Pressure measurement in gas flows using laser-induced grating lifetime.

Optical diagnostics of gas-phase pressure are relatively unusual. In this work, we demonstrate a novel, rapid, and robust method to use laser-induced grating scattering (LIGS) to derive this property in real time. Previous pressure measurements with LIGS have employed a signal fitting method, but this is relatively time-consuming and requires specialist understanding. In this paper, we directly measure a decay lifetime from a LIGS signal and then employ a calibration surface constructed using a physics-based model to convert this value to pressure. This method was applied to an optically accessible single-cylinder internal combustion engine, yielding an accuracy of better than 10% at all tested conditions above atmospheric pressure. This new approach complements the existing strength of LIGS in precisely and accurately deriving temperature with a simple analysis method, by adding pressure information with a similarly simple method.

Flame thermometry using laser-induced-grating spectroscopy of nitric oxide.

A systematic study of laser-induced thermal-grating scattering (LITGS) using nitric oxide as an absorbing species is presented as a means of thermometry in air-fed combustion. The relative contributions to the scattered signal from degenerate four-wave mixing, DFWM, and from laser-induced thermal-grating scattering, LITGS, are studied in the time domain for NO in N2 buffer gas up to 4 bar, using a pulsed laser system to excite the (0,0) γ-bands of NO at 226.21 nm. LITGS signals from combustion-generated NO in a laminar, pre-mixed CH4/O2/N2 flame on an in-house constructed slot burner were used to derive temperature values as a function of O2 concentration and position in the flame at 1 and 2.5 bar total pressure. Temperature values consistent with the calculated adiabatic flame temperature were derived from averaged LITGS signals over 50-100 single shots at 10 Hz repetition rate in the range 1600-2400 K with a pressure-dependent uncertainty of ± 1.8% at 1 bar to ± 1.4% at 2.5 bar. Based on observed signal-to-noise ratios, the minimum detectable concentration of NO in the flame is estimated to be 80 ppm for a 5 s measurement time at 10 Hz repetition rate.

Carotid Ultrasound Maximum Plaque Height-A Sensitive Imaging Biomarker for the Assessment of Significant Coronary Artery Disease.

OBJECTIVES: We investigated the use of carotid intima-media thickness and carotid plaque in predicting significant angiographic coronary stenosis. METHODS: Three hundred eighteen consecutive outpatients underwent angiography and carotid ultrasound on the same day. The extent of coronary stenosis was determined using an established scoring system. Mean far distal carotid intima-media thickness of the common carotid artery, maximum plaque height, and total plaque area in the bulbs were measured by ultrasound. Cutoff values were identified using a receiver operating characteristic curve for predicting and ruling out coronary artery disease. RESULTS: The mean ± SD carotid intima-media thickness (≥50% stenosis = 0.91 ± 0.23 mm, <50% stenosis = 0.82 ± 0.18 mm), maximum plaque height (≥50% stenosis = 2.64 ± 0.85 mm, <50% stenosis = 1.72 ± 1.04 mm), and total plaque area (≥50% stenosis = 39.1 ± 27.7 mm(2) , <50% stenosis = 22.2 ± 23.4 mm(2) ) were significantly higher in patients with coronary artery disease (P ≤ 0.001 for all three comparisons). Increased CIMT, plaque height, and area correlated with increased number of affected vessels. Plaque height had the best negative likelihood ratio for ruling out disease (0.15). The optimal threshold values for predicting coronary disease were 0.82 mm for carotid intima-media thickness, 1.54 mm for plaque height, and 25.6 mm(2) for total plaque area. CONCLUSION: Increased carotid intima-media thickness and plaque measurements are indicative of the presence of epicardial coronary stenosis. Plaque burden is a more sensitive imaging biomarker for ruling out significant coronary artery disease, including in younger individuals.

Simultaneous voltage and calcium mapping of genetically purified human induced pluripotent stem cell-derived cardiac myocyte monolayers.

