Functional imaging localization of complex organic hallucinations.

Background: fMRI of mental phenomena is quite difficult to perform because lack of patient's cooperation or because the symptoms are stable. In some exceptional cases, however, fMRI and DTI are capable to provide insights on the anatomy of organic hallucinations. Methods: In this report we describe a 14-year-old boy with a left fronto-dorsal tumor who experienced chronic complex brief, frequent and repetitive complex visual and auditory hallucinations. His clinical picture included multiple and severe social and mood problems. During a presurgical fMRI mapping the patient complained of having the visual and auditory hallucinations. A block-design FMRI paradigm was obtained from the event timecourse. Deterministic DTI of the brain was obtained seeding the lesion as ROI. The patient underwent surgery and electrocorticography of the lesional area. Results: The fMRI of the hallucinations showed activation in the left inferior frontal gyrus (IFG) and the peri-lesional area. The tractography of the tumor revealed structural aberrant connectivity to occipital and temporal areas in addition to the expected connectivity with the IFG via the aslant fasciculus and homotopic contralateral areas. Intraoperative EEG demonstrated epileptic discharges in the tumor and neighboring areas. After resection, the patient's hallucinations stopped completely. He regained his normal social life and recover his normal mood. He remained asymptomatic for 90 days. Afterwards, hallucinations reappeared but with less intensity. Conclusions: To our knowledge, this is the first reported case of combined functional and structural connectivity imaging demonstrating brain regions participating in a network involved in the generation of complex auditory and visual hallucinations.

Fiber pathways supporting early literacy development in 5-8-year-old children.

The development of fluent reading is an extended process that requires the recruitment of a comprehensive system of perisylvian brain regions connected by an extensive network of fiber pathways. In the present cross-sectional study, we focused on fiber pathways-the arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and vertical occipital fasciculus (VOF)-proposed to support early literacy in typical 5-8-year-old children. We related quantitative metrics of fiber pathway microstructure in these pathways to early literacy measures of phonological awareness and decoding. We found that diffusion properties of the AF, ILF, and VOF not only show age-related differences, but also are predictive of early literacy skills after controlling for the effects of age, general white matter development, sex, IQ, and phonological skill. Perhaps most novel, we provide evidence supporting the involvement of the recently re-identified VOF in early literacy, and further, we provide evidence that a bilateral network of fiber pathways supports early literacy development.

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY): an epileptogenic neoplasm with oligodendroglioma-like components, aberrant CD34 expression, and genetic alterations involving the MAP kinase pathway.

Epileptogenic tumors affecting children and young adults are a morphologically diverse collection of neuroepithelial neoplasms that, as a group, exhibit varying levels of glial and/or neuronal differentiation. Recent advances in molecular profiling technology, including comprehensive DNA sequencing and methylation analysis, have enabled the application of more precise and biologically relevant classification schemes to these tumors. In this report, we describe a morphologically and molecularly distinct epileptogenic neoplasm, the polymorphous low-grade neuroepithelial tumor of the young (PLNTY), which likely accounts for a sizable portion of oligodendroglioma-like tumors affecting the pediatric population. Characteristic microscopic findings most notably include infiltrative growth, the invariable presence of oligodendroglioma-like cellular components, and intense immunolabeling for cluster of differentiation 34 (CD34). Moreover, integrative molecular profiling reveals a distinct DNA methylation signature for PLNTYs, along with frequent genetic abnormalities involving either B-Raf proto-oncogene (BRAF) or fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3). These findings suggest that PLNTY represents a distinct biological entity within the larger spectrum of pediatric, low-grade neuroepithelial tumors.

Squamosal Suture Synostosis: Incidence, Associations, and Implications for Treatment.

Squamosal suture craniosynostosis is thought to be a relatively rare entity. In the authors' experience, it is underreported in imaging examinations and the existing literature. The authors sought to determine the incidence of squamosal synostosis, whether it is increasing in frequency, and its relationship with synostosis of the major calvarial sutures.Patients undergoing computed tomography imaging for suspected craniosynostosis over a 15-year period were reviewed by a plastic surgeon and pediatric neuroradiologist. Patients with synostosis of the squamosal sutures were identified and involvement of additional sutures, gender, and the presence of a known syndromic diagnosis were recorded. Patients greater than 4 years of age or those with prior craniofacial surgery were excluded.One hundred twenty-five patients met inclusion criteria, 26 of whom had squamosal suture synostosis (26/125, 20.8%). Squamosal synostosis was found in isolation in 3 patients (3/26, 11.5%), with 1 additional major suture in 10 patients (10/26, 38.5%), and ≥2 major sutures in 13 patients (13/26, 50%). Squamosal synostosis was more common in patients with a syndromic diagnosis (11/26 syndromic, 15/99 nonsyndromic, P < 0.001). Eleven of 26 patients with squamosal synostosis were identified in the radiology report (42.3%).Craniosynostosis of the squamosal suture is much more common than previously reported and can contribute to abnormal head shape in isolation, or in combination with major sutures. Squamosal suture synostosis is underdiagnosed clinically and radiologically, although insufficient evidence exists to determine if its true incidence is increasing.

