Evaluation of 3D T1-weighted spoiled gradient echo MR image quality using artificial intelligence image reconstruction techniques in the pediatric brain.

PURPOSE: To assess image quality and diagnostic confidence of 3D T1-weighted spoiled gradient echo (SPGR) MRI using artificial intelligence (AI) reconstruction. MATERIALS AND METHODS: This prospective, IRB-approved study enrolled 50 pediatric patients (mean age = 11.8 ± 3.1 years) undergoing clinical brain MRI. In addition to standard of care (SOC) compressed SENSE (CS = 2.5), 3D T1-weighted SPGR images were obtained with higher CS acceleration factors (5 and 8) to evaluate the ability of AI reconstruction to improve image quality and reduce scan time. Images were reviewed independently on dedicated research PACS workstations by two neuroradiologists. Quantitative analysis of signal intensities to calculate apparent grey and white matter signal to noise (aSNR) and grey-white matter apparent contrast to noise ratios (aCNR) was performed. RESULTS: AI improved overall image quality compared to standard CS reconstruction in 35% (35/100) of evaluations in CS = 2.5 (average scan time = 221 ± 6.9 s), 100% (46/46) of CS = 5 (average scan time = 113.3 ± 4.6 s) and 94% (47/50) of CS = 8 (average scan time = 74.1 ± 0.01 s). Quantitative analysis revealed significantly higher grey matter aSNR, white matter aSNR and grey-white matter aCNR with AI reconstruction compared to standard reconstruction for CS 5 and 8 (all p-values < 0.001), however not for CS 2.5. CONCLUSIONS: AI reconstruction improved overall image quality and gray-white matter qualitative and quantitative aSNR and aCNR in highly accelerated (CS = 5 and 8) 3D T1W SPGR images in the majority of pediatric patients.

MRI and pathology comparisons in Rasmussen's encephalitis: a multi-institutional examination of hemispherotomy outcomes relative to imaging and histological severity.

PURPOSE: Rasmussen encephalitis (RE) is a very rare chronic neurological disorder of unilateral inflammation of the cerebral cortex. Hemispherotomy provides the best chance at achieving seizure freedom in RE patients, but with significant risks and variable long-term outcomes. The goal of this study is to utilize our multicenter pediatric cohort to characterize if differences in pathology and/or imaging characterization of RE may provide a window into post-operative seizure outcomes, which in turn could guide decision-making for parents and healthcare providers. METHODS: This multi-institutional retrospective review of medical record, imaging, and pathology samples was approved by each individual institution's review board. Data was collected from all known pediatric cases of peri-insular functional hemispherotomy from the earliest available electronic medical records. Mean follow-up time was 4.9 years. Clinical outcomes were measured by last follow-up visit using both Engel and ILAE scoring systems. Relationships between categorical and continuous variables were analyzed with Pearson correlation values. RESULTS: Twenty-seven patients met study criteria. No statistically significant correlations existed between patient imaging and pathology data. Pathology stage, MRI brain imaging stages, and a combined assessment of pathology and imaging stages showed no statistically significant correlation to post-operative seizure freedom rates. Hemispherectomy Outcome Prediction Scale scoring demonstrated seizure freedom in only 71% of patients receiving a score of 1 and 36% of patients receiving a score of 2 which were substantially lower than predicted. CONCLUSIONS: Our analysis did not find evidence for either independent or combined analysis of imaging and pathology staging being predictive for post peri-insular hemispherotomy seizure outcomes, prompting the need for other biomarkers to be explored. Our data stands in contrast to the recently proposed Hemispherectomy Outcome Prediction Scale and does not externally validate this metric for an RE cohort.

Evaluation of T2W FLAIR MR image quality using artificial intelligence image reconstruction techniques in the pediatric brain.

