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Biology subjects

Mahler, S.

Publications and source records attributed to Mahler, S..

6 recordsLinked to original sources

Longitudinal, Non-Invasive Imaging of the Developing Chick Heart, Vasculature, and Chorioallantoic Membrane (CAM)

The chick embryo is a widely used vertebrate model for developmental biology, cardiovascular, and bioengineering research. We present an automated laser speckle contrast imaging (LSCI) platform for non-invasive, longitudinal, label-free imaging of the developing heart and extraembryonic vasculature of the chick embryo through the intact eggshell. The platform can detect blood vessels as small as 70 +/- 17 um in diameter and enable repeated imaging from day 0 to day 8 of incubation without disturbing normal embryonic development. It provides both structural (a map of growing extraembryonic blood vessels) and functional (blood flow dynamics and heart rate) information. Using this system, we generated the first continuous, non-invasive, time-lapse recordings of the early functioning chick heart and its extraembryonic vessels. Longitudinal imaging was performed on 15 embryos from different chicken breeds with eggshell colors white, brown and green. Analysis revealed slight variability in early cardiac and vascular morphogenesis across breeds and shell types and shows its potential for automated developmental staging. Finally, for the first time, the growing vasculature of the yolk sac and the chorioallantoic (CAM) membrane was imaged from day 4 to 8. The heart rate and growth of the extraembryonic blood vessels were quantified automatically during imaging.

developmental biology↗

Noninvasive Laser SCOS Monitoring of Rat Brain Hemodynamics During Intracerebral Injection

Cerebral blood volume (CBV) and blood flow (CBF) constitute key metrics for cerebrovascular monitoring, enabling assessment of stroke severity and risk-prediction, aging-related changes, and neurological diseases. CBF and CBV monitoring are key aspects in diagnosis, treatment triage, and clinical outcome of ischemic and hemorrhagic strokes. In recent years, there have been ongoing efforts toward the development of optical devices for noninvasive monitoring of CBV and CBF. Speckle contrast optical spectroscopy (SCOS) has recently emerged as a strong candidate for clinical translation in monitoring CBF and CBV, due to its affordability, compact and wearable design, and noninvasive nature. However, experimental demonstrations that SCOS can effectively monitor brain hemodynamics remain sparse. This is primarily due to challenges in design experiments that isolate cerebral blood dynamics from those in the scalp and skull. In this paper, we report experiments using SCOS to monitor cerebral hemodynamics in rats during intracerebral blood flow modulation. To modify cerebral blood dynamics, a surgical procedure was performed to insert a catheter for direct injection of flow modulation fluids into the brain. Using the SCOS device, we monitored changes in CBV during deliberate CBF interventions into the brains of five rats. A saline solution was also injected as a sham control of the flow intervention. The results show a significant decrease in CBV during injection, followed by a return to baseline. This behavior is consistent with physiological expectations, as the injected fluids dilute the blood, leading to a transient reduction in blood volume. Notably, the CBV decrease induced by the flow modulation fluid solution required more than twice as long to recover to baseline compared with the saline solution, which is consistent with the delayed clearance of the flow modulation fluid by design. These experimental results demonstrate the effectiveness of SCOS for monitoring cerebral hemodynamics in animal models and highlight its potential for translation to human studies. Moreover, this work paves the way for the testing and characterization of cerebral therapeutic agents intended for blood flow modulation in animal models.

biophysics↗

Exploring non-invasive sexing of early chick embryos in intact eggs using Laser Speckle Contrast Imaging (LSCI) and Deep Neural Network (DNN)

The ability to image blood flow in early-stage avian embryos has significant applications in developmental biology, drug and vaccine testing, as well as determining sex differentiation. In this project, we used our recently developed laser speckle contrast imaging (LSCI) system to non-invasively image extraembryonic blood vessels and used these images to attempt early sex identification of chick embryos. Specifically, we captured images of blood vessels from 1,251 living chicken embryos between day three and day four of incubation. We then applied deep neural network (DNN) models to evaluate whether it is possible to differentiate sex based on vascular patterns. Using ResNetBiT and YOLOv5 models, our results indicate that sex differentiation from extraembryonic blood vessel images was not achievable with sufficiently high accuracy or statistical significance for practical use. Specifically, ResNetBiT had a five-fold cross-validated average accuracy of 59%{+/-}5% (fold-wise p-value, p [≤] 0.3) at day 3 and 61%{+/-}3% (fold-wise, p [≤] 0.04) at day 4. YOLOv5 had a five-fold cross-validated average accuracy of 55%{+/-}3% (fold-wise, p [≤] 0.3) at day 3 and 53%{+/-}3% (fold-wise, p [≤] 0.5) at day 4. Our findings suggest that using vascular pattern imaging alone is inconclusive for reliable early sex identification in chicken embryos.

