Connectivity of the insular subdivisions differentiates posttraumatic headache-associated from nonheadache-associated mild traumatic brain injury: an arterial spin labelling study.

OBJECTIVE: The insula is an important part of the posttraumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) neuropathological activity pattern. It is composed of functionally different subdivisions and each of which plays different role in PTH neuropathology. METHODS: Ninety-four mTBI patients were included in this study. Based on perfusion imaging data obtained from arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI), this study evaluated the insular subregion perfusion-based functional connectivity (FC) and its correlation with clinical characteristic parameters in patients with PTH after mTBI and non-headache mTBI patients. RESULTS: The insular subregions of mTBI + PTH (mTBI patients with PTH) and mTBI-PTH (mTBI patients without PTH) group had positive perfusion-based functional connections with other insular nuclei and adjacent discrete cortical regions. Compared with mTBI-PTH group, significantly increased resting-state perfusion-based FC between the anterior insula (AI) and middle cingulate cortex (MCC)/Rolandic operculum (ROL), between posterior insula (PI) and supplementary motor area (SMA), and decreased perfusion-based FC between PI and thalamus were found in mTBI + PTH group. Changes in the perfusion-based FC of the left posterior insula/dorsal anterior insula with the thalamus/MCC were significant correlated with headache characteristics. CONCLUSIONS: Our findings provide new ASL-based evidence for changes in the perfusion-based FC of the insular subregion in PTH patients attributed to mTBI and the association with headache features, revealing the possibility of potential neuroplasticity after PTH. These findings may contribute to early diagnosis of the disease and follow-up of disease progression.

Aberrant dynamic properties of whole-brain functional connectivity in acute mild traumatic brain injury revealed by hidden Markov models.

OBJECTIVES: This study aimed to investigate the temporal dynamics of brain activity and characterize the spatiotemporal specificity of transitions and large-scale networks on short timescales in acute mild traumatic brain injury (mTBI) patients and those with cognitive impairment in detail. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 71 acute mTBI patients and 57 age-, sex-, and education-matched healthy controls (HCs). A hidden Markov model (HMM) analysis of rs-fMRI data was conducted to identify brain states that recurred over time and to assess the dynamic patterns of activation states that characterized acute mTBI patients and those with cognitive impairment. The dynamic parameters (fractional occupancy, lifetime, interval time, switching rate, and probability) between groups and their correlation with cognitive performance were analyzed. RESULTS: Twelve HMM states were identified in this study. Compared with HCs, acute mTBI patients and those with cognitive impairment exhibited distinct changes in dynamics, including fractional occupancy, lifetime, and interval time. Furthermore, the switching rate and probability across HMM states were significantly different between acute mTBI patients and patients with cognitive impairment (all p < 0.05). The temporal reconfiguration of states in acute mTBI patients and those with cognitive impairment was associated with several brain networks (including the high-order cognition network [DMN], subcortical network [SUB], and sensory and motor network [SMN]). CONCLUSIONS: Hidden Markov models provide additional information on the dynamic activity of brain networks in patients with acute mTBI and those with cognitive impairment. Our results suggest that brain network dynamics determined by the HMM could reinforce the understanding of the neuropathological mechanisms of acute mTBI patients and those with cognitive impairment.

Disrupted resting-state functional connectivity and network topology in mild traumatic brain injury: an arterial spin labelling study.

