Longitudinal alteration of cortical thickness and volume in high-impact sports.

Collegiate football athletes are subject to repeated head impacts. The purpose of this study was to determine whether this exposure can lead to changes in brain structure. This prospective cohort study was conducted with up to 4 years of follow-up on 63 football (high-impact) and 34 volleyball (control) male collegiate athletes with a total of 315 MRI scans (after exclusions: football n â€‹= â€‹50, volleyball n â€‹= â€‹24, total scans â€‹= â€‹273) using high-resolution structural imaging. Volumetric and cortical thickness estimates were derived using FreeSurfer 5.3's longitudinal pipeline. A linear mixed-effects model assessed the effect of group (football vs. volleyball), time from baseline MRI, and the interaction between group and time. We confirmed an expected developmental decrement in cortical thickness and volume in our cohort (p â€‹< â€‹.001). Superimposed on this, total cortical gray matter volume (p â€‹= â€‹.03) and cortical thickness within the left hemisphere (p â€‹= â€‹.04) showed a group by time interaction, indicating less age-related volume reduction and thinning in football compared to volleyball athletes. At the regional level, sport by time interactions on thickness and volume were identified in the left orbitofrontal (p â€‹= â€‹.001), superior temporal (p â€‹= â€‹.001), and postcentral regions (p â€‹< â€‹.001). Additional cortical thickness interactions were found in the left temporal pole (p â€‹= â€‹.003) and cuneus (p â€‹= â€‹.005). At the regional level, we also found main effects of sport in football athletes characterized by reduced volume in the right hippocampus (p â€‹= â€‹.003), right superior parietal cortical gray (p â€‹< â€‹.001) and white matter (p â€‹< â€‹.001), and increased volume of the left pallidum (p â€‹= â€‹.002). Within football, cortical thickness was higher with greater years of prior play (left hemisphere p â€‹= â€‹.013, right hemisphere p â€‹= â€‹.005), and any history of concussion was associated with less cortical thinning (left hemisphere p â€‹= â€‹.010, right hemisphere p â€‹= â€‹.011). Additionally, both position-associated concussion risk (p â€‹= â€‹.002) and SCAT scores (p â€‹= â€‹.023) were associated with less of the expected volume decrement of deep gray structures. This prospective longitudinal study comparing football and volleyball athletes shows divergent age-related trajectories of cortical thinning, possibly reflecting an impact-related alteration of normal cortical development. This warrants future research into the underlying mechanisms of impacts to the head on cortical maturation.

Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features.

PURPOSE: To derive quantitative image features from magnetic resonance (MR) images that characterize the radiographic phenotype of glioblastoma multiforme (GBM) lesions and to create radiogenomic maps associating these features with various molecular data. MATERIALS AND METHODS: Clinical, molecular, and MR imaging data for GBMs in 55 patients were obtained from the Cancer Genome Atlas and the Cancer Imaging Archive after local ethics committee and institutional review board approval. Regions of interest (ROIs) corresponding to enhancing necrotic portions of tumor and peritumoral edema were drawn, and quantitative image features were derived from these ROIs. Robust quantitative image features were defined on the basis of an intraclass correlation coefficient of 0.6 for a digital algorithmic modification and a test-retest analysis. The robust features were visualized by using hierarchic clustering and were correlated with survival by using Cox proportional hazards modeling. Next, these robust image features were correlated with manual radiologist annotations from the Visually Accessible Rembrandt Images (VASARI) feature set and GBM molecular subgroups by using nonparametric statistical tests. A bioinformatic algorithm was used to create gene expression modules, defined as a set of coexpressed genes together with a multivariate model of cancer driver genes predictive of the module's expression pattern. Modules were correlated with robust image features by using the Spearman correlation test to create radiogenomic maps and to link robust image features with molecular pathways. RESULTS: Eighteen image features passed the robustness analysis and were further analyzed for the three types of ROIs, for a total of 54 image features. Three enhancement features were significantly correlated with survival, 77 significant correlations were found between robust quantitative features and the VASARI feature set, and seven image features were correlated with molecular subgroups (P < .05 for all). A radiogenomics map was created to link image features with gene expression modules and allowed linkage of 56% (30 of 54) of the image features with biologic processes. CONCLUSION: Radiogenomic approaches in GBM have the potential to predict clinical and molecular characteristics of tumors noninvasively. Online supplemental material is available for this article.

Neuroradiologic Evaluation of MRI in High-Contact Sports.

