion tensor imaging , 1999, Magnetic resonance in medicine.

[38]  R. Turner,et al.  Diffusion MR imaging: clinical applications. , 1992, AJR. American journal of roentgenology.

[39]  K P Whittall,et al.  Different magnetization transfer effects exhibited by the short and long T2 components in human brain , 2000, Magnetic resonance in medicine.

[40]  F. Barkhof,et al.  Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis , 1998, Neurology.

[41]  Sheng-Kwei Song,et al.  Relative indices of water diffusion anisotropy are equivalent in live and formalin‐fixed mouse brains , 2003, Magnetic resonance in medicine.

[42]  G J Barker,et al.  Estimation of the macromolecular proton fraction and bound pool T2 in multiple sclerosis. , 2004, Multiple sclerosis.

[43]  Diffusion tensor imaging of post-mortem brain slices (fresh and fixed) on a clinical scanner , 2003 .

[44]  Ludwig Kappos,et al.  Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis , 1999, The Lancet.

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

[46]  D. Chari,et al.  Remyelination In Multiple Sclerosis , 2007, International Review of Neurobiology.

[47]  D. N. Landon,et al.  Duration and selectivity of blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis studied by gadolinium-DTPA and protein markers. , 1990, Brain : a journal of neurology.

[48]  G J Barker,et al.  Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations , 2001, Neurology.

[49]  J. Taubenberger,et al.  Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis , 1993, Annals of neurology.

[50]  P. Basser.  Inferring microstructural features and the physiological state of tissues from diffusion‐weighted images , 1995, NMR in biomedicine.

[51]  S. Reingold,et al.  Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria” , 2005, Annals of neurology.

[52]  P S Tofts,et al.  Correlation of apparent myelin measures obtained in multiple sclerosis patients and controls from magnetization transfer and multicompartmental T2 analysis , 2005, Magnetic resonance in medicine.

[53]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

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

[55]  R. Ordidge,et al.  High field MRI correlates of myelin content and axonal density in multiple sclerosis , 2003, Journal of Neurology.

[56]  M. Bronskill,et al.  Characterizing white matter with magnetization transfer and T2 , 1999, Magnetic resonance in medicine.

[57]  F. Barkhof,et al.  Axonal loss in multiple sclerosis lesions: Magnetic resonance imaging insights into substrates of disability , 1999, Annals of neurology.

[58]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[59]  John Russell,et al.  Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water , 2002, NeuroImage.

[60]  P. Tofts.  Quantitative MRI of the Brain , 2003 .

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

[62]  G J Parker,et al.  Accurate multislice gradient echo T1 measurement in the presence of non‐ideal RF pulse shape and RF field nonuniformity , 2001, Magnetic resonance in medicine.

[63]  G. Barker,et al.  Sources of variation in multi-centre brain MTR histogram studies: body-coil transmission eliminates inter-centre differences , 2006, Magnetic Resonance Materials in Physics, Biology and Medicine.

[64]  Rajiv Midha,et al.  MR properties of excised neural tissue following experimentally induced demyelination , 2005, NMR in biomedicine.

[65]  C. D. DE GROOT,et al.  Staging of multiple sclerosis (MS) lesions: pathology of the time frame of MS , 2000, Neuropathology and applied neurobiology.

[66]  A. MacKay,et al.  Are mono‐exponential fits to a few echoes sufficient to determine T2 relaxation for in vivo human brain? , 1999, Magnetic resonance in medicine.

[67]  F. Barkhof,et al.  Magnetic resonance imaging as a tool to examine the neuropathology of multiple sclerosis , 2004, Neuropathology and applied neurobiology.