Cerebellar Microstructural Abnormalities in Obsessive-Compulsive Disorder (OCD): a Systematic Review of Diffusion Tensor Imaging Studies.

Previous neuroimaging studies have suggested that obsessive-compulsive disorder (OCD) is associated with altered resting-state functional connectivity of the cerebellum. In this study, we aimed to describe the most significant and reproducible microstructural abnormalities and cerebellar changes associated with obsessive-compulsive disorder (OCD) using diffusion tensor imaging (DTI) investigations. PubMed and EMBASE were searched for relevant studies using the PRISMA 2020 protocol. A total of 17 publications were chosen for data synthesis after screening titles and abstracts, full-text examination, and executing the inclusion criteria. The patterns of cerebellar white matter (WM) integrity loss, determined by fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) metrics, varied across studies and symptoms. Changes in fractional anisotropy (FA) values were described in six publications, which were decreased in four and increased in two studies. An increase in diffusivity parameters of the cerebellum (i.e., MD, RD, and AD) in OCD patients was reported in four studies. Alterations of the cerebellar connectivity with other brain areas were also detected in three studies. Heterogenous results were found in studies that investigated cerebellar microstructural abnormalities in correlation with symptom dimension or severity. OCD's complex phenomenology may be characterized by changes in cerebellar WM connectivity across wide networks, as shown by DTI studies on OCD patients in both children and adults. Classification features in machine learning and clinical tools for diagnosing OCD and determining the prognosis of the disorder might both benefit from using cerebellar DTI data.

Imaging predictors of 4q12 amplified and RB1 mutated glioblastoma IDH-wildtype.

INTRODUCTION: Recent studies have identified that glioblastoma IDH-wildtype consists of different molecular subgroups with distinct prognoses. In order to accurately describe and classify gliomas, the Visually AcceSAble Rembrandt Images (VASARI) system was developed. The goal of this study was to evaluate the VASARI characteristics in molecular subgroups of IDH-wildtype glioblastoma. METHODS: A retrospective analysis of glioblastoma IDH- wildtype with comprehensive next-generation sequencing and pre-operative and post-operative MRI was performed. VASARI characteristics and 205 genes were evaluated. Multiple comparison adjustment by the Bejamin-Hochberg false discovery rate (BH-FDR) was performed. A 1:3 propensity score match (PSM) with a Caliper of 0.2 was done. RESULTS: 178 patients with GBM IDH-WT met the inclusion criteria. 4q12 amplified patients (n = 20) were associated with cyst presence (30% vs. 12%, p = 0.042), decreased hemorrhage (35% vs. 62%, p = 0.028), and non-restricting/mixed (35%/60%) rather than restricting diffusion pattern (5%), meanwhile, 4q12 non-amplified patients had mostly restricting (47.4%) rather than a non-restricting/mixed diffusion pattern (28.4%/23.4%). This remained statistically significant after BH-FDR adjustment (p = 0.002). PSM by 4q12 amplification showed that diffusion characteristics continued to be significantly different. Among RB1-mutant patients, 96% had well-defined enhancing margins vs. 70.6% of RB1-WT (p = 0.018), however, this was not significant after BH-FDR or PSM. CONCLUSIONS: Patients with glioblastoma IDH-wildtype harboring 4q12 amplification rarely have restricting DWI patterns compared to their wildtype counterparts, in which this DWI pattern is present in ~ 50% of patients. This suggests that some phenotypic imaging characteristics can be identified among molecular subtypes of IDH-wildtype glioblastoma.

Human Adenovirus Type 4 Comprises Two Major Phylogroups with Distinct Replicative Fitness and Virulence Phenotypes.

