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A comparison of digital and analog methods of Doppler spectral analysis for quantifying flow.

Ultrasonic methods can be used for calculating flow when the mean Doppler frequency is representative of spatial average velocity. We have examined the capabilities of two commercially available methods of Doppler spectral analysis for providing measurements of spatial average velocity and flow. In a steady state flow model, Doppler audio spectra were recorded using a 5-MHz duplex scanner. Fast Fourier transform (FFT) spectral analysis was used to determine mean (M), mode (MO), and maximum (MAX) frequencies. An analog method (offset zero crossing detector = ZC) was used to determine root mean square (RMS) frequencies. The results of comparing Doppler flow estimates (QM, QMO, QMAX and QRMS) with direct flow measurements (n = 10; range = 128-1098 ml/min) were (1) QM = 0.67Q + 23 ml/min (SEE = 36 ml/min); (2) QMO = 0.96Q + 152 ml/min (SEE = 32 ml/min); (3) QMAX = 1.19Q + 171 ml/min (SEE = 23 ml/min); and (4) QRMS = 0.93Q + 76ml/min (SEE = 92 ml/min). Estimates of flow using M and RMS frequencies were adversely affected by experimental conditions likely to result in turbulence. We conclude that application of commercially available FFT determined M frequencies could result in significant errors in calculations of spatial average velocity and flow. Alternatively, FFT determined MO frequencies and ZC determined RMS frequencies resulted in accurate estimates of flow in this model. This study demonstrates the importance of evaluating the capabilities of commercially available methods of Doppler spectral analysis when using ultrasound for determining velocity and flow.

Blood Flow Velocity↗

A computer algorithm to impute interrupted heart rate data for the spectral analysis of heart rate variability--the ARIC study.

The shorter term beat-to-beat heart rate data collected from the general population are often interrupted by artifacts, and an arbitrary exclusion of such individuals from analysis may significantly reduce the sample size and/or introduce selection bias. A computer algorithm was developed to label as artifacts any data points outside the upper and lower limits generated by a 5-beat moving average +/- 25% (or set manually by an operator using a mouse) and to impute beat-to-beat heart rate throughout an artifact period to preserve the timing relationships of the adjacent, uncorrupted heart rate data. The algorithm applies Fast Fourier Transformation to the smoothed data to estimate low-frequency (LF; 0.025-0.15 Hz) and high-frequency (HF; 0.16-0.35 Hz) spectral powers and the HF/LF ratio as conventional indices of sympathetic, vagal, and vagal-sympathetic balance components, respectively. We applied this algorithm to resting, supine, 2-min beat-to-beat heart rate data collected in the population-based Atherosclerosis Risk in Communities study to assess the performance (success rate) of the algorithm (N = 526) and the inter-and intra-data-operator repeatability of using this computer algorithm (N = 108). Eighty-eight percent (88%) of the records could be smoothed by the computer-generated limits, an additional 4.8% by manually set limits, and 7.4% of the data could not be processed due to a large number of artifacts in the beginning or the end of the records. For the repeatability study, 108 records were selected at random, and two trained data operators applied this algorithm to the same records twice within a 6-month interval of each process (blinded to each other's results and their own prior results). The inter-data-operator reliability coefficients were 0.86, 0.92, and 0.90 for the HF, LF, and HF/LF components, respectively. The average intra-data-operator reliability coefficients were 0.99, 0.99, and 0.98 for the HF, LF, and HF/LF components, respectively. These results indicate that this computer algorithm is efficient and highly repeatable in processing short-term beat-to-beat heart rate data collected from the general population, given that the data operators are trained according to standardized protocol.

Algorithms↗

The beneficial influence of prior knowledge on the quantitation of in vivo magnetic resonance spectroscopy signals.

RATIONALE AND OBJECTIVES: This work concerns quantitation of in vivo magnetic resonance spectroscopy signals and the influence of prior knowledge on the precision of parameter estimates. The authors point out how prior knowledge can be used for experiments. METHODS: The Cramer-Rao lower bounds formulae of the noise-related standard deviations on spectral parameters for doublets and triplets were derived. Chemical prior knowledge of the multiplet structures was used. RESULTS: The benefit of chemical prior knowledge was estimated for doublet and triplet structures of arbitrary shape. Then, it was used to quantify in vivo 31P time-series signals of rat brain. CONCLUSIONS: Analytic expressions of errors on parameter estimates were derived, enabling prediction of the benefit of prior knowledge on quantitation results. These formulae allow us to state, for a given noise level, if the quantitation of strongly overlapping peaks such as adenosine triphosphate multiplets can be performed successfully.

