The injury progression in acute blast-induced mTBI in rats reflected by DTI and immunohistochemical examination.

Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined acute-phase monitoring and reliable imaging biomarkers hindered its clinical application in early diagnosis of bmTBI, leading to potential long-term disability of patients. Here, we used DTI in a rat model of bmTBI generated by exposing to single lateral blast waves (151.16 and 349.75 kPa, lasting 47.48 ms) released in a confined bioshock tube (BST-I) to investigate whole-brain DTI changes in the acute-phase of bmTBI at 1, 3, 7 days after injury. Combined assessment of immunohistochemical analysis, transmission electron microscopy (TEM) and behavioral readouts allowed for linking DTI changes to synchronous cellular damages and identifying stable imaging biomarkers. The corpus callosum (CC) and brainstem were identified as predominantly affected regions, in which reduced fractional anisotropy (FA) was detected as early as the first day after injury, with a maximum decline occurring at 3 days after injury before returning to near normal levels by 7 days. Axial diffusivity (AD) values within the CC and brainstem also significantly reduced at 3 days after injury. In contrast, the radial diffusivity (RD) in the CC showed acute elevation, peaking at 3 days after injury before normalizing by the 7-day time point. Damages to nerve fibers, including demyelination and axonal degeneration, progressed in lines with changes in DTI parameters, supporting a real-time macroscopic reflection of microscopic neuronal fiber injury by DTI. The most sensitive biomarker was identified as a decrease in FA, AD and an increase in RD within the CC on the third day after injury, supporting the diagnostic utility of DTI in cases of bmTBI in the acute phase.

18F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats.

A majority of blast-induced mild traumatic brain injury (mTBI) patients experience persistent neurological dysfunction with no findings on conventional structural MR imaging. It is urgent to develop advanced imaging modalities to detect and understand the pathophysiology of blast-induced mTBI. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) could detect neuronal function and activity of the injured brain, while MR spectroscopy provides complementary information and assesses metabolic irregularities following injury. This study aims to investigate the effectiveness of combining 18F-FDG PET with MR spectroscopy to evaluate acute and subacute metabolic cerebral alterations caused by blast-induced mTBI. Thirty-two adult male Sprague-Dawley rats were exposed to a single blast (mTBI group) and 32 rats were not exposed to the blast (sham group), followed by 18F-FDG PET, MRI, and histological evaluation at baseline, 1-3 h, 1 day, and 7 days post-injury in three separate cohorts. 18F-FDG uptake showed a transient increase in the amygdala and somatosensory cortex, followed by a gradual return to baseline from day 1 to 7 days post-injury and a continuous rise in the motor cortex. In contrast, decreased 18F-FDG uptake was seen in the midbrain structures (inferior and superior colliculus). Analysis of MR spectroscopy showed that inflammation marker myo-inositol (Ins), oxidative stress marker glutamine + glutamate (Glx), and hypoxia marker lactate (Lac) levels markedly elevated over time in the somatosensory cortex, while the major osmolyte taurine (Tau) level immediately increased at 1-3 h and 1 day, and then returned to sham level on 7 days post-injury, which could be due to the disruption of the blood-brain barrier. Increased 18F-FDG uptake and elevated Ins and Glx levels over time were confirmed by histology analysis which showed increased microglial activation and gliosis in the frontal cortex. These results suggest that 18F-FDG PET and MR spectroscopy can be used together to reflect more comprehensive neuropathological alterations in vivo, which could improve our understanding of the complex alterations in the brain after blast-induced mTBI.

Type 2 Diabetes Mellitus May Exacerbate Gray Matter Atrophy in Patients With Early-Onset Mild Cognitive Impairment.

