This study aimed to develop an automatic segmentation method for brainstem fiber bundles. We utilized the brainstem as a seed region for probabilistic tractography based on multishell, multitissue constrained spherical deconvolution in 40 subjects from the Human Connectome Project (HCP). All tractography data were registered into a common space to construct a brainstem fiber cluster atlas. A total of 100 fiber clusters were identified and annotated. Cortical parcellation-based fiber selection was then performed to extract fibers within the annotated clusters that projected to their corresponding cortical regions. This atlas was applied for automatic brainstem fiber bundle segmentation in 10 HCP subjects and 8 patients with brainstem cavernous malformations. The spatial overlap between automatic and manual reconstruction was assessed. Ultimately, eight fiber bundles were identified in the brainstem atlas on the basis of their trajectories: the corticospinal tract (CST), corticobulbar tract, frontopontine tract, parieto-occipital-pontine tract, medial lemniscus, and superior, middle, and inferior cerebellar peduncles. The mean and standard deviation of the weighted dice (wDice) scores between the automatic and manual reconstructions were 0.9076 ± 0.0950 for the affected CST, 0.9388 ± 0.0439 for the contralateral CST, 0.9130 ± 0.0588 for the affected medial lemniscus, and 0.9600 ± 0.0243 for the contralateral medial lemniscus. This proposed method effectively distinguishes major brainstem fiber bundles across subjects while reducing labor costs and interoperator variability inherent to manual reconstruction. Additionally, this method is robust in that it allows for the visualization and identification of fiber tracts surrounding brainstem cavernous malformations.

