Improved Conductance Blockage Modeling of Cylindrical Nanopores, from 2D to Thick Membranes.

The ionic current blockage from a nanopore sensor is a fundamental metric for characterizing its dimensions and identifying molecules translocating through it. Yet, most analytical models predicting the conductance of a nanopore in both open and obstructed states remain inaccurate. Here, using an oblate spheroidal coordinate framework to study the electrical response of nanopore access regions, we reveal that the widely used model from Kowalczyk et al. significantly overestimates access region contributions when blocked by a cylindrical object, like DNA. To address this, we present an improved analytical model for the obstructed access resistance, which we establish as highly accurate through finite-element simulations, especially for ultrathin membranes and long narrow channels. Equipped with an improved nanopore conductance model, this work provides tools for more accurate calculation of the pore size and for the expected blockade from DNA, of high practical value for many biosensing applications.

DNA origami characterized via a solid-state nanopore: insights into nanostructure dimensions, rigidity and yield.

Due to their programmability via specific base pairing, self-assembled DNA origami structures have proven to be useful for a wide variety of applications, including diagnostics, molecular computation, drug delivery, and therapeutics. Measuring and characterizing these structures is therefore of great interest and an important part of quality control. Here, we show the extent to which DNA nanostructures can be characterized by a solid-state nanopore; a non-destructive, label-free, single-molecule sensor capable of electrically detecting and characterizing charged biomolecules. We demonstrate that in addition to geometrical dimensions, nanopore sensing can provide information on the mechanical properties, assembly yield, and stability of DNA nanostructures. For this work, we use a model structure consisting of a 3 helix-bundle (3HB), i.e. three interconnected DNA double helices using a M13 scaffold folded twice on itself by short DNA staple strands, and translocate it through solid-state nanopores fabricated by controlled breakdown. We present detailed analysis of the passage characteristics of 3HB structures through nanopores under different experimental conditions which suggest that segments of locally higher flexibility are present along the nanostructure contour that allow for the otherwise rigid 3HB to fold inside nanopores. By characterizing partially melted 3HB structures, we find that locally flexible segments are likely due to short staple oligomers missing from the fully assembled structure. The 3HB used herein is a prototypical example to establish nanopores as a sensitive, non-destructive, and label-free alternative to conventional techniques such as gel electrophoresis with which to characterize DNA nanostructures.

Update on Pediatric Nuclear Medicine in Acute Care.

Various radiopharmaceuticals are available for imaging pediatric patients in the acute care setting. This article focuses on the common applications used on a pediatric patient in acute care. To confirm the clinical diagnosis of brain death, brain scintigraphy is considered accurate and has been favorably compared with other methods of detecting the presence or absence of cerebral blood flow. Ventilation-perfusion lung scans are easy and safe to perform with less radiation exposure than computed tomography pulmonary angiography and remain an appropriate procedure to perform on children with suspected pulmonary embolism as a first imaging test in a hemodynamically stable patient with no history of lung disease and normal chest radiograph. 99mTc-pertechnetate scintigraphy (Meckel's scan) is the best noninvasive procedure to establish the diagnosis of ectopic gastric mucosa in Meckel's diverticulum. 99mTcred blood cell scintigraphy generally is useful for assessing lower GI bleeding in patients from any cause. Hepatobiliary scintigraphy is the most accurate diagnostic imaging modality for acute cholecystitis. 99mTc-dimercaptosuccinic acid scintigraphy is the simplest, and the most reliable and sensitive method for the early diagnosis of focal or diffuse functional cortical damage. 99mTcmercaptoacetyltriglycine scintigraphy is used to evaluate for early and late complications of renal transplantation. Bone scintigraphy is a sensitive and noninvasive technique for diagnosis of bone disorders such as osteomyelitis and fracture. 18F-fluorodeoxyglucose-positron emission tomography could be valuable in the evaluation of fever of unknown origin in pediatric patients, with better sensitivity and significantly less radiation exposure than a gallium scan. Moving forward, further refinement of pediatric radiopharmaceutical administered activities, including dose reduction, greater radiopharmaceutical applications, and updated consensus guidelines is warranted, with the use of radionuclide imaging likely to increase.

