Subcortical brain volumes in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Despite treatment with therapeutic hypothermia, hypoxic-ischemic encephalopathy (HIE) is associated with adverse developmental outcomes, suggesting the involvement of subcortical structures including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period. The aims were: (1) to examine subcortical macrostructure in neonates with HIE compared to age- and sex-matched healthy neonates within the first week of life; (2) to determine whether subcortical brain volumes are associated with HIE severity. METHODS: Neonates (n = 56; HIE: n = 28; Healthy newborns from the Developing Human Connectome Project: n = 28) were scanned with MRI within the first week of life. Subcortical volumes were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, gestational age, postmenstrual age, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity. RESULTS: Neonates with HIE had smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to controls (all, p < 0.02). Within the HIE group, mild HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p < 0.007) and the left hippocampus and thalamus (both, p < 0.04). CONCLUSIONS: Findings suggest that, despite advances in neonatal care, HIE is associated with significant alterations in subcortical brain macrostructure. IMPACT: Compared to their healthy counterparts, infants with HIE demonstrate significant alterations in subcortical brain macrostructure on MRI acquired as early as 4 days after birth. Smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia, and cerebellum, were seen in infants with HIE. Mild and moderate HIE were associated with smaller subcortical volumes.

Imaging blood-brain barrier dysfunction: A state-of-the-art review from a clinical perspective.

The blood-brain barrier (BBB) consists of specialized cells that tightly regulate the in- and outflow of molecules from the blood to brain parenchyma, protecting the brain's microenvironment. If one of the BBB components starts to fail, its dysfunction can lead to a cascade of neuroinflammatory events leading to neuronal dysfunction and degeneration. Preliminary imaging findings suggest that BBB dysfunction could serve as an early diagnostic and prognostic biomarker for a number of neurological diseases. This review aims to provide clinicians with an overview of the emerging field of BBB imaging in humans by answering three key questions: (1. Disease) In which diseases could BBB imaging be useful? (2. Device) What are currently available imaging methods for evaluating BBB integrity? And (3. Distribution) what is the potential of BBB imaging in different environments, particularly in resource limited settings? We conclude that further advances are needed, such as the validation, standardization and implementation of readily available, low-cost and non-contrast BBB imaging techniques, for BBB imaging to be a useful clinical biomarker in both resource-limited and well-resourced settings.

The performance of machine learning approaches for attenuation correction of PET in neuroimaging: A meta-analysis.

PURPOSE: This systematic review provides a consensus on the clinical feasibility of machine learning (ML) methods for brain PET attenuation correction (AC). Performance of ML-AC were compared to clinical standards. METHODS: Two hundred and eighty studies were identified through electronic searches of brain PET studies published between January 1, 2008, and August 1, 2022. Reported outcomes for image quality, tissue classification performance, regional and global bias were extracted to evaluate ML-AC performance. Methodological quality of included studies and the quality of evidence of analysed outcomes were assessed using QUADAS-2 and GRADE, respectively. RESULTS: A total of 19 studies (2371 participants) met the inclusion criteria. Overall, the global bias of ML methods was 0.76 ± 1.2%. For image quality, the relative mean square error (RMSE) was 0.20 ± 0.4 while for tissues classification, the Dice similarity coefficient (DSC) for bone/soft tissue/air were 0.82 ± 0.1 / 0.95 ± 0.03 / 0.85 ± 0.14. CONCLUSIONS: In general, ML-AC performance is within acceptable limits for clinical PET imaging. The sparse information on ML-AC robustness and its limited qualitative clinical evaluation may hinder clinical implementation in neuroimaging, especially for PET/MRI or emerging brain PET systems where standard AC approaches are not readily available.

The role of the temporal pole in temporal lobe epilepsy: A diffusion kurtosis imaging study.