During the development and treatment of adolescent idiopathic scoliosis (AIS), obvious soft tissue injury around the vertebrae and back pain are always present.1, 2 Abnormal paraspinal muscle development can affect the progression and rehabilitation of scoliosis.3 However, there is insufficient attention to the pathogenesis and personalised treatment for addressing the abnormal changes in the paraspinal muscles in patients with AIS. Our study found that the activation of the NLRP3/GSDMD pathway, a key factor in paraspinal muscle injury of patients with AIS, and a nano-drug delivery system we designed can effectively inhibit this damage. In this study, we enrolled a total of 30 patients with AIS and 15 age- and gender-matched patients with non-AIS (Table S1). Clinical imaging analysis revealed high levels of fat infiltration in AIS paraspinal muscle, but no significant differences were observed between concave and convex sides (Figure S1A,B). Next, we investigated anomalous changes in the paravertebral muscle tissues of patients with AIS, including increased muscle cell pyroptosis and apoptosis, increased inflammatory infiltration and decreased proliferation ability of primary paravertebral muscle cells (Figures 1A–C and S1). Subsequently, RNA sequencing was performed on paravertebral muscle tissues to identify essential genes associated with AIS paraspinal muscle injury. Through various bioinformatic analyses and qPCR validation, we identified NLRP3, an important regulator in pyroptosis pathway,4 as a key candidate gene (Figures 1D–G and S2A,B). The sequences of all qPCR primers are listed in Table S2. Subsequently, various validation confirmed that the pyroptosis and apoptosis pathway proteins in paravertebral muscle of AIS were significantly higher than those in non-AIS (Figures 1H–K and S2C–E). Then, we overexpressed NLRP3 in C2C12 cells using lentiviral transfection and found that not only the NLRP3/GSDMD/IL-1β signalling pathway was activated (Figures 2A–F and S3A–C), but also the apoptosis pathway was upregulated (Figures 2E–H and S3D–F). Meanwhile, knocking down NLRP3 expression in primary paravertebral muscle cells of AIS using siRNA transfection significantly inhibited cell pyroptosis and apoptosis (Figure S4). The sequences of all interfering RNAs are presented in Tables S3 and S4. Some studies have reported that the N-terminal peptides of GSDM protein families, such as GSDMD/GSDME, can activate apoptotic pathway through entering the mitochondrial.5 Therefore, we further explored the mechanism by which NLRP3 simultaneously activates pyroptosis and apoptosis in AIS paraspinal muscle cells. Using Crispr-Cas9 technology to knockout GSDMD expression in C2C12 cells, we found that both the activation of pyroptotic and apoptotic pathway caused by OE-NLRP3 were inhibited (Figures S5 and S6). Moreover, JC1 staining suggested that GSDMD-N activated the cell apoptosis by affecting the mitochondrial membrane potential and increasing the expression of CYTC (Figure 3D–G). In addition, novel material-based drugs have been demonstrated to have promising applications in many diseases, such as aneurysm.6, 7 Here, we designed a nanoparticle (NP) drug containing disulphiram (DSF), a recognised inhibitor of GSDMD.8 The NP we constructed contains thioketal bonds, which would break and release DSF under oxidative stress stimulation.9 Through multiple analyses, we examined a variety of physicochemical properties of NP (Figure S7). In vitro experiments showed that it could be effectively taken up by muscle cells (Figure 3A,B), and could effectively inhibit the pyroptosis and apoptosis of AIS primary paravertebral muscle cells at appropriate doses (Figure 3C–K). In vivo study, OE-NLRP3 and OE-NLRP3 + NP groups were established via paraspinal muscle injection adenovirus or NP. The results suggested that at the appropriate concentration, NP could effectively inhibited the activation of the pyroptosis pathway and the necrosis of paraspinal muscle fibres caused by OE-NLRP3 (Figure 3L–T). Figure 4 is the schematic diagram of the critical role of NLRP3 in causing paravertebral muscle Injury in patients with AIS. In conclusion, we first demonstrated that the high level of NLRP3 in AIS mediates severe inflammatory events, further inducing pyroptosis and apoptosis through the activation of GSDMD, which is an important pathogenic factor in paraspinal muscle injury in AIS. Moreover, the use of NP can effectively alleviate the paraspinal muscle injury caused by OE-NLRP3, offering potential targets for effective and personalised clinical treatment of AIS and providing new insights for the development of novel drugs. Conceived and completed the experiment: Zhuo-Tao Liang, Hao Tang and Meng-Jun Li. Data analysis and interpretation: Jia-Ke Li. Assembly and collection of data: Jiong Li and Zhuo-Tao Liang. Administrative and financial support: Hong-Qi Zhang and Chao-Feng Guo. Manuscript writing: Zhuo-Tao Liang. Guidance for writing and submission: Hong-Qi Zhang and Chao-Feng Guo. The authors would like to express their gratitude to Rong Rong (Hunan Key Laboratory of Ophthalmology, Changsha, Hunan 410008, P. R. China) for the guidance of nanoparticle design and other technical support. The authors would also like to thank EditSprings (https://www.editsprings.com/) for the expert linguistic services provided. This study was supported by the National Natural Science Foundation of China (81772298, 82072390 and 82270937) and the National Natural Science Foundation of China (82170901). The authors declare they have no conflicts of interest. The human sample study and animal study were reviewed and approved by the Ethics Committee approval of Xiangya Hospital. Informed written consent was given by all the participants and their legal guardians before study. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Mild traumatic brain injury (mTBI) is a known risk factor for neurodegenerative diseases, yet the precise pathophysiological mechanisms remain poorly understand, often obscured by group-level analysis in non-invasive neuroimaging studies. Individual-based method is critical to exploring heterogeneity in mTBI. We recruited 80 mTBI patients and 40 matched healthy controls, obtaining high-resolution structural MRI for constructing Individual Differential Structural Covariance Networks (IDSCN). Comparisons were conducted at both the individual and group levels. Connectome-based Predictive Modeling (CPM) was applied to predict cognitive performance based on whole-brain connectivity. During the acute stage of mTBI, patients exhibited significant heterogeneity in the count and direction of altered edges, obscured by group-level analysis. In the chronic stage, the number of altered edges decreased and became more consistent, aligning with clinical observations of acute cognitive impairment and gradual improvement. Subgroup analysis based on loss of consciousness/post-traumatic amnesia revealed distinct patterns of alterations. The temporal lobe, particularly regions related to the limbic system, significantly predicted cognitive function from acute to chronic stage. The use of IDSCN and CPM has provided valuable individual-level insights, reconciling discrepancies from previous studies. Additionally, the limbic system may be an appropriate target for future intervention efforts.

