Pathogenic variant in NFIA associated with subdural hematomas mimicking nonaccidental trauma.

Subdural hematoma (SDH) in infants raises the concern for nonaccidental trauma (NAT), especially when presenting with associated injuries. However, isolated SDH could be caused by multiple etiologies. NFIA (MIM# 600727) encodes nuclear factor I A protein (NFI-A), a transcription factor which plays important roles in gliogenesis. Loss-of-function variants in NFIA are associated with autosomal dominant brain malformations with or without urinary tract defects (MIM# 613735). Intracranial hemorrhage of various types besides SDH has been reported in patients with this condition. Here, we report a patient with a heterozygous novel NFIA pathogenic variant affecting splicing who initially presented with SDH concerning for NAT. We also review previous NFIA-related disorder cases with intracranial hemorrhage. This report emphasizes the importance of genetic evaluation in infants presenting with isolated SDH.

The Role of SPECT and PET in Epilepsy.

OBJECTIVE. The purpose of this article is to summarize the role of molecular imaging of the brain by use of SPECT, FDG PET, and non-FDG PET radiotracers in epilepsy. CONCLUSION. Quantitative image analysis with PET and SPECT has increased the diagnostic utility of these modalities in localizing epileptogenic onset zones. A multi-modal platform approach integrating the functional imaging of PET and SPECT with the morphologic information from MRI in presurgical evaluation of epilepsy can greatly improve outcomes.

Molecular and histologic characteristics of pseudoprogression in diffuse gliomas.

During the 6 month period following chemoradiotherapy, gliomas frequently develop new areas of contrast enhancement, which are due to treatment effect rather than tumor progression. We sought to characterize this phenomenon in oligodendrogliomas (OG) and mixed oligoastrocytomas (MOA). We reviewed the imaging findings from 143 patients with a WHO grade II or III OG or MOA for evidence of pseudoprogression (PsP) or early tumor progression. We characterized these cases for 1p/19q codeletions by FISH, IDH1 R132H mutation by immunohistochemistry, and TP53, ATRX, and EGFR mutations by next generation sequencing. We then reviewed the pathologic specimens of the patient cases in which a re-resection was performed. We found that OG and MOA that are 1p/19q intact developed PsP at a higher rate than tumors that are 1p/19q codeleted (27 vs. 8 %). Moreover, IDH1 wild-type (WT) tumors developed PsP at a higher rate than IDH1 R132H cases (27 vs. 11 %). Patients with ATRX or TP53 mutations developed PsP at an intermediate rate of 21 %. Ten patients in our cohort underwent a re-resection for early contrast enhancement; these tumors were predominantly 1p/19q intact (90 %) and had a low rate of IDH1 R132H mutation (50 %). 8 of 10 tumors demonstrated primarily treatment effects, while the remaining 2 of 10 demonstrated recurrent/residual tumor of the same grade. Early contrast enhancement that develops during the first 6 months after chemoradiotherapy is typically due to PsP and occurs primarily in OG and MOA that are 1p/19q intact and IDH WT.

Multimodality Review of Amyloid-related Diseases of the Central Nervous System.

Amyloid-ß (Aß) is ubiquitous in the central nervous system (CNS), but pathologic accumulation of Aß results in four distinct neurologic disorders that affect middle-aged and elderly adults, with diverse clinical presentations ranging from chronic debilitating dementia to acute life-threatening intracranial hemorrhage. The characteristic imaging patterns of Aß-related CNS diseases reflect the pathophysiology of Aß deposition in the CNS. Aß is recognized as a key component in the neuronal damage that characterizes the pathophysiology of Alzheimer disease, the most common form of dementia. Targeted molecular imaging shows pathologic accumulation of Aß and tau protein, and fluorine 18 fluorodeoxyglucose positron emission tomography and anatomic imaging allow differentiation of typical patterns of neuronal dysfunction and loss in patients with Alzheimer disease from those seen in patients with other types of dementia. Cerebral amyloid angiopathy (CAA) is an important cause of cognitive impairment and spontaneous intracerebral hemorrhage in the elderly. Hemorrhage and white matter injury seen at imaging reflect vascular damage caused by the accumulation of Aß in vessel walls. The rare forms of inflammatory angiopathy attributed to Aß, Aß-related angiitis and CAA-related inflammation, cause debilitating neurologic symptoms that improve with corticosteroid therapy. Imaging shows marked subcortical and cortical inflammation due to perivascular inflammation, which is incited by vascular Aß accumulation. In the rarest of the four disorders, cerebral amyloidoma, the macroscopic accumulation of Aß mimics the imaging appearance of tumors. Knowledge of the imaging patterns and pathophysiology is essential for accurate diagnosis of Aß-related diseases of the CNS. (©)RSNA, 2016.

