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When planning for brain tumor resection, a balance between maximizing resection and minimizing injury to eloquent brain parenchyma is paramount. The advent of blood oxygenation level-dependent functional magnetic resonance (fMR) imaging has allowed researchers and clinicians to reliably measure physiologic fluctuations in brain oxygenation related to neuronal activity with good spatial resolution. fMR imaging can offer a unique insight into preoperative planning for brain tumors by identifying eloquent areas of the brain affected or spared by the neoplasm. This article discusses the fMR imaging techniques and their applications in neurosurgical planning.

The incidence and effects of stenosis of the cerebral venous system are poorly understood. When noninvasive computed tomography venography (CTV) of the head and neck suggests complete internal jugular vein (IJV) occlusion, invasive catheter-directed venography can discordantly show venous patency. We compared CTV vs digital subtraction venography (DSV) in the evaluation of patency/occlusion in the suspected IJV and contralateral IJV. We queried the venous intervention database of our U.S. academic tertiary-care hospital to identify patients with complete or near-complete IJV occlusion per CTV from March 1, 2019 to March 1, 2020. We included patients with both noninvasive and invasive imaging of the target segment and the contralateral IJV. Four patients had suspected occlusion of the IJV at the skull base. Invasive catheter-directed venography consisted of DSV to assess direction of flow and vessel caliber, as well as manometry proximal and distal to areas of suspected stenosis. DSV showed patency in all 4 IJVs for which CTV had shown suspected occlusions. CTV findings of the contralateral IJVs were patency (n = 2), moderate stenosis (n = 1), and severe/critical stenosis (n = 1). Contralateral IJV caliber, measured by DSV, was concordant with CTV findings. Median mean-pressure gradients across the apparent occlusion and contralateral segments were 1 (range, 1-4) mmHg and 0 (range, 0-5) mmHg, respectively. Although noninvasive CTV may suggest absence of or attenuated flow within the IJV, this technique may be insufficient to establish complete occlusion. Catheter-directed venography can be used to evaluate patency, vessel caliber, and mean-pressure gradient.

The goal of this study was to demonstrate that a novel resting state BOLD ALFF (amplitude of low frequency fluctuations)-based correction method can substantially enhance the detectability of motor task activation in the presence of tumor-induced neurovascular uncoupling (NVU). Twelve de novo brain tumor patients who underwent comprehensive clinical BOLD fMRI exams including task fMRI and resting state fMRI (rsfMRI) were evaluated. Each patient displayed decreased/absent task fMRI activation in the ipsilesional primary motor cortex in the absence of corresponding motor deficit or suboptimal task performance, consistent with NVU. Z-score maps for the motor tasks were obtained from general linear model (GLM) analysis (reflecting motor activation vs. rest). ALFF maps were calculated from rsfMRI data. Precentral and postcentral gyri in contralesional (CL) and ipsilesional (IL) hemispheres were parcellated using an Automated Anatomical Labeling (AAL) template for each patient. A novel ALFF-based correction method was used to identify the NVU affected voxels in the ipsilesional primary motor cortex (PMC), and a correction factor was applied to normalize the baseline Z-scores for these voxels. In all cases, substantially greater activation was seen on post-ALFF correction motor activation maps within the ipsilesional precentral gyri than in the pre-ALFF correction activation maps. We have demonstrated the feasibility of a new resting state ALFF-based technique for effective correction of brain tumor-related NVU in the primary motor cortex.

Dynamic functional connectivity adds another dimension to resting-state functional MR imaging analysis. In recent years, dynamic functional connectivity has been increasingly used in resting-state functional MR imaging, and several studies have demonstrated that dynamic functional connectivity patterns correlate with different physiologic and pathologic brain states. In fact, evidence suggests that dynamic functional connectivity is a more sensitive marker than static functional connectivity; therefore, it might be a promising tool to add to clinical functional neuroimaging. This article provides a broad overview of dynamic functional connectivity and reviews its general principles, techniques, and potential clinical applications.

Context Craniopharyngiomas, while benign, have the highest morbidity of all nonmalignant sellar tumors. Studies on weight and metabolic outcomes in adult-onset craniopharyngioma (AOCP) remain sparse. Objective To examine postsurgical weight and metabolic outcomes in AOCP and to identify any clinical predictors of weight gain. Methods Retrospective chart review of patients with AOCP who underwent surgery between January 2014 and May 2019 in a single pituitary center. The study included 45 patients with AOCP with a minimum follow-up of 3 months. Median follow-up time was 26 months (interquartile range [IQR] 10-44). Main outcome measures were the changes in weight/body mass index (BMI), metabolic comorbidities, and pituitary deficiencies between preoperative and last follow-up. Results Both weight and BMI were higher at last follow-up, with a mean increase of 3.4 kg for weight (P = .015) and 1.15 kg/m2 for BMI (P = .0095). Median % weight change was 2.7% (IQR –1.1%, 8.8%). Obesity rate increased from 37.8% at baseline to 55.6% at last follow-up. One-third of patients had ~15% median weight gain. The prevalence of metabolic comorbidities at last follow-up was not different from baseline. Pituitary deficiencies increased postoperatively, with 58% of patients having ≥3 hormonal deficiencies. Preoperative BMI was inversely associated with postoperative weight gain, which remained significant after adjusting for age, sex, race, tumor, and treatment characteristics. Patients with ≥3 hormonal deficiencies at last follow-up also had higher postoperative weight gain. Conclusion In this AOCP cohort, those with a lower BMI at the preoperative visit had higher postoperative weight gain. Our finding may help physicians better counsel patients and provide anticipatory guidance on postoperative expectations and management.

Brainstem lesions can arise from the midbrain, pons, or medulla. Oftentimes, these lesions will affect adjacent nuclei/pathways or result in mass-effect within the posterior fossa. Imaging of brainstem lesions can be achieved by utilizing multiple modalities, each of which offer modality-specific advantages and disadvantages. Imaging may include magnetic resonance imaging (MRI), computed tomography (CT), and/or positron emission tomography (PET) imaging. Ultrasound imaging may also be utilized to evaluate the posterior fossa of newborns. The density of the skull base typically presents an obstacle for imaging of the posterior fossa. MRI is the modality of choice for the evaluation and characterization of brainstem lesions. Imaging characteristics of different brainstem lesions can provide invaluable pretreatment information to aid in the diagnosis, assess impact on adjacent structures, and assist in treatment planning. When evaluating neoplastic lesions, imaging may also serve to distinguish between neoplastic progression versus development of post-treatment changes. In this chapter, we provide an overview of the typical imaging appearance of common neoplastic and non-neoplastic lesions within the brainstem.

