As raw sensory data are partial, our visual system extensively fills in missing details, creating enriched percepts based on incomplete bottom-up information. Despite evidence for internally ...generated representations at early stages of cortical processing, it is not known whether these representations include missing information of dynamically transforming objects. Long-range apparent motion (AM) provides a unique test case because objects in AM can undergo changes both in position and in features. Using fMRI and encoding methods, we found that the “intermediate” orientation of an apparently rotating grating, never presented in the retinal input but interpolated during AM, is reconstructed in population-level, feature-selective tuning responses in the region of early visual cortex (V1) that corresponds to the retinotopic location of the AM path. This neural representation is absent when AM inducers are presented simultaneously and when AM is visually imagined. Our results demonstrate dynamic filling-in in V1 for object features that are interpolated during kinetic transformations.
Lean muscle mass (LMM) is an important aspect of human health. Temporalis muscle thickness is a promising LMM marker but has had limited utility due to its unknown normal growth trajectory and ...reference ranges and lack of standardized measurement. Here, we develop an automated deep learning pipeline to accurately measure temporalis muscle thickness (iTMT) from routine brain magnetic resonance imaging (MRI). We apply iTMT to 23,876 MRIs of healthy subjects, ages 4 through 35, and generate sex-specific iTMT normal growth charts with percentiles. We find that iTMT was associated with specific physiologic traits, including caloric intake, physical activity, sex hormone levels, and presence of malignancy. We validate iTMT across multiple demographic groups and in children with brain tumors and demonstrate feasibility for individualized longitudinal monitoring. The iTMT pipeline provides unprecedented insights into temporalis muscle growth during human development and enables the use of LMM tracking to inform clinical decision-making.
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.
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.
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.
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.
Abstract MR imaging is central to the assessment of tumor burden and changes over time in neuro-oncology. Several response assessment guidelines have been set forth by the Response Assessment in ...Pediatric Neuro-Oncology (RAPNO) working groups in different tumor histologies; however, the visual delineation of tumor components using MRIs is not always straightforward, and complexities not currently addressed by these criteria can introduce inter- and intra-observer variability in manual assessments. Differentiation of non-enhancing tumors from peritumoral edema, mild enhancement from absence of enhancement, and various cystic components can be challenging; particularly given a lack of sufficient and uniform imaging protocols in clinical practice. Automated tumor segmentation with artificial intelligence (AI) may be able to provide more objective delineations, but rely on accurate and consistent training data created manually (ground truth). Herein, this paper reviews existing challenges and potential solutions to identifying and defining subregions of pediatric brain tumors (PBTs) that are not explicitly addressed by current guidelines. The goal is to assert the importance of defining and adopting criteria for addressing these challenges, as it will be critical to achieving standardized tumor measurements and reproducible response assessment in PBTs, ultimately leading to more precise outcome metrics and accurate comparisons among clinical studies.
Abstract
With medical software platforms moving to cloud environments with scalable storage and computing, the translation of predictive artificial intelligence (AI) models to aid in clinical ...decision-making and facilitate personalized medicine for cancer patients is becoming a reality. Medical imaging, namely radiologic and histologic images, has immense analytical potential in neuro-oncology, and models utilizing integrated radiomic and pathomic data may yield a synergistic effect and provide a new modality for precision medicine. At the same time, the ability to harness multi-modal data is met with challenges in aggregating data across medical departments and institutions, as well as significant complexity in modeling the phenotypic and genotypic heterogeneity of pediatric brain tumors. In this paper, we review recent pathomic and integrated pathomic, radiomic, and genomic studies with clinical applications. We discuss current challenges limiting translational research on pediatric brain tumors and outline technical and analytical solutions. Overall, we propose that to empower the potential residing in radio-pathomics, systemic changes in cross-discipline data management and end-to-end software platforms to handle multi-modal data sets are needed, in addition to embracing modern AI-powered approaches. These changes can improve the performance of predictive models, and ultimately the ability to advance brain cancer treatments and patient outcomes through the development of such models.
Theories of embodied cognition propose that we recognize tools in part by reactivating sensorimotor representations of tool use in a process of simulation. If motor simulations play a causal role in ...tool recognition then performing a concurrent motor task should differentially modulate recognition of experienced vs. non-experienced tools. We sought to test the hypothesis that an incompatible concurrent motor task modulates conceptual processing of learned vs. non-learned objects by directly manipulating the embodied experience of participants. We trained one group to use a set of novel, 3-D printed tools under the pretense that they were preparing for an archeological expedition to Mars (manipulation group); we trained a second group to report declarative information about how the tools are stored (storage group). With this design, familiarity and visual attention to different object parts was similar for both groups, though their qualitative interactions differed. After learning, participants made familiarity judgments of auditorily presented tool names while performing a concurrent motor task or simply sitting at rest. We showed that familiarity judgments were facilitated by motor state-dependence; specifically, in the manipulation group, familiarity was facilitated by a concurrent motor task, whereas in the spatial group familiarity was facilitated while sitting at rest. These results are the first to directly show that manipulation experience differentially modulates conceptual processing of familiar vs. unfamiliar objects, suggesting that embodied representations contribute to recognizing tools.
Clinical management in neuro-oncology has changed to an integrative approach that incorporates molecular profiles alongside histopathology and imaging findings. While the World Health Organization ...(WHO) guideline recommends the genotyping of informative alterations as a routine clinical practice for central nervous system (CNS) tumors, the acquisition of tumor tissue in the CNS is invasive and not always possible. Liquid biopsy is a non-invasive approach that provides the opportunity to capture the complex molecular heterogeneity of the whole tumor through the detection of circulating tumor biomarkers in body fluids, such as blood or cerebrospinal fluid (CSF). Despite all of the advantages, the low abundance of tumor-derived biomarkers, particularly in CNS tumors, as well as their short half-life has limited the application of liquid biopsy in clinical practice. Thus, it is crucial to identify the factors associated with the presence of these biomarkers and explore possible strategies that can increase the shedding of these tumoral components into biological fluids. In this review, we first describe the clinical applications of liquid biopsy in CNS tumors, including its roles in the early detection of recurrence and monitoring of treatment response. We then discuss the utilization of imaging in identifying the factors that affect the detection of circulating biomarkers as well as how image-guided interventions such as focused ultrasound can help enhance the presence of tumor biomarkers through blood–brain barrier (BBB) disruption.
Abstract
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.
Increasing evidence suggests that besides mutational and molecular alterations, the immune component of the tumor microenvironment also substantially impacts tumor behavior and complicates treatment ...response, particularly to immunotherapies. Although the standard method for characterizing tumor immune profile is through performing integrated genomic analysis on tissue biopsies, the dynamic change in the immune composition of the tumor microenvironment makes this approach not feasible, especially for brain tumors. Radiomics is a rapidly growing field that uses advanced imaging techniques and computational algorithms to extract numerous quantitative features from medical images. Recent advances in machine learning methods are facilitating biological validation of radiomic signatures and allowing them to "mine" for a variety of significant correlates, including genetic, immunologic, and histologic data. Radiomics has the potential to be used as a non-invasive approach to predict the presence and density of immune cells within the microenvironment, as well as to assess the expression of immune-related genes and pathways. This information can be essential for patient stratification, informing treatment decisions and predicting patients' response to immunotherapies. This is particularly important for tumors with difficult surgical access such as gliomas. In this review, we provide an overview of the glioma microenvironment, describe novel approaches for clustering patients based on their tumor immune profile, and discuss the latest progress on utilization of radiomics for immune profiling of glioma based on current literature.
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