The role of renal contour change in the diagnosis of cortical scarring after urinary tract infection.

Urinary tract infections in children can lead to permanent renal scarring in approximately 15% of cases. Technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) scintigraphy is the gold standard for identifying renal scarring. Using data and scans from children enrolled at our center in a 2-year prospective clinical trial (RIVUR study), we included children with radiologically confirmed pyelonephritis who exhibited renal scarring on their 1 and/or 2-year follow-up scans and asked 3 blinded pediatric nuclear medicine physicians to reexamine the renal contours in these scans. Five girls met all eligibility criteria (each had two late 99mTc-DMSA scans 1 and 2 years after index UTI). Of the 20 kidneys imaged, 10 exhibited renal scarring and of these, 7 exhibited renal contour abnormalities. These findings suggest that the presence of abnormalities of the renal contour is not necessary for diagnosis of renal scarring.

Digital immunoassay for biomarker concentration quantification using solid-state nanopores.

Single-molecule counting is the most accurate and precise method for determining the concentration of a biomarker in solution and is leading to the emergence of digital diagnostic platforms enabling precision medicine. In principle, solid-state nanopores-fully electronic sensors with single-molecule sensitivity-are well suited to the task. Here we present a digital immunoassay scheme capable of reliably quantifying the concentration of a target protein in complex biofluids that overcomes specificity, sensitivity, and consistency challenges associated with the use of solid-state nanopores for protein sensing. This is achieved by employing easily-identifiable DNA nanostructures as proxies for the presence ("1") or absence ("0") of the target protein captured via a magnetic bead-based sandwich immunoassay. As a proof-of-concept, we demonstrate quantification of the concentration of thyroid-stimulating hormone from human serum samples down to the high femtomolar range. Further optimization to the method will push sensitivity and dynamic range, allowing for development of precision diagnostic tools compatible with point-of-care format.

Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.

BACKGROUND: To evaluate the efficacy of adjuvant systemic corticosteroids in reducing kidney scarring. A previous study suggested that use of adjuvant systemic corticosteroids reduces kidney scarring in children radiologically confirmed to have extensive pyelonephritis. Efficacy of corticosteroids for children with febrile urinary tract infection (UTI) has not been studied. METHODS: Children aged 2 months to 6 years with their first febrile UTI were randomized to corticosteroids or placebo for 3 days (both arms received antimicrobial therapy); kidney scarring was assessed using 99mTc-dimercaptosuccinic acid kidney scan 5-24 months after the initial UTI. RESULTS: We randomized 546 children of which 385 had a UTI and 254 had outcome kidney scans (instead of the 320 planned). Rates of kidney scarring were 9.8% (12/123) and 16.8% (22/131) in the corticosteroid and placebo groups, respectively (p = 0.16), corresponding to an absolute risk reduction of 5.9% (95% confidence interval: - 2.2, 14.1). CONCLUSION: While children randomized to adjuvant corticosteroids tended to develop fewer kidney scars than children who were randomized to receive placebo, a statistically significant difference was not achieved. However, the study was limited by not reaching its intended sample size. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov , NCT01391793, Registered 7/12/2011 Graphical abstract.

Evaluation of the pulmonary radioaerosol mucociliary clearance scan as an adjunctive test for the diagnosis of primary ciliary dyskinesia in children.

