Acute metabolic alterations in the hippocampus are associated with decreased acetylation after blast induced TBI.

INTRODUCTION: Blast induced Traumatic brain injury (BI-TBI) is common among military personnels as well as war affected civilians. In the war zone, people can also encounter repeated exposure of blast wave, which may affect their cognition and metabolic alterations. OBJECTIVE: In this study we assess the metabolic and histological changes in the hippocampus of rats at 24 h post injury. METHOD: Rats were divided into four groups: (i) Sham; (ii) Mild TBI (mi); (iii) Moderate TBI (mo); and (iv) Repetitive mild TBI (rm TBI) and then subjected to different intensities of blast exposure. Hippocampal tissues were collected after 24 h of injury for proton nuclear magnetic resonance spectroscopy (1H NMR spectroscopy) and immunohistochemical (IHC) analysis. RESULTS: The metabolic alterations were found in the hippocampal tissue samples and these alterations showed significant change in glutamate, N-Acetylaspartic acid (NAA), acetate, creatine, phosphoethanolamine (PE), ethanolamine and PC/choline concentrations in rmTBI rats only. IHC studies revealed that AH3 (Acetyl histone) positive cells were decreased in rm TBI tissue samples in comparison to other TBI groups and sham rats. This might reflect an epigenetic alteration due to repeated blast exposure at 24 h post injury. Additionally, astrogliosis was observed in miTBI and moTBI hippocampal tissue while no change was observed in rmTBI tissues. CONCLUSION: The present study reports altered acetylation in the presence of altered metabolism in hippocampal tissue of blast induced rmTBI at 24 h post injury. Mechanistic understanding of these intertwined processes may help in the development of better therapeutic pathways and agents for blast induced TBI in near future.

Altered metabolites of the rat hippocampus after mild and moderate traumatic brain injury - a combined in vivo and in vitro 1 H-MRS study.

Traumatic brain injury (TBI) has been shown to affect hippocampus-associated learning, memory and higher cognitive functions, which may be a consequence of metabolic alterations. Hippocampus-associated disorders may vary depending on the severity of injury [mild TBI (miTBI) and moderate TBI (moTBI)] and time since injury. The underlying hippocampal metabolic irregularities may provide an insight into the pathological process following TBI. In this study, in vivo and in vitro proton magnetic resonance spectroscopy (1 H-MRS) data were acquired from the hippocampus region of controls and TBI groups (miTBI and moTBI) at D0 (pre-injury), 4 h, Day 1 and Day 5 post-injury (PI). In vitro MRS results indicated trauma-induced changes in both miTBI and moTBI; however, in vivo MRS showed metabolic alterations in moTBI only. miTBI and moTBI showed elevated levels of osmolytes indicating injury-induced edema. Altered levels of citric acid cycle intermediates, glutamine/glutamate and amino acid metabolism indicated injury-induced aberrant bioenergetics, excitotoxicity and oxidative stress. An overall similar pattern of pathological process was observed in both miTBI and moTBI, with the distinction of depleted N-acetylaspartate levels (indicating neuronal loss) at 4 h and Day 1 and enhanced lactate production (indicating heightened energy depletion leading to the commencement of the anaerobic pathway) at Day 5 in moTBI. To the best of our knowledge, this is the first study to investigate the hippocampus metabolic profile in miTBI and moTBI simultaneously using in vivo and in vitro MRS.

Potential for differentiation of glioma recurrence from radionecrosis using integrated 18F-fluoroethyl-L-tyrosine (FET) positron emission tomography/magnetic resonance imaging: A prospective evaluation.

