Accurate Neonatal Face Detection for Improved Pain Classification in the Challenging NICU Setting.

There is a tendency for object detection systems using off-the-shelf algorithms to fail when deployed in complex scenes. The present work describes a case for detecting facial expression in post-surgical neonates (newborns) as a modality for predicting and classifying severe pain in the Neonatal Intensive Care Unit (NICU). Our initial testing showed that both an off-the-shelf face detector and a machine learning algorithm trained on adult faces failed to detect facial expression of neonates in the NICU.

A novel deep learning-based method for automatic stereology of microglia cells from low magnification images.

Microglial cells mediate diverse homeostatic, inflammatory, and immune processes during normal development and in response to cytotoxic challenges. During these functional activities, microglial cells undergo distinct numerical and morphological changes in different tissue volumes in both rodent and human brains. However, it remains unclear how these cytostructural changes in microglia correlate with region-specific neurochemical functions.

Novel stereological method for estimation of cell counts in 3D collagen scaffolds.

Current methods for assessing cell proliferation in 3D scaffolds rely on changes in metabolic activity or total DNA, however, direct quantification of cell number in 3D scaffolds remains a challenge. To address this issue, we developed an unbiased stereology approach that uses systematic-random sampling and thin focal-plane optical sectioning of the scaffolds followed by estimation of total cell number (StereoCount). This approach was validated against an indirect method for measuring the total DNA (DNA content); and the Bürker counting chamber, the current reference method for quantifying cell number.

Attentional Generative Multimodal Network for Neonatal Postoperative Pain Estimation.

Artificial Intelligence (AI)-based methods allow for automatic assessment of pain intensity based on continuous monitoring and processing of subtle changes in sensory signals, including facial expression, body movements, and crying frequency. Currently, there is a large and growing need for expanding current AI-based approaches to the assessment of postoperative pain in the neonatal intensive care unit (NICU). In contrast to acute procedural pain in the clinic, the NICU has neonates emerging from postoperative sedation, usually intubated, and with variable energy reserves for manifesting forceful pain responses.

A Review of Nuclei Detection and Segmentation on Microscopy Images Using Deep Learning With Applications to Unbiased Stereology Counting.

The detection and segmentation of stained cells and nuclei are essential prerequisites for subsequent quantitative research for many diseases. Recently, deep learning has shown strong performance in many computer vision problems, including solutions for medical image analysis. Furthermore, accurate stereological quantification of microscopic structures in stained tissue sections plays a critical role in understanding human diseases and developing safe and effective treatments.

A disector-based framework for the automatic optical fractionator.

Stereology-based methods provide the current state-of-the-art approaches for accurate quantification of numbers and other morphometric parameters of biological objects in stained tissue sections. The advent of artificial intelligence (AI)-based deep learning (DL) offers the possibility of improving throughput by automating the collection of stereology data. We have recently shown that DL can effectively achieve comparable accuracy to manual stereology but with higher repeatability, improved throughput, and less variation due to human factors by quantifying the total number of immunostained cells at their maximal profile of focus in extended depth of field (EDF) images.

Future roles of artificial intelligence in early pain management of newborns.

The advent of increasingly sophisticated medical technology, surgical interventions, and supportive healthcare measures is raising survival probabilities for babies born premature and/or with life-threatening health conditions. In the United States, this trend is associated with greater numbers of neonatal surgeries and higher admission rates into neonatal intensive care units (NICU) for newborns at all birth weights. Following surgery, current pain management in NICU relies primarily on narcotics (opioids) such as morphine and fentanyl (about 100 times more potent than morphine) that lead to a number of complications, including prolonged stays in NICU for opioid withdrawal.

Stereological Changes in Microvascular Parameters in Hippocampus of a Transgenic Rat Model of Alzheimer's Disease.

Background: Microcirculatory factors play an important role in amyloid-β (Aβ)-related neuropathology in Alzheimer's disease (AD). Transgenic (Tg) rat models of mutant Aβ deposition can enhance our understanding of this microvascular pathology.

Objective: Here we report stereology-based quantification and comparisons (between- and within-group) of microvessel length and number and associated parameters in hippocampal subregions in Tg model of AD in Fischer 344 rats and non-Tg littermates.

An adaptive digital stain separation method for deep learning-based automatic cell profile counts.

Background: Quantifying cells in a defined region of biological tissue is critical for many clinical and preclinical studies, especially in the fields of pathology, toxicology, cancer and behavior. As part of a program to develop accurate, precise and more efficient automatic approaches for quantifying morphometric changes in biological tissue, we have shown that both deep learning-based and hand-crafted algorithms can estimate the total number of histologically stained cells at their maximal profile of focus in Extended Depth of Field (EDF) images. Deep learning-based approaches show accuracy comparable to manual counts on EDF images but significant enhancement in reproducibility, throughput efficiency and reduced error from human factors.

Low doses of Bisphenol S affect post-translational modifications of sperm proteins in male mice.

Background: Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A in the manufacture of products containing polycarbonates and epoxy resins. However, further studies of BPS exposure are needed for the assessment of health risks to humans. In this study we assessed the potential harmfulness of low-dose BPS on reproduction in male mice.

Age-Related Decrease in Tyrosine Hydroxylase Immunoreactivity in the Substantia Nigra and Region-Specific Changes in Microglia Morphology in HIV-1 Tg Rats.