The widespread utilization of plastic and cobalt alloy products in industries and medicine has led to the increased presence of their degradation byproducts, microplastics (MPs), and cobalt nanoparticles (Co NPs), in the environment and organisms. While these particles can circulate throughout the body via the circulatory system, their specific adverse effects and mechanisms on the vascular system remain unclear. Employing scanning electron microscope (SEM) analysis and other methodologies, we demonstrate the potential adsorption and aggregation phenomena between MPs and Co NPs. In vitro experiments illustrate that ingestion of either MPs or Co NPs compromises vascular endothelial cell function and induces the generation of reactive oxygen species (ROS). Notably, this effect is markedly attenuated when a combination of MPs and Co NPs is administered compared to MPs alone. Additionally, zebrafish experiments validate our in vitro findings. Mechanistic studies have demonstrated that both MPs and Co NPs induce aberrant Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Intriguingly, a weaker activation level is observed when these agents are administered in combination compared to when they are administered individually. Our study provides novel insights into the interaction between MPs and Co NPs and their detrimental effects on vascular endothelial cells.

The retinogeniculate visual pathway (RGVP) plays an important role in the visual system. Diffusion MRI-based tractography has been successfully used to identify RGVP. However, challenges of RGVP tractography remain because of its highly curved path and intricate anatomical environment. One of the key challenges is the large false-positive fibers generated from RGVP tractography that requires the labor costs to hand-draw ROIs for fiber filtering. Therefore, we presented a pipeline to enable automated RGVP identification in dMRI tractography. First, we generated a tractography-based RGVP atlas. Herein, the multi-fiber unscented Kalman filter tractography was performed using high-resolution data from 50 subjects. Then, we transformed the 50 tractography cases into a common space and implemented data-driven fiber clustering to group the neighboring fibers with similar trajectories into one cluster. Two experienced anatomists were responsible for RGVP annotation in the tractography atlas. Second, the high-dimensional RGVP atlas was applied to identify subject-specific RGVP in testing datasets and two patients with different scanning parameters. Experimental results showed that our automatic identification results have ideal colocalization with expert manual identification in terms of hausdorff distance, fiber distance, and visualization. Therefore, the proposed method provides an efficient tool for analyzing large-scale datasets in vision-related neuroscience research.

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.

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.

Background: Osteoporosis is a systemic skeletal disorder characterized by decreased bone density and the degradation of bone tissue microarchitecture. Ginsenoside Rg1, derived from Panax ginseng, has been a part of traditional Chinese medicine in China for centuries, particularly for treating osteoporosis. However, there remains limited research on the osteogenic potential of Rg1 within the glucocorticoid-induced osteoporosis (GIOP) model and its specific mechanisms. Purpose: The primary objective of this study is to investigate the osteogenic potential of Rg1 within the GIOP model and explore the signaling pathways associated with its in vivo and in vitro effects. Methods: Cell proliferation, differentiation and mineralization were evaluated by the Cell counting kit 8(CCK8) assay, alkaline phosphatase (ALP) test and Alizarin Red S staining, respectively. The qPCR technique was used to determine the relative expression of mRNA and the western blot was used to determine the relative expression of protein. In vivo experiments, spinal vertebrae staining in zebrafish larvae was accomplished by alizarin red S staining. Results: Zebrafish larvae's hatching, survival, malformation, and heart rate were unaffected by 50 mu M of Rg1 in vivo, while the MEC3T3-E1 cell line's proliferation was unaffected by 50 mu M of Rg1 in vitro. Meanwhile, Rg1 was shown to improve osteogenic differentiation or bone formation as well as the level of mRNA expression of osteogenic markers in vivo and in vitro. Treatment with Rg1 significantly increased the expression of G proteincoupled estrogen receptor (GPER) and pAKT. In addition, the GPER inhibitor G15 could significantly reduce the mRNA and protein expression levels of GPER and phosphorylated AKT, LY294002, a PI3K/AKT pathway inhibitor, markedly suppresses the expression of phosphorylated AKT, yet shows no significant impact on GPER expression. Both G15 and LY294002 can significantly blocked the Rg1-mediated enhancement of osteogenesis capacity in the GIOP model. In contrast, when both the agonists G1 of GPER and LY294002 were added, G1 increased the relative expression of mRNA and protein of GPER, but not the expression of osteogenic capacity and osteogenic markers. Conclusions: This study investigates the mineralization effects and mechanisms of Ginsenoside Rg1 both in vitro and in vivo. For the first time, we propose that Rg1 might regulate osteogenesis by modulating AKT phosphorylation through mediating GPER expression within the PI3K/AKT pathway in the GIOP model. This discovery introduces novel targets and avenues for osteoporosis treatment.