This study aimed to evaluate the use of diffusion kurtosis imaging (DKI) to detect microstructural abnormalities within the temporal pole (TP) and its temporopolar cortex in temporal lobe epilepsy (TLE) patients. DKI quantitative maps were obtained from fourteen lesional TLE and ten non-lesional TLE patients, along with twenty-three healthy controls. Data collected included mean (MK); radial (RK) and axial kurtosis (AK); mean diffusivity (MD) and axonal water fraction (AWF). Automated fiber quantification (AFQ) was used to quantify DKI measurements along the inferior longitudinal (ILF) and uncinate fasciculus (Unc). ILF and Unc tract profiles were compared between groups and tested for correlation with disease duration. To characterize temporopolar cortex microstructure, DKI maps were sampled at varying depths from superficial white matter (WM) towards the pial surface. Patients were separated according to the temporal lobe ipsilateral to seizure onset and their AFQ results were used as input for statistical analyses. Significant differences were observed between lesional TLE and controls, towards the most temporopolar segment of ILF and Unc proximal to the TP within the ipsilateral temporal lobe in left TLE patients for MK, RK, AWF and MD. No significant changes were observed with DKI maps in the non-lesional TLE group. DKI measurements correlated with disease duration, mostly towards the temporopolar segments of the WM bundles. Stronger differences in MK, RK and AWF within the temporopolar cortex were observed in the lesional TLE and noticeable differences (except for MD) in non-lesional TLE groups compared to controls. This study demonstrates that DKI has potential to detect subtle microstructural alterations within the temporopolar segments of the ILF and Unc and the connected temporopolar cortex in TLE patients including non-lesional TLE subjects. This could aid our understanding of the extrahippocampal areas, more specifically the temporal pole role in seizure generation in TLE and might inform surgical planning, leading to better seizure outcomes.

Natural history of pediatric morphine leukoencephalopathy on CT and MRI.

An increased awareness of opioids and the imaging appearance in opioid overdose-related leukoencephalopathy has rapidly become crucial with respect to its identification by emergency radiologists. It is a potentially life-threatening condition and is associated with devastating neurological outcomes. Thus, early diagnosis and management are paramount. We report a rare case of toxic leukoencephalopathy in a 20-month-old male patient secondary to morphine overdose in the outpatient setting following discharge from uncomplicated urethroplasty. Although pediatric toxic leukoencephalopathy has been reported previously in the literature, our case report is unique as it involves morphine, a less commonly used opioid in the outpatient setting. Moreover, we have provided brain computed tomography and magnetic resonance imaging and highlighted findings in the acute and chronic stages of the disease trajectory. This case report highlights the importance for radiologists, especially those involved in emergency care, to have a high index of suspicion for toxic leukoencephalopathy, a potentially devastating but treatable condition.

Moyamoya Syndrome in an Infant with Aicardi-Goutières and Williams Syndromes: A Case Report.

Stroke in infancy is a rare phenomenon but can lead to significant long-term disability. We present the story of a 6-month-old Old Order Amish infant with underlying Williams syndrome, a rare neurodevelopmental disorder caused by a microdeletion, encompassing the elastin gene that produces abnormalities in elastic fibers of the lungs and vessels. This infant presented with lethargy, irritability, and a new-onset generalized tonic-clonic seizure. Brain magnetic resonance imaging (MRI) was consistent with ischemic stroke in the supratentorial regions. MR angiogram demonstrated bilateral narrowing of the internal carotid arteries with "ivy sign," suggestive of Moyamoya. Moyamoya disease/syndrome is a cerebrovascular condition that is associated with progressive stenosis of the intracranial vessels and can cause ischemic stroke in young children. Targeted mutation analysis revealed a homozygous c.1411-2A > G splice site variant in the SAMHD1 gene, consistent with a diagnosis of Aicardi-Goutières syndrome type 5 (AGS5), an autosomal recessive condition with multisystem involvement. In our unique case of infantile stroke with Moyamoya syndrome and dual diagnosis of Williams syndrome and AGS5, both diagnoses likely contributed to the cerebrovascular pathology. This case report highlights the importance of suspecting and testing for multiple genetic abnormalities in children presenting with Moyamoya-related stroke.

Blood-brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood-brain barrier (BBB) permeability in patients with iTTP at the start of remission and 6 months later. This prospective pilot study included 7 adult patients with incident iTTP. Eligibility criteria included ADAMTS13 activity < 10% and detectable inhibitor at diagnosis. Patients were recruited from London Health Sciences Centre in Canada (2017-2019) within 3 days of hospital admission and followed for 6 months after remission (defined as normalization of platelet count and lactate dehydrogenase with no clinical signs or symptoms of microvascular injury for more than 30 days after the last plasma exchange). All patients had cerebral computed tomography perfusion scans with BBB permeability surface product measurements. Patients (5 women, 2 men) had a mean age of 48 years (range, 21-77 years). At diagnosis, patients had a mean platelet count of 22 (standard deviation [SD], 25) × 109/L. At the start of remission, mean BBB permeability surface product was 0.91 (0.30) mL/min/100 g. Six months later, the mean permeability surface product was 0.56 (0.22) mL/min/100 g, with a mean difference of -0.312 mL/min/100 g (95% confidence interval: -0.4729 to -0.1510; P = .0032). In this pilot study of patients with iTTP, pathologically increased BBB permeability was evident, and although there was some improvement, this persisted 6 months after remission. Future work will explore the chronicity of these findings and their clinical implications.