We present a novel deep learning framework that uses dynamic functional connectivity to simultaneously localize the language and motor areas of the eloquent cortex in brain tumor patients. Our method leverages convolutional layers to extract graph-based features from the dynamic connectivity matrices and a long-short term memory (LSTM) attention network to weight the relevant time points during classification. The final stage of our model employs multi-task learning to identify different eloquent subsystems. Our unique training strategy finds a shared representation between the cognitive networks of interest, which enables us to handle missing patient data. We evaluate our method on resting-state fMRI data from 56 brain tumor patients while using task fMRI activations as surrogate ground-truth labels for training and testing. Our model achieves higher localization accuracies than conventional deep learning approaches and can identify bilateral language areas even when trained on left-hemisphere lateralized cases. Hence, our method may ultimately be useful for preoperative mapping in tumor patients.

Localizing the eloquent cortex is a crucial part of presurgical planning. While invasive mapping is the gold standard, there is increasing interest in using noninvasive fMRI to shorten and improve the process. However, many surgical patients cannot adequately perform task-based fMRI protocols. Resting-state fMRI has emerged as an alternative modality, but automated eloquent cortex localization remains an open challenge. In this paper, we develop a novel deep learning architecture to simultaneously identify language and primary motor cortex from rs-fMRI connectivity. Our approach uses the representational power of convolutional neural networks alongside the generalization power of multi-task learning to find a shared representation between the eloquent subnetworks. We validate our method on data from the publicly available Human Connectome Project and on a brain tumor dataset acquired at the Johns Hopkins Hospital. We compare our method against feature-based machine learning approaches and a fully-connected deep learning model that does not account for the shared network organization of the data. Our model achieves significantly better performance than competing baselines. We also assess the generalizability and robustness of our method. Our results clearly demonstrate the advantages of our graph convolution architecture combined with multi-task learning and highlight the promise of using rs-fMRI as a presurgical mapping tool.

Functional connectivity in resting-state functional magnetic resonance imaging (rs-fMRI) has received substantial attention since the initial findings of Biswal et al. Traditional network correlation metrics assume that the functional connectivity in the brain remains stationary over time. However, recent studies have shown that robust temporal fluctuations of functional connectivity among as well as within functional networks exist, challenging this assumption. In this study, these dynamic correlation differences were investigated between the dorsal and ventral sensorimotor networks by applying the dynamic conditional correlation model to rs-fMRI data of 20 healthy subjects. k-Means clustering was used to determine an optimal number of discrete connectivity states (k = 10) of the sensorimotor system across all subjects. Our analysis confirms the existence of differences in dynamic correlation between the dorsal and ventral networks, with highest connectivity found within the ventral motor network.

Sarcopenia is an important prognostic consideration in surgical oncology that has received relatively little attention in brain tumor patients. Temporal muscle thickness (TMT) has recently been proposed as a novel radiographic marker of sarcopenia that can be efficiently obtained within existing workflows. We investigated the prognostic value of TMT in primary and progressive glioblastoma.TMT measurements were performed on magnetic resonance images of 384 patients undergoing 541 surgeries for glioblastoma. Relationships between TMT and clinical characteristics were examined on bivariate analysis. Optimal TMT cutpoints were established using maximally selected rank statistics. Predictive value of TMT upon postoperative survival (PS) was assessed using Cox proportional hazards regression adjusted for age, sex, Karnofsky performance status (KPS), Stupp protocol completion, extent of resection, and tumor molecular markers.Average TMT for the primary and progressive glioblastoma cohorts was 9.55 mm and 9.40 mm, respectively. TMT was associated with age (r = -0.14, p = 0.0008), BMI (r = 0.29, p 0.0001), albumin (r = 0.11, p = 0.0239), and KPS (r = 0.11, p = 0.0101). Optimal TMT cutpoints for the primary and progressive cohorts were ≤ 7.15 mm and ≤ 7.10 mm, respectively. High TMT was associated with increased Stupp protocol completion (p = 0.001). On Cox proportional hazards regression, high TMT predicted increased PS in progressive [HR 0.47 (95% confidence interval (CI)) 0.25-0.90), p = 0.023] but not primary [HR 0.99 (95% CI 0.64-1.51), p = 0.949] glioblastoma.TMT correlates with important prognostic variables in glioblastoma and predicts PS in patients with progressive, but not primary, disease. TMT may represent a pragmatic neurosurgical biomarker in glioblastoma that could inform treatment planning and perioperative optimization.

// Lode J. Swinnen 1 , Anne O’Neill 2 , Philip H. Imus 1 , Sachin Gujar 1 , David Schiff 3 , Lawrence R. Kleinberg 1 , Ranjana H. Advani 4 , Erin M. Dunbar 5 , Dennis Moore 6 and Stuart A. Grossman 1 1 Johns Hopkins University, Baltimore, Maryland, USA 2 Dana Farber Cancer Institute, Boston, Massachusetts, USA 3 University of Virginia, Charlottesville, Virginia, USA 4 Stanford Cancer Institute, Stanford, California, USA 5 University of Florida, Gainesville, Florida, USA 6 Wichita NCORP, Wichita, Kansas, USA Correspondence to: Lode J. Swinnen, email: lswinne1@jhmi.edu Keywords: primary CNS lymphoma; rituximab; high-dose methotrexate; blood-brain barrier; PCNSL Received: August 25, 2017 Accepted: September 16, 2017 Published: November 06, 2017 ABSTRACT Background: Therapy of primary CNS lymphoma (PCNSL) has focused on multi-agent chemotherapy designed to cross the blood brain barrier. Rituximab has demonstrated activity in PCNSL. E1F05 is an ECOG-ACRIN multicenter phase 2 prospective trial of rituximab with high-dose methotrexate (HD-MTX)-based chemotherapy similar to the RTOG 93-10 regimen, omitting radiotherapy. Methods: Immunocompetent patients with newly diagnosed PCNSL received HD-MTX 3.5g/m2 with vincristine every two weeks for 5 doses; procarbazine for 7 days in weeks 1, 5, and 9; cytarabine 3g/m2/day IV for 2 days in weeks 11 and 14; a dexamethasone taper over 6 weeks; and rituximab 375mg/m2 IV infusion 3 times per week for weeks 1-4. Subjects with CSF involvement received intrathecal methotrexate 12mg every two weeks. Results: Twenty-six patients were enrolled; median age was 57. Sixteen subjects (65%) completed treatment per protocol; the most common reason for discontinuation was adverse events, and 2 subjects discontinued due to progressive disease (PD). Complete response (CR) + unconfirmed CR (CRu) was 16/25 (64%), overall response rate was 20/25 (80%), and 4/25(16%) had PD as best response. Median progression free survival (PFS) was 34 months, and median overall survival has not been reached at 40 months’ median follow up. Two year PFS was 63%. The most common grade 3-4 toxicities were hematologic. Conclusion: The addition of rituximab to multi-agent chemotherapy is well tolerated. Outcomes are comparable to or better than those seen in RTOG 93-10, which included RT. These and other results suggest rituximab has activity in the CNS. [ECOG-ACRIN E1F05] Clinical Trial Registration: NCT00335140, clinicaltrials.gov