BACKGROUND: Artificial intelligence (AI) reconstruction techniques have the potential to improve image quality and decrease imaging time. However, these techniques must be assessed for safe and effective use in clinical practice. OBJECTIVE: To assess image quality and diagnostic confidence of AI reconstruction in the pediatric brain on fluid-attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: This prospective, institutional review board (IRB)-approved study enrolled 50 pediatric patients (median age=12 years, Q1=10 years, Q3=14 years) undergoing clinical brain MRI. T2-weighted (T2W) FLAIR images were reconstructed by both standard clinical and AI reconstruction algorithms (strong denoising). Images were independently rated by two neuroradiologists on a dedicated research picture archiving and communication system (PACS) to indicate whether AI increased, decreased, or had no effect on image quality compared to standard reconstruction. Quantitative analysis of signal intensities was also performed to calculate apparent signal to noise (aSNR) and apparent contrast to noise (aCNR) ratios. RESULTS: AI reconstruction was better than standard in 99% (reader 1, 49/50; reader 2, 50/50) for overall image quality, 99% (reader 1, 49/50; reader 2, 50/50) for subjective SNR, and 98% (reader 1, 49/50; reader 2, 49/50) for diagnostic preference. Quantitative analysis revealed significantly higher gray matter aSNR (30.6±6.5), white matter aSNR (21.4±5.6), and gray-white matter aCNR (7.1±1.6) in AI-reconstructed images compared to standard reconstruction (18±2.7, 14.2±2.8, 4.4±0.8, p<0.001) respectively. CONCLUSION: We conclude that AI reconstruction improved T2W FLAIR image quality in most patients when compared with standard reconstruction in pediatric patients.

Comparing electrical stimulation functional mapping with subdural electrodes and stereoelectroencephalography.

OBJECTIVE: Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM-induced seizures (EISs) between the two electrode types. METHODS: Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates. RESULTS: We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication. SIGNIFICANCE: SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM.

Neuropsychological outcomes after epilepsy surgery: A comparison of stereo electroencephalography and subdural electrodes.

BACKGROUND AND PURPOSE: We analyzed the association of neuropsychological outcomes after epilepsy surgery with the intracranial electrode type (stereo electroencephalography [SEEG] and subdural electrodes [SDE]), and electrical stimulation mapping (ESM) of speech/language. METHODS: Drug-resistant epilepsy patients who underwent comprehensive neuropsychological evaluation before and 1 year after epilepsy surgery were included. SEEG and SDE subgroups were matched by age, handedness, operated hemisphere, and seizure freedom. Postsurgical neuropsychological outcomes (adjusted for presurgical scores) and reliable change indices were analyzed as functions of electrode type and ESM. RESULTS: Ninety-nine patients aged 6-29 years were included with similar surgical resection/ablation volumes in the SEEG and SDE subgroups. Most of the neuropsychological outcomes were comparable between SEEG and SDE subgroups; however, Working Memory and Processing Speed were significantly improved in the SEEG subgroup. Undergoing language ESM was associated with significant improvements in Spelling, Letter-Word Identification, Vocabulary, Verbal Comprehension, Verbal Learning, and Story Memory scores, but a decline in Calculation scores. CONCLUSIONS: Intracranial evaluations with SEEG and SDE are comparable in terms of long-term postsurgical neuropsychological outcomes. Our data suggest that SEEG may be associated with improvements in working memory and processing speed, representing cognitive domains served by spatially distributed networks. Our study also supports wider use of language ESM before epilepsy surgery, preferably using other language tasks in addition to visual naming. Rather than the type of electrode, postsurgical neuropsychological outcomes are driven by whether language ESM was performed or not, with beneficial effects of language mapping.

Extraneural Metastases of Diffuse Midline Glioma, H3 K27M-Mutant at Diagnosis: Case Report, Review of the Literature, and Identifying Targetable Alterations.

