Bundle-specific tractogram distribution estimation using higher-order streamline differential equation.

Streamline tractography locally traces peak directions extracted from fiber orientation distribution (FOD) functions, lacking global information about the trend of the whole fiber bundle. Therefore, it is prone to producing erroneous tracks while missing true positive connections. In this work, we propose a new bundle-specific tractography (BST) method based on a bundle-specific tractogram distribution (BTD) function, which directly reconstructs the fiber trajectory from the start region to the termination region by incorporating the global information in the fiber bundle mask. A unified framework for any higher-order streamline differential equation is presented to describe the fiber bundles with disjoint streamlines defined based on the diffusion vectorial field. At the global level, the tractography process is simplified as the estimation of BTD coefficients by minimizing the energy optimization model, and is used to characterize the relations between BTD and diffusion tensor vector under the prior guidance by introducing the tractogram bundle information to provide anatomic priors. Experiments are performed on simulated Hough, Sine, Circle data, ISMRM 2015 Tractography Challenge data, FiberCup data, and in vivo data from the Human Connectome Project (HCP) for qualitative and quantitative evaluation. Results demonstrate that our approach reconstructs complex fiber geometry more accurately. BTD reduces the error deviation and accumulation at the local level and shows better results in reconstructing long-range, twisting, and large fanning tracts.

Characterization of local white matter microstructural alterations in Alzheimer's disease: A reproducible study.

Alzheimer's disease (AD) is a neurodegenerative disease with a close association with microstructural alterations in white matter (WM). Current studies lack the characterization and further validation of specific regions in WM fiber tracts in AD. This study subdivided fiber tracts into multiple fiber clusters on the basis of automated fiber clustering and performed quantitative analysis along the fiber clusters to identify local WM microstructural alterations in AD. Diffusion tensor imaging data from a public dataset (53 patients with AD and 70 healthy controls [HCs]) and a clinical dataset (27 patients with AD and 19 HCs) were included for mutual validation. Whole-brain tractograms were automatically subdivided into 800 clusters through the automatic fiber clustering approach. Then, 100 segments were divided along the clusters, and the diffusion properties of each segment were calculated. Results showed that patients with AD had significantly lower fraction anisotropy (FA) and significantly higher mean diffusivity (MD) in some regions of the fiber clusters in the cingulum bundle, uncinate fasciculus, external capsule, and corpus callosum than HCs. Importantly, these changes were reproducible across the two datasets. Correlation analysis revealed a positive correlation between FA and Mini-Mental State Examination (MMSE) scores and a negative correlation between MD and MMSE in these clusters. The accuracy of the constructed classifier reached 89.76% with an area under the curve of 0.93. This finding indicates that this study can effectively identify local WM microstructural changes in AD and provides new insight into the analysis and diagnosis of WM abnormalities in patients with AD.

Preoperative diffusion tensor imaging: Fiber-trajectory-distribution-based tractography to identify facial nerve in vestibular schwannoma.

PURPOSE: Tractography of the facial nerve based on diffusion MRI is instrumental before surgery for the resection of vestibular schwannoma, but no excellent methods usable for the suppression of motion and image noise have been proposed. The aim of this study was to effectively suppress noise and provide accurate facial nerve reconstruction by extend a fiber trajectory distribution function based on the fourth-order streamline differential equations. METHODS: Preoperative MRI from 33 patients with vestibular schwannoma who underwent surgical resection were utilized in this study. First, T1WI and T2WI were used to obtain mask images and regions of interest. Second, probabilistic tractography was employed to obtain the fibers representing the approximate facial nerve pathway, and these fibers were subsequently translated into orientation information for each voxel. Last, the voxel orientation information and the peaks of the fiber orientation distribution were combined to generate a fiber trajectory distribution function, which was used to parameterize the anatomical information. The parameters were determined by minimizing the cost between the trajectory of fibers and the estimated directions. RESULTS: Qualitative and visual analyses were used to compare facial nerve reconstruction with intraoperative recordings. Compared with other methods (SD_Stream, iFOD1, iFOD2, unscented Kalman filter, parallel transport tractography), the fiber-trajectory-distribution-based tractography provided the most accurate facial nerve reconstructions. CONCLUSION: The fiber-trajectory-distribution-based tractography can effectively suppress the effect of noise. It is a more valuable aid for surgeons before vestibular schwannoma resection, which may ultimately improve the postsurgical patient's outcome.