RATIONALE: Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer a powerful in vitro tool to investigate disease mechanisms and to perform patient-specific drug screening. To date, electrophysiological analysis of iPSC-CMs has been limited to single-cell recordings or low-resolution microelectrode array mapping of small cardiomyocyte aggregates. New methods of generating and optically mapping impulse propagation of large human iPSC-CM cardiac monolayers are needed. OBJECTIVE: Our first aim was to develop an imaging platform with versatility for multiparameter electrophysiological mapping of cardiac preparations, including human iPSC-CM monolayers. Our second aim was to create large electrically coupled human iPSC-CM monolayers for simultaneous action potential and calcium wave propagation measurements. METHODS AND RESULTS: A fluorescence imaging platform based on electronically controlled light-emitting diode illumination, a multiband emission filter, and single camera sensor was developed and utilized to monitor simultaneously action potential and intracellular calcium wave propagation in cardiac preparations. Multiple, large-diameter (≥1 cm), electrically coupled human cardiac monolayers were then generated that propagated action potentials and calcium waves at velocities similar to those commonly observed in rodent cardiac monolayers. CONCLUSIONS: The multiparametric imaging system presented here offers a scalable enabling technology to measure simultaneously action potential and intracellular calcium wave amplitude and dynamics of cardiac monolayers. The advent of large-scale production of human iPSC-CMs makes it possible to now generate sufficient numbers of uniform cardiac monolayers that can be utilized for the study of arrhythmia mechanisms and offers advantages over commonly used rodent models.

Simultaneous measurement and modulation of multiple physiological parameters in the isolated heart using optical techniques.

Whole-heart multi-parametric optical mapping has provided valuable insight into the interplay of electrophysiological parameters, and this technology will continue to thrive as dyes are improved and technical solutions for imaging become simpler and cheaper. Here, we show the advantage of using improved 2nd-generation voltage dyes, provide a simple solution to panoramic multi-parametric mapping, and illustrate the application of flash photolysis of caged compounds for studies in the whole heart. For proof of principle, we used the isolated rat whole-heart model. After characterising the blue and green isosbestic points of di-4-ANBDQBS and di-4-ANBDQPQ, respectively, two voltage and calcium mapping systems are described. With two newly custom-made multi-band optical filters, (1) di-4-ANBDQBS and fluo-4 and (2) di-4-ANBDQPQ and rhod-2 mapping are demonstrated. Furthermore, we demonstrate three-parameter mapping using di-4-ANBDQPQ, rhod-2 and NADH. Using off-the-shelf optics and the di-4-ANBDQPQ and rhod-2 combination, we demonstrate panoramic multi-parametric mapping, affording a 360° spatiotemporal record of activity. Finally, local optical perturbation of calcium dynamics in the whole heart is demonstrated using the caged compound, o-nitrophenyl ethylene glycol tetraacetic acid (NP-EGTA), with an ultraviolet light-emitting diode (LED). Calcium maps (heart loaded with di-4-ANBDQPQ and rhod-2) demonstrate successful NP-EGTA loading and local flash photolysis. All imaging systems were built using only a single camera. In conclusion, using novel 2nd-generation voltage dyes, we developed scalable techniques for multi-parametric optical mapping of the whole heart from one point of view and panoramically. In addition to these parameter imaging approaches, we show that it is possible to use caged compounds and ultraviolet LEDs to locally perturb electrophysiological parameters in the whole heart.

Cardiac electrophysiological imaging systems scalable for high-throughput drug testing.

Multi-parametric electrophysiological measurements using optical methods have become a highly valued standard in cardiac research. Most published optical mapping systems are expensive and complex. Although some applications demand high-cost components and complex designs, many can be tackled with simpler solutions. Here, we describe (1) a camera-based voltage and calcium imaging system using a single 'economy' electron-multiplying charge-coupled device camera and demonstrate the possibility of using a consumer camera for imaging calcium transients of the heart, and (2) a photodiode-based voltage and calcium high temporal resolution measurement system using single-element photodiodes and an optical fibre. High-throughput drug testing represents an application where system scalability is particularly attractive. Therefore, we tested our systems on tissue exposed to a well-characterized and clinically relevant calcium channel blocker, nifedipine, which has been used to treat angina and hypertension. As experimental models, we used the Langendorff-perfused whole-heart and thin ventricular tissue slices, a preparation gaining renewed interest by the cardiac research community. Using our simplified systems, we were able to monitor simultaneously the marked changes in the voltage and calcium transients that are responsible for the negative inotropic effect of the compound.

