AI-Based Chest CT Analysis for Rapid COVID-19 Diagnosis and Prognosis: A Practical Tool to Flag High-Risk Patients and Lower Healthcare Costs

peer reviewedEarly diagnosis of COVID-19 is required to provide the best treatment to our patients, to prevent the epidemic from spreading in the community, and to reduce costs associated with the aggravation of the disease. We developed a decision tree model to evaluate the impact of using an artificial intelligence-based chest computed tomography (CT) analysis software (icolung, icometrix) to analyze CT scans for the detection and prognosis of COVID-19 cases. The model compared routine practice where patients receiving a chest CT scan were not screened for COVID-19, with a scenario where icolung was introduced to enable COVID-19 diagnosis. The primary outcome was to evaluate the impact of icolung on the transmission of COVID-19 infection, and the secondary outcome was the in-hospital length of stay. Using EUR 20000 as a willingness-to-pay threshold, icolung is cost-effective in reducing the risk of transmission, with a low prevalence of COVID-19 infections. Concerning the hospitalization cost, icolung is cost-effective at a higher value of COVID-19 prevalence and risk of hospitalization. This model provides a framework for the evaluation of AI-based tools for the early detection of COVID-19 cases. It allows for making decisions regarding their implementation in routine practice, considering both costs and effects

Cellular and molecular neuropathology of the cuprizone mouse model : clinical relevance for multiple sclerosis

AbstractThe cuprizone mouse model allows the investigation of the complex molecular mechanisms behind nonautoimmune-mediated demyelination and spontaneous remyelination. While it is generally accepted that oligodendrocytes are specifically vulnerable to cuprizone intoxication due to their high metabolic demands, a comprehensive overview of the etiology of cuprizone-induced pathology is still missing to date. In this review we extensively describe the physico-chemical mode of action of cuprizone and discuss the molecular and enzymatic mechanisms by which cuprizone induces metabolic stress, oligodendrocyte apoptosis, myelin degeneration and eventually axonal and neuronal pathology. In addition, we describe the dual effector function of the immune system which tightly controls demyelination by effective induction of oligodendrocyte apoptosis, but in contrast also paves the way for fast and efficient remyelination by the secretion of neurotrophic factors and the clearance of cellular and myelinic debris. Finally, we discuss the many clinical symptoms that can be observed following cuprizone treatment, and how these strengthened the cuprizone model as a useful tool to study human multiple sclerosis, schizophrenia and epilepsy

Are subventricular zone endogenous neural stem cells responsible for the remyelination of the corpus callosum in the Cuprizone mouse model? An in-vivo bioluminescence and magnetic resonance imaging study

Guglielmetti C., Praet J., Vreys R., Rangarajan J.R., Maes F., Verhoye M., Ponsaerts P., Van der Linden A., ''Are subventricular zone endogenous neural stem cells responsible for the remyelination of the corpus callosum in the Cuprizone mouse model? An in-vivo bioluminescence and magnetic resonance imaging study'', World molecular imaging congress - WMIC 2012, September 5-8, 2012, Dublin, Ireland.status: publishe

Multimodal imaging of subventricular zone neural stem/progenitor cells in the cuprizone mouse model reveals increased neurogenic potential for the olfactory bulb pathway, but no contribution to remyelination of the corpus callosum

Multiple sclerosis is a devastating demyelinating disease of the central nervous system (CNS) in which endogenous remyelination, and thus recovery, often fails. Although the cuprizone mouse model allowed elucidation of many molecular factors governing remyelination, currently very little is known about the spatial origin of the oligodendrocyte progenitor cells that initiate remyelination in this model. Therefore, we here investigated in this model whether subventricular zone (SVZ) neural stem/progenitor cells (NSPCs) contribute to remyelination of the splenium following cuprizone-induced demyelination. Experimentally, from the day of in situ NSPC labeling, C57BL/6J mice were fed a 0.2% cuprizone diet during a 4-week period and then left to recover on a normal diet for 8weeks. Two in situ labeling strategies were employed: (i) NSPCs were labeled by intraventricular injection of micron-sized iron oxide particles and then followed up longitudinally by means of magnetic resonance imaging (MRI), and (ii) SVZ NSPCs were transduced with a lentiviral vector encoding the eGFP and Luciferase reporter proteins for longitudinal monitoring by means of in vivo bioluminescence imaging (BLI). In contrast to preceding suggestions, no migration of SVZ NSPC towards the demyelinated splenium was observed using both MRI and BLI, and further validated by histological analysis, thereby demonstrating that SVZ NSPCs are unable to contribute directly to remyelination of the splenium in the cuprizone model. Interestingly, using longitudinal BLI analysis and confirmed by histological analysis, an increased migration of SVZ NSPC-derived neuroblasts towards the olfactory bulb was observed following cuprizone treatment, indicative for a potential link between CNS inflammation and increased neurogenesis.Guglielmetti C., Praet J., Rangarajan J.R., Vreys R., De Vocht N., Maes F., Verhoye M., Ponsaerts P., Van der Linden A., ''Multimodal imaging of subventricular zone neural stem/progenitor cells in the cuprizone mouse model reveals increased neurogenic potential for the olfactory bulb pathway, but no contribution to remyelination of the corpus callosum'', NeuroImage, vol. 86, no. 1, pp. 99-110, February 2014.status: publishe

