Unsupervised machine learning using K-means identifies radiomic subgroups of pediatric low-grade gliomas that correlate with key molecular markers.

INTRODUCTION: Despite advancements in molecular and histopathologic characterization of pediatric low-grade gliomas (pLGGs), there remains significant phenotypic heterogeneity among tumors with similar categorizations. We hypothesized that an unsupervised machine learning approach based on radiomic features may reveal distinct pLGG imaging subtypes. METHODS: Multi-parametric MR images (T1 pre- and post-contrast, T2, and T2 FLAIR) from 157 patients with pLGGs were collected and 881 quantitative radiomic features were extracted from tumorous region. Clustering was performed using K-means after applying principal component analysis (PCA) for feature dimensionality reduction. Molecular and demographic data was obtained from the PedCBioportal and compared between imaging subtypes. RESULTS: K-means identified three distinct imaging-based subtypes. Subtypes differed in mutational frequencies of BRAF (p < 0.05) as well as the gene expression of BRAF (p<0.05). It was also found that age (p < 0.05), tumor location (p < 0.01), and tumor histology (p < 0.0001) differed significantly between the imaging subtypes. CONCLUSION: In this exploratory work, it was found that clustering of pLGGs based on radiomic features identifies distinct, imaging-based subtypes that correlate with important molecular markers and demographic details. This finding supports the notion that incorporation of radiomic data could augment our ability to better characterize pLGGs.

Automated Tumor Segmentation and Brain Tissue Extraction from Multiparametric MRI of Pediatric Brain Tumors: A Multi-Institutional Study.

Background: Brain tumors are the most common solid tumors and the leading cause of cancer-related death among all childhood cancers. Tumor segmentation is essential in surgical and treatment planning, and response assessment and monitoring. However, manual segmentation is time-consuming and has high interoperator variability. We present a multi-institutional deep learning-based method for automated brain extraction and segmentation of pediatric brain tumors based on multi-parametric MRI scans. Methods: Multi-parametric scans (T1w, T1w-CE, T2, and T2-FLAIR) of 244 pediatric patients (n=215 internal and n=29 external cohorts) with de novo brain tumors, including a variety of tumor subtypes, were preprocessed and manually segmented to identify the brain tissue and tumor subregions into four tumor subregions, i.e., enhancing tumor (ET), non-enhancing tumor (NET), cystic components (CC), and peritumoral edema (ED). The internal cohort was split into training (n=151), validation (n=43), and withheld internal test (n=21) subsets. DeepMedic, a three-dimensional convolutional neural network, was trained and the model parameters were tuned. Finally, the network was evaluated on the withheld internal and external test cohorts. Results: Dice similarity score (median±SD) was 0.91±0.10/0.88±0.16 for the whole tumor, 0.73±0.27/0.84±0.29 for ET, 0.79±19/0.74±0.27 for union of all non-enhancing components (i.e., NET, CC, ED), and 0.98±0.02 for brain tissue in both internal/external test sets. Conclusions: Our proposed automated brain extraction and tumor subregion segmentation models demonstrated accurate performance on segmentation of the brain tissue and whole tumor regions in pediatric brain tumors and can facilitate detection of abnormal regions for further clinical measurements. Key Points: We proposed automated tumor segmentation and brain extraction on pediatric MRI.The volumetric measurements using our models agree with ground truth segmentations. Importance of the Study: The current response assessment in pediatric brain tumors (PBTs) is currently based on bidirectional or 2D measurements, which underestimate the size of non-spherical and complex PBTs in children compared to volumetric or 3D methods. There is a need for development of automated methods to reduce manual burden and intra- and inter-rater variability to segment tumor subregions and assess volumetric changes. Most currently available automated segmentation tools are developed on adult brain tumors, and therefore, do not generalize well to PBTs that have different radiological appearances. To address this, we propose a deep learning (DL) auto-segmentation method that shows promising results in PBTs, collected from a publicly available large-scale imaging dataset (Children's Brain Tumor Network; CBTN) that comprises multi-parametric MRI scans of multiple PBT types acquired across multiple institutions on different scanners and protocols. As a complementary to tumor segmentation, we propose an automated DL model for brain tissue extraction.

