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Myeloarchitectonic mapping of cortical gray matter with 3D inhomogeneous magnetization transfer (ihMT)1Division of MRI research, Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, 2CRMBM, Aix Marseille Univ, CNRS, Marseille, France, 3Global MR Applications and Workflow, GE Healthcare, Boston, MA, United States
Synopsis
Advances in inhomogeneous magnetization transfer (ihMT) imaging have enabled improved volumetric imaging of gray matter. We performed a cortical surface-based analysis of the ihMT ratio (ihMTR) and the inverse ihMT ratio (ihMTRinv) to investigate the distribution of myelin in cortical gray matter. IhMT MRI, and especially ihMTRinv, displayed regional differences in cortical myelination, in agreement with postmortem studies. These findings support the myelin sensitivity and specificity of ihMTRinv and its use for gray matter characterization.
Introduction
Myeloarchitecture of gray matter, which refers to the patterns of myelinated fibers and their features (size, density and myelination), has been extensively studied in the past decades. Myelin content can be estimated using various types of MRI contrasts. Previous cortical surface-based analyses demonstrated that T1-weighted1, T2*-weighted2,3, T1w/T2w4,5 images intensities and magnetization transfer ratio (MTR)3 are associated with myelin content in gray matter, leading to a new parcellation of the cerebral cortex6. Inhomogeneous magnetization transfer (ihMT) is a novel MRI technique that can be made selectively sensitive to relatively long-lasting dipolar couplings within lipid chains, making it more specific to the high membrane density in myelin7–9.
Recently, 3-5 fold increases in the ihMT signal have been demonstrated through use of the low-duty cycle MT pulses10,15. This sensitivity improvement is particularly useful for measurements involving gray matter. The ihMT ratio (ihMTR) is a useful tool to measure myelin content11,12, but its quantification can be hampered by other contributions that vary the signal (B1+ and T1). The inverse ihMTR, ihMTRinv, shows a linear relationship with power13, and has been used in spoiled gradient-echo acquisitions along with a high-flip angle reference for greater B1+ and T1 insensitivity13,14. This work aims to make use of a low duty-cycle ihMT 3D sequence to investigate the distribution of myelin in the cortex using ihMTR and ihMTRinv.
Methods
Five healthy volunteers aged 18 to 35 years were scanned on a 3T scanner (GE Discovery MR750) and a 32-ch head coil (Nova Medical) with a 1mm isotropic 3D T1w FSPGR sequence and a 1.6mm isotropic 3D ihMTRAGE sequence composed of an ihMT preparation (5ms off-resonance pulses (cosine-modulated for dual-frequency irradiation), Δf=7kHz, B1,peak=14μT, RF pulses every 100ms for 1s) combined with a rapid gradient echo (RAGE) sequence (radial-fan beam view-ordering; FOV=24x24x16cm3; FA=10°; 90 readouts per TRihMTRAGE; TE/TR/TRihMTRAGE=1.8/4.6/2000ms). A high-flip angle (hfa) reference was also acquired for calculation of ihMTRinv, by substitution of the ihMT preparation with 1s of RF spoiled FA=45° pulses applied on-resonance every 25ms. IhMTR and ihMTRinv were computed as follows15:
$$ihMTR = \frac{M_{z,positive}+M_{z,negative}-2M_{z,dual}}{M_{0}} (1)$$
$$ihMTR_{inv}=M_{hfa}\left(\frac{2}{M_{z,dual}}-\frac{1}{M_{z, positive}}-\frac{1}{M_{z, negative}}\right) (2)$$
We computed a cortical surface-based analysis of ihMTR and ihMTRinv in order to assess the sensitivity of ihMT to cortical myelination using FreeSurfer (http:// surfer.nmr.mgh.harvard.edu). The pre-processing pipeline included: (1) reconstruction of the pial and white surfaces using the 3D T1w image, (2) realignment of each MT-weighted image to the M0 image, (3) calculation of ihMTR and ihMTRinv, (4) skull-stripping of ihMTR and ihMTRinv, (5) registration of ihMTR and ihMTRinv images to the T1w volume using boundary-based registration method, (6) sampling of z-transformed ihMTR and z-transformed ihMTRinv maps at the mid-distance between white and pial surfaces (50% depth), (7) projection of both maps to an average surface (fsaverage), averaging across subjects and smoothing along the surface with a 5mm FWHM Gaussian kernel. Though ihMTRinv can be absolutely quantified, we converted to z-scores to facilitate comparison with prior studies. For each subject, the z-score was calculated as z = (x – m)/σ, where x is the ihMTR or ihMTRinv value at the vertex and m and σ are the mean and standard deviation of ihMTR or ihMTRinv values in the left and right cortices.
Results & Discussion
Figure 1 displays the high-resolution ihMTR and ihMTRinv maps computed following the equations (1) and (2) respectively, detailed in the methods section. Cortical surface-based analysis of ihMTRinv displays regional differences in cortical myelination. The primary motor, primary somato-sensory, visual cortices and posterior cingulate display high myelination while the insula and the temporal lobe display low myelination (Figure 2). This spatial distribution of myelin is in agreement with postmortem studies16 and previous in vivo MR-based analyses1–5. Except for the motor and visual cortices, the ihMTR pattern does not match with the literature (Figure 3). The ihMTR can be affected by T1 and B1+ heterogeneity, likely making the metric less specific to myelin content and could induce some variance in the data.Conclusion
IhMT MRI, and especially calculated ihMTRinv, is specifically sensitive to myelin content in cortical gray matter and can be used to map the laminar distribution of myelin in the cortex. These results also broadly support the myelin sensitivity and specificity of the ihMT technique for applications in the CNS.Acknowledgements
No acknowledgement found.References
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