INTRODUCTION: The accuracy of primary ciliary dyskinesia (PCD) diagnosis has improved but no single test is diagnostic and some cases remain unsolved. Data regarding the accuracy of pulmonary radioaerosol mucociliary clearance scan (PRMCC) for the diagnosis of PCD are limited to predominantly adults using a 24-hour test. This study was performed to determine the accuracy of a 60-minute PRMCC test for diagnosing PCD in children. METHODS: Children with suspected PCD and inconclusive clinical diagnostic testing in an expert center were selected for PRMCC testing. Nebulized 99m Tc sulfur colloid was inhaled and dynamic imaging acquired for 60 to 120 minutes. Two independent radiologists blinded to the clinical diagnosis and health records overread PRMCC studies. The PRMCC result was compared with the reference standard diagnosis of PCD made by two physicians using the cumulative health record, blinded to PRMCC results. RESULTS: From 2008 to 2018, 57 patients (6-17 years) participated, of which 16 met criteria for the reference diagnosis of PCD. The PRMCC test was conclusive in 54 patients (94.7%) and had a sensitivity of 100% (95% confidence interval [CI] = 78.2-100), specificity of 85.7% (95% CI = 69.7-95.2), positive predictive value of 75% (95% CI = 57.1-87.1), negative predictive value of 100% (95% CI = 90.2-100), and accuracy of 90% (95% CI = 78.2-96.7). CONCLUSION: The 60-minute PRMCC test is noninvasive and feasible in children with a high negative predictive value for PCD. It may be a helpful adjunctive test to rule out PCD when clinical suspicion remains after guideline recommended first-line clinical testing.

Precise DNA Concentration Measurements with Nanopores by Controlled Counting.

Using a solid-state nanopore to measure the concentration of clinically relevant target analytes, such as proteins or specific DNA sequences, is a major goal of nanopore research. This is usually achieved by measuring the capture rate of the target analyte through the pore. However, progress is hindered by sources of systematic error that are beyond the level of control currently achievable with state-of-the-art nanofabrication techniques. In this work, we show that the capture rate process of solid-state nanopores is subject to significant sources of variability, both within individual nanopores over time and between different nanopores of nominally identical size, which are absent from theoretical electrophoretic capture models. We experimentally reveal that these fluctuations are inherent to the nanopore itself and make nanopore-based molecular concentration determination insufficiently precise to meet the standards of most applications. In this work, we present a simple method by which to reduce this variability, increasing the reliability, accuracy, and precision of single-molecule nanopore-based concentration measurements. We demonstrate controlled counting, a concentration measurement technique, which involves measuring the simultaneous capture rates of a mixture of both the target molecule and an internal calibrator of precisely known concentration. Using this method on linear DNA fragments, we show empirically that the requirements for precisely controlling the nanopore properties, including its size, height, geometry, and surface charge density or distribution, are removed while allowing for higher-precision measurements. The quantitative tools presented herein will greatly improve the utility of solid-state nanopores as sensors of target biomolecule concentration.

Correction to: FDG uptake in cervical lymph nodes in children without head and neck cancer.

The original version of this article unfortunately contained a mistake. Author name Alaa Bakkari was incorrect. The correct spelling is given above.

Laser-induced plasmonic colours on metals.

Plasmonic resonances in metallic nanoparticles have been used since antiquity to colour glasses. The use of metal nanostructures for surface colourization has attracted considerable interest following recent developments in plasmonics. However, current top-down colourization methods are not ideally suited to large-scale industrial applications. Here we use a bottom-up approach where picosecond laser pulses can produce a full palette of non-iridescent colours on silver, gold, copper and aluminium. We demonstrate the process on silver coins weighing up to 5 kg and bearing large topographic variations (∼1.5 cm). We find that colours are related to a single parameter, the total accumulated fluence, making the process suitable for high-throughput industrial applications. Statistical image analyses of laser-irradiated surfaces reveal various nanoparticle size distributions. Large-scale finite-difference time-domain computations based on these nanoparticle distributions reproduce trends seen in reflectance measurements, and demonstrate the key role of plasmonic resonances in colour formation.

FDG uptake in cervical lymph nodes in children without head and neck cancer.

