Neuroimaging of Neonatal Stroke: Venous Focus.

Perinatal venous infarcts are underrecognized clinically and at imaging. Neonates may be susceptible to venous infarcts because of hypercoagulable state, compressibility of the dural sinuses and superficial veins due to patent sutures, immature cerebral venous drainage pathways, and drastic physiologic changes of the brain circulation in the perinatal period. About 43% of cases of pediatric cerebral sinovenous thrombosis occur in the neonatal period. Venous infarcts can be recognized by ischemia or hemorrhage that does not respect an arterial territory. Knowledge of venous drainage pathways and territories can help radiologists recognize characteristic venous infarct patterns. Intraventricular hemorrhage in a term neonate with thalamocaudate hemorrhage should raise concern for internal cerebral vein thrombosis. A striato-hippocampal pattern of hemorrhage indicates basal vein of Rosenthal thrombosis. Choroid plexus hemorrhage may be due to obstruction of choroidal veins that drain the internal cerebral vein or basal vein of Rosenthal. Fan-shaped deep medullary venous congestion or thrombosis is due to impaired venous drainage into the subependymal veins, most commonly caused by germinal matrix hemorrhage in the premature infant and impeded flow in the deep venous system in the term infant. Subpial hemorrhage, an underrecognized hemorrhage stroke type, is often observed in the superficial temporal region, and its cause is probably multifactorial. The treatment of cerebral sinovenous thrombosis is anticoagulation, which should be considered even in the presence of intracranial hemorrhage. ©RSNA, 2024 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results.

Neuroblastomas harbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-generation ALK inhibitor lorlatinib. We conducted a first-in-child study evaluating lorlatinib with and without chemotherapy in children and adults with relapsed or refractory ALK-driven neuroblastoma. The trial is ongoing, and we report here on three cohorts that have met pre-specified primary endpoints: lorlatinib as a single agent in children (12 months to <18 years); lorlatinib as a single agent in adults (≥18 years); and lorlatinib in combination with topotecan/cyclophosphamide in children (<18 years). Primary endpoints were safety, pharmacokinetics and recommended phase 2 dose (RP2D). Secondary endpoints were response rate and 123I-metaiodobenzylguanidine (MIBG) response. Lorlatinib was evaluated at 45-115 mg/m2/dose in children and 100-150 mg in adults. Common adverse events (AEs) were hypertriglyceridemia (90%), hypercholesterolemia (79%) and weight gain (87%). Neurobehavioral AEs occurred mainly in adults and resolved with dose hold/reduction. The RP2D of lorlatinib with and without chemotherapy in children was 115 mg/m2. The single-agent adult RP2D was 150 mg. The single-agent response rate (complete/partial/minor) for <18 years was 30%; for ≥18 years, 67%; and for chemotherapy combination in <18 years, 63%; and 13 of 27 (48%) responders achieved MIBG complete responses, supporting lorlatinib's rapid translation into active phase 3 trials for patients with newly diagnosed high-risk, ALK-driven neuroblastoma. ClinicalTrials.gov registration: NCT03107988 .

Development of an ultrafast brain MR neuronavigation protocol for ventricular shunt placement.

OBJECTIVE: Advancements in MRI technology have provided improved ways to acquire imaging data and to more seamlessly incorporate MRI into modern pediatric surgical practice. One such situation is image-guided navigation for pediatric neurosurgical procedures, including intracranial catheter placement. Image-guided surgery (IGS) requires acquisition of CT or MR images, but the former carries the risk of ionizing radiation and the latter is associated with long scan times and often requires pediatric patients to be sedated. The objective of this project was to circumvent the use of CT and standard-sequence MRI in ventricular neuronavigation by investigating the use of fast MR sequences on the basis of 3 criteria: scan duration comparable to that of CT acquisition, visualization of ventricular morphology, and image registration with surface renderings comparable to standard of care. The aim of this work was to report image development, implementation, and results of registration accuracy testing in healthy subjects. METHODS: The authors formulated 11 candidate MR sequences on the basis of the standard IGS protocol, and various scan parameters were modified, such as k-space readout direction, partial k-space acquisition, sparse sampling of k-space (i.e., compressed sensing), in-plane spatial resolution, and slice thickness. To evaluate registration accuracy, the authors calculated target registration error (TRE). A candidate sequence was selected for further evaluation in 10 healthy subjects. RESULTS: The authors identified a candidate imaging protocol, termed presurgical imaging with compressed sensing for time optimization (PICO). Acquisition of the PICO protocol takes 25 seconds. The authors demonstrated noninferior TRE for PICO (3.00 ± 0.19 mm) in comparison with the default MRI neuronavigation protocol (3.35 ± 0.20 mm, p = 0.20). CONCLUSIONS: The developed and tested sequence of this work allowed accurate intraoperative image registration and provided sufficient parenchymal contrast for visualization of ventricular anatomy. Further investigations will evaluate use of the PICO protocol as a substitute for CT and conventional MRI protocols in ventricular neuronavigation.

MR Neuroimaging in Pediatric Inborn Errors of Metabolism.

