Children surviving cardiac arrest are at high risk of neurological morbidity and mortality; however, there is a lack of validated prognostic biomarkers. We aimed to evaluate brain magnetic resonance ...imaging (MRI) and spectroscopy (MRS) as predictors of death and disability. Secondly, we evaluated whether MRI/S by randomized group.
This single center study analyzed clinically indicated brain MRI/S data from children enrolled in a randomized controlled trial of 24 vs. 72 h of hypothermia following cardiac arrest. Two pediatric radiologists scored conventional MRIs. Lactate and N-acetyl-aspartate (NAA) concentrations (mmol/kg) were determined from spectra acquired from the basal ganglia, thalamus, parietal white matter and parietooccipital gray matter. Mortality and neurological outcomes (favorable = Pediatric Cerebral Performance Category PCPC 1, 2, 3 or increase < 2) were assessed at hospital discharge. Non-parametric tests were used to test for associations between MRI/S biomarkers and outcome and randomized group.
23 children with (median interquartile range) age of 1.5 (0.3−4.0) years. Ten (44%) had favorable outcome. There were more T2 brain lesions in the lentiform nuclei in children with unfavorable 12 (92%) vs. favorable 3 (33%) outcome, p = 0.007. Increased lactate and decreased NAA concentrations in the parietooccipital gray matter and decreased NAA in the parietal white matter were associated with unfavorable outcome (p’s < 0.05). There were no differences for any biomarker by randomized group.
Regional cerebral and metabolic MRI/S biomarkers are predictive of neurological outcomes at hospital discharge in pediatric cardiac arrest and should undergo validation testing in a large sample.
Complex congenital heart disease (CHD) is associated with neurodevelopmental impairment, the mechanism of which is unknown. Cerebral cortical dysmaturation in CHD is linked to white matter ...abnormalities, including developmental vulnerability of the subplate, in relation to oxygen delivery and metabolism deficits. In this study, we report associations between subcortical morphology and white matter metabolism in neonates with CHD using quantitative magnetic resonance imaging (MRI) and spectroscopy (MRS). Multi-modal brain imaging was performed in three groups of neonates close to term-equivalent age: (1) term CHD (n = 56); (2) preterm CHD (n = 37) and (3) preterm control group (n = 22). Thalamic volume and cerebellar transverse diameter were obtained in relation to cerebral metrics and white matter metabolism. Short echo single-voxel MRS of parietal and frontal white matter was used to quantitate metabolites related to brain maturation (n-acetyl aspartate NAA, choline, myo-inositol), neurotransmitter (glutamate), and energy metabolism (glutamine, citrate, creatine and lactate). Multi-variate regression was performed to delineate associations between subcortical morphological measurements and white matter metabolism controlling for age and white matter injury. Reduced thalamic volume, most pronounced in the preterm control group, was associated with increased citrate levels in all three group in the parietal white matter. In contrast, reduced cerebellar volume, most pronounced in the preterm CHD group, was associated with reduced glutamine in parietal grey matter in both CHD groups. Single ventricle anatomy, aortic arch obstruction, and cyanotic lesion were predictive of the relationship between reduced subcortical morphometry and reduced GLX (particularly glutamine) in both CHD cohorts (frontal white matter and parietal grey matter). Subcortical morphological associations with brain metabolism were also distinct within each of the three groups, suggesting these relationships in the CHD groups were not directly related to prematurity or white matter injury alone. Taken together, these findings suggest that subplate vulnerability in CHD is likely relevant to understanding the mechanism of both cortical and subcortical dysmaturation in CHD infants. Future work is needed to link this potential pattern of encephalopathy of CHD (including the constellation of grey matter, white matter and brain metabolism deficits) to not only abnormal fetal substrate delivery and oxygen conformance, but also regional deficits in cerebral energy metabolism.
