Autonomous precision resuscitation during ground and air transport of an animal hemorrhagic shock model.

We tested the ability of a physiologically driven minimally invasive closed-loop algorithm, called Resuscitation based on Functional Hemodynamic Monitoring (ReFit), to stabilize for up to 3 h a porcine model of noncompressible hemorrhage induced by severe liver injury and do so during both ground and air transport. Twelve animals were resuscitated using ReFit to drive fluid and vasopressor infusion to a mean arterial pressure (MAP) > 60 mmHg and heart rate < 110 min 30 min after MAP < 40 mmHg following liver injury. ReFit was initially validated in 8 animals in the laboratory, then in 4 animals during air (23nm and 35nm) and ground (9 mi) to air (9.

Altered Gene Expression Within the Renin-Angiotensin System in Normal Aging and Dementia.

The renin-angiotensin system (RAS) is dysregulated in Alzheimer's disease (AD). In this study, we have explored the hypothesis that an -age--related imbalance in brain RAS is a trigger for RAS dysregulation in AD. We characterized RAS gene expression in the frontal cortex from (i) a cohort of normal aging (n = 99, age range = 19-96 years) and (ii) a case-control cohort (n = 209) including AD (n = 66), mixed dementia (VaD + AD; n = 50), pure vascular dementia (VaD; n = 42), and age-matched controls (n = 51).

Elevated late-life blood pressure may maintain brain oxygenation and slow amyloid-β accumulation at the expense of cerebral vascular damage.

Hypertension in midlife contributes to cognitive decline and is a modifiable risk factor for dementia. The relationship between late-life hypertension and dementia is less clear. We have investigated the relationship of blood pressure and hypertensive status during late life (after 65 years) to post-mortem markers of Alzheimer's disease (amyloid-β and tau loads); arteriolosclerosis and cerebral amyloid angiopathy; and to biochemical measures of ante-mortem cerebral oxygenation (the myelin-associated glycoprotein:proteolipid protein-1 ratio, which is reduced in chronically hypoperfused brain tissue, and the level of vascular endothelial growth factor-A, which is upregulated by tissue hypoxia); blood-brain barrier damage (indicated by an increase in parenchymal fibrinogen); and pericyte content (platelet-derived growth factor receptor β, which declines with pericyte loss), in Alzheimer's disease ( = 75), vascular ( = 20) and mixed dementia ( = 31) cohorts.

Age-related reduction in brain ACE-2 is not exacerbated by Alzheimer's disease pathology in mouse models of Alzheimer's disease.

An imbalance in the circulatory and organ-specific renin-angiotensin system (RAS) pathways is associated with age-related dysfunction and disease including cardiovascular burden and more recently Alzheimer's disease (AD). It is currently unclear whether an age-associated imbalance in components of the RAS within the brain precedes the onset of AD or whether a RAS imbalance is associated with the onset of disease pathology and cognitive decline. Angiotensin-converting enzyme-1 (ACE-1) and -2 (ACE-2) protein (ELISA) and enzyme activity (FRET assay), markers of the classical and counter-regulatory RAS axis respectively, and Ang-II and Ang-(1-7) peptide levels (ELISA), were measured in the left cortex across four transgenic AD mouse models of amyloid pathology (5xFAD - 2, 6, and 12 months of age; Apd9 - 3-4, 12, and 18 months of age; Tg2576 - 3-4 and 24 months of age; and PDAPP - 3-4, 7, 11, 15, and 18 months of age) and littermate wild-type (WT) controls.

Dysregulation of ACE-1 in Normal Aging and the Early Stages of Alzheimer's Disease.

An imbalance in the renin-angiotensin system (RAS) is associated with cognitive decline and disease pathology in Alzheimer's disease (AD). In this study, we have investigated changes in the brain angiotensin-converting enzyme-1 (ACE-1) and angiotensin-II (Ang-II), and the counter-regulatory angiotensin-converting enzyme-2 (ACE-2), in the frontal and temporal cortex during normal aging and in the early stages of AD. We studied a cohort of normal aging (n = 121; 19-95 years age-at-death) from the Sudden Death Brain Bank, University of Edinburgh, United Kingdom, and AD and age-matched controls (n = 60) from the South West Dementia Brain Bank, University of Bristol, United Kingdom, stratified according to Braak tangle stage (BS): 0-II, III-IV (intermediate disease), and V-VI (end-stage disease).

