Interregional connections of the brain measured with diffusion tractography can be used to infer valuable information regarding both brain structure and function. However, different tractography algorithms can generate networks that exhibit different characteristics, resulting in poor reproducibility across studies. Therefore, it is important to benchmark different tractography algorithms to quantitatively assess their performance. Here we systematically evaluated a newly introduced tracking algorithm, global tractography, to derive anatomical brain networks in a fiber phantom, 2 post-mortem macaque brains, and 20 living humans, and compared the results with an established local tracking algorithm. Our results demonstrated that global tractography accurately characterized the phantom network in terms of graph-theoretic measures, and significantly outperformed the local tracking approach. Results in brain tissues (post-mortem macaques and in vivo humans), however, showed that although the performance of global tractography demonstrated a trend of improvement, the results were not vastly different than that of local tractography, possibly resulting from the increased fiber complexity of real tissues. When using macaque tracer-derived connections as the ground truth, we found that both global and local algorithms generated non-random patterns of false negative and false positive connections that were probably related to specific fiber systems and largely independent of the tractography algorithm or tissue type (post-mortem vs. in vivo) used in the current study. Moreover, a close examination of the transcallosal motor connections, reconstructed via either global or local tractography, demonstrated that the lateral transcallosal fibers in humans and macaques did not exhibit the denser homotopic connections found in primate tracer studies, indicating the need for more robust brain mapping techniques based on diffusion MRI data.
Accurate assessment of connectional anatomy of primate brains can be an important avenue to better understand the structural and functional organization of brains. To this end, numerous connectome projects have been initiated to create a comprehensive map of the connectional anatomy over a large spatial expanse. Tractography based on diffusion MRI (dMRI) data has been used as a tool by many connectome projects in that it is widely used to visualize axonal pathways and reveal microstructural features on living brains. However, the measures obtained from dMRI are indirect inference of microstructures. This intrinsic limitation reduces the reliability of dMRI in constructing connectomes for brains. In this work, we proposed a framework to increase the accuracy of constructing a dMRI-based connectome on macaque brains by integrating meso-scale connective information from tract-tracing data and micro-scale axonal orientation information from myelin stain data. Our results suggest that this integrative framework could advance the mapping accuracy of dMRI based connections and axonal pathways, and demonstrate the prospect of the proposed framework in constructing a large-scale connectome on living primate brains.
Purpose: This work develops a compressive sensing approach for diffusion-weighted (DW) MRI.Theory and Methods: A phase-constrained low-rank (PCLR) approach was developed using the image coherence across the DW directions for efficient compressive DW MRI, while accounting for drastic phase changes across the DW directions, possibly as a result of eddy current, and rigid and nonrigid motions. In PCLR, a low-resolution phase estimation was used for removing phase inconsistency between DW directions. In our implementation, GRAPPA (generalized autocalibrating partial parallel acquisition) was incorporated for better phase estimation while allowing higher undersampling factor. An efficient and easy-to-implement image reconstruction algorithm, consisting mainly of partial Fourier update and singular value decomposition, was developed for solving PCLR.Results: The error measures based on diffusion-tensorderived metrics and tractography indicated that PCLR, with its joint reconstruction of all DW images using the image coherence, outperformed the frame-independent reconstruction through zero-padding FFT. Furthermore, using GRAPPA for phase estimation, PCLR readily achieved a four-fold undersampling.Conclusion: The PCLR is developed and demonstrated for compressive DW MRI. A four-fold reduction in k-space sampling could be readily achieved without substantial degradation of reconstructed images and diffusion tensor measures, making it possible to significantly reduce the data acquisition in DW MRI and/or improve spatial and angular resolutions.