Adenosine Triphosphate↗

Comparison between ocean-acoustic fluctuations in parabolic-equation simulations and estimates from integral approximations.

Line-integral approximations to the acoustic path integral have been used to estimate the magnitude of the fluctuations in an acoustic signal traveling through an ocean filled with internal waves. These approximations for the root-mean-square (rms) fluctuation and the bias of travel time, rms fluctuation in a vertical arrival angle, and the spreading of the acoustic pulse are compared here to estimates from simulations that use the parabolic equation (PE). PE propagations at 250 Hz with a maximum range of 1000 km were performed. The model environment consisted of one of two sound-speed profiles perturbed by internal waves conforming to the Garrett-Munk (GM) spectral model with strengths of 0.5, 1, and 2 times the GM reference energy level. Integral-approximation (IA) estimates of rms travel-time fluctuations were within statistical uncertainty at 1000 km for the SLICE89 profile, and in disagreement by between 20% and 60% for the Canonical profile. Bias estimates were accurate for the first few hundred kilometers of propagation, but became a strong function of time front ID beyond, with some agreeing with the PE results and others very much larger. The IA structure functions of travel time with depth are predicted to be quadratic with the form theta(2)vc0(-2)deltaz(2), where deltaz is vertical separation, c0 is a reference sound speed, and thetav is the rms fluctuation in an arrival angle. At 1000 km, the PE results were close to quadratic at small deltaz, with values of thetav in disagreement with those of the integral approximation by factors of order 2. Pulse spreads in the PE results were much smaller than predicted by the IA estimates. Results imply that acoustic tomography of internal waves at ranges up to 1000 km can use the IA estimate of travel-time variance with reasonable reliability.

Journal Article↗

Acoustic analysis of newborn infant cry signals.

This paper aims at estimating the fundamental frequency (pitch) and the vocal tract resonant frequencies (formants) from newborn infant cry signals. Such parameters are of interest in exploring brain function at early stages of child development, for the timely diagnosis of neonatal disease and malformation. The paper compares a spectral parametric technique and the cepstrum approach, extending previous results. The parametric technique is based on autoregressive models whose order is adaptively estimated on subsequent signal frames by means of a new method. This allows the correct tracking of pitch and formant variations with time. The traditional cepstrum approach is modified in order to follow signal variability. In particular, the cepstrum spectral resolution is improved by applying the chirp Z-transform (CZT) and by adaptively varying the 'lifter' length. The two methods are tested on simulated data, as far as robustness to noise and spectral resolution are concerned, and are then applied to real baby cry data.

Acoustics↗

The effect of blood transfusion on alpha EEG activity in thalassemic patients.

EEG signal analysis could be very helpful in the detection of signs of adverse reaction to the brain by a systemic disease. We performed an EEG spectral analysis in 12 young patients with thalassemia before and after their regular blood transfusion, and in 10 volunteer students. Our aim was to test if the EEG analysis could detect signs of brain dysfunction due to the cerebral hypoxia as a result of the anemia. We analyzed the EEG signals on line using a dedicated computer system estimating the power of the delta, theta, alpha, sigma and beta bands of the EEG. After transfusion, the power spectral density of the alpha band showed a significant enhancement in most areas of the brain, in the group of the thalassemia patients as compared to the normals. These differences correlated with the levels of hemoglobin of the patients, and possibly reflect the degree of oxygenation of the brain. Since the visual interpretation of the EEG is not efficient for estimating the brain dysfunction in the anemic state in thalassemia, the signal analysis of the EEG may provide a more sensitive alternative to study the effects of hypoxia on brain function.

Adolescent↗

Response distributions in intensity resolution and speech discrimination.

In this paper the assumption of an equal, Gaussian distribution of the response to each stimulus in an experiment, an assumption which has to be met if d' is to be estimated by calculating the difference between z(H) and z(FA), is tested for two different sets of stimuli: 1000-Hz tones differing in level only, and a continuum of stop consonants, obtained by full spectral interpolation between /p/, /t/, and /k/. Response distributions were measured directly by means of a form of non-numerical magnitude estimation, in which subjects had to indicate the position of each stimulus on a quasi-continuous rating scale. It could be shown that, in general, all distributions were sufficiently unimodal, but that their variances differed. The consequences for the calculation of d' are unlikely to be serious.

Female↗

Properties of single voltage-gated proton channels in human eosinophils estimated by noise analysis and by direct measurement.

