Parametric Probability Distribution Functions for Axon Diameters of Corpus Callosum

Axon diameter is an important neuroanatomical characteristic of the nervous system that alters in the course of neurological disorders such as multiple sclerosis. Axon diameters vary, even within a fiber bundle, and are not normally distributed. An accurate distribution function is therefore beneficial, either to describe axon diameters that are obtained from a direct measurement technique (e.g., microscopy), or to infer them indirectly (e.g., using diffusion-weighted MRI). The gamma distribution is a common choice for this purpose (particularly for the inferential approach) because it resembles the distribution profile of measured axon diameters which has been consistently shown to be non-negative and right-skewed. In this study we compared a wide range of parametric probability distribution functions against empirical data obtained from electron microscopy images. We observed that the gamma distribution fails to accurately describe the main characteristics of the axon diameter distribution, such as location and scale of the mode and the profile of distribution tails. We also found that the generalized extreme value distribution consistently fitted the measured distribution better than other distribution functions. This suggests that there may be distinct subpopulations of axons in the corpus callosum, each with their own distribution profiles. In addition, we observed that several other distributions outperformed the gamma distribution, yet had the same number of unknown parameters; these were the inverse Gaussian, log normal, log logistic and Birnbaum-Saunders distributions

The relation of structural integrity and task-related functional connectivity in the aging brain.

The relations among structural integrity, functional connectivity (FC), and cognitive performance in the aging brain are still understudied. Here, we used multimodal and multivariate approaches to specifically examine age-related changes in task-related FC, gray-matter volumetrics, white-matter integrity, and performance. Our results are two-fold, showing (i) age-related differences in FC of the working memory network and (ii) age-related recruitment of a compensatory network associated with better accuracy on the task. Increased connectivity in the compensatory network correlates positively with preserved white-matter integrity in bilateral frontoparietal tracks and with larger gray-matter volume of right inferior parietal lobule. These findings demonstrate the importance of structural integrity and FC in working memory performance associated with healthy aging

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Recommendations and guidelines from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 1 -- In vivo small-animal imaging

The value of in vivo preclinical diffusion MRI (dMRI) is substantial. Small-animal dMRI has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. Many of the influential works in this field were first performed in small animals or ex vivo samples. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the data. This work aims to serve as a reference, presenting selected recommendations and guidelines from the diffusion community, on best practices for preclinical dMRI of in vivo animals. In each section, we also highlight areas for which no guidelines exist (and why), and where future work should focus. We first describe the value that small animal imaging adds to the field of dMRI, followed by general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss how they are appropriate for different studies. We then give guidelines for in vivo acquisition protocols, including decisions on hardware, animal preparation, imaging sequences and data processing, including pre-processing, model-fitting, and tractography. Finally, we provide an online resource which lists publicly available preclinical dMRI datasets and software packages, to promote responsible and reproducible research. An overarching goal herein is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.Comment: 69 pages, 6 figures, 1 tabl

The effect of prolonged spaceflight on cerebrospinal fluid and perivascular spaces of astronauts and cosmonauts

peer reviewedLong-duration spaceflight induces changes to the brain and cerebrospinal fluid compartments and visual acuity problems known as spaceflight-associated neuro-ocular syndrome (SANS). The clinical relevance of these changes and whether they equally affect crews of different space agencies remain unknown. We used MRI to analyze the alterations occurring in the perivascular spaces (PVS) in NASA and European Space Agency astronauts and Roscosmos cosmonauts after a 6-mo spaceflight on the International Space Station (ISS). We found increased volume of basal ganglia PVS and white matter PVS (WM-PVS) after spaceflight, which was more prominent in the NASA crew than the Roscosmos crew. Moreover, both crews demonstrated a similar degree of lateral ventricle enlargement and decreased subarachnoid space at the vertex, which was correlated with WM-PVS enlargement. As all crews experienced the same environment aboard the ISS, the differences in WM-PVS enlargement may have been due to, among other factors, differences in the use of countermeasures and high-resistive exercise regimes, which can influence brain fluid redistribution. Moreover, NASA astronauts who developed SANS had greater pre- and postflight WM-PVS volumes than those unaffected. These results provide evidence for a potential link between WM-PVS fluid and SANS. Copyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY)

Studying neuroanatomy using MRI

The study of neuroanatomy using imaging enables key insights into how our brains function, are shaped by genes and environment, and change with development, aging, and disease. Developments in MRI acquisition, image processing, and data modelling have been key to these advances. However, MRI provides an indirect measurement of the biological signals we aim to investigate. Thus, artifacts and key questions of correct interpretation can confound the readouts provided by anatomical MRI. In this review we provide an overview of the methods for measuring macro- and mesoscopic structure and inferring microstructural properties; we also describe key artefacts and confounds that can lead to incorrect conclusions. Ultimately, we believe that, though methods need to improve and caution is required in its interpretation, structural MRI continues to have great promise in furthering our understanding of how the brain works

Brain tissue compartment density estimated using diffusion-weighted MRI yields tissue parameters consistent with histology

We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intracellular and intraneurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin density estimates were compared with the results of electron and light microscopy in ex vivo mouse brain and with published density estimates in a healthy human brain. In ex vivo mouse brain, estimated myelin densities in different subregions of the mouse corpus callosum were almost identical to values obtained from electron microscopy (diffusion MRI: 42 +/- 6%, 36 +/- 4%, and 43 +/- 5%; electron microscopy: 41 +/- 10%, 36 +/- 8%, and 44 +/- 12% in genu, body and splenium, respectively). In the human brain, good agreement was observed between estimated fiber density measurements and previously reported values based on electron microscopy. Estimated density values were unaffected by crossing fibers. Hum Brain Mapp 36:3687-3702, 2015. (c) 2015 Wiley Periodicals, Inc