Treatment Options for Brain Metastases.

OPINION STATEMENT: Therapies for brain metastasis continue to evolve as the life expectancies for patients have continued to prolong. Novel advances include the use of improved technology for radiation delivery, surgical guidance, and response assessment, along with systemic therapies that can pass through the blood brain barrier. With increasing complexity of treatments and the increased need for salvage treatments, multi-disciplinary management has become significantly more important.

Automated extraction of heart rate variability from magnetoencephalography signals.

Magnetoencephalography (MEG) measures magnetic fluctuations in the brain generated by neural processes, some of which, such as cardiac signals, are generally removed as artifacts and discarded. However, heart rate variability (HRV) has long been regarded as a biomarker related to autonomic function, suggesting the cardiac signal in MEG contains valuable information that can provide supplemental health information about a patient. To enable access to these ancillary HRV data, we created an automated extraction tool capable of capturing HRV directly from raw MEG data with artificial intelligence. Five scans were conducted with simultaneous MEG and electrocardiogram (ECG) acquisition, which provides a ground truth metric for assessing our algorithms and data processing pipeline. In addition to directly comparing R-peaks between the MEG and ECG signals, this work explores the variation of the corresponding HRV output in time, frequency, and non-linear domains. After removing outlier intervals and aligning the ECG and derived cardiac MEG signals, the RMSE between the RR-intervals of each was RMSE1 = 2 ms, RMSE2 = 2 ms, RMSE3 = 8 ms, RMSE4 = 4 ms, RMSE5 = 13 ms. The findings indicate that cardiac artifacts from MEG data carry sufficient signal to approximate an individual's HRV metrics.

Study of the Natural Crystalline Lens Characteristics Using Dual-Energy Computed Tomography.

There is a paucity of radiologic literature regarding age-related cataract, and little is known about any differences in the imaging appearance of the natural crystalline lens on computed tomography (CT) exams among different demographic groups. In this retrospective review of 198 eyes in 103 adults who underwent dual-energy computed tomography (DECT) exams of the head, regions of interest spanning 3−5 mm were placed over the center of the lens, and the x-ray attenuation of each lens was recorded in Hounsfield Units (HU) at 3 energy levels: 40 keV, 70 keV, and 190 keV. Generalized estimating equations (GEEs) were used to assess the association of clinical or demographic data with lens attenuation. The mean HU values were significantly lower for the older vs. younger group at 40 keV (GEE p-value = 0.022), but there was no significant difference at higher energy levels (p > 0.05). Mean HU values were significantly higher for females vs. males and non-whites vs. non-Hispanic whites at all 3 energy levels in bivariate and multivariable analyses (all p-value < 0.05). There was no significant association between lens attenuation and either diabetes or smoking status. The crystalline lens of females and non-whites had higher attenuation on DECT which may suggest higher density or increased concentration of materials like calcium and increased potential for cataract formation. Given the large scope of cataracts as a cause of visual impairment and the racial disparities that exist in its detection and treatment, further investigation into the role of opportunistic imaging to detect cataract formation is warranted.

Cranial Nerve Anatomy Using a Modular and Multimodal Radiologic Approach.

Introduction: Medical students often struggle with learning cranial nerve anatomy. Typically, cranial nerve anatomy is taught using didactic lectures and textbook illustrations, often leaving students frustrated. Methods: We developed a multimodal radiologic approach to teaching cranial nerve anatomy. First, 150 students were presented with carefully curated preclass material from which to prepare. Next, they received a didactic lecture that was recorded for them to revisit on their own time. Last, students worked in groups in a lab setting with expert radiologists to identify the cranial nerves and related anatomy and learn about some basic pathophysiology. We used a pretest and posttest to examine the effectiveness of our teaching methods and a survey to measure students' satisfaction. Results: Student knowledge of cranial nerve structure was significantly improved after our module, with quiz scores increasing from 4.6 to 6.8 out of 9.0 (p < .001). In addition, students reported feeling more confident in their knowledge of the material and offered high satisfaction scores. Discussion: The breadth of knowledge covered during the preclinical training years continues to expand despite stable or even contracted durations of training, requiring knowledge to be delivered in an ever more efficient manner. Ultimately, the multimodal pedagogy used by our resource leads to students who are more confident and engaged in their learning, resulting in increased knowledge.