Real-time vessel segmentation and reconstruction for virtual fixtures for an active handheld microneurosurgical instrument.

Purpose: Complications related to vascular damage such as intra-operative bleeding may be avoided during neurosurgical procedures such as petroclival meningioma surgery. To address this and improve the patient's safety, we designed a real-time blood vessel avoidance strategy that enables operation on deformable tissue during petroclival meningioma surgery using Micron, a handheld surgical robotic tool.

Methods: We integrated real-time intra-operative blood vessel segmentation of brain vasculature using deep learning, with a 3D reconstruction algorithm to obtain the vessel point cloud in real time.

Variability in Reassessment of Left Ventricular Ejection Fraction After Myocardial Infarction in the Acute Myocardial Infarction Quality Assurance Canada Study.

Importance: Persistently depressed left ventricular ejection fraction (LVEF) after myocardial infarction (MI) is associated with adverse prognosis and directs the use of evidence-based treatments to prevent sudden cardiac death and/or progressive heart failure.

Objective: To assess adherence with guideline-recommended LVEF reassessment and to study the evolution of LVEF over 6 months of follow-up.

Design, Setting, And Participants: This was a multicenter cohort study at Canadian academic and community hospitals with on-site cardiac catheterization services.

Monocular Vision-Based Retinal Membrane Peeling With a Handheld Robot.

Retinal membrane peeling requires delicate manipulation. The presence of the surgeon's physiological tremor, the high variability and often low quality of the ophthalmic image, and excessive forces make the tasks more challenging. Preventing unintended movement caused by tremor and unintentional forces can reduce membrane injury.

Multirate Kalman Filter Rejects Impulse Noise in Frequency-Domain-Multiplexed Tracker Measurements.

Frequency domain multiplexing (FDM) is a useful for making multiple measurements simultaneously, such as in optical and electromagnetic position trackers. Much interference is periodic (e.g.

Toward Monocular Camera-Guided Retinal Vein Cannulation with an Actively Stabilized Handheld Robot.

In this paper we describe work towards retinal vessel cannulation using an actively stabilized handheld robot, guided by monocular vision. We employ a previously developed monocular camera based surface reconstruction method using automated laser beam scanning over the retina. We use the reconstructed plane to find a coordinate transform between the 2D image plane coordinate system and the global 3D frame.

Electromagnetic Tracker for Active Handheld Robotic Systems.

We describe the development of the In-Loop Electromagnetic Tracker (ILEMT), designed to meet the demanding latency and resolution requirements for active stabilization of hand motion during precision manipulations such as microsurgery. The prototype surpasses the fastest commercial EM trackers by > 4× in root bandwidth/resolution and 2× in latency. The use of two widely spaced carrier frequencies (e.

Comparative Evaluation of Handheld Robot-Aided Intraocular Laser Surgery.

This paper presents robot-aided intraocular laser surgery using a handheld robot known as Micron. The micromanipulator incorporated in Micron enables visual servoing of a laser probe, while maintaining a constant distance of the tool tip from the retinal surface. The comparative study was conducted with various control methods for evaluation of robot-aided intraocular laser surgery.

Hybrid position/force control of an active handheld micromanipulator for membrane peeling.

Background: Peeling procedures in retinal surgery require micron-scale manipulation and control of sub-tactile forces.

Methods: Hybrid position/force control of an actuated handheld microsurgical instrument is presented as a means for simultaneously improving positioning accuracy and reducing forces to prevent avoidable trauma to tissue. The system response was evaluated, and membrane-peeling trials were performed by four test subjects in both artificial and animal models.

Toward Automated Intraocular Laser Surgery Using a Handheld Micromanipulator.

This paper presents a technique for automated intraocular laser surgery using a handheld micromanipulator known as Micron. The novel handheld manipulator enables the automated scanning of a laser probe within a cylinder of 4 mm long and 4 mm in diameter. For the automation, the surface of the retina is reconstructed using a stereomicroscope, and then preplanned targets are placed on the surface.

Manipulator Design and Operation for a Six-Degree-of-Freedom Handheld Tremor-Canceling Microsurgical Instrument.