Voltage-gated proton channels were studied under voltage clamp in excised, inside-out patches of human eosinophils, at various pHi with pHo 7.5 or 6.5 pipette solutions. H+ current fluctuations were observed consistently when the membrane was depolarized to voltages that activated H+ current. At pHi < or = 5.5 the variance increased nonmonotonically with depolarization to a maximum near the midpoint of the H+ conductance-voltage relationship, gH-V, and then decreased, supporting the idea that the noise is generated by H+ channel gating. Power spectral analysis indicated Lorentzian and 1/f components, both related to H+ currents. Unitary H+ current amplitude was estimated from stationary or quasi-stationary variance, sigmaH2. We analyze sigmaH2 data obtained at various voltages on a linearized plot that provides estimates of both unitary conductance and the number of channels in the patch, without requiring knowledge of open probability. The unitary conductance averaged 38 fS at pHi 6.5, and increased nearly fourfold to 140 fS at pHi 5.5, but was independent of pHo. In contrast, the macroscopic gH was only 1.8-fold larger at pHi 5.5 than at pHi 6.5. The maximum H+ channel open probability during large depolarizations was 0.75 at pHi 6.5 and 0.95 at pHi 5.5. Because the unitary conductance increases at lower pHi more than the macroscopic gH, the number of functional channels must decrease. Single H+ channel currents were too small to record directly at physiological pH, but at pHi < or = 5.5 near Vthreshold (the voltage at which gH turns on), single channel-like current events were observed with amplitudes 7-16 fA.

Adult↗

Cobalt complexes of terpyridine ligand: crystal structure and photocleavage of DNA.

Two new cobalt complexes, [Co(pytpy)(2)](ClO(4))(2), 1, and [Co(pytpy)(2)](ClO(4))(3), 2 where pytpy=pyridine terpyridine, have been synthesized and characterized. Single-crystal X-ray structure of both the complexes has been resolved. The structure shows the complexes to be a monomeric cobalt(II) and cobalt(III) species with two pytpy ligands coordinated to the metal ion to give a six coordinate complex. Both cobalt(II) and cobalt(III) complexes crystallize in meridional configuration. The interaction of these complexes with calf thymus DNA has been explored by using absorption, emission spectral, electrochemical studies and viscosity measurements. From the experimental results the DNA binding constants of 1 and 2 are found to be (1.97+/-0.15)x10(4)M(-1) and (2.7+/-0.20)x10(4)M(-1) respectively. The ratio of DNA binding constants of 1 and 2 have been estimated to be 0.82 from electrochemical studies, which is in close agreement with the value of 0.73 obtained from spectral studies. The observed changes in viscosity of DNA in the presence of increasing amount of complexes 1 and 2 suggest intercalating binding of these complexes to DNA. Results of DNA cleaving experiments reveal that complex 2 efficiently cleaves DNA under photolytic conditions while complex 1 does not cleave DNA under similar conditions.

Animals↗

[Decomposition fluorescence spectra of tryptophan residues in proteins based on log-normal components by a least squares method].

An algorithm of decomposition of protein tryptophan spectra into components was developed. The spectral shape of components is described by a uniparametric log-normal function. Rise of certainty and accuracy of resolution of widely overlapping smooth spectral components (a typical uncorrect reverse problem) was achieved using several regularizing factors: (i) the set of experimental spectra used were measured at several quencher concentrations; (ii) the functional being minimized, along with the root mean square residuals of intensities, the term depending on the obedience to the Stern-Volmer law; (iii) an extra information is used--the number of experimental values greatly exceeds the number of parameters to be estimated. The minimum of functional is determined by a consecutive setting of all possible combinations of component spectral maxima values, which allows to avoid sticking in the local minima of noisy functional. The real experimental noise restricts the decomposition into not more than three components. The decomposition error does not exceed the experimental one. The algorithm functioning is illustrated by resolution of tryptophan fluorescence spectra of papain into one, two, and three components.

Algorithms↗

Combining principal component and spectral analyses with the method of moments in studies of quantal transmission.