Human adenovirus type 4 (HAdV-E4) is the only type (and serotype) classified at present within species Human mastadenovirus E that has been isolated from a human host. Recent phylogenetic analysis of whole-genome sequences of strains representing the spectrum of intratypic genetic diversity described to date identified two major evolutionary lineages designated phylogroups (PGs) I and II and validated the early clustering of HAdV-E4 genomic variants into two major groups by low-resolution restriction fragment length polymorphism analysis. In this study, we expanded our original analysis of intra- and inter-PG genetic variability and used a panel of viruses representative of the spectrum of genetic diversity described for HAdV-E4 to examine the magnitude of inter- and intra-PG phenotypic diversity using an array of cell-based assays and a cotton rat model of HAdV respiratory infection. Our proteotyping of HAdV-E strains using concatenated protein sequences in selected coding regions including E1A, E1B-19K and -55K, DNA polymerase, L4-100K, various E3 proteins, and E4-34K confirmed that the two clades encode distinct variants/proteotypes at most of these loci. Our in vitro and in vivo studies demonstrated that PG I and PG II differ in their growth, spread, and cell-killing phenotypes in cell culture and in their pulmonary pathogenic phenotypes. Surprisingly, the differences in replicative fitness documented in vitro between PGs did not correlate with the differences in virulence observed in the cotton rat model. This body of work is the first reporting phenotypic correlates of naturally occurring intratypic genetic variability for HAdV-E4. IMPORTANCE Human adenovirus type 4 (HAdV-E4) is a prevalent causative agent of acute respiratory illness of variable severity and of conjunctivitis and comprises two major phylogroups that carry distinct coding variations in proteins involved in viral replication and modulation of host responses to infection. Our data show that phylogroup (PG) I and PG II are intrinsically different regarding their ability to grow and spread in culture and to cause pulmonary disease in cotton rats. This is the first report of phenotypic divergence among naturally occurring known genetic variants of an HAdV type of medical importance. This research reveals readily detectable phenotypic differences between strains representing phylogroups I and II, and it introduces a unique experimental system for the elucidation of the genetic basis of adenovirus fitness and virulence and thus for increasing our understanding of the implications of intratypic genetic diversity in the presentation and course of HAdV-E4-associated disease.

Evolution of protection after maternal immunization for respiratory syncytial virus in cotton rats.

Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life. In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge. Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization. We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth. However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age. This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy. The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.

The Cortico-Limbo-Thalamo-Cortical Circuits: An Update to the Original Papez Circuit of the Human Limbic System.

The Papez circuit, first proposed by James Papez in 1937, is a circuit believed to control memory and emotions, composed of the cingulate cortex, entorhinal cortex, parahippocampal gyrus, hippocampus, hypothalamus, and thalamus. Pursuant to James Papez, Paul Yakovlev and Paul MacLean incorporated the prefrontal/orbitofrontal cortex, septum, amygdalae, and anterior temporal lobes into the limbic system. Over the past few years, diffusion-weighted tractography techniques revealed additional limbic fiber connectivity, which incorporates multiple circuits to the already known complex limbic network. In the current review, we aimed to comprehensively summarize the anatomy of the limbic system and elaborate on the anatomical connectivity of the limbic circuits based on the published literature as an update to the original Papez circuit.

Cerebellar Microstructural Abnormalities in Parkinson's Disease: a Systematic Review of Diffusion Tensor Imaging Studies.

Diffusion tensor imaging (DTI) is now having a strong momentum in research to evaluate the neural fibers of the CNS. This technique can study white matter (WM) microstructure in neurodegenerative disorders, including Parkinson's disease (PD). Previous neuroimaging studies have suggested cerebellar involvement in the pathogenesis of PD, and these cerebellum alterations can correlate with PD symptoms and stages. Using the PRISMA 2020 framework, PubMed and EMBASE were searched to retrieve relevant articles. Our search revealed 472 articles. After screening titles and abstracts, and full-text review, and implementing the inclusion criteria, 68 papers were selected for synthesis. Reviewing the selected studies revealed that the patterns of reduction in cerebellum WM integrity, assessed by fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity measures can differ symptoms and stages of PD. Cerebellar diffusion tensor imaging (DTI) changes in PD patients with "postural instability and gait difficulty" are significantly different from "tremor dominant" PD patients. Freezing of the gate is strongly related to cerebellar involvement depicted by DTI. The "reduced cognition," "visual disturbances," "sleep disorders," "depression," and "olfactory dysfunction" are not related to cerebellum microstructural changes on DTI, while "impulsive-compulsive behavior" can be linked to cerebellar WM alteration. Finally, higher PD stages and longer disease duration are associated with cerebellum white matter alteration depicted by DTI. Depiction of cerebellar white matter involvement in PD is feasible by DTI. There is an association with disease duration and severity and several clinical presentations with DTI findings. This clinical-imaging association may eventually improve disease management.

