Mapping the aggregate g-ratio of white matter tracts using multi-modal MRI.

The g-ratio of a myelinated axon is defined as the ratio of the inner-to-outer diameter of the myelin sheath and modulates conduction speed of action potentials along axons. This g-ratio can be mappedat the macroscopic scale across the entire human brain using multi-modal MRI and sampled along white matter streamlines reconstructed from diffusion-weighted images to derive the g-ratio of a white matter tract. This tractometry approach has shown spatiotemporal variations in g-ratio across white matter tracts and networks.

Quantitative tractography: joys and sorrows.

Quantitative tractography is the term used to indicate informing the estimation of the major axonal pathways of the brain from diffusion MRI with microstructural information (such as volume, myelin, axonal densities, etc.) to deliver veridical and biologically meaningful connectomes. The literature is replete with studies showing promising results obtained with such methods; however, did you know that these methods also have some subtle pitfalls that aren't immediately apparent but, if neglected, could result in incorrect or biased conclusions? This brief paper provides an overview of such pitfalls and solutions to mitigate them.

MRI and non-MRI quantifiable neuroanatomical and functional parameters are useful for tractography.

Tractography provides a powerful framework to reconstruct white matter pathways from diffusion magnetic resonance imaging (dMRI) but remains challenged by its inherent ambiguity and lack of direct biological specificity. This short communication summarizes the key points of a debate held at the 2024 Tract-Anat Retreat on the utility of MRI and non-MRI quantifiable neuroanatomical and functional parameters for improving tractography. During the discussion, concerns were raised about the availability of histological properties only on post-mortem tissues, the disparity in scale between MRI and other modalities and the additional costs (both in time and money) of such additional parameters.

Animal models are useful in studying human neuroanatomy with tractography.

Despite the impact of tractography on human brain mapping, direct validation and biological interpretation remain challenging. This short communication summarizes the key points of a debate held at the 2024 Tract-Anat Retreat on whether animal models are useful for studying human neuroanatomy with diffusion MRI tractography. While recognizing limitations, such as anatomical and biological differences between species, hardware and acquisition considerations and direct translation and interpretation, we identified immense value and utility of animal models for tractography including validation with histology, acquiring high-resolution datasets, exploring disease mechanisms, and advancing comparative neuroanatomy.

An Investigation of Corticospinal Tract Microstructural Integrity in ARSACS Using a Profilometry MRI Analysis: Results From the PROSPAX Study.

Background: Spasticity represents a core clinical feature of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) patients. Nonetheless, its pathophysiological substrate is poorly investigated. We assessed the microstructural integrity of the corticospinal tract (CST) using diffusion MRI (dMRI) via profilometry analysis to understand its possible role in the development of spasticity in ARSACS.

The "central vein sign" to differentiate multiple sclerosis from migraine.

Objective: To investigate, in two cohorts including patients with multiple sclerosis (MS) and migraine, (i) the prevalence of the "central vein sign" (CVS), (ii) the spatial distribution of positive CVS (CVS+) lesions, (iii) the threshold of CVS+ lesions able to distinguish MS from migraine with high sensitivity and specificity.

Methods: A total of 70 patients with MS/clinically isolated syndrome and 50 age- and sex-matched patients with migraine underwent a 3-T magnetic resonance imaging scan. The CVS was evaluated according to current guidelines, excluding eight patients with migraine who did not show white matter (WM) lesions.

Relationship between sodium and diffusion MRI metrics in multiple sclerosis.

Sodium MRI can measure sodium concentrations in people with multiple sclerosis, but the extent to which these alterations reflect metabolic dysfunction in the absence of tissue damage or neuroaxonal loss remains uncertain. Increases in total sodium concentration and extracellular sodium concentration are believed to be indicative of tissue disruption and extracellular space expansion. Conversely, increase in intracellular sodium concentration may represent early and transient responses to neuronal insult, preceding overt tissue damage.

Developmental differences in canonical cortical networks: Insights from microstructure-informed tractography.