Sliding transformer with uncertainty estimation for vestibular schwannoma automatic segmentation.

Objective.Automated segmentation of vestibular schwannoma (VS) using magnetic resonance imaging (MRI) can enhance clinical efficiency. Though many advanced methods exist for automated VS segmentation, the accuracy is hindered by ambivalent tumor borders and cystic regions in some patients. In addition, these methods provide results that do not indicate segmentation uncertainty, making their translation into clinical workflows difficult due to potential errors. Providing a definitive segmentation result along with segmentation uncertainty or self-confidence is crucial for the conversion of automated segmentation programs to clinical aid diagnostic tools.Approach.To address these issues, we propose a U-shaped cascade transformer structure with a sliding window that utilizes multiple sliding samples, a segmentation head, and an uncertainty head to obtain both the segmentation mask and uncertainty map. We collected multimodal MRI data from 60 clinical patients with VS from Xuanwu Hospital. Each patient case includes T1-weighted images, contrast-enhanced T1-weighted images, T2-weighted images, and a tumor mask. The images exhibit an in-plane resolution ranging from 0.70 × 0.70 to 0.76 × 0.76 mm, an in-plane matrix spanning from 216 × 256 to 284 × 256, a slice thickness varying between 0.50 and 0.80 mm, and a range of slice numbers from 72 to 120.Main results.Extensive experimental results show that our method achieves comparable or higher results than previous state-of-the-art brain tumor segmentation methods. On our collected multimodal MRI dataset of clinical VS, our method achieved the dice similarity coefficient (DSC) of 96.08% ± 1.30. On a publicly available VS dataset, our method achieved the mean DSC of 94.23% ± 2.53.Significance.The method efficiently solves the VS segmentation task while providing an uncertainty map of the segmentation results, which helps clinical experts review the segmentation results more efficiently and helps to transform the automated segmentation program into a clinical aid diagnostic tool.

Tractography-based automated identification of the retinogeniculate visual pathway with novel microstructure-informed supervised contrastive learning.

The retinogeniculate visual pathway (RGVP) is responsible for carrying visual information from the retina to the lateral geniculate nucleus. Identification and visualization of the RGVP are important in studying the anatomy of the visual system and can inform the treatment of related brain diseases. Diffusion MRI (dMRI) tractography is an advanced imaging method that uniquely enables in vivo mapping of the 3D trajectory of the RGVP. Currently, identification of the RGVP from tractography data relies on expert (manual) selection of tractography streamlines, which is time-consuming, has high clinical and expert labor costs, and is affected by inter-observer variability. In this paper, we present a novel deep learning framework, DeepRGVP , to enable fast and accurate identification of the RGVP from dMRI tractography data. We design a novel microstructure-informed supervised contrastive learning method that leverages both streamline label and tissue microstructure information to determine positive and negative pairs. We propose a simple and successful streamline-level data augmentation method to address highly imbalanced training data, where the number of RGVP streamlines is much lower than that of non-RGVP streamlines. We perform comparisons with several state-of-the-art deep learning methods that were designed for tractography parcellation, and we show superior RGVP identification results using DeepRGVP. In addition, we demonstrate a good generalizability of DeepRGVP to dMRI tractography data from neurosurgical patients with pituitary tumors and we show DeepRGVP can successfully identify RGVPs despite the effect of lesions affecting the RGVPs. Overall, our study shows the high potential of using deep learning to automatically identify the RGVP.

Investigation into white matter microstructure differences in visual training by using an automated fiber tract subclassification segmentation quantification method.