The Role of Apparent Diffusion Coefficient Values in Glioblastoma: Differentiating Tumor Progression Versus Treatment-Related Changes.

OBJECTIVE: Glioblastoma represents the most common primary brain malignancy with a median survival of 15 months. Follow-up examinations are crucial to establish the presence of tumor recurrence, as well as treatment-associated changes such as ischemic infarction and radiation effects. Even though magnetic resonance imaging is a valuable tool, a histopathological diagnosis is often required because of imaging overlap between tumor recurrence and treatment associated changes. We set out to measure the apparent diffusion coefficient (ADC) values of the lesions in magnetic resonance imaging scans of treated glioblastoma patients to investigate if ADC values could accurately differentiate between tumor progression, radiation-related changes, and ischemic infarctions. METHODS: We evaluated ADC values among 3 groups, patients with tumor progression, radiation necrosis, and ischemic infarctions. The regions of interest were placed in the areas of greatest hypointensity among solid lesions using the ADC maps, excluding areas with necrotic, cystic, or hemorrhagic changes. The ADC values of the contralateral normal appearing white matter were also measured as the reference value for each patient. The relative ADC (rADC) values were measured for all 3 groups. Comparison between lesions and normal white matter was evaluated by Wilcoxon signed test. RESULTS: A total of 157 patients were included in the study; 49 patients classified as tumor progression, 58 patients as radiation necrosis, and 50 patients as ischemic infarctions. The mean ± SD ADC value was 752.8 ± 132.5 for tumor progression, 479.0 ± 105.2 for radiation-related changes, and 250.1 ± 57.2 for ischemic infarctions. The mean ± SD rADC value was 1.07 ± 0.22 for tumor progression, 0.66 ± 0.14 for radiation necrosis, and 0.34 ± 0.08 for ischemic infarctions. The mean rADC values were significantly higher in tumor progression, compared with both radiation necrosis and ischemic changes ( P < 0.001). CONCLUSIONS: The present study demonstrates that ADC values are a helpful tool to differentiate between tumor progression, radiation necrosis, and posttreatment ischemic changes.

Alternative Virus-Like Particle-Associated Prefusion F Proteins as Maternal Vaccines for Respiratory Syncytial Virus.

