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Diffuse intrinsic pontine glioma (DIPG) is the most severe paediatric solid tumour, with no significant therapeutic progress made in the past 50 years. Recent studies suggest that diffuse midline glioma, H3 - K27M mutant, may comprise more than one biological entity. The aim of the study was to determine the clinical and biological variables that most impact their prognosis. Ninety-one patients with classically defined DIPG underwent a systematic stereotactic biopsy and were included in this observational retrospective study. Histone H3 genes mutations were assessed by immunochemistry and direct sequencing, whilst global gene expression profiling and chromosomal imbalances were determined by microarrays. A full description of the MRI findings at diagnosis and at relapse was integrated with the molecular profiling data and clinical outcome. All DIPG but one were found to harbour either a somatic H3-K27M mutation and/or loss of H3K27 trimethylation. We also discovered a novel K27M mutation in HIST2H3C , and a lysine-to-isoleucine substitution (K27I) in H3F3A , also creating a loss of trimethylation. Patients with tumours harbouring a K27M mutation in H3.3 ( H3F3A ) did not respond clinically to radiotherapy as well, relapsed significantly earlier and exhibited more metastatic recurrences than those in H3.1 ( HIST1H3B/C ). H3.3-K27M-mutated DIPG have a proneural/oligodendroglial phenotype and a pro-metastatic gene expression signature with PDGFRA activation, while H3.1-K27M-mutated tumours exhibit a mesenchymal/astrocytic phenotype and a pro-angiogenic/hypoxic signature supported by expression profiling and radiological findings. H3K27 alterations appear as the founding event in DIPG and the mutations in the two main histone H3 variants drive two distinct oncogenic programmes with potential specific therapeutic targets.

Objectives The diffuse intrinsic pontine gliomas (DIPGs) are now defined by the type of histone H3 mutated at lysine 27. We aimed to correlate the multimodal MRI features of DIPGs, H3K27M mutant, with their histological and molecular characteristics. Methods Twenty-seven treatment-naïve children with histopathologically confirmed DIPG H3K27M mutant were prospectively included. MRI performed prior to biopsy included multi-b-value diffusion-weighted imaging, ASL, and dynamic susceptibility contrast (DSC) perfusion imaging. The ADC and cerebral blood flow (CBF) and blood volume (CBV) were measured at the biopsy site. We assessed quantitative histological data, including microvascular density, nuclear density, and H3K27M-positive nuclear density. Gene expression profiling was also assessed in the samples. We compared imaging and histopathological data according to histone subgroup. We correlated MRI quantitative data with histological data and gene expression. Results H3.1K27M mutated tumors showed higher ADC values (median 3151 μm 2 /s vs 1741 μm 2 /s, p = 0.003), and lower perfusion values (DSC-rCBF median 0.71 vs 1.43, p = 0.002, and DSC-rCBV median 1.00 vs 1.71, p = 0.02) than H3.3K27M ones. They had similar microvascular and nuclear density, but lower H3K27M-positive nuclear density ( p = 0.007). The DSC-rCBV was positively correlated to the H3K27M-positive nuclear density (rho = 0.74, p = 0.02). ADC values were not correlated with nuclear density nor perfusion values with microvascular density. The expression of gated channel activity–related genes tended to be inversely correlated with ADC values and positively correlated with DSC perfusion. Conclusions H3.1K27M mutated tumors have higher ADC and lower perfusion values than H3.3K27M ones, without direct correlation with microvascular or nuclear density. This may be due to tissular edema possibly related to gated channel activity–related gene expression. Key Points • H3.1K27M mutant DIPG had higher apparent diffusion coefficient (p = 0.003), lower α (p = 0.048), and lower relative cerebral blood volume (p = 0.02) than H3.3K27M mutant DIPG at their biopsy sites. • Biopsy samples obtained within the tumor’s enhancing portion showed higher microvascular density (p = 0.03) than samples obtained outside the tumor’s enhancing portion, but similar H3K27M-positive nuclear density (p = 0.84). • Relative cerebral blood volume measured at the biopsy site was significantly correlated with H3K27M-positive nuclear density (rho = 0.74, p = 0.02).

