Light-Scattering Technique for the Study of Dynamic Thickness Fluctuations in Thin Liquid Films

The authors describe a light-scattering technique capable of probing the dynamics of thickness fluctuations in lipid bilayers. The technique, which they call reflectance fluctuation spectroscopy (RFS), is keenly sensitive to light scattered from the squeeze modes of motion in a thin liquid film, and insensitive to light scattered from the bend modes. A laser beam is focused to a small spot on the film, and the power in the specularly reflected beam is recorded in real time. Thickness fluctuations associated with the squeeze modes of motion give rise to fluctuations in the power of the specularly reflected light. The frequency spectrum of the fluctuations in detected power (RFS spectrum) can be analyzed to yield values for the film viscosity and thickness compressibility. The authors present two independent theoretical derivations of the RFS spectrum and show that scattering from the bend mode can be neglected. The theoretical expression for the RFS spectrum is compared with experimental spectra obtained from glycerylmonooleate-decane bilayers. The fit of the theory to the data is excellent and the values deduced for the film viscosity and thickness compressibility are reasonable

Improved Phase Modulation for an En-face Scanning Three-dimensional Optical Coherence Microscope

We have previously described an inexpensive method for modulating the interferometer of an en-face scanning, focus-tracking, three-dimensional optical coherence microscope (OCM). In this OCM design, a reference mirror is mounted on a piezoelectric stack driven at a resonance frequency of about 100 kHz. We perform a partial discrete Fourier transform of the digitally sampled output fringe signal. In the original design, we obtained the amplitude of the backscattered light by summing the powers in the fundamental (1ω) and first harmonic (2ω) of the modulation frequency. We used the particular piezoamplitude that eliminates the effects of interferometer phase drift. However, as the reference mirror was stepped to scan at different sample depths, variations in the back-coupled reference power added noise to the fringe signal at the fundamental piezodriving frequency. We report here a technique to eliminate the effects of this piezowobble by using instead the sum of the 2ω and 3ω powers as a measure of the backscattered light intensity. Images acquired before and after this improvement are presented to illustrate the enhancement to image quality deep within the sample

An optical coherence microscope for 3-dimensional imaging in developmental biology

An optical coherence microscope (OCM) has been designed and constructed to acquire 3-dimensional images of highly scattering biological tissue. Volume-rendering software is used to enhance 3-D visualization of the data sets. Lateral resolution of the OCM is 5 mm (FWHM), and the depth resolution is 10 mm (FWHM) in tissue. The design trade-offs for a 3-D OCM are discussed, and the fundamental photon noise limitation is measured and compared with theory. A rotating 3-D image of a frog embryo is presented to illustrate the capabilities of the instrument

Python for Information Theoretic Analysis of Neural Data

Information theory, the mathematical theory of communication in the presence of noise, is playing an increasingly important role in modern quantitative neuroscience. It makes it possible to treat neural systems as stochastic communication channels and gain valuable, quantitative insights into their sensory coding function. These techniques provide results on how neurons encode stimuli in a way which is independent of any specific assumptions on which part of the neuronal response is signal and which is noise, and they can be usefully applied even to highly non-linear systems where traditional techniques fail. In this article, we describe our work and experiences using Python for information theoretic analysis. We outline some of the algorithmic, statistical and numerical challenges in the computation of information theoretic quantities from neural data. In particular, we consider the problems arising from limited sampling bias and from calculation of maximum entropy distributions in the presence of constraints representing the effects of different orders of interaction in the system. We explain how and why using Python has allowed us to significantly improve the speed and domain of applicability of the information theoretic algorithms, allowing analysis of data sets characterized by larger numbers of variables. We also discuss how our use of Python is facilitating integration with collaborative databases and centralised computational resources

Phase Modulation at 125 kHz in a Michelson Interferometer Using an Inexpensive Piezoelectric Stack Driven at Resonance

Fast phase modulation has been achieved in a Michelson interferometer by attaching a lightweight reference mirror to a piezoelectric stack and driving the stack at a resonance frequency of about 125 kHz. The electrical behavior of the piezo stack and the mechanical properties of the piezo-mirror arrangement are described. A displacement amplitude at resonance of about 350 nm was achieved using a standard function generator. Phase drift in the interferometer and piezo wobble were readily circumvented. This approach to phase modulation is less expensive by a factor of roughly 50 than one based on an electro-optic effect

Role of Beat Noise in Limiting the Sensitivity of Optical Coherence Tomography

The sensitivity and dynamic range of optical coherence tomography (OCT) are calculated for instruments utilizing two common interferometer configurations and detection schemes. Previous researchers recognized that the performance of dual-balanced OCT instruments is severely limited by beat noise, which is generated by incoherent light backscattered from the sample. However, beat noise has been ignored in previous calculations of Michelson OCT performance. Our measurements of instrument noise confirm the presence of beat noise even in a simple Michelson interferometer configuration with a single photodetector. Including this noise, we calculate the dynamic range as a function of OCT light source power, and find that instruments employing balanced interferometers and balanced detectors can achieve a sensitivity up to six times greater than those based on a simple Michelson interferometer, thereby boosting image acquisition speed by the same factor for equal image quality. However, this advantage of balanced systems is degraded for source powers greater than a few milliwatts. We trace the concept of beat noise back to an earlier paper [J. Opt. Soc. Am. 52, 1335 (1962)]

Motion-Sensitive 3-D Optical Coherence Microscope Operating at 1300 nm for the Visualization of Early Frog Development

We present 3-dimensional volume-rendered in vivo images of developing embryos of the African clawed frog Xenopus laevis taken with our new en-face-scanning, focus-tracking OCM system at 1300 nm wavelength. Compared to our older instrument which operates at 850 nm, we measure a decrease in the attenuation coefficient by 33%, leading to a substantial improvement in depth penetration. Both instruments have motion-sensitivity capability. By evaluating the fast Fourier transform of the fringe signal, we can produce simultaneously images displaying the fringe amplitude of the backscattered light and images showing the random Brownian motion of the scatterers. We present time-lapse movies of frog gastrulation, an early event during vertebrate embryonic development in which cell movements result in the formation of three distinct layers that later give rise to the major organ systems. We show that the motion-sensitive images reveal features of the different tissue types that are not discernible in the fringe amplitude images. In particular, we observe strong diffusive motion in the vegetal (bottom) part of the frog embryo which we attribute to the Brownian motion of the yolk platelets in the endoderm

A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve.

AimsThe mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.Materials and resultsRandomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041).ConclusionsIn this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects.Trial registrationclinicaltrials.gov Identifier: NCT01342029