This paper presents the design and actuation of a six-degree-of-freedom (6-DOF) manipulator for a handheld instrument, known as "Micron," which performs active tremor compensation during microsurgery. The design incorporates a Gough-Stewart platform based on piezoelectric linear motor, with a specified minimum workspace of a cylinder 4 mm long and 4 mm in diameter at the end-effector. Given the stall force of the motors and the loading typically encountered in vitreoretinal microsurgery, the dimensions of the manipulator are optimized to tolerate a transverse load of 0.

Toward Hybrid Position/Force Control for an Active Handheld Micromanipulator.

Vitreoretinal microsurgery requires precise hand-eye coordination to manipulate delicate structures within the eye on the order of tens of microns. To achieve these tasks, surgeons use tools of diameter 0.9 mm or less to access the eye's interior structures.

Vision-Based Control of a Handheld Surgical Micromanipulator with Virtual Fixtures.

Performing micromanipulation and delicate operations in submillimeter workspaces is difficult because of destabilizing tremor and imprecise targeting. Accurate micromanipulation is especially important for microsurgical procedures, such as vitreoretinal surgery, to maximize successful outcomes and minimize collateral damage. Robotic aid combined with filtering techniques that suppress tremor frequency bands increases performance; however, if knowledge of the operator's goals is available, virtual fixtures have been shown to further improve performance.

Improvement of optical coherence tomography using active handheld micromanipulator in vitreoretinal surgery.

An active handheld micromanipulator has been developed to cancel hand tremor during microsurgery. The micromanipulator is also applicable in optical coherence tomography to improve the quality of scanning and minimize surgical risks during the scans. The manipulator can maneuver the tool tip with six degrees of freedom within a cylindrical workspace 4 mm in diameter and 4 mm high.

Performance of a 6-degree-of-freedom active microsurgical manipulator in handheld tasks.

This paper presents the first experimental results from human users of a new 6-degree-of-freedom handheld micromanipulator. This is the latest prototype of a fully-handheld system, known as "Micron," which performs active compensation of hand tremor for microsurgery. The manipulator is a miniature Gough-Stewart platform incorporating linear ultrasonic motors that provide a cylindrical workspace 4 mm long and 4 mm wide.

Optical coherence tomography scanning with a handheld vitreoretinal micromanipulator.

An active handheld micromanipulator has been developed that is capable of automated intraocular acquisition of B-mode and C-mode optical coherence tomography scans that are up to 4 mm wide. The manipulator is a handheld Gough-Stewart platform actuated by ultrasonic linear motors. The manipulator has been equipped with a Fourier-domain common-path intraocular OCT probe that fits within a 25-gauge needle.

Comparison of Baseline Tremor Under Various Microsurgical Conditions.

This paper presents the characterization and comparison of physiological tremor for pointing tasks in multiple environments, as a baseline for performance evaluation of microsurgical robotics. Previous studies have examined the characteristics of physiological tremor under laboratory settings as well as different operating conditions. However, different test methods make the comparison of results across trials and conditions difficult.

Position-Based Virtual Fixtures for Membrane Peeling with a Handheld Micromanipulator.

Peeling delicate retinal membranes, which are often less than 5 µm thick, is one of the most challenging retinal surgeries. Preventing rips and tears caused by tremor and excessive force can decrease injury and reduce the need for follow up surgeries. We propose the use of a fully handheld microsurgical robot to suppress tremor while enforcing helpful constraints on the motion of the tool.

Towards Vision-Based Control of a Handheld Micromanipulator for Retinal Cannulation in an Eyeball Phantom.

Injecting clot-busting drugs such as t-PA into tiny vessels thinner than a human hair in the eye is a challenging procedure, especially since the vessels lie directly on top of the delicate and easily damaged retina. Various robotic aids have been proposed with the goal of increasing safety by removing tremor and increasing precision with motion scaling. We have developed a fully handheld micromanipulator, Micron, that has demonstrated reduced tremor when cannulating porcine retinal veins in an "open sky" scenario.

Design and Analysis of 6 DOF Handheld Micromanipulator.

This paper presents the design and analysis of a handheld manipulator for vitreoretinal microsurgery and other biomedical applications. The design involves a parallel micromanipulator utilizing six piezoelectric linear actuators, combining compactness with a large range of motion and relatively high stiffness. Given the available force of the actuators, the overall dimension of the micromanipulator was optimized considering realistic external loads on a remote center of motion representing the point of expected contact with the sclera of the eye during microsurgery.