We evaluated the fiber bundles in mild traumatic brain injury (mTBI) patients using differential and correlational tractography in a longitudinal analysis. Diffusion MRI data were acquired in 34 mTBI patients at 7 days (acute stage) and 3 months or longer (chronic stage) after mTBI. Trail Making Test A (TMT-A) and Digital Symbol Substitution Test changes were used to evaluate the cognitive performance. Longitudinal correlational tractography showed decreased anisotropy in the corpus callosum during the chronic mTBI stage. The changes in anisotropy in the corpus callosum were significantly correlated with the changes in TMT-A (false discovery rate [FDR] = 0.000094). Individual longitudinal differential tractography found that anisotropy decreased in the corpus callosum in 30 mTBI patients. Group cross-sectional differential tractography found that anisotropy increased (FDR = 0.02) in white matter in the acute mTBI patients, while no changes occurred in the chronic mTBI patients. Our study confirms the feasibility of using correlational and differential tractography as tract-based monitoring biomarkers to evaluate the disease progress of mTBI, and indicates that normalized quantitative anisotropy could be used as a biomarker to monitor the injury and/or repairs of white matter in individual mTBI patients.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in young women, but its pathogenesis remains unclear. The primary pathogenic factors contributing to its development include genetics, abnormal bone metabolism, and endocrine factors. Bone marrow stem cells (BMSCs) play a crucial role in the pathogenesis of AIS by regulating its occurrence and progression. Noncoding RNAs (ncRNAs) are also involved in the pathogenesis of AIS, and their role in regulating BMSCs in patients with AIS requires further evaluation. In this review, we discuss the relevant literature regarding the osteogenic, chondrogenic, and lipogenic differentiation of BMSCs. The corresponding mechanisms of ncRNA-mediated BMSC regulation in patients with AIS, recent advancements in AIS and ncRNA research, and the importance of ncRNA translation profiling and multiomics are highlighted.

Background. The pathogenesis of osteoarthritis (OA) is complex and there is no specific drug for treatment. The aim of this study was to identify the molecular targets of OA therapy, focusing on the expression and biological functions of miR-182-5p and its target genes in OA. Methods. miR-182-5p and fibroblast growth factor 9 (FGF9) were overexpressed or knocked down in IL-1β-induced chondrocytes. An OA knee model was performed by surgically destroying the medial meniscus. The gene expression of miR-182-5p and FGF9 was calculated. The protein FGF9 was tested by western blotting. Cell counting kit-8 (CCK8), plate cloning assay, and flow cytometry were conducted to evaluate cell proliferation and apoptosis. The expression of inflammatory factors, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and interleukin (IL)-8, was evaluated using enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assays validated the targeting relationship between miR-182-5p and FGF9. Hematoxylin–eosin (HE) and safranin O-fast Green (S–O) staining were utilized to access cartilage damage. Ki67 expression in cartilage was detected using immunohistochemistry (IHC). TdT-mediated dUTP nick-end labeling (TUNEL) assays were used to calculate the apoptosis rate of cartilage. Results. The expression of miR-182-5p was upregulated, and FGF9 was downregulated in the IL-1β-induced chondrocytes. OA chondrocytes proliferation ability in the miR-182-5p mimics group was decreased, and the apoptosis rate and inflammatory factor were increased. Transfection with miR-182-5p inhibitor increased the proliferative ability and decreased the apoptosis rate in the IL-1β-induced chondrocytes. Transfection with miR-182-5p inhibitor reversed IL-1β-induced inflammatory factor release in chondrocytes. Targeted binding sites existed between miR-182-5p and FGF9. After overexpression of FGF9, the miR-182-5p effect on OA chondrocytes was reversed. The hyaline cartilage thickness and proteoglycan content decreased in OA rats, and this was reversed by miR-182-5p inhibitor treatment. Conclusions. miR-182-5p expression levels were increased in OA chondrocytes and regulated chondrocyte proliferation, apoptosis, and inflammation by targeting FGF9. miR-182-5p is a potential gene for OA treatment.

Patients with mild traumatic brain injury have a diverse clinical presentation, and the underlying pathophysiology remains poorly understood. Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neurobiological markers after mild traumatic brain injury. This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury. Graph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function. However, most previous mild traumatic brain injury studies using graph theory have focused on specific populations, with limited exploration of simultaneous abnormalities in structural and functional connectivity. Given that mild traumatic brain injury is the most common type of traumatic brain injury encountered in clinical practice, further investigation of the patient characteristics and evolution of structural and functional connectivity is critical. In the present study, we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury. In this longitudinal study, we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 weeks of injury, as well as 36 healthy controls. Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis. In the acute phase, patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network. More than 3 months of follow-up data revealed signs of recovery in structural and functional connectivity, as well as cognitive function, in 22 out of the 46 patients. Furthermore, better cognitive function was associated with more efficient networks. Finally, our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury. These findings highlight the importance of integrating structural and functional connectivity in understanding the occurrence and evolution of mild traumatic brain injury. Additionally, exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.

