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Spectral analysis of clinical signals: an interface between medical statisticians and medical engineers.

This paper reviews the current use of spectral analysis in clinical medicine. We cover the problems of aliasing and estimation of the spectrum using windowing and autoregressive techniques. These techniques are modified for nonstationary data to include evolutionary spectral analysis and recursive autoregressive methods. The relationship between evolutionary spectral analysis and the time-frequency methods such as the Wigner-Ville distribution is discussed. Other techniques covered are Walsh Transforms and cosinor analysis. The methods are shown to apply in the analysis of signals from heart rate, blood pressure, EEG, other electrical signals and hormone levels. The engineering and statistical approaches are contrasted.

Blood Pressure↗

Discrimination of binocular color mixtures in dichromacy: evaluation of the Maxwell-Cornsweet conjecture.

We tested the Maxwell-Cornsweet conjecture that differential spectral filtering of the two eyes can increase the dimensionality of a dichromat's color vision. Sex-linked dichromats wore filters that differentially passed long- and middle-wavelength regions of the spectrum to each eye. Monocularly, temporal modulation thresholds (1.5 Hz) for color mixtures from the Rayleigh region of the spectrum were accounted for by a single, univariant mechanism. Binocularly, univariance was rejected because, as in monocular viewing by trichromats, in no color direction could silent substitution of the color mixtures be obtained. Despite the filter-aided increase in dimension, estimated wavelength discrimination was quite poor in this spectral region, suggesting a limit to the effectiveness of this technique.

Adult↗

Increases in the power spectral slope of background electroencephalogram just prior to asymmetric spike and wave complexes in epileptic patients.

Moment-to-moment electroencephalogram (EEG) changes just before spike and wave complexes (SWCs) were investigated by using a non-stationary power spectral analysis in 10 epileptic patients with asymmetric SWCs. The instantaneous power spectra of background EEG were estimated for a 10-s period just before SWCs in 10 locations. The spectral shape, showing a l/f amplitude characteristic, was assessed by the negative slope (spectral slope) of a straight line on a plot of log power versus frequency. Spectral slope significantly increased toward SWCs at locations with greater SWCs. This finding suggested structural changes in EEG frequency composition just before SWCs because of an epileptogenic process.

Adolescent↗

MAP estimation for hyperspectral image resolution enhancement using an auxiliary sensor.

This paper presents a novel maximum a posteriori estimator for enhancing the spatial resolution of an image using co-registered high spatial-resolution imagery from an auxiliary sensor. Here, we focus on the use of high-resolution panchomatic data to enhance hyperspectral imagery. However, the estimation framework developed allows for any number of spectral bands in the primary and auxiliary image. The proposed technique is suitable for applications where some correlation, either localized or global, exists between the auxiliary image and the image being enhanced. To exploit localized correlations, a spatially varying statistical model, based on vector quantization, is used. Another important aspect of the proposed algorithm is that it allows for the use of an accurate observation model relating the "true" scene with the low-resolutions observations. Experimental results with hyperspectral data derived from the airborne visible-infrared imaging spectrometer are presented to demonstrate the efficacy of the proposed estimator.

Algorithms↗

Doppler echocardiographic estimation of left ventricular end-diastolic pressure after MI in rats.

The spectral Doppler mitral flow pattern, alone or combined with tissue Doppler mitral annulus velocity, can be used to predict left ventricular (LV) filling pressure in humans, whereas invasive hemodynamic measurements are still required in the rat. This study was undertaken to assess whether LV end-diastolic pressure (LVEDP) can be estimated using Doppler echocardiography in the rat after myocardial infarction (MI). Thirty-seven rats (23 rats with MI after left coronary artery ligation and 14 sham-operated rats) were evaluated 3 mo after surgery with echo-Doppler and invasive hemodynamic measurements. Pulse wave spectral Doppler at the mitral valve tip was used to measure the E wave, the E wave deceleration time (DT), and the A wave; spectral Doppler tissue imaging was used to measure the early diastolic lateral mitral annulus velocity (E(a)). We found weak correlations between LVEDP and the peak velocity of the early mitral inflow (E), E/peak velocity of the late mitral inflow, and DT, and strong correlations with E(a) and especially with E/E(a) [R(2) = 0.89, LVEDP (in mmHg) = 0.987E/E(a) - 4.229]. Longitudinal followup of a subgroup of rats with MI revealed a marked rise of E/E(a) between days 7 and 21 in rats with heart failure only. We conclude that Doppler echocardiography can be used for serial assessment of LV diastolic function in rats with MI.

