Concurrent Middle Cerebral Artery and Basilar Artery Occlusions Treated With Mechanical Thrombectomy in a Patient With Active COVID-19 Infection.

We report a rare case of acute ischemic stroke from concurrent large vessel occlusions (LVOs) and subsequent successful mechanical thrombectomy revascularization in a patient with active coronavirus disease 2019 (COVID-19) pneumonia. A 59-year-old woman presented to the emergency department after one week of intermittent chest pain, dyspnea, and diarrhea found to have COVID-19 pneumonia. On hospital day three, the patient developed acute altered mental status and hemiparesis with a National Institutes of Health Stroke Scale (NIHSS) of 22. CT with angiography demonstrated concurrent occlusions of the basilar artery and the M1 segment of the right middle cerebral artery (MCA) without intracranial hemorrhage. The patient was taken for urgent mechanical thrombectomy of the basilar artery, followed by the MCA, both of which were successful (thrombolysis in cerebral infarction (TICI) 3 and 2B) and timely. Despite early revascularization, the patient did not improve clinically with absent brainstem reflexes and a full MCA territorial infarct on imaging. This case describes a rare stroke syndrome of concurrent LVOs with rapid infarct progression despite timely revascularization. This example illustrates a severe cerebrovascular complication of active COVID-19 infection and the importance of vigilance regarding stroke prevention and neurological examination monitoring.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

Morning glory disc anomaly and its implications in moyamoya arteriopathy: a retrospective case series.

OBJECTIVE: Morning glory disc anomaly (MGDA), a congenital abnormality of the optic nerve, may be associated with moyamoya arteriopathy, a cerebrovascular abnormality. In this study, the authors aimed to define the temporal evolution of cerebrovascular arteriopathy in patients with MGDA to characterize a rational strategy for screening and management over time. METHODS: The records of pediatric neurosurgical patients at two academic institutions were retrospectively reviewed to identify cases of cerebral arteriopathy and MGDA, including radiographic and clinical records documenting patient outcomes of medical and surgical management. RESULTS: Thirteen cases of moyamoya syndrome (MMS) associated with MGDA were identified in 13 children aged 0.6-17 years. The pattern of arteriopathy resembled that of non-MGDA MMS, with predominantly anterior circulation involvement. The arteriopathy lateralized with the MGDA, although 3 patients also had contralateral involvement. The overall group was followed for a median of 3.2 years. Radiological biomarkers of cerebral ischemia were applied to guide surgical decisions, and more than half of the patients (7 of 13) had evidence of stroke or progression on serial imaging. Nine patients underwent revascularization surgery, and 4 were managed medically. CONCLUSIONS: Cerebral arteriopathy observed in association with MGDA resembles MMS seen in patients without MGDA and is dynamic, with progression observed over months to years and an associated risk of cerebral ischemia that indicates a role for surgical revascularization. Radiological biomarkers may augment clinical data to identify candidates for revascularization surgery.

Neurolymphomatosis of the brachial plexus from atypical primary central nervous system lymphoma lesions: A case report and review of the literature.

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive and extranodal non-Hodgkin lymphoma limited to the neuroaxis. In immunocompetent individuals, PCNSL is more common in older adults and lacks the association with the Epstein-Barr virus found in individuals with AIDS-associated PCNSL. Because the clinical presentation and radiographic findings of PCNSL are highly variable, stereotactic brain biopsy is typically required for definitive diagnosis. High-dose methotrexate, in combination with other chemotherapeutic agents with or without whole brain radiation, is the mainstay of treatment. Case Description: A 70-year-old HIV-negative woman presented with confusion, acute flaccid left arm weakness, and left hand numbness. Head computed tomography without contrast demonstrated a 1 cm hyperdense round lesion in the suprasellar cistern that prompted further evaluation. Gadolinium-enhanced brain magnetic resonance imaging demonstrated enhancing lesions with heterogeneous signal intensity in the suprasellar, pineal, and right periatrial regions that did not explain the limb weakness and numbness. Serum and cerebrospinal fluid (CSF) studies were unrevealing, and a diagnosis of PCNSL was made following stereotactic biopsy. The patient's liver cirrhosis precluded chemotherapy, but treatment with whole-brain radiation was pursued. Conclusion: The myriad clinical presentations and insidious course of PCNSL contribute to diagnostic difficulties, delays in treatment, and poor outcomes. Stereotactic brain biopsy is the primary method of PCNSL diagnosis since malignant cells are typically not detected in CSF. PCNSL should be considered in the differential diagnosis when immunocompetent elderly patients present with multiple intracranial lesions, even in the presence of lower motor neuron findings.

