Whole brain myelin mapping using T1- and T2-weighted MR imaging data

Despite recent advancements in MR imaging, non-invasive mapping of myelin in the brain still remains an open issue. Here we attempted to provide a potential solution. Specifically, we developed a processing workflow based on T1-w and T2-w MR data to generate an optimized myelin enhanced contrast image. The workflow allows whole brain mapping using the T1-w/T2-w technique, which was originally introduced as a non-invasive method for assessing cortical myelin content. The hallmark of our approach is a retrospective calibration algorithm, applied to bias-corrected T1-w and T2-w images, that relies on image intensities outside the brain. This permits standardizing the intensity histogram of the ratio image, thereby allowing for across-subject statistical analyses. Quantitative comparisons of image histograms within and across different datasets confirmed the effectiveness of our normalization procedure. Not only did the calibrated T1-w/T2-w images exhibit a comparable intensity range, but also the shape of the intensity histograms was largely corresponding. We also assessed the reliability and specificity of the ratio image compared to other MR-based techniques, such as magnetization transfer ratio (MTR), fractional anisotropy (FA), and fluid-attenuated inversion recovery (FLAIR). With respect to these other techniques, T1-w/T2-w had consistently high values, as well as low inter-subject variability, in brain structures where myelin is most abundant. Overall, our results suggested that the T1-w/T2-w technique may be a valid tool supporting the non-invasive mapping of myelin in the brain. Therefore, it might find important applications in the study of brain development, aging and disease.

[1]  A. Barkovich Magnetic resonance techniques in the assessment of myelin and myelination , 2005, Journal of Inherited Metabolic Disease.

[2]  Y. Assaf,et al.  Diffusion Tensor Imaging (DTI)-based White Matter Mapping in Brain Research: A Review , 2007, Journal of Molecular Neuroscience.

[3]  Mark H. Johnson,et al.  Mapping Infant Brain Myelination with Magnetic Resonance Imaging , 2011, The Journal of Neuroscience.

[4]  Leonard E White,et al.  Diffusion tensor imaging assessment of brain white matter maturation during the first postnatal year. , 2007, AJR. American journal of roentgenology.

[5]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[6]  C. Beaulieu,et al.  Multicomponent water proton transverse relaxation and T2-discriminated water diffusion in myelinated and nonmyelinated nerve. , 1998, Magnetic resonance imaging.

[7]  D. V. van Essen,et al.  Mapping Human Cortical Areas In Vivo Based on Myelin Content as Revealed by T1- and T2-Weighted MRI , 2011, The Journal of Neuroscience.

[8]  E. Miot-Noirault,et al.  T2 relaxation time as a marker of brain myelination: experimental MR study in two neonatal animal models , 1997, Journal of Neuroscience Methods.

[9]  R I Grossman,et al.  Magnetization transfer: theory and clinical applications in neuroradiology. , 1994, Radiographics : a review publication of the Radiological Society of North America, Inc.

[10]  J. Rademacher,et al.  Measuringin VivoMyelination of Human White Matter Fiber Tracts with Magnetization Transfer MR , 1999, NeuroImage.

[11]  H A Vrooman,et al.  Global estimation of myelination in the developing brain on the basis of magnetization transfer imaging: a preliminary study. , 2001, AJNR. American journal of neuroradiology.

[12]  Min Chen,et al.  Multi-parametric neuroimaging reproducibility: A 3-T resource study , 2011, NeuroImage.

[13]  A. Mackay,et al.  In vivo measurement of T2 distributions and water contents in normal human brain , 1997, Magnetic resonance in medicine.

[14]  N. Obletter,et al.  MRI assessment of myelination: an age standardization , 2005, Pediatric Radiology.

[15]  John M Pauly,et al.  Echo time optimization for linear combination myelin imaging , 2005, Magnetic resonance in medicine.

[16]  Heidi Johansen-Berg,et al.  Myelin water imaging reflects clinical variability in multiple sclerosis , 2012, NeuroImage.

[17]  Matthew F. Glasser,et al.  Trends and Properties of Human Cerebral Cortex: Correlations with Cortical Myelin Content Introduction and Review , 2022 .

[18]  Nikolaus Weiskopf,et al.  Unified segmentation based correction of R1 brain maps for RF transmit field inhomogeneities (UNICORT) , 2011, NeuroImage.

[19]  A. MacKay,et al.  Magnetic resonance imaging of myelin , 2007, Neurotherapeutics.

[20]  J Ashburner,et al.  The role of registration and spatial normalisation in detecting activations in functional imaging , 1997 .

[21]  Mark Jenkinson,et al.  The minimal preprocessing pipelines for the Human Connectome Project , 2013, NeuroImage.

