Anatomical characterization of human fetal brain development with diffusion tensor magnetic resonance imaging

Thehumanbrain is extraordinarily complex, and yet its origin is a simple tubular structure. Characterizing its anatomy at different stages of human fetal brain development not only aids in understanding this highly ordered process but also provides clues to detecting abnormalities caused by genetic or environmental factors. During the second trimester of human fetal development, neural structures in the brain undergo significant morphological changes. Diffusion tensor imaging (DTI), a novel method of magnetic resonance imaging, is capable of delineating anatomical components with high contrast and revealing structures at the microscopic level. In this study, high-resolution and high-signal-to-noise-ratio DTI data of fixed tissues of second-trimester human fetal brains were acquired and analyzed. DTI color maps and tractography revealed that important white matter tracts, such as the corpus callosum and uncinate and inferior longitudinal fasciculi, become apparent during this period. Three-dimensional reconstruction shows that major brain fissures appear while most of the cerebral surface remains smooth until the end of the second trimester. A dominant radial organization was identified at 15 gestational weeks, followed by both laminar and radial architectures in the cerebral wall throughout the remainder of the second trimester. Volumetric measurements of different structures indicate that the volumes of basal ganglia and ganglionic eminence increase along with that of the whole brain, while the ventricle size decreases in the later second trimester. The developing fetal brain DTI database presented can be used for education, as an anatomical research reference, and for data registration

Laminar fMRI: applications for cognitive neuroscience

The cortex is a massively recurrent network, characterized by feedforward and feedback connections between brain areas as well as lateral connections within an area. Feedforward, horizontal and feedback responses largely activate separate layers of a cortical unit, meaning they can be dissociated by lamina-resolved neurophysiological techniques. Such techniques are invasive and are therefore rarely used in humans. However, recent developments in high spatial resolution fMRI allow for non-invasive, in vivo measurements of brain responses specific to separate cortical layers. This provides an important opportunity to dissociate between feedforward and feedback brain responses, and investigate communication between brain areas at a more fine- grained level than previously possible in the human species. In this review, we highlight recent studies that successfully used laminar fMRI to isolate layer-specific feedback responses in human sensory cortex. In addition, we review several areas of cognitive neuroscience that stand to benefit from this new technological development, highlighting contemporary hypotheses that yield testable predictions for laminar fMRI. We hope to encourage researchers with the opportunity to embrace this development in fMRI research, as we expect that many future advancements in our current understanding of human brain function will be gained from measuring lamina-specific brain responses

Surface‐based laminar analysis of diffusion abnormalities in cortical and white matter layers in neocortical epilepsy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97224/1/epi12129.pd

Magnetic Resonance Imaging of Anatomical Layer Specificity in the Cat Retina

Purpose: To demonstrate the ability to resolve the three distinct anatomical layers of the cat retina using T2-weighted, diffusion-weighted, and contrast-enhanced magnetic resonance imaging (MRI). Methods: MRI of the in vivo cat retina (n=5) was performed on a 4.7-Tesla MRI scanner at 50x100um or 100x100um in-plane resolution. Fast spin-echo T2-weighted images were acquired with four effective echo times, diffusion images were acquired with two b-values, and T1-weighted images were acquired before and after the intravenous administration of a magnetic-resonance contrast agent Gd-DTPA. T2 maps, apparent-diffusion-coefficient (ADC) maps, and subtraction of pre- and post-contrast images were generated for evaluation and visualization of the retinal layers. Results: Three distinct anatomical layers within the retina were observed. The inner strip exhibited a relatively long T2, high ADC, and high water spin density, which corresponded well with the expected MRI signature from the ganglion cell layer and the retinal vasculature. The middle strip exhibited a relatively short T2, low ADC, and low water spin density, which corresponded well with the expected MRI signature from the bipolar cell layer. The outer strip exhibited similar characteristics as the inner strip, which corresponded well with the expected MRI signature from the photoreceptor layer and the choroid vascular layer. The Gd-DTPA T1-weighted images showed signal enhancement at the retina-vitreous boundary and an even greater signal enhancement at the retina-choroid boundary, both consistent with the vascular flow in the retinal and choroid vessels respectively, and with the higher choroid vascular perfusion. The overall retinal thickness including the retinal and choroid vascular complex was 400-550um, consistent with histologically determined values. Conclusions: The potential for layer-specific imaging of the retina to yield physiologic and functional information in one setting could substantially enhance the diagnostic utility of high-resolution MRI to retinal evaluation. Furthermore, the similarity of retinal layers to the layers and the columns in the visual cortex may allow the application of the MRI techniques presented herein to the physiologic and functional studies of the visual cortex at improved spatial resolution and specificity