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

Chiari 1 and Hydrocephalus - A Review.

Chari 1 malformation, a radiologic finding of caudal cerebellar tonsillar displacement, has a clinical course that can range from benign to complications involving life-threatening hydrocephalus. While the pathophysiologic processes underlying this variation in outcome remain a matter of scientific debate, the clinical realities and decision-making conundrums that these patients pose require a coherent approach to this entity. In this review, we seek to highlight the various processes underlying the development of hydrocephalus in patients with Chiari 1 malformations. Hydrocephalus may occur as a cause, consequence, or in parallel with the development of Chiari 1 malformation, and understanding the etiology of such hydrocephalus is critical to the treatment of Chiari 1 malformations with associated hydrocephalus. We further discuss the literature pertaining to the management of these patients and unify the current scientific thinking on Chiari 1 malformations with the extant data on operative management of Chiari 1 to develop a structured and pragmatic approach to the diagnosis and management of patients with Chiari 1-associated hydrocephalus.

Glioblastomas located in proximity to the subventricular zone (SVZ) exhibited enrichment of gene expression profiles associated with the cancer stem cell state.

INTRODUCTION: Conflicting results have been reported in the association between glioblastoma proximity to the subventricular zone (SVZ) and enrichment of cancer stem cell properties. Here, we examined this hypothesis using magnetic resonance (MR) images derived from 217 The Cancer Imaging Archive (TCIA) glioblastoma subjects. METHODS: Pre-operative MR images were segmented automatically into contrast enhancing (CE) tumor volumes using Iterative Probabilistic Voxel Labeling (IPVL). Distances were calculated from the centroid of CE tumor volumes to the SVZ and correlated with gene expression profiles of the corresponding glioblastomas. Correlative analyses were performed between SVZ distance, gene expression patterns, and clinical survival. RESULTS: Glioblastoma located in proximity to the SVZ showed increased mRNA expression patterns associated with the cancer stem-cell state, including CD133 (P = 0.006). Consistent with the previous observations suggesting that glioblastoma stem cells exhibit increased DNA repair capacity, glioblastomas in proximity to the SVZ also showed increased expression of DNA repair genes, including MGMT (P = 0.018). Reflecting this enhanced DNA repair capacity, the genomes of glioblastomas in SVZ proximity harbored fewer single nucleotide polymorphisms relative to those located distant to the SVZ (P = 0.003). Concordant with the notion that glioblastoma stem cells are more aggressive and refractory to therapy, patients with glioblastoma in proximity to SVZ exhibited poorer progression free and overall survival (P < 0.01). CONCLUSION: An unbiased analysis of TCIA suggests that glioblastomas located in proximity to the SVZ exhibited mRNA expression profiles associated with stem cell properties, increased DNA repair capacity, and is associated with poor clinical survival.

Epilepsy surgery in tuberous sclerosis complex (TSC): emerging techniques and redefinition of treatment goals.

Epilepsy occurs in nearly all patients with tuberous sclerosis and is often refractory to medical treatment. The definition of surgical candidacy in these patients has broadened in recent years due to philosophical and technological advances. The goals of surgery have shifted to focusing on quality of life and maximizing neurodevelopmental potential in patients unable to obtain seizure freedom. Novel diagnostic, ablative, and neuromodulatory techniques have been developed that may help patients that were previously considered inoperable to have an improved quality of life. In the coming years, it is expected that these techniques will be further refined and lead to an improvement of neurological prognosis in patients with tuberous sclerosis.

Accuracy and Workflow Improvements for Responsive Neurostimulation Hippocampal Depth Electrode Placement Using Robotic Stereotaxy.