Assessment of diffusion tensor image quality across sites and vendors using the American College of Radiology head phantom.

The purpose of this study was to explore the feasibility of assessing quality of diffusion tensor imaging (DTI) from multiple sites and vendors using American College of Radiology (ACR) phantom. Participating sites (Siemens (n = 2), GE (n= 2), and Philips (n = 4)) reached consensus on parameters for DTI and used the widely available ACR phantom. Tensor data were processed at one site. B0 and eddy current distortions were assessed using grid line displacement on phantom Slice 5; signal-to-noise ratio (SNR) was measured at the center and periphery of the b = 0 image; fractional anisotropy (FA) and mean diffusivity (MD) were assessed using phantom Slice 7. Variations of acquisition parameters and deviations from specified sequence parameters were recorded. Nonlinear grid line distortion was higher with linear shimming and could be corrected using the 2nd order shimming. Following image registration, eddy current distortion was consistently smaller than acquisi-tion voxel size. SNR was consistently higher in the image periphery than center by a factor of 1.3-2.0. ROI-based FA ranged from 0.007 to 0.024. ROI-based MD ranged from 1.90 × 10-3 to 2.33 × 10-3 mm2/s (median = 2.04 × 10-3 mm2/s). Two sites had image void artifacts. The ACR phantom can be used to compare key qual-ity measures of diffusion images acquired from multiple vendors at multiple sites.

Pediatric applications of functional magnetic resonance imaging.

Pediatric functional MRI has been used for the last 2 decades but is now gaining wide acceptance in the preoperative workup of children with brain tumors and medically refractory epilepsy. This review covers pediatrics-specific difficulties such as sedation and task paradigm selection according to the child's age and cognitive level. We also illustrate the increasing uses of functional MRI in the depiction of cognitive function, neuropsychiatric disorders and response to pharmacological agents. Finally, we review the uses of resting-state fMRI in the evaluation of children and in the detection of epileptogenic regions.

Conventional and advanced MRI features of pediatric intracranial tumors: posterior fossa and suprasellar tumors.

OBJECTIVE: In this article, we review the most common posterior fossa and suprasellar intracranial neoplasms in the pediatric population. We briefly discuss basic MRI concepts used in the initial evaluation of a pediatric brain tumor and then discuss sophisticated MRI techniques that give insight into the physiology and chemical makeup of these tumors to help the radiologist make a more specific diagnosis. CONCLUSION: Diagnosis and treatment of pediatric CNS tumors necessitate a multi-disciplinary approach and require expertise and diligence of all parties involved. Imaging is an essential component has evolved greatly over the past decade. We are becoming better at making a preoperative diagnosis of that tumor type, detecting recurrence, and guiding surgical management to avoid injury to vital brain structures.

Conventional and advanced MRI features of pediatric intracranial tumors: supratentorial tumors.

OBJECTIVE. Our objective is to review the imaging characteristics and applications of conventional and advanced neuroimaging techniques of supratentorial intracranial masses in the pediatric population. Specifically, we review astrocytomas, oligodendrogliomas, primary neuroectodermal tumors, dysembryoplastic neuroepithelial tumors, gangliogliomas, arachnoid cysts, and choroid plexus and pineal region masses. CONCLUSION. Advanced imaging methods, such as MR spectroscopy, perfusion MRI, functional MRI, diffusion-tensor imaging, and tractography, help develop a more accurate differential diagnosis and aid in planning tumor treatment.

Incidence, follow-up, and postnatal clinical progress of children with central nervous system anomalies on fetal MRI.