BACKGROUND AND PURPOSE: Resting-state fMRI readily identifies the dorsal but less consistently the ventral somatomotor network. Our aim was to assess the relative utility of resting-state fMRI in the identification of the ventral somatomotor network via comparison with task-based fMRI in patients with brain tumor. MATERIALS AND METHODS: We identified 26 surgically naive patients referred for presurgical fMRI brain mapping who had undergone both satisfactory ventral motor activation tasks and resting-state fMRI. Following standard preprocessing for task-based fMRI and resting-state fMRI, general linear model analysis of the ventral motor tasks and independent component analysis of resting-state fMRI were performed with the number of components set to 20, 30, 40, and 50. Visual overlap of task-based fMRI and resting-state fMRI at different component levels was assessed and categorized as full match, partial match, or no match. Rest-versus-task-fMRI concordance was calculated with Dice coefficients across varying fMRI thresholds before and after noise removal. Multithresholded Dice coefficient volume under the surface was calculated. RESULTS: The ventral somatomotor network was identified in 81% of patients. At the subject level, better matches between resting-state fMRI and task-based fMRI were seen with an increasing order of components (53% of cases for 20 components versus 73% for 50 components). Noise-removed group-mean volume under the surface improved as component numbers increased from 20 to 50, though ANOVA demonstrated no statistically significant difference among the 4 groups. CONCLUSIONS: In most patients, the ventral somatomotor network can be identified with an increase in the probability of a better match at a higher component number. There is variable concordance of the ventral somatomotor network at the single-subject level between resting-state and task-based fMRI.

Regadenoson is an FDA approved adenosine receptor agonist which increases blood–brain barrier (BBB) permeability in rodents. Regadenoson is used clinically for pharmacologic cardiac stress testing using SPECT or CT imaging agents that do not cross an intact BBB. This study was conducted to determine if standard doses of regadenoson transiently disrupt the human BBB allowing higher concentrations of systemically administered imaging agents to enter the brain. Patients without known intracranial disease undergoing clinically indicated pharmacologic cardiac stress tests were eligible for this study. They received regadenoson (0.4 mg) followed by brain imaging with either 99mTc-sestamibi for SPECT or visipaque for CT imaging. Pre- and post-regadenoson penetration of imaging agents into brain were quantified [SPECT: radioactive counts, CT: Hounsfield units (HU)] and compared using a matched-pairs t-test. Twelve patients (33% male, median 60 yo) were accrued: 7 SPECT and 5 CT. No significant differences were noted in pre- and post-regadenoson values using mean radionuclide counts (726 vs. 757) or HU (29 vs. 30). While animal studies have demonstrated that regadenoson transiently increases the permeability of the BBB to dextran and temozolomide, we were unable to document changes in the penetration of contrast agents in humans with intact BBB using the FDA approved doses of regadenoson for cardiac evaluation. Further studies are needed exploring alternate regadenoson dosing, schedules, and studies in patients with brain tumors; as transiently disrupting the BBB to improve drug entry into the brain is critical to improving the care of patients with CNS malignancies.

Clinical use of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a relatively new phenomenon, with only about 3 decades of collective experience. Nevertheless, task-based BOLD fMRI has been widely accepted for presurgical planning, over traditional methods, which are invasive and at times perilous. Many studies have demonstrated the ability of BOLD fMRI to make substantial clinical impact with respect to surgical planning and preoperative risk assessment, especially to localize the eloquent motor and visual areas. Reproducibility and repeatability of language fMRI are important in the assessment of its clinical usefulness. There are national efforts currently underway to standardize language fMRI. The American Society of Functional Neuroradiology (ASFNR) has recently provided guidelines on fMRI paradigm algorithms for presurgical language assessment for language lateralization and localization. In this review article, we provide a comprehensive overview of current standards of language fMRI mapping and its reproducibility.

We develop a novel method to localize the language and motor areas of the eloquent cortex in brain tumor patients based on resting-state fMRI (rs-fMRI) connectivity. Our method leverages the representation power of convolutional neural networks through specialized filters that act topologically on the rs-fMRI connectivity data. This Graph Neural Network (GNN) classifies each parcel in the brain into eloquent cortex, tumor, or background gray matter, thus accommodating varying tumor characteristics across patients. Our loss function also reflects the large class-imbalance present in our data. We evaluate our GNN on rs-fMRI data from 60 brain tumor patients with different tumor sizes and locations. We use motor and language task fMRI for validation. Our model achieves better localization than linear SVM, random forest, and a multilayer perceptron architecture. Our GNN is able to correctly identify bilateral language areas in the brain even when trained on patients whose language network is lateralized to the left hemisphere.

In the current era of neuroimaging, presurgical mapping of brain tumors involves a multimodality approach including high-resolution anatomic imaging, MR perfusion imaging, blood oxygen level–dependent functional MRI, and diffusion tensor imaging. In this chapter, we focus primarily on the functional and physiologic imaging modalities for both characterization of de novo brain tumors and presurgical mapping. We include brief discussions of the basic principles underlying such imaging methods and then describe their application specifically to the evaluation of brain tumors. Both advantages and limitations of such techniques are discussed, and examples of their clinical applications are included in the figures. Although there are certainly numerous other clinical applications of these methods outside of neuro-oncology, we will limit our discussion to evaluation of brain tumors. These advanced imaging methods have revolutionized the neurosurgical planning strategies for resection of such lesions.

