Computer-aided quantification of retinal neovascularization.
Ontology highlight
ABSTRACT:
SUBMITTER: Stahl A
PROVIDER: S-EPMC4005267 | biostudies-literature | 2009
REPOSITORIES: biostudies-literature
Publications
Computer-aided quantification of retinal neovascularization.
Stahl A A Connor K M KM Sapieha P P Willett K L KL Krah N M NM Dennison R J RJ Chen J J Guerin K I KI Smith L E H LE
Angiogenesis 20090101 3
Rodent models of retinal angiogenesis play a pivotal role in angiogenesis research. These models are a window to developmental angiogenesis, to pathological retinopathy, and are also in vivo tools for anti-angiogenic drug screening in cancer and ophthalmic research. The mouse model of oxygen-induced retinopathy (OIR) has emerged as one of the leading in vivo models for these purposes. Many of the animal studies that laid the foundation for the recent breakthrough of anti-angiogenic treatments in ...[more]
Similar Datasets
Project description:To present a computer-aided detection tool for identifying, quantifying, and evaluating tuberculosis (TB) cavities in the infected lungs from computed tomography (CT) scans.The authors' proposed method is based on a novel shape-based automated detection algorithm on CT scans followed by a fuzzy connectedness (FC) delineation procedure. In order to assess interaction between cavities and airways, the authors first roughly identified air-filled structures (airway, cavities, esophagus, etc.) by thresholding over Hounsfield unit of CT image. Then, airway and cavity structure detection was conducted within the support vector machine classification algorithm. Once airway and cavities were detected automatically, the authors extracted airway tree using a hybrid multiscale approach based on novel affinity relations within the FC framework and segmented cavities using intensity-based FC algorithm. At final step, the authors refined airway structures within the local regions of FC with finer control. Cavity segmentation results were compared to the reference truths provided by expert radiologists and cavity formation was tracked longitudinally from serial CT scans through shape and volume information automatically determined through the authors' proposed system. Morphological evolution of the cavitary TB were analyzed accordingly with this process. Finally, the authors computed the minimum distance between cavity surface and nearby airway structures by using the linear time distance transform algorithm to explore potential role of airways in cavity formation and morphological evolution.The proposed methodology was qualitatively and quantitatively evaluated on pulmonary CT images of rabbits experimentally infected with TB, and multiple markers such as cavity volume, cavity surface area, minimum distance from cavity surface to the nearest bronchial-tree, and longitudinal change of these markers (namely, morphological evolution of cavities) were determined precisely. While accuracy of the authors' cavity detection algorithm was 94.61%, airway detection part of the proposed methodology showed even higher performance by 99.8%. Dice similarity coefficients for cavitary segmentation experiments were found to be approximately 99.0% with respect to the reference truths provided by two expert radiologists (blinded to their evaluations). Moreover, the authors noted that volume derived from the authors' segmentation method was highly correlated with those provided by the expert radiologists (R(2) = 0.99757 and R(2) = 0.99496, p < 0.001, with respect to the observer 1 and observer 2) with an interobserver agreement of 98%. The authors quantitatively confirmed that cavity formation was positioned by the nearby bronchial-tree after exploring the respective spatial positions based on the minimum distance measurement. In terms of efficiency, the core algorithms take less than 2 min on a linux machine with 3.47 GHz CPU and 24 GB memory.The authors presented a fully automatic method for cavitary TB detection, quantification, and evaluation. The performance of every step of the algorithm was qualitatively and quantitatively assessed. With the proposed method, airways and cavities were automatically detected and subsequently delineated in high accuracy with heightened efficiency. Furthermore, not only morphological information of cavities were obtained through the authors' proposed framework, but their spatial relation to airways, and longitudinal analysis was also provided to get further insight on cavity formation in tuberculosis disease. To the authors' best of knowledge, this is the first study in computerized analysis of cavitary tuberculosis from CT scans.
| S-EPMC3815073 | biostudies-other
Project description:Multimaterials deposition, a distinct advantage in bioprinting, overcomes material's limitation in hydrogel-based bioprinting. Multimaterials are deposited in a build/support configuration to improve the structural integrity of three-dimensional bioprinted construct. A combination of rapid cross-linking hydrogel has been chosen for the build/support setup. The bioprinted construct was further chemically cross-linked to ensure a stable construct after print. This paper also proposes a file segmentation and preparation technique to be used in bioprinting for printing freeform structures.