Amyloid-ß efflux from the central nervous system into the plasma.

OBJECTIVE: The aim of this study was to measure the flux of amyloid-ß (Aß) across the human cerebral capillary bed to determine whether transport into the blood is a significant mechanism of clearance for Aß produced in the central nervous system (CNS). METHODS: Time-matched blood samples were simultaneously collected from a cerebral vein (including the sigmoid sinus, inferior petrosal sinus, and the internal jugular vein), femoral vein, and radial artery of patients undergoing inferior petrosal sinus sampling. For each plasma sample, Aß concentration was assessed by 3 assays, and the venous to arterial Aß concentration ratios were determined. RESULTS: Aß concentration was increased by ∼7.5% in venous blood leaving the CNS capillary bed compared to arterial blood, indicating efflux from the CNS into the peripheral blood (p < 0.0001). There was no difference in peripheral venous Aß concentration compared to arterial blood concentration. INTERPRETATION: Our results are consistent with clearance of CNS-derived Aß into the venous blood supply with no increase from a peripheral capillary bed. Modeling these results suggests that direct transport of Aß across the blood-brain barrier accounts for ∼25% of Aß clearance, and reabsorption of cerebrospinal fluid Aß accounts for ∼25% of the total CNS Aß clearance in humans. Ann Neurol 2014;76:837-844.

FGFR3-related condition: a skeletal dysplasia with similarities to thanatophoric dysplasia and SADDAN due to Lys650Met.

Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for six related skeletal dysplasia conditions: achondroplasia, hypochondroplasia, thanatophoric dysplasia types 1 and 2, SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), and platyspondylic lethal skeletal dysplasia, San Diego type. This group of disorders has very characteristic clinical and radiologic features, which distinguish them from other skeletal dysplasias. They display a spectrum of severity in the skeletal findings, ranging from relatively mild hypochondroplasia to lethal thanatophoric dysplasia. We report a patient who has the missense FGFR3 mutation, Lys650Met, previously reported in association only with SADDAN, who exhibits some findings similar to both thanatophoric dysplasia (types 1 and 2) in addition to those findings characteristic of SADDAN.

Good Gone Bad: Complications of Chemotherapy, Immunotherapy, and Radiotherapy on the CNS.

With recent advancements in cancer therapy, especially immunotherapy, overall survival of many cancers has increased and patient toxicity has been reduced. However, many complications of traditional cancer therapy are still prevalent and complications of novel therapies are just beginning to appear. The neuroradiologist may be the first to visualize signs of these complications on imaging. This article describes the notable imaging findings of several unique and characteristic complications of CNS cancer therapy, including toxicities of chemotherapies, immunotherapies, and radiotherapy. Complications of chemotherapeutic agents covered include methotrexate-induced and disseminated necrotizing leukoencephalopathy, and chemotherapy-induced myelopathy. Immunotherapy complications included are Tacrolimus-related Optic Neuropathy, Rituximab and Immune reconstitution inflammatory syndrome-associated Progressive Multifocal Leukoencephalopathy, Bevacizumab-associated late radiation-induced neurotoxicity, and Ipilimumab-induced hypophysitis. Lastly, radiation-induced neurotoxicities are covered, including myelopathy, radiation necrosis, cerebral atrophy, leukoencephalopathy, optic neuropathy, mineralizing microangiopathy, stroke-like migraine attacks, osteonecrosis, and vasculopathies. Neuroradiologists will increasingly encounter patients who have undergone treatment with more than 1 therapeutic modality, resulting in overlapping findings as well. Recognition of the common complications of these therapies on imaging is critical to minimizing the effects of these potential short- and long-term complications.

