High spatial overlap but diverging age‐related trajectories of cortical magnetic resonance imaging markers aiming to represent intracortical myelin and microstructure

Abstract

Statistical effects of cortical metrics derived from standard T1‐ and T2‐weighted magnetic resonance imaging (MRI) images, such as gray–white matter contrast (GWC), boundary sharpness coefficient (BSC), T1‐weighted/T2‐weighted ratio (T1w/T2w), and cortical thickness (CT), are often interpreted as representing or being influenced by intracortical myelin content with little empirical evidence to justify these interpretations. We first examined spatial correspondence with more biologically specific microstructural measures, and second compared between‐marker age‐related trends with the underlying hypothesis that different measures primarily driven by similar changes in myelo‐ and microstructural underpinnings should be highly related. Cortical MRI markers were derived from MRI images of 127 healthy subjects, aged 18–81, using cortical surfaces that were generated with the CIVET 2.1.0 pipeline. Their gross spatial distributions were compared with gene expression‐derived cell‐type densities, histology‐derived cytoarchitecture, and quantitative R1 maps acquired on a subset of participants. We then compared between‐marker age‐related trends in their shape, direction, and spatial distribution of the linear age effect. The gross anatomical distributions of cortical MRI markers were, in general, more related to myelin and glial cells than neuronal indicators. Comparing MRI markers, our results revealed generally high overlap in spatial distribution (i.e., group means), but mostly divergent age trajectories in the shape, direction, and spatial distribution of the linear age effect. We conclude that the microstructural properties at the source of spatial distributions of MRI cortical markers can be different from microstructural changes that affect these markers in aging.

Assessing regional intracortical myelination in schizophrenia spectrum and bipolar disorders using the optimized T1w/T2w-ratio

“…The absence of lower regional T1w/T2w-ratio values in patients contrasts with our previous study on the GWC (Jørgensen et al, 2016). While these are different measures, they show moderate to high correlations, with a reported overall correlation of 0.73 (Parent et al, 2023). Our results also differed from previous findings of lower global and regional T1w/ T2w-ratio values in patients with schizophrenia spectrum disorders (Ganzetti et al, 2015;Iwatani et al, 2015).…”

Assessing regional intracortical myelination in schizophrenia spectrum and bipolar disorders using the optimized T1w/T2w-ratio

“…The absence of lower regional T1w/T2w-ratio values in patients contrasts with our previous study on the GWC (Jorgensen et al, 2016). While these are different measures, they show moderate to high correlations, with a reported overall correlation of 0.73 (Parent et al, 2023). Our results also differed from previous findings of lower global and regional T1w/T2w-ratio values in patients with schizophrenia spectrum disorders (Ganzetti et al, 2015;Iwatani et al, 2015).…”

“…For instance, low correlations have been found with the myelin-water fraction (MWF) in densely myelinated regions in white matter (Sandrone et al, 2023;Uddin et al, 2019). High correlations have, however, been found between the T1w/T2w-ratio and T1 relaxation time mapping of the cerebral cortex (Parent et al, 2023;Shams et al, 2019). Still, strong conclusions regarding microstructural tissue properties should be avoided since the T1w/T2w-ratio remains a complex measure and other tissue properties than myelin content, such as iron content or dendritic density, may also influence it (Righart et al, 2017).…”

Increased Cortical Thickness in Alzheimer's Disease

“…In brain development and learning, increased cortical thickness is attributed to increased neuropil with increased dendritic spines, dendritic and axonal arborization, and glial presence 70,71 . Additionally, cortical myelination could account for changes in cortical thickness measurements, since quantification of cortical thickness relies on the detection of the gray‐white matter boundary, which can be affected by myelin distribution 72,73 . Finally, prior research examining older adults with exceptionally preserved memory capacity found both increased cortical thickness in a region of the ACC as well as an overabundance of von Economo neurons 74 .…”

“…70,71 Additionally, cortical myelination could account for changes in cortical thickness measurements, since quantification of cortical thickness relies on the detection of the gray-white matter boundary, which can be affected by myelin distribution. 72,73 Finally, prior research examining older adults with exceptionally preserved memory capacity found both increased cortical thickness in a region of the ACC as well as an overabundance of von Economo neurons. 74 This overabundance of von Economo neurons may be related to increased thickness in area 33 prime among AD patients as well, especially those with lower cognitive impairment.…”