BACKGROUND: Reactive cervical lymphadenopathy is common in children and may demonstrate increased 18F-fluoro-deoxyglucose (18F-FDG) uptake on positron emission tomography/computed tomography (PET/CT). OBJECTIVE: We sought to evaluate the frequency and significance of 18F-FDG uptake by neck lymph nodes in children with no history of head and neck cancer. MATERIALS AND METHODS: The charts of 244 patients (114 female, mean age: 10.4 years) with a variety of tumors such as lymphoma and post-transplant lymphoproliferative diseases (PTLD), but no head and neck cancers, who had undergone 18F-FDG PET/CT were reviewed retrospectively. Using the maximum standardized uptake value (SUVmax), increased 18F-FDG uptake by neck lymph nodes was recorded and compared with the final diagnosis based on follow-up studies or biopsy results. RESULTS: Neck lymph node uptake was identified in 70/244 (28.6%) of the patients. In 38 patients, the lymph nodes were benign. In eight patients, the lymph nodes were malignant (seven PTLD and one lymphoma). In 24 patients, we were not able to confirm the final diagnosis. Seven out of the eight malignant lymph nodes were positive for PTLD. The mean SUVmax was significantly higher in malignant lesions (4.2) compared with benign lesions (2.1) (P = 0.00049). CONCLUSION: 18F-FDG uptake in neck lymph nodes is common in children and is frequently due to reactive lymph nodes, especially when the SUVmax is <3.2. The frequency of malignant cervical lymph nodes is higher in PTLD patients compared with other groups.

A Pilot Study of 18F-FLT PET/CT in Pediatric Lymphoma.

We performed an observational pilot study of 18F-FLT PET/CT in pediatric lymphoma. Eight patients with equivocal 18F-FDG PET/CT underwent imaging with 18F-FLT PET/CT. No immediate adverse reactions to 18F-FLT were observed. Compared to 18F-FDG, 18F-FLT uptake was significantly higher in bone marrow and liver (18F-FLT SUV 8.6 ± 0.6 and 5.0 ± 0.3, versus 18F-FDG SUV 1.9 ± 0.1 and 3.4 ± 0.7, resp., p < 0.05). In total, 15 lesions were evaluated with average 18F-FDG and 18F-FLT SUVs of 2.6 ± 0.1 and 2.0 ± 0.4, respectively. Nonspecific uptake in reactive lymph nodes and thymus was observed. Future studies to assess the clinical utility of 18F-FLT PET/CT in pediatric lymphoma are planned.

Measurement of Differential Renal Function by Scintigraphy in Hydronephrotic Kidneys: Importance of Conjugate Views for Accurate Evaluation.

PURPOSE: Traditionally a single posterior view is used to measure differential renal function during nuclear renal scintigraphy. Nevertheless, experimental data show important variation in this measurement in the setting of significant hydronephrosis. To date, the impact of degree of hydronephrosis on the accuracy of differential renal function determination has not been addressed. We evaluated the discrepancy between function measured by anterior and posterior views, and the relationship to varying degrees of hydronephrosis. MATERIALS AND METHODS: We retrospectively reviewed consecutive mercaptoacetyltriglycine renal scans from 2009 to 2011. Ultrasounds were reviewed and degree of hydronephrosis was recorded using anteroposterior pelvic diameter. Absolute percent difference in differential renal function between each view (anterior minus posterior) was calculated and correlated to anteroposterior pelvic diameter. Patients were stratified into 4 groups according to anteroposterior pelvic diameter, ie less than 10 mm, greater than 10 mm, greater than 15 mm and greater than 25 mm. RESULTS: A total of 519 scans with corresponding ultrasounds were analyzed. Median patient age was 2.26 years. Kidneys with a larger anteroposterior pelvic diameter had a greater discrepancy in function on anterior and posterior views. There was a meaningful discrepancy for anteroposterior pelvic diameter greater than 10 mm (p = 0.034) and greater than 25 mm (p = 0.032). Several statistical models were used to identify a meaningful cut point of 15 mm, where the discrepancy in anterior and posterior views became significant (p = 0.001). CONCLUSIONS: The use of single views during nuclear renography for grossly hydronephrotic kidneys is often inaccurate. The discrepancy in differential renal function obtained on the anterior and posterior views is adversely impacted especially as anteroposterior pelvic diameter increases beyond 15 mm. Therefore, we suggest incorporation of conjugate views for estimating differential renal function in patients with hydronephrosis.

