The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders.

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics, and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals: the largest single cohort to date. Core clinical features were developmental delay or intellectual disability (DD/ID, 90%), seizures (83%), hypotonia (72%), and motor symptoms (64%). Prognostic and biologically significant neuroimaging features included cerebral atrophy (75%), cerebellar atrophy (60%), callosal anomalies (57%), and symmetric restricted diffusion of the central tegmental tracts (60%). Sixty-one individuals had multisystem involvement including gastrointestinal (66%), cardiac (19%), and renal (14%) anomalies. Though dysmorphic features were appreciated in 82%, no single dysmorphic feature had a prevalence >30%, indicating substantial phenotypic heterogeneity. Follow-up data were available for all individuals, 15 of whom were deceased at the time of writing. Median age at seizure onset was 6 months. Individuals with variants in synthesis stage genes of the GPI-AP exhibited a significantly shorter time to seizure onset than individuals with variants in transamidase and remodelling stage genes of the GPI-AP (P=0.046). Forty individuals had intractable epilepsy. The majority of individuals experienced delayed or absent speech (95%); motor delay with non-ambulance (64%); and severe-to-profound DD/ID (59%). Individuals with a developmental epileptic encephalopathy (51%) were at greater risk of intractable epilepsy (P=0.003), non-ambulance (P=0.035), ongoing enteral feeds (P<0.001), and cortical visual impairment (P=0.007). Serial neuroimaging showed progressive cerebral volume loss in 87.5% and progressive cerebellar atrophy in 70.8%, indicating a neurodegenerative process. Genetic analyses identified 93 unique variants (106 total), including 22 novel variants. Exploratory analyses of genotype-phenotype correlations using unsupervised hierarchical clustering identified novel genotypic predictors of clinical phenotype and long-term outcome with meaningful implications for management. In summary, we expand both the mild and severe phenotypic extremities of the IGDs; provide insights into their neurological basis; and, vitally, enable meaningful genetic counselling for affected individuals and their families.

Pediatric nasal chondromesenchymal hamartomas: a case series.

PURPOSE: Nasal chondromesenchymal hamartomas (NCMH) are rare, predominantly benign tumors of the sinonasal tract. The distinction from higher grade malignancy may be challenging based on imaging features alone. To increase the awareness of this entity among radiologists, we present a multi-institutional case series of pediatric NCMH patients showing the varied imaging presentation. METHODS: Descriptive assessment of imaging appearances of the lesions on computed tomography (CT) and magnetic resonance imaging (MRI) was performed. In addition, we reviewed demographic information, clinical data, results of genetic testing, management, and follow-up data. RESULTS: Our case series consisted of 10 patients, with a median age of 0.5 months. Intraorbital and intracranial extensions were both observed in two cases. Common CT findings included bony remodeling, calcifications, and bony erosions. MRI showed heterogeneous expansile lesion with predominantly hyperintense T2 signal and heterogenous post-contrast enhancement in the majority of cases. Most lesions exhibited increased diffusivity on diffusion weighted imaging and showed signal drop-out on susceptibility weighted images in the areas of calcifications. Genetic testing was conducted in 4 patients, revealing the presence of DICER1 pathogenic variant in three cases. Surgery was performed in all cases, with one recurrence in two cases and two recurrences in one case on follow-up. CONCLUSION: NCMHs are predominantly benign tumors of the sinonasal tract, typically associated with DICER1 pathogenic variants and most commonly affecting pediatric population. They may mimic aggressive behavior on imaging; therefore, awareness of this pathology is important. MRI and CT have complementary roles in the diagnosis of this entity.

Whole-Spine MRI in Children With Suspected Abusive Head Trauma.

