In-vivo multi-exponential T2, magnetization transfer and quantitative histology in a rat model of intramyelinic edema☆☆☆

Two MRI methods, multi-exponential analysis of transverse relaxation (MET2) and quantitative magnetization transfer (qMT), were used along with quantitative evaluation of histology in a study of intra-myelinic edema in rat spinal white matter. The results showed a strong linear correlation between a distinct long-T2 signal from MET2 analysis and the edema water volume fraction as measured by histology, although this analysis overestimated the edema water content by ≈ 100% relative to quantitative histological measurements. This overestimation was reasoned to result from the effects of inter-compartmental water exchange on observed transverse relaxation. Commonly studied MRI markers for myelin, the myelin water fraction (from MET2 analysis) and the macromolecular pool size ratio (from qMT analysis) produced results that could not be explained purely by changes in myelin content. The results demonstrate the potential for MET2 analysis as well as the limits of putative myelin markers for characterizing white matter abnormalities involving intra-myelinic edema.

[1]  V. Simplaceanu,et al.  Water compartments in the myelinated nerve. III. Pulsed NMR result , 1978, Experientia.

[2]  F A Jolesz,et al.  Proton magnetic resonance studies of triethyltin-induced edema during perinatal brain development in rabbits. , 1989, Journal of neurosurgery.

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

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

[5]  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.

[6]  B. Mädler,et al.  MR evidence of long T2 water in pathological white matter , 2007, Journal of magnetic resonance imaging : JMRI.

[7]  Craig K. Jones,et al.  Applications of stimulated echo correction to multicomponent T2 analysis , 2012, Magnetic resonance in medicine.

[8]  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.

[9]  P. Allen,et al.  Proton Relaxation Studies of Water Compartmentalization in a Model Neurological System , 1992, Magnetic resonance in medicine.

[10]  T. Huisman,et al.  T2 hyperintense signal of the central tegmental tracts in children: disease or normal maturational process? , 2012, Neuroradiology.

[11]  S. Trottier,et al.  The neuropathology of vigabatrin. , 1988, British journal of clinical practice. Supplement.

[12]  Paul A. Viola,et al.  Alignment by Maximization of Mutual Information , 1997, International Journal of Computer Vision.

[13]  W. H. Butler,et al.  Vigabatrin-induced lesions in the rat brain demonstrated by quantitative magnetic resonance imaging , 1994, Epilepsy Research.

[14]  Shu-Wei Sun,et al.  Quantitative magnetization transfer measured pool‐size ratio reflects optic nerve myelin content in ex vivo mice , 2009, Magnetic resonance in medicine.

[15]  H. Goodkin,et al.  Cerebral MRI abnormalities associated with vigabatrin therapy , 2009, Epilepsia.

[16]  G. Kennedy,et al.  Histopathologic changes produced by hexachlorophene in the rat as a function of both magnitude and number of doses , 1976 .

[17]  R. Kimbrough,et al.  Hexachlorophene effects on the rat brain: study of high doses by light and electron microscopy. , 1971, Archives of environmental health.

[18]  R. Lebel,et al.  Transverse relaxometry with stimulated echo compensation , 2010, Magnetic resonance in medicine.

[19]  D. Woessner.  Brownian motion and its effects in NMR chemical exchange and relaxation in liquids , 1996 .

[20]  P. Narayana,et al.  In vivo relaxation times of gray matter and white matter in spinal cord. , 1999, Magnetic resonance imaging.

[21]  Yong Tang,et al.  A stereological method for estimating the total length and size of myelin fibers in human brain white matter , 1997, Journal of Neuroscience Methods.

[22]  A. van Harreveld,et al.  Perfusion fixation with glutaraldehyde and post-fixation with osmium tetroxide for electron microscopy. , 1968, Journal of cell science.

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

[24]  Alex L. MacKay,et al.  Rapid whole cerebrum myelin water imaging using a 3D GRASE sequence , 2012, NeuroImage.

[25]  D. Gochberg,et al.  Multiexponential T2, magnetization transfer, and quantitative histology in white matter tracts of rat spinal cord , 2010, Magnetic resonance in medicine.

[26]  Mark D Does,et al.  Multicomponent T2 analysis of dithiocarbamate-mediated peripheral nerve demyelination. , 2007, Neurotoxicology.

[27]  Qing Ji,et al.  Multi‐slice myelin water imaging for practical clinical applications at 3.0 T , 2013, Magnetic Resonance in Medicine.

[28]  J. O'brien,et al.  Hexachlorophene encephalopathy , 2004, Acta Neuropathologica.

