Search for: All records

Abstract Understanding the mechanics linking cortical folding and brain connectivity is crucial for both healthy and abnormal brain development. Despite the importance of this relationship, existing models fail to explain how growing axon bundles navigate the stress field within a folding brain or how this bidirectional and dynamic interaction shapes the resulting surface morphologies and connectivity patterns. Here, we propose the concept of “axon reorientation” and formulate a mechanical model to uncover the dynamic multiscale mechanics of the linkages between cortical folding and connectivity development. Simulations incorporating axon bundle reorientation and stress-induced growth reveal potential mechanical mechanisms that lead to higher axon bundle density in gyri (ridges) compared to sulci (valleys). In particular, the connectivity patterning resulting from cortical folding exhibits a strong dependence on the growth rate and mechanical properties of the navigating axon bundles. Model predictions are supported by in vivo diffusion tensor imaging of the human brain. 

Abstract Understanding the processes of axonal growth and pathfinding during cortical folding in the brain is crucial to unravel the mechanisms underlying brain disorders that disturb connectivity throughout human brain development. However, this topic remains incompletely understood, highlighting the need for further investigation. Here, we propose and evaluate a diffusion based-mechanistic model to understand how axons grow and navigate in the folding brain. To do so, a bilayer growth model simulating the brain was devised involving a thin gray matter overlying a thick white matter. Innovatively, the stochastic model of axonal growth was linked with the stress and deformation fields of the folding bilayer system. The results showed that the modulus ratio of the gray matter to the white matter and the axonal growth rate are two potentially critical parameters that significantly influence axon pathfinding in the folding brain. The model demonstrated robust predictability in identifying axonal termination points and offered a potential mechanism explaining why axons settle more in gyri (ridges) than sulci (valleys) of the brain. Importantly, the results explain how alterations in the mechanical properties of the folding system can impact the underlying connectivity patterning. This mechanistic insight not only enhances our understanding of brain connectivity development during the fetal stage but also sheds light on brain disorders characterized by linked abnormalities in cortical folds and disruptions in connectivity. 

Abstract Finding the stiffness map of biological tissues is of great importance in evaluating their healthy or pathological conditions. However, due to the heterogeneity and anisotropy of biological fibrous tissues, this task presents challenges and significant uncertainty when characterized only by single-mode loading experiments. In this study, we propose a new theoretical framework to map the stiffness landscape of fibrous tissues, specifically focusing on brain white matter tissue. Initially, a finite element (FE) model of the fibrous tissue was subjected to six loading cases, and their corresponding stress–strain curves were characterized. By employing multiobjective optimization, the material constants of an equivalent anisotropic material model were inversely extracted to best fit all six loading modes simultaneously. Subsequently, large-scale FE simulations were conducted, incorporating various fiber volume fractions and orientations, to train a convolutional neural network capable of predicting the equivalent anisotropic material properties solely based on the fibrous architecture of any given tissue. The proposed method, leveraging brain fiber tractography, was applied to a localized volume of white matter, demonstrating its effectiveness in precisely mapping the anisotropic behavior of fibrous tissue. In the long-term, the proposed method may find applications in traumatic brain injury, brain folding studies, and neurodegenerative diseases, where accurately capturing the material behavior of the tissue is crucial for simulations and experiments. 

BackgroundA lack of in utero imaging data hampers our understanding of the connections in the human fetal brain. Generalizing observations from postmortem subjects and premature newborns is inaccurate due to technical and biological differences. PurposeTo evaluate changes in fetal brain structural connectivity between 23 and 35 weeks postconceptional age using a spatiotemporal atlas of diffusion tensor imaging (DTI). Study TypeRetrospective. PopulationPublicly available diffusion atlases, based on 60 healthy women (age 18–45 years) with normal prenatal care, from 23 and 35 weeks of gestation. Field Strength/Sequence3.0 Tesla/DTI acquired with diffusion‐weighted echo planar imaging (EPI). AssessmentWe performed whole‐brain fiber tractography from DTI images. The cortical plate of each diffusion atlas was segmented and parcellated into 78 regions derived from the Edinburgh Neonatal Atlas (ENA33). Connectivity matrices were computed, representing normalized fiber connections between nodes. We examined the relationship between global efficiency (GE), local efficiency (LE), small‐worldness (SW), nodal efficiency (NE), and betweenness centrality (BC) with gestational age (GA) and with laterality. Statistical TestsLinear regression was used to analyze changes in GE, LE, NE, and BC throughout gestation, and to assess changes in laterality. Thet‐tests were used to assess SW.P‐values were corrected using Holm‐Bonferroni method. A correctedP‐value <0.05 was considered statistically significant. ResultsNetwork analysis revealed a significant weekly increase in GE (5.83%/week, 95% CI 4.32–7.37), LE (5.43%/week, 95% CI 3.63–7.25), and presence of SW across GA. No significant hemisphere differences were found in GE (P = 0.971) or LE (P = 0.458). Increasing GA was significantly associated with increasing NE in 41 nodes, increasing BC in 3 nodes, and decreasing BC in 2 nodes. Data ConclusionExtensive network development and refinement occur in the second and third trimesters, marked by a rapid increase in global integration and local segregation. Level of Evidence3 Technical EfficacyStage 2 