Background and Purpose: Athletes participating in high-contact sports experience repeated head trauma. Anatomical findings, such as a cavum septum pellucidum, prominent CSF spaces, and hippocampal volume reductions, have been observed in cases of mild traumatic brain injury. The extent to which these neuroanatomical findings are associated with high-contact sports is unknown. The purpose of this study was to determine whether there are subtle neuroanatomic differences between athletes participating in high-contact sports compared to low-contact athletic controls. Materials and Methods: We performed longitudinal structural brain MRI scans in 63 football (high-contact) and 34 volleyball (low-contact control) male collegiate athletes with up to 4 years of follow-up, evaluating a total of 315 MRI scans. Board-certified neuroradiologists performed semi-quantitative visual analysis of neuroanatomic findings, including: cavum septum pellucidum type and size, extent of perivascular spaces, prominence of CSF spaces, white matter hyperintensities, arterial spin labeling perfusion asymmetries, fractional anisotropy holes, and hippocampal size. Results: At baseline, cavum septum pellucidum length was greater in football compared to volleyball controls (p = 0.02). All other comparisons were statistically equivalent after multiple comparison correction. Within football at baseline, the following trends that did not survive multiple comparison correction were observed: more years of prior football exposure exhibited a trend toward more perivascular spaces (p = 0.03 uncorrected), and lower baseline Standardized Concussion Assessment Tool scores toward more perivascular spaces (p = 0.02 uncorrected) and a smaller right hippocampal size (p = 0.02 uncorrected). Conclusion: Head impacts in high-contact sport (football) athletes may be associated with increased cavum septum pellucidum length compared to low-contact sport (volleyball) athletic controls. Other investigated neuroradiology metrics were generally equivalent between sports.

Longitudinal Changes in Hippocampal Subfield Volume Associated with Collegiate Football.

Collegiate football athletes are subject to repeated traumatic brain injuriesthat may cause brain injury. The hippocampus is composed of several distinct subfields with possible differential susceptibility to injury. The aim of this study is to determine whether there are longitudinal changes in hippocampal subfield volume in collegiate football. A prospective cohort study was conducted over a 5-year period tracking 63 football and 34 volleyball male collegiate athletes. Athletes underwent high-resolution structural magnetic resonance imaging, and automated segmentation provided hippocampal subfield volumes. At baseline, football (n = 59) athletes demonstrated a smaller subiculum volume than volleyball (n = 32) athletes (-67.77 mm3; p = 0.012). A regression analysis performed within football athletes similarly demonstrated a smaller subiculum volume among those at increased concussion risk based on athlete position (p = 0.001). For the longitudinal analysis, a linear mixed-effects model assessed the interaction between sport and time, revealing a significant decrease in cornu ammonis area 1 (CA1) volume in football (n = 36) athletes without an in-study concussion compared to volleyball (n = 23) athletes (volume difference per year = -35.22 mm3; p = 0.005). This decrease in CA1 volume over time was significant when football athletes were examined in isolation from volleyball athletes (p = 0.011). Thus, this prospective, longitudinal study showed a decrease in CA1 volume over time in football athletes, in addition to baseline differences that were identified in the downstream subiculum. Hippocampal changes may be important to study in high-contact sports.

CT, MRI, PET, PET/CT, and ultrasound in the evaluation of obstetric and gynecologic patients.

The role of imaging in obstetrics and gynecology has undergone a revolution over the past few decades. Well-established methods such as endovaginal ultrasound have had a central role in the evaluation of nongravid patients with pelvic pain, as well as in the workup for ectopic pregnancy and evaluation of adnexal masses. Additional tools include MRI in the evaluation of appendicitis and other potentially surgical conditions in pregnant patients and MRI and CT in the evaluation of surgical complications. Newer tools in the radiology armamentarium include PET scanning which, alongside MRI and CT, are often helpful in staging gynecologic malignancy. The role of imaging in the obstetric and gynecology patient will continue to change as new modalities and techniques are introduced.

Asymmetric Hearing Loss Prompting MRI Referral in a Military Population: Redefining Audiometric Criteria.