Mild traumatic brain injury can cause different degrees of cognitive impairment and abnormal brain structure and functional connectivity, but there is still a lack of research on the functional connectivity and topological organization of cerebral blood flow fluctuations. This study explored the cerebral blood flow, functional connectivity and topological organization of the cerebral blood flow network in acute mild traumatic brain injury patients. In total, 48 mild traumatic brain injury patients and 46 well-matched healthy controls underwent resting-state arterial spin labelling perfusion MRI and neuropsychological assessments. The functional connectivity and topological organization of the cerebral blood flow network were analysed. Then, the correlation between the changes in cerebral blood flow network characteristics and cognitive function was explored. Acute mild traumatic brain injury patients showed decreased cerebral blood flow in the right insula and increased cerebral blood flow in the right inferior temporal gyrus and left superior temporal gyrus. Abnormal cerebral blood flow network connection patterns mainly occur in sensorimotor network, default mode network, cingulo-opercular network and occipital network-related regions. Furthermore, mild traumatic brain injury disrupted the topological organization of the whole brain, which manifested as (i) reduced global efficiency; (ii) abnormal degree centrality, betweenness centrality, nodal clustering coefficient and nodal efficiency; and (iii) decreased intermodular connectivity between the occipital network and sensorimotor network. Finally, the change in network topology was correlated with the cognitive score of the mild traumatic brain injury. This study provided evidence of abnormal functional connectivity and network topology based on cerebral blood flow in acute mild traumatic brain injury patients, revealing their potential use as early markers for mild traumatic brain injury, which may contribute to both disease diagnosis and assessment.

Functional-structural large-scale brain networks are correlated with neurocognitive impairment in acute mild traumatic brain injury.

Background: This study was conducted to investigate topological changes in large-scale functional connectivity (FC) and structural connectivity (SC) networks in acute mild traumatic brain injury (mTBI) and determine their potential relevance to cognitive impairment. Methods: Seventy-one patients with acute mTBI (29 males, 42 females, mean age 43.54 years) from Nanjing First Hospital and 57 matched healthy controls (HC) (33 males, 24 females, mean age 46.16 years) from the local community were recruited in this prospective study. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were acquired within 14 days (mean 3.29 days) after the onset of mTBI. Then, large-scale FC and SC networks with 116 regions from the automated anatomical labeling (AAL) brain atlas were constructed. Graph theory analysis was used to analyze global and nodal metrics. Finally, correlations were assessed between topological properties and neurocognitive performances evaluated by the Montreal Cognitive Assessment (MoCA). Bonferroni correction was performed out for multiple comparisons in all involved analyses. Results: Compared with HC, acute mTBI patients had a higher normalized clustering coefficient (γ) for FC (Cohen's d=4.076), and higher γ and small worldness (σ) for SC (Cohen's d=0.390 and Cohen's d=0.395). The mTBI group showed aberrant nodal degree (Dc), nodal efficiency (Ne), and nodal local efficiency (Nloc) for FC and aberrant Dc, nodal betweenness (Bc), nodal clustering coefficient (NCp) and Ne for SC mainly in the frontal and temporal, cerebellum, and subcortical areas. Acute mTBI patients also had higher functional-structural coupling strength at both the group and individual levels (Cohen's d=0.415). These aberrant global and nodal topological properties at functional and structural levels were associated with attention, orientation, memory, and naming performances (all P<0.05). Conclusions: Our findings suggested that large-scale FC and SC network changes, higher correlation between FC and SC and cognitive impairment can be detected in the acute stage of mTBI. These network aberrances may be a compensatory mechanism for cognitive impairment in acute mTBI patients.

Causal interactions with an insular-cortical network in mild traumatic brain injury.

PURPOSE: This study aimed to investigate the insula-based directional effective connectivity in mild traumatic brain injury (mTBI) using resting-state functional magnetic resonance imaging (fMRI) and to explore its relationship with cognitive performance. METHODS: Sixty mTBI patients and 55 age-, gender- and years of education- matched healthy controls (HC) were recruited in this study. Using granger causality analysis (GCA), we selected bilateral insula as two individual seed regions to compare the difference of directional effective connectivity of insula between mTBI group and HC group, and analyze its relationship with cognitive performance. RESULTS: Compared with HC, acute mTBI group showed decreased outflows from the left insula to the left middle frontal gyrus (MFG) and right rolandic operculum (Rol), increased inflow from the left supplementary motor area (SMA) to the left insula, decreased outflows from the right insula to the left superior frontal gyrus (SFG), as well as increased outflows from the right insula to the left superior temporal gyrus (STG). No significantly different inflows to the right insula from other regions were found. Correlation analyses revealed that the abnormal connectivity between insula and MFG, as well as insula and STG were associated with the cognitive function score. CONCLUSIONS: Our data demonstrated abnormalities in the effective connection pathways of insula in acute mTBI patients, while abnormal effective connectivity significantly correlated with cognitive function score. These findings may shed light on the pathophysiological mechanisms of cognitive impairment after mTBI.