In response to a growing interest in refining brain connectivity assessments, this study focuses on integrating white matter fiber-specific microstructural properties into structural connectomes. Spanning ages 8-19 years in a developmental sample, it explores age-related patterns of microstructure-informed network properties at both local and global scales. First, the diffusion-weighted signal fraction associated with each tractography-reconstructed streamline was constructed.

Gradient of microstructural damage along the dentato-thalamo-cortical tract in Friedreich ataxia.

Objective: The dentato-thalamo-cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others.

An MRI evaluation of white matter involvement in paradigmatic forms of spastic ataxia: results from the multi-center PROSPAX study.

Background: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Spastic Paraplegia Type 7 (SPG7) are paradigmatic spastic ataxias (SPAX) with suggested white matter (WM) involvement. Aim of this work was to thoroughly disentangle the degree of WM involvement in these conditions, evaluating both macrostructure and microstructure via the analysis of diffusion MRI (dMRI) data.

Material And Methods: In this multi-center prospective study, ARSACS and SPG7 patients and Healthy Controls (HC) were enrolled, all undergoing a standardized dMRI protocol and a clinimetrics evaluation including the Scale for the Assessment and Rating of Ataxia (SARA).

Brain lesion microstructure in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein disease.

Background And Purpose: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) diagnosis are based on the presence of serological and magnetic resonance imaging (MRI) biomarkers. Diffusion tensor imaging (DTI), neurites orientation dispersion and density imaging (NODDI), and the Spherical Mean Technique (SMT) may be helpful to provide a microstructural characterization of the different types of white matter lesions and give an insight about their different pathological mechanisms. The aim of the study was to characterize microstructural differences between brain typical lesions (TLs) and nontypical lesions (nTLs).

Multiparametric Characterization and Spatial Distribution of Different MS Lesion Phenotypes.

Background And Purpose: MS lesions exhibit varying degrees of axonal and myelin damage. A comprehensive description of lesion phenotypes could contribute to an improved radiologic evaluation of smoldering inflammation and remyelination processes. This study aimed to identify in vivo distinct MS lesion types using quantitative susceptibility mapping and susceptibility mapping-weighted imaging and to characterize them through T1-relaxometry, myelin mapping, and diffusion MR imaging.

Blurred streamlines: A novel representation to reduce redundancy in tractography.

Tractography is a powerful tool to study brain connectivity in vivo, but it is well known to suffer from an intrinsic trade-off between sensitivity and specificity. A critical - but usually underrated - parameter to choose that can heavily impact the quality of the estimates is the number of streamlines to be reconstructed for a given data set. In fact, sensitivity can be improved by generating more and more streamlines, as all real anatomical connections are likely reconstructed, but lots of false positives are inevitably introduced, too.

Evaluation of tractography-based myelin-weighted connectivity across the lifespan.

Introduction: Recent studies showed that the myelin of the brain changes in the life span, and demyelination contributes to the loss of brain plasticity during normal aging. Diffusion-weighted magnetic resonance imaging (dMRI) allows studying brain connectivity by mapping axons in white matter with tractography algorithms. However, dMRI does not provide insight into myelin; thus, is necessary to investigate myelin-weighted brain connectivity.

The human brain connectome weighted by the myelin content and total intra-axonal cross-sectional area of white matter tracts.

A central goal in neuroscience is the development of a comprehensive mapping between structural and functional brain features, which facilitates mechanistic interpretation of brain function. However, the interpretability of structure-function brain models remains limited by a lack of biological detail. Here, we characterize human structural brain networks weighted by multiple white matter microstructural features including total intra-axonal cross-sectional area and myelin content.

Clinical and radiological correlates of apathy in multiple sclerosis.

Background: Although apathy has been associated with fronto-striatal dysfunction in several neurological disorders, its clinical and magnetic resonance imaging (MRI) correlates have been poorly investigated in people with multiple sclerosis (PwMS).

Objectives: To evaluate clinical variables and investigate microstructural integrity of fronto-striatal grey matter (GM) and white matter (WM) structures using diffusion tensor imaging (DTI).

Methods: 123 PwMS (age: 40.

Dual-encoded magnetization transfer and diffusion imaging and its application to tract-specific microstructure mapping.