| S-EPMC7294690 | biostudies-literature
Project description:Recent clinical trials using antibodies with low toxicity and high efficiency have raised expectations for the development of next-generation protein therapeutics. However, the process of obtaining therapeutic antibodies remains time consuming and empirical. This review summarizes recent progresses in the field of computer-aided antibody development mainly focusing on antibody modeling, which is divided essentially into two parts: (i) modeling the antigen-binding site, also called the complementarity determining regions (CDRs), and (ii) predicting the relative orientations of the variable heavy (V(H)) and light (V(L)) chains. Among the six CDR loops, the greatest challenge is predicting the conformation of CDR-H3, which is the most important in antigen recognition. Further computational methods could be used in drug development based on crystal structures or homology models, including antibody-antigen dockings and energy calculations with approximate potential functions. These methods should guide experimental studies to improve the affinities and physicochemical properties of antibodies. Finally, several successful examples of in silico structure-based antibody designs are reviewed. We also briefly review structure-based antigen or immunogen design, with application to rational vaccine development.
| S-EPMC3449398 | biostudies-literature
Project description:Ferrochelatase (FECH) is the terminal enzyme in heme biosynthesis. We previously showed that FECH is required for endothelial cell growth in vitro and choroidal neovascularization in vivo. But FECH has not been explored in retinal neovascularization, which underlies diseases like proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the inhibition of FECH using genetic and chemical approaches in the oxygen-induced retinopathy (OIR) mouse model. In OIR mice, FECH expression is upregulated and co-localized with neovascular tufts. Partial loss-of-function Fechm1Pas mutant mice showed reduced retinal neovascularization and endothelial cell proliferation in OIR. An intravitreal injection of the FECH inhibitor N-methyl protoporphyrin had similar effects. Griseofulvin is an antifungal drug that inhibits FECH as an off-target effect. Strikingly, intravitreal griseofulvin decreased both pathological tuft formation and areas of vasoobliteration compared to vehicle, suggesting potential as a FECH-targeting therapy. Ocular toxicity studies revealed that intravitreal injection of griseofulvin in adult mice does not disrupt retinal vasculature, function, or morphology. In sum, mutation and chemical inhibition of Fech reduces retinal neovascularization and promotes physiological angiogenesis, suggesting a dual effect on vascular repair upon FECH inhibition, without ocular toxicity. These findings suggest that FECH inhibitors could be repurposed to treat retinal neovascularization.
| S-EPMC7726024 | biostudies-literature
Project description:The analysis of the pulsation of unruptured intracranial aneurysms might improve the assessment of their stability and risk of rupture. Pulsations can easily be concealed due to the small movements of the aneurysm wall, making post-processing highly demanding. We hypothesized that the quantification of aneurysm pulsation is technically feasible and can be improved by computer-aided post-processing.Images of 14 cerebral aneurysms were acquired with an ECG-triggered 4D CTA. Aneurysms were post-processed manually and computer-aided on a 3D model. Volume curves and random noise-curves were compared with the arterial pulse wave and volume curves were compared between both post-processing modalities.The aneurysm volume curves showed higher similarity with the pulse wave than the random curves (Hausdorff-distances 0.12 vs 0.25, p<0.01). Both post-processing methods did not differ in intra- (r = 0.45 vs r = 0.54, p>0.05) and inter-observer (r = 0.45 vs r = 0.54, p>0.05) reliability. Time needed for segmentation was significantly reduced in the computer-aided group (3.9 ± 1.8 min vs 20.8 ± 7.8 min, p<0.01).Our results show pulsatile changes in a subset of the studied aneurysms with the final prove of underlying volume changes remaining unsettled. Semi-automatic post-processing significantly reduces post-processing time but cannot yet replace manual segmentation.
| S-EPMC5120820 | biostudies-literature
Project description:Virus-cell fusion is the primary means by which the human immunodeficiency virus-1 (HIV) delivers its genetic material into the human T-cell host. Fusion is mediated in large part by the viral glycoprotein 41 (gp41) which advances through four distinct conformational states: (i) native, (ii) pre-hairpin intermediate, (iii) fusion active (fusogenic), and (iv) post-fusion. The pre-hairpin intermediate is a particularly attractive step for therapeutic intervention given that gp41 N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) domains are transiently exposed prior to the formation of a six-helix bundle required for fusion. Most peptide-based inhibitors, including the FDA-approved drug T20, target the intermediate and there are significant efforts to develop small molecule alternatives. Here, we review current approaches to studying interactions of inhibitors with gp41 with an emphasis on atomic-level computer modeling methods including molecular dynamics, free energy analysis, and docking. Atomistic modeling yields a unique level of structural and energetic detail, complementary to experimental approaches, which will be important for the design of improved next generation anti-HIV drugs.