Atypical Histopathological Features and the Risk of Treatment Failure in Nonmalignant Meningiomas: A Multi-Institutional Analysis.

BACKGROUND: Histopathological grading of meningiomas is insufficient for optimal risk stratification. The purpose of the present study was to determine the prognostic value of atypical histopathological features across all nonmalignant meningiomas (World Health Organization [WHO] grade I-II). METHODS: The data from 334 patients with WHO grade I (n = 275) and grade II (n = 59) meningiomas who had undergone surgical resection from 2001 to 2015 at 2 academic centers were pooled. Progression/recurrence (P/R) was determined radiographically and measured from the date of surgery. RESULTS: The median follow-up was 52 months. The patients were stratified by the number of atypical features: 0 (n = 151), 1 (n = 71), 2 (n = 66), 3 (n = 22), and 4 or 5 (n = 24). The risk of P/R increased with an increasing number of atypical features (log-rank test, P = 0.001). The 5-year actuarial rates of P/R stratified by the number of atypical features were as follows: 0, 16.3% (95% confidence interval [CI], 10.7-24.4); 1, 21.7% (95% CI, 12.8-35.2); 2, 28.2% (95% CI, 18.4-41.7); 3, 30.4% (95% CI, 13.8-58.7); and 4 or 5, 51.4% (95% CI, 31.7-74.5). On univariate analysis, the presence of high nuclear/cytoplasmic ratio (P = 0.007), prominent nucleoli (P = 0.007), and necrosis (P < 0.00005) were associated with an increased risk of P/R. On multivariate analysis, the number of atypical features (hazard ratio [HR], 1.30; 95% CI, 1.03-1.63; P = 0.03), ≥4 mitoses per high-power fields (HR, 2.45; 95% CI, 1.17-5.15; P = 0.02), subtotal resection (HR, 3.9; 95% CI, 2.5-6.3; P < 0.0005), and the lack of adjuvant radiotherapy (HR, 2.40; 95% CI, 1.19-4.80; P = 0.01) were associated with an increased risk of P/R. CONCLUSIONS: An increased number of atypical features, ≥4 mitoses per 10 high-power fields, subtotal resection, and the lack of adjuvant radiotherapy were independently associated with P/R of WHO grade I-II meningiomas. Patients with these features might benefit from intensified therapy.

[18F]Fluciclovine PET discrimination between high- and low-grade gliomas.

BACKGROUND: The ability to accurately and non-invasively distinguish high-grade glioma from low-grade glioma remains a challenge despite advances in molecular and magnetic resonance imaging. We investigated the ability of fluciclovine (18F) PET as a means to identify and distinguish these lesions in patients with known gliomas and to correlate uptake with Ki-67. RESULTS: Sixteen patients with a total of 18 newly diagnosed low-grade gliomas (n = 6) and high grade gliomas (n = 12) underwent fluciclovine PET imaging after histopathologic assessment. Fluciclovine PET analysis comprised tumor SUVmax and SUVmean, as well as metabolic tumor thresholds (1.3*, 1.6*, 1.9*) to normal brain background (TBmax, and TBmean). Comparison was additionally made to the proliferative status of the tumor as indicated by Ki-67 values. Fluciclovine uptake greater than normal brain parenchyma was found in all lesions studied. Time activity curves demonstrated statistically apparent flattening of the curves for both high-grade gliomas and low-grade gliomas starting 30 min after injection, suggesting an influx/efflux equilibrium. The best semiquantitative metric in discriminating HGG from LGG was obtained utilizing a metabolic 1 tumor threshold of 1.3* contralateral normal brain parenchyma uptake to create a tumor: background (TBmean1.3) cutoff of 2.15 with an overall sensitivity of 97.5% and specificity of 95.5%. Additionally, using a SUVmax > 4.3 cutoff gave a sensitivity of 90.9% and specificity of 97.5%. Tumor SUVmean and tumor SUVmax as a ratio to mean normal contralateral brain were both found to be less relevant predictors of tumor grade. Both SUVmax (R = 0.71, p = 0.0227) and TBmean (TBmean1.3: R = 0.81, p = 0.00081) had a high correlation with the tumor proliferative index Ki-67. CONCLUSIONS: Fluciclovine PET produces high-contrast images between both low-grade and high grade gliomas and normal brain by visual and semiquantitative analysis. Fluciclovine PET appears to discriminate between low-grade glioma and high-grade glioma, but must be validated with a larger sample size.

