Magnetization transfer and multicomponent T2 relaxation measurements with histopathologic correlation in an experimental model of MS

Magnetization transfer and multicomponent T2 imaging techniques were implemented to study guinea pig in vivo. A chronic‐progressive model of experimental allergic encephalomyelitis (EAE) was produced, and the inflammatory component of the disease was manipulated using antibodies against integrin. The magnetization transfer ratio (MTR) and T2 relaxation properties were measured in normal‐appearing white matter (NAWM) with histological comparisons. Significant reductions in both the mean MTR and the myelin water percentage were measured in NAWM of EAE guinea pig brain. However, the MTR and myelin water percentage appear to measure different aspects of pathology in NAWM in EAE. Reductions in the MTR were prevented or reversed with suppression of inflammation. However, modulation of inflammatory activity was not reflected in the measurement of the myelin water percentage. Since the amount of myelin is not expected to vary with inflammatory‐related changes, these observations support our hypothesis that the MTR is sensitive to physiological changes to myelin induced by inflammation, while the short T2 component is a more specific indicator of myelin content in tissue. Pathologic features other than demyelination may be important in the determination of the MTR. J. Magn. Reson. Imaging 2000;11:586–595. © 2000 Wiley‐Liss, Inc.

[1]  G. Comi,et al.  Short-term evolution of individual enhancing MS lesions studied with magnetization transfer imaging. , 1999, Magnetic resonance imaging.

[2]  A. MacKay,et al.  Spin‐spin relaxation in experimental allergic Encephalomyelitis. Analysis of CPMG data using a non‐linear least squares method and linear inverse theory , 1993, Magnetic resonance in medicine.

[3]  R I Grossman,et al.  Microscopic disease in normal-appearing white matter on conventional MR images in patients with multiple sclerosis: assessment with magnetization-transfer measurements. , 1995, Radiology.

[4]  F. Lublin Susceptibility to experimental allergic encephalomyelitis in animal models of autoimmunity. , 1992, Current Opinion in Neurology and Neurosurgery.

[5]  R I Grossman,et al.  Magnetization transfer in multiple sclerosis , 1994, Annals of neurology.

[6]  R E Lenkinski,et al.  Correlation of spectroscopy and magnetization transfer imaging in the evaluation of demyelinating lesions and normal appearing white matter in multiple sclerosis , 1994, Magnetic resonance in medicine.

[7]  D. Finelli Magnetization transfer in neuroimaging. , 1998, Magnetic resonance imaging clinics of North America.

[8]  I. Namer,et al.  Magnetic resonance imaging of antibody-mediated demyelinating experimental allergic encephalomyelitis , 1994, Journal of Neuroimmunology.

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

[10]  J. Frank,et al.  Serial MR imaging of experimental autoimmune encephalomyelitis induced by human white matter or by chimeric myelin-basic and proteolipid protein in the common marmoset. , 1999, AJNR. American journal of neuroradiology.

[11]  R S Balaban,et al.  Magnetization transfer contrast in magnetic resonance imaging. , 1992, Magnetic resonance quarterly.

[12]  M Filippi,et al.  Long-term changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis. , 1999, AJNR. American journal of neuroradiology.

[13]  H. Lassmann,et al.  Histopathological characterization of magnetic resonance imaging-detectable brain white matter lesions in a primate model of multiple sclerosis: a correlative study in the experimental autoimmune encephalomyelitis model in common marmosets (Callithrix jacchus). , 1998, The American journal of pathology.

[14]  P. Allen,et al.  Application of continuous relaxation time distributions to the fitting of data from model systmes and excised tissue , 1991, Magnetic resonance in medicine.

[15]  S. Karlik,et al.  A monoclonal antibody to α4‐integrin reverses the MR‐detectable signs of experimental allergic encephalomyelitis in the Guinea pig , 1995 .

[16]  I. Vavasour,et al.  A comparison between magnetization transfer ratios and myelin water percentages in normals and multiple sclerosis patients , 1998, Magnetic resonance in medicine.

[17]  M Filippi,et al.  A Magnetization Transfer Imaging Study of Normal-Appearing White Matter in Multiple Sclerosis , 1995, Neurology.