Background: Robotic stereotaxy is increasingly common in epilepsy surgery for the implantation of stereo-electroencephalography (sEEG) electrodes for intracranial seizure monitoring. The use of robots is also gaining popularity for permanent stereotactic lead implantation applications such as in deep brain stimulation and responsive neurostimulation (RNS) procedures. Objective: We describe the evolution of our robotic stereotactic implantation technique for placement of occipital-approach hippocampal RNS depth leads. Methods: We performed a retrospective review of 10 consecutive patients who underwent robotic RNS hippocampal depth electrode implantation. Accuracy of depth lead implantation was measured by registering intraoperative post-implantation fluoroscopic CT images and post-operative CT scans with the stereotactic plan to measure implantation accuracy. Seizure data were also collected from the RNS devices and analyzed to obtain initial seizure control outcome estimates. Results: Ten patients underwent occipital-approach hippocampal RNS depth electrode placement for medically refractory epilepsy. A total of 18 depth electrodes were included in the analysis. Six patients (10 electrodes) were implanted in the supine position, with mean target radial error of 1.9 ± 0.9 mm (mean ± SD). Four patients (8 electrodes) were implanted in the prone position, with mean radial error of 0.8 ± 0.3 mm. The radial error was significantly smaller when electrodes were implanted in the prone position compared to the supine position (p = 0.002). Early results (median follow-up time 7.4 months) demonstrate mean seizure frequency reduction of 26% (n = 8), with 37.5% achieving ≥50% reduction in seizure frequency as measured by RNS long episode counts. Conclusion: Prone positioning for robotic implantation of occipital-approach hippocampal RNS depth electrodes led to lower radial target error compared to supine positioning. The robotic platform offers a number of workflow advantages over traditional frame-based approaches, including parallel rather than serial operation in a bilateral case, decreased concern regarding human error in setting frame coordinates, and surgeon comfort.

Utility of Immediate Postprocedural Cone Beam Computed Tomography Scan in the Detection of Ischemic and Hemorrhagic Complications in Pediatric Neurointerventional Surgery.

BACKGROUND: Cone beam computed tomography (CBCT) imaging is used commonly in neurointerventional surgery for rapid intraprocedural assessment and planning of intracranial interventions. Our goal was to evaluate the ability of immediate postprocedural CBCT scan in assessing potential complications in pediatric patients. METHODS: A retrospective review was completed to include all pediatric patients at our hospital with an immediate postprocedural CBCT scan with the Artis Q system. Demographic, clinical, and imaging data were examined. CBCT images were reviewed by 3 independent neurointerventionalists to assess ventricular system/subarachnoid spaces, gray-white differentiation, and ischemia or hemorrhage if present. Each assessment was rated qualitatively on a 4-point scale and was compared with conventional computed tomography (cCT) scan when available. Interrater reliability was assessed and radiation dose data were reviewed. RESULTS: Thirty-five patients were included with an average age of 11.0 ± 5.1 years (median, 10.9; range, 1.1-18 years). Of the patients, 54.3% were boys; 34.3% were Hispanic and 34.3% were non-Hispanic white. Diagnoses included a variety of vascular pathologies. CBCT scan had a mean score of 2.69 ± 0.54 out of 3 for ventricular and subarachnoid space assessment with a combined interrater reliability of 0.82, 1.71 ± 1.38 for hemorrhage with a combined interrater reliability of 1.00, and 0.52 ± 0.60 for gray-white differentiation with a combined interrater reliability of 0.79. CONCLUSIONS: Immediate postprocedural CBCT images were adequate to detect ventricular size/subarachnoid spaces changes and large volume hemorrhage compared with cCT scan in pediatric patients. However, there are limitations using immediate CBCT images to detect small volume hemorrhage and ischemic changes.

Treatment strategies for glioblastoma in older patients: age is just a number.

BACKGROUND/PURPOSE: Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival. METHODS: A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. RESULTS: A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63-0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11-0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67-4.12) were independently associated with improved OS. CONCLUSIONS: Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.

An update on pediatric surgical epilepsy: Part I.