Background Many patients with neuromuscular scoliosis (NMS) experience a variety of difficult medical problems that aggravate the development effects of progressive scoliosis and pelvic obliquity (PO). The objective of the current study was to assess the safety and effectiveness of multi-rod posterior correction only (MRPCO) with halo-femoral traction (HFT) for the management of adult NMS (> 100°) with severe PO. Methods From 2012 to 2017, 13 adult patients who suffered from NMS (> 100°) with severe PO underwent MRPCO with HFT. The radiography parameters in a sitting position, such as the coronal Cobb angle of the main curve, the PO and the trunk shift (TS), were measured at the preoperative, postoperative and final follow-up stages. The preoperative and final follow-up assessment of the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) was taken. Results The average follow-up span was 68.15 ± 6.78 months. There was decreased postoperative coronal Cobb angle with an average mean of 125.24° ± 11.78° to 47.55° ± 12.10°, with a correction rate of 62.43%; the PO was reduced to 6.25° ± 1.63° from 36.93° ± 4.25° with a correction rate of 83.07%; the TS was reduced to 2.41 cm ± 1.40 cm from 9.19 cm ± 3.07 cm. There was significant improvement in all parameters compared to the preoperative data. The VAS score reduced from 4.77 ± 0.93 to 0.69 ± 0.75, and the ODI score reduced from 65.38 ± 16.80 to 28.62 ± 12.29 at the final follow-up. Conclusions Treatment of adult NMS (> 100°) with severe PO could be safe and effective with MRPCO with HFT. In order to obtain the optimum sitting balance, this could reduce the prevalence of complications and rectify the curvature and the correction of PO.

Differential tractography and correlation tractography are new tractography modalities to study neuronal changes in brain diseases, but their performances in detecting neuronal injuries are yet to be investigated in patients with mild traumatic brain injury (mTBI). Here we investigated the white matter injury in mTBI patients using differential and correlation tractography. The diffusion MRI was acquired at 33 mTBI patients and 31 health controls. 7 of the mTBI patients had one-year follow-up scans, and differential tractography was used to evaluate injured fiber bundles on these 7 patients. All subjects were evaluated using digital symbol substitution test (DSST) and trail making test A (TMT-A), and the correlation tractography was performed to explore the exact pathways related to the cognitive performance. Our results showed that differential tractography revealed neuronal changes in the corpus callosum in all 7 follow-up mTBI patients with FDR between 0.007 and 0.17. Further, the correlation tractography showed that the splenium of the corpus callosum, combined with the right superior longitudinal fasciculus and right cingulum, were correlated with DSST (FDR = 0.001669) in the acute mTBI patients. The cognitive impairment findings in the acute stage and the longitudinal findings in the corpus callosum in the chronic stage of mTBI patients suggest that differential tractography and correlation tractography are valuable tools in the diagnostic and prognostic evaluation of neuronal injuries in mTBI patients.

Morphometric changes in cortical thickness (CT), cortical surface area (CSA), and cortical volume (CV) can reflect pathological changes after acute mild traumatic brain injury (mTBI). Most previous studies focused on changes in CT, CSA, and CV in subacute or chronic mTBI, and few studies have examined changes in CT, CSA, and CV in acute mTBI. Furthermore, acute mTBI patients typically show transient cognitive impairment, and few studies have reported on the relationship between cerebral morphological changes and cognitive function in patients with mTBI. This prospective cohort study included 30 patients with acute mTBI (15 males, 15 females, mean age 33.7 years) and 27 matched healthy controls (12 males, 15 females, mean age 37.7 years) who were recruited from the Second Xiangya Hospital of Central South University between September and December 2019. High-resolution T1-weighted images were acquired within 7 days after the onset of mTBI. The results of analyses using FreeSurfer software revealed significantly increased CSA and CV in the right lateral occipital gyrus of acute-stage mTBI patients compared with healthy controls, but no significant changes in CT. The acute-stage mTBI patients also showed reduced executive function and processing speed indicated by a lower score in the Digital Symbol Substitution Test, and reduced cognitive ability indicated by a longer time to complete the Trail Making Test-B. Both increased CSA and CV in the right lateral occipital gyrus were negatively correlated with performance in the Trail Making Test part A. These findings suggest that cognitive deficits and cortical alterations in CSA and CV can be detected in the acute stage of mTBI, and that increased CSA and CV in the right lateral occipital gyrus may be a compensatory mechanism for cognitive dysfunction in acute-stage mTBI patients. This study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University, China (approval No. 086) on February 9, 2019.