Visual training has emerged as a useful framework for investigating training-related brain plasticity, a highly complex task involving the interaction of visual orientation, attention, reasoning, and cognitive functions. However, the effects of long-term visual training on microstructural changes within white matter (WM) is poorly understood. Therefore, a set of visual training programs was designed, and automated fiber tract subclassification segmentation quantification based on diffusion magnetic resonance imaging was performed to obtain the anatomical changes in the brains of visual trainees. First, 40 healthy matched participants were randomly assigned to the training group or the control group. The training group underwent 10 consecutive weeks of visual training. Then, the fiber tracts of the subjects were automatically identified and further classified into fiber clusters to determine the differences between the two groups on a detailed scale. Next, each fiber cluster was divided into segments that can analyze specific areas of a fiber cluster. Lastly, the diffusion metrics of the two groups were comparatively analyzed to delineate the effects of visual training on WM microstructure. Our results showed that there were significant differences in the fiber clusters of the cingulate bundle, thalamus frontal, uncinate fasciculus, and corpus callosum between the training group compared and the control group. In addition, the training group exhibited lower mean fractional anisotropy, higher mean diffusivity and radial diffusivity than the control group. Therefore, the long-term cognitive activities, such as visual training, may systematically influence the WM properties of cognition, attention, memory, and processing speed.

Reconstructing the somatotopic organization of the corticospinal tract remains a challenge for modern tractography methods.

The corticospinal tract (CST) is a critically important white matter fiber tract in the human brain that enables control of voluntary movements of the body. The CST exhibits a somatotopic organization, which means that the motor neurons that control specific body parts are arranged in order within the CST. Diffusion magnetic resonance imaging (MRI) tractography is increasingly used to study the anatomy of the CST. However, despite many advances in tractography algorithms over the past decade, modern, state-of-the-art methods still face challenges. In this study, we compare the performance of six widely used tractography methods for reconstructing the CST and its somatotopic organization. These methods include constrained spherical deconvolution (CSD) based probabilistic (iFOD1) and deterministic (SD-Stream) methods, unscented Kalman filter (UKF) tractography methods including multi-fiber (UKF2T) and single-fiber (UKF1T) models, the generalized q-sampling imaging (GQI) based deterministic tractography method, and the TractSeg method. We investigate CST somatotopy by dividing the CST into four subdivisions per hemisphere that originate in the leg, trunk, hand, and face areas of the primary motor cortex. A quantitative and visual comparison is performed using diffusion MRI data (N = 100 subjects) from the Human Connectome Project. Quantitative evaluations include the reconstruction rate of the eight anatomical subdivisions, the percentage of streamlines in each subdivision, and the coverage of the white matter-gray matter (WM-GM) interface. CST somatotopy is further evaluated by comparing the percentage of streamlines in each subdivision to the cortical volumes for the leg, trunk, hand, and face areas. Overall, UKF2T has the highest reconstruction rate and cortical coverage. It is the only method with a significant positive correlation between the percentage of streamlines in each subdivision and the volume of the corresponding motor cortex. However, our experimental results show that all compared tractography methods are biased toward generating many trunk streamlines (ranging from 35.10% to 71.66% of total streamlines across methods). Furthermore, the coverage of the WM-GM interface in the largest motor area (face) is generally low (under 40%) for all compared tractography methods. Different tractography methods give conflicting results regarding the percentage of streamlines in each subdivision and the volume of the corresponding motor cortex, indicating that there is generally no clear relationship, and that reconstruction of CST somatotopy is still a large challenge. Overall, we conclude that while current tractography methods have made progress toward the well-known challenge of improving the reconstruction of the lateral projections of the CST, the overall problem of performing a comprehensive CST reconstruction, including clinically important projections in the lateral (hand and face areas) and medial portions (leg area), remains an important challenge for diffusion MRI tractography.

Metabolic and functional substrates of impulsive decision-making in individuals with heroin addiction after prolonged methadone maintenance treatment.