Cerebral blood flow network differences correlated with cognitive impairment in mild traumatic brain injury.

Purpose: To examine whether the cerebral blood flow (CBF) and CBF connectivity differences are sex-specific and whether these differences are correlated with cognitive impairment in mTBI. Methods: Resting-state perfusion magnetic resonance imaging was performed in 40 patients with acute mTBI and 40 healthy controls by using pseudocontinuous arterial spin labeling within 14 days following injury. The differences in normalized CBF were first compared and CBF connectivity of the brain regions with significant CBF differences were compared next. The association between the normalized CBF and CBF connectivity differences and cognitive function were further investigated. Results: Men patients had lower normalized CBF in the frontal gyrus, temporal gyrus and hippocampus and decreased negative CBF connectivity between brain regions including the hippocampus, temporal gyrus, postcentral gyrus and lenticular nucleus, putamen, compared with men controls. Women patients had lower normalized CBF in the frontal gyrus, however had higher normalized CBF in the temporal gyrus and hippocampus, compared with women controls. Additionally, women patients showed increased positive CBF connectivity between the seed region of interest (ROI) of the right inferior temporal gyrus and temporal gyrus and frontal gyrus, and had increased positive CBF connectivity between the seed ROI of the right hippocampus and the temporal gyrus. Furthermore, men patients had higher CBF in the right middle temporal gyrus and left precentral gyrus than women patients. Conclusion: This study provides evidence of sex differences in both decreased and increased CBF and CBF connectivity and association with cognitive outcome in the acute stage after mTBI.

Rich-club reorganization of functional brain networks in acute mild traumatic brain injury with cognitive impairment.

Background: Mild traumatic brain injury (mTBI) is typically characterized by temporally limited cognitive impairment and regarded as a brain connectome disorder. Recent findings have suggested that a higher level of organization named the "rich-club" may play a central role in enabling the integration of information and efficient communication across different systems of the brain. However, the alterations in rich-club organization and hub topology in mTBI and its relationship with cognitive impairment after mTBI have been scarcely elucidated. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 88 patients with mTBI and 85 matched healthy controls (HCs). Large-scale functional brain networks were established for each participant. Rich-club organizations and network properties were assessed and analyzed between groups. Finally, we analyzed the correlations between the cognitive performance and changes in rich-club organization and network properties. Results: Both mTBI and HCs groups showed significant rich-club organization. Meanwhile, the rich-club organization was aberrant, with enhanced functional connectivity (FC) among rich-club nodes and peripheral regions in acute mTBI. In addition, significant differences in partial global and local network topological property measures were found between mTBI patients and HCs (P<0.01). In patients with mTBI, changes in rich-club organization and network properties were found to be related to early cognitive impairment after mTBI (P<0.05). Conclusions: Our findings suggest that such patterns of disruption and reorganization will provide the basic functional architecture for cognitive function, which may subsequently be used as an earlier biomarker for cognitive impairment after mTBI.

Neuropathological Mechanisms of Mild Traumatic Brain Injury: A Perspective From Multimodal Magnetic Resonance Imaging.

Mild traumatic brain injury (mTBI) accounts for more than 80% of the total number of TBI cases. The mechanism of injury for patients with mTBI has a variety of neuropathological processes. However, the underlying neurophysiological mechanism of the mTBI is unclear, which affects the early diagnosis, treatment decision-making, and prognosis evaluation. More and more multimodal magnetic resonance imaging (MRI) techniques have been applied for the diagnosis of mTBI, such as functional magnetic resonance imaging (fMRI), arterial spin labeling (ASL) perfusion imaging, susceptibility-weighted imaging (SWI), and diffusion MRI (dMRI). Various imaging techniques require to be used in combination with neuroimaging examinations for patients with mTBI. The understanding of the neuropathological mechanism of mTBI has been improved based on different angles. In this review, we have summarized the application of these aforementioned multimodal MRI techniques in mTBI and evaluated its benefits and drawbacks.

