•Gut composition influences brain development and function.•Combining neuroimaging and microbiota analysis can provide insights into neuroinflammatory processes.•Innovative techniques to handle big ...data are needed.
The gut-brain axis communicates the brain with the gut microbiota, a bidirectional conduit that has received increasing attention in recent years thanks to its emerging role in brain development and function. Alterations in microbiota composition have been associated to neurological and psychiatric disorders, and several studies suggest that the immune system plays a fundamental role in the gut-brain interaction. Recent advances in brain imaging and in microbiome sequencing have generated a large amount of information, yet the data from both these sources need to be combined efficiently to extract biological meaning, and any diagnostic and/or prognostic benefit from these tools. In addition, the causal nature of the gut-brain interaction remains to be fully established, and preclinical findings translated to humans. In this “Perspective” article, we discuss recent efforts to combine data on the gut microbiota with the features that can be obtained from the conversion of brain images into mineable data. The subsequent analysis of these data for diagnostic and prognostic purposes is an approach we call radiomicrobiomics and it holds tremendous potential to enhance our understanding of this fascinating connection.
Fundamental to increasing our understanding of the role of white matter microstructure in normal/abnormal function in the living human is the development of MR-based metrics that provide increased ...specificity to distinct attributes of the white matter (e.g., local fibre architecture, axon morphology, and myelin content). In recent years, different approaches have been developed to enhance this specificity, and the Tractometry framework was introduced to combine the resulting multi-parametric data for a comprehensive assessment of white matter properties.
The present work exploits that framework to characterise the statistical properties, specifically the variance and covariance, of these advanced microstructural indices across the major white matter pathways, with the aim of giving clear indications on the preferred metric(s) given the specific research question.
A cohort of healthy subjects was scanned with a protocol that combined multi-component relaxometry with conventional and advanced diffusion MRI acquisitions to build the first comprehensive MRI atlas of white matter microstructure. The mean and standard deviation of the different metrics were analysed in order to understand how they vary across different brain regions/individuals and the correlation between them. Characterising the fibre architectural complexity (in terms of number of fibre populations in a voxel) provides clear insights into correlation/lack of correlation between the different metrics and explains why DT-MRI is a good model for white matter only some of the time. The study also identifies the metrics that account for the largest inter-subject variability and reports the minimal sample size required to detect differences in means, showing that, on the other hand, conventional DT-MRI indices might still be the safest choice in many contexts.
•We report an atlas of key white matter pathways in standard space.•CHARMED provide more specific measures of axonal properties than DT-MRI metrics.•Crossing fibres explain the correlation between myelin and diffusion indices.•DT-MRI metrics need the smallest sample size to detect differences between groups.
Alcohol dependence is characterized by a gradual reduction in cognitive control and inflexibility to contingency changes. The neuroadaptations underlying this aberrant behavior are poorly understood. ...Using an animal model of alcohol use disorders (AUD) and complementing diffusion-weighted (dw)-MRI with quantitative immunohistochemistry and electrophysiological recordings, we provide causal evidence that chronic intermittent alcohol exposure affects the microstructural integrity of the fimbria/fornix, decreasing myelin basic protein content, and reducing the effective communication from the hippocampus (HC) to the prefrontal cortex (PFC). Using a simple quantitative neural network model, we show how disturbed HC-PFC communication may impede the extinction of maladaptive memories, decreasing flexibility. Finally, combining dw-MRI and psychometric data in AUD patients, we discovered an association between the magnitude of microstructural alteration in the fimbria/fornix and the reduction in cognitive flexibility. Overall, these findings highlight the vulnerability of the fimbria/fornix microstructure in AUD and its potential contribution to alcohol pathophysiology. Fimbria vulnerability to alcohol underlies hippocampal-prefrontal cortex dysfunction and correlates with cognitive impairment.
