Relationship of In Vivo MR Parameters to Histopathological and Molecular Characteristics of Newly Diagnosed, Nonenhancing Lower-Grade Gliomas.

The goal of this research was to elucidate the relationship between WHO 2016 molecular classifications of newly diagnosed, nonenhancing lower grade gliomas (LrGG), tissue sample histopathology, and magnetic resonance (MR) parameters derived from diffusion, perfusion, and 1H spectroscopic imaging from the tissue sample locations and the entire tumor. A total of 135 patients were scanned prior to initial surgery, with tumor cellularity scores obtained from 88 image-guided tissue samples. MR parameters were obtained from corresponding sample locations, and histograms of normalized MR parameters within the T2 fluid-attenuated inversion recovery lesion were analyzed in order to evaluate differences between subgroups. For tissue samples, higher tumor scores were related to increased normalized apparent diffusion coefficient (nADC), lower fractional anisotropy (nFA), lower cerebral blood volume (nCBV), higher choline (nCho), and lower N-acetylaspartate (nNAA). Within the T2 lesion, higher tumor grade was associated with higher nADC, lower nFA, and higher Cho to NAA index. Pathological analysis confirmed that diffusion and metabolic parameters increased and perfusion decreased with tumor cellularity. This information can be used to select targets for tissue sampling and to aid in making decisions about treating residual disease.

Patterns of paediatric emergency presentations to a tertiary referral centre in the Northern Territory.

OBJECTIVE: To describe epidemiological data concerning paediatric attendances at the ED of Royal Darwin Hospital (RDH). METHODS: We conducted a retrospective cohort study of paediatric emergency presentations to the RDH ED during 2004 and 2013. Epidemiological data, including demographics, admission rates and diagnostic grouping, were analysed using descriptive and comparative statistical methods. We compared data with findings from a baseline epidemiological study by the Paediatric Research in Emergency Departments International Collaborative (PREDICT) conducted in 2004. RESULTS: A total of 12 745 and 15 378 paediatric presentations (age 0-18 years) to the RDH ED were analysed for the years 2004 and 2013 respectively. In 2004, the mean age of children presenting to RDH was 7.1 years, and 56.0% were female. Indigenous patients accounted for 31.2% of presentations at RDH and were significantly more likely to be admitted than non-Indigenous patients (31.6% vs 12.8%, OR 3.24, 95% CI 2.95-3.55). Children <5 years old accounted for the highest number of presentations (45.2%) and admissions (51.2%), and there was a high proportion of adolescent presentations (18.0%). Similar to the PREDICT study, viral infectious conditions (bronchiolitis, gastroenteritis, upper respiratory tract infections) were the most common cause for presentations. Key differences included a higher proportion of patients presenting with cellulitis and head injury at RDH and an increasing proportion of adolescent psychiatric presentations at RDH from 2004 to 2013. CONCLUSION: This study provides important information regarding paediatric presentations to a major referral hospital in the Northern Territory. Overall, there was a disproportionate rate of presentation and admission among Indigenous children. Other key findings were higher proportions of cellulitis, head injury and adolescent presentations. These findings can assist in service planning and in directing future research specific to children in the Northern Territory.

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy.

Quantitative multi-modal MR imaging as a non-invasive prognostic tool for patients with recurrent low-grade glioma.

Low-grade gliomas can vary widely in disease course and therefore patient outcome. While current characterization relies on both histological and molecular analysis of tissue resected during surgery, there remains high variability within glioma subtypes in terms of response to treatment and outcome. In this study we hypothesized that parameters obtained from magnetic resonance data would be associated with progression-free survival for patients with recurrent low-grade glioma. The values considered were derived from the analysis of anatomic imaging, diffusion weighted imaging, and 1H magnetic resonance spectroscopic imaging data. Metrics obtained from diffusion and spectroscopic imaging presented strong prognostic capability within the entire population as well as when restricted to astrocytomas, but demonstrated more limited efficacy in the oligodendrogliomas. The results indicate that multi-parametric imaging data may be applied as a non-invasive means of assessing prognosis and may contribute to developing personalized treatment plans for patients with recurrent low-grade glioma.

Magnetic resonance analysis of malignant transformation in recurrent glioma.

BACKGROUND: Patients with low-grade glioma (LGG) have a relatively long survival, and a balance is often struck between treating the tumor and impacting quality of life. While lesions may remain stable for many years, they may also undergo malignant transformation (MT) at the time of recurrence and require more aggressive intervention. Here we report on a state-of-the-art multiparametric MRI study of patients with recurrent LGG. METHODS: One hundred and eleven patients previously diagnosed with LGG were scanned at either 1.5 T or 3 T MR at the time of recurrence. Volumetric and intensity parameters were estimated from anatomic, diffusion, perfusion, and metabolic MR data. Direct comparisons of histopathological markers from image-guided tissue samples with metrics derived from the corresponding locations on the in vivo images were made. A bioinformatics approach was applied to visualize and interpret these results, which included imaging heatmaps and network analysis. Multivariate linear-regression modeling was utilized for predicting transformation. RESULTS: Many advanced imaging parameters were found to be significantly different for patients with tumors that had undergone MT versus those that had not. Imaging metrics calculated at the tissue sample locations highlighted the distinct biological significance of the imaging and the heterogeneity present in recurrent LGG, while multivariate modeling yielded a 76.04% accuracy in predicting MT. CONCLUSIONS: The acquisition and quantitative analysis of such multiparametric MR data may ultimately allow for improved clinical assessment and treatment stratification for patients with recurrent LGG.