A Multimedia Strategy to Integrate Introductory Broad-Based Radiation Science Education in US Medical Schools.

US physicians in multiple specialties who order or conduct radiological procedures lack formal radiation science education and thus sometimes order procedures of limited benefit or fail to order what is necessary. To this end, a multidisciplinary expert group proposed an introductory broad-based radiation science educational program for US medical schools. Suggested preclinical elements of the curriculum include foundational education on ionizing and nonionizing radiation (eg, definitions, dose metrics, and risk measures) and short- and long-term radiation-related health effects as well as introduction to radiology, radiation therapy, and radiation protection concepts. Recommended clinical elements of the curriculum would impart knowledge and practical experience in radiology, fluoroscopically guided procedures, nuclear medicine, radiation oncology, and identification of patient subgroups requiring special considerations when selecting specific ionizing or nonionizing diagnostic or therapeutic radiation procedures. Critical components of the clinical program would also include educational material and direct experience with patient-centered communication on benefits of, risks of, and shared decision making about ionizing and nonionizing radiation procedures and on health effects and safety requirements for environmental and occupational exposure to ionizing and nonionizing radiation. Overarching is the introduction to evidence-based guidelines for procedures that maximize clinical benefit while limiting unnecessary risk. The content would be further developed, directed, and integrated within the curriculum by local faculties and would address multiple standard elements of the Liaison Committee on Medical Education and Core Entrustable Professional Activities for Entering Residency of the Association of American Medical Colleges.

Update of the AMSER National Medical Student Curriculum.

Since the first steps of creating the Alliance of Medical Student Educators in Radiology (AMSER) curriculum 20 years ago, dramatic advances in medical imaging, patient care, and medical education have occurred necessitating an update of this valuable resource. The 2020 update of the AMSER curriculum aims to address as many of these changes while providing a succinct resource that will hopefully remain useful for years to come. The updated AMSER curriculum document is freely available for download via the AMSER website at https://www.aur.org/en/affinity-groups/amser/curriculum.

Neuroimaging of Adult Lacrimal Drainage System.

The lacrimal drainage system (LDS) pathology is frequently encountered in the ophthalmology setting but is rarely discussed in the radiology literature. This is even truer for adult LDS lesions despite increase utilization of computed tomography and magnetic resonance in imaging for diagnosis of LDS pathology. The purpose of this image rich review is to highlight common adult LDS pathologies and introduce the radiologist to rare disease entities affecting this pathology rich anatomical region with emphasis on imaging findings, clinical presentation, and differential generation.

Dynamic 18F-FDOPA-PET/MRI for the preoperative evaluation of gliomas: correlation with stereotactic histopathology.

BACKGROUND: MRI alone has limited accuracy for delineating tumor margins and poorly predicts the aggressiveness of gliomas, especially when tumors do not enhance. This study evaluated simultaneous 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (FDOPA)-PET/MRI to define tumor volumes compared to MRI alone more accurately, assessed its role in patient management, and correlated PET findings with histopathology. METHODS: Ten patients with known or suspected gliomas underwent standard of care surgical resection and/or stereotactic biopsy. FDOPA-PET/MRI was performed prior to surgery, allowing for precise co-registration of PET, MR, and biopsies. The biopsy sites were modeled as 5-mm spheres, and the local FDOPA uptake at each site was determined. Correlations were performed between measures of tumor histopathology, and static and dynamic PET values: standardized uptake values (SUVs), tumor to brain ratios, metabolic tumor volumes, and tracer kinetics at volumes of interest (VOIs) and biopsy sites. RESULTS: Tumor FDOPA-PET uptake was visualized in 8 patients. In 2 patients, tracer uptake was similar to normal brain reference with no histological findings of malignancy. Eight biopsy sites confirmed for glioma had FDOPA uptake without T1 contrast enhancement. The PET parameters were highly correlated only with the cell proliferation marker, Ki-67 (SUVmax: r = 0.985, P = .002). In this study, no statistically significant difference between high-grade and low-grade tumors was demonstrated. The dynamic PET analysis of VOIs and biopsy sites showed decreasing time-activity curves patterns. FDOPA-PET imaging directly influenced patient management. CONCLUSIONS: Simultaneous FDOPA-PET/MRI allowed for more accurate visualization and delineation of gliomas, enabling more appropriate patient management and simplified validation of PET findings with histopathology.