This chapter considers methods for measurements of postsynaptic responses and simple approaches to the estimation of parameters of quantal release in synapses of the central nervous system of vertebrates. The use of these methods is illustrated by the analysis of single-fibre and "minimal" monosynaptic postsynaptic potentials (PSPs) or currents (PSCs) recorded from neurons of the frog spinal cord and rat hippocampus. First, we briefly discuss traditional methods of the response measurements using peak amplitudes or areas, further focusing on a novel method based on multivariate statistical techniques of the principal component analysis (PCA). This approach provides typically better signal-to-noise ratios and is able to separate two or more response components, which can arise due to activation of more than one presynaptic fibre, axon collaterals, receptor subtypes or spatially separated transmission sites. Second, spectral analysis is introduced as the method of choice to verify whether the amplitude fluctuations of the postsynaptic responses have a quantal nature and to obtain estimations of the "basic" quantal parameters, i.e. the quantal size (Q) and mean quantal content (m), without introducing assumptions on release statistics. Third, we show how the method of moments could be applied in the framework of the Poisson and binomial models to estimate the basic quantal parameters and parameters p and n, which reflect the release probability and maximum number of quanta released (or the number of effective release sites), respectively. Fourth, we show that the analysis of the moments can also be instrumental to reveal non-uniformity of release probabilities and compare how several competing models of neurotransmitter release fit to multiple experimental data sets.

Animals↗

Echo-Doppler angle determination for noninvasive transmitral blood velocity calculations in normal and porcine bioprosthetic mitral valves.

Doppler incident angle (DA) determination is a critical factor in the noninvasive attempt to measure transmitral blood velocity (TMBV) and to estimate volumetric flow. The error in TMBV varies with the cosine of DA. Using an echo-Doppler duplex scanner (DS), we studied transmitral flow velocities in 10 normal subjects (Group I) and 10 asymptomatic patients with procine mitral valve (PMV) bioprostheses. A 3-MHz scanhead with three medium focused rotating transducers was positioned at the left ventricular apex, and standard apical four-chamber views of the heart were obtained. The position of the Doppler sample volume (SV) was adjusted within the valve orifice until the maximal power of the Doppler audio spectra reflecting TMBV was recorded by a spectral analyzer. At this location of the SV, images were recorded and protractors were used to estimate DA. DA ranged from 10 to 40 degrees (x = 22.5 degrees +/- 10.8 degrees) in Group I and from 0 to 15 degrees (x = 4.5 degrees +/- 5.0 degrees) in Group II. Mean values of DA in Groups I and II were significantly different (p less than 0.01). We conclude: (1) in normal subjects, DA measured from the apex into the MV varies significantly and thus may compromise the accuracy of TMBV measurements; (2) the truncated funnel shape of the stent of the PMV bioprosthesis allows a DA less than 15 degrees and thus a smaller error in TMBV calculations.

Adult↗

Comparison of standard autonomic tests and power spectral analysis in normal adults.

Standard autonomic measures [heart rate response to deep breathing (HR[DB]), systolic blood pressure response to orthostatic load, the 30:15 ratio, and the Valsalva ratio (VR)] and spectral measures of the heart rate (HR) and the arterial blood pressure (ABP) (MF: mid-frequency band at 0.05-0.15 Hz; HF: high-frequency band at 0.15-0.33 Hz) were performed in 50 healthy subjects. The supine HR-HF and the tilt ABP-MF were taken as indicators of parasympathetic and sympathetic outflow, respectively. The transfer function magnitude of HR related to the ABP in the mid-frequency band estimated the baroreflex sensitivity. The HR[DB] and the 30:15 ratio were correlated with the parasympathetic spectral measure, and the VR was, surprisingly, only correlated with the sympathetic spectral measure. Significant baroreflex contribution was only evident for the 30:15 ratio. The spectral HR data were highly correlated with their corresponding spectral data of ABP. These results provide insights into autonomic regulation, but further studies on both basic physiological mechanisms of these methods and their clinical value have to be performed before a broad application can be recommended.

Adult↗

Spectral quantitation by principal component analysis using complex singular value decomposition.

Principal component analysis (PCA) is a powerful method for quantitative analysis of nuclear magnetic resonance spectral data sets. It has the advantage of being model independent, making it well suited for the analysis of spectra with complicated or unknown line shapes. Previous applications of PCA have required that all spectra in a data set be in phase or have implemented iterative methods to analyze spectra that are not perfectly phased. However, improper phasing or imperfect convergence of the iterative methods has resulted in systematic errors in the estimation of peak areas with PCA. Presented here is a modified method of PCA, which utilizes complex singular value decomposition (SVD) to analyze spectral data sets with any amount of variation in spectral phase. The new method is shown to be completely insensitive to spectral phase. In the presence of noise, PCA with complex SVD yields a lower variation in the estimation of peak area than conventional PCA by a factor of approximately 2. The performance of the method is demonstrated with simulated data and in vivo 31P spectra from human skeletal muscle.

Analysis of Variance↗

Applying spectral fingerprinting to the analysis of FRET images.