Background The cortico-ponto-cerebellar tract (CPCT) is the largest projection pathway, which synapses at the pons. Remote effects of supratentorial brain tumors have not been evaluated along the infratentorial course of the CPCT. Aim The purpose of this study is to evaluate the possible lateralization of the diffusion tensor metrics of the affected CPCT in patients with supratentorial brain tumor. Methods and results We included 39 patients with 29 left-sided tumors (LST) and 10 right-sided tumors, retrospectively. We measured the magnitude of changes of the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the CPCT prior to the brain surgery at the level of crus cerebri and middle cerebellar peduncle. Regions of interest (ROIs) were placed on the lateral side of crus cerebri, and ROI-1 (anterior 1/3), ROI-2 (middle 1/3), ROI-3 (posterior 1/3), and ROI-4 were placed at the level of middle cerebellar peduncle. We hypothesized that there would be decreased FA and increased ADC values of the ipsilesional CPCT compared with contralesional CPCT. Ipsilesional FA values were decreased with simultaneous increased ADC value along the CPCT compared with contralesional CPCT in following ROIs, ROI-1 (LST FA: P = .005, ADC: P = .037) and ROI-3 (LST FA: P = .049, ADC: P = .049), respectively. Affected ROI-4 in LST cases also showed lower FA values, although not statistically significant. Conclusion We observed a statistically significant FA value decrease and ADC increase along the left ROI-1 and ROI-3 as well as the nonstatistically significant FA decrease of the left ROI-4 at the second neuron level when there was a related supratentorial tumor. These findings are suggestive of presynaptic and postsynaptic microstructural changes of these tracts following the presynaptic involvement by a primary supratentorial brain tumor.

To assess the within-subject intra-scan session repeatability of language functional MRI (fMRI) activation maps in patients with brain tumors who were undergoing presurgical fMRI as part of their preoperative clinical workup. Sentence completion (SC) and silent word generation (SWG) tasks were used for language localization and hemispheric lateralization for identifying the primary language cortex. Within-subject repeatability for each of these paradigms was assessed in right-handed patients-37 for SC and 78 for SWG. Repeatability of activation maps between consecutive runs of the same task within the same scan session was evaluated by comparing lateralization indexes in holohemispheric and regional language areas. Displacement of center of activation between consecutive runs was also used to assess the repeatability of activation maps. Holohemispheric and regional language lateralization results demonstrated high intra-subject intra-scan repeatability when lateralization indices were calculated using threshold-dependent and threshold-independent approaches. The high repeatability is demonstrated both when centers of mass of activation are considered within key eloquent regions of the brain, such as Broca's area and Wernicke's area, as well as in larger more inclusive expressive and receptive language regions. We examined two well-known and widely accepted language tasks that are known to activate eloquent language cortex. We have demonstrated very high degree of repeatability at a single-subject level within single scan sessions of language mapping in a large cohort of brain tumor patients undergoing presurgical fMRI across several years at our institution.

BACKGROUND AND PURPOSE: The supplementary motor area can be a critical region in the preoperative planning of patients undergoing brain tumor resection because it plays a role in both language and motor function. While primary motor regions have been successfully identified using resting-state fMRI, there is variability in the literature regarding the identification of the supplementary motor area for preoperative planning. The purpose of our study was to compare resting-state fMRI to task-based fMRI for localization of the supplementary motor area in a large cohort of patients with brain tumors presenting for preoperative brain mapping. MATERIALS AND METHODS: Sixty-six patients with brain tumors were evaluated with resting-state fMRI using seed-based analysis of hand and orofacial motor regions. Rates of supplementary motor area localization were compared with those in healthy controls and with localization results by task-based fMRI. RESULTS: Localization of the supplementary motor area using hand motor seed regions was more effective than seeding using orofacial motor regions for both patients with brain tumor (95.5% versus 34.8%, P < .001) and controls (95.2% versus 45.2%, P < .001). Bilateral hand motor seeding was superior to unilateral hand motor seeding in patients with brain tumor for either side (95.5% versus 75.8%/75.8% for right/left, P < .001). No difference was found in the ability to identify the supplementary motor area between patients with brain tumors and controls. CONCLUSIONS: In addition to task-based fMRI, seed-based analysis of resting-state fMRI represents an equally effective method for supplementary motor area localization in patients with brain tumors, with the best results obtained with bilateral hand motor region seeding.

We propose a hierarchical Bayesian model that refines a population-based atlas using resting-state fMRI (rs-fMRI) coherence. Our method starts from an initial parcellation and then iteratively reassigns the voxel memberships at the subject level. Our algorithm uses a maximum a posteriori inference strategy based on the neighboring voxel assignments and the Pearson correlation coefficients between the voxel time series and the parcel reference signals. Our method is generalizable to different initial atlases, ensures spatial and temporal contiguity in the final network organization, and can handle subjects with brain lesions, whose rs-fMRI data varies tremendously from that of a healthy cohort. We validate our method by comparing the intra-network cohesion and the motor network identification against two baselines: a standard functional parcellation with no reassignment and a recently published method with a purely data-driven reassignment procedure. Our method outperforms the original functional parcellation in intra-network cohesion and both methods in motor network identification.