OBJECTIVE: MRI is increasingly employed to assess intrauterine fetal anomalies. Central nervous system (CNS) anomalies are common structural conditions that warrant evaluation with fetal MRI and subsequent prenatal consultation with a pediatric neurosurgeon. As the use of fetal MRI increases, there is greater impetus to understand the most common CNS structural anomalies diagnosed in utero, as well as their natural histories. METHODS: The authors performed a single-center retrospective review of fetal MRI evaluations performed between January 2012 and December 2020. Children who underwent both prenatal and postnatal neurosurgical evaluations of CNS anomalies were included. Specific CNS anomalies on fetal MRI, associated extra-CNS findings, and suspicion for genetic abnormality or syndromes were noted. Postnatal clinical status and interventions were assessed. RESULTS: Between January 2012 and December 2020, a total of 469 fetal MRI evaluations were performed; of these, 114 maternal-fetal pairs had CNS anomalies that warranted prenatal consultation and postnatal pediatric neurosurgical follow-up. This cohort included 67 male infants (59%), with a mean ± SD follow-up of 29.8 ± 25.0 months after birth. Fetal MRI was performed at 27.3 ± 5.8 weeks of gestational age. The most frequently reported CNS abnormalities were ventriculomegaly (57%), agenesis or thinning of the corpus callosum (33%), Dandy-Walker complex (DWC) (21%), neuronal migration disorders (18%), and abnormalities of the septum pellucidum (17%). Twenty-one children (18%) required neurosurgical intervention at a mean age of 2.4 ± 3.7 months. The most common surgical conditions included myelomeningocele, moderate to severe ventriculomegaly, encephalocele, and arachnoid cyst. Corpus callosum agenesis or thinning was associated with developmental delay (p = 0.02) and systemic anomalies (p = 0.05). The majority of prenatal patients referred for DWC had Dandy-Walker variants that did not require surgical intervention. CONCLUSIONS: The most common conditions for prenatal neurosurgical assessment were ventriculomegaly, corpus callosum anomaly, and DWC, whereas the most common surgical conditions were myelomeningocele, hydrocephalus, and arachnoid cyst. Only 18% of prenatal neurosurgical consultations resulted in surgical intervention during infancy. The majority of referrals for prenatal mild ventriculomegaly and DWC were not associated with developmental or surgical sequelae. Patients with corpus callosum abnormalities should be concurrently referred to a neurologist for developmental assessments.

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) is an incisionless procedure capable of thermoablation through the focus of multiple acoustic beams. Although MRgFUS is currently approved for the treatment of tremor in adults, its safety and feasibility profile for intracranial lesions in the pediatric and young adult population remains unknown. METHODS: The long-term outcomes of a prospective single-center, single-arm trial of MRgFUS at Nicklaus Children's Hospital in Miami, Florida, are presented. Patients 15-22 years of age with centrally located lesions were recruited, clinically consistent with WHO grade I tumors that require surgical intervention. This cohort consisted of 4 patients with hypothalamic hamartoma (HH), and 1 patient with tuberous sclerosis complex harboring a subependymal giant cell astrocytoma (SEGA). RESULTS: In each case, high-intensity FUS was used to target the intracranial lesion. Real-time MRI was used to monitor the thermoablations. Primary outcomes of interest were tolerability, feasibility, and safety of FUS. The radiographic ablation volume on intra- and postoperative MRI was also assessed. All 5 patients tolerated the procedure without any complications. Successful thermoablation was achieved in 4 of the 5 cases; the calcified SEGA was undertreated due to intratumor calcification, which prevented attainment of the target ablation temperature. The HHs underwent target tissue thermoablations that led to MR signal changes at the treatment site. For the patients harboring HHs, FUS thermoablations occurred without procedure-related complications and led to improvement in seizure control or hypothalamic hyperphagia. All 5 patients were discharged home on postoperative day 1 or 2, without any readmissions. There were no cases of hemorrhage, electrolyte derangement, endocrinopathy, or new neurological deficit in this cohort. CONCLUSIONS: This experience demonstrates that FUS thermoablation of centrally located brain lesions in adolescents and young adults can be performed safely and that it provides therapeutic benefit for associated symptoms.

Hemangiomas revisited: the useful, the unusual and the new. Part 2: endangering hemangiomas and treatment.

Hemangiomas, although benign tumors, can when located in particular regions threaten vital structures or in certain clinical circumstances be associated with other abnormalities, carrying significant morbidity and mortality. We review these endangering hemangiomas. We also discuss briefly the treatment with emphasis on the recent use of propranolol.

Hemangiomas revisited: the useful, the unusual and the new. Part 1: overview and clinical and imaging characteristics.