Thalamic structural co-variation with cortical regions has been demonstrated in preterm infants, but its relationship to cortical function and severity of non-cystic white matter injury (non-cystic ...WMI) is unclear. The relationship between thalamic morphology and both cortical network synchronization and cortical structural connectivity has not been established. We tested the hypothesis that in preterm neonates, thalamic volume would correlate with primary cortical visual function and microstructural integrity of cortico-cortical visual association pathways. A total of 80 term-equivalent preterm and 44 term-born infants underwent high-resolution structural imaging coupled with visual functional magnetic resonance imaging or diffusion tensor imaging. There was a strong correlation between thalamic volume and primary visual cortical activation in preterms with non-cystic WMI (r = 0.81, p-value = 0.001). Thalamic volume also correlated strongly with interhemispheric cortico-cortical connectivity (splenium) in preterm neonates with a relatively higher severity of non-cystic WMI (p-value < 0.001). In contrast, there was lower correlation between thalamic volume and intrahemispheric cortico-cortical connectivity, including the inferior longitudinal fasciculus and inferior frontal orbital fasciculus. This study shows distinct temporal overlap in the disruption of thalamo-cortical and interhemispheric cortico-cortical connectivity in preterm infants suggesting developmental synergy between thalamic morphology and the emergence of cortical networks in the last trimester.
Background
Fetal magnetic resonance imaging (MRI) and spectroscopy (MRS) provide a unique opportunity to non‐invasively measure markers of neurodevelopment in survivors of twin‐twin transfusion ...syndrome (TTTS).
Objective
To characterize fetal brain maturation after laser surgery for TTTS by measuring brain volumes and cerebral metabolite concentrations using fetal MRI + MRS.
Study Design
Prospective study of dual surviving fetuses treated with laser surgery for TTTS. At 4–5 postoperative weeks, fetal MRI was used together with novel image analysis to automatically extract major brain tissue volumes. Fetal MRS was used to measure major metabolite concentrations in the fetal brain.
Results
Twenty‐one twin pairs were studied. The average (±SD) gestational age at MRI was 25.89 (±2.37) weeks. Total brain volume (TBV) was lower in the donors, although cerebral volumes were not different between twin pairs. Recipients showed lower proportions of cortical and cerebellar volumes, normalized to TBV and cerebral volumes. MRS data showed that biochemical differences between twin brains were related to discrepancy in their brain volumes.
Conclusion
Although donors have a smaller TBV compared to recipients, proportionality of brain tissue volumes are preserved in donors. MRS maturational markers of fetal brain development show that recovery in donors persists 4 weeks after surgery.
The potential benefits of peptide-based immunotherapy for pediatric brain tumors are under investigation. Treatment-related heterogeneity has resulted in radiographic challenges, including ...pseudoprogression. Conventional MR imaging has limitations in assessment of different forms of treatment-related heterogeneity, particularly regarding distinguishing true tumor progression from efficacious treatment responses. Advanced neuroimaging techniques, including diffusion magnetic resonance (MR), perfusion MR, and MR spectroscopy, may add value in the assessment of treatment-related heterogeneity. Observations suggest that recent delineation of specific response criteria for immunotherapy of adult brain tumors is likely relevant to the pediatric population and further validation in multicenter pediatric brain tumor peptide-based vaccine studies is warranted.