Objective To reevaluate asymmetric sensorineural hearing loss (ASNHL) criteria used to justify magnetic resonance imaging (MRI) in the evaluation of retrocochlear tumors in a military population. Study Design Retrospective case-control study. Setting Tertiary care military medical center. Subjects and Methods Patients with military service and a history of ASNHL prompting referral for MRI, with or without retrocochlear tumors, were compared between 2005 and 2016. Predictor variables included pure tone ASNHL, speech audiometry, and a history of noise exposure. Logistic regression models for hearing asymmetries were performed, and receiver operator curves were used to calculate sensitivity and specificity. Results Thirty-eight retrocochlear tumors were identified. The MRI diagnosis rate for patients with ASHNL was 0.85%. Patients with tumors were slightly older (42 vs 37 years, P = .021) and had less noise exposure (47% vs 85%, P < .001). A sensitivity of 0.83 and a specificity of 0.58 were calculated for asymmetries ≥10 dB at 2000 Hz without adjusting for noise exposure. Instituting this imaging threshold would have reduced the number of MRI scans by half while missing 16% of tumors. Conclusion The tumor diagnosis rate among those undergoing MRI for ASNHL is low in the military population, likely because service-related noise exposure commonly causes ASNHL. Optimal MRI referral criteria should conserve resources while balancing the risks of over- and underdiagnosis. For those with a history of military service, an asymmetry ≥10 dB at 2000 Hz among patients meeting current ANSHL referral criteria is most predictive of a retrocochlear tumor.

Magnetic resonance perfusion image features uncover an angiogenic subgroup of glioblastoma patients with poor survival and better response to antiangiogenic treatment.

BACKGROUND: In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies. METHODS: Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts. Unsupervised consensus clustering was performed to identify robust clusters of GBM in each cohort. Cox survival and gene set enrichment analyses were conducted to characterize the clinical significance and molecular pathway activities of the clusters. The differential treatment efficacy of antiangiogenic therapy between the clusters was evaluated. RESULTS: A subgroup of patients with elevated perfusion features was identified and was significantly associated with poor patient survival after accounting for other clinical covariates (P values <.01; hazard ratios > 3) consistently found in both cohorts. Angiogenesis and hypoxia pathways were enriched in this subgroup of patients, suggesting the potential efficacy of antiangiogenic therapy. Patients of the angiogenic subgroups pooled from both cohorts, who had chemotherapy information available, had significantly longer survival when treated with antiangiogenic therapy (log-rank P=.022). CONCLUSIONS: Our findings suggest that an angiogenic subtype of GBM patients may benefit from antiangiogenic therapy with improved overall survival.

Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities.

Glioblastoma (GBM) is the most common and highly lethal primary malignant brain tumor in adults. There is a dire need for easily accessible, noninvasive biomarkers that can delineate underlying molecular activities and predict response to therapy. To this end, we sought to identify subtypes of GBM, differentiated solely by quantitative magnetic resonance (MR) imaging features, that could be used for better management of GBM patients. Quantitative image features capturing the shape, texture, and edge sharpness of each lesion were extracted from MR images of 121 single-institution patients with de novo, solitary, unilateral GBM. Three distinct phenotypic "clusters" emerged in the development cohort using consensus clustering with 10,000 iterations on these image features. These three clusters--pre-multifocal, spherical, and rim-enhancing, names reflecting their image features--were validated in an independent cohort consisting of 144 multi-institution patients with similar tumor characteristics from The Cancer Genome Atlas (TCGA). Each cluster mapped to a unique set of molecular signaling pathways using pathway activity estimates derived from the analysis of TCGA tumor copy number and gene expression data with the PARADIGM (Pathway Recognition Algorithm Using Data Integration on Genomic Models) algorithm. Distinct pathways, such as c-Kit and FOXA, were enriched in each cluster, indicating differential molecular activities as determined by the image features. Each cluster also demonstrated differential probabilities of survival, indicating prognostic importance. Our imaging method offers a noninvasive approach to stratify GBM patients and also provides unique sets of molecular signatures to inform targeted therapy and personalized treatment of GBM.

Linoleic acid metabolites act to increase contractility in isolated rat heart.