Maternal vaccination may be the most effective and safest approach to the protection of infants from respiratory syncytial virus (RSV) infection, a severe acute lower respiratory tract disease in infants and young children worldwide. We previously compared five different virus-like particle (VLP)-associated, mutation-stabilized prefusion F (pre-F) proteins, including the prototype DS-Cav1 F VLPs. We showed that alternative versions of prefusion F proteins have different conformations and induce different populations of anti-F protein antibodies. Two of these alternative pre-F VLPs, the UC-2 F and UC-3 F VLPs, stimulated in mice higher titers of neutralizing antibodies than DS-Cav1 F VLPs (M. L. Cullen, R. M. Schmidt, M. G. Torres, A. A. Capoferri, et al., Vaccines 7:21-41, 2019, https://doi.org/10.3390/vaccines7010021). Here we describe a comparison of these two pre-F VLPs with DS-Cav1 F VLPs as maternal vaccines in cotton rats and report that UC-3 F VLPs significantly increased the neutralizing antibody (NAb) titers in pregnant dams compared to DS-Cav1 F VLPs. The neutralizing antibody titers in the sera of the offspring of the dams immunized with UC-3 F VLPs were significantly higher than those in the sera of the offspring of dams immunized with DS-Cav1 VLPs. This increase in serum NAb titers translated to a 6- to 40-fold lower virus titer in the lungs of the RSV-challenged offspring of dams immunized with UC-3 F VLPs than in the lungs of the RSV-challenged offspring of dams immunized with DS-Cav1 F VLPs. Importantly, the offspring of UC-3 F VLP-immunized dams showed significant protection from lung pathology and from induction of inflammatory lung cytokine mRNA expression after RSV challenge. Immunization with UC-3 F VLPs also induced durable levels of high-titer neutralizing antibodies in dams.IMPORTANCE Respiratory syncytial virus (RSV) is a significant human pathogen severely impacting neonates and young children, but no vaccine exists to protect this vulnerable population. Furthermore, direct vaccination of neonates is likely ineffective due to the immaturity of their immune system, and neonate immunization is potentially unsafe. Maternal vaccination may be the best and safest approach to the protection of neonates through the passive transfer of maternal neutralizing antibodies in utero to the fetus after maternal immunization. Here we report that immunization of pregnant cotton rats, a surrogate model for human maternal immunization, with novel RSV virus-like particle (VLP) vaccine candidates containing stabilized prefusion RSV F proteins provides significant levels of protection of the offspring of immunized dams from RSV challenge. We also found that antibodies induced by VLPs containing different versions of the prefusion F protein varied by 40-fold in the extent of protection provided to the offspring of vaccinated dams upon RSV challenge.

Automated image quality evaluation of structural brain MRI using an ensemble of deep learning networks.

BACKGROUND: Deep learning (DL) is a promising methodology for automatic detection of abnormalities in brain MRI. PURPOSE: To automatically evaluate the quality of multicenter structural brain MRI images using an ensemble DL model based on deep convolutional neural networks (DCNNs). STUDY TYPE: Retrospective. POPULATION: The study included 1064 brain images of autism patients and healthy controls from the Autism Brain Imaging Data Exchange (ABIDE) database. MRI data from 110 multiple sclerosis patients from the CombiRx study were included for independent testing. SEQUENCE: T1 -weighted MR brain images acquired at 3T. ASSESSMENT: The ABIDE data were separated into training (60%), validation (20%), and testing (20%) sets. The ensemble DL model combined the results from three cascaded networks trained separately on the three MRI image planes (axial, coronal, and sagittal). Each cascaded network consists of a DCNN followed by a fully connected network. The quality of image slices from each plane was evaluated by the DCNN and the resultant image scores were combined into a volumewise quality rating using the fully connected network. The DL predicted ratings were compared with manual quality evaluation by two experts. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve, area under ROC curve (AUC), sensitivity, specificity, accuracy, and positive (PPV) and negative (NPV) predictive values. RESULTS: The AUC, sensitivity, specificity, accuracy, PPV, and NPV for image quality evaluation of the ABIDE test set using the ensemble model were 0.90, 0.77, 0.85, 0.84, 0.42, and 0.96, respectively. On the CombiRx set the same model achieved performance of 0.71, 0.41, 0.84, 0.73, 0.48, and 0.80. DATA CONCLUSION: This study demonstrated the high accuracy of DL in evaluating image quality of structural brain MRI in multicenter studies. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1260-1267.

Standardizing Magnetic Resonance Imaging Protocols, Requisitions, and Reports in Multiple Sclerosis: An Update for Radiologist Based on 2017 Magnetic Resonance Imaging in Multiple Sclerosis and 2018 Consortium of Multiple Sclerosis Centers Consensus Guidelines.