Common normal variants of pediatric vertebral development that mimic fractures: a pictorial review from a national longitudinal bone health study.

Children with glucocorticoid-treated illnesses are at risk for osteoporotic vertebral fractures, and growing awareness of this has led to increased monitoring for these fractures. However scant literature describes developmental changes in vertebral morphology that can mimic fractures. The goal of this paper is to aid in distinguishing between normal variants and fractures. We illustrate differences using lateral spine radiographs obtained annually from children recruited to the Canada-wide STeroid-Associated Osteoporosis in the Pediatric Population (STOPP) observational study, in which 400 children with glucocorticoid-treated leukemia, rheumatic disorders, and nephrotic syndrome were enrolled near glucocorticoid initiation and followed prospectively for 6 years. Normal variants mimicking fractures exist in all regions of the spine and fall into two groups. The first group comprises variants mimicking pathological vertebral height loss, including not-yet-ossified vertebral apophyses superiorly and inferiorly, which can lead to a vertebral shape easily over-interpreted as anterior wedge fracture, physiological beaking, or spondylolisthesis associated with shortened posterior vertebral height. The second group includes variants mimicking other radiologic signs of fractures: anterior vertebral artery groove resembling an anterior buckle fracture, Cupid's bow balloon disk morphology, Schmorl nodes mimicking concave endplate fractures, and parallax artifact resembling endplate interruption or biconcavity. If an unexpected vertebral body contour is detected, careful attention to its location, detailed morphology, and (if available) serial changes over time may clarify whether it is a fracture requiring change in management or simply a normal variant. Awareness of the variants described in this paper can improve accuracy in the diagnosis of pediatric vertebral fractures.

Kinetics of nanopore fabrication during controlled breakdown of dielectric membranes in solution.

Nanopore fabrication by controlled breakdown (CBD) overcomes many of the challenges of traditional nanofabrication techniques, by reliably forming solid-state nanopores sub-2 nm in size in a low-cost and scalable way for nucleic acid analysis applications. Herein, the breakdown kinetics of thin dielectric membranes immersed in a liquid environment are investigated in order to gain deeper insights into the mechanism of solid-state nanopore formation by high electric fields. For various fabrication conditions, we demonstrate that nanopore fabrication time is Weibull-distributed, in support of the hypothesis that the fabrication mechanism is a stochastic process governed by the probability of forming a connected path across the membrane (i.e. a weakest-link problem). Additionally, we explore the roles that various ions and solvents play in breakdown kinetics, revealing that asymmetric pH conditions across the membrane can significantly affect nanopore fabrication time for a given voltage polarity. These results, characterizing the stochasticity of the nanopore fabrication process and highlighting the parameters affecting it, should assist researchers interested in exploiting the potential of CBD for nanofluidic channel fabrication, while also offering guidance towards the conceivable manufacturing of solid-state nanopore-based technologies for DNA sequencing applications.

