ADC Histogram Analysis of Pediatric Low-Grade Glioma Treated with Selumetinib: A Report from the Pediatric Brain Tumor Consortium.

BACKGROUND AND PURPOSE: Selumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging-derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib. MATERIALS AND METHODS: Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549-BRAF fusion or the BRAF V600E mutation (stratum 1), neurofibromatosis type 1-associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment. RESULTS: Each stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1-associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1-associated OPHG. CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.

Myelination as assessed by conventional MR imaging is normal in young children with idiopathic developmental delay.

BACKGROUND AND PURPOSE: A common isolated reported finding in brain imaging studies on developmentally delayed children is delayed myelination. We hypothesized that brain MR imaging scans of these children would show delayed subcortical myelination of white matter with specific involvement of the subcortical U-fibers as these represent terminal zones of myelination and are the last areas to myelinate. MATERIALS AND METHODS: A total of 93 children (31 controls, 62 with idiopathic developmental delay [IDD]) aged 17 to 46 months were identified on the basis of having brain MR imaging for evaluation of IDD (cases) or for another condition (controls). Children with diseases that primarily affect white matter or overt intracranial lesions or malformations were excluded. IDD was defined as psychomotor retardation without a clear cause on the basis of history, physical, genetic, metabolic, and neuroimaging examinations. Developmental quotients (DQs) were calculated for all children with IDD on the basis of clinical history, examination, and psychometric testing. Three board-certified pediatric neuroradiologists examined axial T2-weighted brain images and used a published scoring system to rate the extent of myelination in the frontal, temporal, parietal, and peritrigonal brain regions. In addition, subcortical U-fibers in the frontal, temporal, and parietal lobes were scored separately. Data were analyzed at both the intraobserver and interobserver levels, and scores were compared between groups and tested for interactions with age and DQ. RESULTS: There were no differences in the timing or extent of myelination in the control and IDD groups at any age in any brain region. In the IDD group, there was no relationship between myelination scores and DQ or developmental domain. CONCLUSIONS: Our findings did not support the hypothesis that there is a correlation between IDD and the maturity of myelination, including the terminal zones, as seen on conventional brain MR imaging. Neuroimaging evaluation of maturity of subcortical myelination is not a marker of IDD in young children, and the isolated "finding" of delayed myelination should be interpreted with caution.