Yield of computed tomography of the cervical spine in cases of simple assault.

BACKGROUND: Computed tomography (CT) of the cervical spine (C-spine) is routinely ordered for low-impact, non-penetrating or "simple" assault at our institution and others. Common clinical decision tools for C-spine imaging in the setting of trauma include the National Emergency X-Radiography Utilization Study (NEXUS) and the Canadian Cervical Spine Rule for Radiography (CCR). While NEXUS and CCR have served to decrease the amount of unnecessary imaging of the C-spine, overutilization of CT is still of concern. METHODS: A retrospective, cross-sectional study was performed of the electronic medical record (EMR) database at an urban, Level I Trauma Center over a 6-month period for patients receiving a C-spine CT. The primary outcome of interest was prevalence of cervical spine fracture. Secondary outcomes of interest included appropriateness of C-spine imaging after retrospective application of NEXUS and CCR. The hypothesis was that fracture rates within this patient population would be extremely low. RESULTS: No C-spine fractures were identified in the 460 patients who met inclusion criteria. Approximately 29% of patients did not warrant imaging by CCR, and 25% by NEXUS. Of note, approximately 44% of patients were indeterminate for whether imaging was warranted by CCR, with the most common reason being lack of assessment for active neck rotation. CONCLUSIONS: Cervical spine CT is overutilized in the setting of simple assault, despite established clinical decision rules. With no fractures identified regardless of other factors, the likelihood that a CT of the cervical spine will identify clinically significant findings in the setting of "simple" assault is extremely low, approaching zero. At minimum, adherence to CCR and NEXUS within this patient population would serve to reduce both imaging costs and population radiation dose exposure.

Utility of computed tomographic imaging of the cervical spine in trauma evaluation of ground-level fall.

BACKGROUND: Computed tomography (CT) of the cervical spine (C-spine) is routinely ordered for low-risk mechanisms of injury, including ground-level fall. Two commonly used clinical decision rules (CDRs) to guide C-spine imaging in trauma are the National Emergency X-Radiography Utilization Study (NEXUS) and the Canadian Cervical Spine Rule for Radiography (CCR). METHODS: Retrospective cross-sectional study of 3,753 consecutive adult patients presenting to an urban Level I emergency department who received C-spine CT scans were obtained over a 6-month period. The primary outcome of interest was prevalence of C-spine fracture. Secondary outcomes included fracture stability, appropriateness of imaging by NEXUS and CCR criteria, and estimated radiation dose exposure and costs associated with C-spine imaging studies. RESULTS: Of the 760 patients meeting inclusion criteria, 7 C-spine fractures were identified (0.92% ± 0.68%). All fractures were identified by NEXUS and CCR criteria with 100% sensitivity. Of all these imaging studies performed, only 69% met NEXUS indications for imaging (50% met CCR indications). C-spine CT scans in patients not meeting CDR indications were associated with costs of $15,500 to $22,000 by NEXUS ($14,600-$25,600 by CCR) in this single center during the 6-month study period. CONCLUSION: For ground-level fall, C-spine CT is overused. The consistent application of CDR criteria would reduce annual nationwide imaging costs in the United States by $6.8 to $9.6 million based on NEXUS ($6.4-$15.6 million based on CCR) and would reduce population radiation dose exposure by 0.8 to 1.1 million mGy based on NEXUS (0.7-1.9 million mGy based on CCR) if applied across all Level I trauma centers. Greater use of evidence-based CDRs plays an important role in facilitating emergency department patient management and reducing systemwide radiation dose exposure and imaging expenditures. LEVEL OF EVIDENCE: Diagnostic study, level III.