BACKGROUND: The precise physiopathological association between the courses of neurodegeneration and cognitive decline in type 2 diabetes mellitus (T2DM) remains unclear. This study sought to comprehensively investigate the distribution characteristics of gray matter atrophy in middle-aged T2DM patients with newly diagnosed mild cognitive impairment (MCI). METHODS: Four groups, including 28 patients with early-onset MCI, 28 patients with T2DM, 28 T2DM patients with early-onset MCI (T2DM-MCI), and 28 age-, sex-, and education-matched healthy controls underwent three-dimensional high-resolution structural magnetic resonance imaging. Cortical and subcortical gray matter volumes were calculated, and a structural covariance method was used to evaluate the morphological relationships within the default mode network (DMN). RESULTS: Overlapped and unique cortical/subcortical gray matter atrophy was found in patients with MCI, T2DM and T2DM-MCI in our study, and patients with T2DM-MCI showed lower volumes in several areas than patients with MCI or T2DM. Volume loss in subcortical areas (including the thalamus, putamen, and hippocampus), but not in cortical areas, was related to cognitive impairment in patients with MCI and T2DM-MCI. No associations between biochemical measurements and volumetric reductions were found. Furthermore, patients with MCI and those with T2DM-MCI showed disrupted structural connectivity within the DMN. CONCLUSION: These findings provide further evidence that T2DM may exacerbate atrophy of specific gray matter regions, which may be primarily associated with MCI. Impairments in gray matter volume related to T2DM or MCI are independent of cardiovascular risk factors, and subcortical atrophy may play a more pivotal role in cognitive impairment than cortical alterations in patients with MCI and T2DM-MCI. The enhanced structural connectivity within the DMN in patients with T2DM-MCI may suggest a compensatory mechanism for the chronic neurodegeneration.

Alterations of Brain Structural Network Connectivity in Type 2 Diabetes Mellitus Patients With Mild Cognitive Impairment.

Patients with type 2 diabetes mellitus (T2DM) are highly susceptible to developing dementia, especially for those with mild cognitive impairment (MCI), but its underlying cause is still unclear. This study aims to investigate the early detection of white matter structural network changes in T2DM patients with MCI and assess the relationship between cognitive impairment and structural network alterations in T2DM patients. In this study, we performed a battery of neuropsychological tests and diffusion tensor MRI in 30 T2MD-MCI patients, 30 T2DM patients with normal cognition (T2DM-NC) and 30 age-, sex-, and education-matched healthy control (HC) individuals. Cognitive performance exhibited obvious differences among the three groups. The structural network was significantly disrupted in both global and regional levels in T2DM patients. The T2DM-MCI group showed more severe impairment of global network efficiency, and lower nodal efficiency and fewer connections within multiple regions like the limbic system, basal ganglia, and several cortical structures. Moreover, a subnetwork impaired in T2DM-MCI patients was characterized by cortical-limbic fibers, and commissural fibers and pathways within the frontal, temporal, and occipital lobes. These altered global and nodal parameters were significantly correlated with cognitive function in T2DM-MCI patients. In particular, executive dysfunction and working memory impairment in T2DM-MCI patients correlated with nodal efficiency in the right opercular part and triangular part of the inferior frontal gyrus, which indicated that white matter disruption in these regions may act as potential biomarkers for T2DM-associated MCI detection. Our investigation provides a novel insight into the neuropathological effects of white matter network disruption on cognition impairments induced by T2DM.

White Matter Atrophy in Type 2 Diabetes Mellitus Patients With Mild Cognitive Impairment.

Type 2 diabetes mellitus (T2DM) patients are highly susceptible to developing dementia, especially for those with mild cognitive impairment (MCI), but its underlying cause is still unclear. In this study, we performed a battery of neuropsychological tests and high-resolution sagittal T1-weighted structural imaging to explore how T2DM affects white matter volume (WMV) and cognition in 30 T2DM-MCI patients, 30 T2DM with normal cognition (T2DM-NC) patients, and 30 age-, sex-, and education-matched healthy control (HC) individuals. The WMV of the whole brain was obtained with automated segmentation methods. Correlations between the WMV of each brain region and neuropsychological tests were analyzed in the T2DM patients. The T2DM-NC patients and HC individuals did not reveal any significant differences in WMV. Compared with the T2DM-NC group, the T2DM-MCI group showed statistically significant reduction in the WMV of seven brain regions, mainly located in the frontotemporal lobe and limbic system, five of which significantly correlated with Montreal Cognitive Assessment (MoCA) scores. Subsequently, we evaluated the discriminative ability of these five regions for MCI in T2DM patients. The WMV of four regions, including left posterior cingulate, precuneus, insula, and right rostral middle frontal gyrus had high diagnostic value for MCI detection in T2DM patients (AUC > 0.7). Among these four regions, left precuneus WMV presented the best diagnostic value (AUC: 0.736; sensitivity: 70.00%; specificity: 73.33%; Youden index: 0.4333), but with no significant difference relative to the minimum AUC. In conclusion, T2DM could give rise to the white matter atrophy of several brain regions. Each WMV of left posterior cingulate, precuneus, insula, and right rostral middle frontal gyrus could be an independent imaging biomarker to detect cognitive impairment at the early stage in T2DM patients and play an important role in its pathophysiological mechanism.