Mapping anatomical brain networks with graph-theoretic analysis of diffusion tractography has recently gained popularity, because of its presumed value in understanding brain function. However, this approach has seldom been used to compare brain connectomes across species, which may provide insights into brain evolution. Here, we employed a data-driven approach to compare interregional brain connections across three primate species: 1) the intensively studied rhesus macaque, 2) our closest living primate relative, the chimpanzee, and 3) humans. Specifically, we first used random parcellations and surface-based probabilistic diffusion tractography to derive the brain networks of the three species under various network densities and resolutions. We then compared the characteristics of the networks using graph-theoretic measures. In rhesus macaques, our tractography-defined hubs showed reasonable overlap with hubs previously identified using anterograde and retrograde tracer data. Across all three species, hubs were largely symmetric in the two hemispheres and were consistently identified in medial parietal, insular, retrosplenial cingulate and ventrolateral prefrontal cortices, suggesting a conserved structural architecture within these regions. However, species differences were observed in the inferior parietal cortex, polar and medial prefrontal cortices. The potential significance of these interspecies differences is discussed.
Evolution of the brain has been an inherently interesting problem for centuries. Recent studies have indicated that neuroimaging is a powerful technique for studying brain evolution. In particular, a variety of reports have demonstrated that consistent white matter fiber connection patterns derived from diffusion tensor imaging (DTI) tractography reveal common brain architecture and are predictive of brain functions. In this paper, based on our recently discovered 358 dense individualized and common connectivity-based cortical landmarks (DICCCOL) defined by consistent fiber connection patterns in DTI datasets of human brains, we derived 65 DICCCOLs that are common in macaque monkey, chimpanzee and human brains and 175 DICCCOLs that exhibit significant discrepancies amongst these three primate species. Qualitative and quantitative evaluations not only demonstrated the consistencies of anatomical locations and structural fiber connection patterns of these 65 common DICCCOLs across three primates, suggesting an evolutionarily preserved common brain architecture but also revealed regional patterns of evolutionarily induced complexity and variability of those 175 discrepant DICCCOLs across the three species.
Background
Most humans are right handed, and most humans exhibit left-right asymmetries of the precentral corticospinal system. Recent studies indicate that chimpanzees also show a population-level right-handed bias, although it is less strong than in humans.
Methodology/Principal Findings
We used in vivo diffusion-weighted and T1-weighted magnetic resonance imaging (MRI) to study the relationship between the corticospinal tract (CST) and handedness in 36 adult female chimpanzees. Chimpanzees exhibited a hemispheric bias in fractional anisotropy (FA, left>right) and mean diffusivity (MD, right>left) of the CST, and the left CST was centered more posteriorly than the right. Handedness correlated with central sulcus depth, but not with FA or MD.
Conclusions/Significance
These anatomical results are qualitatively similar to those reported in humans, despite the differences in handedness. The existence of a left>right FA, right>left MD bias in the corticospinal tract that does not correlate with handedness, a result also reported in some human studies, suggests that at least some of the structural asymmetries of the corticospinal system are not exclusively related to laterality of hand preference.
Background: 3q29 deletion syndrome is caused by a recurrent hemizygous 1.6Mb deletion on the long arm of chromosome 3. The syndrome is rare (1 in 30,000 individuals) and is associated with mild to moderate intellectual disability, increased risk for autism and anxiety, and a 40-fold increased risk for schizophrenia, along with a host of physical manifestations. However, the disorder is poorly characterized, the range of manifestations is not well described, and the underlying molecular mechanism is not understood. We designed the Emory 3q29 Project to document the range of neurodevelopmental and psychiatric manifestations associated with 3q29 deletion syndrome. We will also create a biobank of samples from our 3q29 deletion carriers for mechanistic studies, which will be a publicly-available resource for qualified investigators. The ultimate goals of our study are three-fold: first, to improve management and treatment of 3q29 deletion syndrome. Second, to uncover the molecular mechanism of the disorder. Third, to enable cross-disorder comparison with other rare genetic syndromes associated with neuropsychiatric phenotypes. Methods: We will ascertain study subjects, age 6 and older, from our existing registry ( 3q29deletion.org ). Participants and their families will travel to Atlanta, GA for phenotypic assessments, with particular emphasis on evaluation of anxiety, cognitive ability, autism symptomatology, and risk for psychosis via prodromal symptoms and syndromes. Evaluations will be performed using standardized instruments. Structural, diffusion, and resting-state functional MRI data will be collected from eligible study participants. We will also collect blood from the 3q29 deletion carrier and participating family members, to be banked at the NIMH Repository and Genomics Resource (NRGR). Discussion: The study of3q29 deletion has the potential to transform our understanding of complex disease. Study of individuals with the deletion may provide insights into long term care and management of the disorder. Our project describes the protocol for a prospective study of the behavioral and clinical phenotype associated with 3q29 deletion syndrome. The paradigm described here could easily be adapted to study additional CNV or single gene disorders with high risk for neuropsychiatric phenotypes, and/or transferred to other study sites, providing a means for data harmonization and cross-disorder analysis.
