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Friedreich's ataxia (FRDA) is a rare genetic disorder leading to degenerative processes. So far, no effective treatment has been found. Therefore, it is important to assist the development of medication with imaging biomarkers reflecting disease status and progress. Ten FRDA patients (mean age 37 ± 14 years; four female) and 10 age- and sex-matched controls were included. Acquisition of magnetic resonance imaging (MRI) data for quantitative susceptibility mapping, R 1 , R 2 relaxometry and diffusion imaging was performed at 7 Tesla. Results of volume of interest (VOI)-based analyses of the quantitative data were compared with a voxel-based morphometry (VBM) evaluation. Differences between patients and controls were assessed using the analysis of covariance (ANCOVA; p < 0.01) with age and sex as covariates, effect size of group differences, and correlations with disease characteristics with Spearman correlation coefficient. For the VBM analysis, a statistical threshold of 0.001 for uncorrected and 0.05 for corrected p-values was used. Statistically significant differences between FRDA patients and controls were found in five out of twelve investigated structures, and statistically significant correlations with disease characteristics were revealed. Moreover, VBM revealed significant white matter atrophy within regions of the brainstem, and the cerebellum. These regions overlapped partially with brain regions for which significant differences between healthy controls and patients were found in the VOI-based quantitative MRI evaluation. It was shown that two independent analyses provided overlapping results. Moreover, positive results on correlations with disease characteristics were found, indicating that these quantitative MRI parameters could provide more detailed information and assist the search for effective treatments., (© 2020 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Structural high-resolution imaging of the brainstem can be of high importance in clinical practice. However, ultra-high field magnetic resonance imaging (MRI) is still restricted in use due to limited availability. Therefore, quantitative MRI techniques (quantitative susceptibility mapping [QSM], relaxation measurements [ R 2 * , R 1 ], diffusion tensor imaging [DTI]) and T 2 - and proton density (PD)-weighted imaging in the human brainstem at 3 T and 7 T are compared. Five healthy volunteers (mean age: 21.5 ± 1.9 years) were measured at 3 T and 7 T using multi-echo gradient echo sequences for susceptibility mapping and R 2 * relaxometry, magnetization-prepared 2 rapid acquisition gradient echo sequences for R 1 relaxometry, turbo-spin echo sequences for PD- and T 2 -weighted imaging and readout-segmented echo planar sequences for DTI. Susceptibility maps were computed using Laplacian-based phase unwrapping, V-SHARP for background field removal and the streaking artifact reduction for QSM algorithm for dipole inversion. Contrast-to-noise ratios (CNRs) were determined at 3 T and 7 T in ten volumes of interest (VOIs). Data acquired at 7 T showed higher CNR. However, in four VOIs, lower CNR was observed for R 2 * at 7 T. QSM was shown to be the contrast with which the highest number of structures could be identified. The depiction of very fine tracts such as the medial longitudinal fasciculus throughout the brainstem was only possible in susceptibility maps acquired at 7 T. DTI effectively showed the main tracts (crus cerebri, transverse pontine fibers, corticospinal tract, middle and superior cerebellar peduncle, pontocerebellar tract, and pyramid) at both field strengths. Assessing the brainstem with quantitative MRI methods such as QSM, R 2 * , as well as PD- and T 2 -weighted imaging with great detail, is also possible at 3 T, especially when using susceptibility mapping calculated from a gradient echo sequence with a wide range of echo times from 10.5 to 52.5 ms. However, tracing smallest structures strongly benefits from imaging at ultra-high field., (© 2019 John Wiley & Sons, Ltd.)

White matter makes up about fifty percent of the human brain. Maturation of white matter accompanies biological development and undergoes the most dramatic changes during childhood and adolescence. Despite the advances in neuroimaging techniques, controversy concerning spatial, and temporal patterns of myelination, as well as the degree to which the microstructural characteristics of white matter can vary in a healthy brain as a function of age, gender and cognitive abilities still exists. In a selective review we describe methods of assessing myelination and evaluate effects of age and gender in nine major fiber tracts, highlighting their role in higher-order cognitive functions. Our findings suggests that myelination indices vary by age, fiber tract, and hemisphere. Effects of gender were also identified, although some attribute differences to methodological factors or social and learning opportunities. Findings point to further directions of research that will improve our understanding of the complex myelination-behavior relation across development that may have implications for educational and clinical practice.