Förster resonance energy transfer (FRET) allows one to study interactions between two fluorescently labeled molecules (donors and acceptors) at distances on the order of 5 nm. Many studies have described methods of how to measure the efficiency of FRET. However, few have addressed the question of how fluorescence from unpaired donors and acceptors can be determined in addition to that from FRET-pairs and how the signal-to-noise ratio (SNR) of such estimates depends on the presence of the partner species. Such knowledge, however, is essential for many biological applications, in which-after initial characterization of the spectral properties of a well-defined donor-acceptor complex-the in vivo affinity and stoichiometry of the complex is of interest. Here, we provide a theoretical analysis on how spectral fingerprinting can be applied to separate fluorescence of FRET pairs from that originating from unpaired donors and acceptors and how to select imaging parameters to optimize the SNR of the estimates. Thereby, we uncover a fundamental problem in this application and discuss ways to evade its adverse consequences. We compare the expected resolution of traditional FRET measures with that of optimized spectral fingerprinting and analyze the resolution of a method for FRET measurements that combines spectral with fluorescence lifetime information.

Cells↗

Age-related changes of heart rate power spectra in a diabetic man during orthostasis.

We used spectral analysis of heart rate variability during orthostatic load in diabetic patients in order to provide quantitative information about first, the alterations of vagal and beta-adrenergic nervous system influence on the heart and secondly, the relation of spectral components of heart rate variability to age. The respiration-related power, and indirect estimate of vagal cardiac control, was significantly reduced in diabetics as compared with controls in both the supine (diabetics: 0.39 (0.18-1.15) l/min2 [median and 25-75% percentiles], controls: 1.52 (0.54-3.84) l/min2, 2P less than 0.01) and the standing (diabetics: 0.27 (0.12-0.84) l/min2, controls: 2.22 (0.67-5.14) l/min2, 2P less than 0.0001) body posture. The difference between supine and standing values of mid-frequency power (delta MF power) that represents beta-adrenergically mediated heart rate variability was significantly smaller in diabetics (delta MF: 0.79 (0.18-3.84) l/min2) than in controls (delta MF: 8.07 (4.35-17.99) l/min2) (2P less than 0.0001). Power of almost all frequency components declined exponentially with age in both positions and groups studied. The decline in power of heart rate variability was more pronounced in controls than in diabetics for either posture. An age-associated significant decrease in delta MF was found in controls (Y = 33.16-0.60X, P less than 0.05, r = -0.49) as compared to diabetics (Y = 8.70-0.16X, P greater than 0.05, r = -0.24). Our results suggest a decreased vagal and sympathetic nervous system input into the heart in diabetics. The premature loosened coupling between heart rate spectral power and age suggests that diabetes mellitus accelerates the aging process. Computerized spectral analysis of heart rate variability seems to be a very sensitive tool to evaluate the influence of the autonomic nervous system on the heart.

Adult↗

Membrane conductances and spectral sensitivities of Pecten photoreceptors.

The electrical and spectral properties of depolarizing (proximal) and hyperpolarizing (distal) photoreceptors in the eye of the scallop, Pecten irradians, were examined. Both depolarizing and hyperpolarizing responses are associated with an increase in membrane conductance; in addition, the depolarizing response is characterized by a secondary decrease in conductance at light intensities which inactivate the response. Both responses can be reversed in polarity by applied current across the cell membrane. The depolarizing response has a reversal potential of approximately +10 mv, whereas the estimated reversal potential for the hyperpolarizing response is near -70 mv. The two responses have the same spectral sensitivity function, which agrees with a Dartnall nomogram for a rhodospin with a lambda(max) at 500 nm. It is suggested that the photochemical reactions produce different end products which give responses of opposite polarity in proximal and distal cells, or alternatively, that the reactions of the respective cell membranes to the same end product are different.

Adaptation, Physiological↗

The molecular scanner in microscope mode.

The combination of microscope mode matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) with protein identification methodology: the molecular scanner, was explored. The molecular scanner approach provides improvement of sensitivity of detection and identification of high-mass proteins in microscope mode IMS. The methodology was tested on protein distributions obtained after separation by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE). High-quality, high-spatial-resolution ion images were recorded on a TRIFT-II ion microscope after gold coating of the MALDI sample preparation on the poly(vinylidenedifluoride) capture membranes. The sensitivity of the combined method is estimated to be 5 pmol. The minimum amount of sample consumed, needed for identification, was estimated to be better than 100 fmol. Software tools were developed to analyze the spectral data and to generate broad mass range and single molecular component microscope mode ion images and single mass-to-charge ratio microprobe mode images.

Animals↗