Aging of the optic nerve can result in reduced visual sensitivity or vision loss. Normal optic nerve aging has been investigated previously in tissue specimens but poorly explored in vivo. In the present study, the normal aging of optic nerve was evaluated by diffusion tensor imaging (DTI) in non-human primates. Adult female rhesus monkeys at the ages of 9 to 13 years old (young group, n=8) and 21 to 27 years old (old group, n=7) were studied using parallel-imaging-based DTI on a clinical 3T scanner. Compared to young adults, the old monkeys showed 26% lower fractional anisotropy (P<0.01), and 44% greater radial diffusivity, although the latter difference was of marginal statistical significance (P=0.058). These MRI findings are largely consistent with published results of light and electron microscopic studies of optic nerve aging in macaque monkeys, which indicate a loss of fibers and degenerative changes in myelin sheaths.
Though fetal alcohol syndrome and fetal alcohol spectrum disorders are among the most common developmental disorders, their understanding is incomplete. Diffusion tensor imaging, which is sensitive to microstructural organization in white matter, may provide a relevant measure in this population demonstrating incompletely characterized white matter pathology. In this study, tract-based spatial statistics routine and a skeleton-based region of interest analyses were employed to detect differences in diffusion tensor imaging derived metrics between young adults who were alcohol exposed and an unexposed control group. Participants include twenty-eight with dysmorphic features associated with fetal alcohol syndrome, twenty-nine who were prenatally exposed but do not show physical effects, and twenty-five with the same low socioeconomic status but unexposed. The tract-based spatial statistics analysis revealed a statistically significant decrease in fractional anisotropy at the isthmus of the corpus callosum and its connected callosal fibers in dysmorphic individuals relative to controls (cluster-wise pFWE < 0.05). This finding was consistent with that of the follow-up skeleton-based region of interest analysis (F(2,79)=3.256, p=0.044). In addition, the patterns in axial and radial diffusivity changes suggest that demyelination may be associated with the degraded white matter integrity observed in the dysmorphic group.
Diffusion tensor imaging (DTI), high angular resolution diffusion imaging (HARDI), and diffusion spectrum imaging (DSI) have been widely used in the neuroimaging field to examine the macro-scale fiber connection patterns in the cerebral cortex. However, the topographic and geometric relationships between diffusion imaging derived streamline fiber connection patterns and cortical folding patterns remain largely unknown. This paper specifically identifies and characterizes the U-shapes of diffusion imaging derived streamline fibers via a novel fiber clustering framework and examines their co-localization patterns with cortical sulci based on DTI, HARDI, and DSI datasets of human, chimpanzee and macaque brains. We verified the presence of these U-shaped streamline fibers that connect neighboring gyri by coursing around cortical sulci such as the central sulcus, pre-central sulcus, post-central sulcus, superior temporal sulcus, inferior frontal sulcus, and intra-parietal sulcus. This study also verified the existence of U-shape fibers across data modalities (DTI/HARDI/DSI) and primate species (macaque, chimpanzee and human), and suggests that the common pattern of U-shape fibers coursing around sulci is evolutionarily-preserved in cortical architectures.