[29]  W. Norton,et al.  Biochemical and pathological studies of myelin in hexachlorophene intoxication , 1975, Brain Research.

[30]  E. Widjaja,et al.  Abnormal Axial Diffusivity in the Deep Gray Nuclei and Dorsal Brain Stem in Infantile Spasm Treated with Vigabatrin , 2010, American Journal of Neuroradiology.

[31]  Jeffrey A. Cohen,et al.  The Potential for Vigabatrin‐Induced Intramyelinic Edema in Humans , 2000, Epilepsia.

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

[33]  H. T. Edzes,et al.  Water in brain edema. Observations by the pulsed nuclear magnetic resonance technique. , 1975, Archives of neurology.

[34]  R M Henkelman,et al.  Diffusional anisotropy of T2 components in bovine optic nerve , 1998, Magnetic resonance in medicine.

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

[36]  C. Tanaka,et al.  Proton nuclear magnetic resonance studies on brain edema. , 1982, Journal of neurosurgery.

[37]  H. Igisu,et al.  Hexachlorophene-induced brain edema in rat observed by proton magnetic resonance , 2000, Brain Research.

[38]  P. Anderson,et al.  White matter pathology in phenylketonuria. , 2010, Molecular genetics and metabolism.

[39]  E. Karaarslan,et al.  Diffusion weighted MR imaging in non-infarct lesions of the brain. , 2008, European journal of radiology.

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

[41]  R M Henkelman,et al.  MR properties of rat sciatic nerve following trauma , 2001, Magnetic resonance in medicine.

[42]  Vaibhav A. Janve,et al.  Optimized inversion recovery sequences for quantitative T1 and magnetization transfer imaging , 2010, Magnetic resonance in medicine.

[43]  A. Righini,et al.  Water Apparent Diffusion Coefficient and T2 Changes in the Acute Stage of Maple Syrup Urine Disease: Evidence of Intramyelinic and Vasogenic‐Interstitial Edema , 2003, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[44]  Meher R. Juttukonda,et al.  Characterizing inter‐compartmental water exchange in myelinated tissue using relaxation exchange spectroscopy , 2013, Magnetic resonance in medicine.

[45]  R E Snyder,et al.  Multiexponential T2 relaxation in degenerating peripheral nerve , 1996, Magnetic resonance in medicine.

[46]  K. D. Harkins,et al.  Effect of intercompartmental water exchange on the apparent myelin water fraction in multiexponential T2 measurements of rat spinal cord , 2012, Magnetic resonance in medicine.

[47]  G. B. Pike,et al.  Characterizing healthy and diseased white matter using quantitative magnetization transfer and multicomponent T2 relaxometry: A unified view via a four‐pool model , 2009, Magnetic resonance in medicine.

[48]  C. Westall,et al.  Vigabatrin‐associated reversible MRI signal changes in patients with infantile spasms , 2010, Epilepsia.

[49]  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.

[50]  C. Laule,et al.  Water content and myelin water fraction in multiple sclerosis , 2004, Journal of Neurology.

[51]  D. N. Landon,et al.  Magnetic resonance imaging of experimental cerebral oedema. , 1986, Journal of neurology, neurosurgery, and psychiatry.

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

[53]  D. N. Landon,et al.  Quantitative nuclear magnetic resonance imaging: characterisation of experimental cerebral oedema. , 1987, Journal of neurology, neurosurgery, and psychiatry.

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

[55]  Craig K. Jones,et al.  Pulsed magnetization transfer imaging with body coil transmission at 3 Tesla: Feasibility and application , 2006, Magnetic resonance in medicine.

[56]  J. Schneider,et al.  Are vigabatrin induced T2 hyperintensities in cranial MRI associated with acute encephalopathy and extrapyramidal symptoms? , 2013, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[57]  Burkhard Mädler,et al.  Normal-appearing white matter in patients with phenylketonuria: water content, myelin water fraction, and metabolite concentrations. , 2007, Radiology.

[58]  W. Brittin,et al.  Nuclear Magnetic Resonance Studies in Multiple Phase Systems: Lifetime of a Water Molecule in an Adsorbing Phase on Silica Gel , 1957 .

[59]  D. Peterson,et al.  Neurite growth from, and neuronal survival within, cultured explants of the nervous system: A critical review of morphometric and stereological methods, and suggestions for the future , 1991, Progress in Neurobiology.

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

[61]  P. Joseph,et al.  High-resolution MR of the spinal cord in humans and rats. , 1989, AJNR. American journal of neuroradiology.

[62]  S. Renowden,et al.  Magnetic Resonance of Myelination and Myelin Disorders , 2006, Journal of Neurology.