Elevated impulsivity has been frequently reported in individuals with opioid addiction receiving methadone maintenance therapy (MMT), but the underlying neural mechanisms and cognitive subprocesses are not fully understood. We acquired functional magnetic resonance imaging (fMRI) data from 37 subjects with heroin addiction receiving long-term MMT and 33 healthy controls who performed a probabilistic reversal learning task, and measured their resting-state brain glucose using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Subjects receiving MMT exhibited significantly elevated self-reported impulsivity, and computational modeling revealed a marked impulsive decision bias manifested as switching more frequently without available evidence. Moreover, this impulsive decision bias was associated with the dose and duration of methadone use, irrelevant to the duration of heroin use. During the task, the switch-related hypoactivation in the left rostral middle frontal gyrus was correlated with the impulsive decision bias while the function of reward sensitivity was intact in subjects receiving MMT. Using prior brain-wide receptor density data, we found that the highest variance of regional metabolic abnormalities was explained by the spatial distribution of µ-opioid receptors among 10 types of neurotransmitter receptors. Heightened impulsivity in individuals receiving prolonged MMT is manifested as atypical choice bias and noise in decision-making processes, which is further driven by deficits in top-down cognitive control, other than reward sensitivity. Our findings uncover multifaceted mechanisms underlying elevated impulsivity in subjects receiving MMT, which might provide insights for developing complementary therapies to improve retention during MMT.

Uncertainty-guided transformer for brain tumor segmentation.

Multi-model data can enhance brain tumor segmentation for the rich information it provides. However, it also introduces some redundant information that interferes with the segmentation estimation, as some modalities may catch features irrelevant to the tissue of interest. Besides, the ambiguous boundaries and irregulate shapes of different grade tumors lead to a non-confidence estimate of segmentation quality. Given these concerns, we exploit an uncertainty-guided U-shaped transformer with multiple heads to construct drop-out format masks for robust training. Specifically, our drop-out masks are composed of boundary mask, prior probability mask, and conditional probability mask, which can help our approach focus more on uncertainty regions. Extensive experimental results show that our method achieves comparable or higher results than previous state-of-the-art brain tumor segmentation methods, achieving average dice coefficients of [Formula: see text] and Hausdorff distance of 4.91 on the BraTS2021 dataset. Our code is freely available at https://github.com/chaineypung/BTS-UGT.

Super-resolved q-space learning of diffusion MRI.

BACKGROUND: Diffusion magnetic resonance imaging (dMRI) provides a powerful tool to non-invasively investigate neural structures in the living human brain. Nevertheless, its reconstruction performance on neural structures relies on the number of diffusion gradients in the q-space. High-angular (HA) dMRI requires a long scan time, limiting its use in clinical practice, whereas directly reducing the number of diffusion gradients would lead to the underestimation of neural structures. PURPOSE: We propose a deep compressive sensing-based q-space learning (DCS-qL) approach to estimate HA dMRI from low-angular dMRI. METHODS: In DCS-qL, we design the deep network architecture by unfolding the proximal gradient descent procedure that addresses the compressive sense problem. In addition, we exploit a lifting scheme to design a network structure with reversible transform properties. For implementation, we apply a self-supervised regression to enhance the signal-to-noise ratio of diffusion data. Then, we utilize a semantic information-guided patch-based mapping strategy for feature extraction, which introduces multiple network branches to handle patches with different tissue labels. RESULTS: Experimental results show that the proposed approach can yield a promising performance on the tasks of reconstructed HA dMRI images, microstructural indices of neurite orientation dispersion and density imaging, fiber orientation distribution, and fiber bundle estimation. CONCLUSIONS: The proposed method achieves more accurate neural structures than competing approaches.

Local white matter abnormalities in Parkinson's disease with mild cognitive impairment: Assessed with neurite orientation dispersion and density imaging.