PURPOSE: To assess the utility of 18F-fluoroethyl-L-tyrosine (FET) positron emission tomography/magnetic resonance imaging (PET/MRI) in distinguishing recurrence from radionecrosis. MATERIALS AND METHODS: Thirty-two patients (25 males, 7 females) of glioma who had already undergone surgery/chemoradiotherapy and had enhancing brain lesions suspicious of recurrence were evaluated using integrated 18F-FET PET/MRI, and followed up with histopathology or clinical follow-up and/or MRI/PET/MRI imaging. Manually drawn regions of interest over areas of maximal enhancement or FET uptake were used to calculate tumor to background ratios [TBRmax, TBRmean], choline: creatine ratio [Cho: Cr ratio], normalized relative cerebral blood volume [N rCBVmean] and apparent diffusion coefficient [ADCmean]. Correlations were evaluated using Pearson's coefficient. Accuracy of each parameter was calculated using independent t-test and receiver operator curve (ROC) analysis while utility of all four parameters together using multivariate analysis of variance (MANOVA) for differentiating recurrence vs. radionecrosis was evaluated. Positive histopathology and imaging/clinical follow up served as the gold standard. RESULTS: Twenty-four of the 32 patients were diagnosed with recurrent disease and 8 with radiation necrosis. Significant correlations were observed between TBRmaxand N rCBVmean (ρ =0.503; P = 0.003), TBRmean, and N rCBVmean (ρ =0.414; P = 0.018), TBRmaxand ADCmean (ρ = -0.52; P = 0.002), and TBRmeanand ADCmean(ρ = -0.518; P = 0.002). TBRmax, TBRmean, ADCmean, Cho: Cr ratios, and N rCBVmeanwere significant in differentiating recurrence from radiation necrosis with an accuracy of 94.1%, 88.2%, 80.4%, 96.4%, and 89.9%, respectively. MANOVA indicated that combination of all parameters demonstrated better evaluation of recurrence vs. necrosis than any single parameter. The diagnostic accuracy, sensitivity, and specificity using all MRI parameters were 93.75%, 96%, and 85.7%, and using all FET PET/MRI parameters was 96.87%, 100%, and 85.7%, respectively. CONCLUSIONS: Synergetic effect of multiple MR parameters evaluated together in addition to FET PET uptake highlights the fact that integrated 18F-FET PET/MRI might have the potential to impact management of patients with glioma by timely and conclusive recognition of true recurrence from radiation necrosis.

Genochondromatosis type I: A clinicoradiological study of four family members.

Genochondromatosis is an extremely rare autosomal dominant disorder, which manifests during childhood and tends to regress in adult life. The bony lesions are symmetrically distributed with characteristic localization at the metaphysis of proximal humerus and distal femur. Two types have been described based on the involvement of clavicle. Usually asymptomatic, sometimes patients may present with pathological fractures. In this communication, we describe four members of a family with Genochondromatosis type I, with some additional clinical and radiological findings not reported previously.

A method to improve sensitivity of Ferrous ammonium sulfate - Benzoic acid - Xylenol orange (FBX) aqueous radiation dosimeter.

Ferrous ammonium sulfate - Benzoic acid - Xylenol orange (FBX) solution is known for its dosimetry properties in the dose range applicable in radiation oncology. Several attempts at improving its dose sensitivity have been reported in literature. The current work explores a novel method to improve the dose response of the system in the range 0-10 Gy with the original standard composition of the solution. Value of the sensitivity of the dosimeter was found to be 7.471/Gy with excellent linearity using the developed method. This is 115 times higher than the sensitivity obtained using the conventional methods.

Altered DTI scalars in the hippocampus are associated with morphological and structural changes after traumatic brain injury.

Blunt and diffuse injury is a highly prevalent form of traumatic brain injury (TBI) which can result in microstructural alterations in the brain. The blunt impact on the brain can affect the immediate contact region but can also affect the vulnerable regions like hippocampus, leading to functional impairment and long-lasting cognitive deficits. The hippocampus of the moderate weight drop injured male rats was longitudinally assessed for microstructural changes using in vivo MR imaging from 4 h to Day 30 post-injury (PI). The DTI analysis found a prominent decline in the apparent diffusion coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD) values after injury. The perturbed DTI scalars accompanied histological changes in the hippocampus, wherein both the microglia and astrocytes showed changes in the morphometric parameters at all timepoints. Along with this, the hippocampus showed presence of Aß positive fibrils and neurite plaques after injury. Therefore, this study concludes that TBI can lead to a complex morphological, cellular, and structural alteration in the hippocampus which can be diagnosed using in vivo MR imaging techniques to prevent long-term functional deficits.