Automated tumor segmentation and brain tissue extraction from multiparametric MRI of pediatric brain tumors: A multi-institutional study.

Background: Brain tumors are the most common solid tumors and the leading cause of cancer-related death among all childhood cancers. Tumor segmentation is essential in surgical and treatment planning, and response assessment and monitoring. However, manual segmentation is time-consuming and has high interoperator variability. We present a multi-institutional deep learning-based method for automated brain extraction and segmentation of pediatric brain tumors based on multi-parametric MRI scans. Methods: Multi-parametric scans (T1w, T1w-CE, T2, and T2-FLAIR) of 244 pediatric patients ( n = 215 internal and n = 29 external cohorts) with de novo brain tumors, including a variety of tumor subtypes, were preprocessed and manually segmented to identify the brain tissue and tumor subregions into four tumor subregions, i.e., enhancing tumor (ET), non-enhancing tumor (NET), cystic components (CC), and peritumoral edema (ED). The internal cohort was split into training ( n = 151), validation ( n = 43), and withheld internal test ( n = 21) subsets. DeepMedic, a three-dimensional convolutional neural network, was trained and the model parameters were tuned. Finally, the network was evaluated on the withheld internal and external test cohorts. Results: Dice similarity score (median ± SD) was 0.91 ± 0.10/0.88 ± 0.16 for the whole tumor, 0.73 ± 0.27/0.84 ± 0.29 for ET, 0.79 ± 19/0.74 ± 0.27 for union of all non-enhancing components (i.e., NET, CC, ED), and 0.98 ± 0.02 for brain tissue in both internal/external test sets. Conclusions: Our proposed automated brain extraction and tumor subregion segmentation models demonstrated accurate performance on segmentation of the brain tissue and whole tumor regions in pediatric brain tumors and can facilitate detection of abnormal regions for further clinical measurements.

A multi-institutional pediatric dataset of clinical radiology MRIs by the Children's Brain Tumor Network.

Pediatric brain and spinal cancers remain the leading cause of cancer-related death in children. Advancements in clinical decision-support in pediatric neuro-oncology utilizing the wealth of radiology imaging data collected through standard care, however, has significantly lagged other domains. Such data is ripe for use with predictive analytics such as artificial intelligence (AI) methods, which require large datasets. To address this unmet need, we provide a multi-institutional, large-scale pediatric dataset of 23,101 multi-parametric MRI exams acquired through routine care for 1,526 brain tumor patients, as part of the Children's Brain Tumor Network. This includes longitudinal MRIs across various cancer diagnoses, with associated patient-level clinical information, digital pathology slides, as well as tissue genotype and omics data. To facilitate downstream analysis, treatment-naïve images for 370 subjects were processed and released through the NCI Childhood Cancer Data Initiative via the Cancer Data Service. Through ongoing efforts to continuously build these imaging repositories, our aim is to accelerate discovery and translational AI models with real-world data, to ultimately empower precision medicine for children.

Radiomics and radiogenomics in pediatric neuro-oncology: A review.

The current era of advanced computing has allowed for the development and implementation of the field of radiomics. In pediatric neuro-oncology, radiomics has been applied in determination of tumor histology, identification of disseminated disease, prognostication, and molecular classification of tumors (ie, radiogenomics). The field also comes with many challenges, such as limitations in study sample sizes, class imbalance, generalizability of the methods, and data harmonization across imaging centers. The aim of this review paper is twofold: first, to summarize existing literature in radiomics of pediatric neuro-oncology; second, to distill the themes and challenges of the field and discuss future directions in both a clinical and technical context.