Mapping language function with task-based vs. resting-state functional MRI.

BACKGROUND: Use of functional MRI (fMRI) in pre-surgical planning is a non-invasive method for pre-operative functional mapping for patients with brain tumors, especially tumors located near eloquent cortex. Currently, this practice predominantly involves task-based fMRI (T-fMRI). Resting state fMRI (RS-fMRI) offers an alternative with several methodological advantages. Here, we compare group-level analyses of RS-fMRI vs. T-fMRI as methods for language localization. PURPOSE: To contrast RS-fMRI vs. T-fMRI as techniques for localization of language function. METHODS: We analyzed data obtained in 35 patients who had both T-fMRI and RS-fMRI scans during the course of pre-surgical evaluation. The RS-fMRI data were analyzed using a previously trained resting-state network classifier. The T-fMRI data were analyzed using conventional techniques. Group-level results obtained by both methods were evaluated in terms of two outcome measures: (1) inter-subject variability of response magnitude and (2) sensitivity/specificity analysis of response topography, taking as ground truth previously reported maps of the language system based on intraoperative cortical mapping as well as meta-analytic maps of language task fMRI responses. RESULTS: Both fMRI methods localized major components of the language system (areas of Broca and Wernicke) although not with equal inter-subject consistency. Word-stem completion T-fMRI strongly activated Broca's area but also several task-general areas not specific to language. RS-fMRI provided a more specific representation of the language system. CONCLUSION: We demonstrate several advantages of classifier-based mapping of language representation in the brain. Language T-fMRI activated task-general (i.e., not language-specific) functional systems in addition to areas of Broca and Wernicke. In contrast, classifier-based analysis of RS-fMRI data generated maps confined to language-specific regions of the brain.

Select Atrophied Regions in Alzheimer disease (SARA): An improved volumetric model for identifying Alzheimer disease dementia.

INTRODUCTION: Volumetric biomarkers for Alzheimer disease (AD) are attractive due to their wide availability and ease of administration, but have traditionally shown lower diagnostic accuracy than measures of neuropathological contributors to AD. Our purpose was to optimize the diagnostic specificity of structural MRIs for AD using quantitative, data-driven techniques. METHODS: This retrospective study assembled several non-overlapping cohorts (total n = 1287) with publicly available data and clinical patients from Barnes-Jewish Hospital (data gathered 1990-2018). The Normal Aging Cohort (n = 383) contained amyloid biomarker negative, cognitively normal (CN) participants, and provided a basis for determining age-related atrophy in other cohorts. The Training (n = 216) and Test (n = 109) Cohorts contained participants with symptomatic AD and CN controls. Classification models were developed in the Training Cohort and compared in the Test Cohort using the receiver operating characteristics areas under curve (AUCs). Additional model comparisons were done in the Clinical Cohort (n = 579), which contained patients who were diagnosed with dementia due to various etiologies in a tertiary care outpatient memory clinic. RESULTS: While the Normal Aging Cohort showed regional age-related atrophy, classification models were not improved by including age as a predictor or by using volumetrics adjusted for age-related atrophy. The optimal model used multiple regions (hippocampal volume, inferior lateral ventricle volume, amygdala volume, entorhinal thickness, and inferior parietal thickness) and was able to separate AD and CN controls in the Test Cohort with an AUC of 0.961. In the Clinical Cohort, this model separated AD from non-AD diagnoses with an AUC 0.820, an incrementally greater separation of the cohort than by hippocampal volume alone (AUC of 0.801, p = 0.06). Greatest separation was seen for AD vs. frontotemporal dementia and for AD vs. non-neurodegenerative diagnoses. CONCLUSIONS: Volumetric biomarkers distinguished individuals with symptomatic AD from CN controls and other dementia types but were not improved by controlling for normal aging.