Aberrant Static and Dynamic Functional Network Connectivity in Acute Mild Traumatic Brain Injury with Cognitive Impairment.

PURPOSE: This study aimed to investigate differences in static and dynamic functional network connectivity (FNC) and explore their association with neurocognitive performance in acute mild traumatic brain injury (mTBI). METHODS: A total of 76 patients with acute mTBI and 70 age-matched and sex-matched healthy controls were enrolled (age 43.79 ± 10.22 years vs. 45.63 ± 9.49 years; male/female: 34/42 vs. 38/32; all p > 0.05) and underwent resting-state functional magnetic resonance imaging (fMRI) scan (repetition time/echo time = 2000/30 ms, 230 volumes). Independent component analysis was conducted to evaluate static and dynamic FNC patterns on the basis of nine resting-state networks, namely, auditory network (AUDN), dorsal attention network (dAN), ventral attention network (vAN), default mode network (DMN), left frontoparietal network (LFPN), right frontoparietal network (RFPN), somatomotor network (SMN), visual network (VN), and salience network (SN). Spearman's correlation among aberrances in FNC values, and Montreal cognitive assessment (MoCA) scores was further measured in mTBI. RESULTS: Compared with controls, patients with mTBI showed wide aberrances of static FNC, such as reduced FNC in DMN-vAN and VN-vAN pairs. The mTBI patients exhibited aberrant dynamic FNC in state 2, involving reduced FNC aberrance in the vAN with AUDN, VN with DMN and dAN, and SN with SMN and vAN. Reduced dFNC in the SN-vAN pair was negatively correlated with the MoCA score. CONCLUSION: Our findings suggest that aberrant static and dynamic FNC at the acute stage may contribute to cognitive symptoms, which not only may expand knowledge regarding FNC cognition relations from the static perspective but also from the dynamic perspective.

Altered static and dynamic functional network connectivity in post-traumatic headache.

BACKGROUND: Post-traumatic headache (PTH) is a very common symptom following mild traumatic brain injury (mTBI), yet much remains unknown about the underlying pathophysiological mechanisms of PTH. Neuroimaging studies suggest that aberrant functional network connectivity (FNC) may be an important factor in pain disorders. The present study aimed to investigate the functional characteristics of static FNC (sFNC) and dynamic FNC (dFNC) in mTBI patients with PTH. METHODS: With Institutional Review Board (IRB) approval, we prospectively recruited 50 mTBI patients with PTH, who were diagnosed with ICHD-3 beta diagnostic criteria and 39 mTBI without PTH who were well matched for age, gender and education. Resting-state functional magnetic resonance imaging (fMRI) scanning (3.0 T, Philips Medical Systems, Netherlands), Montreal Cognitive Assessment (MoCA) and headache symptom measurement (headache frequency and headache intensity) were performed. The resting-state fMRI sequence took 8 min and 10 s. Independent component analysis and sliding window method were applied to examine the FNC on the basis of nine resting-state networks, namely, default mode network (DMN), sensorimotor network (SMN), executive control network (ECN), auditory network (AuN), attention network (AN), salience network (SN), visual network (VN), and cerebellum network (CN). The differences in sFNC and dFNC were determined and correlated with clinical variables using Pearson rank correlation. RESULTS: For sFNC, compared with mTBI patients without PTH, mTB with PTH group showed four altered interactions, including decreased interactions in SN-SMN and VN-DMN pairs, increased sFNC in SN-ECN and SMN-DMN pairs. For dFNC, significant group differences were found in State 2, including increased connectivity alteration in the DMN with CN, DMN with SMN, and AuN with CN. Significant reduced connectivity changes in the DMN with VN was found in State 4. Furthermore, the number of transitions (r=0.394, p=0.005) between states was positively associated with headache frequency. Additionally, dwell time (r=-0.320, p=0.025) in State 1 was negatively correlated with MoCA score. CONCLUSIONS: MTBI patients with PTH are characterized with altered sFNC and dFNC, which could provide new perspective to understand the neuropathological mechanism underlying the PTH to determine more appropriate management, and may be a useful imaging biomarker for identifying and predicting mTBI with PTH.

