Isocitrate dehydrogenase (IDH) mutational status is pivotal in the management of gliomas. Patients with IDH-mutated (IDH-MUT) tumors have a better prognosis and benefit more from extended surgical resection than IDH wild-type (IDH-WT). Raman spectroscopy (RS) is a minimally invasive optical technique with great potential for intraoperative diagnosis. We evaluated the RS’s ability to characterize the IDH mutational status onto unprocessed glioma biopsies. We extracted 2073 Raman spectra from thirty-eight unprocessed samples. The classification performance was assessed using the eXtreme Gradient Boosted trees (XGB) and Support Vector Machine with Radial Basis Function kernel (RBF-SVM). Measured Raman spectra displayed differences between IDH-MUT and IDH-WT tumor tissue. From the 103 Raman shifts screened as input features, the cross-validation loop identified 52 shifts with the highest performance in the distinction of the two groups. Raman analysis showed differences in spectral features of lipids, collagen, DNA and cholesterol/phospholipids. We were able to distinguish between IDH-MUT and IDH-WT tumors with an accuracy and precision of 87%. RS is a valuable and accurate tool for characterizing the mutational status of IDH mutation in unprocessed glioma samples. This study improves RS knowledge for future personalized surgical strategy or in situ target therapies for glioma tumors.

BackgroundTumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, non-invasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as positron emission tomography (PET) imaging.ObjectivesThis study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity.Materials and MethodsSeventeen patients harboring HGGs underwent a pre-operative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats’ spatial distribution, quantitative features and histopathological characteristics were analyzed.ResultsA highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend toward a higher representation of the most aggressive clusters in WHO (World Health Organization) grade IV compared to WHO III was observed.ConclusionPreliminary findings demonstrated high reproducibility of the PET and MRI hypoxia, perfusion, and tissue diffusion spatial habitat maps and correlation with disease-specific histopathological features.

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A link between maternal anxiety during pregnancy and adverse socio‐emotional outcomes in childhood has been consistently sustained on the very early neurodevelopmental alteration of structural pathways between fetal limbic and cortical brain regions. In this study, we provide follow‐up evidence for a feed‐forward model linking (i) maternal anxiety, (ii) fetal functional neurodevelopment, (iii) neonatal functional network organization with (iv) socio‐emotional neurobehavioral development in early childhood. Namely, we investigate a sample of 16 mother–fetus dyads and show how a maternal state–trait anxiety profile with pregnancy‐specific worries can significantly influence functional synchronization patterns between regions of the fetal limbic system (i.e., hippocampus and amygdala) and the neocortex, as assessed through resting‐state functional magnetic resonance imaging. Generalization of the findings was supported by leave‐one‐out cross‐validation. We further show how this maternal–fetal cross‐talk propagates to functional network topology in the neonate, specifically targeting connector hubs, and further maps onto socio‐emotional profiles, assessed through Bayley‐III socio‐emotional scale in early childhood (i.e., in the 12–24 months range). Based on this evidence, we put forward the hypothesis of a “Maternal‐Fetal‐Neonatal Anxiety Backbone”, through which neurobiological changes driven by maternal anxiety could trigger a divergence in the establishment of a cognitive–emotional development blueprint, in terms of the nascent functional homeostasis between bottom‐up limbic and top‐down higher‐order neuronal circuitry.

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