The role of ultrasound in the follow-up of children with differentiated thyroid cancer.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy with relatively good prognosis in children. However, unlike adults, children usually present with more advanced disease and have a higher local recurrence and distant metastases. Thus surveillance for recurrence is a major goal of long-term follow-up. OBJECTIVE: This retrospective study evaluates the diagnostic value of ultrasound (US) imaging in the post-therapy surveillance of children with differentiated thyroid cancer. MATERIALS AND METHODS: We reviewed the charts of 54 children (40 girls; mean age 14.3 ± 3.6 years) with differentiated thyroid cancer treated with total or near-total thyroidectomy. Forty children (29 girls and 11 boys) who had routine follow-up US examinations (112 studies) were included for the evaluation of US accuracy in the follow-up of pediatric differentiated thyroid cancer. Histopathology, stimulated thyroglobulin determination, post-therapy whole-body iodine scan and clinical follow-up were used as the standards of reference. RESULTS: Mean period of follow-up was 34 months. The frequency of recurrence was 42% (17/40). Seventeen percent of the children had lung metastases either at presentation or on follow-up. In all cases of lung metastases, stimulated thyroglobulin level was greater than 10 ng/ml. The sensitivity was 85.7%, specificity 89.4%, negative predictive value 94.4% and positive predictive value 75% for US in detecting loco-regional recurrence in follow-up studies of pediatric differentiated thyroid cancer. In 17.3% (18/104) of studies, the results of stimulated thyroglobulin and US were discordant. CONCLUSION: US showed very good sensitivity and specificity and a high negative predictive value for evaluation of loco-regional involvement in follow-up of pediatric differentiated thyroid cancer. Diagnostic whole-body iodine scan is indicated when serum anti-thyroglobulin Ab is high, or in cases of discordant findings between US and stimulated thyroglobulin levels, or when stimulated thyroglobulin levels are >10 ng/ml (to evaluate for lung metastasis).

Neuroendocrine tumor in liver with positive ACTH receptor: a case report.

A rare case of possible primary ectopic adrenocorticotropic hormone (ACTH)-producing tumor in the liver mimicking a liver hemangioma is reported. A 9-year-old boy, with Cushing syndrome, was referred for the assessment of ectopic ACTH-producing tumor. Ultrasound, CT scan, and MRI of the abdomen revealed a liver lesion suggestive of a hemangioma. (111)In-octreotide scintigraphy revealed focal activity in the liver, indicative of a somatostatin-positive lesion. (99m)Tc-labeled RBC scintigraphy was negative for hemangioma. After surgical resection of the tumor, the cortisol level converted to a normal range indicative of a rare possible primary ACTH-producing tumor in the liver, which was confirmed by histopathology.

The role of PET/CT in assessing pulmonary nodules in children with solid malignancies.

OBJECTIVE. The purpose of this article is to assess the feasibility and utility of PET/CT in distinguishing benign from malignant pulmonary nodules in patients with solid childhood malignancies. SUBJECTS AND METHODS. This prospective study was conducted between March 2008 and August 2010. We enrolled 25 subjects 21 years old or younger with solid childhood malignancies and at least one pulmonary nodule measuring 0.5-3.0 cm. PET/CT was performed within 3 weeks of diagnostic chest CT. Three panels of three reviewers each reviewed diagnostic CT only (panel 1), PET/CT only (panel 2), or diagnostic CT and PET/CT concurrently (panel 3) and predicted each nodule's histologic diagnosis as benign, malignant, or indeterminate. Interreviewer agreement was assessed with the kappa statistic. Using nodule biopsy or clinical follow-up as reference standards, the sensitivity, specificity, and accuracy for each panel was assessed. Logistic regression was used to assess the nodule's maximum standardized uptake value (SUVmax) association with its histologic diagnosis. RESULTS. There were 75 nodules with a median size of 0.74 cm (range, 0.18-2.38 cm); 48 nodules were malignant. Sensitivity was 85% (41/48) for panel 1, 60% (29/48) for panel 2, and 67% (32/48) for panel 3. All panels had poor specificities. Interreviewer agreement was moderate for panel 1 (0.43) and poor for panels 2 (0.22) and 3 (0.33). SUVmax was a significant predictor of histologic diagnosis (p = 0.004). CONCLUSION. PET/CT assessment of pulmonary nodules is feasible in children with solid malignancies but may not reliably improve our ability to predict a nodule's histologic diagnosis. The SUVmax may improve the performance of PET/CT in this setting.