Detection and Semiquantitative Analysis of Cardiomegaly, Pneumothorax, and Pleural Effusion on Chest Radiographs.

PURPOSE: To develop and evaluate deep learning models for the detection and semiquantitative analysis of cardiomegaly, pneumothorax, and pleural effusion on chest radiographs. MATERIALS AND METHODS: In this retrospective study, models were trained for lesion detection or for lung segmentation. The first dataset for lesion detection consisted of 2838 chest radiographs from 2638 patients (obtained between November 2018 and January 2020) containing findings positive for cardiomegaly, pneumothorax, and pleural effusion that were used in developing Mask region-based convolutional neural networks plus Point-based Rendering models. Separate detection models were trained for each disease. The second dataset was from two public datasets, which included 704 chest radiographs for training and testing a U-Net for lung segmentation. Based on accurate detection and segmentation, semiquantitative indexes were calculated for cardiomegaly (cardiothoracic ratio), pneumothorax (lung compression degree), and pleural effusion (grade of pleural effusion). Detection performance was evaluated by average precision (AP) and free-response receiver operating characteristic (FROC) curve score with the intersection over union greater than 75% (AP75; FROC score75). Segmentation performance was evaluated by Dice similarity coefficient. RESULTS: The detection models achieved high accuracy for detecting cardiomegaly (AP75, 98.0%; FROC score75, 0.985), pneumothorax (AP75, 71.2%; FROC score75, 0.728), and pleural effusion (AP75, 78.2%; FROC score75, 0.802), and they also weakened boundary aliasing. The segmentation effect of the lung field (Dice, 0.960), cardiomegaly (Dice, 0.935), pneumothorax (Dice, 0.827), and pleural effusion (Dice, 0.826) was good, which provided important support for semiquantitative analysis. CONCLUSION: The developed models could detect cardiomegaly, pneumothorax, and pleural effusion, and semiquantitative indexes could be calculated from segmentations.Keywords: Computer-Aided Diagnosis (CAD), Thorax, CardiacSupplemental material is available for this article.© RSNA, 2021.

Cerebral Blood Flow and Its Connectivity Deficits in Mild Traumatic Brain Injury at the Acute Stage.

Objective: The influence of cognitive impairment after mild traumatic brain injury (mTBI) on cerebral vascular perfusion has been widely concerned, yet the resting-state cerebral blood flow (CBF) connectivity alterations based on arterial spin labeling (ASL) in mild traumatic brain injury (mTBI) remain unclear. This study investigated region CBF and CBF connectivity features in acute mTBI patients, as well as the associations between CBF changes and cognitive impairment. Materials and Methods: Forty-five acute mTBI patients and 42 health controls underwent pseudocontinuous arterial spin labeling (pCASL) perfusion magnetic resonance imaging (MRI). The alterations in regional CBF and relationship between the CBF changes and cognitive impairment were detected. The ASL-CBF connectivity of the brain regions with regional CBF significant differences was also compared between two groups. Neuropsychological tests covered seven cognitive domains. Associations between the CBF changes and cognitive impairment were further investigated. Results: Compared with the healthy controls, the acute mTBI patients exhibited increased CBF in the bilateral inferior temporal gyrus (ITG) and decreased CBF in the right middle frontal gyrus (MFG), the bilateral superior frontal gyrus (SFG), and the right cerebellum posterior lobe (CPL). In the mTBI patients, significant correlations were identified between the CBF changes and cognitive impairment. Importantly, the acute mTBI patients exhibited CBF disconnections between the right CPL and right fusiform gyrus (FG) as well as bilateral ITG, between the left SFG and left middle occipital gyrus (MOG), and between the right SFG and right FG as well as right parahippocampal gyrus. Conclusion: Our results suggest that acute mTBI patients exhibit both regional CBF abnormalities and CBF connectivity deficits, which may underlie the cognitive impairment of the acute mTBI patients.

Altered hypothalamic functional connectivity in post-traumatic headache after mild traumatic brain injury.

