Interactive effects of vascular risk burden and advanced age on cerebral blood flow.

Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to increased risk of cognitive impairment and Alzheimer's disease (AD); however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs) previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors), advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor). This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines

User-centered visual analysis using a hybrid reasoning architecture for intensive care units

One problem pertaining to Intensive Care Unit information systems is that, in some cases, a very dense display of data can result. To ensure the overview and readability of the increasing volumes of data, some special features are required (e.g., data prioritization, clustering, and selection mechanisms) with the application of analytical methods (e.g., temporal data abstraction, principal component analysis, and detection of events). This paper addresses the problem of improving the integration of the visual and analytical methods applied to medical monitoring systems. We present a knowledge- and machine learning-based approach to support the knowledge discovery process with appropriate analytical and visual methods. Its potential benefit to the development of user interfaces for intelligent monitors that can assist with the detection and explanation of new, potentially threatening medical events. The proposed hybrid reasoning architecture provides an interactive graphical user interface to adjust the parameters of the analytical methods based on the users' task at hand. The action sequences performed on the graphical user interface by the user are consolidated in a dynamic knowledge base with specific hybrid reasoning that integrates symbolic and connectionist approaches. These sequences of expert knowledge acquisition can be very efficient for making easier knowledge emergence during a similar experience and positively impact the monitoring of critical situations. The provided graphical user interface incorporating a user-centered visual analysis is exploited to facilitate the natural and effective representation of clinical information for patient care

Optical Coherence Tomography Angiography Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

PurposeThe purpose of this study was to compare retinal nerve fiber layer (RNFL) thickness and optical coherence tomography angiography (OCT-A) retinal vasculature measurements in healthy, glaucoma suspect, and glaucoma patients.MethodsTwo hundred sixty-one eyes of 164 healthy, glaucoma suspect, and open-angle glaucoma (OAG) participants from the Diagnostic Innovations in Glaucoma Study with good quality OCT-A images were included. Retinal vasculature information was summarized as a vessel density map and as vessel density (%), which is the proportion of flowing vessel area over the total area evaluated. Two vessel density measurements extracted from the RNFL were analyzed: (1) circumpapillary vessel density (cpVD) measured in a 750-μm-wide elliptical annulus around the disc and (2) whole image vessel density (wiVD) measured over the entire image. Areas under the receiver operating characteristic curves (AUROC) were used to evaluate diagnostic accuracy.ResultsAge-adjusted mean vessel density was significantly lower in OAG eyes compared with glaucoma suspects and healthy eyes. (cpVD: 55.1 ± 7%, 60.3 ± 5%, and 64.2 ± 3%, respectively; P < 0.001; and wiVD: 46.2 ± 6%, 51.3 ± 5%, and 56.6 ± 3%, respectively; P < 0.001). For differentiating between glaucoma and healthy eyes, the age-adjusted AUROC was highest for wiVD (0.94), followed by RNFL thickness (0.92) and cpVD (0.83). The AUROCs for differentiating between healthy and glaucoma suspect eyes were highest for wiVD (0.70), followed by cpVD (0.65) and RNFL thickness (0.65).ConclusionsOptical coherence tomography angiography vessel density had similar diagnostic accuracy to RNFL thickness measurements for differentiating between healthy and glaucoma eyes. These results suggest that OCT-A measurements reflect damage to tissues relevant to the pathophysiology of OAG

Extracorporeal membrane oxygenation simulation-based training: methods, drawbacks and a novel solution

Introduction: Patients under the error-prone and complication-burdened extracorporeal membrane oxygenation (ECMO) are looked after by a highly trained, multidisciplinary team. Simulation-based training (SBT) affords ECMO centers the opportunity to equip practitioners with the technical dexterity required to manage emergencies. The aim of this article is to review ECMO SBT activities and technology followed by a novel solution to current challenges. ECMO simulation: The commonly-used simulation approach is easy-to-build as it requires a functioning ECMO machine and an altered circuit. Complications are simulated through manual circuit manipulations. However, scenario diversity is limited and often lacks physiological and/or mechanical authenticity. It is also expensive to continuously operate due to the consumption of highly specialized equipment. Technological aid: Commercial extensions can be added to enable remote control and to automate circuit manipulation, but do not improve on the realism or cost-effectiveness. A modular ECMO simulator: To address those drawbacks, we are developing a standalone modular ECMO simulator that employs affordable technology for high-fidelity simulation.Peer reviewe

Effects of Blood Pressure and Intraocular Pressure on Ocular Arterial Blood Flow: Studies on in vitro Models

Placed in 1st Place in the category of Cell Biology and Physiology, Denman ForumGlaucoma is the second leading cause of blindness around the world. Diagnosis of this disease often occurs after the detection of noticeable symptoms, by which point irreversible damage has already been incurred. Glaucoma develops when stress factors induce retinal ganglion cell death, resulting in vision loss. In particular, prolonged reduction in blood flow into the eye may lead to ocular tissue malnutrition and hypoxia, eventually leading to cell death. The posterior ciliary arteries are the main blood supply to the optic nerve head, where glaucoma damages occur first. These arteries traverse the posterior peripapillary sclera to penetrate the eye. This study aims to investigate the effects that different combinations of intraocular pressure, blood pressure, and scleral stiffness have on blood flow of in vitro posterior ciliary artery models. To perform this study, a modeling system of the peripapillary sclera was developed. A number of different polymers (including agarose, polydimethylsiloxane, and industrial TC-5005 gels) were explored to model scleral tissues with various compressive moduli. Multiple models of industrial TC-5005 and agarose were made to mimic sclera of increasing stiffness. The polymers were molded and cured into wall-less vessels and placed into a perfusion chamber where pressure was separately applied to the outside (intraocular) and inside (blood) the vessel at different combinations. Five models of stiffness ranging from 30 – 415 kPa were fabricated for flow tests. The resulting change in fluid flow rate was recorded to determine the combinatory effects of the two pressures through these phantoms. It was found that across all combinations of pressures, the fluid flow would initially increase with stiffness, then upon reaching ~60 kPa achieve a maximum flow. For models much stiffer than 60 kPa, a significant decrease in fluid flow as much as 87% was observed. The initial increase in fluid flow from 30 to 60 kPa may be evidence of the protective effects of scleral stiffening predicted in previous research. This study represents a first step in understanding the potential impacts of the scleral compressive modulus on the fluid flow rate under biological effects by IOP and BP, supporting the hypothesis that sclera stiffness may play an important role in glaucomatous development.Research is partially supported by NIHRO1EY020929A one-year embargo was granted for this item.Academic Major: Biomedical Engineerin

Dose escalation of desmoteplase for acute ischemic stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset

<p><b>Background and Purpose:</b> Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke.</p> <p><b>Methods:</b> DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 μg/kg and 125 μg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined.</p> <p><b>Results:</b> Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 μg/kg: n=14; 125 μg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 μg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 μg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 μg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 μg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 μg/kg desmoteplase (P=0.022).</p> <p><b>Conclusions:</b> Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 μg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).</p&gt

Changes in Pulmonary Arterial Wall Mechanical Properties and Lumenal Architecture with Induced Vascular Remodeling

To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling