Resolution considerations in imaging of the cortical layers.

The cortical layers are a finger print of brain development, function, connectivity and pathology. Obviously, the formation of the layers and their composition is essential to cognition and behavior. The layers were traditionally measured by histological means but recent studies utilizing MRI suggested that T1 relaxation imaging consist of enough contrast to separate the layers. Indeed extreme resolution, post mortem, studies demonstrated this phenomenon. Yet, one of the limiting factors of using T1 MRI to visualize the layers in neuroimaging research is partial volume effect. This happen when the image resolution is not high enough and two or more layers resides within the same voxel. In this paper we demonstrate that due to the physical small thickness of the layers it is highly unlikely that high resolution imaging could resolve the layers. By contrast, we suggest that low resolution multi T1 mapping conjugate with composition analysis could provide practical means for measuring the T1 layers. We suggest an acquisition platform that is clinically feasible and could quantify measures of the layers. The key feature of the suggested platform is that separation of the layers is better achieved in the T1 relaxation domain rather than in the spatial image domain.

Tutorial: a guide to diffusion MRI and structural connectomics.

Diffusion magnetic resonance imaging (dMRI) is a versatile imaging technique that has gained popularity thanks to its sensitive ability to measure displacement of water molecules within a living tissue on a micrometer scale. Although dMRI has been around since the early 1990s, its applications are constantly evolving, primarily regarding the inference of structural connectomics from nerve fiber trajectories. However, these applications require expertise in image processing and statistics, and it can be difficult for a newcomer to choose an appropriate pipeline to fit their research needs, not least because dMRI is such a flexible methodology that dozens of acquisition and analysis pipelines have been developed over the years. This introductory guide is designed for graduate students and researchers in the neuroscience community who are interested in integrating this new methodology regardless of their background in neuroimaging and computational tools. The guide provides a brief overview of the basic dMRI methodologies but focuses on its applications in neuroplasticity and connectomics. The guide starts with dMRI experimental designs and a complete step-by-step pipeline for structural connectomics. The following section covers the basics of dMRI, including parameters and clinical applications (apparent diffusion coefficient, mean diffusivity, fractional anisotropy and microscopic fractional anisotropy), as well as different approaches and models. The final section focuses on structural connectomics, covering subjects from fiber tracking (techniques, evaluation and limitations) to structural networks (constructing, analyzing and visualizing a network).

Clustering the cortical laminae: in vivo parcellation.

The laminar microstructure of the cerebral cortex has distinct anatomical characteristics of the development, function, connectivity, and even various pathologies of the brain. In recent years, multiple neuroimaging studies have utilized magnetic resonance imaging (MRI) relaxometry to visualize and explore this intricate microstructure, successfully delineating the cortical laminar components. Despite this progress, T1 is still primarily considered a direct measure of myeloarchitecture (myelin content), rather than a probe of tissue cytoarchitecture (cellular composition). This study aims to offer a robust, whole-brain validation of T1 imaging as a practical and effective tool for exploring the laminar composition of the cortex. To do so, we cluster complex microstructural cortical datasets of both human (N = 30) and macaque (N = 1) brains using an adaptation of an algorithm for clustering cell omics profiles. The resulting cluster patterns are then compared to established atlases of cytoarchitectonic features, exhibiting significant correspondence in both species. Lastly, we demonstrate the expanded applicability of T1 imaging by exploring some of the cytoarchitectonic features behind various unique skillsets, such as musicality and athleticism.

Expanding connectomics to the laminar level: A perspective.

Despite great progress in uncovering the complex connectivity patterns of the human brain over the last two decades, the field of connectomics still experiences a bias in its viewpoint of the cerebral cortex. Due to a lack of information regarding exact end points of fiber tracts inside cortical gray matter, the cortex is commonly reduced to a single homogenous unit. Concurrently, substantial developments have been made over the past decade in the use of relaxometry and particularly inversion recovery imaging for exploring the laminar microstructure of cortical gray matter. In recent years, these developments have culminated in an automated framework for cortical laminar composition analysis and visualization, followed by studies of cortical dyslamination in epilepsy patients and age-related differences in laminar composition in healthy subjects. This perspective summarizes the developments and remaining challenges of multi-T1 weighted imaging of cortical laminar substructure, the current limitations in structural connectomics, and the recent progress in integrating these fields into a new model-based subfield termed 'laminar connectomics'. In the coming years, we predict an increased use of similar generalizable, data-driven models in connectomics with the purpose of integrating multimodal MRI datasets and providing a more nuanced and detailed characterization of brain connectivity.

Modelling Cortical Laminar Connectivity in the Macaque Brain.