BACKGROUND AND PURPOSE To determine whether lesion to activation distance (LAD) on presurgical blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) and degree of white matter involvement by primary or metastatic brain lesions predict perioperative motor and language deficits. METHODS We retrospectively evaluated 76 patients with intra-axial brain lesions referred for presurgical fMRI and diffusion tensor imaging (DTI). We measured expressive, receptive, global language and motor LAD and assessed degree of involvement of the corticospinal tract (CST) and the superior longitudinal fasciculus (SLF). We performed a Wilcoxon rank-sum test to determine whether the LAD and the degree of CST/SLF involvement were statistically significantly different between patients with and without preoperative or postoperative neurological deficits. RESULTS In preoperatively symptomatic patients, motor and expressive language LAD were significantly lower (z = –3.78, P = .0002, and z = –2.51, P = .01, respectively) than in asymptomatic patients. No significant difference was noted in LAD between postoperative symptomatic and asymptomatic patients, except for a trend level effect for motor LAD (P = .07). The degree of CST involvement was significantly different between symptomatic and asymptomatic patients (z = 3.40, P = .0007 and z = 2.97, P = .003, respectively, for pre- and postoperative motor deficits).The degree of SLF involvement was significantly different between preoperatively (but not postoperatively) symptomatic and asymptomatic patients (z = 2.85, P = .004). CONCLUSION Presurgical motor and expressive language LAD as well as degree of tract involvement on DTI are predictive of preoperative but not postoperative deficits, except for CST DTI and (trend level) motor LAD; inability of language LAD to predict postoperative deficits suggests that preoperative fMRI is valuable to neurosurgeons in avoiding resection of eloquent cortex.

Background Acute necrotizing encephalopathy is a rare childhood syndrome associated with distinct and unifying neuroimaging features that are often used for the diagnosis of this entity. Patient We describe a previously healthy 9-month-old girl who presented with upper respiratory symptoms, suspected seizures, and positive nasopharyngeal rapid antigen test for influenza A virus. Magnetic resonance imaging revealed signal abnormality in both thalami, bilateral caudate nuclei, brainstem tegmentum, subcortical white matter, and cerebellar hemispheres, suggestive of acute necrotizing encephalopathy. She subsequently had a cardiac arrest, was placed on extracorporeal membrane oxygenation, and treated with methylprednisone, intravenous immunoglobulin, and plasmapheresis without apparent clinical response. On autopsy, neuropathology showed evidence of hypoxic-ischemic injury but lacked evidence of hemorrhagic necrosis, which is typically associated with acute necrotizing encephalopathy. Conclusion Combined clinical and neuroimaging features may be suggestive but not sufficient for the diagnosis of acute necrotizing encephalopathy.

In this review, limitations affecting the results of presurgical mapping with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) are discussed. There is a great need to standardize fMRI acquisition and analysis methods and establish guidelines to address quality control issues. Several national and international organizations are formulating guidelines and standards for both clinical and research applications of BOLD fMRI. Consensus regarding management of these issues will likely both improve the clinical standard of care and enhance future research applications of fMRI.

There has been a rapid increase in resting-state functional magnetic resonance imaging (rs-fMRI) literature in the past few years. We aim to highlight the variability in the current reporting practices of rs-fMRI acquisition and preprocessing parameters. The PubMed database was searched for the selection of appropriate articles in the rs-fMRI literature and the most recent 100 articles were selected based on our criteria. These articles were evaluated based on a checklist for reporting of certain preprocessing steps. All of the studies reported the temporal resolution for the scan and the software used for the analysis. Less than half of the studies reported physiologic monitoring, despiking, global signal regression, framewise displacement, and volume censoring. A majority of the studies mentioned the scanning duration, eye status, and smoothing kernel. Overall, we demonstrate the wide variability in reporting of preprocessing methods in rs-fMRI studies. Although there might be potential variability in reporting across studies due to individual requirements for a study, we suggest the need for standardizing reporting guidelines to ensure reproducibility.

BACKGROUND AND PURPOSE: Ulceration in carotid plaque is a risk indicator for ischemic stroke. Our aim was to compare plaque ulcer detection by standard TOF and CE-MRA techniques and to identify factors that influence its detection. MATERIALS AND METHODS: Carotid MR imaging scans were acquired on 2066 participants in the ARIC study. We studied the 600 thickest plaques. TOF-MRA, CE-MRA, and black-blood MR images were analyzed together to define ulcer presence (plaque surface niche ≥2 mm in depth). Sixty ulcerated arteries were detected. These arteries were randomly assigned, along with 40 nonulcerated plaques from the remaining 540, for evaluation of ulcer presence by 2 neuroradiologists. Associations between ulcer detection and ulcer characteristics, including orientation, location, and size, were determined and explored by CFD modeling. RESULTS: One CE-MRA and 3 TOF-MRAs were noninterpretable and excluded. Of 71 ulcers in 56 arteries, readers detected an average of 39 (55%) on both TOF-MRA and CE-MRA, 26.5 (37.5%) only on CE-MRA, and 1 (1.5%) only on TOF-MRA, missing 4.5 (6%) ulcers by both methods. Ulcer detection by TOF-MRA was associated with its orientation (distally pointing versus perpendicular: OR = 5.57 [95% CI, 1.08–28.65]; proximally pointing versus perpendicular: OR = 0.21 [95% CI, 0.14–0.29]); location relative to point of maximum stenosis (distal versus isolevel: OR = 5.17 [95% CI, 2.10–12.70]); and neck-to-depth ratio (OR = 1.96 [95% CI, 1.11–3.45]) after controlling for stenosis and ulcer volume. CONCLUSIONS: CE-MRA detects more ulcers than TOF-MRA in carotid plaques. Missed ulcers on TOF-MRA are influenced by ulcer orientation, location relative to point of maximum stenosis, and neck-to-depth ratio.

Purpose To compare language networks derived from resting-state fMRI (rs-fMRI) with task-fMRI in patients with brain tumors and investigate variables that affect rs-fMRI vs task-fMRI concordance. Materials and Methods Independent component analysis (ICA) of rs-fMRI was performed with 20, 30, 40, and 50 target components (ICA20 to ICA50) and language networks identified for patients presenting for presurgical fMRI mapping between 1/1/2009 and 7/1/2015. 49 patients were analyzed fulfilling criteria for presence of brain tumors, no prior brain surgery, and adequate task-fMRI performance. Rs-vs-task-fMRI concordance was measured using Dice coefficients across varying fMRI thresholds before and after noise removal. Multi-thresholded Dice coefficient volume under the surface (DiceVUS) and maximum Dice coefficient (MaxDice) were calculated. One-way Analysis of Variance (ANOVA) was performed to determine significance of DiceVUS and MaxDice between the four ICA order groups. Age, Sex, Handedness, Tumor Side, Tumor Size, WHO Grade, number of scrubbed volumes, image intensity root mean square (iRMS), and mean framewise displacement (FD) were used as predictors for VUS in a linear regression. Results Artificial elevation of rs-fMRI vs task-fMRI concordance is seen at low thresholds due to noise. Noise-removed group-mean DiceVUS and MaxDice improved as ICA order increased, however ANOVA demonstrated no statistically significant difference between the four groups. Linear regression demonstrated an association between iRMS and DiceVUS for ICA30-50, and iRMS and MaxDice for ICA50. Conclusion Overall there is moderate group level rs-vs-task fMRI language network concordance, however substantial subject-level variability exists; iRMS may be used to determine reliability of rs-fMRI derived language networks. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