The advent of magnetic resonance imaging has improved our understanding of the pathophysiology and natural course of multiple sclerosis (MS). The ability of magnetic resonance imaging to show the evolution of MS lesions on sequential scans has brought it to be one of the endpoints in clinical trials for disease-modifying therapies. Based on the most updated consensus guidelines from the American (Consortium of MS Centers) and European (Magnetic Resonance Imaging in MS) boards of experts in MS, this document shows the most relevant landmarks related to imaging findings, diagnostic criteria, indications to obtain a magnetic resonance, scan protocols and sequence options for patients with MS. Although incorporating the knowledge derived from the research arena into the daily clinical practice is always challenging, in this article, the authors provide useful recommendations to improve the information contained in the magnetic resonance report oriented to facilitate communication between radiologists and specialized medical teams involved in MS patients' multidisciplinary care.

Mapping the trajectory of the amygdalothalamic tract in the human brain.

Although the thalamus is not considered primarily as a limbic structure, abundant evidence indicates the essential role of the thalamus as a modulator of limbic functions indirectly through the amygdala. The amygdala is a central component of the limbic system and serves an essential role in modulating the core processes including the memory, decision-making, and emotional reactions. The amygdalothalamic pathway is the largest direct amygdalo-diencephalic connection in the primates including the human brain. Given the crucial role of the amygdalothalamic tract (ATT) in memory function and diencephalic amnesia in stroke patients, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. To date, few diffusion-weighted studies have focused on the amygdala, yet the fine neuronal connection of the amygdala and thalamus known as the ATT has yet to be elucidated. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the ATT in the human brain. We studied 15 healthy right-handed human subjects (12 men and 3 women with age range of 24-37 years old). Using a high-resolution diffusion tensor tractography technique, for the first time, we were able to reconstruct and measure the trajectory of the ATT. We further revealed the close relationship of the ATT with the temporopontine tract and the fornix bilaterally in 15 healthy adult human brains.

Proximal Tibia Fracture Through Suture Augmentation Sites Following ACL/MCL Repairs: A Case Report.

CASE: A 35-year-old man sustained a proximal tibia fracture from a low-energy mechanism 1 year after anterior cruciate and medial collateral ligament repairs with suture augmentation (SA). The fracture propagated through both tibial SA anchor sites. Following intramedullary tibial nailing, he returned to his prior level of function. CONCLUSION: While complications of SA for ligamentous procedures are rare, these techniques are being implemented more frequently and the full complication profile is yet to be determined. Our report documents a new complication and potential risk factors that surgeons should consider when performing SA for multiligament knee surgery in active individuals.

Automatic Active Lesion Tracking in Multiple Sclerosis Using Unsupervised Machine Learning.

BACKGROUND: Identifying active lesions in magnetic resonance imaging (MRI) is crucial for the diagnosis and treatment planning of multiple sclerosis (MS). Active lesions on MRI are identified following the administration of Gadolinium-based contrast agents (GBCAs). However, recent studies have reported that repeated administration of GBCA results in the accumulation of Gd in tissues. In addition, GBCA administration increases health care costs. Thus, reducing or eliminating GBCA administration for active lesion detection is important for improved patient safety and reduced healthcare costs. Current state-of-the-art methods for identifying active lesions in brain MRI without GBCA administration utilize data-intensive deep learning methods. OBJECTIVE: To implement nonlinear dimensionality reduction (NLDR) methods, locally linear embedding (LLE) and isometric feature mapping (Isomap), which are less data-intensive, for automatically identifying active lesions on brain MRI in MS patients, without the administration of contrast agents. MATERIALS AND METHODS: Fluid-attenuated inversion recovery (FLAIR), T2-weighted, proton density-weighted, and pre- and post-contrast T1-weighted images were included in the multiparametric MRI dataset used in this study. Subtracted pre- and post-contrast T1-weighted images were labeled by experts as active lesions (ground truth). Unsupervised methods, LLE and Isomap, were used to reconstruct multiparametric brain MR images into a single embedded image. Active lesions were identified on the embedded images and compared with ground truth lesions. The performance of NLDR methods was evaluated by calculating the Dice similarity (DS) index between the observed and identified active lesions in embedded images. RESULTS: LLE and Isomap, were applied to 40 MS patients, achieving median DS scores of 0.74 ± 0.1 and 0.78 ± 0.09, respectively, outperforming current state-of-the-art methods. CONCLUSIONS: NLDR methods, Isomap and LLE, are viable options for the identification of active MS lesions on non-contrast images, and potentially could be used as a clinical decision tool.