[18]  B. Rutt,et al.  In vivo measurements of multi-component T2 relaxation behaviour in guinea pig brain. , 1999, Magnetic resonance imaging.

[19]  M Filippi,et al.  Normal-appearing white matter changes in multiple sclerosis: the contribution of magnetic resonance techniques , 1999, Multiple sclerosis.

[20]  M Filippi,et al.  Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI , 1999, Neurology.

[21]  C. Metz,et al.  Magnetization transfer: a potential method to determine the age of multiple sclerosis lesions. , 1994, AJNR. American journal of neuroradiology.

[22]  K. Nicolay,et al.  Longitudinal in vivo magnetic resonance imaging studies in experimental allergic encephalomyelitis: effect of a neurotrophic treatment on cortical lesion development , 1997, Neuroscience.

[23]  B. Trapp,et al.  Pathogenesis of tissue injury in MS lesions , 1999, Journal of Neuroimmunology.

[24]  J. Pauly,et al.  Parameter relations for the Shinnar-Le Roux selective excitation pulse design algorithm [NMR imaging]. , 1991, IEEE transactions on medical imaging.

[25]  A Van der Linden,et al.  In vivo noninvasive determination of abnormal water diffusion in the rat brain studied in an animal model for multiple sclerosis by diffusion-weighted NMR imaging. , 1996, Magnetic resonance imaging.

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

[27]  S. Karlik,et al.  Gadolinium enhancement in acute and chronic‐progressive experimental allergic encephalomyelitis in the guinea pig , 1993, Magnetic resonance in medicine.

[28]  F. Jolesz,et al.  CPMG imaging sequences for high field in vivo transverse relaxation studies , 1990, Magnetic resonance in medicine.

[29]  F. Barkhof,et al.  Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR. , 1998, AJNR. American journal of neuroradiology.

[30]  J. Caillé,et al.  Early structural changes in acute MS lesions assessed by serial magnetization transfer studies , 1998, Neurology.

[31]  G. Barker,et al.  Correlation of magnetization transfer ration with clinical disability in multiple sclerosis , 1994, Annals of neurology.

[32]  H P Hartung,et al.  In vivo MRI and its histological correlates in acute adoptive transfer experimental allergic encephalomyelitis. Quantification of inflammation and oedema. , 1996, Brain : a journal of neurology.

[33]  R S Balaban,et al.  Quantitative 1H magnetization transfer imaging in vivo , 1991, Magnetic resonance in medicine.

[34]  R. Petersen,et al.  Experimental allergic encephalomyelitis in non‐human primates: mri and mrs may predict the type of brain damage , 1995, NMR in biomedicine.

[35]  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.

[36]  Finelli Da Magnetization transfer in neuroimaging. , 1998 .

[37]  D. Laidlaw,et al.  MR microscopy of transgenic mice that spontaneously acquire experimental allergic encephalomyelitis , 1998, Magnetic resonance in medicine.

[38]  R E Snyder,et al.  T2 relaxation of peripheral nerve measured in vivo. , 1995, Magnetic resonance imaging.

[39]  J A Frank,et al.  In vivo three-dimensional MR microscopy of mice with chronic relapsing experimental autoimmune encephalomyelitis after treatment with insulin-like growth factor-I. , 1998, AJNR. American journal of neuroradiology.

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

[41]  Alex L. MacKay,et al.  Quantitative interpretation of NMR relaxation data , 1989 .

[42]  I. Cohen,et al.  On the regulation of EAE. , 1993, International reviews of immunology.

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

[44]  M. Filippi,et al.  Magnetization transfer ratios of multiple sclerosis lesions with variable durations of enhancement , 1998, Journal of the Neurological Sciences.

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

[46]  S. Karlik,et al.  Apoptotic Cells Are Present in the CNS throughout Acute and Chronic-Progressive EAE in the Absence of Clinical Recovery , 1998, Journal of neuropathology and experimental neurology.

[47]  G S Francis,et al.  Combined magnetization transfer and proton spectroscopic imaging in the assessment of pathologic brain lesions in multiple sclerosis. , 1999, AJNR. American journal of neuroradiology.