Animal models have been used to study cellular processes related to human immunodeficiency virus-1 (HIV-1)-associated neurocognitive disorders (HAND). The HIV-1 transgenic (Tg) rat expresses HIV viral genes except the gag-pol replication genes and exhibits neuropathological features similar to HIV patients receiving combined antiretroviral therapy (cART). Using this rat, alterations in dopaminergic function have been demonstrated; however, the data for neuroinflammation and glial reactivity is conflicting.

No Evidence of Neurogenesis in Adult Rat Sympathetic Ganglia Following Guanethidine-Induced Neuronal Loss.

The potential for neurogenesis in the cranial (superior) cervical ganglia (SCG) of the sympathetic nervous system was evaluated. Eleven consecutive daily doses of guanethidine (100 mg/kg/d) were administered intraperitoneally to rats in order to destroy postganglionic sympathetic neurons in SCG. Following the last dose, animals were allowed to recover 1, 3, or 6 months.

Reduced Hippocampal Dendrite Branching, Spine Density and Neurocognitive Function in Premature Rabbits, and Reversal with Estrogen or TrkB Agonist Treatment.

Preterm-born children suffer from neurological and behavioral disorders. Herein, we hypothesized that premature birth and non-maternal care of preterm newborns might disrupt neurobehavioral function, hippocampal dendritic arborization, and dendritic spine density. Additionally, we assessed whether 17β-estradiol (E2) replacement or the TrkB receptor agonist, 7,8-dihydroxyflavone (DHF), would reverse compromised dendritic development and cognitive function in preterm newborns.

Automatic ground truth for deep learning stereology of immunostained neurons and microglia in mouse neocortex.

Collection of unbiased stereology data currently relies on relatively simple, low throughput technology developed in the mid-1990s. In an effort to improve the accuracy and efficiency of these integrated hardware-software-digital microscopy systems, we have developed an automatic segmentation algorithm (ASA) for automatic stereology counts using the unbiased optical fractionator method. Here we report on a series of validation experiments in which immunostained neurons (NeuN) and microglia (Iba1) were automatically counted in tissue sections through a mouse neocortex.

Automatic stereology of mean nuclear size of neurons using an active contour framework.

The use of unbiased stereology to quantify structural parameters such as mean cell and nuclear size (area and volume) can be useful for a wide variety of biological studies. Here we propose a novel segmentation framework using an Active Contour Model to automate the collection of stereology from stained cells and other objects in tissue sections. This approach is demonstrated for stained brain sections from young adult Fischer 344 rats.

Automated Cell Counts on Tissue Sections by Deep Learning and Unbiased Stereology.

In recent decades stereology-based studies have played a significant role in understanding brain aging and developing novel drug discovery strategies for treatment of neurological disease and mental illness. A major obstacle to further progress in a wide range of neuroscience sub-disciplines remains the lack of high-throughput technology for stereology analyses. Though founded on methodologically unbiased principles, commercially available stereology systems still rely on well-trained humans to manually count hundreds of cells within each region of interest (ROI).

A framework for nucleus and overlapping cytoplasm segmentation in cervical cytology extended depth of field and volume images.

We propose a framework to detect and segment nuclei and segment overlapping cytoplasm in cervical cytology images. This is a challenging task due to folded cervical cells with spurious edges, poor contrast of cytoplasm and presence of neutrophils and artifacts. The algorithm segments nuclei and cell clumps in extended depth of field (EDF) images and uses volume images to segment overlapping cytoplasm.

Anti-NGF monoclonal antibody muMab 911 does not deplete neurons in the superior cervical ganglia of young or old adult rats.

Nerve growth factor (NGF) blocking therapies are an emerging and effective approach to pain management. However, concerns about the potential for adverse effects on the structure and function of the peripheral nervous system have slowed their development. Early studies using NGF antisera in adult rats reported effects on the size and number of neurons in the sympathetic chain ganglia.

Developmental neurotoxicity of 3,3',4,4'-tetrachloroazobenzene with thyroxine deficit: Sensitivity of glia and dentate granule neurons in the absence of behavioral changes.

Thyroid hormones (TH) regulate biological processes implicated in neurodevelopmental disorders and can be altered with environmental exposures. Developmental exposure to the dioxin-like compound, 3,3',4,4'-tetrachloroazobenzene (TCAB), induced a dose response deficit in serum T4 levels with no change in 3,5,3'- triiodothyronine or thyroid stimulating hormone. Female Sprague-Dawley rats were orally gavaged (corn oil, 0.

A post-mortem stereological study of striatal cell number in human obesity.

Objective: Neuroimaging studies have revealed abnormalities in brain structure, including the striatum, in obese people. In this study, the cellular and parenchymal basis for these findings in post-mortem brain tissue was investigated.

Methods: Design-based (unbiased) stereology combined with histochemical and immunocytochemical staining was used to quantify total number of neurons and astrocytes in post-mortem striatal brain samples from nine obese (BMI 40.

Patches of disorganization in the neocortex of children with autism.

Background: Autism involves early brain overgrowth and dysfunction, which is most strongly evident in the prefrontal cortex. As assessed on pathological analysis, an excess of neurons in the prefrontal cortex among children with autism signals a disturbance in prenatal development and may be concomitant with abnormal cell type and laminar development.

Methods: To systematically examine neocortical architecture during the early years after the onset of autism, we used RNA in situ hybridization with a panel of layer- and cell-type-specific molecular markers to phenotype cortical microstructure.