Maximum plaque height in carotid ultrasound predicts cardiovascular disease outcomes: a population-based validation study of the American society of echocardiography's grade II-III plaque characterization and protocol.

The presence of carotid arterial plaque by ultrasound enhances cardiovascular risk stratification beyond traditional risk factors. However, plaque quantification techniques require further outcomes-based investigation. The purpose of this study was to evaluate the utility of a focused carotid ultrasound protocol and novel plaque grading system developed by the American Society of Echocardiography (ASE). A retrospective analysis of 514 outpatients who were referred for coronary angiography between 2011 and 2014 was performed using a province-sponsored health database. All participants prospectively received a focused carotid ultrasound. Maximum plaque height (MPH) of arterial carotid plaque was quantified, using the Grade II-III plaque definition of MPH ≥ 1.5 mm for stratification, according to recent ASE recommendations. Participants were followed for 1.33-5.11 years (average follow-up = 3.60 ± 1.65 years) to identify the occurrence of cardiovascular events. Major events (death, myocardial infarction [MI], stroke, and transient ischemic attack [TIA]) were correlated to MPH. Participants with MPH ≥ 1.5 mm were more likely to experience stable angina, coronary artery bypass grafting, and stress testing at both 1-year and total follow-up. After adjusting for cardiac risk factors, increased MPH was shown to be predictive for TIA (odds ratio [OR] = 1.33, 95% confidence interval (CI) = 1.01-1.75); p = 0.04), whereas the odds of non-ST-elevation MI (OR = 1.55, 95% CI = 0.99-2.43; p = 0.06) approached significance. Using Kaplan-Meier survival analysis, MPH ≥ 1.5 mm demonstrated good separation for the composite outcome of death, MI, stroke, and TIA over total follow-up (p = 0.02). This rapid, office-based quantification of MPH in carotid ultrasound may serve as a stratification tool for predicting major cardiovascular events.

Presence of Calcium-Like Tissue Composition in Carotid Plaque is Indicative of Significant Coronary Artery Disease in High-Risk Patients.

BACKGROUND: Grayscale pixel ranges from ultrasound images, indicating differences in atherosclerotic plaque echogenicity, have been shown to represent different tissue types. Our objective was to determine whether carotid plaque composition was correlated with severity of coronary artery disease (CAD) and risk of cardiovascular (CV) events. METHODS: A focused carotid ultrasound was performed in 522 participants who had recently undergone coronary angiography. In 468 participants found to have atherosclerotic plaque in at least one carotid artery, plaque composition was assessed for tissue-like types: grayscale ranges 0-4 (blood), 8-26 (fat), 41-76 (muscle), 112-196 (fibrous), and 211-255 (calcium). Logistic regression was used to evaluate correlations with significant CAD (≥50% stenosis). Cox proportional hazards models were used to determine risk for 5-year CV outcomes. RESULTS: Carotid plaque percent fibrous and percent calcium increased with severity of CAD (P < .02). When adjusted for age, sex, body mass index, estimated glomerular filtration rate, and traditional cardiac risk factors, maximum plaque height and percent calcium remained independent contributors of significant CAD (P < .01). Plaque height (≥2.74 mm), percent calcium (≥0.11%), and percent fat (11.6%) were associated with increased risk for CV events. Combined plaque height and percent fat gave the highest risk for events (risk ratio = 2.02; CI, 1.41-2.94, P = .0002). CONCLUSIONS: Carotid plaque fibrous and calcium-like tissues are correlated with increased CAD. Increased percent fat or percent calcium is associated with risk for CV events; however, a combination of plaque height, percent calcium, and/or percent fat increases risk for CV events. Incorporating ultrasound carotid plaque composition into screening practice may improve patient risk stratification for heart disease.

Infra-red multi-mode absorption spectroscopy of acetylene using an Er/Yb:glass micro-laser.