Extraneural metastases are rare in pediatric high-grade gliomas and little is known about the genomic profiles of tumors that disseminate beyond the central nervous system. We describe a pediatric patient with H3 K27M-mutant diffuse midline glioma of the brain and spine with biopsy-confirmed osseous metastases present at diagnosis and suspected metastatic parenchymal pulmonary disease. Several potentially clinically and/or therapeutically relevant genomic alterations were identified, including H3F3A and TP53 mutations as well as MET, CDK6, EMSY, and PIK3CG amplifications. Sequencing is critical to improve our understanding of the molecular drivers of distant metastases and discover therapeutic targets that penetrate all disease sites.

Comparison of outcomes after stereoelectroencephalography and subdural grid monitoring in pediatric tuberous sclerosis complex.

OBJECTIVE: Patients with tuberous sclerosis complex (TSC) epilepsy present with unique clinical challenges such as early seizure onset and high rates of intractability and multifocality. Although there are numerous studies about the safety and efficacy of stereoelectroencephalography (SEEG), this topic has not been studied in TSC patients who have distinct epilepsy profiles. The authors investigated subdural grid (SDG) and SEEG monitoring to determine whether these procedures lead to similar seizure and safety outcomes and to identify features unique to this pediatric population. METHODS: TSC patients who underwent SDG or SEEG placement and a second epilepsy surgery during the period from 2007 to 2021 were included in this single-center retrospective cohort analysis. Various patient, hospitalization, and epilepsy characteristics were collected. RESULTS: A total of 50 TSC patients were included in this study: 30 were included in the SDG cohort and 20 in the SEEG cohort. Baseline weekly seizure count did not significantly differ between the 2 groups (p = 0.412). The SEEG group had a greater mean baseline number of antiepileptic drugs (AEDs) (3.0 vs 2.0, p = 0.003), higher rate of previous surgical interventions (25% vs 0%, p = 0.007), and larger proportion of patients who underwent bilateral monitoring (50% vs 13.3%, p = 0.005). Despite this, there was no significant difference in seizure freedom between the SDG and SEEG cohorts. The mean reduction in seizure count was 84.9% and 47.8% of patients were seizure free at last follow-up (mean 79.4 months). SEEG trended toward being a safer procedure than SDG monitoring, with a shorter mean ICU stay (0.7 days vs 3.9 days, p < 0.001), lower blood transfusion rate (0% vs 13.3%, p = 0.140), and lower surgical complication rate (0% vs 10%, p = 0.265). CONCLUSIONS: In the comparison of the SDG and SEEG cohorts, the SEEG group included patients who appeared to receive more aggressive management and have a higher rate of multifocality, more prior surgical interventions, more AEDs at baseline, and a higher rate of bilateral invasive monitoring. Despite this, the SEEG cohort had similar seizure outcomes and a trend toward increased safety. Based on these findings, SEEG appears to allow for monitoring of a wider breadth of TSC patients given its minimally invasive nature and its relative simplicity for monitoring numerous regions of the brain.

The effects of internal jugular vein compression for modulating and preserving white matter following a season of American tackle football: A prospective longitudinal evaluation of differential head impact exposure.

The purpose of this clinical trial was to examine whether internal jugular vein compression (JVC)-using an externally worn neck collar-modulated the relationships between differential head impact exposure levels and pre- to postseason changes in diffusion tensor imaging (DTI)-derived diffusivity and anisotropy metrics of white matter following a season of American tackle football. Male high-school athletes (n = 284) were prospectively assigned to a non-collar group or a collar group. Magnetic resonance imaging data were collected from participants pre- and postseason and head impact exposure was monitored by accelerometers during every practice and game throughout the competitive season. Athletes' accumulated head impact exposure was systematically thresholded based on the frequency of impacts of progressively higher magnitudes (10 g intervals between 20 to 150 g) and modeled with pre- to postseason changes in DTI measures of white matter as a function of JVC neck collar wear. The findings revealed that the JVC neck collar modulated the relationships between greater high-magnitude head impact exposure (110 to 140 g) and longitudinal changes to white matter, with each group showing associations that varied in directionality. Results also revealed that the JVC neck collar group partially preserved longitudinal changes in DTI metrics. Collectively, these data indicate that a JVC neck collar can provide a mechanistic response to the diffusion and anisotropic properties of brain white matter following the highly diverse exposure to repetitive head impacts in American tackle football. Clinicaltrials.gov: NCT# 04068883.