Antiinflammatory Properties of a Plant-Derived Nonsteroidal, Dissociated Glucocorticoid Receptor Modulator in Experimental Autoimmune Encephalomyelitis

Compound A (CpdA), a plant-derived phenyl aziridine precursor, was recently characterized as a fully dissociated nonsteroidal antiinflammatory agent, acting via activation of the glucocorticoid receptor, thereby down-modulating nuclear factor- B-mediated transactivation, but not supporting glucocorticoid response element-driven gene expression. The present study demonstrates the effectiveness of CpdA in inhibiting the disease progress in experimental autoimmune encephalomyelitis (EAE), a well-characterized animal model of multiple sclerosis. CpdA treatment of mice, both early and at the peak of the disease, markedly suppressed the clinical symptoms of EAE induced by myelin oligodendrocyte glycoprotein peptide immunization. Attenuation of the clinical symptoms of EAE by CpdA was accompanied by reduced leukocyte infiltration in the spinal cord, reduced expression of inflammatory cytokines and chemokines, and reduced neuronal damage and demyelination. In vivo CpdA therapy suppressed the encephalogenicity of myelin oligodendrocyte glycoprotein peptide-specific T cells. Moreover, CpdA was able to inhibit TNF- and lipopolysaccharide-induced nuclear factor- B activation in primary microglial cells in vitro, in a differential mechanistic manner as compared with dexamethasone. Finally, in EAE mice the therapeutic effect of CpdA, in contrast to that of dexamethasone, occurred in the absence of hyperinsulinemia and in the absence of a suppressive effect on the hypothalamic-pituitary-adrenal axis. Based on these results, we propose CpdA as a compound with promising antiinflammatory characteristics useful for therapeutic intervention in multiple sclerosis and other neuroinflammatory diseases

Multimodal imaging of subventricular zone neural stem/progenitor cells in the cuprizone mouse model reveals increased neurogenic potential for the olfactory bulb pathway, but no contribution to remyelination of the corpus callosum

AbstractMultiple sclerosis is a devastating demyelinating disease of the central nervous system (CNS) in which endogenous remyelination, and thus recovery, often fails. Although the cuprizone mouse model allowed elucidation of many molecular factors governing remyelination, currently very little is known about the spatial origin of the oligodendrocyte progenitor cells that initiate remyelination in this model. Therefore, we here investigated in this model whether subventricular zone (SVZ) neural stem/progenitor cells (NSPCs) contribute to remyelination of the splenium following cuprizone-induced demyelination. Experimentally, from the day of in situ NSPC labeling, C57BL/6J mice were fed a 0.2% cuprizone diet during a 4-week period and then left to recover on a normal diet for 8weeks. Two in situ labeling strategies were employed: (i) NSPCs were labeled by intraventricular injection of micron-sized iron oxide particles and then followed up longitudinally by means of magnetic resonance imaging (MRI), and (ii) SVZ NSPCs were transduced with a lentiviral vector encoding the eGFP and Luciferase reporter proteins for longitudinal monitoring by means of in vivo bioluminescence imaging (BLI). In contrast to preceding suggestions, no migration of SVZ NSPC towards the demyelinated splenium was observed using both MRI and BLI, and further validated by histological analysis, thereby demonstrating that SVZ NSPCs are unable to contribute directly to remyelination of the splenium in the cuprizone model. Interestingly, using longitudinal BLI analysis and confirmed by histological analysis, an increased migration of SVZ NSPC-derived neuroblasts towards the olfactory bulb was observed following cuprizone treatment, indicative for a potential link between CNS inflammation and increased neurogenesis