Inborn errors of metabolism (IEM) are a group of disorders due to functional defects in one or more metabolic pathways that can cause considerable morbidity and death if not diagnosed early. While individually rare, the estimated global prevalence of IEMs comprises a substantial number of neonatal and infantile disorders affecting the central nervous system. Clinical manifestations of IEMs may be nonspecific. Newborn metabolic screens do not capture all IEMs, and likewise, genetic testing may not always detect pathogenic variants. Neuroimaging is a critical component of the work-up, given that imaging sometimes occurs before prenatal screen results are available, which may allow for recognition of imaging patterns that lead to early diagnosis and treatment of IEMs. This review will demonstrate the role of magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS) in the evaluation of IEMs. The focus will be on scenarios where MRI and 1H MRS are suggestive of or diagnostic for IEMs, or alternatively, refute the diagnosis.

Clinical 1H MRS in childhood neurometabolic diseases - part 2: MRS signatures.

Proton MRS of the brain provides the ability to gather direct information regarding the metabolic status of the brain at the time of MRI. Although selective vulnerability of brain tissue may yield distinct imaging patterns in neurometabolic disorders, it is not uncommon for the brain MRI to be normal, nonspecific, or show ambiguous abnormalities among several possible diagnoses, metabolic, or otherwise. This review highlights childhood neurometabolic diseases in which 1H MRS may show diagnostic or suggestive metabolic profiles without complicated acquisition or postprocessing techniques.

Clinical 1H MRS in childhood neurometabolic diseases-part 1: technique and age-related normal spectra.

Despite its vigorous ability to detect and measure metabolic disturbances, 1H MRS remains underutilized in clinical practice. MRS increases diagnostic yield and provides therapeutic measures. Because many inborn metabolic errors are now treatable, early diagnosis is crucial to prevent or curb permanent brain injury. Therefore, patients with known or suspected inborn metabolic errors stand to benefit from the addition of MRS. With education and practice, all neuroradiologists can perform and interpret MRS notwithstanding their training and prior experience. In this two-part review, we cover the requisite concepts for clinical MRS interpretation including technical considerations and normal brain spectral patterns based on age, location, and methodology.

Attention-guided deep learning for gestational age prediction using fetal brain MRI.

Magnetic resonance imaging offers unrivaled visualization of the fetal brain, forming the basis for establishing age-specific morphologic milestones. However, gauging age-appropriate neural development remains a difficult task due to the constantly changing appearance of the fetal brain, variable image quality, and frequent motion artifacts. Here we present an end-to-end, attention-guided deep learning model that predicts gestational age with R2 score of 0.945, mean absolute error of 6.7 days, and concordance correlation coefficient of 0.970. The convolutional neural network was trained on a heterogeneous dataset of 741 developmentally normal fetal brain images ranging from 19 to 39 weeks in gestational age. We also demonstrate model performance and generalizability using independent datasets from four academic institutions across the U.S. and Turkey with R2 scores of 0.81-0.90 after minimal fine-tuning. The proposed regression algorithm provides an automated machine-enabled tool with the potential to better characterize in utero neurodevelopment and guide real-time gestational age estimation after the first trimester.

An Inverted Acetabular Labrum Is Predictive of Pavlik Harness Treatment Failure in Children With Developmental Hip Dysplasia.

INTRODUCTION: The failure rate of Pavlik harness treatment for developmental dysplasia of the hip (DDH) has been reported as high as 55%. The purpose of this study is to investigate the effect of an inverted acetabular labrum on outcomes of Pavlik harness treatment for DDH. METHODS: A retrospective review was conducted on DDH patients at a tertiary care pediatric hospital from 2004 to 2016. DDH patients that underwent index treatment with Pavlik harness and had minimum 12 months follow-up were included. Medical charts were reviewed for demographics, treatment, and outcomes. Outcomes were compared between patients with an inverted labrum versus those without an inverted labrum. RESULTS: A total of 156 patients with 229 dysplastic hips were included. The mean age at initiation of Pavlik harness treatment was 1.9±1.4 months and mean follow-up was 37.7±23.0 months. Bilateral DDH was diagnosed in 46% (73/156) of patients. In all, 37% (75/229) of hips failed Pavlik harness index treatment. Second-line treatment was rigid hip abduction bracing in 91% (68/75) of hips, closed reduction in 5% (4/75) of hips, and open reduction in 4% (3/75) of hips. An inverted labrum was present in 10% (22/229) of all hips. The incidence of Pavlik harness treatment failure was 91% (20/22) in the inverted labrum group compared with 27% (55/207) in the control group (P<0.001). Closed or open reduction was required in 86% (15/22) of the inverted labrum group compared with 3% (7/207) of hips in the control group (P<0.001). The incidence of avascular necrosis was 18% (4/22) in hips with an inverted labrum compared with 0.4% (1/207) in the control group (P<0.001). CONCLUSIONS: In children with DDH undergoing index treatment in a Pavlik harness, the presence of an inverted acetabular labrum is strongly predictive of treatment failure. Dysplastic hips with an inverted labrum also have a significantly higher risk of requiring closed or open reduction and developing avascular necrosis compared with those without an inverted labrum. LEVEL OF EVIDENCE: Level III.