Heterogeneity Diffusion Imaging of gliomas: Initial experience and validation.

OBJECTIVES: Primary brain tumors are composed of tumor cells, neural/glial tissues, edema, and vasculature tissue. Conventional MRI has a limited ability to evaluate heterogeneous tumor pathologies. We developed a novel diffusion MRI-based method-Heterogeneity Diffusion Imaging (HDI)-to simultaneously detect and characterize multiple tumor pathologies and capillary blood perfusion using a single diffusion MRI scan. METHODS: Seven adult patients with primary brain tumors underwent standard-of-care MRI protocols and HDI protocol before planned surgical resection and/or stereotactic biopsy. Twelve tumor sampling sites were identified using a neuronavigational system and recorded for imaging data quantification. Metrics from both protocols were compared between World Health Organization (WHO) II and III tumor groups. Cerebral blood volume (CBV) derived from dynamic susceptibility contrast (DSC) perfusion imaging was also compared with the HDI-derived perfusion fraction. RESULTS: The conventional apparent diffusion coefficient did not identify differences between WHO II and III tumor groups. HDI-derived slow hindered diffusion fraction was significantly elevated in the WHO III group as compared with the WHO II group. There was a non-significantly increasing trend of HDI-derived tumor cellularity fraction in the WHO III group, and both HDI-derived perfusion fraction and DSC-derived CBV were found to be significantly higher in the WHO III group. Both HDI-derived perfusion fraction and slow hindered diffusion fraction strongly correlated with DSC-derived CBV. Neither HDI-derived cellularity fraction nor HDI-derived fast hindered diffusion fraction correlated with DSC-derived CBV. CONCLUSIONS: Conventional apparent diffusion coefficient, which measures averaged pathology properties of brain tumors, has compromised accuracy and specificity. HDI holds great promise to accurately separate and quantify the tumor cell fraction, the tumor cell packing density, edema, and capillary blood perfusion, thereby leading to an improved microenvironment characterization of primary brain tumors. Larger studies will further establish HDI's clinical value and use for facilitating biopsy planning, treatment evaluation, and noninvasive tumor grading.

Utility of CT angiography in screening for traumatic cerebrovascular injury.

OBJECTIVE: Computed tomographic angiography (CTA) is increasingly utilized to evaluate for traumatic cerebrovascular injury (TCVI). The purpose of this study was to determine the yield, management effect, and risk of stroke or poor outcome of a positive CTA in a large cohort of trauma patients. PATIENTS AND METHODS: A retrospective analysis was performed on 1290 consecutive trauma patients that underwent head and/or neck CTA at our level I trauma center from 2006 to 2015. Clinical variables assessed include mechanism of injury, neurological status, CTA findings, subsequent imaging results, patient management, and clinical outcomes. RESULTS: Among 1290 patients who underwent CTA, 200 (15.5%) were positive for TCVI, higher in blunt than penetrating trauma patients. In a generalized linear model, factors that increased likelihood of positive CTA included multiple cervical fractures, fractures with foraminal involvement, gunshot injury, Glasgow Coma Scale ≤ 13, and focal neurological deficit. Excluding cases with these factors lowered the positive rate to 4.3%. Of the 200 CTA-positives, 99 were treated for TCVI and 9 (4.5%) developed a subsequent stroke as compared to 5 (0.5%) in CTA-negative patients (odds ratio 10.2, Fisher exact test, p < 0.001). Risk of death or nursing facility discharge location was also higher in CTA-positive patients, correcting for age and presenting GCS (p < 0.01). CONCLUSION: CTA had a modest yield in identifying TCVI in this cohort. When positive, CTA influenced management and predicted an increased risk of subsequent stroke and poor outcome.