Differential diagnosis of parkinsonian syndromes using F-18 fluorodeoxyglucose positron emission tomography.

INTRODUCTION: Positron emission tomography (PET) imaging with F-18 fluorodeoxyglucose (FDG) has been used to identify characteristic patterns of regional glucose metabolism in patients with idiopathic Parkinson's disease (IPD) and the atypical parkinsonian syndromes of progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). We undertook this study to assess the utility of fluorodeoxyglucose-PET in the differential diagnosis of individual patients with clinical parkinsonism. "Visual" and "computer-supported" reading of the fluorodeoxyglucose-PET scans were used for image interpretation and compared with each other. METHODS: One hundred thirty-six parkinsonian patients were referred from movement disorder clinics in specialty neurology centers for the fluorodeoxyglucose-PET study. Imaging-based diagnosis was obtained by visual assessment of individual scans by a PET physician blinded to the clinical diagnosis and also by computer-assisted interpretation using statistical parametric mapping (SPM) analysis. The results were compared with a 2-year follow-up clinical assessment made by a movement disorder specialist. RESULTS: Concordance of visual evaluation of fluorodeoxyglucose-PET with clinical diagnosis was achieved in 91.7% of patients scanned, 97.6% IPD, 80% MSA, 76.6% PSP, and 100% CBS. Blinded computer assessment using SPM was concordant with the clinical diagnosis in 91% of cases evaluated (90.4% IPD, 80% MSA, 93.3% PSP, and 100% CBS). CONCLUSIONS: Fluorodeoxyglucose-PET performed at the time of initial referral for parkinsonism is useful for the differential diagnosis of IPD, PSP, MSA, and CBS. Computer-assisted methods can be used for objective evaluation especially when expert readers are not available.

18F-FDG 18F-FDG Positron Emission Tomography Imaging of Cortical Reorganization in Spinal Trauma.

Objective: Spinal cord injury (SCI) extensively impacts the sensorimotor reorganization in the brain. The effects can be both anatomical and functional. To date, not many studies using 18F-Fluoro-2-Deoxyglucose positron emission tomography (18F-FDG PET) to evaluate metabolic changes in the brain are done. Understanding such changes is crucial for developing clinical management and evidence-based rehabilitation strategies for these patients. Subjects and Methods: In this study, we compared 18F-FDG PET imaging of 6 SCI patients with complete paraplegia and 19 controls. Statistical parametric mapping software was utilized to compare the images on a voxel to voxel basis (significance level P < 0.05 and clusters having >50 voxels). Results: The study showed raised metabolism in supplementary motor areas, comprehension centers, some areas in the parietal and temporal lobe, putamen and cerebellum while reduced metabolic uptake in areas like anterior cingulate gyrus, hippocampus and sensory cortical areas when SCI patients were compared against healthy controls. The frontal lobe showed varied results where certain regions showed higher metabolism while the others showed lower in patients compared with controls. Conclusion: Cerebral deafferentation or disuse atrophy can be linked with reduced metabolism while raised uptake can be associated with initiation and planning of movement and cognitive changes in the brain posttrauma.

Does the initial chest radiograph severity in COVID-19 impact the short- and long-term outcome? - a perspective from India.