We present a novel dual-encoded magnetization transfer (MT) and diffusion-weighted sequence and demonstrate its potential to resolve distinct properties of white matter fiber tracts at the sub-voxel level. The sequence was designed and optimized for maximal MT ratio (MTR) efficiency. The resulting whole brain 2.

Evaluation of tractogram filtering methods using human-like connectome phantoms.

Tractography algorithms are prone to reconstructing spurious connections. The set of streamlines generated with tractography can be post-processed to retain the streamlines that are most biologically plausible. Several microstructure-informed filtering algorithms are available for this purpose, however, the comparative performance of these methods has not been extensively evaluated.

Variability and reproducibility of multi-echo relaxometry: Insights from multi-site, multi-session and multi-subject MRI acquisitions.

Quantitative magnetic resonance imaging (qMRI) can increase the specificity and sensitivity of conventional weighted MRI to underlying pathology by comparing meaningful physical or chemical parameters, measured in physical units, with normative values acquired in a healthy population. This study focuses on multi-echo relaxometry, a qMRI technique that probes the complex tissue microstructure by differentiating compartment-specific relaxation times. However, estimation methods are still limited by their sensitivity to the underlying noise.

Mapping tissue microstructure across the human brain on a clinical scanner with soma and neurite density image metrics.

Soma and neurite density image (SANDI) is an advanced diffusion magnetic resonance imaging biophysical signal model devised to probe in vivo microstructural information in the gray matter (GM). This model requires acquisitions that include b values that are at least six times higher than those used in clinical practice. Such high b values are required to disentangle the signal contribution of water diffusing in soma from that diffusing in neurites and extracellular space, while keeping the diffusion time as short as possible to minimize potential bias due to water exchange.

Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations.

In-vivo characterization of macro- and microstructural injury of the subventricular zone in relapsing-remitting and progressive multiple sclerosis.

Introduction: The subventricular zone (SVZ) represents one of the main adult brain neurogenesis niche. In-vivo imaging of SVZ is very challenging and little is known about MRI correlates of SVZ macro- and micro-structural injury in multiple sclerosis (MS) patients.

Methods: The aim of the present study is to evaluate differences in terms of volume and microstructural changes [as assessed with the novel Spherical Mean Technique (SMT) model, evaluating: Neurite Signal fraction (INTRA); Extra-neurite transverse (EXTRATRANS) and mean diffusivity (EXTRAMD)] in SVZ between relapsing-remitting (RR) or progressive (P) MS patients and healthy controls (HC).

Central vein sign and diffusion MRI differentiate microstructural features within white matter lesions of multiple sclerosis patients with comorbidities.

Introduction: The Central Vein Sign (CVS) has been suggested as a potential biomarker to improve diagnostic specificity in multiple sclerosis (MS). Nevertheless, the impact of comorbidities on CVS performance has been poorly investigated so far. Despite the similar features shared by MS, migraine and Small Vessel Disease (SVD) at T2-weighted conventional MRI sequences, studies demonstrated their heterogeneous histopathological substrates.

An investigation of the association between focal damage and global network properties in cognitively impaired and cognitively preserved patients with multiple sclerosis.

Introduction: The presence of focal cortical and white matter damage in patients with multiple sclerosis (pwMS) might lead to specific alterations in brain networks that are associated with cognitive impairment. We applied microstructure-weighted connectomes to investigate (i) the relationship between global network metrics and information processing speed in pwMS, and (ii) whether the disruption provoked by focal lesions on global network metrics is associated to patients' information processing speed.

Materials And Methods: Sixty-eight pwMS and 92 healthy controls (HC) underwent neuropsychological examination and 3T brain MRI including multishell diffusion (dMRI), 3D FLAIR, and MP2RAGE.

Evaluating the central vein sign in paediatric-onset multiple sclerosis: A case series study.

The central vein sign (CVS) has been proposed as a biomarker of multiple sclerosis (MS). In adult-onset MS (AOMS), 40%-threshold of CVS positive (+) lesions demonstrated high accuracy for MS diagnosis. However, CVS+ lesions' performance has not been characterized in paediatric-onset (POMS) yet.