| S-EPMC3666032 | biostudies-literature
Project description:Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation, and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field.
| S-EPMC5857607 | biostudies-literature
Project description:Computer-aided drug design (CADD) approaches are playing an increasingly important role in understanding the fundamentals of ligand-receptor interactions and helping medicinal chemists design therapeutics. About 5 years ago, we presented a chapter devoted to an overview of CADD methods and covered typical CADD protocols including structure-based drug design (SBDD) and ligand-based drug design (LBDD) approaches that were frequently used in the antibiotic drug design process. Advances in computational hardware and algorithms and emerging CADD methods are enhancing the accuracy and ability of CADD in drug design and development. In this chapter, an update to our previous chapter is provided with a focus on new CADD approaches from our laboratory and other peers that can be employed to facilitate the development of antibiotic therapeutics.
| S-EPMC9838881 | biostudies-literature
Project description:Recent data indicates limited awareness and compliance on infection prevention procedures by dental offices and by dental laboratories. Guidelines for infection prevention in dentistry have been published by Centres for Disease Control and Prevention since 2003; the section "IX-Special consideration" includes a subsection concerning the prevention in dental laboratories, but it has not been modernised in later versions to fit the needs of traditional and computer-aided technology. Traditional techniques required disinfecting items (impression, chewing waxes, and appliances) with well-suited products, which are also chosen for limiting impression changes or appliance deterioration. Effective procedures are available with difficulties. Some of these contain irritant or non-eco-friendly disinfectants. The transport of impression, to dental laboratories, is often delayed with limited precautions for limiting cross-infection. Gypsum casts are frequently contaminated mainly by bacteria and their antibiotic-resistant strains and even stored for long periods during dental implant supported restoration and orthodontic therapy, becoming a hidden source of infection. Nowadays, computer-aided design/computer-aided manufacturing technology seems to be an interesting way to promote both business and safety, being more comfortable for patients and more accurate than traditional technology. A further advantage is easier infection prevention since, for the most part, mainly digital impression and casts are not a source of cross-infection and the transport of contaminated items is reduced and limited to try-in stages. Nevertheless, a peculiar feature is that a digital electronic file is of course unalterable, but may be ruined by a computer virus. Additionally, the reconditioning of scanner tips is determinant for the optical characteristics and long term use of the scanner, but information for its reconditioning from producers is often limited. This study focuses on some critical points including (a) insufficient guidelines, (b) choice of proper procedure for scanner reconditioning, and (c) data protection in relation to patient privacy.
| S-EPMC6699473 | biostudies-other
Project description:Control of plant diseases is largely dependent on use of agrochemicals. However, there are widening gaps between our knowledge on plant diseases gained from genetic/mechanistic studies and rapid translation of the knowledge into target-oriented development of effective agrochemicals. Here we propose that the time is ripe for computer-aided drug discovery/design (CADD) in molecular plant pathology. CADD has played a pivotal role in development of medically important molecules over the last three decades. Now, explosive increase in information on genome sequences and three dimensional structures of biological molecules, in combination with advances in computational and informational technologies, opens up exciting possibilities for application of CADD in discovery and development of agrochemicals. In this review, we outline two categories of the drug discovery strategies: structure- and ligand-based CADD, and relevant computational approaches that are being employed in modern drug discovery. In order to help readers to dive into CADD, we explain concepts of homology modelling, molecular docking, virtual screening, and de novo ligand design in structure-based CADD, and pharmacophore modelling, ligand-based virtual screening, quantitative structure activity relationship modelling and de novo ligand design for ligand-based CADD. We also provide the important resources available to carry out CADD. Finally, we present a case study showing how CADD approach can be implemented in reality for identification of potent chemical compounds against the important plant pathogens, Pseudomonas syringae and Colletotrichum gloeosporioides.
| S-EPMC5720600 | biostudies-literature