Overcoming barriers to establishing autopsy procurement programs in pediatric patients with central nervous system tumors: a call to develop regional centers.

BACKGROUND: While autopsy-repository programs with a variety of pediatric central nervous system (CNS) tumor types are a critical resource for preclinical neuro-oncology research, few exist and there is no published guidance on how to develop one. The goal of this prospective Pediatric Brain Tumor Repository (PBTR) study was to develop such a program at Cincinnati Children's Hospital Medical Center (CCHMC) and then publish the quantitative and experiential data as a guide to support the development of similar programs. METHODS: Protocols and infrastructure were established-to educate oncologists and families, establish eligibility, obtain consent, address pre- and post-autopsy logistics (e.g., patient and tissue transportation), process and authenticate tissue samples, and collect and analyze data. RESULTS: Of the 129 pediatric CNS tumor patients at CCHMC who died between 2013 and 2018, 109 were eligible for our study. Of these, 74% (81 of 109) were approached for PBTR donation, and 68% (55 of 81) consented. In the final year of the study, approach and consent rates were 93% and 85%, respectively. Median time from death to autopsy (postmortem interval, PMI) was 10 h (range, 1.5-30). In the outpatient setting, PMI increased with distance (from the hospice/home where the patient died to CCHMC). In all patients, PMI appeared to be lower, when consent was obtained more than 24 h before death. CONCLUSIONS: Procurement of autopsy specimens need not be a barrier in neuro-oncology research. Regional centers, strict timing-of-consent, patient education, and dedicated staff are all needed to minimize PMI and, thereby, increase the value of the procured tissue for an array of basic and translational research applications.

Subtraction ictal SPECT co-registered to MRI (SISCOM) patterns in children with temporal lobe epilepsy.

OBJECTIVE: We evaluated SISCOM patterns and their relationship with surgical outcome in children with temporal lobe epilepsy (TLE) who had undergone a temporal lobe surgery. METHODS: This was an observational study evaluating SISCOM patterns in 40 children with TLE. We classified SISCOM patterns into 4 categories; (i) unilateral anteromesial and/or anterolateral temporal pattern; (ii) unilateral anteromesial and/or anterolateral temporal plus posterior extension pattern; (iii) bilateral anteromesial and/or anterolateral temporal pattern; and (iv) atypical pattern. Determinants of SISCOM pattern and correlation between postoperative outcomes and SISCOM patterns were evaluated. RESULTS: Pattern (i), (ii), (iii), and (iv) were identified in 10 (25%), 14 (35%), 0 (0%), and 16 (40%) patients, respectively. There was no significant correlation between patterns and postoperative outcomes. SISCOM patterns significantly associated with the presence of hippocampal sclerosis and type of focal cortical dysplasia (p-value = 0.048 and 0.036, respectively). Patients with HS had 5 times the odds of having unilateral temporal pattern, compared to patients with other neuropathology (OR = 5, 95% CI 0.92 to 27.08). Patients with FCD type 2 had 9.71 times the odds of having atypical pattern, compared to patients with other types of FCD (OR = 9.71, 95% CI 0.92 to 103.04). Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcomes (p-value = 0.018 and 0.013, respectively). CONCLUSION: Three SISCOM patterns were seen. Patients with HS had increased odds of having unilateral temporal pattern while patients with FCD type 2 had increased odds of having atypical pattern. However, there was no significant correlation between SISCOM patterns and postoperative outcomes. Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcome. SIGNIFICANCE: This study shows that the distribution of SISCOM patterns and their relationship with postoperative outcomes in children with TLE are different from adult population. Besides, SISCOM may add only limited diagnostic and prognostic information in children with drug-resistant TLE undergoing epilepsy surgery. Further evaluation to identify patient populations that may benefit from SISCOM is desirable.