In 1991, Felleman and Van Essen published their seminal study regarding hierarchical processing in the primate cerebral cortex. Their work encompassed a widescale analysis of connections reported through tracing between 35 regions in the macaque visual cortex, extending from cortical regions to the laminar level. In this work, we revisit laminar-level connectivity in the macaque brain using a whole-brain MRI-based approach. We use multimodal ex-vivo MRI imaging of the macaque brain in both white and grey matter, which are then integrated via a simple model of laminar connectivity. This model uses a granularity-based approach to define a set of rules that expands cortical connections to the laminar level. Different fiber tracking routines are then examined in order to explore the ability of our model to infer laminar connectivity. The network of macaque cortical laminar connectivity resulting from the chosen routine is then validated in the visual cortex by comparison to findings from Felleman and Van Essen with an 83% accuracy level. By using a more comprehensive definition of the cortex that addresses its heterogenous laminar composition, we can explore a new avenue of structural connectivity on the laminar level.

Modelling the laminar connectome of the human brain.

The human connectome is the complete structural description of the network of connections and elements that form the 'wiring diagram' of the brain. Due to the current scarcity of information regarding laminar end points of white matter tracts inside cortical grey matter, tractography remains focused on cortical partitioning into regions, while ignoring radial partitioning into laminar components. To overcome this biased representation of the cortex as a single homogenous unit, we use a recent data-derived model of cortical laminar connectivity, which has been further explored and corroborated in the macaque brain by comparison to published studies. The model integrates multimodal MRI imaging datasets of both white matter connectivity and grey matter laminar composition into a laminar-level connectome. In this study, we model the laminar connectome of healthy human brains (N = 30) and explore them via a set of complex network measures. Our analysis demonstrates a subdivision of network hubs that appear in the standard connectome into each individual component of the laminar connectome, giving a fresh look into the role of laminar components in cortical connectivity and offering new prospects in the fields of both structural and functional connectivity.

An MRI-Based, Data-Driven Model of Cortical Laminar Connectivity.

Over the past two centuries, great scientific efforts have been spent on deciphering the structure and function of the cerebral cortex using a wide variety of methods. Since the advent of MRI neuroimaging, significant progress has been made in imaging of global white matter connectivity (connectomics), followed by promising new studies regarding imaging of grey matter laminar compartments. Despite progress in both fields, there still lacks mesoscale information regarding cortical laminar connectivity that could potentially bridge the gap between the current resolution of connectomics and the relatively higher resolution of cortical laminar imaging. Here, we systematically review a sample of prominent published articles regarding cortical laminar connectivity, in order to offer a simplified data-driven model that integrates white and grey matter MRI datasets into a novel way of exploring whole-brain tissue-level connectivity. Although it has been widely accepted that the cortex is exceptionally organized and interconnected, studies on the subject display a variety of approaches towards its structural building blocks. Our model addresses three principal cortical building blocks: cortical layer definitions (laminar grouping), vertical connections (intraregional, within the cortical microcircuit and subcortex) and horizontal connections (interregional, including connections within and between the hemispheres). While cortical partitioning into layers is more widely accepted as common knowledge, certain aspects of others such as cortical columns or microcircuits are still being debated. This study offers a broad and simplified view of histological and microscopical knowledge in laminar research that is applicable to the limitations of MRI methodologies, primarily regarding specificity and resolution.

A framework for cortical laminar composition analysis using low-resolution T1 MRI images.

The layer composition of the cerebral cortex represents a unique anatomical fingerprint of brain development, function, connectivity, and pathology. Historically, the cortical layers were investigated solely ex-vivo using histological means, but recent magnetic resonance imaging (MRI) studies suggest that T1 relaxation images can be utilized to separate the layers. Despite technological advancements in the field of high-resolution MRI, accurate estimation of whole-brain cortical laminar composition has remained limited due to partial volume effects, leaving some layers far beyond the image resolution. In this study, we offer a simple and accurate method for cortical laminar composition analysis, resolving partial volume effects and cortical curvature heterogeneity. We use a low-resolution 3T MRI echo planar imaging inversion recovery (EPI IR) scan protocol that provides fast acquisition (~ 12 min) and enables extraction of multiple T1 relaxation time components per voxel, which are assigned to types of brain tissue and utilized to extract the subvoxel composition of six T1 layers. While previous investigation of the layers required the estimation of cortical normals or smoothing of layer widths (similar to VBM), here we developed a sphere-based approach to explore the inner mesoscale architecture of the cortex. Our novel algorithm conducts spatial analysis using volumetric sampling of a system of virtual spheres dispersed throughout the entire cortical space. The methodology offers a robust and powerful framework for quantification and visualization of the cortical laminar structure on the cortical surface, providing a basis for quantitative investigation of its role in cognition, physiology and pathology.