"One-stop hybrid procedure" in the treatment of vascular injury of lower extremity.

As a new surgical technique, "one-stop hybrid procedure" is rarely applied in trauma patients. This paper aims to explore its role in vascular injury of the lower extremity. Vascular intervention combined with open surgery was performed to treat three cases of vessel injuries of the lower extremity in our hybrid operating room. One patient with stab injury to the left femoral vein was treated by temporary artery blocking after excluding arterial injury by angiography, followed by blocking surgery and debridement and repair of the injured vein. The other two patients with drug addiction history, who were found to have pricking injuries to the femoral artery combined with local infection, were successfully treated by endovascular techniques and open debridement. One-stop hybrid procedure in treating vascular injury patients could simplify the operation procedure, reduce operative risk, and achieve good curative effect.

LDA-SVM-based EGFR mutation model for NSCLC brain metastases: an observational study.

Epidermal growth factor receptor (EGFR) activating mutations are a predictor of tyrosine kinase inhibitor effectiveness in the treatment of non-small-cell lung cancer (NSCLC). The objective of this study is to build a model for predicting the EGFR mutation status of brain metastasis in patients with NSCLC. Observation and model set-up. This study was conducted between January 2003 and December 2011 in 6 medical centers in Southwest China. The study included 31 NSCLC patients with brain metastases. Eligibility requirements were histological proof of NSCLC, as well as sufficient quantity of paraffin-embedded lung and brain metastases specimens for EGFR mutation detection. The linear discriminant analysis (LDA) method was used for analyzing the dimensional reduction of clinical features, and a support vector machine (SVM) algorithm was employed to generate an EGFR mutation model for NSCLC brain metastases. Training-testing-validation (3 : 1 : 1) processes were applied to find the best fit in 12 patients (validation test set) with NSCLC and brain metastases treated with a tyrosine kinase inhibitor and whole-brain radiotherapy. Primary and secondary outcome measures: EGFR mutation analysis in patients with NSCLC and brain metastases and the development of a LDA-SVM-based EGFR mutation model for NSCLC brain metastases patients. EGFR mutation discordance between the primary lung tumor and brain metastases was found in 5 patients. Using LDA, 13 clinical features were transformed into 9 characteristics, and 3 were selected as primary vectors. The EGFR mutation model constructed with SVM algorithms had an accuracy, sensitivity, and specificity for determining the mutation status of brain metastases of 0.879, 0.886, and 0.875, respectively. Furthermore, the replicability of our model was confirmed by testing 100 random combinations of input values. The LDA-SVM-based model developed in this study could predict the EGFR status of brain metastases in this small cohort of patients with NSCLC. Further studies with larger cohorts should be carried out to validate our findings in the clinical setting.

White matter integrity and cognition in mild traumatic brain injury following motor vehicle accident.