The Use of Apparent Diffusion Coefficient Values for Differentiating Bevacizumab-Related Cytotoxicity from Tumor Recurrence and Radiation Necrosis in Glioblastoma.

OBJECTIVES: Glioblastomas (GBM) are the most common primary invasive neoplasms of the brain. Distinguishing between lesion recurrence and different types of treatment related changes in patients with GBM remains challenging using conventional MRI imaging techniques. Therefore, accurate and precise differentiation between true progression or pseudoresponse is crucial in deciding on the appropriate course of treatment. This retrospective study investigated the potential of apparent diffusion coefficient (ADC) map values derived from diffusion-weighted imaging (DWI) as a noninvasive method to increase diagnostic accuracy in treatment response. METHODS: A cohort of 21 glioblastoma patients (mean age: 59.2 ± 11.8, 12 Male, 9 Female) that underwent treatment with bevacizumab were selected. The ADC values were calculated from the DWI images obtained from a standardized brain protocol across 1.5-T and 3-T MRI scanners. Ratios were calculated for rADC values. Lesions were classified as bevacizumab-induced cytotoxicity based on characteristic imaging features (well-defined regions of restricted diffusion with persistent diffusion restriction over the course of weeks without tissue volume loss and absence of contrast enhancement). The rADC value was compared to these values in radiation necrosis and recurrent lesions, which were concluded in our prior study. The nonparametric Wilcoxon signed rank test with p < 0.05 was used for significance. RESULTS: The mean ± SD age of the selected patients was 59.2 ± 11.8. ADC values and corresponding mean rADC values for bevacizumab-induced cytotoxicity were 248.1 ± 67.2 and 0.39 ± 0.10, respectively. These results were compared to the ADC values and corresponding mean rADC values of tumor progression and radiation necrosis. Significant differences between rADC values were observed in all three groups (p < 0.001). Bevacizumab-induced cytotoxicity had statistically significant lower ADC values compared to both tumor recurrence and radiation necrosis. CONCLUSION: The study demonstrates the potential of ADC values as noninvasive imaging biomarkers for differentiating recurrent glioblastoma from radiation necrosis and bevacizumab-induced cytotoxicity.

Comparison of 2 Robotic Systems for Pediatric Stereoelectroencephalography Implantation.

BACKGROUND: Stereoelectroencephalography (SEEG) remains critical in guiding epilepsy surgery. Robot-assisted techniques have shown promise in improving SEEG implantation outcomes but have not been directly compared. In this single-institution series, we compared ROSA and Stealth AutoGuide robots in pediatric SEEG implantation. METHODS: We retrospectively reviewed 21 sequential pediatric SEEG implantations consisting of 6 ROSA and 15 AutoGuide procedures. We determined mean operative time, time per electrode, root mean square (RMS) registration error, and surgical complications. Three-dimensional radial distances were calculated between each electrode's measured entry and target points with respective errors from the planned trajectory line. RESULTS: Mean overall/per electrode operating time was 73.5/7.5 minutes for ROSA and 126.1/10.9 minutes for AutoGuide (P = 0.030 overall, P = 0.082 per electrode). Mean RMS registration error was 0.77 mm (0.55-0.93 mm) for ROSA and 0.6 mm (0.2-1.0 mm) for AutoGuide (P = 0.26). No procedures experienced complications. The mean radial (entry point error was 1.23 ± 0.11 mm for ROSA and 2.65 ± 0.12 mm for AutoGuide (P < 0.001), while the mean radial target point error was 1.86 ± 0.15 mm for ROSA and 3.25 ± 0.16 mm for AutoGuide (P < 0.001). CONCLUSIONS: Overall operative time was greater for AutoGuide procedures, although there was no statistically significant difference in time per electrode. Both systems are highly accurate with no significant RMS error difference. While the ROSA robot yielded significantly lower entry and target point errors, both robots are safe and reliable for deep electrode insertion in pediatric epilepsy.

