Biology subjects

Weis, V. G.

Publications and source records attributed to Weis, V. G..

5 recordsLinked to original sources

bioRxiv2026

Quantifying the Localization of Histological Staining Markers within the GI Epithelial Unit Axis: A Gastrointestinal Spatial Pathology Plugin for ImageJ

Histological analysis is crucial for understanding gastrointestinal (GI) tract homeostasis and disease pathophysiology. Various histological stains are commonly used in research settings for assessing development, disease pathogenesis, and therapeutic impacts. Specifically in the ordered architecture of the GI epithelium, current semi-quantitative analysis of histological staining relies heavily on manual scoring rubrics and often lacks robust spatial assessment. To address this gap, we developed an open-source ImageJ plugin, building on a closed-source predecessor, aimed at analyzing the spatial localization pattern of user-defined points-of-interest, such as positively stained cells, along the GI epithelial units. The plugin, developed using ImageJ 1.53.0 and Java programming language in Eclipse, interfaces with ImageJ and leverages Java libraries for data processing. The workflow involves uploading a microscopy image of the GI tissue of interest, determining base and top orientation landmarks of the GI epithelial units through manual identification, and annotating point-of-interest coordinates using ImageJ. The output includes centroid coordinates for each point-of-interest, the absolute distances of the points from the base and top landmarks, and the normalized distances of the points relative to the total height of the GI unit. The plugin generates histograms for displaying average point-of-interest distances along the GI unit axis. This information facilitates quantification of total points-of interest counts, analysis of height localization within the GI unit, and determination of average GI unit heights. The plugin serves as a crucial tool for robustly assessing various biological mechanisms within the GI tract, including EdU localization, migration distances, changes in cell type localization, and identification of new expression patterns along the GI unit axis. Overall, this open-source ImageJ plugin provides a semi-automated, user-friendly solution for leveraging important insights into spatial localization of tissue histology expression patterns within the GI structured architecture, with streamlined post-processing pipelines for robust large-scale analysis.

bioengineering↗

bioRxiv2025

Photoacoustic imaging assessment of acute kidney injury associated with experimental necrotizing enterocolitis

BackgroundNecrotizing enterocolitis (NEC) is a devastating gastrointestinal condition increasingly recognized to cause systemic complications, including acute kidney injury (AKI). However, the underlying mechanisms and variations in renal impairment remain largely unknown, and there is a lack of non-invasive imaging methods for detecting early kidney injury. MethodsWe evaluated kidney injury through a multimodal approach, using a neonatal rat model of experimental NEC. Plasma and renal tissue were analyzed for pro-inflammatory cytokines (TNF-, IL-6, IL-1{beta}) by ELISA. Histological analysis and immunofluorescence staining were used to identify renal abnormalities and expressions of KIM-1 and NGAL. Photoacoustic imaging (PAI) was used to assess renal oxygenation and total hemoglobin as functional imaging biomarkers of kidney injury. ResultsNEC pups showed significant elevations of systemic and renal cytokines, as well as increased expression of KIM-1, NGAL and CD31 in proximal tubules of the kidney. Histological examination further confirms renal injury in the NEC cohort. PAI demonstrated reduction in renal oxygen saturation, offering non-invasive assessment of physiological kidney damage. ConclusionThis study characterizes AKI associated with NEC as an inflammatory and hypoxic response in the neonatal rat NEC model and introduces PAI as a promising imaging modality for non-invasive evaluation of renal injury in NEC.

bioengineering↗

bioRxiv2023

Photoacoustic Imaging for Non-Invasive Assessment of Physiological Biomarkers of Intestinal Injury in Experimental Necrotizing Enterocolitis

BackgroundNecrotizing enterocolitis (NEC) is an often-lethal disease of the premature infants intestinal tract that is exacerbated by significant difficulties in early and accurate diagnosis. In NEC disease, the intestine often exhibits hypoperfusion and dysmotility, which contributes to advanced disease pathogenesis. However, these physiological features cannot be accurately and quantitively assessed within the current constraints of imaging modalities frequently used in the clinic (plain film X-ray and ultrasound). We have previously demonstrated the ability of photoacoustic imaging (PAI) to non-invasively and quantitively assess intestinal tissue oxygenation and motility in a healthy neonatal rat model. As a first-in-disease application, we evaluated NEC pathogenesis using PAI to assess intestinal health biomarkers in a preclinical neonatal rat experimental model of NEC. MethodsNEC was induced in neonatal rat pups from birth to 4 days old via hypertonic formula feeding, full-body hypoxic stress, and lipopolysaccharide administration to mimic bacterial colonization. Healthy breastfed (BF) controls and NEC rat pups were imaged at 2- and 4-days old. Intestinal tissue oxygen saturation was measured with PAI imaging for oxy- and deoxyhemoglobin levels. To measure intestinal motility, ultrasound and co-registered PAI cine recordings were used to capture intestinal peristalsis motion and contrast agent (indocyanine green) transit within the intestinal lumen. Additionally, both midplane two-dimensional and volumetric three-dimensional imaging acquisitions were assessed for oxygenation and motility. ResultsNEC pups showed a significant decrease of intestinal tissue oxygenation as compared to healthy BF controls at both ages (2-days old: 55.90% +/-3.77% vs 44.12% +/-7.18%; 4-days old: 56.13% +/-3.52% vs 38.86% +/-8.33%). Intestinal motility, assessed using a computational intestinal deformation analysis, demonstrated a significant reduction in the intestinal motility index in both early (2-day) and established (4-day) NEC. Extensive NEC damage was confirmed with histology and dysmotility was confirmed by small intestinal transit assay. ConclusionsThis study presents PAI as a successful emerging diagnostic imaging modality for both intestinal tissue oxygenation and intestinal motility disease hallmarks in a rat NEC model. PAI presents enormous significance and potential for fundamentally changing current clinical paradigms for detecting and monitoring intestinal pathologies in the premature infant.