Sorafenib is an inhibitor of multiple kinases that has demonstrated antiproliferative and antiangiogenic activity in a number of in vitro and in vivo model systems. A phase I study was conducted to determine the maximum tolerated dose (MTD) of sorafenib in patients with recurrent malignant glioma. Sorafenib was given orally, twice a day (BID), continuously in 28-day cycles. The dose was escalated in 2 groups of patients stratified by use of enzyme-inducing antiseizure drugs (± EIASDs). Dose-limiting toxicity (DLT) was defined as any grades 3-4 nonhematological toxicity, grade 4 hematological toxicity, and febrile neutropenia. The number of evaluable patients enrolled in the +EIASD and -EIASD arms were 23 and 24, respectively. DLTs were predominantly dermatological and gastrointestinal effects, as observed in previous clinical trials of sorafenib. The MTD was 600 mg BID for patients receiving EIASDs and 800 mg BID for those who were not. The plasma pharmacokinetics of sorafenib were not significantly affected by the concurrent administration of EIASDs. The MTD of sorafenib given orally BID on a continuous basis was established as 600 mg BID in patients with malignant glioma who were concurrently receiving EIASDs and 800 mg BID in those who were not. Further evaluation is warranted of sorafenib at the recommended MTD against recurrent or progressive malignant glioma in combination with other molecularly targeted drugs or in the newly diagnosed setting concurrent with chemoradiation.

BACKGROUND AND PURPOSE: Head and neck cancer can cause substantial morbidity and mortality. Our aim was to evaluate the potential usefulness of a computerized system for segmenting lesions in head and neck CT scans and for estimation of volume change of head and neck malignant tumors in response to treatment. MATERIALS AND METHODS: CT scans from a pretreatment examination and a post 1-cycle chemotherapy examination of 34 patients with 34 head and neck primary-site cancers were collected. The computerized system was developed in our laboratory. It performs 3D segmentation on the basis of a level-set model and uses as input an approximate bounding box for the lesion of interest. The 34 tumors included tongue, tonsil, vallecula, supraglottic, epiglottic, and hard palate carcinomas. As a reference standard, 1 radiologist outlined full 3D contours for each of the 34 primary tumors for both the pre- and posttreatment scans and a second radiologist verified the contours. RESULTS: The correlation between the automatic and manual estimates for both the pre- to post-treatment volume change and the percentage volume change for the 34 primary-site tumors was 0.95, with an average error of −2.4 ± 8.5% by automatic segmentation. There was no substantial difference and specific trend in the automatic segmentation accuracy for the different types of primary head and neck tumors, indicating that the computerized segmentation performs relatively robustly for this application. CONCLUSIONS: The tumor size change in response to treatment can be accurately estimated by the computerized segmentation system relative to radiologists' manual estimations for different types of head and neck tumors. Auto : automatic GTV : gross tumor volume GUI : graphic user interface ICC : intra-class correlation MDCT : multidetector row CT RECIST : Response Evaluation Criteria In Solid Tumors RT : radiation therapy TV : tumor volume WHO : World Health Organization

The objective of our study was to investigate the feasibility of computerized segmentation of lesions on head and neck CT scans and evaluate its potential for estimating changes in tumor volume in response to treatment of head and neck cancers.Twenty-six CT scans were retrospectively collected from the files of 13 patients with 35 head and neck lesions. The CT scans were obtained from an examination performed before treatment (pretreatment scan) and an examination performed after one cycle of chemotherapy (posttreatment scan). Thirteen lesions were primary site cancers and 22 were metastatic lymph nodes. An experienced radiologist (radiologist 1) marked the 35 lesions and outlined each lesion's 2D contour on the best slice on both the pre- and posttreatment scans. Full 3D contours were also manually extracted for the 13 primary tumors. Another experienced radiologist (radiologist 2) verified and modified, if necessary, all manually drawn 2D and 3D contours. An in-house-developed computerized system performed 3D segmentation based on a level set model.The computer-estimated change in tumor volume and percentage change in tumor volume between the pre- and posttreatment scans achieved a high correlation (intraclass correlation coefficient [ICC] = 0.98 and 0.98, respectively) with the estimates from manual segmentation for the 13 primary tumors. The average error in estimating the percentage change in tumor volume by automatic segmentation relative to the radiologists' average error was -1.5% +/- 5.4% (SD). For the 35 lesions, the ICC between the automatic and manual estimates of change in pre- to posttreatment tumor area was 0.93 and of percentage change in pre- to posttreatment tumor area was 0.85. The average error in estimating the percentage change in tumor area by automatic segmentation was -3.2% +/- 15.3%.Preliminary results indicate that this computerized segmentation system can reliably estimate changes in tumor size on CT scans relative to radiologists' manual segmentation. This information can be used to calculate changes in tumor size on pre- and posttreatment scans to assess response to treatment.

This article briefly discusses the imaging approach to lesions of the anterior skull base. A brief review of normal anatomy and imaging techniques is followed by a discussion about common neoplastic and non-neoplastic pathologies involving this region.

The authors have developed a semiautomatic system for segmentation of a diverse set of lesions in head and neck CT scans. The system takes as input an approximate bounding box, and uses a multistage level set to perform the final segmentation. A data set consisting of 69 lesions marked on 33 scans from 23 patients was used to evaluate the performance of the system. The contours from automatic segmentation were compared to both 2D and 3D gold standard contours manually drawn by three experienced radiologists. Three performance metric measures were used for the comparison. In addition, a radiologist provided quality ratings on a 1 to 10 scale for all of the automatic segmentations. For this pilot study, the authors observed that the differences between the automatic and gold standard contours were larger than the interobserver differences. However, the system performed comparably to the radiologists, achieving an average area intersection ratio of 85.4% compared to an average of 91.2% between two radiologists. The average absolute area error was 21.1% compared to 10.8%, and the average 2D distance was 1.38 mm compared to 0.84 mm between the radiologists. In addition, the quality rating data showed that, despite the very lax assumptions made on the lesion characteristics in designing the system, the automatic contours approximated many of the lesions very well.