Mild cognitive impairment is a nonmotor complication in Parkinson's disease (PD) that have a high risk of developing dementia. White matter is associated with cognitive function in PD and the alterations may occur before the symptoms of the disease. Previous diffusion tensor imaging (DTI) studies lacked specificity to characterize the concrete contributions of distinct white matter tissue properties. This may lead to inconsistent conclusions about the alteration of white matter microstructure. Here, we used neurite orientation dispersion and density imaging (NODDI) and white matter fiber clustering method to uncover local white matter microstructures in PD with mild cognitive impairment (PD-MCI). This study included 23 PD-MCI and 20 PD with normal cognition (PD-NC) and 21 healthy controls (HC). To probe specific and fine-grained differences, metrics of NODDI and DTI in white matter fiber clusters were evaluated using along-tract analysis. Our results showed that PD-MCI patients had significantly lower neurite density index (NDI) and orientation dispersion index (ODI) in white matter fiber clusters in the prefrontal region. Correlation analysis and receiver operating characteristic (ROC) analysis revealed that the diagnostic performance of NODDI-derived metrics in cingulum bundle (2 clusters) and thalamo-frontal (2 clusters) were superior to DTI metrics. Our study provides a more specific insight to uncover local white matter abnormalities in PD-MCI, which benefit understanding the underlying mechanism of cognitive decline in PD and predicting the disease in advance.

CNTSeg: A multimodal deep-learning-based network for cranial nerves tract segmentation.

The segmentation of cranial nerves (CNs) tracts based on diffusion magnetic resonance imaging (dMRI) provides a valuable quantitative tool for the analysis of the morphology and course of individual CNs. Tractography-based approaches can describe and analyze the anatomical area of CNs by selecting the reference streamlines in combination with ROIs-based (regions-of-interests) or clustering-based. However, due to the slender structure of CNs and the complex anatomical environment, single-modality data based on dMRI cannot provide a complete and accurate description, resulting in low accuracy or even failure of current algorithms in performing individualized CNs segmentation. In this work, we propose a novel multimodal deep-learning-based multi-class network for automated cranial nerves tract segmentation without using tractography, ROI placement or clustering, called CNTSeg. Specifically, we introduced T1w images, fractional anisotropy (FA) images, and fiber orientation distribution function (fODF) peaks into the training data set, and design the back-end fusion module which uses the complementary information of the interphase feature fusion to improve the segmentation performance. CNTSeg has achieved the segmentation of 5 pairs of CNs (i.e. optic nerve CN II, oculomotor nerve CN III, trigeminal nerve CN V, and facial-vestibulocochlear nerve CN VII/VIII). Extensive comparisons and ablation experiments show promising results and are anatomically convincing even for difficult tracts. The code will be openly available at https://github.com/IPIS-XieLei/CNTSeg.

A unified global tractography framework for automatic visual pathway reconstruction.

The human visual pathway starts from the retina, passes through the retinogeniculate visual pathway, the optic radiation, and finally connects to the primary visual cortex. Diffusion MRI tractography is the only technology that can noninvasively reconstruct the visual pathway. However, complete and accurate visual pathway reconstruction is challenging because of the skull base environment and complex fiber geometries. Specifically, the optic nerve within the complex skull base environment can cause abnormal diffusion signals. The crossing and fanning fibers at the optic chiasm, and a sharp turn of Meyer's loop at the optic radiation, contribute to complex fiber geometries of the visual pathway. A fiber trajectory distribution (FTD) function-based tractography method of our previous work and several high sensitivity tractography methods can reveal these complex fiber geometries, but are accompanied by false-positive fibers. Thus, the related studies of the visual pathway mostly applied the expert region of interest selection strategy. However, interobserver variability is an issue in reconstructing an accurate visual pathway. In this paper, we propose a unified global tractography framework to automatically reconstruct the visual pathway. We first extend the FTD function to a high-order streamline differential equation for global trajectory estimation. At the global level, the tractography process is simplified as the estimation of global trajectory distribution coefficients by minimizing the cost between trajectory distribution and the selected directions under the prior guidance by introducing the tractography template as anatomic priors. Furthermore, we use a deep learning-based method and tractography template prior information to automatically generate the mask for tractography. The experimental results demonstrate that our proposed method can successfully reconstruct the visual pathway with high accuracy.

Semi-supervised region-connectivity-based cerebrovascular segmentation for time-of-flight magnetic resonance angiography image.