A chronic phase following repetitive mild traumatic brain injury can present as chronic traumatic encephalopathy in some cases, which requires a neuropathological examination to make a definitive diagnosis. Positron emission tomography (PET) is a molecular imaging modality that has high sensitivity for detecting even very small molecular changes, and can be used to quantitatively measure a range of molecular biological processes in the brain using different radioactive tracers. Functional changes have also been reported in patients with different forms of traumatic brain injury, especially mild traumatic brain injury and subsequent chronic traumatic encephalopathy. Thus, PET provides a novel approach for the further evaluation of mild traumatic brain injury at molecular levels. In this review, we discuss the recent advances in PET imaging with different radiotracers, including radioligands for PET imaging of glucose metabolism, tau, amyloid-beta, γ-aminobutyric acid type A receptors, and neuroinflammation, in the identification of altered neurological function. These novel radiolabeled ligands are likely to have widespread clinical application, and may be helpful for the treatment of mild traumatic brain injury. Moreover, PET functional imaging with different ligands can be used in the future to perform large-scale and sequential studies exploring the time-dependent changes that occur in mild traumatic brain injury.

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.

White matter (WM) disruption is an important determinant of cognitive impairment after mild traumatic brain injury (mTBI), but traditional diffusion tensor imaging (DTI) shows some limitations in assessing WM damage. Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) show advantages over DTI in this respect. Therefore, we used these three diffusion models to investigate complex WM changes in the acute stage after mTBI. From 32 mTBI patients and 31 age-, sex-, and education-matched healthy controls, we calculated eight diffusion metrics based on DTI (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), DKI (mean kurtosis), and NODDI (orientation dispersion index, volume fraction of intracellular water (Vic), and volume fraction of the isotropic diffusion compartment). We used tract-based spatial statistics to identify group differences at the voxel level, and we then assessed the correlation between diffusion metrics and cognitive function. We also performed subgroup comparisons based on loss of consciousness. Patients showed WM abnormalities and cognitive deficit. And these two changes showed positive correlation. The correlation between Vic of the splenium of the corpus callosum and Digit Symbol Substitution Test scores showed the smallest p-value (p = 0.000, r = 0.481). We concluded that WM changes, especially in the splenium of the corpus callosum, correlate to cognitive deficit in this study. Furthermore, the high voxel count of NODDI results and the consistency of mean kurtosis and the volume fraction of intracellular water in previous studies and our study showed the functional complementarity of DKI and NODDI to DTI.

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.

The aim of this study was to make a thorough investigation of the trajectory of the ansa lenticularis (AL) and its subcomponents using high-resolution fiber-tracking tractography. The subcomponents of the AL were reconstructed from one region of interest (ROI) in the area of the globus pallidus combined with another ROI in the red nucleus, substantia nigra, subthalamic nucleus, or thalamus. This fiber-tracking protocol was tested in an HCP-1065 template, 35 healthy subjects from Massachusetts General Hospital (MGH), and 20 healthy subjects from the human connectome project (HCP) using generalized q-sampling imaging (GQI)-based tractography. Quantitative anisotropy and fractional anisotropy were also computed for the AL subcomponents. The subcomponents of the AL could be reconstructed in the HCP-1065 template, 35 MGH healthy subjects, and 20 HCP healthy subjects. The AL descends from the globus pallidus and joins the ansa peduncularis for a short distance, subdividing later into fibers that continue separately to the red nucleus, substantia nigra, subthalamic nucleus, and thalamus. The study demonstrated the trajectory of the ansa lenticularis and its subcomponents using GQI-based tractography, improving our understanding of the anatomical connectivity between the globus pallidus and the thalamo-subthalamic region in the human brain. One Sentence Summary The investigation of the ansa lenticularis and its subcomponents using high-resolution diffusion images based tractography.