BACKGROUND. Abusive head trauma (AHT) in children has recently been associated with findings on cervical spine MRI. OBJECTIVE. The purpose of this study was to evaluate whether whole-spine MRI in children with suspected AHT shows additional abnormalities not identified on cervical spine MRI. METHODS. This retrospective study included 256 children younger than 3 years old (170 boys, 86 girls; mean age, 5.9 months) who underwent skeletal survey and head MRI for suspected child abuse from January 2019 to December 2020. Per institutional protocol, children with suspected AHT also underwent whole-spine MRI. AHT diagnoses were established by a combination of clinical information from medical record review and injuries described in reports from skeletal survey, head MRI, and head CT (if performed). Two pediatric neuroradiologists independently reviewed whole-spine MRI examinations for presence and level of intraspinal hemorrhage (classified as subarachnoid, subdural, or epidural), ligamentous injury, spinal cord edema, and vertebral fractures; subdural hematoma, epidural hematoma, ligamentous injury, and fracture unidentified by skeletal survey were considered major findings. Interobserver agreement was assessed; a third radiologist resolved discrepancies. Findings were summarized with attention to injuries isolated to the thoracolumbar spine. RESULTS. A total of 148 of 256 (57.8%) children underwent whole-spine MRI. AHT was diagnosed in 79 of 148 (53.4%) children who underwent whole-spine MRI versus in 2 of 108 (1.9%) who did not undergo whole-spine MRI (p < .001). Interobserver agreement, expressed as kappa coefficient, was 0.90 for intraspinal hemorrhage, 0.69 for ligamentous injury, 0.66 for spinal cord edema, and 0.95 for fracture. A total of 57 of 148 (38.5%) whole-spine MRI examinations showed injuries, and 34 of 148 (23.0%) showed injuries localized to the thoracolumbar spine. A total of 47 of 148 (31.8%) whole-spine MRI examinations showed major findings, of which 24 (51.1%) were localized to the thoracolumbar spine. Isolated thoracolumbar injuries included 23 of 34 spinal subdural hematomas, 2 of 3 spinal epidural hematomas, and 9 of 11 vertebral fractures, including five fractures not identified by skeletal survey. Diagnosis of AHT was more common in children with positive, versus negative, whole-spine MRI examinations (76.8% vs 39.1%; p < .001). CONCLUSION. In children with suspected AHT, whole-spine MRI commonly shows isolated thoracolumbar injuries. CLINICAL IMPACT. The results support performing whole-spine MRI rather than cervical spine MRI in children with suspected AHT.

Thalamocortical functional connectivity in infants with prenatal opioid exposure correlates with severity of neonatal opioid withdrawal syndrome.

PURPOSE: Prenatal opioid exposure (POE) is a growing public health concern due to its associated adverse outcomes including neonatal opioid withdrawal syndrome (NOWS). The aim of this study was to assess alterations in thalamic functional connectivity in neonates with POE using resting-state functional magnetic resonance imaging (rs-fMRI) and identify whether these altered connectivity measures were associated with NOWS severity. METHODS: In this prospective, IRB-approved study, we performed rs-fMRI in 19 infants with POE and 20 healthy control infants without POE. Following standard pre-processing, we performed seed-based functional connectivity analysis with the right and left thalamus as the regions of interest. We performed post hoc analysis in the prenatal opioid exposure group to identify associations of altered thalamocortical connectivity with severity of NOWS. P value of < .05 was considered statistically significant. RESULTS: There were several regions of significantly altered thalamic to cortical functional connectivity in infants with POE compared to the healthy infants. Distinct regions of thalamocortical functional connectivity correlated with maximum modified Finnegan score. Association between thalamocortical connectivity and severity of NOWS was nominally modified by maternal psychological conditions and polysubstance use. CONCLUSION: Our findings reveal prenatal opioid exposure-related alterations in thalamic functional connectivity in the infant brain that are correlated with severity of NOWS. Future studies may benefit from evaluation of thalamocortical resting state functional connectivity in infants with POE to help  stratify risk of long term neurodevelopmental outcomes.

Utilization of neonatal sedation and anesthesia: an SPR survey.