Deep-learning-based methods have achieved state-of-the-art results in cerebrovascular segmentation. However, it is costly and time-consuming to acquire labeled data because of the complex structure of cerebral vessels. In this paper, we propose a novel semi-supervised cerebrovascular segmentation with a region-connectivity-based mean teacher model (RC-MT) from time-of-flight magnetic resonance angiography (TOF-MRA), where unlabeled data is introduced into the training. Concretely, the RC-MT framework consists of a mean teachers (MT) model and a region-connectivity-based model. The region-connectivity-based model dynamically controls the balance between the supervised loss and unsupervised consistency loss by taking into account that the predicted vessel voxels should be continuous in the underlying anatomy of the brain. Meanwhile, we design a novel multi-scale channel attention fusion Unet (MSCAF-Unet) as a backbone for the student model and the teacher model. The MSCAF-Unet is a multi-scale channel attention fusion layer used to construct an image pyramid input and achieve multi-level receptive field fusion. The proposed method is evaluated on diverse TOF-MRA datasets (three clinical datasets and a public dataset). Experimental results show that the proposed method achieves high-performance gains by incorporating the unlabeled data and outperforms competing semi-supervised-based methods. The code will be openly available at https://github.com/IPIS-XieLei/RC-MT.

Automated quantification of brain connectivity in Alzheimer's disease using ClusterMetric.

Diffusion magnetic resonance imaging tractography allows investigating brain structural connections in a noninvasive way and has been widely used for understanding neurological disease. Quantification of brain connectivity along with its length by dividing a fiber bundle into multiple segments (node) is a powerful approach to assess biological properties, which is termed as tractometry. However, current tractometry methods face challenges in node identification along with the length of complex bundles whose morphology is difficult to summarize. In addition, the anatomic measure reflecting the macroscopic fiber cross-section has not been followed in previous tractometry. In this paper, we propose an automated fiber bundle quantification, which we refer to as ClusterMetric. The ClusterMetric uses a data-driven approach to identify fiber clusters corresponding to subdivisions of the white matter anatomy and identify consistent space nodes along the length of clusters across individuals. The proposed method is demonstrated by applicating to our collected dataset including 23 Alzheimer's disease (AD) patients and 22 healthy controls (HCs) and a public dataset of ADNI including 53 AD patients and 85 HCs. The altered white matter tracts in AD group are observed using both datasets, which involve several major fiber tracts including the corpus callosum, corona-radiata-frontal, arcuate fasciculus, inferior occipito-frontal fasciculus, uncinate fasciculus, thalamo-frontal, superior longitudinal fasciculus, inferior cerebellar peduncle, cingulum bundle, and extreme capsule. These fiber clusters represent the white matter connections that could be most affected in AD, suggesting the ability of our method in identifying potential abnormalities specific to local regions within a fiber cluster.

Mapping brain-wide excitatory projectome of primate prefrontal cortex at submicron resolution and comparison with diffusion tractography.

Resolving trajectories of axonal pathways in the primate prefrontal cortex remains crucial to gain insights into higher-order processes of cognition and emotion, which requires a comprehensive map of axonal projections linking demarcated subdivisions of prefrontal cortex and the rest of brain. Here, we report a mesoscale excitatory projectome issued from the ventrolateral prefrontal cortex (vlPFC) to the entire macaque brain by using viral-based genetic axonal tracing in tandem with high-throughput serial two-photon tomography, which demonstrated prominent monosynaptic projections to other prefrontal areas, temporal, limbic, and subcortical areas, relatively weak projections to parietal and insular regions but no projections directly to the occipital lobe. In a common 3D space, we quantitatively validated an atlas of diffusion tractography-derived vlPFC connections with correlative green fluorescent protein-labeled axonal tracing, and observed generally good agreement except a major difference in the posterior projections of inferior fronto-occipital fasciculus. These findings raise an intriguing question as to how neural information passes along long-range association fiber bundles in macaque brains, and call for the caution of using diffusion tractography to map the wiring diagram of brain circuits.