bioengineering↗

Automated non-invasive laser speckle imaging of the chick heart rate and extraembryonic blood vessels and their response to nifedipine and amlodipine drugs

Using our recently developed laser speckle contrast imaging (LSCI) to visualize blood vessels and monitor blood flow, here we test the utility of the chick embryo for drug screening. To this end, we examined the effects of antihypertensive agents Nifedipine and Amlodipine, belonging to the L-type calcium channel antagonist family, on blood flow visualized noninvasively through the intact shell. Guided by the live view mode, the drugs were injected through the shell and ventral to HH16-19 chick embryos. Our results show a significant reduction in the chick heart rate, blood flow, and vascular size within 5-20 minutes after Nifedipine or Amlodipine injection. For moderate Nifedipine concentrations, these parameters returned to initial values within 2-3 hours. In contrast, Amlodipine showed a rapid reduction in heart rate and blood flow dynamics at a more than ten times higher concentration than Nifedipine. These findings show that our LSCI system can monitor and distinguish the chick hearts response to injected drugs from the same family. This serves as proof-of-concept, paving the way for a rapid, cost effective, and quantitative test system for screening drugs that affect the cardiovascular system of live chick embryos. Live noninvasive imaging may also provide insights into the development and functioning of the vertebrate heart. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/609812v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@c22831org.highwire.dtl.DTLVardef@dcab67org.highwire.dtl.DTLVardef@1792bf3org.highwire.dtl.DTLVardef@346fb0_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LINon-invasive Laser Speckle Contrast Imaging (LSCI) of the chick chorioallantoic membrane (CAM) in whole incubated eggs C_LIO_LISimultaneous recording images of the CAM, dynamics of blood flow, and heart rate C_LIO_LILive view mode to identify size, heart position, and location of the embryo in the egg C_LIO_LIAutomated system for data acquisition and analysis C_LIO_LILongitudinal quantification of the impact of a calcium channel antagonists, nifedipidine and amlodipine on the embryonic heart rate, CAMs blood flow, size and number of vessels C_LI

bioengineering↗

Non-invasive laser speckle imaging of extra-embryonic blood vessels in intact few-days-old avian eggs

Imaging blood vessels in early-stage avian embryos has a wide range of practical applications for developmental biology studies, drug and vaccine testing, and early sex determination. Optical imaging such as brightfield transmission imaging offers a compelling solution due to its safe non-ionizing radiation, and operational benefits. However, it comes with challenges such as eggshell opacity and light scattering. To address these, we have revisited an approach based on laser speckle contrast imaging (LSCI) and demonstrated a high quality, comprehensive and non-invasive visualization of blood vessels in few-days-old chicken eggs, with blood vessel as small as 100 {micro}m in diameter (with LSCI profile full-width-at-half-maximum of 275 {micro}m). We present its non-invasive use for monitoring blood flow, measuring the embryos heartbeat, and determining the embryos developmental stages using machine learning with 85% accuracy from stage HH15 to HH22. This method can potentially be used for non-invasive longitudinal studies of cardiovascular development and angiogenesis, as well as egg screening for the poultry industry.

bioengineering↗

Automatic structural analysis of bioinspired percolating network materials using graph theory

Mimicking numerous biological membranes and nanofiber-based tissues, there are multiple materials that are structured as percolating nanoscale networks (PPNs). They reveal unique combination of properties and the family of PNN-based composites and nanoporous materials is rapidly expanding. Their technological significance and the necessity of their structural design require a unifying approach for their structural description. However, their complex aperiodic architectures are difficult to describe using traditional methods that are tailored for crystals. A related problem is the lack of computational tools that enable one to capture and enumerate the patterns of stochastically branching fibrils that are typical for these composites. Here, we describe a conceptual methodology and a computational package, StructuralGT, to automatically produce a graph theoretical (GT) description of PNNs from various micrographs. Using nanoscale networks formed by aramid nanofibers (ANFs) as examples, we demonstrate structural analysis of PNNs with 13 GT parameters. Unlike qualitative assessments of physical features employed previously, StructuralGT allows quantitative description of the complex structural attributes of PNNs enumerating the networks morphology, connectivity, and transfer patterns. Accurate conversion and analysis of micrographs is possible for various levels of noise, contrast, focus, and magnification while a dedicated graphical user interface provides accessibility and clarity. The GT parameters are expected to be correlated to material properties of PNNs (e.g. ion transport, conductivity, stiffness) and utilized by machine learning tools for effectual materials design. Table of Content O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/438877v1_ufig1.gif" ALT="Figure 1"> View larger version (144K): org.highwire.dtl.DTLVardef@1c929f0org.highwire.dtl.DTLVardef@1e07168org.highwire.dtl.DTLVardef@357e7aorg.highwire.dtl.DTLVardef@28d21_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