BACKGROUND: There is little data regarding the use of sedation and anesthesia for neonatal imaging, with practice patterns varying widely across institutions. OBJECTIVE: To understand the current utilization of sedation and anesthesia for neonatal imaging, and review the current literature and recommendations. MATERIALS AND METHODS: One thousand, two hundred twenty-six questionnaire invitations were emailed to North American physician members of the Society for Pediatric Radiology using the Survey Monkey platform. Descriptive statistical analysis of the responses was performed. RESULTS: The final results represented 59 institutions from 26 U.S. states, the District of Columbia and three Canadian provinces. Discrepant responses from institutions with multiple respondents (13 out of 59 institutions) were prevalent in multiple categories. Of the 80 total respondents, slightly more than half (56%) were associated with children's hospitals and 44% with the pediatric division of an adult radiology department. Most radiologists (70%) were cognizant of the neonatal sedation policies in their departments. A majority (89%) acknowledged awareness of neurotoxicity concerns in the literature and agreed with the validity of these concerns. In neonates undergoing magnetic resonance imaging (MRI), 46% of respondents reported attempting feed and bundle in all patients and an additional 46% attempt on a case-by-case basis, with most (35%) using a single swaddling attempt before sedation. Sedation was most often used for neonatal interventional procedures (93%) followed by MR (85%), nuclear medicine (48%) and computed tomography (31%). More than half of respondents (63%) reported an average success rate of greater than 50% when using neonatal sedation for MR. CONCLUSION: Current practice patterns, policies and understanding of the use of sedation and anesthesia for neonatal imaging vary widely across institutions in North America, and even among radiologists from the same institution. Our survey highlights the need for improved awareness, education, and standardization at both the institutional level and the societal level. Awareness of the potential for anesthetic neurotoxicity and success of non-pharmacologic approaches to neonatal imaging is crucial, along with education of health care personnel, systematic approaches to quality control and improvement, and integration of evidence-based protocols into clinical practice.

Pilot study of fetal brain development and morphometry in prenatal opioid exposure and smoking on fetal MRI.

PURPOSE: The purpose of this study was to assess for any differences in brain maturation, structure and morphometry in fetuses exposed to opioids in utero, compared to non-opioid exposed fetuses on fetal MRI. METHODS: We performed a prospective study in pregnant women using opioids and healthy pregnant women without prenatal opioid use. We evaluated brain maturation, structure, and morphometry on second or third trimester fetal MRI and assessed group differences. RESULTS: 28 pregnant women were enrolled, 12 with opioid exposure (average gestational age 33.67, range 28-39 w), 9 of whom also smoked, and 16 without opioid exposure (average gestational age 32.53, range 27-38 w). There was a significant difference in the anteroposterior diameter of the fetal cerebellar vermis in the opioid exposed fetuses compared to non-opioid exposed fetuses (p = 0.004). There were no significant differences in brain biparietal diameter, fronto-occipital diameter, transverse cerebellar diameter and anteroposterior dimension of the pons in opioid exposed fetuses compared to non-opioid exposed fetuses. There were no abnormalities in brain maturation and no major brain structural abnormalities in the opioid exposed fetuses. CONCLUSION: Smaller fetal anteroposterior cerebellar vermian dimension was associated with in utero opioid exposure. There were no abnormalities in brain maturation or major structural abnormalities in fetuses exposed to opioids.

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.

Resting state functional MRI in infants with prenatal opioid exposure-a pilot study.

PURPOSE: Exposure to prenatal opioids may adversely impact the developing brain networks. The aim of this pilot study was to evaluate alterations in amygdalar functional connectivity in human infants with prenatal opioid exposure. METHODS: In this prospective IRB approved study, we performed resting state functional MRI (rs-fMRI) in 10 infants with prenatal opioid exposure and 12 infants without prenatal drug exposure at < 48 weeks corrected gestational age. Following standard preprocessing, we performed seed-based functional connectivity analysis with the right and left amygdala as the regions of interest after correcting for maternal depression and infant sex. We compared functional connectivity of the amygdala network between infants with and without prenatal opioid exposure. RESULTS: There were significant differences in connectivity of the amygdala seed regions to the several cortical regions including the medial prefrontal cortex in infants who had prenatal opioid exposure when compared with opioid naïve infants. CONCLUSION: This finding of increased amygdala functional connectivity in infants with in utero opioid exposure suggests a potential role of maternal opioid exposure on infants' altered amygdala function. This association with prenatal exposure needs to be replicated in future larger studies.

Neuroimaging in infants with prenatal opioid exposure: Current evidence, recent developments and targets for future research.

Prenatal opioid exposure (POE) has shown to be a risk factor for adverse long-term cognitive and behavioral outcomes in offspring. However, the neural mechanisms of these outcomes remain poorly understood. While preclinical and human studies suggest that these outcomes may be due to opioid-mediated changes in the fetal and early postnatal brain, other maternal, social, and environmental factors are also shown to play a role. Recent neuroimaging studies reveal brain alterations in children with POE. Early neuroimaging and novel methodology could provide an in vivo mechanistic understanding of opioid mediated alterations in developing brain. However, this is an area of ongoing research. In this review we explore recent imaging developments in POE, with emphasis on the neonatal and infant brain, and highlight some of the challenges of imaging the developing brain in this population. We also highlight evidence from animal models and imaging in older children and youth to understand areas where future research may be targeted in infants with POE.