Integration of resting state functional MRI into clinical practice - A large single institution experience.

Functional magnetic resonance imaging (fMRI) is an important tool for pre-surgical evaluation of eloquent cortex. Classic task-based paradigms require patient participation and individual imaging sequence acquisitions for each functional domain that is being assessed. Resting state fMRI (rs-fMRI), however, enables functional localization without patient participation and can evaluate numerous functional domains with a single imaging session. To date, post-processing of this resting state data has been resource intensive, which limits its widespread application for routine clinical use. Through a novel automated algorithm and advanced imaging IT structure, we report the clinical application and the large-scale integration of rs-fMRI into routine neurosurgical practice. One hundred and ninety one consecutive patients underwent a 3T rs-fMRI, 83 of whom also underwent both motor and language task-based fMRI. Data were processed using a novel, automated, multi-layer perceptron algorithm and integrated into stereotactic navigation using a streamlined IT imaging pipeline. One hundred eighty-five studies were performed for intracranial neoplasm, 14 for refractory epilepsy and 33 for vascular malformations or other neurological disorders. Failure rate of rs-fMRI of 13% was significantly better than that for task-based fMRI (38.5%,) (p <0.001). In conclusion, at Washington University in St. Louis, rs-fMRI has become an integral part of standard imaging for neurosurgical planning. Resting state fMRI can be used in all patients, and due to its lower failure rate than task-based fMRI, it is useful for patients who are unable to cooperate with task-based studies.

Neurologic Applications of PET/MR Imaging.

PET/MR imaging benefits neurologic clinical care and research by providing spatially and temporally matched anatomic MR imaging, advanced MR physiologic imaging, and metabolic PET imaging. MR imaging sequences and PET tracers can be modified to target physiology specific to a neurologic disease process, with applications in neurooncology, epilepsy, dementia, cerebrovascular disease, and psychiatric and neurologic research. Simultaneous PET/MR imaging provides efficient acquisition of multiple temporally matched datasets, and opportunities for motion correction and improved anatomic assignment of PET data. Current challenges include optimizing MR imaging-based attenuation correction and necessity for dual expertise in PET and MR imaging.

Multiparametric MRI and [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging Is a Potential Prognostic Imaging Biomarker in Recurrent Glioblastoma.

PURPOSE/OBJECTIVES: Multiparametric advanced MR and [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging may be important biomarkers for prognosis as well for distinguishing recurrent glioblastoma multiforme (GBM) from treatment-related changes. METHODS/MATERIALS: We retrospectively evaluated 30 patients treated with chemoradiation for GBM and underwent advanced MR and FDG-PET for confirmation of tumor progression. Multiparametric MRI and FDG-PET imaging metrics were evaluated for their association with 6-month overall (OS) and progression-free survival (PFS) based on pathological, radiographic, and clinical criteria. RESULTS: 17 males and 13 females were treated between 2001 and 2014, and later underwent FDG-PET at suspected recurrence. Baseline FDG-PET and MRI imaging was obtained at a median of 7.5 months [interquartile range (IQR) 3.7-12.4] following completion of chemoradiation. Median follow-up after FDG-PET imaging was 10 months (IQR 7.2-13.0). Receiver-operator characteristic curve analysis identified that lesions characterized by a ratio of the SUVmax to the normal contralateral brain (SUVmax/NB index) >1.5 and mean apparent diffusion coefficient (ADC) value of ≤1,400 × 10-6 mm2/s correlated with worse 6-month OS and PFS. We defined three patient groups that predicted the probability of tumor progression: SUVmax/NB index >1.5 and ADC ≤1,400 × 10-6 mm2/s defined high-risk patients (n = 7), SUVmax/NB index ≤1.5 and ADC >1,400 × 10-6 mm2/s defined low-risk patients (n = 11), and intermediate-risk (n = 12) defined the remainder of the patients. Median OS following the time of the FDG-PET scan for the low, intermediate, and high-risk groups were 23.5, 10.5, and 3.8 months (p < 0.01). Median PFS were 10.0, 4.4, and 1.9 months (p = 0.03). Rates of progression at 6-months in the low, intermediate, and high-risk groups were 36, 67, and 86% (p = 0.04). CONCLUSION: Recurrent GBM in the molecular era is associated with highly variable outcomes. Multiparametric MR and FDG-PET biomarkers may provide a clinically relevant, non-invasive and cost-effective method of predicting prognosis and improving clinical decision making in the treatment of patients with suspected tumor recurrence.

