Weakly Supervised Detection of Pheochromocytomas and Paragangliomas in CT.

Pheochromocytomas and Paragangliomas (PPGLs) are rare adrenal and extra-adrenal tumors which have the potential to metastasize. For the management of patients with PPGLs, CT is the preferred modality of choice for precise localization and estimation of their progression. However, due to the myriad variations in size, morphology, and appearance of the tumors in different anatomical regions, radiologists are posed with the challenge of accurate detection of PPGLs. Since clinicians also need to routinely measure their size and track their changes over time across patient visits, manual demarcation of PPGLs is quite a time-consuming and cumbersome process. To ameliorate the manual effort spent for this task, we propose an automated method to detect PPGLs in CT studies via a proxy segmentation task. As only weak annotations for PPGLs in the form of prospectively marked 2D bounding boxes on an axial slice were available, we extended these 2D boxes into weak 3D annotations and trained a 3D full-resolution nnUNet model to directly segment PPGLs. We evaluated our approach on a dataset consisting of chest-abdomen-pelvis CTs of 255 patients with confirmed PPGLs. We obtained a precision of 70% and sensitivity of 64.1% with our proposed approach when tested on 53 CT studies. Our findings highlight the promising nature of detecting PPGLs via segmentation, and furthers the state-of-the-art in this exciting yet challenging area of rare cancer management.

Weakly supervised detection of pheochromocytomas and paragangliomas in CT using noisy data.

Pheochromocytomas and Paragangliomas (PPGLs) are rare adrenal and extra-adrenal tumors that have metastatic potential. Management of patients with PPGLs mainly depends on the makeup of their genetic cluster: SDHx, VHL/EPAS1, kinase, and sporadic. CT is the preferred modality for precise localization of PPGLs, such that their metastatic progression can be assessed. However, the variable size, morphology, and appearance of these tumors in different anatomical regions can pose challenges for radiologists. Since radiologists must routinely track changes across patient visits, manual annotation of PPGLs is quite time-consuming and cumbersome to do across all axial slices in a CT volume. As such, PPGLs are only weakly annotated on axial slices by radiologists in the form of RECIST measurements. To ameliorate the manual effort spent by radiologists, we propose a method for the automated detection of PPGLs in CT via a proxy segmentation task. Weak 3D annotations (derived from 2D bounding boxes) were used to train both 2D and 3D nnUNet models to detect PPGLs via segmentation. We evaluated our approaches on an in-house dataset comprised of chest-abdomen-pelvis CTs of 255 patients with confirmed PPGLs. On a test set of 53 CT volumes, our 3D nnUNet model achieved a detection precision of 70% and sensitivity of 64.1%, and outperformed the 2D model that obtained a precision of 52.7% and sensitivity of 27.5% (p< 0.05). SDHx and sporadic genetic clusters achieved the highest precisions of 73.1% and 72.7% respectively. Our state-of-the art findings highlight the promising nature of the challenging task of automated PPGL detection.

MEA-NAP compares microscale functional connectivity, topology, and network dynamics in organoid or monolayer neuronal cultures.

Microelectrode array (MEA) recordings are commonly used to compare firing and burst rates in neuronal cultures. MEA recordings can also reveal microscale functional connectivity, topology, and network dynamics-patterns seen in brain networks across spatial scales. Network topology is frequently characterized in neuroimaging with graph theoretical metrics. However, few computational tools exist for analyzing microscale functional brain networks from MEA recordings. Here, we present a MATLAB MEA network analysis pipeline (MEA-NAP) for raw voltage time-series acquired from single- or multi-well MEAs. Applications to 3D human cerebral organoids or 2D human-derived or murine cultures reveal differences in network development, including topology, node cartography, and dimensionality. MEA-NAP incorporates multi-unit template-based spike detection, probabilistic thresholding for determining significant functional connections, and normalization techniques for comparing networks. MEA-NAP can identify network-level effects of pharmacologic perturbation and/or disease-causing mutations and, thus, can provide a translational platform for revealing mechanistic insights and screening new therapeutic approaches.

Rett Syndrome: A Tale of Altered Genetics, Synaptic Plasticity, and Neurodevelopmental Dynamics.

Rett syndrome (RTT) is a neurodevelopmental disorder that is a leading cause of severe cognitive and physical impairment. RTT typically occurs in females, although rare cases of males with the disease exist. Its genetic cause, symptoms, and clinical progression timeline have also become well-documented since its initial discovery. However, a relatively late diagnosis and lack of an available cure signify that our understanding of the disease is incomplete. Innovative research methods and tools are thereby helping to fill gaps in our knowledge of RTT. Specifically, mouse models of RTT, video analysis, and retrospective parental analysis are well-established tools that provide valuable insights into RTT. Moreover, current and anticipated treatment options are improving the quality of life of the RTT patient population. Collectively, these developments are creating optimistic future perspectives for RTT.

Development and validation of a Bayesian network predicting neurosurgical intervention after injury in children and adolescents.

BACKGROUND: Timely surgical decompression improves functional outcomes and survival among children with traumatic brain injury and increased intracranial pressure. Previous scoring systems for identifying the need for surgical decompression after traumatic brain injury in children and adults have had several barriers to use. These barriers include the inability to generate a score with missing data, a requirement for radiographic imaging that may not be immediately available, and limited accuracy. To address these limitations, we developed a Bayesian network to predict the probability of neurosurgical intervention among injured children and adolescents (aged 1-18 years) using physical examination findings and injury characteristics observable at hospital arrival. METHODS: We obtained patient, injury, transportation, resuscitation, and procedure characteristics from the 2017 to 2019 Trauma Quality Improvement Project database. We trained and validated a Bayesian network to predict the probability of a neurosurgical intervention, defined as undergoing a craniotomy, craniectomy, or intracranial pressure monitor placement. We evaluated model performance using the area under the receiver operating characteristic and calibration curves. We evaluated the percentage of contribution of each input for predicting neurosurgical intervention using relative mutual information (RMI). RESULTS: The final model included four predictor variables, including the Glasgow Coma Scale score (RMI, 31.9%), pupillary response (RMI, 11.6%), mechanism of injury (RMI, 5.8%), and presence of prehospital cardiopulmonary resuscitation (RMI, 0.8%). The model achieved an area under the receiver operating characteristic curve of 0.90 (95% confidence interval [CI], 0.89-0.91) and had a calibration slope of 0.77 (95% CI, 0.29-1.26) with a y intercept of 0.05 (95% CI, -0.14 to 0.25). CONCLUSION: We developed a Bayesian network that predicts neurosurgical intervention for all injured children using four factors immediately available on arrival. Compared with a binary threshold model, this probabilistic model may allow clinicians to stratify management strategies based on risk. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.