Active cooling temperature required to achieve therapeutic hypothermia correlates with short-term outcome in neonatal hypoxic-ischaemic encephalopathy.

KEY POINTS: Hypoxic-ischaemic encephalopathy (HIE) affects 2-4/1000 live term births. Treatment with therapeutic hypothermia (TH) improves the long-term neurodevelopmental outcome of neonates with moderate to severe HIE. However, early prediction of outcome still remains challenging, and no reliable and easily obtainable biomarker has been identified to date. Neonates with HIE display impaired thermoregulation, resulting in spontaneous hypothermia. The degree of cooling required to achieve TH may therefore act as a biomarker of injury severity. The present study demonstrates a correlation between servo-controlled mattress temperature during TH and short-term outcome. Neonates with an unfavourable outcome require less cooling to maintain a core temperature between 33 and 34°C during TH compared to neonates with a favourable outcome. The degree of impaired temperature regulation was strongly associated with a high magnetic resonance imaging injury score and death. Cooling device output temperature is a potential and easily obtainable early physiological biomarker of outcome in infants with HIE undergoing TH. ABSTRACT: Neonatal hypoxic-ischaemic encephalopathy (HIE) is a leading cause of death and disability in children. Therapeutic hypothermia (TH) at 33.5°C for 72 h is the only therapy to date shown to improve outcome in moderate to severe HIE; however, assessment of severity and prediction of outcome remains challenging. Infants with HIE display significant physiological perturbations, including spontaneous hypothermia. We hypothesized that neonates with more severe brain injury on magnetic resonance imaging (MRI) would exhibit a greater degree of spontaneous hypothermia, and thus require less active cooling to attain TH. Twenty-eight neonates with moderate or severe HIE treated with TH were included in the present study. MRI images obtained on day of life 4-7 were scored according to standardized injury criteria. Unfavourable outcome was defined as death or significant grey matter injury on MRI according to a previously validated scoring system. A significantly higher cooling device output temperature was seen in infants with an unfavourable outcome. All neonates who required the mattress to provide a temperature ≥32°C to maintain their core body temperature at 33.5°C had a high likelihood of unfavourable outcome (likelihood ratio = 14.4). By contrast, infants who never required a device output temperature ≥32°C had a low likelihood of an unfavourable outcome (likelihood ratio = 0.07, P < 0.001). Infants with significant grey matter injury on MRI require less active cooling to maintain target temperature during TH. The cooling device output temperature has the potential to be an easily accessible physiological biomarker and predictor of injury and mortality in neonates with moderate or severe HIE.

Alterations in Brain Function After Cognitive Behavioral Therapy for Migraine in Children and Adolescents.

OBJECTIVES: This basic mechanistic study examined the changes in brain activation and resting-state connectivity after 8 weeks of CBT in youth with migraine. BACKGROUND: Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known. METHODS: Eighteen adolescents with migraine (15 females, age 15.1 ± 2.1 years [mean ± SD]) completed 8 weekly CBT sessions. Before the first and after the final CBT session, participants underwent structural and resting-state blood-oxygen-level-dependent contrast MRI scans. Arterial spin labeling was also used to examine brain activation during the resting state. For connectivity analyses, the right and left amygdala were chosen as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. RESULTS: Headache frequency decreased from 15 ± 7.4 headaches per month before CBT to 10 ± 7.4 after CBT (P < .001). After CBT, greater brain activations in frontal regions involved in cognitive regulation of pain were found. In addition, after CBT increased connectivity between the amygdala and frontal regions was observed. Associations between brain activation and amygdalar connectivity with a reduction in headache frequency were also observed. CONCLUSIONS: Alterations in brain function and amygdalar connectivity with areas involved in nociceptive processing, cognitive function, and emotional regulation may underlie the ability of CBT to aid in the prevention of headaches in migraine patients.

Frontal Occipital and Frontal Temporal Horn Ratios: Comparison and Validation of Head Ultrasound-Derived Indexes With MRI and Ventricular Volumes in Infantile Ventriculomegaly.