Epilepsy affects many children worldwide, with drug-resistant epilepsy affecting 20-40% of all children with epilepsy. This carries a significant burden for patients and their families and is strongly correlated with poor cognitive outcomes, depression, anxiety, developmental delay, and impaired activities of daily living. For this reason, we sought to explore the role of pediatric epilepsy surgery and provide an overview of the factors contributing to epilepsy surgery planning and execution. We review the necessary preoperative evaluations, surgical indications, planning considerations, and surgical options to provide a clear pathway in the evaluation and planning of pediatric epilepsy surgery.

Molecular physiology of contrast enhancement in glioblastomas: An analysis of The Cancer Imaging Archive (TCIA).

The physiologic processes underlying MRI contrast enhancement in glioblastoma patients remain poorly understood. MRIs of 148 glioblastoma subjects from The Cancer Imaging Archive were segmented using Iterative Probabilistic Voxel Labeling (IPVL). Three aspects of contrast enhancement (CE) were parametrized: the mean intensity of all CE voxels (CEi), the intensity heterogeneity in CE (CEh), and volumetric ratio of CE to necrosis (CEr). Associations between these parameters and patterns of gene expression were analyzed using DAVID functional enrichment analysis. Glioma CpG island methylator phenotype (G-CIMP) glioblastomas were poorly enhancing. Otherwise, no differences in CE parameters were found between proneural, neural, mesenchymal, and classical glioblastomas. High CEi was associated with expression of genes that mediate inflammatory responses. High CEh was associated with increased expression of genes that regulate remodeling of extracellular matrix (ECM) and endothelial permeability. High CEr was associated with increased expression of genes that mediate cellular response to stressful metabolic states, including hypoxia and starvation. Our results indicate that CE in glioblastoma is associated with distinct biological processes involved in inflammatory response and tissue hypoxia. Integrative analysis of these CE parameters may yield meaningful information pertaining to the biologic state of glioblastomas and guide future therapeutic paradigms.

Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles.

Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that glioblastoma EVs may be important mediators of immunosuppression and that PD-L1 could play a role. We show that glioblastoma EVs block T cell activation and proliferation in response to T cell receptor stimulation. PD-L1 was expressed on the surface of some, but not of all, glioblastoma-derived EVs, with the potential to directly bind to PD1. An anti-PD1 receptor blocking antibody significantly reversed the EV-mediated blockade of T cell activation but only when PD-L1 was present on EVs. When glioblastoma PD-L1 was up-regulated by IFN-γ, EVs also showed some PD-L1-dependent inhibition of T cell activation. PD-L1 expression correlated with the mesenchymal transcriptome profile and was anatomically localized in the perinecrotic and pseudopalisading niche of human glioblastoma specimens. PD-L1 DNA was present in circulating EVs from glioblastoma patients where it correlated with tumor volumes of up to 60 cm3. These results suggest that PD-L1 on EVs may be another mechanism for glioblastoma to suppress antitumor immunity and support the potential of EVs as biomarkers in tumor patients.

Quantification of glioblastoma mass effect by lateral ventricle displacement.

Mass effect has demonstrated prognostic significance for glioblastoma, but is poorly quantified. Here we define and characterize a novel neuroimaging parameter, lateral ventricle displacement (LVd), which quantifies mass effect in glioblastoma patients. LVd is defined as the magnitude of displacement from the center of mass of the lateral ventricle volume in glioblastoma patients relative to that a normal reference brain. Pre-operative MR images from 214 glioblastoma patients from The Cancer Imaging Archive (TCIA) were segmented using iterative probabilistic voxel labeling (IPVL). LVd, contrast enhancing volumes (CEV) and FLAIR hyper-intensity volumes (FHV) were determined. Associations with patient survival and tumor genomics were investigated using data from The Cancer Genome Atlas (TCGA). Glioblastoma patients had significantly higher LVd relative to patients without brain tumors. The variance of LVd was not explained by tumor volume, as defined by CEV or FLAIR. LVd was robustly associated with glioblastoma survival in Cox models which accounted for both age and Karnofsky's Performance Scale (KPS) (p = 0.006). Glioblastomas with higher LVd demonstrated increased expression of genes associated with tumor proliferation and decreased expression of genes associated with tumor invasion. Our results suggest LVd is a quantitative measure of glioblastoma mass effect and a prognostic imaging biomarker.