Background To illustrate that Breast-MRI performed in high spatial resolution and low temporal resolution (1 minute) allows the measurement of kinetic parameters that can assess the final pathologic response to neoadjuvant chemotherapy in breast cancer. Methods Breast-MRI was performed in 24 women before and after treatment. Eight series of 1.11 minute-duration were acquired with a sub-millimeter spatial resolution. Transfer constant (K trans ) and leakage space (V e ) were calculated using measured and theoretical Arterial Input Function (AIF). Changes in kinetic parameters after treatment obtained with both AIFs were compared with final pathologic response graded in non-responder (< 50% therapeutic effect), partial-responder (> 50% therapeutic effect) and complete responder. Accuracies to identify non-responders were compared with receiver operating characteristic curves. Results With measured-AIF, changes in kinetic parameters measured after treatment were in agreement with the final pathological response. Changes in V e and K trans were significantly different between non-(N = 11), partial-(N = 7), and complete (N = 6) responders, (P = 0.0092 and P = 0.0398 respectively). A decrease in V e of more than -72% and more than -84% for K trans resulted in 73% sensitivity for identifying non-responders (specificity 92% and 77% respectively). A decrease in V e of more than -87% helped to identify complete responders (Sensitivity 89%, Specificity 83%). With theoretical-AIF, changes in kinetic parameters had lower accuracy. Conclusion There is a good agreement between pathological findings and changes in kinetic parameters obtained with breast-MRI in high spatial and low temporal resolution when measured-AIF is used. Further studies are necessary to confirm whether MRI contrast kinetic parameters can be used earlier as a response predictor to neoadjuvant chemotherapy.

Tumour lesion segmentation is a key step to study and characterise cancer from MR neuroradiological images. Presently, numerous deep learning segmentation architectures have been shown to perform well on the specific tumour type they are trained on (e.g., glioblastoma in brain hemispheres). However, a high performing network heavily trained on a given tumour type may perform poorly on a rare tumour type for which no labelled cases allows training or transfer learning. Yet, because some visual similarities exist nevertheless between common and rare tumours, in the lesion and around it, one may split the problem into two steps: object detection and segmentation. For each step, trained networks on common lesions could be used on rare ones following a domain adaptation scheme without extra fine-tuning. This work proposes a resilient tumour lesion delineation strategy, based on the combination of established elementary networks that achieve detection and segmentation. Our strategy allowed us to achieve robust segmentation inference on a rare tumour located in an unseen tumour context region during training. As an example of a rare tumour, Diffuse Intrinsic Pontine Glioma (DIPG), we achieve an average dice score of 0.62 without further training or network architecture adaptation.

Objectives To assess the impact of different protocols on radiation dose and image quality for paediatric coronary computed tomography (cCT). Materials and methods From January-2012 to June-2014, 140 children who underwent cCT on a 64-slice scanner were included. Two consecutive changes in imaging protocols were performed: 1) the use of adaptive statistical iterative reconstruction (ASIR); 2) the optimization of acquisition parameters. Effective dose (ED) was calculated by conversion of the dose-length product. Image quality was assessed as excellent, good or with significant artefacts. Results Patients were divided in three age groups: 0–4, 5–7 and 8–18 years. The use of ASIR combined to the adjustment of scan settings allowed a reduction in the median ED of 58 %, 82 % and 85 % in 0–4, 5–7 and 8–18 years group, respectively (7.3 ± 1.4 vs 3.1 ± 0.7 mSv, 5.5 ± 1.6 vs 1 ± 1.9 mSv and 5.3 ± 5.0 vs 0.8 ± 2.0 mSv, all p < 0,05). Prospective protocol was used in 51 % of children. The reduction in radiation dose was not associated with reduction in diagnostic image quality as assessed by the frequency of coronary segments with excellent or good image quality (88 %). Conclusions cCT can be obtained at very low radiation doses in children using ASIR, and prospective acquisition with optimized imaging parameters. Key points • Using ASIR allows 25  % to 41  % reduction in the ED . • Prospective protocol is used up to 51  % of children after premedication . • Low dose is possible using ASIR and optimized prospective paediatric cCT

Humans show great interindividual variability in the degree they engage in social relationship. The neural basis of this variability is still poorly understood, particularly in children. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is social perception, in typically developing children. For that purpose, we first used eye-tracking to objectively measure eye-gaze processing during passive visualization of social movie clips in 24 children and adolescents (10.5 ± 2.9 y). Secondly, we correlated eye-tracking data with measures of fractional anisotropy, an index of white matter microstructure, obtained using diffusion tensor imaging MRI. The results showed a large interindividual variability in the number of fixations to the eyes of characters during visualization of social scenes. In addition, whole-brain analysis showed a significant positive correlation between FA and number of fixations to the eyes,mainly in the temporal part of the superior longitudinal fasciculi bilaterally, adjacent to the posterior superior temporal cortex. Our results indicate the existence of a neural signature associated with the interindividual variability in social perception in children, contributing for better understanding the neural basis of typical and atypical development of a broader social expertise.