In the brain is a web of interconnected nerve cells that send messages to one another via spindly projections called axons. These axons join together at junctions called synapses to create circuits of nerve cells which connect neighboring or distant brain regions. Notably, long-range neural connections underpin higher-order cognitive skills (such as planning and emotion regulation) which make humans distinct from our primate relatives. Only by untangling these far-reaching networks can researchers begin to delineate what sets the human brain apart from other species. Researchers deploy a range of imaging techniques to map neural networks: scanning entire brains using MRI machines, or imaging thin slices of fluorescently labelled brain tissue using powerful microscopes. However, tracing long-range axons at a high resolution is challenging, and has stirred up debate about whether some neural tracts, such as the inferior fronto-occipital fasciculus, are present in all primates or only humans. To address these discrepancies, Yan, Yu et al. employed a two-pronged approach to map neural circuits in the brains of macaques. First, two techniques ­ called viral tracing and two-photon microscopy ­ were used to create a three-dimensional, fine-grain map showing how the ventrolateral prefrontal cortex (vlPFC), which regulates complex behaviors, connects to the rest of the brain. This revealed prominent axons from the vlPFC projecting via a single synapse to distant brain regions involved in higher-order functions, such as encoding memories and processing emotion. However, there were no direct, monosynaptic connections between the vlPFC and the occipital lobe, the brain's visual processing center at the back of the head. Next, Yan, Yu et al. used a specialized MRI scanner to create an atlas of neural circuits connected to the vlPFC, and compared these results to a technique tracing axons stained with a fluorescent dye. In general, there was good agreement between the two methods, except for major differences in the rear-end projections that typically form the inferior fronto-occipital fasciculus. This suggests that this long-range neural pathway exists in monkeys, but it connects via multiple synapses instead of a single junction as was previously thought. The findings of Yan, Yu et al. provide new insights on the far-reaching neural pathways connecting distant parts of the macaque brain. It also suggests that atlases of neural circuits from whole brain scans should be taken with caution and validated using neural tracing experiments.

Brain network connectivity feature extraction using deep learning for Alzheimer's disease classification.

Early diagnosis and therapeutic intervention for Alzheimer's disease (AD) is currently the only viable option for improving clinical outcomes. Combining structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI) to diagnose AD has yielded promising results. Most studies assume fixed time lags when constructing functional networks. Since the propagation delays between brain signals are constantly changing, these methods cannot reflect more detailed relationships between brain regions. In this work, we use a deep learning-based Granger causality estimator for brain connectivity construction. It exploits the strength of long short-term memory in ever-changing time series processing. This research involves data analysis from sMRI and rs-fMRI. We use sMRI to analyze the cerebral cortex properties and use rs-fMRI to analyze the graph metrics of functional networks. We extract a small subset of optimal features from both types of data. A support vector machine (SVM) is trained and tested to classify AD (n = 27) from healthy controls (n = 20) using rs-fMRI and sMRI features. Using a subset of optimal features in SVM, we achieve a classification accuracy of 87.23% for sMRI, 78.72% for rs-fMRI, and 91.49% for combined sMRI with rs-fMRI. The results show the potential to identify AD from healthy controls by integrating rs-fMRI and sMRI. The integration of sMRI and rs-fMRI modalities can provide supplemental information to improve the diagnosis of AD relative to either the sMRI or fMRI modalities alone.

Alterations of white matter tracts and topological properties of structural networks in hemifacial spasm.