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

Mapping the human cortical surface by combining quantitative T(1) with retinotopy

We combined quantitative relaxation rate (R1= 1/T1) mapping-to measure local myelination-with fMRI-based retinotopy. Gray-white and pial surfaces were reconstructed and used to sample R1 at different cortical depths. Like myelination, R1 decreased from deeper to superficial layers. R1 decreased passing from V1 and MT, to immediately surrounding areas, then to the angular gyrus. High R1 was correlated across the cortex with convex local curvature so the data was first "de-curved". By overlaying R1 and retinotopic maps, we found that many visual area borders were associated with significant R1 increases including V1, V3A, MT, V6, V6A, V8/VO1, FST, and VIP. Surprisingly, retinotopic MT occupied only the posterior portion of an oval-shaped lateral occipital R1 maximum. R1 maps were reproducible within individuals and comparable between subjects without intensity normalization, enabling multi-center studies of development, aging, and disease progression, and structure/function mapping in other modalities

Diffusion MR microscopy of cortical development in the mouse embryo

Cortical development in the mouse embryo involves complex changes in the microstructure of the telencephalic wall, which are challenging to examine using three-dimensional (3D) imaging techniques. In this study, high-resolution 3D diffusion magnetic resonance (dMR) microscopy of the embryonic mouse cortex is presented. Using diffusion-weighted gradient- and spin-echo based acquisition, dMR microimaging data were acquired from fixed mouse embryos at 7 developmental stages from embryonic day (E)12.5 to E18.5. The dMR imaging (dMRI) contrasts revealed microscopic structural detail in the mouse telencephalic wall, allowing delineation of transient zones in the developing cortex based on their unique diffusion signatures. With the high-resolution 3D data of the mouse embryo, we were able to visualize the complex microstructure of embryonic cerebral tissue and to resolve its regional and temporal evolution during cortical formation. Furthermore, averaged dMRI contrasts generated via deformable registration revealed distinct spatial and temporal gradients of anisotropy variation across the developing embryonic cortical plate and the ventricular zone. The findings of this study demonstrate the potential of 3D dMRI to resolve the complex microstructure of the embryonic mouse cortex, and will be important for investigations of corticogenesis and its disruption in embryonic mouse models

Diffusion tensor imaging: application to the study of the developing brain

pre-printObjective: To provide an overview of diffusion tensor imaging (DTI) and its application to the study of white matter in the developing brain, in both healthy and clinical samples. Method: The development of DTI and its application to brain imaging of white matter tracts is discussed. 48 studies using DTI to examine diffusion properties of the developing brain are reviewed in the context of the structural magnetic resonance imaging (MRI) literature. Reports of how brain diffusion properties are affected in pediatric clinical samples and how they relate to cognitive and behavioral phenotypes are reviewed. Results: DTI has been successfully used to describe white matter development in pediatric samples. Changes in white matter diffusion properties are consistent across studies, with anisotropy increasing and overall diffusion decreasing with age. Diffusion measures in relevant white matter regions correlate with behavioral measures in healthy children and in clinical pediatric samples. Conclusions: DTI is an important tool for providing a more detailed picture of developing white matter than can be obtained with conventional MRI alone. Keywords: brain, development, white matter, diffusion tensor imaging, magnetic resonance imaging