Multivariate combination of magnetization transfer, T 2 * and B0 orientation to study the myelo-architecture of the in vivo human cortex

Abstract

Recently, T2* imaging at 7 tesla (T) MRI was shown to reveal microstructural features of the cortical myeloarchitecture thanks to an increase in contrast-to-noise ratio. However, several confounds hamper the specificity of T2* measures (iron content, blood vessels, tissues orientation). Another metric, magnetization transfer ratio (MTR), is known to also be sensitive to myelin content and thus would be an excellent complementary measure because its underlying contrast mechanisms are different than that from T2*. The goal of this study was thus to combine MTR and T2* using multivariate statistics in order to gain insights into cortical myelin content. Seven healthy subjects were scanned at 7T and 3T to obtain T2* and MTR data, respectively. A multivariate myelin estimation model (MMEM) was developed, and consists in (i) normalizing T2* and MTR values and (ii) extracting their shared information using independent component analysis (ICA). B0 orientation dependence and cortical thickness were also computed and included in the model. Results showed high correlation between MTR and T2* in the whole cortex (r=0.76, p<10−16), suggesting that both metrics are partly driven by a common source of contrast, here assumed to be the myelin. Average MTR and T2* were respectively 31.0 +/− 0.3% and 32.1 +/− 1.4 ms. Results of the MMEM spatial distribution showed similar trends to that from histological work stained for myelin (r=0.77, p<0.01). Significant right-left differences were detected in the primary motor cortex (p<0.05), the posterior cingulate cortex (p<0.05) and the visual cortex (p<0.05). This study demonstrates that MTR and T2* are highly correlated in the cortex. The combination of MTR, T2*, CT and B0 orientation may be a useful means to study cortical myeloarchitecture with more specificity than using any of the individual methods. The MMEM framework is extendable to other contrasts such as T1 and diffusion MRI.

Studying cyto and myeloarchitecture of the human cortex at ultra-high field with quantitative imaging: R1, R2* and magnetic susceptibility

“…In this study we have tried to combine the information from in vivo quantitative R 1 , R 2 * and susceptibility maps of the cortex and build iron and myelin maps of the cortex. A similar analysis, but using T * 2 and MTR maps was able to create myelin maps using similar linear models (Mangeat et al, 2015). The model used in Eqs.…”

“…Other than the ability to distinguish Brodmann areas, the study by Cohen-Adad et al also observed that, within each region, there was a small dependence on the orientation of the cortical surface in respect to the magnetic field, suggesting that, in part, this contrast is not only modulated by iron load but is also due to the structurally organized myelin bundles running through the cortex. The same group has extended their analysis to include not only T 2 * cortical maps acquired at 7 T but also magnetization transfer ratio (MTR) obtained at 3 T and created "combined myelin estimation" maps (Mangeat et al, 2015). When looking exclusively at cortical R 1 maps, it was observed that the boundaries obtained using R 1 maps were in good agreement with those obtained using functional imaging to define on a single subject basis V1, MT (Sereno et al, 2013) and the auditory cortex (Dick et al, 2012).…”

The association between intra- and juxta-cortical pathology and cognitive impairment in multiple sclerosis by quantitative T 2 * mapping at 7 T MRI

“…Our findings are based on cross-sectional observations; longitudinal studies are needed to provide a more definite evaluation on the temporal relationship between cortical degeneration as measured by q-T 2 * and cognitive worsening in MS. Confirmatory studies are also needed to clarify how myelin and iron content independently contribute to q-T 2 * changes in MS (Yao et al, 2014), both inside and outside focal cortical lesions. Other quantitative contrasts could be combined with q-T 2 * to increase pathological specificity to cortical pathology (Mangeat et al, 2015). …”

A subject-specific framework for in vivo myeloarchitectonic analysis using high resolution quantitative MRI

“…T 1 maps gain most of their contrast from myelin Geyer et al, 2011), whereas T * 2 maps show intracortical contrast due to the spatial distribution of iron (Fukunaga et al, 2010;Deistung et al, 2013;Stüber et al, 2014), which is mainly found in the cell soma of oligodendrocytes (Connor et al, 1990). Other MR contrasts can be used to characterize cortical microstructure, such as diffusion metrics (McNab et al, 2013;Leuze et al, 2014;Nagy et al, 2013;Aggarwal et al, 2015), magnetization transfer (Mangeat et al, 2015) and magnetic susceptibility maps (Deistung et al, 2015). These recent advances in high resolution and quantitative MRI bring us closer to the goal of delineating cortical areas in vivo in individual subjects based on their microstructure, similar to the pioneering work of Brodmann and Vogt & Vogt. Classically, the anatomy of the cortex has been analyzed with experienced eyes, which is highly subjective and labor intensive, thus preventing large sample sizes.…”

“…Mangeat et al (2015) have combined two different contrast mechanisms, magnetization transfer ratio images and T * 2 maps, to create a multivariate model that is more specific to their underlying common source of contrast, myelin. Alternatively, multiple complementary MR contrasts can be used to better differentiate cortical areas.…”