PubMed · 12066792
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2002. Optimizing those brain cells.. https://pubmed.ncbi.nlm.nih.gov/12066792/
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Background: DNA methylation profiling is a tool that provides key support for central nervous system (CNS) tumor classification. However, diagnostically ambiguous pediatric cases may result in discordant outputs across classifiers. We developed MAGIBU, a cross-platform, projection-based framework that embeds individual methylomes into a fixed CNS reference landscape, ranking diagnostic entities by local epigenetic proximity to support clinician-led integrative diagnosis. Methods: As a proof-of-concept, we evaluated MAGIBU in eight morphologically challenging pediatric/juvenile CNS tumors with unresolved diagnoses after institutional and central pathology review. To establish a benchmark in the absence of a definitive histopathological ground truth, a consensus epigenetic reference was defined a priori for cases showing concordant results between the Heidelberg CNS Tumor Methylation Classifier and Methylscape Analysis. Comparisons were also performed with Epigenomic Digital Pathology (EpiDiP). To validate MAGIBU beyond this discovery cohort, performance was assessed at the family level across the CNS methylation spectrum (n = 678, 28 methylation families), on non-array platforms (whole-genome bisulfite sequencing and Oxford Nanopore), and in a focused analysis of the low-grade glioma and diffuse midline glioma compartment across four independent cohorts (n = 670). Results: In the discovery cohort, MAGIBU achieved high concordance with the consensus reference (Cohen's κ = 0.855), outperforming EpiDiP (κ = 0.278), which frequently placed low-grade tumors in proximity to higher-grade reference regions. Conclusions: MAGIBU provides a stable, quantitative differential diagnosis framework that mitigates the limitations of rigid categorical assignments. By leveraging a distance-based proximity metric, it offers a transparent decision-support tool that integrates effectively with clinical, radiological, and molecular data. While performance is inherently dependent on reference atlas composition, MAGIBU represents a robust complementary approach for the diagnostic workup of ambiguous CNS tumors.
Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
PURPOSE: The stereotactic radiotherapy (SRT) system verifies isocenter accuracy in patient space. In this study, we evaluate isocenter accuracy in frameless SRT using implanted cranial gold markers. MATERIALS AND METHODS: We performed frameless SRT on 43 intracranial tumor patients between August 1997 and December 2000. The treatment technique was determined by the tumor shape and volume, and by the location of critical organs. The coordinates of anterior-posterior and lateral port film were inputted to ISOLOC software, which calculated (1) the couch moves translation distance required to bring the target point to the isocenter, and (2) the intermarker distance comparisons between the CT study and the treatment machine films. We evaluated the isocenter deviation based on the error between orthogonal film target coordinates and isocenter coordinates. RESULTS: The mean treatment isocenter deviations (x, y, z) were -0.03, 0.14, and -0.04 mm, respectively. The systematic component isocenter standard deviations were 0.28, 0.31, and 0.35 mm (1 SD), respectively, and the random component isocenter standard deviations were 0.53, 0.52, and 0.50 mm (1 SD), respectively. CONCLUSIONS: The isocenter accuracy in the frameless SRT-implanted fiducial system is highly reliable and is comparable to that of other stereotactic radiosurgery systems.