Purpose: Pediatric recurrent medulloblastoma and atypical teratoid/rhabdoid tumor (ATRT) are largely incurable and warrant novel therapies. PNOC005 is a phase I clinical trial investigating the safety and tolerability of intratumoral or intrathecal administration of oncolytic measles virus (MV-NIS) in children and young adults with recurrent medulloblastoma or ATRT. Patients and Methods: We investigated (i) the safety of a measles virus variant, MV-NIS, in a pediatric phase I study and (ii) the mechanisms of MV-NIS and the potential benefit of combination with immune checkpoint inhibition (ICI). Pediatric patients with recurrent medulloblastoma or ATRT were treated with intratumoral injections for local recurrence or via lumbar puncture for disseminated recurrence. We evaluated local immune responses to MV-NIS with and without ICI via single-cell and bulk RNA sequencing in an intracranial, immunocompetent, syngeneic murine model. Results: MV-NIS given intratumorally or via repeat intrathecal dosing was safe. MV-NIS prolonged survival in murine models but did not demonstrate an additive benefit with ICI. No changes in tumor-infiltrating immune cell composition or activation were observed in response to MV-NIS treatment; however, MV-NIS induced local expression of neutralizing antibodies, complement cascade, and phagocytosis-related genes. Conclusions: This is the first trial investigating intratumoral as well as repeated intrathecal delivery of MV-NIS in children with medulloblastoma and ATRT. We show that the therapy is safe and well tolerated, with minimal adverse effects. Immune markers and biological correlates preliminarily indicate antiviral effects in tumors.

SUMMARY: This paper will review how artificial intelligence (AI) will play an increasingly important role in pediatric neuroradiology in the future. A safe, transparent, and human-centric AI is needed to tackle the quadruple aim of improved health outcomes, enhanced patient and family experience, reduced costs, and improved well-being of the healthcare team in pediatric neuroradiology. Equity, diversity and inclusion, data safety, and access to care will need to always be considered. In the next decade, AI algorithms are expected to play an increasingly important role in access to care, workflow management, abnormality detection, classification, response prediction, prognostication, report generation, as well as in the patient and family experience in pediatric neuroradiology. Also, AI algorithms will likely play a role in recognizing and flagging rare diseases and in pattern recognition to identify previously unknown disorders. While AI algorithms will play an important role, humans will not only need to be in the loop, but in the center of pediatric neuroimaging. AI development and deployment will need to be closely watched and monitored by experts in the field. Patient and data safety need to be at the forefront, and the risks of a dependency on technology will need to be contained. The applications and implications of AI in pediatric neuroradiology will differ from adult neuroradiology.

BACKGROUND AND PURPOSE: The purpose of the study is to characterize diffusion tensor imaging indices in the developing spinal cord, evaluating differences based on age and cord region. Describing the progression of DTI indices in the pediatric cord increases our understanding of spinal cord development. MATERIALS AND METHODS: A retrospective analysis was performed on DTI acquired in 121 pediatric patients (mean, 8.6 years; range, 0.3–18.0 years) at Monroe Carell Jr. Children9s Hospital at Vanderbilt from 2017 to 2018. Diffusion-weighted images (15 directions; b = 750 s/mm²; slice thickness, 5 mm; in-plane resolution, 1.0 × 1.0 mm²) were acquired on a 3T scanner in the cervicothoracic and/or thoracolumbar cord. Manual whole-cord segmentation was performed. Images were masked and further segmented into cervical, upper thoracic, thoracolumbar, and conus regions. Analyses of covariance were performed for each DTI-derived index to investigate how age affects diffusion across cord regions, and 95% confidence intervals were calculated across age for each derived index and region. Post hoc testing was performed to analyze regional differences. RESULTS: Analyses of covariance revealed significant correlations of age with axial diffusivity, mean diffusivity, and fractional anisotropy (all, P < .001). There were also significant differences among cord regions for axial diffusivity, radial diffusivity, mean diffusivity, and fractional anisotropy (all, P < .001). CONCLUSIONS: This research demonstrates that diffusion evolves in the pediatric spinal cord during development, dependent on both cord region and the diffusion index of interest. Future research could investigate how diffusion may be affected by common pediatric spinal pathologies.

Background: ²³Na MRI correlates with tumor proliferation, and studies in pediatric patients are lacking. The purpose of the study: (1) to compare total sodium concentration (TSC) between pediatric glioma and non-neoplastic brain tissue using ²³Na MRI; (2) compare tissue conspicuity of bound sodium concentration (BSC) using ²³Na MRI dual echo relative to TSC imaging. Methods: TSC was measured in: (1) non-neoplastic brain tissues and (2) three types of manually segmented gliomas (diffuse intrinsic brainstem glioma (DIPG), recurrent supratentorial low-grade glioma (LGG), and high-grade glioma (HGG)). In a subset of patients, serial changes in both TSC and BSC (dual echo ²³Na MRI) were assessed. Results: Twenty-six pediatric patients with gliomas (median age of 12.0 years, range 4.9–23.3 years) were scanned with ²³Na MRI. DIPG treated with RT demonstrated higher TSC values than the uninvolved infratentorial tissues (p < 0.001). Recurrent supratentorial LGG and HGG exhibited higher TSC values than the uninvolved white matter (WM) and gray matter (GM) (p < 0.002 for LGG, and p < 0.02 for HGG). The dual echo ²³Na MRI suppressed the sodium signal within both CSF and necrotic foci. Conclusion: Quantitative ²³Na MRI of pediatric gliomas demonstrates a range of values that are higher than non-neoplastic tissues. Dual echo ²³Na MRI of BCS improves tissue conspicuity relative to TSC imaging.