BACKGROUND: Post-traumatic headache (PTH) is one of the most frequent symptoms following mild traumatic brain injury (mTBI). Neuroimaging studies implicate hypothalamic function connectivity (FC) disruption as an important factor in pain disorders. However, it is unknown whether there are alterations in the hypothalamus-based resting state FC within PTH following mTBI at the acute stage and its relationship with headache symptom measurement. METHODS: Forty-four mTBI patients with PTH, 27 mTBI patients without PTH and 43 healthy controls who were well matched for age, gender, and years of education were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning as well as headache symptom measurement and cognitive assessment. Hypothalamic resting state networks were characterized by using a standard seed-based whole-brain correlation method. The bilateral hypothalamic FC was compared among the three groups. Furthermore, the correlations between hypothalamic resting state networks and headache frequency, headache intensity and MoCA scores was investigated in mTBI patients with PTH using Pearson rank correlation. RESULTS: Compared with mTBI patients without PTH, mTBI patients with PTH at the acute stage presented significantly decreased left hypothalamus-based FC with the right middle frontal gyrus (MFG) and right medial superior frontal gyrus (mSFG), and significantly decreased right hypothalamus-based FC with the right MFG. Decreased FC of the right MFG was significantly positively associated with headache frequency and headache intensity (r = 0.339, p = 0.024; r = 0.408, p = 0.006, respectively). Decreased FC of the right mSFG was significantly positively associated with headache frequency and headache intensity (r = 0.740, p < 0.0001; r = 0.655, p < 0.0001, respectively). CONCLUSION: Our data provided evidence of disrupted hypothalamic FC in patients with acute mTBI with PTH, while abnormal FC significantly correlated with headache symptom measurement. Taken together, these changes may play an essential role in the neuropathological mechanism of mTBI patients with PTH.

Disrupted functional network connectivity predicts cognitive impairment after acute mild traumatic brain injury.

AIMS: This study aimed to detect alterations of brain functional connectivity (FC) in acute mild traumatic brain injury (mTBI) and to estimate the extent to which these FC differences predicted the characteristics of posttraumatic cognitive impairment. METHODS: Resting-state fMRI data were acquired from acute mTBI patients (n = 50) and healthy controls (HCs) (n = 43). Resting-state networks (RSNs) were established based on independent component analysis (ICA), and functional network connectivity (FNC) analysis was performed. Subsequently, we analyzed the correlations between FNC abnormalities and cognitive impairment outcomes. RESULTS: Altered FC within the salience network (SN), sensorimotor network (SMN), default mode network (DMN), executive control network (ECN), visual network (VN), and cerebellum network (CN) was found in the mTBI group relative to the HC group. Moreover, different patterns of altered network interactions were found between the mTBI patients and HCs, including the SN-CN, VN-SMN, and ECN-DMN connections. Correlations between functional disconnection and cognitive impairment measurements in acute mTBI patients were also found. CONCLUSION: This study indicated that widespread FNC impairment and altered integration existed in mTBI patients at acute stage, suggesting that FNC disruption as a biomarker may be applied for the early diagnosis and prediction of cognitive impairment in mTBI.

Functional connectivity dysfunction of insular subdivisions in cognitive impairment after acute mild traumatic brain injury.

PURPOSE: This study aimed to investigate the early functional connectivity alterations between insula subdivisions and other cortical regions in patients with acute mild traumatic brain injury (mTBI) and subsequently to explore the relationship between functional connectivity changes of insula subdivisions with other cortical regions and cognitive function. METHODS: Fifty-three mTBI patients and 37 age-, gender- and education level- matched healthy controls were included in this study. All participants obtained resting state functional magnetic resonance imaging (rs-fMRI) and clinical and neuropsychological evaluations (Montreal cognitive assessment, MoCA) at the acute stage. Functional connectivity alterations of insula subdivisions and correlations with MoCA were further explored by seed-voxel functional connectivity. RESULTS: Compared with healthy controls, patients with acute mTBI showed significantly decreased functional connectivity between the L-vAI and the left middle temporal gyrus and right superior frontal gyrus and significantly decreased functional connectivity between the R-vAI and the right middle frontal gyrus and right hippocampus. While significantly decreased functional connectivity were observed between the L-dAI and the right superior frontal gyrus. In addition, significantly increased functional connectivity was observed between the R-PI and the left inferior frontal gyrus. Furthermore, the mTBI group demonstrated positive correlations between performances in orientation and insula and middle temporal gyrus and superior frontal gyrus and middle frontal gyrus functional connectivities. Abstraction scores for mTBI patients positively correlated with functional connectivity between insula and middle frontal gyrus. CONCLUSIONS: The present study demonstrated functional connectivity dysfunction of insula subdivisions and correlations between these alterations and cognitive performance, which provide a novel insight into the neurophysiological mechanism of cognitive impairment in patients with mTBI at the acute stage.