Fast Automated Stereo-EEG Electrode Contact Identification and Labeling Ensemble.

INTRODUCTION: Stereotactic electroencephalography (SEEG) has emerged as the preferred modality for intracranial monitoring in drug-resistant epilepsy (DRE) patients being evaluated for neurosurgery. After implantation of SEEG electrodes, it is important to determine the neuroanatomic locations of electrode contacts (ECs), to localize ictal onset and propagation, and integrate functional information to facilitate surgical decisions. Although there are tools for coregistration of preoperative MRI and postoperative CT scans, identification, sorting, and labeling of SEEG ECs is often performed manually, which is resource intensive. We report development and validation of a software named Fast Automated SEEG Electrode Contact Identification and Labeling Ensemble (FASCILE). METHODS: FASCILE is written in Python 3.8.3 and employs a novel automated method for identifying ECs, assigning them to respected SEEG electrodes, and labeling. We compared FASCILE with our clinical process of identifying, sorting, and labeling ECs, by computing localization error in anteroposterior, superoinferior, and lateral dimensions. We also measured mean Euclidean distances between ECs identified by FASCILE and the clinical method. We compared time taken for EC identification, sorting, and labeling for the software developer using FASCILE, a first-time clinical user using FASCILE, and the conventional clinical process. RESULTS: Validation in 35 consecutive DRE patients showed a mean overall localization error of 0.73 ± 0.15 mm. FASCILE required 10.7 ± 5.5 min/patient for identifying, sorting, and labeling ECs by a first-time clinical user, compared to 3.3 ± 0.7 h/patient required for the conventional clinical process. CONCLUSION: Given the accuracy, speed, and ease of use, we expect FASCILE to be used frequently for SEEG-driven epilepsy surgery. It is freely available for noncommercial use. FASCILE is specifically designed to expedite localization of ECs, assigning them to respective SEEG electrodes (sorting), and labeling them and not for coregistration of CT and MRI data as there are commercial software available for this purpose.

Response assessment in diffuse intrinsic pontine glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Optimising the conduct of clinical trials for diffuse intrinsic pontine glioma involves use of consistent, objective disease assessments and standardised response criteria. The Response Assessment in Pediatric Neuro-Oncology working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. A working group was formed specifically to address response assessment in children and young adults with diffuse intrinsic pontine glioma and to develop a consensus on recommendations for response assessment. Response should be assessed using MRI of brain and spine, neurological examination, and anti-inflammatory or antiangiogenic drugs. Clinical imaging standards are defined. As with previous consensus recommendations, these recommendations will need to be validated in prospective clinical trials.

Aromatic Stacking Facilitated Self-Assembly of Ultrashort Ionic Complementary Peptide Sequence: ß-Sheet Nanofibers with Remarkable Gelation and Interfacial Properties.

Understanding peptide self-assembly mechanisms and stability of the formed assemblies is crucial for the development of functional nanomaterials. Herein, we have adopted a rational design approach to demonstrate how a minimal structural modification to a nonassembling ultrashort ionic self-complementary tetrapeptide FEFK (Phe4) remarkably enhanced the stability of self-assembly into ß-sheet nanofibers and induced hydrogelation. This was achieved by replacing flexible phenylalanine residue (F) by the rigid phenylglycine (Phg), resulting in a constrained analogue PhgEPhgK (Phg4), which positioned aromatic rings in an orientation favorable for aromatic stacking. Phg4 self-assembly into stable ß-sheet ladders was facilitated by π-staking of aromatic side chains alongside hydrogen bonding between backbone amides along the nanofiber axis. The contribution of these noncovalent interactions in stabilizing self-assembly was predicted by in silico modeling using molecular dynamics simulations and semiempirical quantum mechanics calculations. In aqueous medium, Phg4 ß-sheet nanofibers entangled at a critical gelation concentration ≥20 mg/mL forming a network of nanofibrous hydrogels. Phg4 also demonstrated a unique surface activity in the presence of immiscible oils and was superior to commercial emulsifiers in stabilizing oil-in-water (O/W) emulsions. This was attributed to interfacial adsorption of amphiphilic nanofibrils forming nanofibrilized microspheres. To our knowledge, Phg4 is the shortest ionic self-complementary peptide rationally designed to self-assemble into stable ß-sheet nanofibers capable of gelation and emulsification. Our results suggest that ultrashort ionic-complementary constrained peptides or UICPs have significant potential for the development of cost-effective, sustainable, and multifunctional soft bionanomaterials.