Background Delayed posthypoxic leukoencephalopathy (DPHL) is a rare and underrecognized entity where patients manifest a neurological relapse after initial recovery from an acute hypoxic episode. We sought to describe the magnetic resonance imaging (MRI) findings in a group of patients with DPHL and review the available literature. Methods Retrospective case series including patients who presented with neurological and/or psychiatric symptoms after recovery from an acute hypoxic episode. The history and clinical presentation were reviewed from the electronic medical records. MRI scans were evaluated from the picture archiving and communication system. We performed a comprehensive review of the English medical literature for prior published cases of DPHL and describe the key imaging findings that have been reported related to this condition. Results A total of five patients were identified, including four patients with respiratory failure due to drug overdoses from benzodiazepines, opioids, and/or barbiturates, and one patient who presented after cardiopulmonary arrest due to pulmonary embolism. All patients showed diffuse, extensive, and confluent white matter signal abnormalities including prominent restricted diffusion, extending to the subcortical white matter and respecting the U-fibers. There was no gyral edema or contrast enhancement. In one case histopathology was available, which highlighted patchy subcortical myelin loss with sparing of U-fibers and demonstrated prominent macrophage/microglial inflammation with extensive axonal damage. Of the other four patients, two were at their neurological baselines and two had persistent neurological deficits at the time of discharge. Conclusions The described constellation of MRI findings is highly suggestive of DPHL in the appropriate clinical setting.

To determine whether lesion to activation distance (LAD) on presurgical blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) and degree of white matter involvement by primary or metastatic brain lesions predict perioperative motor and language deficits.We retrospectively evaluated 76 patients with intra-axial brain lesions referred for presurgical fMRI and diffusion tensor imaging (DTI). We measured expressive, receptive, global language and motor LAD and assessed degree of involvement of the corticospinal tract (CST) and the superior longitudinal fasciculus (SLF). We performed a Wilcoxon rank-sum test to determine whether the LAD and the degree of CST/SLF involvement were statistically significantly different between patients with and without preoperative or postoperative neurological deficits.In preoperatively symptomatic patients, motor and expressive language LAD were significantly lower (z = -3.78, P = .0002, and z = -2.51, P = .01, respectively) than in asymptomatic patients. No significant difference was noted in LAD between postoperative symptomatic and asymptomatic patients, except for a trend level effect for motor LAD (P = .07). The degree of CST involvement was significantly different between symptomatic and asymptomatic patients (z = 3.40, P = .0007 and z = 2.97, P = .003, respectively, for pre- and postoperative motor deficits).The degree of SLF involvement was significantly different between preoperatively (but not postoperatively) symptomatic and asymptomatic patients (z = 2.85, P = .004).Presurgical motor and expressive language LAD as well as degree of tract involvement on DTI are predictive of preoperative but not postoperative deficits, except for CST DTI and (trend level) motor LAD; inability of language LAD to predict postoperative deficits suggests that preoperative fMRI is valuable to neurosurgeons in avoiding resection of eloquent cortex.

3 T MR imaging brings with it the possibility of a doubled signal-to-noise ratio compared with 1.5 T systems and the possibility of decreased scan times without reduction in quality. Higher cost and other issues however, also need to be examined.

Magnetic resonance spectroscopy (MRS) complements magnetic resonance imaging (MRI) as a non-invasive means for the characterization of tissue. While MRI uses the signal from hydrogen protons to form anatomic images, proton MRS uses this information to determine the concentration of brain metabolites such as N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate in the tissue examined. The most widely used clinical application of MRS has been in the evaluation of central nervous system disorders.MRS has its limitations and is not always specific but, with good technique and in combination with clinical information and conventional MRI, can be very helpful in diagnosing certain entities. For example, a specific pattern of metabolites can be seen in disorders such as Canavan's disease, creatine deficiency, and untreated bacterial brain abscess. MRS may also be helpful in the differentiation of high grade from low grade brain tumors, and perhaps in separating recurrent brain neoplasm from radiation injury.

We present a case of an intranasal meningoencephalocele masquerading as an 'intranasal polyp' in a 17-month-old child. Nasal meningoencephaloceles are uncommon anomalies and require a high index of suspicion for their diagnosis. Biopsy of such lesions without prior imaging studies can be detrimental because of the risk of cerebrospinal fluid leak and meningitis, and is therefore contraindicated. This case reiterates the fact that any child with an intranasal mass should undergo appropriate imaging studies prior to excisional biopsy.

We report a case of intravitreal silicone oil migration into the subarachnoid space and cerebral ventricles, as seen on CT and MRI. During several admissions over the course of 23 months, the silicone oil was seen tracking along the optic apparatus and subsequently appeared in the ventricles as free-floating droplets. The patient experienced repeated headaches, but was worked up extensively for possible intracranial hemorrhage before the correct diagnosis was recognized.

The aim of this study was to determine various imaging features of intraosseous meningiomas (IOMs) and differentiate low-grade from high-grade tumors. The histopathologic evaluation revealed World Health Organization (WHO) grade I tumor in 56 (86%) patients, grade II in 8 (12%), and grade III in 1 (2%) patient. WHO grade I was considered low grade and II and III were designated as high grade. Hyperostosis was observed most commonly in low-grade IOMs. Mixed hyperostotic/lytic pattern with radial bony spiculations and presence of a scalp mass seem to be more frequently associated with higher-grade IOMs.