White matter makes up about fifty percent of the human brain. Maturation of white matter accompanies biological development and undergoes the most dramatic changes during childhood and adolescence. Despite the advances in neuroimaging techniques, controversy concerning spatial, and temporal patterns of myelination, as well as the degree to which the microstructural characteristics of white matter can vary in a healthy brain as a function of age, gender and cognitive abilities still exists. In a selective review we describe methods of assessing myelination and evaluate effects of age and gender in nine major fiber tracts, highlighting their role in higher-order cognitive functions. Our findings suggests that myelination indices vary by age, fiber tract, and hemisphere. Effects of gender were also identified, although some attribute differences to methodological factors or social and learning opportunities. Findings point to further directions of research that will improve our understanding of the complex myelination-behavior relation across development that may have implications for educational and clinical practice. [ABSTRACT FROM AUTHOR]

• Provides a complete, accurate, and detailed mapping of subcortical structures, including the brainstem with the cerebellum. • Uses multiple MRI parameters acquired at 7T. • Utilizes both high-resolution MRI with 100-200 μm resolution and corresponding histology information from the same brain specimen to map anatomical structures in-depth. • Provides a useful anatomical standard for the region definition of subcortical targets and the generation of a 3D digital template atlas for the marmoset brain research. Subcortical nuclei and other deep brain structures play essential roles in regulating the central and peripheral nervous systems. However, many of these nuclei and their subregions are challenging to identify and delineate in conventional MRI due to their small size, hidden location, and often subtle contrasts compared to neighboring regions. To address these limitations, we scanned the whole brain of the marmoset monkeys in ex vivo using a clinically feasible diffusion MRI method, called the mean apparent propagator (MAP)-MRI, along with T2W and MTR (T1-like contrast) images acquired at 7 Tesla. Additionally, we registered these multimodal MRI volumes to the high-resolution images of matched whole-brain histology sections with seven different stains obtained from the same brain specimens. At high spatial resolution, the microstructural parameters and fiber orientation distribution functions derived with MAP-MRI can distinguish the subregions of many subcortical and deep brain structures, including fiber tracts of different sizes and orientations. The good correlation with multiple but distinct histological stains from the same brain serves as a thorough validation of the structures identified with MAP-MRI and other MRI parameters. Moreover, the anatomical details of deep brain structures found in the volumes of MAP-MRI parameters are not visible in conventional T1W or T2W images. The high-resolution mapping using novel MRI contrasts, combined and correlated with histology, can elucidate structures that were previously invisible radiologically. Thus, this multimodal approach offers a roadmap toward identifying salient brain areas in vivo in future neuroradiological studies. It also provides a useful anatomical standard reference for the region definition of subcortical targets and the generation of a 3D digital template atlas for the marmoset brain research (Saleem et al., 2023). Additionally, we conducted a cross-species comparison between marmoset and macaque monkeys using results from our previous studies (Saleem et al., 2021). We found that the two species had distinct patterns of iron distribution in subregions of the basal ganglia, red nucleus, and deep cerebellar nuclei, confirmed with T2W MRI and histology. [ABSTRACT FROM AUTHOR]

Introduction: Q-ball imaging (QBI) is one of the typical data models for quantifying white matter (WM) anisotropy in diffusion-weighted MRI (DwMRI) studies. Brain and spinal investigation by high angular resolution DwMRI (high angular resolution imaging (HARDI)) protocols exhibits higher angular resolution in diffusion imaging compared to low angular resolution models, although with longer acquisition times. We aimed to assess the difference between QBI-derived anisotropy values from high and low angular resolution DwMRI protocols and their potential advantages or shortcomings in neuroradiology. Methods: Brain DwMRI data sets were acquired in seven healthy volunteers using both HARDI ( b = 3000 s/mm, 54 gradient directions) and low angular resolution ( b = 1000 s/mm, 32 gradient directions) acquisition schemes. For both sequences, tract of interest tractography and generalized fractional anisotropy (GFA) measures were extracted by using QBI model and were compared between the two data sets. Results: QBI tractography and voxel-wise analyses showed that some WM tracts, such as corpus callosum, inferior longitudinal, and uncinate fasciculi, were reconstructed as one-dominant-direction fiber bundles with both acquisition schemes. In these WM tracts, mean percent different difference in GFA between the two data sets was less than 5 %. Contrariwise, multidirectional fiber bundles, such as corticospinal tract and superior longitudinal fasciculus, were more accurately depicted by HARDI acquisition scheme. Conclusion: Our results suggest that the design of optimal DwMRI acquisition protocols for clinical investigation of WM anisotropy by QBI models should consider the specific brain target regions to be explored, inducing researchers to a trade-off choice between angular resolution and acquisition time. [ABSTRACT FROM AUTHOR]