The aim of this study is to explore the white matter structure integrity in patients with mild traumatic brain injury (mTBI) using diffusion tensor imaging (DTI), and to analyze the relationship between the white matter structure integrity and cognitive impairment of patients with mTBI. Twenty-five patients with mTBI and 25 healthy control subjects were studied with conventional MR imaging and diffusion tensor imaging. Fractional anisotropy (FA) and mean diffusivity (MD) maps of patients with mTBI were calculated and compared, with these control maps using tract-based spatial statistics (TBSS). Significantly lower fractional anisotropy was found in patients in the uncinate fasciculus, superior longitudinal fasciculus, inferior longitudinal fasciculus, and internal capsule. Mean diffusivity was significantly elevated in the body of corpus callosum, uncinate fasciculus, superior longitudinal fasciculus, and internal capsule in the mTBI group compared with the control group (P<0.05). The mTBI group showed a significant negative correlation between the elevated mean diffusivity of the uncinate fasciculus and the working memory index (WMI) (R(2)=0.51, P<0.05), and the internal capsule of MD values was significantly negatively related to processing speed index (PSI) (R(2)=0.45, P<0.05). There was a positive correlation between the FA value of the uncinate fasciculus and Mini Mental State Examination (MMSE) in the mTBI patient group (R(2)=0.36, P<0.05). TBSS analysis of DTI suggests that patients with mTBI have focal axonal injury, and the pathophysiology is significantly related to the MMSE and IQ of mTBI patients. Diffusion tensor imaging can be a powerful technique for in vivo detection of mTBI, and can help in the diagnosis of patients with mTBI.

Diffusion tensor imaging and magnetic resonance spectroscopy in traumatic brain injury: a review of recent literature.

Concussion is the most common form of traumatic brain injury (TBI), but diagnosis remains controversial because the brain appears quite normal in conventional computed tomography and magnetic resonance imaging (MRI). These conventional tools are not sensitive enough to detect diffuse traumatic axonal injury, and cannot depict aberrations in mild TBIs. Advanced MRI modalities including diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS), make it possible to detect brain injuries in TBI. The purpose of this review is to provide the latest information regarding the visualization and quantification of important abnormalities in TBI and new insights into their clinical significance. Advanced imaging modalities allow the discovery of biomarkers of injury and the detection of changes in brain injury over time. Such tools will likely be used to evaluate treatment efficacy in research. Combining multiple imaging modalities would not only provide greater insight into the underlying physiological changes in TBI, but also improve diagnostic accuracy in predicting outcomes. In this review we present evidence of brain abnormalities in TBI based on investigations using MRI, including DTI and MRS. Our review provides a summary of some of the important studies published from 2002 to 2012 on the topic of MRI findings in head trauma. With the growing realization that even mild head injury can lead to neurocognitive deficits, medical imaging has assumed preeminence for detecting abnormalities associated with TBI. Advanced MRI modalities such as DTI and MRS have an important role in the diagnosis of lesions for TBI patients.

Negative emotion regulation in patients with posttraumatic stress disorder.

OBJECTIVE: To explore the neural mechanisms of negative emotion regulation in patients with post-traumatic stress disorder (PTSD). METHODS: Twenty PTSD patients and 20 healthy subjects were recruited. Event-related functional magnetic resonance imaging (fMRI) was used to investigate the modification of emotional responses to negative stimuli. Participants were required to regulate their emotional reactions according to the auditory regulation instructions via headphones, to maintain, enhance or diminish responses to negative stimuli during fMRI scans. RESULTS: The PTSD group showed poorer modification performance than the control group when diminishing responses to negative stimuli. On fMRI, the PTSD group showed decreased activation in the inferior frontal cortex, inferior parietal lobule, insula and putamen, and increased activation in posterior cingulate cortex and amygdala during up-regulation of negative emotion. Similar decreased activation regions were found during down-regulation of negative emotion, but no increased activation was found. CONCLUSION: Trauma exposure might impair the ability to down-regulate negative emotion. The present findings will improve our understanding of the neural mechanisms of emotion regulation underlying PTSD.

Left coronary artery-to-right atrium fistula: an evaluation of MSCT angiography before and after transcatheter closure with a PDA occluder.

The MSCT manifestations of a left coronary artery-to-right atrium fistula before and after the transcatheter closure were reported. Before treatment, MSCT showed a dilated left coronary sinus and the dilated left main trunk, which coursed along the coronary sulcus to form the left circumflex artery, draining directly into the right atrium in the left middle part. The fistula was occluded with a PDA occluder. Four days after the occlusion, MSCT showed that the fistula was completely occluded and there was massive thrombosis in the central part and around the occluder. The thrombus was found even in the segment near to the start point of the oblique marginal artery.