Reduced Hemispheric Asymmetry of White Matter Microstructure in Autism Spectrum Disorder.

OBJECTIVE: Many past studies have suggested atypical functional and anatomical hemispheric asymmetries in autism spectrum disorder (ASD). However, almost all of these have examined only language-related asymmetries. Here, we conduct a comprehensive investigation of microstructural asymmetries across a large number of fiber tracts in ASD. METHOD: We used diffusion tensor imaging for a comprehensive investigation of anatomical white matter asymmetries across the entire white matter skeleton, using tract-based spatial statistics in 41 children and adolescents with ASD and a matched group of 44 typically developing (TD) participants. RESULTS: We found significant asymmetries in the TD group, being rightward for fractional anisotropy and leftward for mean diffusivity (with concordant asymmetries for radial and axial diffusivity). These asymmetries were significantly reduced in the group with ASD: in whole brain analysis for fractional anisotropy, and in a region where several major association and projection tracts travel in close proximity within occipital white matter for mean diffusivity, axial diffusivity, and radial diffusivity. No correlations between global white matter asymmetry and age or socio-communicative abilities were detected. CONCLUSION: Our findings in TD children and adolescents can be interpreted as reflecting different processing modes (more integrative in the right and more specialized in the left hemisphere). These asymmetries and the "division of labor" between hemispheres implied by them appear to be diminished in autism spectrum disorder.

Differential localization of glioblastoma subtype: implications on glioblastoma pathogenesis.

INTRODUCTION: The subventricular zone (SVZ) has been implicated in the pathogenesis of glioblastoma. Whether molecular subtypes of glioblastoma arise from unique niches of the brain relative to the SVZ remains largely unknown. Here, we tested whether these subtypes of glioblastoma occupy distinct regions of the cerebrum and examined glioblastoma localization in relation to the SVZ. METHODS: Pre-operative MR images from 217 glioblastoma patients from The Cancer Imaging Archive were segmented automatically into contrast enhancing (CE) tumor volumes using Iterative Probabilistic Voxel Labeling (IPVL). Probabilistic maps of tumor location were generated for each subtype and distances were calculated from the centroid of CE tumor volumes to the SVZ. Glioblastomas that arose in a Genetically Modified Murine Model (GEMM) model were also analyzed with regard to SVZ distance and molecular subtype. RESULTS: Classical and mesenchymal glioblastomas were more diffusely distributed and located farther from the SVZ. In contrast, proneural and neural glioblastomas were more likely to be located in closer proximity to the SVZ. Moreover, in a GFAP-CreER; PtenloxP/loxP; Trp53loxP/loxP; Rb1loxP/loxP; Rbl1-/- GEMM model of glioblastoma where tumor can spontaneously arise in different regions of the cerebrum, tumors that arose near the SVZ were more likely to be of proneural subtype (p < 0.0001). CONCLUSIONS: Glioblastoma subtypes occupy different regions of the brain and vary in proximity to the SVZ. These findings harbor implications pertaining to the pathogenesis of glioblastoma subtypes.

Characterization and Correction of Geometric Distortions in 814 Diffusion Weighted Images.

INTRODUCTION: Diffusion Weighted Imaging (DWI), which is based on Echo Planar Imaging (EPI) protocols, is becoming increasingly important for neurosurgical applications. However, its use in this context is limited in part by significant spatial distortion inherent to EPI. METHOD: We evaluated an efficient algorithm for EPI distortion correction (EPIC) across 814 DWI scans from 250 brain tumor patients and quantified the magnitude of geometric distortion for whole brain and multiple brain regions. RESULTS: Evaluation of the algorithm's performance revealed significantly higher mutual information between T1-weighted pre-contrast images and corrected b = 0 images than the uncorrected b = 0 images (p < 0.001). The distortion magnitude across all voxels revealed a median EPI distortion effect of 2.1 mm, ranging from 1.2 mm to 5.9 mm, the 5th and 95th percentile, respectively. Regions adjacent to bone-air interfaces, such as the orbitofrontal cortex, temporal poles, and brain stem, were the regions most severely affected by DWI distortion. CONCLUSION: Using EPIC to estimate the degree of distortion in 814 DWI brain tumor images enabled the creation of a topographic atlas of DWI distortion across the brain. The degree of displacement of tumors boundaries in uncorrected images is severe but can be corrected for using EPIC. Our results support the use of distortion correction to ensure accurate and careful application of DWI to neurosurgical practice.