OBJECTIVE. The purpose of our study was to assess whether linear ventricular dimensions-specifically, the frontal occipital horn ratio (FOHR) and frontal temporal horn ratio (FTHR) obtained from ultrasound (US)-are reliable measures of ventriculomegaly in infants. Our hypothesis was that these US measures would show good correlation with linear ventricular indexes and ventricular volumes obtained from MRI. MATERIALS AND METHODS. We retrospectively identified 90 infants (age ≤ 6 months corrected gestational age) with ventriculomegaly from 2014 to 2017 who had a total of 100 sets of US and MRI studies performed in a 3-day period. FOHR and FTHR were independently measured on US and MRI by two pediatric radiologists and two pediatric neuroradiologists, respectively. Ventricular and brain volumes were segmented from the MR images, and the ventricle-to-intracranial volume ratio was calculated. MRI served as the reference standard. Intraclass correlation coefficients and Bland-Altman analyses were generated to evaluate interobserver and US-MRI concordance. We assessed correlation of the FOHR and FTHR with the ventricle-to-intracranial volume ratio. RESULTS. Bland-Altman plots of the FOHR and FTHR between US and MRI showed excellent concordance with a bias of 0.05 (95% CI, -0.04 to 0.14) and 0.03 (95% CI, -0.06 to 0.13), respectively. There was good-to-excellent interobserver concordance for FOHR and FTHR on head US or MRI (r = 0.86-0.96). There was good correlation between ventricle-to-intracranial volume ratios and US- and MRI-derived FOHRs and FTHRs (r = 0.79-0.87). CONCLUSION. FOHR and FTHR obtained from US in infants with ventriculomegaly have excellent interobserver concordance, are concordant with MRI-derived linear ratios, and correlate with MRI-derived ventricular volumes. Therefore, US-derived FOHR and FTHR are reliable indexes for clinical follow-up of infantile ventriculomegaly.

Emergent Imaging of Pediatric Cervical Spine Trauma.

Owing to physiologic and biomechanical differences, the incidence, patterns, distributions, and mechanisms of spinal injury in children differ from those in adults. Furthermore, evaluation of the spine can be complicated by synchondroses, developmental and/or anatomic variants, and interpretative pitfalls that are unique to the developing spine of a child. Although the incidence of spinal injury is lower in children, the sequelae are more severe, with higher morbidity and mortality. Mechanistic differences, notably nonaccidental trauma in infants and toddlers; physiologic differences, notably a disproportionately large head relative to body size and ligamentous and soft-tissue laxity; and the propensity of these injuries to occur at higher spinal levels (craniocervical junction to C3) are contributing factors. In addition, imaging recommendations for children are different. Assessment of spinal alignment and adjacent soft tissues, particularly at the craniocervical junction, with a low threshold for performing MRI, is key to diagnosing these serious injuries. The patterns of common pediatric cervical spine injuries, including craniocervical junction injury and spinal cord injury without a correlating radiographic abnormality, are reviewed. ©RSNA, 2019.

Black bone MRI with 3D reconstruction for the detection of skull fractures in children with suspected abusive head trauma.

PURPOSE: The purpose of this study was to determine the accuracy of "black bone" (BB) MRI for the detection of skull fractures in children with potential abusive head trauma. METHODS: A total of 34 pediatric patients were evaluated for potential abusive head trauma. All patients had both a non-contrast head CT (HCT) with multiplanar reformatted images and 3D volumetric reformatted images where available (gold standard) for fracture diagnosis and BB of the head with multiplanar reformatted images and 3D volumetric images. BB was performed using an ultrashort TE pointwise encoding time reduction with radial acquisition (PETRA) sequence at 1.5 T or 3 T. BB datasets were post-processed and 3D images created using Fovia's High Definition Volume Rendering® software. Two board-certified pediatric neuroradiologists independently reviewed the HCT and BB imaging, blinded to the findings from the other modality. RESULTS: Median patient age was 4 months (range 1.2-30 months). A total of 20 skull fractures in six patients (18% incidence of skull fractures) were detected on HCT. BB demonstrated 83% sensitivity (95%[CI] 36-99%), 100% specificity (95%[CI] 88-100%), 100% PPV (95%[CI] 46-100%), 97% NPV (95%[CI] 82-99%), and 97% accuracy (95%[CI] 85-99%) for diagnosis of a skull fracture. BB detected 95% (19/20) of the skull fractures detected by CT. CONCLUSION: A black bone MRI sequence may provide high sensitivity and specificity for detection of skull fractures in pediatric patients with abusive head trauma.