Previous in vivo studies in dogs suggest that the 9,10-monoepoxide of linoleic acid (9,10-cis-epoxyoctadecenoic acid [9,10-EOA]) has toxic cardiovascular effects that result in death at higher doses. More recent work with rabbit renal proximal tubule cells suggests that the 12,13-metabolites of linoleic acid are more toxic than the 9,10-isomers. Thus, in the current study, we tested the hypothesis that 12,13-EOA and 12,13-dihydroxyoctadecadienoic acid (12,13-DHOA) have direct adverse effects on the heart. Langendorff-perfused rat hearts were exposed to 30 microM linoleic acid, 30 microM 12,13-EOA, or 30 microM 12,13-DHOA for 60 min followed by a 30-min recovery period. As indicated by peak left intraventricular pressure and/or +dP/dt(max), all three of the agents elicited moderate increases in contractile function that peaked within 10 20 min. The effects of linoleic acid and 12,13-EOA returned to control values during the remainder of the 60-min exposure, whereas the positive inotropic response to 12,13-DHOA was maintained until washout. Sustained arrhythmias and negative inotropic actions were not observed with any of the three compounds. Subsequently, the monoepoxides were infused into conscious rats (35 mg/kg/h) while blood pressure, heart rate, and EKG were monitored for 24 h using biotelemetry techniques. The only effect observed was a slight decline in blood pressure. Thus, current data suggest that linoleic acid and its oxidative metabolites do not have direct cardiotoxic effects during acute exposure.

Linoleic acid, cis-epoxyoctadecenoic acids, and dihydroxyoctadecadienoic acids are toxic to Sf-21 cells in the absence of albumin.

Conversion of 12,13-cis-epoxyoctadecenoic acid (12,13-EOA) to 12,13-dihydroxyoctadecenoic acid (12,13-DHOA) by soluble epoxide hydrolase has been suggested to be a critical step in mediating the toxicity of epoxidized linoleic acid. The current study tests the hypothesis that low levels of albumin in the normal culturing media of Sf-21 cells can protect these cells from exposures to 12,13-EOA, but not 12,13-DHOA. In albumin-free media, Sf-21 cells exposed to 100 microM 12,13-EOA, and 12,13-DHOA for 1 min showed significant signs of mitochondrial dysfunction which led to cytotoxicity. The addition of bovine serum albumin (BSA) at a concentration (3 microM) found in normal serum-supplemented media protected Sf-21 cells exposed to 12,13-EOA, but not 12,13-DHOA while BSA (500 microM) fully protected Sf-21 cells exposed to these fatty acids. These data resolve previous discrepancies observed among in vitro models and help clarify our understanding of how these metabolites affect human health.

Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset thunderclap headache and focal neurologic deficits. Once thought to be a rare syndrome, more advanced non-invasive imaging has led to an increase in RCVS diagnosis. Unilateral vertebral artery dissection has been described in fewer than 40% of cases of RCVS. Bilateral vertebral artery dissection has rarely been reported. We describe the case of a patient with RCVS and bilateral vertebral artery dissection presenting with an intramedullary infarct treated successfully with medical management and careful close follow-up. This rare coexistence should be recognized as the treatment differs.

Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset thunderclap headache and focal neurologic deficits. Once thought to be a rare syndrome, more advanced non-invasive imaging has led to an increase in RCVS diagnosis. Unilateral vertebral artery dissection has been described in fewer than 40% of cases of RCVS. Bilateral vertebral artery dissection has rarely been reported. We describe the case of a patient with RCVS and bilateral vertebral artery dissection presenting with an intramedullary infarct treated successfully with medical management and careful close follow-up. This rare coexistence should be recognized as the treatment differs.

Spinal epidural abscess due to tropical pyomyositis in immunocompetent adolescents.

Pyomyositis, a suppurative infection of skeletal muscle, is a disease not frequently encountered by neurosurgical providers. While previously considered an infection localized to tropical and semitropical locations, clinical reports of pyomyositis in temperate climates have increased over the past decade. Paraspinal involvement is uncommon in pyomyositis; however, the potential exists for spread into the epidural space resulting in a spinal epidural abscess (SEA). Early diagnosis of an SEA is frequently hampered by the absence of specific signs, unfamiliarity with the disease, atypical manifestations, and a broad differential diagnosis that includes more common causes of back pain. To date, 1 such case of paraspinal pyomyositis associated with an SEA has been reported in the neurosurgical literature. The authors present 2 cases of pyomyositis with an SEA and review the epidemiology, pathophysiology, diagnostic workup, and management of this disorder.

Paraspinal Tropical Pyomyositis and Epidural Abscesses Presenting as Low Back Pain.

We present the case of a 13-year-old patient who presented to the Emergency Department with low back and flank pain. Cross sectional imaging revealed paraspinal pyomyositis and epidural abscess. A detailed patient history revealed a recent lower extremity skin infection consistent with tropical pyomyositis. Review of this case shows the importance for recommending either contrast enhanced computed tomography (CT) imaging of the spine and/or magnetic resonance imaging (MRI) in patients with a recent skin infection and acute onset of back pain.