bioengineering↗

bioRxiv2023

Photoacoustic Imaging as a Novel Non-Invasive Biomarker to Assess Intestinal Tissue Oxygenation and Motility in Neonatal Rats

BackgroundWithin the premature infant intestine, oxygenation and motility play key physiological roles in healthy development and disease such as necrotizing enterocolitis. To date, there are limited techniques to reliably assess these physiological functions that are also clinically feasible for critically ill infants. To address this clinical need, we hypothesized that photoacoustic imaging (PAI) can provide non-invasive assessment of intestinal tissue oxygenation and motility to characterize intestinal physiology and health. MethodsUltrasound and photoacoustic images were acquired in 2-day and 4-day old neonatal rats. For PAI assessment of intestinal tissue oxygenation, an inspired gas challenge was performed using hypoxic, normoxic, and hyperoxic inspired oxygen (FiO2). For intestinal motility, oral administration of ICG contrast agent was used to compare control animals to an experimental model of loperamide-induced intestinal motility inhibition. ResultsPAI demonstrated progressive increases in oxygen saturation (sO2) as FiO2 increased, while the pattern of oxygen localization remained relatively consistent in both 2-day and 4-day old neonatal rats. Analysis of intraluminal ICG contrast enhanced PAI images yielded a map of the motility index in control and loperamide treated rats. From PAI analysis, loperamide significantly inhibited intestinal motility, with a 32.6% decrease in intestinal motility index scores in 4-day old rats. ConclusionThese data establish the feasibility and application of PAI to non-invasively and quantitatively measure intestinal tissue oxygenation and motility. This proof-of-concept study is an important first step in developing and optimizing photoacoustic imaging to provide valuable insight into intestinal health and disease to improve the care of premature infants. HighlightsO_LIIntestinal tissue oxygenation and intestinal motility are important biomarkers of intestinal physiology in health and disease of premature infants. C_LIO_LIThis proof-of-concept preclinical rat study is the first to report application of photoacoustic imaging for the neonatal intestine. C_LIO_LIPhotoacoustic imaging is demonstrated as a promising non-invasive diagnostic imaging method for quantifying intestinal tissue oxygenation and intestinal motility in premature infants. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=145 HEIGHT=200 SRC="FIGDIR/small/545971v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@585d0forg.highwire.dtl.DTLVardef@145a2bcorg.highwire.dtl.DTLVardef@bf0c46org.highwire.dtl.DTLVardef@bed354_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Human placental-derived stem cell therapy ameliorates experimental necrotizing enterocolitis and supports restoration of the intestinal stem cell niche

Necrotizing enterocolitis (NEC), a life-threatening intestinal disease, is becoming a larger proportionate cause of morbidity and mortality in premature infants. To date, therapeutic options remain elusive. Based on recent cell therapy studies, we investigated the effect of a human placental-derived stem cell (hPSC) therapy on intestinal damage in an experimental NEC rat pup model. NEC was induced in newborn Sprague-Dawley rat pups for 4 days via formula feeding, hypoxia, and LPS. NEC pups received intraperitoneal (ip) injections of either saline or hPSC (NEC-hPSC) at 32 and 56 hours into NEC induction. At 4 days, intestinal macroscopic and histological damage, epithelial cell composition, and inflammatory marker expression of the ileum was assessed. Breastfed (BF) littermates were used as controls. NEC pups developed significant bowel dilation and fragility in the ileum. Further, NEC induced loss of normal villi-crypt morphology, disruption of epithelial proliferation and apoptosis, and loss of Paneth cells and LGR5+ stem cells in the crypt. hPSC treatment improved macroscopic intestinal health with reduced ileal dilation and fragility. Histologically, hPSC administration had a significant reparative effect on the villi-crypt morphology and epithelium. In addition to a trend of decreased inflammatory marker expression, hPSC-NEC pups had increased epithelial proliferation and decreased apoptosis when compared to NEC littermates. Further, the intestinal stem cell niche of Paneth cells and LGR5+ stem cells was increased with hPSC therapy. Together, these data demonstrate hPSC can promote epithelial healing of NEC intestinal damage in part through support of the intestinal stem cell niche. New and NoteworthyThese studies demonstrate a human placental-derived stem cell (hPSC) therapeutic strategy for necrotizing enterocolitis (NEC). In an experimental model of NEC, hPSC administration improved macroscopic intestinal health, ameliorated epithelial morphology, and supported the intestinal stem cell niche. Our data suggest that hPSC are a potential therapeutic approach to attenuate established intestinal NEC damage. Further, we show hPSC are a novel research tool that can now be utilized to elucidate critical neonatal repair mechanisms to overcome NEC disease.

cell biology↗