Fetal brain morphometry on prenatal magnetic resonance imaging in congenital diaphragmatic hernia.

BACKGROUND: Many infants with congenital diaphragmatic hernia (CDH) show brain abnormality on postnatal brain MRI related to severity of CDH, degree of lung hypoplasia, intrathoracic liver, right diaphragmatic hernia and large diaphragmatic defect. It is not known whether these factors affect brain growth in utero in CDH. OBJECTIVE: To assess prenatal brain morphometry and abnormalities on fetal MR in congenital diaphragmatic hernia. MATERIALS AND METHODS: We retrospectively reviewed 109 fetal MRIs in 63 fetuses with CDH from 2009 to 2014 (27 died before discharge, 36 survived to discharge). We compared brain injury and gestational-age-corrected z-scores of brain measurements between survivors and non-survivors. We assessed correlations between brain abnormalities and CDH severity. RESULTS: Enlarged extraaxial space was the most common abnormality, frequently seen on fetal MRI at >28 weeks of gestation, similar in survivors versus non-survivors. Anteroposterior cerebellar vermis dimension at >28 weeks of gestation was smaller in non-survivors compared to survivors (P=.02) and positively correlated with observed/expected total fetal lung volume (P=.01). Transverse cerebellar diameter at >28 weeks of gestation was also positively correlated with observed/expected total fetal lung volume (P=.04). We did not identify maturational delay, abnormal parenchymal signal or intracranial hemorrhage on fetal MRI. CONCLUSION: Enlarged extraaxial spaces in the third trimester was the most common abnormality on fetal MRI in congenital diaphragmatic hernia. Cerebellar dimensions on fetal MRI are associated with CDH severity. There was no major brain parenchymal injury on fetal MRI, even in the third trimester, in CDH survivors and non-survivors.

A Retrospective Analysis of the Utility of Head Computed Tomography and/or Magnetic Resonance Imaging in the Management of Benign Macrocrania.

OBJECTIVE: To assess whether computed tomography (CT), magnetic resonance imaging (MRI), and neurosurgical evaluations altered the diagnosis or management of children diagnosed with benign macrocrania of infancy by ultrasonography (US). STUDY DESIGN: We queried our radiology database to identify patients diagnosed with benign macrocrania of infancy by US between 2006 and 2013. Medical records of those with follow-up CT/MRI were reviewed to determine clinical/neurologic status and whether or not CT/MRI imaging resulted in diagnosis of communicating hydrocephalus or required neurosurgical intervention. RESULTS: Patients with benign macrocrania of infancy (n = 466) were identified (mean age at diagnosis: 6.5 months). Eighty-four patients (18.0%) received subsequent head CT/MRI; of these, 10 patients had neurologic abnormalities before 2 years of age, of which 3 had significant findings on MRI (temporal lobe white matter changes, dysmorphic ventricles, thinned corpus callosum). One patient without neurologic abnormalities had nonspecific white matter signal abnormality (stable over 6 months) but no change in management. None required neurosurgical intervention. Another 9/84 patients had incidental findings including Chiari I (3), small subdural bleeds (2), arachnoid cyst (1), small cavernous malformation (1), frontal bone dermoid (1), and a linear parietal bone fracture after a fall (1). CONCLUSIONS: Children diagnosed with benign macrocrania of infancy on US without focal neurologic findings do not require subsequent brain CT/MRI or neurosurgical evaluation. Decreasing unnecessary imaging would decrease costs, minimize radiation and sedation exposures, and increase clinic availability of neurology and neurosurgery specialists.

Clinical validation of synthetic brain MRI in children: initial experience.