Resting-state Functional Magnetic Resonance Imaging in Presurgical Functional Mapping: Sensorimotor Localization.

This article compares resting-state functional magnetic resonance (fMR) imaging with task fMR imaging for presurgical functional mapping of the sensorimotor (SM) region. Before tumor resection, 38 patients were scanned using both methods. The SM area was anatomically defined using 2 different software tools. Overlap of anatomic regions of interest with task activation maps and resting-state networks was measured in the SM region. A paired t-test showed higher overlap between resting-state maps and anatomic references compared with task activation when using a maximal overlap criterion. Resting state-derived maps are more comprehensive than those derived from task fMR imaging.

The use of hippocampal volumetric measurements to improve diagnostic accuracy in pediatric patients with mesial temporal sclerosis.

OBJECTIVE Many patients with medically intractable epilepsy have mesial temporal sclerosis (MTS), which significantly affects their quality of life. The surgical excision of MTS lesions can result in marked improvement or even complete resolution of the epileptic episodes. Reliable radiological diagnosis of MTS is a clinical challenge. The purpose of this study was to evaluate the utility of volumetric mapping of the hippocampi for the identification of MTS in a case-controlled series of pediatric patients who underwent resection for medically refractory epilepsy, using pathology as a gold standard. METHODS A cohort of 57 pediatric patients who underwent resection for medically intractable epilepsy between 2005 and 2015 was evaluated. On pathological investigation, this group included 24 patients with MTS and 33 patients with non-MTS findings. Retrospective quantitative volumetric measurements of the hippocampi were acquired for 37 of these 57 patients. Two neuroradiologists with more than 10 years of experience who were blinded to the patients' MTS status performed the retrospective review of MR images. To produce the volumetric data, MR scans were parcellated and segmented using the FreeSurfer software suite. Hippocampal regions of interest were compared against an age-weighted local regression curve generated with data from the pediatric normal cohort. Standard deviations and percentiles of specific subjects were calculated. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for the original clinical read and the expert readers. Receiver operating characteristic curves were generated for the methods of classification to compare results from the readers with the authors' results, and an optimal threshold was determined. From that threshold the sensitivity, specificity, PPV, and NPV were calculated for the volumetric analysis. RESULTS With the use of quantitative volumetry, a sensitivity of 72%, a specificity of 95%, a PPV of 93%, an NPV of 78%, and an area under the curve of 0.84 were obtained using a percentage difference of normalized hippocampal volume. The resulting specificity (95%) and PPV (93%) are superior to the original clinical read and to Reader A and Reader B's findings (range for specificity 74%-86% and for PPV 64%-71%). The sensitivity (72%) and NPV (78%) are comparable to Reader A's findings (73% and 81%, respectively) and are better than those of the original clinical read and of Reader B (sensitivity 45% and 63% and NPV 71% and 70%, respectively). CONCLUSIONS Volumetric measurement of the hippocampi outperforms expert readers in specificity and PPV, and it demonstrates comparable to superior sensitivity and NPV. Volumetric measurements can complement anatomical imaging for the identification of MTS, much like a computer-aided detection tool would. The implementation of this approach in the daily clinical workflow could significantly improve diagnostic accuracy.