A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

PURPOSE: Cyclin-dependent kinase-retinoblastoma (CDK-RB) pathway is dysregulated in some diffuse intrinsic pontine gliomas (DIPG). We evaluated safety, feasibility, and early efficacy of the CDK4/6-inhibitor ribociclib, administered following radiotherapy in newly-diagnosed DIPG patients. METHODS: Following radiotherapy, eligible patients received ribociclib in 28-day cycles (350 mg/m2; 21 days on/7 days off). Feasibility endpoints included tolerability for at least 6 courses, and a less than 2-week delay in restarting therapy after 1 dose reduction. Early efficacy was measured by 1-year and median overall survival (OS). Patient/parent-by-proxy reported outcomes measurement information system (PROMIS) assessments were completed prospectively. RESULTS: The study included 10 evaluable patients, 9 DIPG and 1 diffuse midline glioma (DMG)-all 3.7 to 19.8 years of age. The median number of courses was 8 (range 3-14). Three patients required dose reduction for grade-4 neutropenia, and 1 discontinued therapy for hematological toxicity following course 4. The most common grade-3/4 toxicity was myelosuppression. After 2 courses, MRI evaluations in 4 patients revealed increased necrotic volume, associated with new neurological symptoms in 3 patients. The 1-year and median OS for DIPG was 89% and 16.1 months (range 10-30), respectively; the DMG patient died at 6 months post-diagnosis. Five patients donated brain tissue and tumor; 3 were RB+ . CONCLUSIONS: Ribociclib administered following radiotherapy is feasible in DIPG and DMG. Increased tumor necrosis may represent a treatment effect. These data warrant further prospective volumetric analyses of tumors with necrosis. Feasibility and stabilization findings support further investigation of ribociclib in combination therapies. TRIAL REGISTRATION: NCT02607124.

Reading in children with drug-resistant epilepsy was related to functional connectivity in cognitive control regions.

AIM: This study aimed to define whether individuals with drug-resistant focal epilepsy also used regions related to cognitive control to facilitate reading. METHODS: We focused on patients with drug-resistant focal epilepsy in 2011-2014, who were aged 8-20 years and were being treated at the Cincinnati Children's Hospital, USA. They performed a verb generation functional magnetic resonance imaging task known to involve language and cognitive control, as well as a formal reading assessment. The reading scores were correlated with functional connectivity of the anterior cingulate cortex (ACC) using seed-to-voxel analysis. RESULTS: There were 81 potential patients and 13 (seven females) met the inclusion criteria. Their age at seizure onset was 0-13 years, and they had a mean age of 12.66 ± 3.17 years at the time of the study. Individuals with epilepsy demonstrated average intelligence and word reading ability. Their reading scores were positively correlated with functional connectivity between the ACC and regions related to emotional processing (right amygdala), learning and language processing (left cerebellum) and visual processing. CONCLUSION: Our results support the role that the ACC plays in proficient reading among children with drug-resistant epilepsy, even in those with epileptogenic foci in areas related to language.

Neonatal Functional and Structural Connectivity Are Associated with Cerebral Palsy at Two Years of Age.