Respiratory system deposition with a novel aerosol delivery system in spontaneously breathing healthy adults.

BACKGROUND: Intravenous magnesium sulfate (MgSO(4)) in children and adults with refractory acute asthma is effective, but therapy may be limited by systemic hypotension that might be avoided with the aerosol route. Inhaled MgSO(4) has a relatively high dose (volume) requirement. This, plus the use of inefficient delivery systems, may explain the lack of efficacy of inhaled MgSO(4) in some studies. An in vitro study suggested that the AeroNeb Go with the Idehaler Pocket and a face mask would deliver 16 mg/min of MgSO(4) to the respiratory system in older children, and approximately a fifth for toddlers, but no in vivo data exist. METHODS: Saline mixed with a radiolabel was used as a proxy for the 100 mg/mL MgSO(4) solution. In 5 adult males the rate of deposition was measured using nuclear medicine techniques. The radiolabel deposition below the vocal cords was converted to the rate of deposition of MgSO(4) and compared to the results from an in vitro model using adult respiratory patterns. RESULTS: The mean ± SD rate of deposition was 12.6 ± 1.9 mg/min. The reasons for this lower deposition, compared to the in vitro estimate, was most likely the exhalation of anatomical dead space aerosol, which would have been captured on the inspiratory filter in vitro. CONCLUSIONS: These in vivo data confirm the deposition data predicted in the in vitro study, although caution should be used in extrapolating the results to children. This device appears suitable for the clinical trial of inhaled MgSO(4) in children and adults with refractory asthma.

FDG-PET and magnetoencephalography in presurgical workup of children with localization-related nonlesional epilepsy.

PURPOSE: 2-[18F]Fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) and magnetoencephalography (MEG) may assist in identifying the epileptogenic zone in children with nonlesional localization-related epilepsy. The aim of this study was to evaluate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG-PET, MEG, FDG-PET + MEG, and FDG-PET/MEG in children with nonlesional localization-related epilepsy. METHODS: Twenty-six children with localization-related epilepsy and who had normal or subtle changes on magnetic resonance imaging (MRI) underwent FDG-PET and MEG. Twenty-two patients had surgical resection, and surgical outcome was assessed using Engel classification. In patients with Engel I seizure outcome, we assessed the sensitivity, specificity, PPV, and NPV of lobar localization of MEG, FDG-PET, FDG-PET + MEG, and FDG-PET/MEG. KEY FINDINGS: Sixteen (72.7%) of 22 had Engel I seizure outcome. MEG was concordant with surgical resection in 18 patients, 14 had Engel I, and four had Engel II-IV outcomes. MEG was nonlocalizing or nonconcordant in four patients; two patients had Engel I and two had Engel II-IV outcomes. FDG-PET was concordant with surgical resection in 14 patients; 9 had Engel I outcome, and 5 had Engel II-IV outcome. FDG-PET was nonlocalizing or nonconcordant in seven patients with Engel I, and one with Engel III outcome. The sensitivity, specificity, PPV, and NPV of MEG were 85.0%, 99.1%, 94.4%, and 97.3%, respectively. The sensitivity, specificity, PPV, and NPV of FDG-PET were 65.0%, 94.4%, 68.4%, and 93.6%, respectively. There was no significant difference between MEG and FDG-PET for concordance with surgical resection (χ(2)  = 2.794, p = 0.095). FDG-PET + MEG, defined as two tests concordant with surgical resection, had reduced sensitivity and NPV, but increased specificity and PPV (55.0%, 92.3%, 100%, and 100%, respectively) relative to individual tests. FDG-PET/MEG, defined as one or both test(s) concordant with surgical resection, had increased sensitivity and NPV but reduced specificity (95.0%, 99.0%, and 93.5%, respectively) relative to individual tests. SIGNIFICANCE: The two tests FDG-PET and MEG were complementary in the assessment of children with localization-related epilepsy, particularly when one test was nonlocalizing or nonconcordant.