Tractography delineation of the vertical occipital fasciculus using quantitative T1 mapping.

The vertical occipital fasciculus (VOF) is a white-matter tract that connects the ventral and dorsal visual streams. The precise borders of the VOF have been a matter of dispute since its discovery in the 19th century. The presence of an adjacent vertical pathway, the posterior arcuate fasciculus, makes it especially hard to determine the anterior extent of the VOF. By integrating diffusion MRI tractography with quantitative T1 mapping we found that the vertical streamlines originating in the ventral occipito-temporal cortex show a pattern of lower T1 in more posterior streamlines. We used this pattern to develop an automatic procedure for VOF identification based on a sharp increase in the streamline T1 signature along the posterior-anterior axis. We studied the cortical endpoints of the VOF and their relation to known cytoarchitectonic and functional divisions of the cortex. These results show that multi-modal MRI information, which characterizes local tissue microstructure such as myelination, can be used to delineate white-matter tracts in vivo.

A comprehensive protocol for quantitative magnetic resonance imaging of the brain at 3 Tesla.

Quantitative MRI (qMRI) has been shown to be clinically useful for numerous applications in the brain and body. The development of rapid, accurate, and reproducible qMRI techniques offers access to new multiparametric data, which can provide a comprehensive view of tissue pathology. This work introduces a multiparametric qMRI protocol along with full postprocessing pipelines, optimized for brain imaging at 3 Tesla and using state-of-the-art qMRI tools. The total scan time is under 50 minutes and includes eight pulse-sequences, which produce range of quantitative maps including T1, T2, and T2* relaxation times, magnetic susceptibility, water and macromolecular tissue fractions, mean diffusivity and fractional anisotropy, magnetization transfer ratio (MTR), and inhomogeneous MTR. Practical tips and limitations of using the protocol are also provided and discussed. Application of the protocol is presented on a cohort of 28 healthy volunteers and 12 brain regions-of-interest (ROIs). Quantitative values agreed with previously reported values. Statistical analysis revealed low variability of qMRI parameters across subjects, which, compared to intra-ROI variability, was x4.1 ± 0.9 times higher on average. Significant and positive linear relationship was found between right and left hemispheres' values for all parameters and ROIs with Pearson correlation coefficients of r>0.89 (P<0.001), and mean slope of 0.95 ± 0.04. Finally, scan-rescan stability demonstrated high reproducibility of the measured parameters across ROIs and volunteers, with close-to-zero mean difference and without correlation between the mean and difference values (across map types, mean P value was 0.48 ± 0.27). The entire quantitative data and postprocessing scripts described in the manuscript are publicly available under dedicated GitHub and Figshare repositories. The quantitative maps produced by the presented protocol can promote longitudinal and multi-center studies, and improve the biological interpretability of qMRI by integrating multiple metrics that can reveal information, which is not apparent when examined using only a single contrast mechanism.

Non-invasive assessment of normal and impaired iron homeostasis in the brain.

Strict iron regulation is essential for normal brain function. The iron homeostasis, determined by the milieu of available iron compounds, is impaired in aging, neurodegenerative diseases and cancer. However, non-invasive assessment of different molecular iron environments implicating brain tissue's iron homeostasis remains a challenge. We present a magnetic resonance imaging (MRI) technology sensitive to the iron homeostasis of the living brain (the r1-r2* relaxivity). In vitro, our MRI approach reveals the distinct paramagnetic properties of ferritin, transferrin and ferrous iron ions. In the in vivo human brain, we validate our approach against ex vivo iron compounds quantification and gene expression. Our approach varies with the iron mobilization capacity across brain regions and in aging. It reveals brain tumors' iron homeostasis, and enhances the distinction between tumor tissue and non-pathological tissue without contrast agents. Therefore, our approach may allow for non-invasive research and diagnosis of iron homeostasis in living human brains.

The robust and independent nature of structural STS asymmetries.

The superior temporal sulcus (STS) is an important region for speech comprehension. The greater language network is known to exhibit asymmetries in both structure and function, and consistent with that theory are reports of STS structural asymmetry in MRI-based, morphological measures such as mean thickness and sulcal depth. However, it is not known how these individual STS structural asymmetries relate to each other, or how they interact with the broader language asymmetry that manifests in other brain regions. In this study, we assess the interrelations of STS asymmetries in the human brain in vivo, using four independent datasets to validate our findings. For morphological measurements, we identify STS laterality effects consistent between our datasets and with the literature: leftward for surface area, and rightward for sulcal depth and mean thickness. We then add two more measurements of STS asymmetry: in T1, a quantitative index of the tissue's underlying biophysical properties; and in the projections to the STS from the arcuate fasciculus, a left-lateralized white-matter bundle that connects temporal regions (including STS) with frontal regions (including Broca's area). For these two new measurements, we identify no effect for T1 and a leftward effect for arcuate projections. We then test for correlations between these STS asymmetries, and find associations mainly between measurements of the same type (e.g., two morphological measurements). Finally, we ask if STS asymmetry is preferentially related to Broca asymmetry, as these are both important language regions and connected via the arcuate fasciculus. Using a linear model with cross-validation, we find that random regions are as successful as Broca's area in predicting STS, and no indication of a hypothesized leftward asymmetry. We conclude that although these different STS asymmetries are robust across datasets, they are not trivially related to each other, suggesting different biological or imaging sources for different aspects of STS lateralities.

Disentangling molecular alterations from water-content changes in the aging human brain using quantitative MRI.

It is an open question whether aging-related changes throughout the brain are driven by a common factor or result from several distinct molecular mechanisms. Quantitative magnetic resonance imaging (qMRI) provides biophysical parametric measurements allowing for non-invasive mapping of the aging human brain. However, qMRI measurements change in response to both molecular composition and water content. Here, we present a tissue relaxivity approach that disentangles these two tissue components and decodes molecular information from the MRI signal. Our approach enables us to reveal the molecular composition of lipid samples and predict lipidomics measurements of the brain. It produces unique molecular signatures across the brain, which are correlated with specific gene-expression profiles. We uncover region-specific molecular changes associated with brain aging. These changes are independent from other MRI aging markers. Our approach opens the door to a quantitative characterization of the biological sources for aging, that until now was possible only post-mortem.