A comparative study of axon diameter imaging techniques using diffusion MRI

Axon diameter and density provide information about the function and performance of white matter pathways. Direct measurement of such microstructure features offers more specific biomarkers than DTI indices. Many techniques to measure axon diameter statistics using diffusion MRI have been proposed in the literature, ranging from model-based approaches to Q-space imaging, but little is known of their relative performance and consistency. This work compares several representative model-based approaches quantitatively to gain insight into how the choices of tissue model and imaging protocol impact the estimation of microstructural features

The CONNECT project: Combining macro- and micro-structure

In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states. The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome

Autoimmune encephalomyelitis in NOD mice is not initially a progressive multiple sclerosis model.

OBJECTIVE: Despite progress in treating relapsing multiple sclerosis (MS), effective inhibition of nonrelapsing progressive MS is an urgent, unmet, clinical need. Animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), provide valuable tools to examine the mechanisms contributing to disease and may be important for developing rational therapeutic approaches for treatment of progressive MS. It has been suggested that myelin oligodendrocyte glycoprotein (MOG) peptide residues 35-55 (MOG35-55 )-induced EAE in nonobese diabetic (NOD) mice resembles secondary progressive MS. The objective was to determine whether the published data merits such claims. METHODS: Induction and monitoring of EAE in NOD mice and literature review. RESULTS: It is evident that the NOD mouse model lacks validity as a progressive MS model as the individual course seems to be an asynchronous, relapsing-remitting neurodegenerative disease, characterized by increasingly poor recovery from relapse. The seemingly progressive course seen in group means of clinical score is an artifact of data handling and interpretation. INTERPRETATION: Although MOG35-55 -induced EAE in NOD mice may provide some clues about approaches to block neurodegeneration associated with the inflammatory penumbra as lesions form, it should not be used to justify trials in people with nonactive, progressive MS. This adds further support to the view that drug studies in animals should universally adopt transparent raw data deposition as part of the publication process, such that claims can adequately be interrogated. This transparency is important if animal-based science is to remain a credible part of translational research in MS.Stichting MS ResearchWellcome TrustMedical Research CouncilNational Multiple Sclerosis Society. Grant Number: RG4132A5/

Visualization of cortical lamination patterns with magnetic resonance imaging

The ability to image the cortex laminar arrangements in vivo is one of the holy grails of neuroscience. Recent studies have visualized the cortical layers ex vivo and in vivo (on a small region of interest) using high-resolution T1/T2 magnetic resonance imaging (MRI). In this study, we used inversion-recovery (IR) MRI to increase the sensitivity of MRI toward cortical architecture and achieving whole-brain characterization of the layers, in vivo, in 3D on humans and rats. Using the IR measurements, we computed 3D signal intensity plots along the cortex termed corticograms to characterize cortical substructures. We found that cluster analyses of the multi-IR images along the cortex divides it into at least 6 laminar compartments. To validate our observations, we compared the IR-MRI analysis with histology and revealed a correspondence, although these 2 measures do not represent similar quantities. The abilities of the method to segment the cortex into layers were demonstrated on the striate cortex (visualizing the stripe of Gennari) and on the frontal cortex. We conclude that the presented methodology can serve as means to study and characterize individual cortical architecture and organization

In vivo measurement of axon diameter distribution in the corpus callosum of rat brain

Here, we present the first in vivo non-invasive measurement of the axon diameter distribution in the rat corpus callosum. Previously, this measurement was only possible using invasive histological methods. The axon diameter, along with other physical properties, such as the intra-axonal resistance, membrane resistance and capacitance etc. helps determine many important functional properties of nerves, such as their conduction velocity. In this work, we provide a novel magnetic resonance imaging method called AxCaliber, which can resolve the distinct signatures of trapped water molecules diffusing within axons as well as water molecules diffusing freely within the extra-axonal space. Using a series of diffusion weighted magnetic resonance imaging brain scans, we can reliably infer both the distribution of axon diameters and the volume fraction of these axons within each white matter voxel. We were able to verify the known microstructural variation along the corpus callosum of the rat from the anterior (genu) to posterior (splenium) regions. AxCaliber yields a narrow distribution centered ∼1 μm in the genu and splenium and much broader distributions centered ∼3 μm in the body of the corpus callosum. The axon diameter distribution found by AxCaliber is generally broader than those usually obtained by histology. One factor contributing to this difference is the significant tissue shrinkage that results from histological preparation. To that end, AxCaliber might provide a better estimate of the in vivo morphology of white matter. Being a magnetic resonance imaging based methodology, AxCaliber has the potential to be used in human scanners for morphological studies of white matter in normal and abnormal development, and white matter related diseases