Chimeric antigen receptor (CAR) T cells targeting the CD19 (cluster of differentiation 19) cell surface glycoprotein have emerged as a highly effective immunologic therapy in patients with relapsed ...or refractory B-cell malignancies. The engagement of CAR T cells with CD19 on the surface of neoplastic B cells causes a systemic cytokine release, which can compromise the blood-brain barrier and cause an immune effector cell-associated neurotoxicity syndrome (ICANS). In a small proportion of ICANS patients who demonstrate neuroimaging abnormalities, certain distinct patterns have been recognized, including signal changes in the thalami, external capsule, and brainstem, the subcortical and/or periventricular white matter, the splenium of the corpus callosum, and the cerebellum. On careful review of the underlying pathophysiology of ICANS, we noticed that these changes closely mirror the underlying blood-brain barrier disruption and neuroinflammatory and excitotoxic effects of the offending cytokines released during ICANS. Furthermore, other uncommon complications of CD19 CAR T-cell therapy such as posterior reversible encephalopathy syndrome, ocular complications, and opportunistic fungal infections can be catastrophic if not diagnosed in a timely manner, with neuroimaging playing a significant role in management. In this narrative review, we will summarize the current literature on the spectrum of neuroimaging findings in ICANS, list appropriate differential diagnoses, and explore the imaging features of other uncommon central nervous system complications of CD19 CAR T-cell therapy using illustrative cases from two tertiary care institutions.
For typically developing infants, the last trimester of fetal development extending into the first post-natal months is a period of rapid brain development. Infants who are born premature face ...significant risk of brain injury (e.g., intraventricular or germinal matrix hemorrhage and periventricular leukomalacia) from complications in the perinatal period and also potential long-term neurodevelopmental disabilities because these early injuries can interrupt normal brain maturation. Neuroimaging has played an important role in the diagnosis and management of the preterm infant. Both cranial US and conventional MRI techniques are useful in diagnostic and prognostic evaluation of preterm brain development and injury. Cranial US is highly sensitive for intraventricular hemorrhage (IVH) and provides prognostic information regarding cerebral palsy. Data are limited regarding the utility of MRI as a routine screening instrument for brain injury for all preterm infants. However, MRI might provide diagnostic or prognostic information regarding PVL and other types of preterm brain injury in the setting of specific clinical indications and risk factors. Further development of advanced MR techniques like volumetric MR imaging, diffusion tensor imaging, metabolic imaging (MR spectroscopy) and functional connectivity are necessary to provide additional insight into the molecular, cellular and systems processes that underlie brain development and outcome in the preterm infant. The adult concept of the “connectome” is also relevant in understanding brain networks that underlie the preterm brain. Knowledge of the preterm connectome will provide a framework for understanding preterm brain function and dysfunction, and potentially even a roadmap for brain plasticity. By combining conventional imaging techniques with more advanced techniques, neuroimaging findings will likely be used not only as diagnostic and prognostic tools, but also as biomarkers for long-term neurodevelopmental outcomes, instruments to assess the efficacy of neuroprotective agents and maneuvers in the NICU, and as screening instruments to appropriately select infants for longitudinal developmental interventions.
Children with recurrent high grade gliomas (HGG) have a dismal outcome with a median progression free survival (PFS) of 12 weeks. Adults with recurrent HGG treated with irinotecan and bevacizumab ...reportedly have a 63% response rate and a median PFS of 23 weeks. There is a paucity of corresponding published pediatric data. We retrospectively reviewed the records of patients less than 21 years of age with recurrent or progressive WHO grade 3–4 gliomas who were treated with bevacizumab containing regimens at our institution between January 2006 and September 2008. We identified eight patients. Six out of eight patients received irinotecan, temozolomide and bevacizumab, one patient received irinotecan and bevacizumab, and one patient received CCNU and bevacizumab. Three patients had stable disease for 30–93 weeks. The remaining five patients developed progressive disease within 17 weeks. The median PFS was 15 weeks and the 6-month PFS was 38%. Contrast enhancing disease responded or remained stable in five out of seven patients whereas non-enhancing disease progressed in three out of four patients. New distant non-enhancing lesions developed in three patients. The most common side effects included diarrhea, vomiting, thrombocytopenia and neutropenia. Bevacizumab was well tolerated when used in combination with conventional chemotherapy (irinotecan in most cases). PFS in our cohort was much shorter and the response rate was inferior in this small cohort of patients when compared with published adult data. However, bevacizumab containing regimens might be effective in a subset of pediatric patients, especially those with predominantly contrast-enhancing disease.
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