Hemifacial spasm (HFS) is characterized by involuntary and paroxysmal muscle contractions on the hemiface. It is generally believed that HFS is caused by neurovascular compression at the root exit zone of the facial nerve. In recent years, the structural alterations of brains with HFS have aroused growing concern. However, little attention has been directed towards the possible involvement of specific white matter (WM) tracts and the topological properties of structural networks in HFS. In the present study, diffusion magnetic resonance imaging tractography was utilized to construct structural networks and perform tractometric analysis. The diffusion tensor imaging scalar parameters along with the WM tracts, and the topological parameters of global networks and subnetworks, were assessed in 62 HFS patients and 57 demographically matched healthy controls (HCs). Moreover, we investigated the correlation of these parameters with disease-clinical-level (DCL) and disease-duration-time (DDT) of HFS patients. Compared with HCs, HFS patients had additional hub regions including the amygdala, ventromedial putamen, lateral occipital cortex, and rostral cuneus gyrus. Furthermore, HFS patients showed significant alternations with specific topological properties in some structural subnetworks, including the limbic, default mode, dorsal attention, somato-motor, and control networks, as well as diffusion properties in some WM tracts, including the superior longitudinal fasciculus, cingulum bundle, thalamo-frontal, and corpus callosum. These subnetworks and tracts were associated with the regulation of emotion, motor function, vision, and attention. Notably, we also found that the parameters with subnetworks and tracts exhibited correlations with DCL and DDT. In addition to corroborating previous findings in HFS, this study demonstrates the changed microstructures in specific locations along with the fiber tracts and changed topological properties in structural subnetworks.

Tractography of the stria terminalis in the human brain.

The aim of this study was to investigate the trajectory of the stria terminalis and develop a protocol for mapping the stria terminalis using multi-shell diffusion images based tractography. The stria terminalis was reconstructed by combining one region of interest at the amygdala with another region of interest at the bed nucleus of stria terminalis. In addition, one region of avoidance was placed on the fornix at the interventricular foramen and another was set at the anterior perforated substance. The fiber-tracking protocol was tested in a Human Connectome Project-842 template, 35 healthy subjects from Massachusetts General Hospital, and 20 healthy subjects from the Human Connectome Project using generalized q-sampling imaging based tractography. The stria terminalis was reconstructed in the Human Connectome Project-842 template, 35 Massachusetts General Hospital healthy subjects, and 20 Human Connectome Project healthy subjects with our protocol. The stria terminalis originated from the amygdala and traveled parallel to the fornix. Then, the stria terminalis followed a C-shaped trajectory around the inferior, posterior, and dorsal surfaces of the thalamus before projecting to the bed nucleus of stria terminalis between the thalamus and caudate nucleus. There were no significant differences in the quantitative anisotropy and fractional anisotropy values between the left and right stria terminalis. The stria terminalis was accurately visualized across subjects using multi-shell diffusion images through generalized q-sampling imaging based tractography. This method could be an important tool for the reconstruction and evaluation of the stria terminalis in various neurological disorders. One Sentence Summary The visualization of the stria terminalis through the multi-shell diffusion images using generalized q-sampling imaging based tractography.

Automatic oculomotor nerve identification based on data-driven fiber clustering.

The oculomotor nerve (OCN) is the main motor nerve innervating eye muscles and can be involved in multiple flammatory, compressive, or pathologies. The diffusion magnetic resonance imaging (dMRI) tractography is now widely used to describe the trajectory of the OCN. However, the complex cranial structure leads to difficulties in fiber orientation distribution (FOD) modeling, fiber tracking, and region of interest (ROI) selection. Currently, the identification of OCN relies on expert manual operation, resulting in challenges, such as the carries high clinical, time-consuming, and labor costs. Thus, we propose a method that can automatically identify OCN from dMRI tractography. First, we choose the multi-shell multi-tissue constraint spherical deconvolution (MSMT-CSD) FOD estimation model and deterministic tractography to describe the 3D trajectory of the OCN. Then, we rely on the well-established computational pipeline and anatomical expertise to create a data-driven OCN tractography atlas from 40 HCP data. We identify six clusters belonging to the OCN from the atlas, including the structures of three kinds of positional relationships (pass between, pass through, and go around) with the red nuclei and two kinds of positional relationships with medial longitudinal fasciculus. Finally, we apply the proposed OCN atlas to identify the OCN automatically from 40 new HCP subjects and two patients with brainstem cavernous malformation. In terms of spatial overlap and visualization, experiment results show that the automatically and manually identified OCN fibers are consistent. Our proposed OCN atlas provides an effective tool for identifying OCN by avoiding the traditional selection strategy of ROIs.