Uncommon acute neuroimaging findings in severe neonatal herpes simplex virus 2 and consequences of delayed diagnosis.

Neonatal herpes simplex virus (HSV) infection of the central nervous system (CNS) is an emergency that can have devastating structural consequences and clinical outcomes. As it presents non-specifically in neonates, it is difficult to rapidly diagnose without neuroimaging. Although once thought to cause widespread parenchymal destruction, neonatal CNS HSV infection may present with more focal parenchymal injury on neuroimaging, not involving the medial temporal lobes as in adults. We report a case of a three-week-old girl with herpes simplex virus type 2 (HSV-2) encephalitis with exclusive bilateral corticospinal and frontal opercular involvement, which remained undiagnosed and untreated until three months of age. Neuroimaging upon presentation to the emergency room demonstrates a highly suggestive pattern of severe neonatal CNS HSV-2 infection which followed the natural history on subsequent imaging, highlighting the importance of emergency neuroimaging as well as having a high index of suspicion for making the diagnosis.

An evaluation of the diagnostic equivalence of 18F-FDG-PET between hybrid PET/MRI and PET/CT in drug-resistant epilepsy: A pilot study.

OBJECTIVE: Hybrid PET/MRI may improve detection of seizure-onset zone (SOZ) in drug-resistant epilepsy (DRE), however, concerns over PET bias from MRI-based attenuation correction (MRAC) have limited clinical adoption of PET/MRI. This study evaluated the diagnostic equivalency and potential clinical value of PET/MRI against PET/CT in DRE. MATERIALS AND METHODS: MRI, FDG-PET and CT images (n = 18) were acquired using a hybrid PET/MRI and a CT scanner. To assess diagnostic equivalency, PET was reconstructed using MRAC (RESOLUTE) and CT-based attenuation correction (CTAC) to generate PET/MRI and PET/CT images, respectively. PET/MRI and PET/CT images were compared qualitatively through visual assessment and quantitatively through regional standardized uptake value (SUV) and z-score assessment. Diagnostic accuracy and sensitivity of PET/MRI and PET/CT for SOZ detection were calculated through comparison to reference standards (clinical hypothesis and histopathology, respectively). RESULTS: Inter-reader agreement in visual assessment of PET/MRI and PET/CT images was 78 % and 81 %, respectively. PET/MRI and PET/CT were strongly correlated in mean SUV (r = 0.99, p < 0.001) and z-scores (r = 0.92, p < 0.001) across all brain regions. MRAC SUV bias was <5% in most brain regions except the inferior temporal gyrus, temporal pole, and cerebellum. Diagnostic accuracy and sensitivity were similar between PET/MRI and PET/CT (87 % vs. 85 % and 83 % vs. 83 %, respectively). CONCLUSION: We demonstrate here that PET/MRI with optimal MRAC can yield similar diagnostic performance as PET/CT. Nevertheless, further exploration of the potential added value of PET/MRI is necessary before clinical adoption of PET/MRI for epilepsy imaging.

Presurgical brain mapping of the language network in pediatric patients with epilepsy using resting-state fMRI.

OBJECTIVE: Epilepsy affects neural processing and often causes intra- or interhemispheric language reorganization, rendering localization solely based on anatomical landmarks (e.g., Broca's area) unreliable. Preoperative brain mapping is necessary to weigh the risk of resection with the risk of postoperative deficit. However, the use of conventional mapping methods (e.g., somatosensory stimulation, task-based functional MRI [fMRI]) in pediatric patients is technically difficult due to low compliance and their unique neurophysiology. Resting-state fMRI (rs-fMRI), a "task-free" technique based on the neural activity of the brain at rest, has the potential to overcome these limitations. The authors hypothesized that language networks can be identified from rs-fMRI by applying functional connectivity analyses. METHODS: Cases in which both task-based fMRI and rs-fMRI were acquired as part of the preoperative clinical protocol for epilepsy surgery were reviewed. Task-based fMRI consisted of 2 language tasks and 1 motor task. Resting-state fMRI data were acquired while the patients watched an animated movie and were analyzed using independent component analysis (i.e., data-driven method). The authors extracted language networks from rs-fMRI data by performing a similarity analysis with functionally defined language network templates via a template-matching procedure. The Dice coefficient was used to quantify the overlap. RESULTS: Thirteen children underwent conventional task-based fMRI (e.g., verb generation, object naming), rs-fMRI, and structural imaging at 1.5T. The language components with the highest overlap with the language templates were identified for each patient. Language lateralization results from task-based fMRI and rs-fMRI mapping were comparable, with good concordance in most cases. Resting-state fMRI-derived language maps indicated that language was on the left in 4 patients (31%), on the right in 5 patients (38%), and bilateral in 4 patients (31%). In some cases, rs-fMRI indicated a more extensive language representation. CONCLUSIONS: Resting-state fMRI-derived language network data were identified at the patient level using a template-matching method. More than half of the patients in this study presented with atypical language lateralization, emphasizing the need for mapping. Overall, these data suggest that this technique may be used to preoperatively identify language networks in pediatric patients. It may also optimize presurgical planning of electrode placement and thereby guide the surgeon's approach to the epileptogenic zone.