Introduction Treatment of PCNSL has focused on multi-agent chemotherapy designed to cross the blood brain barrier (BBB); radiation therapy (RT) has a high response rate, but responses tend to be transient and associated with cognitive toxicity. The addition of rituximab has improved treatment outcomes for virtually all CD20-positive B-cell malignancies. Although rituximab is not believed to cross the BBB, enhancement on MRI corresponds with areas of BBB breakdown that could allow penetration of the antibody. Here we report the results of E1F05, an ECOG-ACRIN multicenter phase 2 prospective trial of rituximab added to a high-dose methotrexate (HD-MTX)-based chemotherapy regimen very similar to that used in the RTOG 93-10 study, but without RT. Methods Immunocompetent patients with newly diagnosed PCNSL, ECOG PS ≤3, with adequate liver and kidney function were eligible. Subjects received HD-MTX 3.5g/m2 with vincristine 1.4mg/m2 IV (flat cap of 2.8mg) weeks 1, 3, 5, 7, and 9, with leucovorin rescue; procarbazine 100mg/m2 PO daily for 7 days in weeks 1, 5, and 9; cytarabine 3g/m2 /day IV over 2 hours for 2 days on weeks 11 and 14; dexamethasone 16mg/day week 1, tapered by 4mg/week for weeks 2 and 3, 2mg/week weeks 4-6; and rituximab 375mg/m2 IV infusion 3 times a per week for weeks 1-4. Subjects with CSF involvement received intrathecal MTX 12mg every two weeks on weeks 2, 4, 6, 8, and 10 with leucovorin rescue. The primary endpoint was complete response rate (CR). Predefined secondary endpoints were PFS, OS. A total of 39 subjects was required to be able to rule out a 50% CR rate, with 90% power to detect a 70% CR rate. An interim analysis was planned after accrual of 23 subjects, requiring >12 CR to proceed to full accrual. Results Twenty-six patients were enrolled from December 2006 to February 2010; one subject was ineligible but included in toxicity evaluation. Median age was 57 (range 30-76); 40% were male (table 1). Sixteen subjects (65%) completed treatment per protocol; the most common reason for discontinuation was adverse events (4 subjects); 2 discontinued due to progressive disease (PD). Central radiology review (per the International PCNSL Collaborative Group) revealed that CR + CRu was 16/25 (64%,.95CI(42.5%-82%); ORR= 20/25 (80%), and 4/25(16%) had PD. Although the primary endpoint was met, the study was not re-opened after the interim analysis due to slow accrual and competing trials. At a median follow-up of 60 months, median PFS is 34 months (compared to 24 months in RTOG93-10), and median OS has not been reached (versus 37 months in RTOG93-10). Four year PFS is 33%, with 4 year OS 72% (approximately 30% in RTOG 93-10). No treatment-related deaths occurred. The most common grade 3-4 toxicities were hematologic (23% anemia, 77% neutropenia, 19% thrombocytopenia). Conclusion The addition of rituximab to multiagent chemotherapy is well tolerated. Response rates, PFS and OS are comparable to or better than those seen in RTOG 93-10, which included RT. These promising results suggest rituximab has activity in the CNS and may improve outcomes in PCNSL. Table 1. Subject Demographics Characteristics N (%) Gender Male 10 (40) Female 15 (60) Age Minimum 30 - 25% 51 - Median 57 - 75% 68 - Maximum 76 - ECOG PS 0-1 16 (64) 2-3 9 (36) Neurologic Function Status No Symptoms - - Minor Symptoms 11 (44) Moderate Symptoms/Fully Active 5 (20) Moderate Symptoms/Less than Fully Active 7 (28) Severe Neurologic Symptoms 2 (8) Table 2. Best overall response Response N (%) CR 7 (28) CRU* 9 (36) PR 4 (16) Stable -- -- PD 4 (16) Unevaluable 1 (4) *CR unconfirmed Table 3. Outcome Median Follow-Up 60 months PFS Median 34 months 2 year 63% 3 year 49% 4 year 33% OS Median ---- 2 year 84% 3 year 80% 4 year 72% Figure 1. Kaplan-Meier PFS Figure 1. Kaplan-Meier PFS Figure 2. Kaplan-Meier OS Figure 2. Kaplan-Meier OS Disclosures Advani: Seattle Genetics, Inc.: Research Funding; Genetech: Consultancy.

A computerized system for segmenting lesions in head and neck CT scans was developed to assist radiologists in estimation of the response to treatment of malignant lesions. The system performs 3D segmentation based on a level set model and uses as input an approximate bounding box for the lesion of interest. We investigated the effect of the interobserver variability of radiologists' marking of the bounding box on the automatic segmentation performance. In this preliminary study, CT scans from a pre-treatment exam and a post one-cycle chemotherapy exam of 34 patients with primary site head and neck neoplasms were used. For each tumor, an experienced radiologist marked the lesion with a bounding box and provided a reference standard by outlining the full 3D contour on both the pre- and post treatment scans. A second radiologist independently marked each tumor again with another bounding box. The correlation between the automatic and manual estimates for both the pre-to-post-treatment volume change and the percent volume change was r=0.95. Based on the bounding boxes by the second radiologist, the correlation between the automatic and manual estimate for the pre-to-post-treatment volume change was r=0.89 and for the percent volume change was r=0.91. The correlation for the automatic estimates obtained from the bounding boxes by the two radiologists was as follows: (1) pretreatment volume r=0.92, (2) post-treatment volume r=0.88, (3) pre-to-post-treatment change r=0.89 and (4) percent preto- post-treatment change r=0.90. The difference between the automatic estimates based on the two sets of bounding boxes did not achieve statistical significance for any of the estimates (p>0.29). The preliminary results indicate that the automated segmentation system can reliably estimate tumor size change in response to treatment relative to radiologist's hand segmentation as reference standard, and that the performance was robust against inter-observer variability in marking the input bounding boxes.

Endotracheal intubation in patients with potential cervical injury is a common dilemma in trauma. Although direct laryngoscopy (DL) with manual in-line stabilization (MILS) is a standard technique there is little data on the effect of MILS on cervical motion. Likewise there is little data available regarding alternative airway techniques in this setting. This study compared intubations with and without MILS in a cadaver model of cervical instability. We also used this model to compare intubations using DL with a Macintosh blade versus a Bullard laryngoscope (BL).Complete C4-C5 disarticulations were surgically created in 10 fresh human cadavers. The cadavers were then intubated in a random order with either BL or DL with and without MILS. The motion at the unstable interspace was measured for subluxation, angulation, and distraction.MILS did not significantly affect maximal motion of this model in any of the three measures using either DL or BL. There were no clinically significant differences in maximal median motion in any of the three measures when comparing the two blades. However, there was significantly more variance in the subluxation caused by DL than by BL.We were unable to demonstrate any significant effect of MILS on the motion of an unstable cervical spine in this cadaver model. The BL appears to be a viable alternative to DL in the setting of an unstable lower cervical spine.