INTRODUCTION: The purpose of this study was to determine the diagnostic accuracy of synthetic MR sequences generated through post-acquisition processing of a single sequence measuring inherent R1, R2, and PD tissue properties compared with sequences acquired conventionally as part of a routine clinical pediatric brain MR exam. METHODS: Thirty-two patients underwent routine clinical brain MRI with conventional and synthetic sequences acquired (22 abnormal). Synthetic axial T1, T2, and T2 fluid attenuation inversion recovery or proton density-weighted sequences were made to match the comparable clinical sequences. Two exams for each patient were de-identified. Four blinded reviewers reviewed eight patients and were asked to generate clinical reports on each exam (synthetic or conventional) at two different time points separated by a mean of 33 days. Exams were rated for overall and specific finding agreement (synthetic/conventional and compared to gold standard consensus review by two senior reviewers with knowledge of clinical report), quality, and diagnostic confidence. RESULTS: Overall agreement between conventional and synthetic exams was 97%. Agreement with consensus readings was 84% (conventional) and 81% (synthetic), p = 0.61. There were no significant differences in sensitivity, specificity, or accuracy for specific imaging findings involving the ventricles, CSF, brain parenchyma, or vasculature between synthetic or conventional exams (p > 0.05). No significant difference in exam quality, diagnostic confidence, or noise/artifacts was noted comparing studies with synthetic or conventional sequences. CONCLUSIONS: Diagnostic accuracy and quality of synthetically generated sequences are comparable to conventionally acquired sequences as part of a standard pediatric brain exam. Further confirmation in a larger study is warranted.

Diffuse phalangeal signal abnormality on magnetic resonance imaging: phalangeal microgeodic disease.

BACKGROUND: Phalangeal microgeodic disease is a rare and benign self-limited condition involving the phalanges, often in the setting of cold exposure, with characteristic MR imaging abnormalities. Radiographic case descriptions are predominantly from Asia and Europe, with only seven cases using MR to characterize phalangeal microgeodic disease. OBJECTIVE: In this study we describe the MR imaging appearance of unusual and striking phalangeal signal abnormality compatible with phalangeal microgeodic disease at our institution in North America. MATERIALS AND METHODS: We retrospectively reviewed cases presenting at our institution with unusual or unexplained phalangeal signal abnormalities between 2001 and 2014. We reviewed the MR imaging appearances in conjunction with radiographs and any other available imaging investigations. RESULTS: Of 189 examinations reviewed during the study period, 8 imaging studies in 6 patients met the study inclusion criteria. Signal abnormality was present in 57 of 112 phalanges (51%), frequently involving the distal phalanges (70%, 28 of 40), followed by the middle phalanges (56%, 18 of 32) and the proximal phalanges (28%, 11 of 40). The pattern of involvement was most commonly diaphysis (38%), followed by metaphysis (32%) and epiphysis (30%). The extent of MR signal abnormality was greater than that suspected based on clinical presentation or on radiographs. CONCLUSION: The presence of unexplained diffuse characteristic marrow involvement of multiple painful phalanges on MR images, often in the setting of cold exposure, should raise the possibility of phalangeal microgeodic disease. Consideration of this diagnosis based on MR findings would lead to a more conservative management and avoid unnecessary invasive diagnostic procedures.

Prospective detection of cortical dysplasia on clinical MRI in pediatric intractable epilepsy.

BACKGROUND: Cortical dysplasia is the most common cause of pediatric refractory epilepsy. MRI detection of epileptogenic lesion is associated with good postsurgical outcome. Additional electrophysiological information is suggested to be helpful in localization of cortical dysplasia. Educational measures were taken to increase the awareness of cortical dysplasia at our institution in the context of a recent International League Against Epilepsy (ILAE 2011) classification of cortical dysplasia. OBJECTIVE: To determine changes in the rate of prospective identification of cortical dysplasia on an initial radiology report and also evaluate the benefit of MRI review as part of a multidisciplinary epilepsy conference in identifying previously overlooked MRI findings. MATERIALS AND METHODS: We retrospectively evaluated surgically treated children with refractory epilepsy from 2007 to 2014 with cortical dysplasia on histopathology. We analyzed the initial radiology report, preoperative MRI interpretation at multidisciplinary epilepsy conference and subsequent retrospective MRI review with knowledge of the resection site. We recorded additional electrophysiological data and the presence of lobar concordance with the MRI findings. RESULTS: Of 78 children (44 MRI lesional) evaluated, 18 had initially overlooked MRI findings. Comparing 2007-2010 to 2011-2014, there was improvement in the rate of overlooked findings on the initial radiology report (54% vs. 13% of lesional cases, respectively; P = 0.008). The majority (72%) were identified at a multidisciplinary conference with lobar concordance of findings with at least one additional electrophysiological investigation in 89%. CONCLUSION: Awareness of current classification schemes of cortical dysplasia and image review in the context of a multidisciplinary conference can lead to improved MRI detection of cortical dysplasia in children.