7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice.

Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.

A curious case of a comestible cough candy.

An 80-year-old woman was seen in the Emergency Department with a history of left jaw pain and headaches, as well as numerous additional comorbidities. Computed tomography examination of the head and face found a circumscribed, ovoid, markedly hyperattenuating mass with areas of internal air within the left buccal space - the density of which was neither that of metal nor bone. After speaking with the patient, she reported having a cough candy in her mouth during the examination. Here we review the imaging appearance of an unusual case of a comestible intraoral foreign body so as to raise awareness of this incidental pseudolesion. Correct recognition of this as an intraoral foreign body rather than true pathology of the oral cavity is important as to save patients the anguish of a significant, albeit incorrect, diagnosis and avoid the additional cost and resource utilization of unnecessary further investigations.

An Important Pediatric Stroke Mimic: Hemiplegic Migraine.

Stroke is relatively rare in children but has become increasingly recognized clinically. Hemiplegic migraine (HM) is a rare subtype of migraine, with attacks typically beginning in childhood or adolescence. Attacks are characterized by migraine headaches and motor weakness, which develop over several minutes. HM may therefore mimic acute stroke; however, symptoms last less than an hour and resolve spontaneously, often without sequela.1-4 Distinction between these entities is important due to their different urgency and management. Neuroimaging is indispensible in working up patients presenting to the Emergency Department with stroke-like symptoms and can be used to distinguish between infarction and HM.

18F-FDG PET-guided diffusion tractography reveals white matter abnormalities around the epileptic focus in medically refractory epilepsy: implications for epilepsy surgical evaluation.

BACKGROUND: Hybrid PET/MRI can non-invasively improve localization and delineation of the epileptic focus (EF) prior to surgical resection in medically refractory epilepsy (MRE), especially when MRI is negative or equivocal. In this study, we developed a PET-guided diffusion tractography (PET/DTI) approach combining 18F-fluorodeoxyglucose PET (FDG-PET) and diffusion MRI to investigate white matter (WM) integrity in MRI-negative MRE patients and its potential impact on epilepsy surgical planning. METHODS: FDG-PET and diffusion MRI of 14 MRI-negative or equivocal MRE patients were used to retrospectively pilot the PET/DTI approach. We used asymmetry index (AI) mapping of FDG-PET to detect the EF as brain areas showing the largest decrease in FDG uptake between hemispheres. Seed-based WM fiber tracking was performed on DTI images with a seed location in WM 3 mm from the EF. Fiber tractography was repeated in the contralateral brain region (opposite to EF), which served as a control for this study. WM fibers were quantified by calculating the fiber count, mean fractional anisotropy (FA), mean fiber length, and mean cross-section of each fiber bundle. WM integrity was assessed through fiber visualization and by normalizing ipsilateral fiber measurements to contralateral fiber measurements. The added value of PET/DTI in clinical decision-making was evaluated by a senior neurologist. RESULTS: In over 60% of the patient cohort, AI mapping findings were concordant with clinical reports on seizure-onset localization and lateralization. Mean FA, fiber count, and mean fiber length were decreased in 14/14 (100%), 13/14 (93%), and 12/14 (86%) patients, respectively. PET/DTI improved diagnostic confidence in 10/14 (71%) patients and indicated that surgical candidacy be reassessed in 3/6 (50%) patients who had not undergone surgery. CONCLUSIONS: We demonstrate here the utility of AI mapping in detecting the EF based on brain regions showing decreased FDG-PET activity and, when coupled with DTI, could be a powerful tool for detecting EF and assessing WM integrity in MRI-negative epilepsy. PET/DTI could be used to further enhance clinical decision-making in epilepsy surgery.

Hypoglossal nerve palsy due to carotid artery dissection: an uncommon presentation of a common problem.