OBJECTIVE: The accuracy of structural magnetic resonance imaging (MRI) to predict later cerebral palsy (CP) in newborns with perinatal brain injury is variable. Diffusion tensor imaging (DTI) and task-based functional MRI (fMRI) show promise as predictive tools. We hypothesized that infants who later developed CP would have reduced structural and functional connectivity as compared with those without CP. STUDY DESIGN: We performed DTI and fMRI using a passive motor task at 40 to 48 weeks' postmenstrual age in 12 infants with perinatal brain injury. CP was diagnosed at age 2 using a standardized examination. RESULTS: Five infants had CP at 2 years of age, and seven did not have CP. Tract-based spatial statistics showed a widespread reduction of fractional anisotropy (FA) in almost all white matter tracts in the CP group. Using the median FA value in the corticospinal tracts as a cutoff, FA was 100% sensitive and 86% specific to predict CP compared with a sensitivity of 60 to 80% and a specificity of 71% for structural MRI. During fMRI, the CP group had reduced functional connectivity from the right supplemental motor area as compared with the non-CP group. CONCLUSION: DTI and fMRI obtained soon after birth are potential biomarkers to predict CP in newborns with perinatal brain injury.

Development of information sharing in language neocortex in childhood-onset drug-resistant epilepsy.

OBJECTIVE: We studied age-related dynamics of information sharing among cortical language regions with electrocorticographic high-gamma modulation during picture-naming and story-listening tasks. METHODS: Seventeen epilepsy patients aged 4-19 years, undergoing extraoperative monitoring with left-hemispheric subdural electrodes, were included. Mutual information (MI), a nondirectional measure of shared information, between 16 pairs of cortical regions of interest, was computed from trial-averaged 70-150 Hz power modulations during language tasks. Impact of age on pairwise MI between language regions and their determinants were ascertained with regression analysis. RESULTS: During picture naming, significant increase in MI with age was seen between pairwise combinations of Broca's area, inferior precentral gyrus (iPreC), and frontal association cortex (FAC); Wernicke's area and posterior association cortex (PAC); and Broca's and Wernicke's areas. During story listening, significant age-related increase in MI was seen between Wernicke's area and either Broca's area, FAC, or PAC; and between Broca's area and FAC. Significant impact of baseline intelligence quotient was seen on the relationship between age and MI for all pairs, except between Broca's area and iPreC. The mean MI was higher during naming compared to listening for pairs including iPreC with Broca's area, FAC, or PAC and was lower for pairs of Wernicke's area or PAC with anterior language regions. SIGNIFICANCE: Information sharing matures with age "within" frontal and temporoparietal language cortices, and "between" Broca's and Wernicke's areas. This study provides evidence for distinct patterns of developmental plasticity within perisylvian language cortex and has implications for planning epilepsy surgery.

Electrical stimulation mapping of language with stereo-EEG.

OBJECTIVE: We prospectively validated stereo-electroencephalography (EEG) electrical stimulation mapping (ESM) of language against a reference standard of meta-analytic functional magnetic resonance imaging (fMRI) framework (Neurosynth). METHODS: Language ESM was performed using 50 Hz, biphasic, bipolar, stimulation at 1-8 mA, with a picture naming task. Electrode contacts (ECs) were scored as ESM+ if ESM interfered with speech/language function. For each patient, presurgical MRI was transformed to a standard space and coregistered with computed tomographic (CT) scan to obtain EC locations. After whole-brain parcellation, this fused image data were intersected with three-dimensional language fMRI (Neurosynth), and each EC was classified as lying within/outside the fMRI language parcel. Diagnostic odds ratio (DOR) and other indices were estimated. Current thresholds for language inhibition and after-discharges (ADs) were analyzed using multivariable linear mixed models. RESULTS: In 10 patients (5 females), aged 5.4-21.2 years, speech/language inhibition was noted with ESM on 87/304 (29%) ECs. Stereo-EEG language ESM was a valid classifier of fMRI (Neurosynth) language sites (DOR: 9.02, p < 0.0001), with high specificity (0.87) but poor sensitivity (0.57). Similar diagnostic indices were seen for ECs in frontal or posterior regions, and gray or white matter. Language threshold (3.1 ±â€¯1.5 mA) was lower than AD threshold (4.0 ±â€¯2.0 mA, p = 0.0001). Language and AD thresholds decreased with age and intelligence quotient. Electrical stimulation mapping triggered seizures/auras represented patients' habitual semiology with 1 Hz stimulation. CONCLUSIONS: Stereo-EEG ESM can reliably identify cerebral parcels with/without language function but may under detect all language sites. We suggest a 50-Hz stimulation protocol for language ESM with stereo-EEG.