Hemangiomas are common vascular tumors occurring in children. Though most of the lesions present in infants and young children with a typical appearance, it is important to understand that they all do not behave in the same way. Rather, they are a group of vascular lesions with different clinico-pathological subtypes, with their clinical behavior varying with the stage of the tumor as well. As such, they can and do have a varied clinical, imaging and pathological appearance according to the location of the tumor and also the stage at which the patient is seen. In this pictorial essay, the classification, pathogenesis, clinical appearance, natural history and imaging characteristics of hemangiomas are reviewed and illustrated.

Neural networks of motor and cognitive inhibition are dissociated between brain hemispheres: an fMRI study.

Paradigms exploring cognitive inhibition involve motor responses, which may confound the results. We compare cognitive inhibition activation obtained without motor involvement, to motor inhibition alone, in a group of young right-handed volunteers, utilizing a classical color Stroop task (CST), and a Stop Task. Comparison of fMRI activation was performed contrasting lateralization indexes of different Regions of Interest (ROI). Cognitive inhibition showed left brain lateralization, while motor inhibition showed right brain lateralization. Homologue brain areas involved the inferior frontal gyrus, inferior parietal lobule, middle temporal gyrus, and anterior cingulate gyrus. These circuitries appear to support that inhibition is a complicated function involving working memory, attention, semantic decision, and motivation modules.

Presurgical hyperconnectivity of the ablation volume is associated with seizure-freedom after magnetic resonance-guided laser interstitial thermal therapy.

PURPOSE: Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) is an emerging minimally-invasive alternative to resective surgery for medically-intractable epilepsy. The precise lesioning effect produced by MRgLITT supplies opportunities to glean insights into epileptogenic regions and their interactions with functional brain networks. In this exploratory analysis, we sought to characterize associations between MRgLITT ablation zones and large-scale brain networks that portended seizure outcome using resting-state fMRI. METHODS: Presurgical fMRI and intraoperatively volumetric structural imaging were obtained, from which the ablation volume was segmented. The network properties of the ablation volume within the brain's large-scale brain networks were characterized using graph theory and compared between children who were and were not rendered seizure-free. RESULTS: Of the seventeen included children, five achieved seizure freedom following MRgLITT. Greater functional connectivity of the ablation volume to canonical resting-state networks was associated with seizure-freedom (p < 0.05, FDR-corrected). The ablated volume in children who subsequently became seizure-free following MRgLITT had significantly greater strength, and eigenvector centrality within the large-scale brain network. CONCLUSIONS: These findings provide novel insights into the interaction between epileptogenic cortex and large-scale brain networks. The association between ablation volume and resting-state networks may supply novel avenues for presurgical planning and patient stratification.

Presurgical thalamocortical connectivity is associated with response to vagus nerve stimulation in children with intractable epilepsy.

Although chronic vagus nerve stimulation (VNS) is an established treatment for medically-intractable childhood epilepsy, there is considerable heterogeneity in seizure response and little data are available to pre-operatively identify patients who may benefit from treatment. Since the therapeutic effect of VNS may be mediated by afferent projections to the thalamus, we tested the hypothesis that intrinsic thalamocortical connectivity is associated with seizure response following chronic VNS in children with epilepsy. Twenty-one children (ages 5-21 years) with medically-intractable epilepsy underwent resting-state fMRI prior to implantation of VNS. Ten received sedation, while 11 did not. Whole brain connectivity to thalamic regions of interest was performed. Multivariate generalized linear models were used to correlate resting-state data with seizure outcomes, while adjusting for age and sedation status. A supervised support vector machine (SVM) algorithm was used to classify response to chronic VNS on the basis of intrinsic connectivity. Of the 21 subjects, 11 (52%) had 50% or greater improvement in seizure control after VNS. Enhanced connectivity of the thalami to the anterior cingulate cortex (ACC) and left insula was associated with greater VNS efficacy. Within our test cohort, SVM correctly classified response to chronic VNS with 86% accuracy. In an external cohort of 8 children, the predictive model correctly classified the seizure response with 88% accuracy. We find that enhanced intrinsic connectivity within thalamocortical circuitry is associated with seizure response following VNS. These results encourage the study of intrinsic connectivity to inform neural network-based, personalized treatment decisions for children with intractable epilepsy.

Fiber tracking of the frontal aslant tract and subcomponents of the arcuate fasciculus in 5-8-year-olds: Relation to speech and language function.