The yeast mitochondrial transport of GTP and GDP is mediated by Ggc1p, a member of the mitochondrial carrier family. The physiological role of Ggc1p in S. cerevisiae is probably to transport GTP into ...mitochondria in exchange for GDP generated in the matrix. ggc1Δ cells exhibit lower levels of GTP and increased levels of GDP in mitochondria, are unable to grow on nonfermentable substrates and lose mtDNA. Because in yeast, succinyl-CoA ligase produces ATP instead of GTP, and the mitochondrial nucleoside diphosphate kinase is localized in the intermembrane space, Ggc1p is the only supplier of mitochondrial GTP required for the maturation of proteins containing Fe-S clusters, such as aconitase 4Fe-4S and ferredoxin 2Fe-2S. In this work, it was demonstrated that citrate is a regulator of purified and reconstituted Ggc1p by trans-activating unidirectional transport of GTP across the proteoliposomal membrane. It was also shown that the binding site of Ggc1p for citrate is different from the binding site for the substrate GTP. It is proposed that the citrate-induced GTP uniport (CIGU) mediated by Ggc1p is involved in the homeostasis of the guanine nucleotide pool in the mitochondrial matrix.
Objective
The objective of this study was to determine the ability of 7T‐MRI for characterizing brain tissue integrity in early relapsing‐remitting MS patients compared to conventional 3T‐MRI and to ...investigate whether 7T‐MRI improves the performance for detecting cortical gray matter neurodegeneration and its associated network reorganization dynamics.
Methods
Seven early relapsing‐remitting MS patients and seven healthy individuals received MRI at 7T and 3T, whereas 30 and 40 healthy controls underwent separate 3T‐ and 7T‐MRI sessions, respectively. Surface‐based cortical thickness (CT) and gray‐to‐white contrast (GWc) measures were used to model morphometric networks, analyzed with graph theory by means of modularity, clustering coefficient, path length, and small‐worldness.
Results
7T‐MRI had lower CT and higher GWc compared to 3T‐MRI in MS. CT and GWc measures robustly differentiated MS from controls at 3T‐MRI. 7T‐ and 3T‐MRI showed high regional correspondence for CT (r = 0.72, P = 2e‐78) and GWc (r = 0.83, P = 5.5e‐121) in MS patients. MS CT and GWc morphometric networks at 7T‐MRI showed higher modularity, clustering coefficient, and small‐worldness than 3T, also compared to controls.
Interpretation
7T‐MRI allows to more precisely quantify morphometric alterations across the cortical mantle and captures more sensitively MS‐related network reorganization. Our findings open new avenues to design more accurate studies quantifying brain tissue loss and test treatment effects on tissue repair.
•Multi-shell diffusion MRI is more sensitive than DTI to multiple sclerosis neurodegeneration under clinical settings.•Multi-shell diffusion MRI at high and ultra-high fields is a viable option for ...imaging tissue changes in multiple sclerosis.•Higher b-values are not beneficial for multiple sclerosis under the tested short-time (10 min acquisition) conditions.
The recent introduction of advanced magnetic resonance (MR) imaging techniques to characterize focal and global degeneration in multiple sclerosis (MS), like the Composite Hindered and Restricted Model of Diffusion, or CHARMED, diffusional kurtosis imaging (DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI) made available new tools to image axonal pathology non-invasively in vivo. These methods already showed greater sensitivity and specificity compared to conventional diffusion tensor-based metrics (e.g., fractional anisotropy), overcoming some of its limitations.
While previous studies uncovered global and focal axonal degeneration in MS patients compared to healthy controls, here our aim is to investigate and compare different diffusion MRI acquisition protocols in their ability to highlight microstructural differences between MS and control tissue over several much used models. For comparison, we contrasted the ability of fractional anisotropy measurements to uncover differences between lesion, normal-appearing white matter (WM), gray matter and healthy tissue under the same imaging protocols. We show that: (1) focal and diffuse differences in several microstructural parameters are observed under clinical settings; (2) advanced models (CHARMED, DKI and NODDI) have increased specificity and sensitivity to neurodegeneration when compared to fractional anisotropy measurements; and (3) both high (3 T) and ultra-high fields (7 T) are viable options for imaging tissue change in MS lesions and normal appearing WM, while higher b-values are less beneficial under the tested short-time (10 min acquisition) conditions.
PDF