PURPOSE: The chest radiograph (CXR) is among the most widely used investigations in coronavirus disease 2019 (COVID-19) patients. Little is known about its predictive role on the long-term outcome. The purpose of this study was to explore its association with the short and long-term outcome in COVID-19 patients. METHODS: A total of 1530 patients were assessed for the presence, radiographic pattern and distribution of lung lesions observed on baseline chest radiographs obtained at admission. The Brixia scoring system was applied for semiquantitative assessment of lesion severity. Short-term outcome was determined by clinical severity, duration of hospitalization and mortality. The 1415 survivors in this group were assessed after 5-6 months for the presence of residual symptoms. RESULTS: About 67% patients had an abnormal baseline CXR. Bilateral involvement with a basal preponderance was observed and ground-glass opacification was the most frequent finding. The Brixia score ranged from 0 to 16, median 2, interquartile range (IQR) [0-6]. About 36% patients were symptomatic on 5-6-month follow-up, with fatigability being the commonest symptom. A good correlation was observed between the CXR score and disease severity as well as duration of hospitalization. On multivariate analysis, the CXR score was found to be a significant independent predictor of in-patient mortality as well as presence of long-term residual symptoms in survivors. CONCLUSIONS: Disease severity as seen on the chest radiograph appears to play an important role in driving the short and long-term consequences of COVID-19 and could serve as a prognostic indicator, which influences short-term management and long-term follow-up.

Intra-cavitary course of right coronary artery: what the cardiologists should be aware of!

We report an unusual case of an anomalous intra-cavitary course of the right coronary artery (RCA) that was detected on multislice computed tomography (CT) angiography. Albeit rare, this anomaly is being picked up with increasing frequency owing to the widespread use of coronary CT angiography (CCTA). Although this entity does not produce symptoms per se, it can result in potentially catastrophic complications during interventional procedures or bypass surgeries if not recognized in time.

A Methodology to Compare Biomechanical Simulations With Clinical Brain Imaging Analysis Utilizing Two Blunt Impact Cases.

According to the US Defense and Veterans Brain Injury Center (DVBIC) and Centers for Disease Control and Prevention (CDC), mild traumatic brain injury (mTBI) is a common form of head injury. Medical imaging data provides clinical insight into tissue damage/injury and injury severity, and helps medical diagnosis. Computational modeling and simulation can predict the biomechanical characteristics of such injury, and are useful for development of protective equipment. Integration of techniques from computational biomechanics with medical data assessment modalities (e.g., magnetic resonance imaging or MRI) has not yet been used to predict injury, support early medical diagnosis, or assess effectiveness of personal protective equipment. This paper presents a methodology to map computational simulations with clinical data for interpreting blunt impact TBI utilizing two clinically different head injury case studies. MRI modalities, such as T1, T2, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC), were used for simulation comparisons. The two clinical cases have been reconstructed using finite element analysis to predict head biomechanics based on medical reports documented by a clinician. The findings are mapped to simulation results using image-based clinical analyses of head impact injuries, and modalities that could capture simulation results have been identified. In case 1, the MRI results showed lesions in the brain with skull indentation, while case 2 had lesions in both coup and contrecoup sides with no skull deformation. Simulation data analyses show that different biomechanical measures and thresholds are needed to explain different blunt impact injury modalities; specifically, strain rate threshold corresponds well with brain injury with skull indentation, while minimum pressure threshold corresponds well with coup-contrecoup injury; and DWI has been found to be the most appropriate modality for MRI data interpretation. As the findings from these two cases are substantiated with additional clinical studies, this methodology can be broadly applied as a tool to support injury assessment in head trauma events and to improve countermeasures (e.g., diagnostics and protective equipment design) to mitigate these injuries.

Alterations of connectivity patterns in functional brain networks in patients with mild traumatic brain injury: A longitudinal resting-state functional magnetic resonance imaging study.