Sacrum and Coccyx Radiographs Have Limited Clinical Impact in the Emergency Department.

OBJECTIVE: The purpose of this study was to determine the yield and clinical impact of sacrum and coccyx radiographs in the emergency department (ED). MATERIALS AND METHODS: Consecutive sacrum and coccyx radiographs obtained in the EDs of four hospitals over a 6-year period were categorized as positive for acute fracture or dislocation, negative, or other. Five follow-up metrics were analyzed: follow-up advanced imaging in the same ED visit, follow-up advanced imaging within 30 days, new analgesic prescriptions, clinic follow-up, and surgical intervention within 60 days. RESULTS: Sacrum and coccyx radiographs from 687 patients (mean age, 48.1 years; 61.6% women and 38.4% men) obtained at level-1 (n = 335) and level-2 (n = 352) trauma centers showed a positivity rate of 8.4% ± 2.1% (n = 58/687). None of the 58 positive cases had surgical intervention. At the level-1 trauma centers, there was no significant association between sacrum and coccyx radiograph positivity and analgesic prescription or clinical follow-up (p = 0.12; odds ratio [OR], 2.3; 95% CI, 0.81-6.20). At the level-2 trauma centers, 97.1% (n = 34/35) of patients with positive sacrum and coccyx radiographs received analgesic prescriptions or clinical referrals, whereas negative cases were at 82.9% (OR, 7.0; 95% CI, 0.94-52.50). Of all cases, 5.7% (n = 39) and 4.3% (n = 29) had advanced imaging in the same ED visit and within 30 days, respectively. Sacrum and coccyx radiography results had no significant correlation with advanced imaging in the same ED visit (level-1, p = 0.351; level-2, p = 0.179). There was no significant difference in 30-day advanced imaging at the level-1 trauma centers (p = 0.8), but there was at the level-2 trauma centers (p = 0.0493). CONCLUSION: ED sacrum and coccyx radiographs showed a low positivity rate and had no quantifiable clinical impact. We recommend that sacrum and coccyx radiographs be eliminated from ED practice and patients treated conservatively on the basis of clinical parameters.

Evolutionary constraints on visual cortex architecture from the dynamics of hallucinations.

In the cat or primate primary visual cortex (V1), normal vision corresponds to a state where neural excitation patterns are driven by external visual stimuli. A spectacular failure mode of V1 occurs when such patterns are overwhelmed by spontaneously generated spatially self-organized patterns of neural excitation. These are experienced as geometric visual hallucinations. The problem of identifying the mechanisms by which V1 avoids this failure is made acute by recent advances in the statistical mechanics of pattern formation, which suggest that the hallucinatory state should be very robust. Here, we report how incorporating physiologically realistic long-range connections between inhibitory neurons changes the behavior of a model of V1. We find that the sparsity of long-range inhibition in V1 plays a previously unrecognized but key functional role in preserving the normal vision state. Surprisingly, it also contributes to the observed regularity of geometric visual hallucinations. Our results provide an explanation for the observed sparsity of long-range inhibition in V1--this generic architectural feature is an evolutionary adaptation that tunes V1 to the normal vision state. In addition, it has been shown that exactly the same long-range connections play a key role in the development of orientation preference maps. Thus V1's most striking long-range features--patchy excitatory connections and sparse inhibitory connections--are strongly constrained by two requirements: the need for the visual state to be robust and the developmental requirements of the orientational preference map.

Emergent oscillations in networks of stochastic spiking neurons.