Abstract The human brain development experiences a complex evolving cortical folding from a smooth surface to a convoluted ensemble of folds. Computational modeling of brain development has played an essential role in better understanding the process of cortical folding, but still leaves many questions to be answered. A major challenge faced by computational models is how to create massive brain developmental simulations with affordable computational sources to complement neuroimaging data and provide reliable predictions for brain folding. In this study, we leveraged the power of machine learning in data augmentation and prediction to develop a machine-learning-based finite element surrogate model to expedite brain computational simulations, predict brain folding morphology, and explore the underlying folding mechanism. To do so, massive finite element method (FEM) mechanical models were run to simulate brain development using the predefined brain patch growth models with adjustable surface curvature. Then, a GAN-based machine learning model was trained and validated with these produced computational data to predict brain folding morphology given a predefined initial configuration. The results indicate that the machine learning models can predict the complex morphology of folding patterns, including 3-hinge gyral folds. The close agreement between the folding patterns observed in FEM results and those predicted by machine learning models validate the feasibility of the proposed approach, offering a promising avenue to predict the brain development with given fetal brain configurations. 

Abstract The important mechanical parameters and their hierarchy in the growth and folding of the human brain have not been thoroughly understood. In this study, we developed a multiscale mechanical model to investigate how the interplay between initial geometrical undulations, differential tangential growth in the cortical plate, and axonal connectivity form and regulate the folding patterns of the human brain in a hierarchical order. To do so, different growth scenarios with bilayer spherical models that features initial undulations on the cortex and uniform or heterogeneous distribution of axonal fibers in the white matter were developed, statistically analyzed, and validated by the imaging observations. The results showed that the differential tangential growth is the inducer of cortical folding, and in a hierarchal order, high-amplitude initial undulations on the surface and axonal fibers in the substrate regulate the folding patterns and determine the location of gyri and sulci. The locations with dense axonal fibers after folding settle in gyri rather than sulci. The statistical results also indicated that there is a strong correlation between the location of positive (outward) and negative (inward) initial undulations and the locations of gyri and sulci after folding, respectively. In addition, the locations of 3-hinge gyral folds are strongly correlated with the initial positive undulations and locations of dense axonal fibers. As another finding, it was revealed that there is a correlation between the density of axonal fibers and local gyrification index, which has been observed in imaging studies but not yet fundamentally explained. This study is the first step in understanding the linkage between abnormal gyrification (surface morphology) and disruption in connectivity that has been observed in some brain disorders such as Autism Spectrum Disorder. Moreover, the findings of the study directly contribute to the concept of the regularity and variability of folding patterns in individual human brains. 

Diffusion-weighted magnetic resonance imaging (dMRI) is widely used to assess the brain white matter. Fiber orientation distribution functions (FODs) are a common way of representing the orientation and density of white matter fibers. However, with standard FOD computation methods, accurate estimation requires a large number of measurements that usually cannot be acquired for newborns and fetuses. We propose to overcome this limitation by using a deep learning method to map as few as six diffusion-weighted measurements to the target FOD. To train the model, we use the FODs computed using multi-shell high angular resolution measurements as target. Extensive quantitative evaluations show that the new deep learning method, using significantly fewer measurements, achieves comparable or superior results than standard methods such as Constrained Spherical Deconvolution and two state-of-the-art deep learning methods. For voxels with one and two fibers, respectively, our method shows an agreement rate in terms of the number of fibers of 77.5% and 22.2%, which is 3% and 5.4% higher than other deep learning methods, and an angular error of 10° and 20°, which is 6° and 5° lower than other deep learning methods. To determine baselines for assessing the performance of our method, we compute agreement metrics using densely sampled newborn data. Moreover, we demonstrate the generalizability of the new deep learning method across scanners, acquisition protocols, and anatomy on two clinical external datasets of newborns and fetuses. We validate fetal FODs, successfully estimated for the first time with deep learning, using post-mortem histological data. Our results show the advantage of deep learning in computing the fiber orientation density for the developing brain from in-vivo dMRI measurements that are often very limited due to constrained acquisition times. Our findings also highlight the intrinsic limitations of dMRI for probing the developing brain microstructure.