AIM: In the present study, we aimed to characterise changes in functional brain networks in individuals who had sustained uncomplicated mild traumatic brain injury (mTBI). We assessed the progression of these changes into the chronic phase. We also attempted to explore how these changes influenced the severity of post-concussion symptoms as well as the cognitive profile of the patients. METHODS: A total of 65 patients were prospectively recruited for an advanced magnetic resonance imaging (MRI) scan within 7 days of sustaining mTBI. Of these, 25 were reassessed at 6 months post injury. Differences in functional brain networks were analysed between cases and age- and sex-matched healthy controls using independent component analysis of resting-state functional MRI. RESULTS: Our study revealed reduced functional connectivity in multiple networks, including the anterior default mode network, central executive network, somato-motor and auditory network in patients who had sustained mTBI. A negative correlation between network connectivity and severity of post-concussive symptoms was observed. Follow-up studies performed 6 months after injury revealed an increase in network connectivity, along with an improvement in the severity of post-concussion symptoms. Neurocognitive tests performed at this time point revealed a positive correlation between the functional connectivity and the test scores, along with a persistence of negative correlation between network connectivity and post-concussive symptom severity. CONCLUSION: Our results suggest that uncomplicated mTBI is associated with specific abnormalities in functional brain networks that evolve over time and may contribute to the severity of post-concussive symptoms and cognitive deficits.

Diffusion tensor tractography in cerebral small vessel disease: correlation with cognitive function.

Background Patients with cerebral small vessel disease may suffer from varying levels of cognitive deficit and may progress on to vascular dementia. The extent of involvement, as seen on conventional magnetic resonance (MR) measures, correlates poorly with the level of cognitive decline. The purpose of this study was to investigate the utility of diffusion tensor imaging (DTI) as a marker for white matter damage in small vessel disease and to assess its correlation with cognitive function. Methods Thirty consecutive patients with cerebral small vessel disease underwent conventional MR imaging, DTI, and neuropsychological assessment. Results On tractographic analysis, fractional anisotropy was significantly reduced while mean diffusivity significantly increased in several white matter tracts. The alteration in DTI indices correlated well with cognitive function. No significant correlation was identified between T2 lesion load and cognitive performance. Conclusions Tractographic analysis of white matter integrity is a useful measure of disease severity and correlates well with cognitive function. It may have a significant potential in monitoring disease progression and may serve as a surrogate marker for treatment trials.

Diffusion tensor MR imaging in spinal cord injury.

BACKGROUND: The ability of diffusion tensor imaging (DTI) to complement conventional MR imaging by diagnosing subtle injuries to the spinal cord is a subject of intense research. We attempted to study change in the DTI indices, namely fractional anisotropy (FA) and mean diffusivity (MD) after traumatic cervical spinal cord injury and compared these with corresponding data from a control group of individuals with no injury. The correlation of these quantitative indices to the neurological profile of the patients was assessed. MATERIAL AND METHODS: 20 cases of acute cervical trauma and 30 age and sex matched healthy controls were enrolled. Scoring of extent of clinical severity was done based on the Frankel grading system. MRI was performed on a 3T system. Following the qualitative tractographic evaluation of white matter tracts, quantitative datametrics were calculated. RESULTS: In patients, the Mean FA value at the level of injury (0.43+/-0.08) was less than in controls (0.62+/-0.06), which was statistically significant (p value <0.001). Further, the Mean MD value at the level of injury (1.30+/-0.24) in cases was higher than in controls (1.07+/-0.12, p value <0.001). Statistically significant positive correlation was found between clinical grading (Frankel grade) and FA values at the level of injury (r value=0.86). Negative correlation was found between clinical grade and Mean MD at the level of injury (r value=-0.38) which was however statistically not significant. CONCLUSION: Quantitative DTI indices are a useful parameter for detection of spinal cord injury. FA value was significantly decreased while MD value was significantly increased at the level of injury in cases as compared to controls. Further, FA showed significant correlation with clinical grade. DTI could thus serve as a reliable objective imaging tool for assessment of white matter integrity and prognostication of functional outcome.

Characterization of 'cold' vertebrae on 18F-FDG PET/CT.