Introduction Diffusion tractography relies on complex mathematical models that provide anatomical information indirectly, and it needs to be validated. In humans, up to now, tractography has mainly been validated by qualitative comparison with data obtained from dissection. No quantitative comparison was possible because Magnetic Resonance Imaging (MRI) and dissection data are obtained in different reference spaces, and because fiber tracts are progressively destroyed by dissection. Here, we propose a novel method and software (FIBRASCAN) that allow accurate reconstruction of fiber tracts from dissection in MRI reference space. Method Five human hemispheres, obtained from four formalin-fixed brains were prepared for Klingler's dissection, placed on a holder with fiducial markers, MR scanned, and then dissected to expose the main association tracts. During dissection, we performed iterative acquisitions of the surface and texture of the specimens using a laser scanner and two digital cameras. Each texture was projected onto the corresponding surface and the resulting set of textured surfaces was coregistered thanks to the fiducial holders. The identified association tracts were then interactively segmented on each textured surface and reconstructed from the pile of surface segments. Finally, the reconstructed tracts were coregistered onto ex vivo MRI space thanks to the fiducials. Each critical step of the process was assessed to measure the precision of the method. Results We reconstructed six fiber tracts (long, anterior and posterior segments of the superior longitudinal fasciculus; Inferior fronto-occipital, Inferior longitudinal and uncinate fasciculi) from cadaveric dissection and ported them into ex vivo MRI reference space. The overall accuracy of the method was of the order of 1 mm: surface-to-surface registration = 0.138 mm (standard deviation (SD) = 0.058 mm), deformation of the specimen during dissection = 0.356 mm (SD = 0.231 mm), and coregistration surface-MRI = 0.6 mm (SD = 0.274 mm). The spatial resolution of the method (distance between two consecutive surface acquisitions) was 0.345 mm (SD = 0.115 mm). Conclusion This paper presents the robustness of a novel method, FIBRASCAN, for accurate reconstruction of fiber tracts from dissection in the ex vivo MR reference space. This is a major step toward quantitative comparison of MR tractography with dissection results. [ABSTRACT FROM AUTHOR]

Gross and microscopic studies by early investigators led the cerebral white matter from being regarded as an amorphous mass to an intricately organized system of fasciculi that facilitate the highest expression of cerebral activity. Here we pay homage to the anatomists whose observations resulted in the evolution of ideas about the cerebral white matter. We also draw attention to limitations of the earlier methodologies and to some of the conflicts and controversies that have characterized this field and that persist in the current literature. We conclude with brief reference to the principles of organization of the fiber pathways derived from our studies in the monkey using the autoradiographic tract tracing technique, another step in the ongoing investigations of the cerebral white matter. This historical review has contemporary relevance because the fiber pathways of the brain are crucial components of the distributed neural circuits that subserve nervous system function; the clinical manifestations of white matter damage are recognized with greater frequency and clarity; and magnetic resonance imaging tractography has made it possible to view these fiber bundles within the living human brain. [ABSTRACT FROM AUTHOR]

Previous work has identified axonal outgrowth and/or guidance defects in the brain and spinal cord of prenatal Frizzled3 (Fz3)[sup -/-] mice. To systematically explore the axonal defects in Fz3[sup -/-] mice and to compare techniques for the global assessment of axon tracts in the developing mouse, we have analyzed wild-type and Fz3[sup -/-] brains using (1) diffusion tensor magnetic resonance imaging (μDTI), (2) neurofilament staining, and (3) two genetically directed neuronal labeling methods. Confirming and extending the previous work of Wanget al. (2002), we find that the following structures/tracts are absent or greatly reduced in the Fz3[sup -/-] brain: the anterior commissure, cerebral peduncle (corticospinal tract), corpus callosum, fornix, internal capsule (thalamocortical and corticothalamic tracts), stria medullaris, stria terminalis, and hippocampal commissure. An aberrant U-shaped fiber bundle immediately caudal to the optic tract connects the left and right sides of the Fz3[sup -/-] thalamus and likely represents a default pathway for thalamic axons that failed to enter the internal capsule. At embryonic day 18, labeling of cortical pyramidal cells with a yellow fluorescent protein reporter reveals widespread fragmentation of axons with no apparent loss of pyramidal cell bodies. Fragmentation likely represents one stage in the process that normally eliminates stalled or mistargeted axons. This work demonstrates the usefulness of μDTI and genetically directed neuronal labeling for the analysis of nervous system defects in the mouse. [ABSTRACT FROM AUTHOR]

Cross-relaxation imaging is a new quantitative MRI modality, which allows mapping of fundamental parameters determining the magnetization transfer (MT) effect in tissues, cross-relaxation rate constant (k) and bound pool fraction (f). This study introduces a new time-efficient technique for cross-relaxation imaging, which obtains three-dimensional (3D) whole-brain k and f maps with scan time of <30 min and isotropic spatial resolution of 1.4 mm. The technical principle of the method is based on four-point fit of a matrix model of pulsed MT to imaging data obtained with variable offset frequency saturation while using a complimentary R1 (=1 / T1) map. Anatomical correlations of in vivo cross-relaxation parametric maps were evaluated in three healthy subjects. The f maps revealed correspondence of areas with highly elevated f = 12–15% to major fiber tracts such as corpus callosum, anterior commissure, optic radiations, and major brain fasciculi. The rest of white matter (WM) demonstrated lower f = 9–11%, resulting in clear visual contrast of fiber tracts. Even lower f = 6.5–8.5% were found in gray matter (GM) with the highest f = 8.5% in the anterior thalamus. Distribution of k was relatively uniform in WM and produced sharp contrast between GM and WM (k = 1.6 and 3.3 s-1, respectively). The most marked feature of k maps was their ability to visualize the corticospinal tract, which had elevated k = 3.4–3.8 s-1 but appeared invisible on f maps. The observed patterns on f maps can be explained by variations in the density of myelinated fibers, while the trends of k may reflect regional differences in axonal organization. Cross-relaxation imaging can be used in various clinical studies focused on brain development and white matter diseases. [Copyright &y& Elsevier]