Multi-mode absorption spectroscopy, MUMAS, in the near-infra-red is reported for the first time. A diode laser pumped Er/Yb:glass micro-cavity laser emitting multiple longitudinal modes at 1.53 microm was used to detect several transitions in the nu(1)+nu(3) overtone band of C2H2.

Relationship between carotid artery atherosclerosis and bulb geometry.

The carotid bifurcation is a common site of atherosclerotic plaque. Plaque development is thought to occur preferentially at geometrically predisposed areas such as arterial branch points. The aim of this study was to investigate the geometric and anatomical variables that contribute to the development of carotid plaque using three-dimensional (3D) ultrasound. Sixty-seven consecutive outpatients referred for elective coronary angiography underwent 3D carotid ultrasound scans for the purpose of carotid plaque quantification. Geometric quantification of the left and right carotid bulbs were performed retrospectively on this study population. Geometric values such as angle, area and length of the carotid bulb and the bifurcation were determined using QLAB software (Philips Healthcare). Plaque volume within the carotid bulb and artery branches was quantified using the stacked contour method. Pearson's correlation and linear regression analysis were used to determine the relationship between anatomical variables and plaque volume. The mean age for the total patient population was 65.9 ± 11.5 years. Carotid bulb inflow area (BIA) (r = 0.28, p = 0.001), bulb volume (BV) (r = 0.21, p = 0.01) and bifurcation angle (BifA) (r = 0.18, p = 0.04) showed a positive linear relationship with plaque volume. In contrast, internal carotid artery angle (ICAA) (r = - 0.18, p = 0.04) and bulb flare (r = - 0.20, p = 0.02) displayed a negative linear relationship with plaque volume. When adjusting for age and sex, only the BIA remained significant (ß = 0.18, p = 0.04). Geometric variables were identified as potential risk factors associated with plaque volume in the carotid bulb. Further analysis of the evolution of the BIA as well as the relationship to other geometric variables could create a stronger predictive model of atherosclerosis as well as assist in preoperative planning.

Photo-induced optical activity in phase-change memory materials.

We demonstrate that optical activity in amorphous isotropic thin films of pure Ge2Sb2Te5 and N-doped Ge2Sb2Te5N phase-change memory materials can be induced using rapid photo crystallisation with circularly polarised laser light. The new anisotropic phase transition has been confirmed by circular dichroism measurements. This opens up the possibility of controlled induction of optical activity at the nanosecond time scale for exploitation in a new generation of high-density optical memory, fast chiroptical switches and chiral metamaterials.

In situ optical mapping of voltage and calcium in the heart.

Electroanatomic mapping the interrelation of intracardiac electrical activation with anatomic locations has become an important tool for clinical assessment of complex arrhythmias. Optical mapping of cardiac electrophysiology combines high spatiotemporal resolution of anatomy and physiological function with fast and simultaneous data acquisition. If applied to the clinical setting, this could improve both diagnostic potential and therapeutic efficacy of clinical arrhythmia interventions. The aim of this study was to explore this utility in vivo using a rat model. To this aim, we present a single-camera imaging and multiple light-emitting-diode illumination system that reduces economic and technical implementation hurdles to cardiac optical mapping. Combined with a red-shifted calcium dye and a new near-infrared voltage-sensitive dye, both suitable for use in blood-perfused tissue, we demonstrate the feasibility of in vivo multi-parametric imaging of the mammalian heart. Our approach combines recording of electrophysiologically-relevant parameters with observation of structural substrates and is adaptable, in principle, to trans-catheter percutaneous approaches.

Simultaneous single-shot measurement of temperature and pressure along a one-dimensional line by use of laser-induced thermal grating spectroscopy.

We report a new technique, based on laser-induced thermal grating spectroscopy (LITGS), for time- and space-resolved simultaneous measurement of temperature and pressure along a one-dimensional line. LITGS signals generated in NO2/N2 mixtures along a 5 mm line produce a time-varying image that is recorded on a streak camera. The temperature is derived with a precision of 0.3% from the streak images using a rapid Fourier method with a spatial resolution of 150 microm along the line. The principle of pressure measurement is demonstrated using a sequence of images, and a simple extension of the method to single-shot pressure measurement is discussed.