Neuroanatomical and functional alterations of insula in mild traumatic brain injury patients at the acute stage.

Cognitive impairment is a major cause of disability and decline in quality of life in mild traumatic brain injury (mTBI) survivors, but the underlying pathophysiology is still poorly understood. The insula has extensive connections to other cortex and is believed to responsible for integrating external and internal processes and controlling cognitive functions. To explore this hypothesis, we investigated early alterations in the gray matter volume (GMV) and brain functional connectivity (FC) of insula in mTBI patients within 7 days after injury and any possible correlations with cognitive function. A total of 58 mTBI patients at the acute stage and 32 matched healthy controls were recruited and underwentT1-weighted magnetic resonance imaging (MRI)andresting-state functional MRI scans within 7 days of injury. FC was characterized using seed-based region of interest analysis method. The patients' cognitive function was evaluated with Montreal Cognitive Assessment (MoCA) score. The resulting of GMV and FC of insula were correlated with cognitive alterations. We found that the GMV was significantly reduced only in the right insula in mTBI patients and no significant GMV increase was observed in either hemisphere. mTBI patients demonstrated decreased FC in the right parahippocampal gyrus and increased FC in the right supramargianl gyrus. In addition, compared to the healthy controls, the mTBI patients in the acute stage presented a decline in the visuospatial/executive (p = 0.013) and attention (p = 0.038) subcategories. In the mTBI group, the changes in GMV in the right insula were positively correlated with poor attention performance (r = 0.316, p = 0.016). Our data demonstrated alterations of the GMV and resting-stateFC of the right insula in mTBI patients at the acute stage. These early changes in GMV and resting-state FC perhaps serve as a potential biomarker for improving the understanding of cognitive decline for mTBI in the acute setting.

Disrupted brain functional hub and causal connectivity in acute mild traumatic brain injury.

There have been an increasing number of functional magnetic resonance imaging (fMRI) reports on brain abnormalities in mild traumatic brain injury (mTBI) at different phases. However, the neural bases and cognitive impairment after acute mTBI are unclear. This study aimed to identify brain functional hubs and connectivity abnormalities in acute mTBI patients and their correlations with deficits in cognitive performance. Within seven days after brain injury, mTBI patients (n=55) and age-, sex-, and educational -matched healthy controls (HCs) (n=41) underwent resting-state fMRI scans and cognitive assessments. We derived functional connectivity (FC) strength of the whole-brain network using degree centrality (DC) and performed Granger causality analysis (GCA) to analyze causal connectivity patterns in acute mTBI. Compared with HCs, acute mTBI patients had significantly decreased network centrality in the left middle frontal gyrus (MFG). Additionally, acute mTBI showed decreased inflows from the left MFG to bilateral middle temporal gyrus (MTG), left medial superior frontal gyrus (mSFG), and left anterior cingulate cortex (ACC). Correlation analyses revealed that changes in network centrality and causal connectivity were associated with deficits in cognitive performance in mTBI. Our findings may help to provide a new perspective for understanding the neuropathophysiological mechanism of acute cognitive impairment after mTBI.

Functional connectivity disruption of the substantia nigra associated with cognitive impairment in acute mild traumatic brain injury.