Restriction Spectrum Imaging As a Potential Measure of Cortical Neurite Density in Autism.

Autism postmortem studies have shown various cytoarchitectural anomalies in cortical and limbic areas including increased cell packing density, laminar disorganization, and narrowed minicolumns. However, there is little evidence on dendritic and axonal organization in ASD. Recent imaging techniques have the potential for non-invasive, in vivo studies of small-scale structure in the human brain, including gray matter. Here, Restriction Spectrum Imaging (RSI), a multi-shell diffusion-weighted imaging technique, was used to examine gray matter microstructure in 24 children with ASD (5 female) and 20 matched typically developing (TD) participants (2 female), ages 7-17 years. RSI extends the spherical deconvolution model to multiple length scales to characterize neurite density (ND) and organization. Measures were examined in 48 cortical regions of interest per hemisphere. To our knowledge, this is the first time that a multi-compartmental diffusion model has been applied to cortical gray matter in ASD. The ND measure detected robust age effects showing a significant positive relationship to age in all lobes except left temporal when groups were combined. Results were also suggestive of group differences (ASDTD) in bilateral parietal regions as well as widespread age effects were detected. Our findings support the value of multi-shell diffusion imaging for assays of cortical gray matter. This approach has the potential to add to postmortem literature, examining intracortical organization, intracortical axonal content, myelination, or caliber. Robust age effects further support the validity of the ND metric for in vivo examination of gray matter microstructure in ASD and across development. While diffusion MRI does not approach the precision of histological studies, in vivo imaging measures of microstructure can complement postmortem studies, by allowing access to large sample sizes, a whole-brain field of view, longitudinal designs, and combination with behavioral and functional assays. This makes multi-shell diffusion imaging a promising technique for understanding the underlying cytoarchitecture of the disorder.

Corticospinal tract anatomy and functional connectivity of primary motor cortex in autism.

OBJECTIVE: Growing evidence indicates that autism spectrum disorder (ASD) stems from abnormal structural and functional connectivity of neural networks. Although diagnostic symptoms are sociocommunicative, motor-related functions (beyond repetitive mannerisms) are also impaired. However, evidence on connectivity at the level of basic motor execution is limited, which we address here. METHOD: We compared right-handed children and adolescents (aged 7-18 years) with ASD (n = 44) to matched typically developing participants (TD, n = 36) using magnetic resonance imaging (MRI). Diffusion-weighted imaging and probabilistic tractography measured microstructure of the corticospinal tract (CST). Intrinsic functional connectivity MRI examined whole-brain voxelwise correlations, both with identical precentral gyrus (PCG) seeds. RESULTS: In the group with ASD, radial and mean diffusivity were increased bilaterally in the CST, particularly in superior segments, and a leftward asymmetry of CST volume detected in the TD group was reversed. Functionally, overconnectivity was found for both left and right PCG with prefrontal, parietal, medial occipital, and cingulate cortices. The group with ASD also showed significantly reduced asymmetry of functional connectivity for both left and right PCG seeds. Finally, in the group with ASD, significant correlations were found for functional overconnectivity of the right PCG seed with anisotropy and mean diffusivity in the right CST. CONCLUSION: The findings, implicating both functional and anatomical connectivity of the primary motor cortex, suggest that network anomalies in ASD go well beyond sociocommunicative domains, affecting basic motor execution. They also suggest that even in right-handed adolescents with ASD, typical left hemisphere dominance is reduced, both anatomically and functionally, with an unusual degree of right hemisphere motor participation.