Microstructural imaging of human neocortex in vivo

Abstract

The neocortex of the human brain is the seat of higher brain function. Modern imaging techniques, chief among them magnetic resonance imaging (MRI), allow non-invasive imaging of this important structure. Knowledge of the microstructure of the neocortex has classically come from post-mortem histological studies of human tissue, and extrapolations from invasive animal studies. From these studies, we know that the scale of important neocortical structure spans six orders of magnitude, ranging from the size of axonal diameters (microns), to the size of cortical areas responsible for integrating sensory information (centimetres). MRI presents an opportunity to move beyond classical methods, because MRI is non-invasive and MRI contrast is sensitive to neocortical microstructure over all these length scales. MRI thus allows inferences to be made about neocortical microstructure in vivo, i.e. MRI-based in vivo histology. We review recent literature that has applied and developed MRI-based in vivo histology to probe the microstructure of the human neocortex, focusing specifically on myelin, iron, and neuronal fibre mapping. We find that applications such as cortical parcellation (using [Formula: see text] maps as proxies for myelin content) and investigation of cortical iron deposition with age (using [Formula: see text] maps) are already contributing to the frontiers of knowledge in neuroscience. Neuronal fibre mapping in the cortex remains challenging in vivo, but recent improvements in diffusion MRI hold promise for exciting applications in the near future. The literature also suggests that utilising multiple complementary quantitative MRI maps could increase the specificity of inferences about neocortical microstructure relative to contemporary techniques, but that further investment in modelling is required to appropriately combine the maps. In vivo histology of human neocortical microstructure is undergoing rapid development. Future developments will improve its specificity, sensitivity, and clinical applicability, granting an ever greater ability to investigate neuroscientific and clinical questions about the human neocortex.

In vivo measurements of irreversible and reversible transverse relaxation rates in human basal ganglia at 7 T: making inferences about the microscopic and mesoscopic structure of iron and calcification deposits

“…This leads to irreversible transverse relaxation, whereas reversible transverse relaxation results from field variations that only reach significance over distances greater than the diffusion length—in what Fernández‐Seara and Wehrli call the mesoscopic scale—since a refocusing pulse will successfully refocus spin populations diffusing through such inhomogeneities. Therefore, an increase in both irreversible and reversible transverse relaxation rates with presumed iron content, as observed here and in other studies, implies that these iron deposits cause both microscopic and mesoscopic field variations, suggesting a rather “heterogeneous” geometry for these deposits; indeed, evidence for a heterogeneous distribution of iron is seen in histological studies of basal ganglia, lending further credence to the idea that MRI might eventually provide a non‐invasive means to probe the cellular distribution of iron …”

“…* Therefore, an increase in both irreversible and reversible transverse relaxation rates with presumed iron content, as observed here and in other studies, 42,43 implies that these iron deposits cause both microscopic and mesoscopic field variations, suggesting a rather "heterogeneous" geometry for these deposits; indeed, evidence for a heterogeneous distribution of iron is seen in histological studies of basal ganglia, 44 lending further credence to the idea that MRI might eventually provide a non-invasive means to probe the cellular distribution of iron. 40,45 Turning now to the individual with calcifications in the globus pallidus, we see that the irreversible transverse relaxation rate in this structure is very much in line with what would be expected based on the predicted iron level for that age, but that the reversible relaxation rate is dramatically higher than expected (see Figures 5a and c). This suggests that the calcifications in this individual primarily induce mesoscopic rather than microscopic field variations.…”

Apparent thinning of visual cortex during childhood is associated with myelination, not pruning

“…In contrast, myelination predicts developmental changes to both white and gray matter. In the white matter, increased myelination predicts lower T 1 18,23 and reduced MD 20,22 . Myelination is most pronounced in deep cortical layers closer to gray--white boundary, which contains more afferent and efferent projections, than layers close to pial surface 24,25 .…”

“…Quantitative MRI enables the measurement and comparison across individuals of the amount of non--water tissue within a voxel (macromolecular tissue volume, MTV) and the relaxation time (T 1 ), which depend on tissue composition (e.g., tissue containing myelin, reduces T 1 more than tissue without it). Additionally, mean diffusivity (MD), obtained from dMRI, depends on the size, density, and structure of the space within tissue through which water diffuses and provides additional insight into microstructural changes during development 20,22 .…”

White matter fascicles and cortical microstructure predict reading-related responses in human ventral temporal cortex

“…That is, we asked whether differences in the gray matter microstructure across the cortical surface may also contribute to the consistent localization of category-selective regions in VTC. Recently developed quantitative MRI (qMRI) methods (Edwards et al, 2018;Lutti et al, 2014;Mezer et al, 2013) now enable assessing characteristics of the tissue microstructure of the gray matter in vivo Lutti et al, 2014;Weiskopf et al, 2013). QMRI measures proton relaxation time (T1), which differs between distinct category-selective regions , changes during development Natu et al, 2019) and correlates with people's performance in certain tasks, such as face processing .…”