PURPOSE: Mild traumatic brain injury is known to have frequent cognitive impairment. Accumulating evidence is pointing to the malfunctioning of the substantia nigra (SN) as an important factor for head trauma. However, it remains unknown whether changes in the SN-based resting state functional connectivity following mTBI at acute stage and its relationship with cognitive function. MATERIALS AND METHODS: 58 patients with mTBI and 30 age-, gender-, and years of education-matched healthy controls were enrolled in the current study. All of participants received resting state functional magnetic resonance imaging as well as neuropsychological assessment. The resting state functional MR imaging data were analyzed by using a standard seed-based whole-brain correlation method to characterize SN resting state networks. Student t tests were used to perform comparisons. The association between SN resting state networks and performance on neuropsychological measures was also investigated in patients with mTBI by using Pearson rank correlation. RESULTS: Patients with mTBI at acute stage exhibited reduced left SN-based functional connectivity with right insula and caudate and increased left SN-based functional connectivity with left precuneus and left middle occipital gyrus, and reduced right SN-based functional connectivity with left insula. Increased functional connectivity of left precuneus was negatively associated with neurocognitive functions as well (r = -0.266; P = 0.049). CONCLUSION: The present study indicated that patients with acute mTBI suffer from disruption in their SN resting state networks. Moreover, abnormal functional connectivity significantly correlated with cognitive function. Taking together, these results may better improve our understanding of the neuropathological mechanism underlying the neurocognitive symptoms associated with acute mTBI.

Small cell lung cancer mimicking lymphoma in CT and 68Ga-DOTA-NOC PET/CT: A case report.

RATIONALE: Small cell lung cancer accounts for 15-20% of all lung cancers and is the most common pulmonary neuroendocrine neoplasm. Most small cell lung cancers arise from lobar or main bronchi, the most common manifestations of small cell lung cancer is a large mass centrally located within the lung parenchyma or a mediastinal mass involving the hilus. Small cell lung cancer is easily ignored by clinicians without lung parenchyma and hilus involvement. Here, we report a case of small cell lung cancer, which was misdiagnosed as the lymphoma in contrast enhanced CT and Ga-DOTA-NOC PET/CT imagings. PATIENT CONCERNS: A 49-year-old male with chief complaint of discontinuous cough for 1 month. DIAGNOSES: Small cell lung cancer. INTERVENTIONS: Radiotherapy and chemotherapy were given thereafter. OUTCOMES: The case had multiple enlarged lymph nodes due to tumor progression. LESSONS: Small cell lung cancer is a malignant and progressive disease, and easy to be ignored in clinical. The case of small cell lung cancer without parenchyma and hilus involvement has never been reported before. Here, we report it and hope it provides a differential diagnosis for clinicians in the following similar cases.

The impact of Kaua'i Care Transition Intervention on hospital readmission rates.

OBJECTIVES: To evaluate the effects of Kaua'i Care Transition Intervention (KCTI), a patient-centered intervention program, on reducing hospital readmission rates among patients 60 years or older. STUDY DESIGN: A prospective quasi-experimental prepost design. METHODS: Hospital admissions data for the year 2010 (January 1 to December 31) served as the baseline data and were used to identify patients at risk of hospital readmission. KCTI was implemented over a 12-month period from April 1, 2012, to March 31, 2013, and 30-day, 60-day, and 1-year readmission rates were assessed for both the intervention and baseline periods. The impact of the intervention was examined by a logistic regression model, controlling for possible patient population differences. RESULTS: During the intervention period, a total of 269 patients 60 years or older were admitted to the hospital, of which, 58 were referred to the KCTI program. Logistic regression controlling for patients' primary health insurance, discharge sites, and certain admitting diagnoses (eg, arrhythmias, cellulitis, chronic obstructive pulmonary disease) found that the intervention reduced the 30-day readmission rate by two-thirds (odds ratio [OR], 0.34; P = .003). Readmission rates within 60 days (OR, 0.42; P < .01) and within a year (OR, 0.48; P < .001) during the intervention period were less than half of the baseline rates. CONCLUSIONS: By selecting patients with identified risk factors, then empowering and educating them with the intervention program, this study was successful in reducing hospital readmission rates. This study also demonstrated the value of carefully selecting patients for intervention programs.