Feasibility of ferumoxytol-enhanced neonatal and young infant cardiac MRI without general anesthesia.

PURPOSE: To assess the feasibility of ferumoxytol-enhanced anesthesia-free cardiac MRI in neonates and young infants for complex congenital heart disease (CHD). MATERIALS AND METHODS: With Institutional Review Board approval, 21 consecutive neonates and young infants (1 day to 11 weeks old; median age of 3 days) who underwent a rapid two-sequence (MR angiography [MRA] and four-dimensional [4D] flow) MRI protocol with intravenous ferumoxytol without sedation (n = 17) or light sedation (n = 4) at 3 Tesla (T) (except one case at 1.5T) between June 2014 and February 2016 were retrospectively identified. Medical records were reviewed for indication, any complications, if further diagnostic imaging was performed after MRI, and surgical findings. Two radiologists scored the images in two sessions on a 5-point scale for overall image quality and delineation of various anatomical structures. Confidence interval of proportions for likelihood of requiring additional diagnostic imaging after MRI was determined. For the possibility of reducing the protocol to a single rapid sequence, Wilcoxon-rank sum test was used to assess whether 4D flow and MRA significantly differed in anatomical delineation. RESULTS: One of 21 patients (4.8%, 80% confidence interval 0-11%) required additional imaging, a computed tomography angiography to assess lung parenchyma and peripheral pulmonary arteries. Only 1 of 13 patients (7.7%) with operative confirmation had a minor discrepancy between radiology and operative reports (80% confidence interval 0-17%). 4D flow was significantly superior to MRA (P < 0.05) for the evaluation of systemic arteries, valves, ventricular trabeculae, and overall quality. Using Cohen's kappa coefficient, there was good interobserver agreement for the evaluation of systemic arteries by 4D flow (κ = 0.782), and systemic veins and pulmonary arteries by MRA (κ > 0.6). Overall 4D flow measurements (mean κ = 0.64-0.74) had better internal agreement compared with MRA (mean κ = 0.30-0.64). CONCLUSION: Ferumoxytol-enhanced cardiac MRI, without anesthesia, is feasible for the evaluation of complex CHD in neonates and young infants, with a low likelihood of need for additional diagnostic studies. The decreased risk by avoiding anesthesia must be balanced against the potential for adverse reactions with ferumoxytol. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1407-1418.

Early characteristic radiographic changes in mucolipidosis II.

BACKGROUND: Although mucolipidosis type II has similar metabolic abnormalities to those found in all the mucopolysaccharidoses and mucolipidoses, there are distinctive diagnostic radiographic changes of mucolipidosis II in the perinatal/newborn/infant period. OBJECTIVE: To describe the early characteristic radiographic changes of mucolipidosis II and to document when these changes manifest and resolve. MATERIALS AND METHODS: We retrospectively reviewed radiographs and clinical records of 19 cases of mucolipidosis II from the International Skeletal Dysplasia Registry (1971-present; fetal age to 2½ years). A radiologist with special expertise in skeletal dysplasias evaluated the radiographs. RESULTS: The most common abnormalities were increased vertebral body height (80%, nonspecific), talocalcaneal stippling (86%), periosteal cloaking (74%) and vertebral body rounding (50%). Unreported findings included sacrococcygeal sclerosis (54%) and vertebral body sclerosis (13%). Rickets and hyperparathyroidism-like (pseudohyperparathyroidism) changes (rarely reported) were found in 33% of cases. These changes invariably started in the newborn period and resolved by 1 year of age. The conversion from these early infantile radiographic features to dysostosis multiplex changes occurred in 41% of cases, and within the first year after birth. CONCLUSION: Several findings strongly suggest the diagnosis of mucolipidosis II, including cloaking in combination with one or more of the following radiographic criteria: talocalcaneal stippling, sacrococcygeal or generalized vertebral body sclerosis, vertebral body rounding, or rickets/hyperparathyroidism-like changes in the perinatal/newborn/infancy period. These findings are not found in the other two forms of mucolipidosis nor in any of the mucopolysaccharidoses.

Shedding light on inflammatory pseudotumor in children: spotlight on inflammatory myofibroblastic tumor.

Inflammatory pseudotumor is a generic term used to designate a heterogeneous group of inflammatory mass-forming lesions histologically characterized by myofibroblastic proliferation with chronic inflammatory infiltrate. Inflammatory pseudotumor is multifactorial in etiology and generally benign, but it is often mistaken for malignancy given its aggressive appearance. It can occur throughout the body and is seen in all age groups. Inflammatory pseudotumor has been described in the literature by many organ-specific names, resulting in confusion. Recently within this generic category of inflammatory pseudotumor, inflammatory myofibroblastic tumor has emerged as a distinct entity and is now recognized as a fibroblastic/myofibroblastic neoplasm with intermediate biological potential and occurring mostly in children. We present interesting pediatric cases of inflammatory myofibroblastic tumors given this entity's tendency to occur in children. Familiarity and knowledge of the imaging features of inflammatory pseudotumor can help in making an accurate diagnosis, thereby avoiding unnecessary radical surgery.