[22]  Guy Marchal,et al.  Automated multi-moda lity image registration based on information theory , 1995 .

[23]  S. H. Koenig,et al.  Cholesterol of myelin is the determinant of gray‐white contrast in MRI of brain , 1991, Magnetic resonance in medicine.

[24]  Hugues Benoit-Cattin,et al.  Intensity non-uniformity correction in MRI: Existing methods and their validation , 2006, Medical Image Anal..

[25]  A J Barkovich Techniques and methods in pediatric magnetic resonance imaging. , 1988, Seminars in ultrasound, CT, and MR.

[26]  J. Ashburner,et al.  Nonlinear spatial normalization using basis functions , 1999, Human brain mapping.

[27]  Kirk M Welker,et al.  Assessment of Normal Myelination with Magnetic Resonance Imaging , 2012, Seminars in Neurology.

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

[29]  R. Ashikaga,et al.  Appearance of normal brain maturation on fluid-attenuated inversion-recovery (FLAIR) MR images. , 1999, AJNR. American journal of neuroradiology.

[30]  Karl J. Friston,et al.  Unified segmentation , 2005, NeuroImage.

[31]  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.

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

[33]  Barkovich Aj Concepts of Myelin and Myelination in Neuroradiology , 2000 .

[34]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[35]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[36]  Suat Fitoz,et al.  The role of classic spin echo and FLAIR sequences for the evaluation of myelination in MR imaging. , 2005, Diagnostic and interventional radiology.

[37]  J W Murakami,et al.  Normal myelination of the pediatric brain imaged with fluid-attenuated inversion-recovery (FLAIR) MR imaging. , 1999, AJNR. American journal of neuroradiology.

[38]  Brian K. Rutt,et al.  Deficient MWF mapping in multiple sclerosis using 3D whole-brain multi-component relaxation MRI , 2012, NeuroImage.

[39]  Barkovich Aj Techniques and methods in pediatric magnetic resonance imaging. , 1988 .

[40]  S. Nelson,et al.  Measurement of in vivo multi-component T2 relaxation times for brain tissue using multi-slice T2 prep at 1.5 and 3 T. , 2006, Magnetic resonance imaging.

[41]  B. Mädler,et al.  Is diffusion anisotropy an accurate monitor of myelination? Correlation of multicomponent T2 relaxation and diffusion tensor anisotropy in human brain. , 2008, Magnetic resonance imaging.

[42]  N M Hylton,et al.  The Value of Relaxation Times and Density Measurements in Clinical MRI , 1987, Investigative radiology.

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

[44]  P S Tofts,et al.  Standardisation and optimisation of magnetic resonance techniques for multicentre studies. , 1998, Journal of neurology, neurosurgery, and psychiatry.

[45]  M A Horsfield,et al.  Mapping eddy current induced fields for the correction of diffusion-weighted echo planar images. , 1999, Magnetic resonance imaging.

[46]  Hao Huang,et al.  White and gray matter development in human fetal, newborn and pediatric brains , 2006, NeuroImage.

[47]  Jeremy D. Schmahmann,et al.  Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers , 2008, NeuroImage.

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

[49]  S. Reingold,et al.  The role of magnetic resonance techniques in understanding and managing multiple sclerosis. , 1998, Brain : a journal of neurology.

[50]  Bostjan Likar,et al.  A Review of Methods for Correction of Intensity Inhomogeneity in MRI , 2007, IEEE Transactions on Medical Imaging.

[51]  P. S. Tofts,et al.  Towards quantitative measurements of relaxation times and other parameters in the brain , 2004, Neuroradiology.

[52]  Alexander Leemans,et al.  The B‐matrix must be rotated when correcting for subject motion in DTI data , 2009, Magnetic resonance in medicine.

[53]  Derek K. Jones,et al.  Gleaning multicomponent T1 and T2 information from steady‐state imaging data , 2008, Magnetic resonance in medicine.

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

[55]  J. Dobbing,et al.  Quantitative growth and development of human brain , 1973, Archives of disease in childhood.

[56]  Frederik Barkhof,et al.  Magnetic resonance imaging pattern recognition in hypomyelinating disorders. , 2010, Brain : a journal of neurology.

[57]  A. Barkovich Concepts of myelin and myelination in neuroradiology. , 2000, AJNR. American journal of neuroradiology.

[58]  Carlo Pierpaoli,et al.  T2 relaxometry of normal pediatric brain development , 2009, Journal of magnetic resonance imaging : JMRI.

[59]  Alan C. Evans,et al.  Maturation of white matter in the human brain: a review of magnetic resonance studies , 2001, Brain Research Bulletin.