Altered brain microstructure in association with repetitive subconcussive head impacts and the potential protective effect of jugular vein compression: a longitudinal study of female soccer athletes.

PURPOSE: To (1) quantify white matter (WM) alterations in female high school athletes during a soccer season and characterise the potential for normalisation during the off-season rest period, (2) determine the association between WM alterations and exposure to repetitive subconcussive head impacts, and (3) evaluate the efficacy of a jugular vein compression collar to prevent WM alterations associated with head impact exposure. METHODS: Diffusion tensor imaging (DTI) data were prospectively collected from high school female soccer participants (14-18 years) at up to three time points over 9 months. Head impacts were monitored using accelerometers during all practices and games. Participants were assigned to a collar (n=24) or non-collar group (n=22). The Tract-Based Spatial Statistics approach was used in the analysis of within-group longitudinal change and between-group comparisons. RESULTS: DTI analyses revealed significant pre-season to post-season WM changes in the non-collar group in mean diffusivity (2.83%±2.46%), axial diffusivity (2.58%±2.34%) and radial diffusivity (3.52%±2.60%), but there was no significant change in the collar group despite similar head impact exposure. Significant correlation was found between head impact exposure and pre-season to post-season DTI changes in the non-collar group. WM changes in the non-collar group partially resolved at 3 months off-season follow-up. DISCUSSION: Microstructural changes in WM occurred during a season of female high school soccer among athletes who did not wear the collar device. In comparison, there were no changes in players who wore the collar, suggesting a potential prophylactic effect of the collar device in preventing changes associated with repetitive head impacts. In those without collar use, the microstructural changes showed a reversal towards normal over time in the off-season follow-up period.

Relative Head Impact Exposure and Brain White Matter Alterations After a Single Season of Competitive Football: A Pilot Comparison of Youth Versus High School Football.

OBJECTIVE: Youth athletes are believed to be more susceptible to white matter (WM) degradation resulting from head impact exposure relative to high school (HS) athletes; this hypothesis has not been objectively tested. The purpose of this study was to determine preseason to postseason changes in WM integrity from repetitive head impacts for youth football (YFB) players compared with HS football players during a competitive football season. DESIGN: Prospective cohort. SETTING: One season of YFB (grades 7 and 8) and varsity HS football (grades 10-12). PATIENTS OR OTHER PARTICIPANTS: Twelve YFB (13.08 ± 0.64 years) and 21 HS (17.5 ± 0.78 years) athletes. INTERVENTIONS: Participants completed 2 magnetic resonance imaging sessions: preseason and postseason. Head impact exposure was recorded during practice and games using a helmet-mounted accelerometer. MAIN OUTCOME MEASURES: Tract-based spatial statistics were used to evaluate group differences in preseason to postseason changes in diffusion tensor imaging, including fractional anisotropy and mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: The HS group exhibited significant preseason to postseason reductions in MD, AD, and RD (P < 0.05, corrected) in widespread WM areas. Significant WM reductions for the YFB group were only observed for AD (P < 0.05, corrected), but was more limited in extent compared with HS. CONCLUSIONS: Significant preseason to postseason AD reduction was found in both YFB and HS groups after one season of competitive play. Our results did not confirm recent speculation that younger children are more susceptible to the deleterious effects of repetitive head impacts compared with their older counterparts.