Elevation of high-mobility group protein box-1 in serum correlates with severity of acute intracerebral hemorrhage.

High-mobility group protein box-1 (HMGB1) is a proinflammatory involved in many inflammatory diseases. However, its roles in intracerebral hemorrhage (ICH) remain unknown. The purpose of this study was to examine the correlation between changes in serum levels of HMGB1 following acute ICH and the severity of stroke as well as the underlying mechanism. Changes in serum levels of HMGB1 in 60 consecutive patients with primary hemispheric ICH within 12 hours of onset of symptoms were determined. The correlation of HMGB1 with disease severity, IL-6, and TNF-α was analyzed. Changes in HMGB1 levels were detected with ELISA and Western blot. Compared with normal controls, patients with ICH had markedly elevated levels of HMGB1, which was significantly correlated with the levels of IL-6 and TNF-α, NIHSS score at the 10th day, and mRS score at 3 months. In comparison with the control group, the levels of HMGB1 in the perihematomal tissue in mice with ICH increased dramatically, peaked at 72 hours, and decreased at 5 days. Meanwhile, heme could stimulate cultured microglia to release large amounts of HMGB1 whereas Fe(2+/3+) ions failed to stimulate HMGB1 production from microglia. Our findings suggest that HMGB1 may play an essential role in the ICH-caused inflammatory injury.

Study on inferior petrosal sinus and its confluence pattern with relevant veins by MSCT.

OBJECTIVE: To explore the anatomic route of inferior petrosal sinus (IPS) after going out of the cranium and its confluence patterns with internal jugular vein (IJV), anterior condylar vein (ACV) and lateral condylar vein (LCV), and to supply knowledge about typing of IPS-IJV junction, so as to provide reference evidence for evaluation of transvenous access route in the diagnosis and treatment of skull base and cavernous sinus lesions. METHODS: In 120 patients, the IPS route and its confluence with IJV, ACV and LCV were shown by multi-planar reconstruction (MPR) and curve multi-planar reconstruction (CMPR). Combining with continuous thin slice, the IPS-IJV junction was further subdivided according to the level of IPS confluence with IJV and whether there is an anastomosis with sigmoid sinus (SS). Furthermore, the IPS length, venous diameter at IPS-IJV junction and IPS-SS communicating branch were determined and compared. RESULTS: Inferior petrosal sinus directly draining into jugular bulb (JB) or/and draining into JB after communication with SS was found in 28 sides (11.7%, pattern A); IPS draining into IJV at the level of exterior opening of hypoglossal canal in 114 sides (47.5%, pattern B); IPS draining into IJV in a lower extracranial level in 83 sides (34.6%, pattern C); IPS with multiple junctions draining into IJV near the jugular foramen in 12 sides (5.0%, pattern D); IPS directly draining into VVP in 1 side (0.4%, pattern E); IPS being absent in 1 side (0.4%, pattern F). IPS draining into VVP via ACV was seen in 218 sides, IPS draining into VVP via LCV in 100 sides and IPS directly draining into IJV in 14 sides. After going out of the cranium, IPS goes along with IJV for a relatively long distance in some cases. The IPS extracranial length over 40 mm was found in ten sides and the lowest level of IPS route was at the inferior margin of the fourth cervical vertebra. The venous diameter at the IPS-IJV confluence was 0.8-5.7 mm (mean 2.51 mm) and it was significantly larger on the right side than on the left (P = 0.01). However, there was no remarkable difference between male patients and female ones. CONCLUSION: Continuous thin-slice scanning by multislice spiral computed tomography in combination with MPR and CMPR can clearly show IPS route and its confluence with relevant veins, and determine the feasibility of procedures via IPS. Therefore, it can be used as an effective method for preoperative evaluation of IPS for diagnosis and treatment of skull base and cavernous sinus lesions by IJV access route.

The role of positron emission tomography imaging of beta-amyloid in patients with Alzheimer's disease.