Spontaneous internal carotid artery dissection occurs in patients of all ages, rarely presenting with hypoglossal nerve palsy. The characteristic imaging findings of internal carotid artery dissection and tongue denervation are reviewed in four patients. Recognition of internal carotid artery dissection is critical for appropriate treatment and to minimise the risk of thromboembolic-ischaemic complications. Radiologists must be aware of the radiological appearance of hypoglossal nerve palsy and maintain a high index of suspicion for internal carotid artery dissection when this finding is present.

Is Rest Really Rest? Resting-State Functional Connectivity During Rest and Motor Task Paradigms.

Numerous studies have identified several large-scale networks within the brain of healthy individuals, some of which have been attributed to ongoing mental activity during the wakeful resting state. While engaged during specific resting-state functional magnetic resonance imaging (fMRI) paradigms, it remains unclear as to whether traditional block-design simple movement fMRI experiments significantly influence these mode networks or other areas. Using blood-oxygen level-dependent fMRI, we characterized the pattern of functional connectivity in healthy subjects during a resting-state paradigm and compared this with the same resting-state analysis performed on motor task data residual time courses after regressing out the task paradigm. Using seed-voxel analysis to define the default mode network, the executive control network (ECN), and sensorimotor, auditory, and visual networks, the resting-state analysis of the residual time courses demonstrated reduced functional connectivity in the motor network and reduced connectivity between the insula and the ECN compared with the standard resting-state data sets. Overall, performance of simple self-directed motor tasks does little to change the resting-state functional connectivity across the brain, especially in nonmotor areas. This would suggest that previously acquired fMRI studies incorporating simple block-design motor tasks could be mined retrospectively for assessment of the resting-state connectivity.

Neuromagnetic responses to tactile stimulation of the fingers: Evidence for reduced cortical inhibition for children with Autism Spectrum Disorder and children with epilepsy.

The purpose of this study was to compare somatosensory responses from a group of children with epilepsy and a group of children with autism spectrum disorder (ASD), with age matched TD controls. We hypothesized that the magnitude of the tactile "P50m" somatosensory response would be reduced in both patient groups, possibly due to reduced GABAergic signaling as has been implicated in a variety of previous animal models and in vivo human MRS studies. We observed significant (~ 25%) decreases in tactile P50m dipole moment values from the source localized tactile P50m response, both for children with epilepsy and for children with ASD. In addition, the latency of the tactile P50m peak was observed to be equivalent between TD and ASD groups but was significantly delayed in children with epilepsy by ~ 6 ms. Our data support the hypothesis of impaired GABAergic signaling in both children with ASD and children with epilepsy. Further work is needed to replicate these findings and directly relate them to both in vivo measures of GABA via e.g. magnetic resonance spectroscopy and psychophysical assessments of somatosensory function, and behavioral indices.

Brain Resting-State Functional Connectivity Is Preserved Under Sevoflurane Anesthesia in Patients with Pervasive Developmental Disorders: A Pilot Study.

Functional connectivity studies play a huge role in understanding the relationship between the network connections and the behavioral phenotype of patients with pervasive developmental disorders (PDD). Some patients with PDD may not be able to tolerate the imaging procedure while they are awake, and, hence, they often need general anesthesia. General anesthesia is a confounding factor in functional imaging studies due to its effect on the functional connectivity. The objective of this study is to look at the resting-state functional connectivity (RS-FC) under sevoflurane anesthesia in patients with PDDs. Thirteen adults with PDD scheduled for magnetic resonance imaging (MRI) of the brain under general anesthesia were recruited for the study. Resting-state functional MRI (fMRI) scans were acquired at 1 minimum alveolar concentration (MAC) of sevoflurane. Spontaneous blood oxygenation level-dependent fluctuations were measured, and a seed-voxel analysis was done to identify the resting-state networks. Subjects' data were compared with data from 16 nonanesthetized healthy controls. Six networks (default mode network [DMN], executive control network [ECN], salience network [SN], auditory, visual, and sensorimotor) were investigated. At 1 MAC sevoflurane anesthesia, RS-FC was preserved in all the networks. Secondary analysis of connectivity showed a decrease in connectivity within the thalamus and an increase in DMN-ECN and DMN-SN cross-network connectivity in the anesthetized patient group compared to healthy controls. Previous reports suggested that even mild levels of anesthesia could reduce overall fluctuation levels in the major brain. However, our results provide strong evidence that most networks can sustain detectable levels of activity in patients with PDDs even under deep levels of anesthesia.