Social behavior is extremely variable among individuals, and the neural basis of this variability is still poorly understood. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is, social perception. For that purpose, we first used eye-tracking to measure social perception during the passive visualization of socially relevant movie clips. Second, we correlated eye-tracking data with measures of rest cerebral blood flow (CBF) obtained using arterial spin-labeling (ASL) MRI, an index of local rest brain function. The results showed a large interindividual variability in the number of fixations to the eyes of characters during passive visualization of movie clips displaying social interactions. Moreover, individual patterns remained stable across time, suggesting an individual signature of social behavior. Whole-brain analyses showed significant positive correlation between the number of fixations to the eyes and rest CBF: individuals who looked more to the eyes were those with higher rest CBF levels within the right superior temporal regions. Our results indicate the existence of a neural and behavioral signature associated with the interindividual variability in social perception.

The diffuse intrinsic pontine gliomas (DIPGs) are now defined by the type of histone H3 mutated at lysine 27. We aimed to correlate the multimodal MRI features of DIPGs, H3K27M mutant, with their histological and molecular characteristics.

Abstract The first year of life is a key period of brain development, characterized by dramatic structural and functional modifications. Here, we measured rest cerebral blood flow (CBF) modifications throughout babies’ first year of life using arterial spin labeling magnetic resonance imaging sequence in 52 infants, from 3 to 12 months of age. Overall, global rest CBF significantly increased during this age span. In addition, we found marked regional differences in local functional brain maturation. While primary sensorimotor cortices and insula showed early maturation, temporal and prefrontal region presented great rest CBF increase across the first year of life. Moreover, we highlighted a late and remarkably synchronous maturation of the prefrontal and posterior superior temporal cortices. These different patterns of regional cortical rest CBF modifications reflect a timetable of local functional brain maturation and are consistent with baby’s cognitive development within the first year of life. Competing Interest Statement The authors have declared no competing interest.

Advances in neuroimaging techniques have significantly improved our understanding of the neural basis of autism spectrum disorder (ASD). Several attempts have been made to label the main neuroimaging phenotype of ASD, mostly by anatomical and functional activation studies, but none of the frameworks have been without controversy. Over the past decade, a renewed interest for rest brain functioning has emerged in the scientific community, reflected on a large number of resting state fMRI (rs-fMRI) studies, but results remain heterogeneous. It is possible today to investigate rest brain functioning by measuring rest cerebral blood flow (CBF) with MRI using arterial spin labeling (ASL). Here, we investigated rest CBF abnormalities using non-invasive ASL-MRI in 18 children with ASD without cognitive delay (10.4 +/- 2.8 y) and 30 typically developing children (10.6 +/- 3.0 y). Following quality control, images from a final sample of 12 children with ASD (11.2 +/- 2.9 y) and 28 typically developing children (10.1 +/- 2.5 y) were analyzed. Whole brain voxel-by-voxel analysis showed significant rest CBF decrease in temporal regions, mainly in the superior temporal sulcus (STS), in children with ASD. This hypoperfusion was individually detected in 83% of children with ASD. Finally, negative correlation was observed between ASD severity scores and rest CBF in the right posterior STS. Strikingly, despite the small sample studied here, our results are extremely similar to previous PET and SPECT findings describing decreased rest CBF in the same superior temporal regions at group and individual levels, as well as correlation with symptoms severity. The congruence between these results, with different methods and in different ASD profiles, reinforce the strength of rest functional abnormalities within these superior temporal regions in ASD and strongly indicates it might be a core characteristic of the disorder. Identifying a core dysfunctional region in ASD bears direct implications to the development of novel therapeutic interventions, such as transcranial magnetic stimulation. In addition, if confirmed in a larger sample, rest temporal hypoperfusion could become a reliable brain imaging biomarker in ASD.