One of the hallmark pathologies of Alzheimer's disease (AD) is amyloid plaque deposition in the brain. Although the advent of new therapeutic strategies aimed at reducing beta-amyloid burden in the brain is to potentially delay cognitive loss, improved methods for amyloid visualization have become more imperative. Studies so far have shown that positron emission tomography (PET) has produced the greatest strides toward accomplishing this ambitious goal. Several PET amyloid imaging ligands have recently been developed and tested in AD patients. High amyloid content can be detected in vivo by PET in prodromal AD preceding the impairment of functional activity. Hopefully, amyloid imaging may help in the early detection of the disease and can be used for evaluating new drug therapies in AD. This study provides an overview of recent advances in the development of amyloid imaging agents and includes a summary of the clinical significance of amyloid imaging.

[Image analysis of puborectalis syndrome and its clinical significance].

OBJECTIVE: To discuss the clinical value and application range of defecography, CT and MRI in diagnosis of puborectalis syndrome (PRS). METHODS: The clinical data of 83 PRS patients, including defecography, CT and MRI scanning in pelvic floor resting and defecation at maximum exertion, measurement of anorectal angle (ARA), length and depth of ARA impression and the thickness of the puborectalis muscle, were collected, and compared with those of 56 normal persons. RESULTS: For normal persons, ARA at maximum exertion was more significantly increased than that at resting. In 62 cases with PRS, ARA at maximum exertion was more obviously reduced than that at resting and associated with puborectalis muscle (PRM) impression. In the other 21 cases, ARA showed no changes at either maximum exertion or resting, a little or no excretion of barium appeared and "shelving syndrome" was showed. The cross-sectional images of CT and MRI showed that the puborectalis of PRS patients were thicker than that of normal persons (P<0.01). PRS patients also showed clear pelvic floor muscle, fasciae and peripheral crevice. CONCLUSIONS: Defecography, manifested the abnormal function of the puborectalis muscles, is a reliable method for diagnosis of PRS. In the meantime, CT and MRI are able to clearly display the position, growth status and size of the puborectalis muscles as well as its relation with adjacent structures, which provide further understandings on anatomical changes, abnormal adjacent structure and other functional diseases of pelvic floor in PRS patients. Therefore, an appropriate combination of the 3 methods play an important role in the early diagnosis of PRS and guidance for surgical treatment.

[Analysis of the causes of misdiagnosis on CT films of 45 patients with lung cancer].

BACKGROUND: To analyze the causes of computed tomographic misdiagnosis of pulmonary carcinoma. METHODS: From September 1991 to January 2002, 45 cases of pulmonary carcinoma misdiagnosed by CT were analyzed retrospectively. Twenty-six cases of pulmonary tuberculosis and 15 cases of pulmonary pneumonia misdiagnosed as pulmonary carcinoma by CT were studied as control subjects. All of these cases were confirmed by surgery and clinical course. The CT appearances of these cases were independently reviewed in a double blind method by three experienced radiologists. Then they discussed together in order to search for the factors of CT misdiagnosis and formed a consensus interpretation. RESULTS: Forty-five cases of pulmonary carcinoma were misdiagnosed as pulmonary tuberculosis in 19 cases, pneumonia in 14 cases, abscess in 4 cases, pleural mesothelioma in 2 cases, normal in 2 cases, and others in 4 cases. The fundamental manifestations of misdiagnosed cases were lobar or segmental shadows (26 cases), solitary mass or nodule (19 cases).The reasons of CT misdiagnosis were very confusing. The main factors were:(i) Missed diagnosis (2 cases, 4.5%). One case had an endobronchial mass and another had the erosion of rib. (ii) Twenty-four cases (53.3%) due to mis interpretation and lack of experience. (iii) The manifestations in CT were atypical (19 cases,42.2%). CONCLUSIONS: Not identifying accurately the CT appearances and excessively emphasizing the specificity of some signs are the main causes of the misdiagnosis. A reasonable and careful CT examination, summarizing analysis combined with clinical findings, and the accumulation of diagnostic experience will help to reduce the CT misdiagnostic rate of pulmonary carcinomas.