INTRODUCTION: A photon-deficient ('cold') vertebra on fluorine-18 fluorodeoxyglucose (F-FDG) PET is a known entity and can arise as a result of varying etiologies. A proper interpretation of this observation is required to make an accurate diagnosis for appropriate management. METHODS: Twelve cases with 'cold' vertebrae on F-FDG PET/computed tomography (CT) were selected and analyzed from a population of 600 patients with a known malignancy who had undergone whole-body F-FDG PET/CT for staging, disease viability assessment, response to treatment, or suspected recurrence purposes. The patterns were studied and correlated with clinical history and the results of the low-dose CT performed with the PET scan for attenuation correction and anatomical localization. RESULTS: The most common cause for cold vertebrae was found to be postexternal radiotherapy, causing photopenia involving multiple vertebrae corresponding to the radiotherapy portals. Two other causes found in the study were the destruction of the vertebral marrow cavity by metastatic tumor cells and vertebral hemangioma. Characteristic features of 'cold' vertebrae have been described in the study with illustrations. CONCLUSION: Pattern recognition coupled with clinical history and CT correlation of 'cold' vertebrae on F-FDG PET/CT can help in diagnosing the correct underlying etiology, which can help in better management of the patients.

Traumatic brain injury and the post-concussion syndrome: A diffusion tensor tractography study.

AIM: The aim of the present study is to evaluate diffusion tensor tractography (DTT) as a tool for detecting diffuse axonal injury in patients of acute, mild, and moderate traumatic brain injury (TBI), using two diffusion variables: Fractional anisotropy (FA) and mean diffusivity (MD). The correlation of these indices with the severity of post-concussive symptoms was also assessed. MATERIALS AND METHODS: Nineteen patients with acute, mild, or moderate TBI and twelve age- and sex-matched healthy controls were recruited. Following Magnetic Resonance Imaging (MRI) on a 3.0-T scanner, DTT was performed using the 'fiber assignment by continuous tracking' (FACT) algorithm for fiber reconstruction. Appropriate statistical tools were used to see the difference in FA and MD values between the control and patient groups. In the latter group, the severity of post-concussive symptoms was assessed six months following trauma, using the Rivermead Postconcussion Symptoms Questionnaire (RPSQ). RESULTS: The patients displayed significant reduction in FA compared to the controls (P < 0.05) in several tracts, notably the corpus callosum, fornix, bilateral uncinate fasciculus, and bilateral superior thalamic radiations. Changes in MD were statistically significant in the left uncinate, inferior longitudinal fasciculus, and left posterior thalamic radiation. A strong correlation between these indices and the RPSQ scores was observed in several white matter tracts. CONCLUSION: Diffusion tensor imaging (DTI)-based quantitative analysis in acute, mild, and moderate TBI can identify axonal injury neuropathology, over and above that visualized on conventional MRI scans. Furthermore, the significant correlation observed between FA and MD indices and the severity of post-concussive symptoms could make it a useful predictor of the long-term outcome.

Combined (18)F-FDG and (11)C-Methionine PET/CT scans in a case of metastatic hepatocellular carcinoma.

A 37-year-old male who underwent a central hepatectomy of the liver for hepatocellular carcinoma (HCC) was referred for an (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) study to rule out tumor recurrence or metastases. The scan showed a recurrent hepatic mass at the operative site, along with low-grade uptake in bilateral pulmonary metastases, mediastinal and hilar lymph nodes, and few skeletal sites. A non-FDG avid intracranial extradural mass was visualized in the right frontal lobe. The (11)C-methionine PET/CT scan performed subsequently revealed a larger area of involvement at the primary site, along with widespread metastases to the lungs, mediastinal, hilar, and abdominal lymph nodes, and multiple skeletal sites. Further, dural metastasis with high tracer uptake was noted in the frontal region. To the best of our knowledge, this is the first case documented in the literature, wherein (11)C-methionine PET/CT played a significant role in delineating the widespread dissemination, including the extremely rare dural involvement in a case of HCC. This report highlights the potential value of (11)C-methionine PET/CT in assessing the hepatic and extrahepatic tumor burden in cases of HCC, especially in clinically unexpected locations.