Networks of neurons produce diverse patterns of oscillations, arising from the network's global properties, the propensity of individual neurons to oscillate, or a mixture of the two. Here we describe noisy limit cycles and quasi-cycles, two related mechanisms underlying emergent oscillations in neuronal networks whose individual components, stochastic spiking neurons, do not themselves oscillate. Both mechanisms are shown to produce gamma band oscillations at the population level while individual neurons fire at a rate much lower than the population frequency. Spike trains in a network undergoing noisy limit cycles display a preferred period which is not found in the case of quasi-cycles, due to the even faster decay of phase information in quasi-cycles. These oscillations persist in sparsely connected networks, and variation of the network's connectivity results in variation of the oscillation frequency. A network of such neurons behaves as a stochastic perturbation of the deterministic Wilson-Cowan equations, and the network undergoes noisy limit cycles or quasi-cycles depending on whether these have limit cycles or a weakly stable focus. These mechanisms provide a new perspective on the emergence of rhythmic firing in neural networks, showing the coexistence of population-level oscillations with very irregular individual spike trains in a simple and general framework.

EEG, temporal correlations, and avalanches.

Epileptiform activity in the EEG is frequently characterized by rhythmic, correlated patterns or synchronized bursts. Long-range temporal correlations (LRTC) are described by power law scaling of the autocorrelation function and have been observed in scalp and intracranial EEG recordings. Synchronous large-amplitude bursts (also called neuronal avalanches) have been observed in local field potentials both in vitro and in vivo. This article explores the presence of neuronal avalanches in scalp and intracranial EEG in the context of LRTC. Results indicate that both scalp and intracranial EEG show LRTC, with larger scaling exponents in scalp recordings than intracranial. A subset of analyzed recordings also show avalanche behavior, indicating that avalanches may be associated with LRTC. Artificial test signals reveal a linear relationship between the scaling exponent measured by detrended fluctuation analysis and the exponent of the avalanche size distribution. Analysis and evaluation of simulated data reveal that preprocessing of EEG (squaring the signal or applying a filter) affect the ability of detrended fluctuation analysis to reliably measure LRTC.

Systematic comparison of the behaviors produced by computational models of epileptic neocortex.

Two existing models of brain dynamics in epilepsy, one detailed (i.e., realistic) and one abstract (i.e., simplified) are compared in terms of behavioral range and match to in vitro mouse recordings. A new method is introduced for comparing across computational models that may have very different forms. First, high-level metrics were extracted from model and in vitro output time series. A principal components analysis was then performed over these metrics to obtain a reduced set of derived features. These features define a low-dimensional behavior space in which quantitative measures of behavioral range and degree of match to real data can be obtained. The detailed and abstract models and the mouse recordings overlapped considerably in behavior space. Both the range of behaviors and similarity to mouse data were similar between the detailed and abstract models. When no high-level metrics were used and principal components analysis was computed over raw time series, the models overlapped minimally with the mouse recordings. The method introduced here is suitable for comparing across different kinds of model data and across real brain recordings. It appears that, despite differences in form and computational expense, detailed and abstract models do not necessarily differ in their behaviors.

Avalanches in a stochastic model of spiking neurons.

Neuronal avalanches are a form of spontaneous activity widely observed in cortical slices and other types of nervous tissue, both in vivo and in vitro. They are characterized by irregular, isolated population bursts when many neurons fire together, where the number of spikes per burst obeys a power law distribution. We simulate, using the Gillespie algorithm, a model of neuronal avalanches based on stochastic single neurons. The network consists of excitatory and inhibitory neurons, first with all-to-all connectivity and later with random sparse connectivity. Analyzing our model using the system size expansion, we show that the model obeys the standard Wilson-Cowan equations for large network sizes ( neurons). When excitation and inhibition are closely balanced, networks of thousands of neurons exhibit irregular synchronous activity, including the characteristic power law distribution of avalanche size. We show that these avalanches are due to the balanced network having weakly stable functionally feedforward dynamics, which amplifies some small fluctuations into the large population bursts. Balanced networks are thought to underlie a variety of observed network behaviours and have useful computational properties, such as responding quickly to changes in input. Thus, the appearance of avalanches in such functionally feedforward networks indicates that avalanches may be a simple consequence of a widely present network structure, when neuron dynamics are noisy. An important implication is that a network need not be "critical" for the production of avalanches, so experimentally observed power laws in burst size may be a signature of noisy functionally feedforward structure rather than of, for example, self-organized criticality.