Unfolding the direct connectivity of the occipital cortex with the hypothalamic, septal and BNST nuclei of the human brain.

The hypothalamus plays essential roles in the human brain by regulating feeding, fear, aggression, reproductive behaviors, and autonomic activities. The septal nuclei and the bed nucleus of stria terminalis (BNST) are also known to be involved in control of autonomic, motivational, learning, emotional and associative processes in the human brain. Multiple animal dissection studies have revealed direct connectivity between central limbic gray matter nuclei and occipital cortex, particularly from the hypothalamic, septal and BNST nuclei. However, the detailed anatomy of this connectivity in the human brain has yet to be determined. The primary objective of this study was to explore the utility of high spatial and high angular resolution diffusion weighted tractography techniques for mapping the connectivity pathways between the occipital cortex and central limbic gray matter nuclei in the human brain. We studied 30 healthy adult human brains, delineated, and reconstructed the trajectory of the occipito-hypothalamic/septal/BNST for the first time in the human brain.

Development of Respiratory Syncytial Virus Vaccine Candidates for the Elderly.

Respiratory syncytial virus (RSV) is a significant threat to elderly populations and repeated infections that occur throughout life are poorly protective. To assess the role of prior RSV infections as well as elderly immune senescence on vaccine efficacy, we compared immune responses after virus-like particle (VLP) immunization of elderly cotton rats and young cotton rats, both previously RSV infected, in order to mimic the human population. We show that immunization of RSV-experienced young or elderly animals resulted in the same levels of anti-pre-F IgG, anti-G IgG, neutralizing antibody titers, and protection from challenge indicating that the delivery of F and G proteins in a VLP is equally effective in activation of protective responses in both elderly and young populations. Our results suggest that F and G protein-containing VLPs induce anti-RSV memory established in prior RSV infections equally well in both young and elderly animals and thus can be an effective vaccine for the elderly.

Introducing the "Temporal Thumb Sign" in Pediatric Patients With New-Onset Idiopathic Seizures With and Without Elevated Cerebrospinal Fluid Opening Pressure.

BACKGROUND: Temporal lobe changes, such as anterior temporal lobe meningoceles or encephaloceles, have been documented as possible epileptogenic foci in a subset of pediatric patients with seizures. In our study, we aim to analyze a different structural change in the temporal lobe, remodeling of the posterior temporal skull base by the inferior temporal gyrus called the "temporal thumb sign" (TTS), in pediatric patients presenting with new-onset seizures with or without elevated opening pressure (OP), patients presenting with confirmed diagnosis of idiopathic intracranial hypertension (IIH) without seizure presentation, and healthy controls. METHODS: Magnetic resonance imaging scans of 163 pediatric patients were studied retrospectively for the presence of TTS. We analyzed the scans of 43 patients with elevated OP and confirmed IIH, 40 patients with elevated OP and new-onset idiopathic seizures, 40 patients with normal OP and new-onset idiopathic seizures, and 40 age- and sex-matched healthy controls. RESULTS: The TTS was detected most frequently in patients with elevated OP and seizures at 72.5% compared with patients with IIH with no seizures and patients with normal OP and seizures (32.6% and 27.5%, respectively). The TTS had a frequency of 12.5% in the control group. The TTS had the highest combination of specificity and sensitivity (72.5% and 72.5%) in patients with seizures and elevated OP compared with patients with seizures and normal OP (P value < 0.001). CONCLUSIONS: Our results suggest the Kamali "temporal thumb sign" is a novel imaging feature that may be used as a sensitive and specific imaging finding associated with seizures and elevated OP in the pediatric population.