Long association cortical fiber pathways support developing networks for speech and language, but we do not have a clear understanding of how they develop in early childhood. Using diffusion-weighted imaging (DWI) we tracked the frontal aslant tract (FAT), arcuate fasciculus (AF), and AF segments (anterior, long, posterior) in 19 typical 5-8-year-olds, an age range in which significant improvement in speech and language function occurs. While the microstructural properties of the FAT and the right AF did not show age-related differences over the age range we investigated, the left AF evidenced increasing fractional anisotropy with age. Microstructural properties of the AF in both hemispheres, however, predicted receptive and expressive language. Length of the left FAT also predicted receptive language, which provides initial suggestion that this pathway is important for language development. These findings have implications for models of language development and for models of the neurobiology of language more broadly.

False lateralization of language cortex on functional MRI after a cluster of focal seizures.

fMRI can define language cortex but its limitations are not yet fully understood. This article describes a child in whom fMRI falsely lateralized language cortex when performed after a cluster of left temporal lobe seizures. Multiple language tasks revealed no activation over the left temporal lobe despite a normal neurologic exam at the time of the study. A second fMRI performed 2 weeks later activated sites predominantly over the left, which were confirmed by extra-operative functional language mapping. fMRI may be unhelpful after frequent seizures.

Visual functional magnetic resonance imaging in patients with Sturge-Weber syndrome.

The purpose of this study is to report different patterns of visual cortex activation in patients with Sturge-Weber syndrome as compared with healthy control subjects. Utilizing a visual paradigm of flashing lights, three children with Sturge-Weber syndrome were studied with functional magnetic resonance imaging. The results are compared with those documented in eight normal sedated children, and six young adult awake volunteers, using the same paradigms. All adult volunteers manifested bilateral activation in primary visual cortex (Brodmann's 17 and 18 areas). Two of them also had activation in secondary visual cortex (Brodmann's 19 area). In the eight sedated normal children, seven manifested activation in primary visual areas. The last exhibited no activation. The patients with Sturge-Weber syndrome demonstrated in the affected occipital lobe increased activation in one patient (11 months old), no activation in the second (12 years of age), and abnormal distribution of the activation in the third (11 months old). This report demonstrates that the vascular malformation of Sturge-Weber syndrome does not necessarily prevent cortical activation in the expected occipital cortex and may be associated with different patterns of abnormal activation. Assessing cortical function with functional magnetic resonance imaging in patients with Sturge-Weber syndrome may be helpful in decisions of surgical management and counseling.

Vesicoureteral reflux imaging in children: comparative cost analysis.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare the costs of voiding cystourethrography (VCUG) versus radionuclide cystography (RNC) for evaluation of vesicoureteral reflux in children. MATERIALS AND METHODS: The variable direct costs of performing 25 VCUG and 25 RNC examinations in age- and general health-matched patients suspected of having vesicoureteral reflux was determined by using time and motion analyses. All personnel directly involved in the cases were tracked, and the involvement times were recorded to the nearest minute. All material items used during the procedures were recorded. The cost of labor was determined from personnel reimbursement data, and the cost of materials, from vendor pricing. The fixed direct costs were assessed from hospital accounting records. Mean, standard deviation, and 95% confidence interval (CI) were determined for all direct (fixed and variable) costs. The total costs were determined for each procedure and compared by using the Student t test. RESULTS: There was a significant difference (P < .0001) between the mean total direct cost of VCUG ($112.17 +/- 10.33) and that of RNC ($64.58 +/- 1.91). VCUG examination for vesicoureteral reflux in children cost 1.74 times more than RNC examination (95% CI: 1.28, 2.36). CONCLUSION: When the technique is clinically appropriate, institutions may obtain substantial cost savings by using RNC in place of VCUG for examining children suspected of having vesicoureteral reflux.

Evidence-based medicine: neuroimaging of seizures.

Evidence-based medicine is useful in epilepsy and neuroimaging (Figs. 1 and 2). An understanding of the pretest probability suggests that focal neurologic deficits are important in predicting the outcome of neuroimaging examinations. In cases of nonacute symptomatic seizures, confusion and postictal deficits should prompt MR evaluation. In remote symptomatic seizures, MR imaging should be performed in a child with unexplained cognitive or motor delays or a child less than 1 year of age. Patients with partial seizures, abnormal EEG, or generalized epilepsy also should be imaged. Acute seizures should be imaged with CT to exclude hemorrhage and because of the availability and speed of the modality. Ictal SPECT is the best neuroimaging examination to localize seizure activity. MR imaging can offer prediction of surgical outcome and may hold promise in the future for dimensional localization of seizure focus. Evidence-based medicine can only work if there is physician communication. The pretest probability is helpful only when an accurate history is provided to the consulting physician. This field will flourish if physicians can develop accurate methods of collating information and reporting it in a timely fashion in the literature.