Biology subjects

Halupnik, G. L.

Publications and source records attributed to Halupnik, G. L..

3 recordsLinked to original sources

bioRxiv2026

Automated Ventricle Assessment via Three-dimensional Anatomical Reconstruction (AVA-TAR): a computational toolkit for autonomous lateral ventricle assessment in preclinical hydrocephalus models

IntroductionCurrent workflows for studying hydrocephalus in rodent models rely on manual segmentation or qualitative assessment of ventricular size on small animal magnetic resonance imaging, which are both inefficient and prone to variability. Atlas-based methods enable more streamlined segmentation, but their analysis is limited to morphologically normal samples. ObjectiveThis study aimed to develop and internally validate a deep learning model that performs automated segmentation of lateral ventricles in rodent brain MRIs, allowing for 3D ventricle reconstruction, morphological analysis, and ventriculomegaly detection. MethodsFour U-Net++ neural networks, each with different encoder backbones, were trained using 307 rodent brain MRIs (262 rats, 45 mice), each with manually segmented lateral ventricles serving as the ground truth. Model performance was evaluated using the Dice coefficient, intersection over union (IoU), and Hausdorff index. The most optimal model was evaluated further for its ability to quantify ventricle volume, convexity, surface area, and symmetry. ResultsThe U-Net++ model with an EfficientNet-B1 encoder achieved high accuracy (Dice: 0.823 {+/-} 0.136; IoU: 0.721 {+/-} 0.85). Further assessment of its morphological predictions found strong correlations with manual measurements of ventricular morphology, with Pearson and interclass correlation coefficients exceeding 0.96 across all metrics. The full validated pipeline was packaged into a publicly available application, hosted at https://ava-tar.org. ConclusionThis study introduces a deep learning tool for automated segmentation and morphological analysis of lateral ventricles in rodent MRIs. The tools efficiency and accuracy in quantifying ventricle morphology offers significant utility in preclinical hydrocephalus research with potential future application in the clinical setting.

neuroscience↗

bioRxiv2024

Cilia dysfunction in the lateral ventricles after neonatal intraventricular hemorrhage does not lead to functional changes in cilia-based CSF flow networks

Intraventricular hemorrhage (IVH) has long been thought to lead to motile cilia dysfunction whereby intraventricular blood breakdown products damage and slough cilia from the ependymal wall. However, specifically how IVH may affect cilia development, structure, and transcriptional activation is not well-understood. Moreover, the impact of blood breakdown product-mediated cilia damage on the functional organization of cilia-based CSF flow networks is unknown. Here, we show hemoglobin exposure affects the number of ciliated ependymal cells in the lateral ventricle (LV) but does not impact in vitro beat frequency of the remaining cilia. Ultrastructurally, IVH decreases the total number of ciliary tufts without impacting axoneme structure. IVH does not result in changes in the expression of cilia-related genes and instead leads to downregulation of neurogenesis markers in parallel with innate immune upregulation. Functionally, we identify three previously uncharacterized cilia-mediated CSF flow domains in the LV lateral wall and show that IVH does not result in widespread disruption of their functional organization. These data de-emphasize cilia as a major contributor to global CSF dysfunction after IVH, and instead call attention to preserving the neurodevelopmental environment and preventing runaway innate immune system activation, as considerations to developing treatment strategies to prevent posthemorrhagic hydrocephalus and other neurodevelopmental sequelae.

neuroscience↗

bioRxiv2023

Meningeal CSF transport is primarily mediated by the arachnoid and pia maters during development

BackgroundThe recent characterization of the glymphatic system and meningeal lymphatics has re-emphasized the role of the meninges in facilitating CSF transport and clearance. Here, we characterize small and large CSF solute distribution patterns along the intracranial and surface meninges in neonatal rodents and compare our findings to a rodent model of intraventricular hemorrhage-posthemorrhagic hydrocephalus. We also examine CSF interactions with the tela choroidea and its pial invaginations into the choroid plexuses of the lateral, third, and fourth ventricles. Methods1.9-nm gold nanoparticles, 15-nm gold nanoparticles, or 3 kDa Red Dextran Tetramethylrhodamine constituted in aCSF were infused into the right lateral ventricle of P7 rats to track CSF circulation. 10 minutes post-1.9-nm gold nanoparticle and Red Dextran Tetramethylrhodamine injection and 4 hours post-15-nm gold nanoparticle injection, animals were sacrificed and brains harvested for histologic analysis to identify CSF tracer localization in the cranial and spine meninges and choroid plexus. Spinal dura and leptomeninges (arachnoid and pia) wholemounts were also performed. ResultsThere was significantly less CSF tracer distribution in the dura compared to the arachnoid and pia maters in neonatal rodents. Both small and large CSF tracers were transported intracranially to the arachnoid and pia mater of the perimesencephalic cisterns and tela choroidea, but not the dura mater of the falx cerebri. CSF tracers followed a similar distribution pattern in the spinal meninges. In the choroid plexus, there was large CSF tracer distribution in the apical surface of epithelial cells, and small CSF tracer along the basolateral surface. There were no significant differences in tracer intensity in the intracranial meninges of control vs. intraventricular hemorrhage-posthemorrhagic hydrocephalus (PHH) rodents, indicating preserved meningeal transport in the setting of PHH. ConclusionsDifferential CSF tracer handling by the leptomeninges suggests that there are distinct roles for CSF handling between the arachnoid-pia and dura maters in the developing brain. Similarly, differences in apical vs. luminal choroid plexus CSF handling may provide insight into particle-size dependent CSF transport at the CSF-choroid plexus border.

neuroscience↗