Animals↗

Phytochrome Cph1 from the cyanobacterium Synechocystis PCC6803. Purification, assembly, and quaternary structure.

The phytochrome Cph1 from the cyanobacterium Synechocystis PCC6803 forms holoprotein adducts with close spectral similarity to plant phytochromes when autoassembled in vitro with bilin chromophores. Cph1 is a 85-kDa protein that acts as a light-regulated histidine kinase seemingly involved in 'two-component' signalling. This paper describes the improvement of Cph1 purification, estimation of the extinction coefficient of holo-Cph1, spectral analyses of the assembly procedure and studies on quaternary structure. During assembly with the natural chromophore phycocyanobilin (PCB), a red-shifted intermediate is observed. A similar result was obtained when phycoerythrobilin was used as chromophore. As shown by SDS/PAGE and Zn2+ fluorescence, the covalent attachment of PCB is blocked by 1 mM iodoacetamide, a cysteine-derivatizing agent. When PCB was incubated with blocked apo-Cph1, again a shoulder at longer wavelengths appeared. It is therefore proposed that the long-wavelength-absorbing form represents the protonated, noncovalently bound bilin. Biliverdin, which is neither protonated nor covalently attached, undergoes spectral changes in its blue-absorbing band upon incubation with apo-Cph1. On the basis of these data we therefore propose a three-step model for phytochrome autoassembly. Size-exclusion chromatography revealed different mobilities for the apoprotein, red-absorbing Cph1-PCB and far-red-absorbing Cph1-PCB. The major peaks of both holoprotein adducts had apparent molecular masses approximately 200 kDa, a result in agreement with the notion that autophosphorylation in sensory histidine kinases requires dimerization. When Cph1-PCB was further purified by preparative native electrophoresis, the mobility on size-exclusion chromatography was approximately 100 kDa, and it was found to have lost its kinase activity, results implying that the material had lost its capacity to dimerize.

Bacterial Proteins↗

Estimated fetal cerebral ultrasound exposures from clinical examinations.

The results of a survey of worst-case in-water values for I(SPTA), acoustic power and peak negative pressure, from a wide range of machines in clinical use, have been used with simple "fixed-path" tissue models to estimate worst-case exposure values at the fetus (in situ). The distributions of the estimated in situ values are peaked more toward their low value ends than is the case for distributions of the corresponding in-water values, with the ratio of maximum to median values being higher. Although the upper tails of the derated I(SPTA) distributions are not heavily populated, they contain important instances of relatively high values, mainly for lower frequency probes. Spectral Doppler (SD) mode produces the highest in situ estimates for all three parameters, particularly for I(SPTA) values, which exceed 5000 mW cm(-2) in a third trimester minimum attenuation model, and 900 mW cm(-2) in a "typical" attenuation model. The maximum and median values of peak negative pressure do not show particularly large differences between modes for any of the attenuation models. Values up to -3 MPa are predicted for the third trimester minimum path model, and up to -1 MPa for the "typical" attenuation model. The maximum and median values of power are dependent on the mode, with the color flow imaging (CFI) and SD modes producing the largest values (approximately 200 mW in the third trimester minimum path model). In a previous publication, more accurate calculations of temperature elevations for a bone target third trimester model were calculated for some of the probes. Extrapolation of these results for different fixed attenuation models suggests that spectral Doppler exposure may produce temperature elevations of around 6 degrees C in minimum attenuation models, and over 1 degrees C in a more "typical" attenuation model. In CFI mode, a worst-case temperature elevation of approximately 1.8 degrees C is estimated for the third trimester, and 1.3 degrees C for the first and second trimesters. For B-mode, the corresponding figures are 1.4 and 1.1 degrees C, respectively. For the case of a "typical" attenuation model, worst-case temperature elevations of approximately 0.3 degrees C are predicted for both B-mode and color flow imaging modes.

Body Temperature↗

Sleep electroencephalogram alterations disclose initial stage of encephalopathy.

UNLABELLED: Minimal hepatic encephalopathy is often present in patients with chronic liver disease. The aim of this work was to determine changes in the dynamics of sleep electroencephalogram (EEG) in cirrhotic patients without overt encephalopathy. Twenty such cirrhotic subjects included in the protocol of hepatic transplantation of our hospital were studied and compared with 20 age-matched healthy volunteers. Spectral analysis of all-night EEG was estimated by computing the fast-Fourier transform in 2-second epochs, and averaging every 60 seconds. Artifacts were off-line suppressed, sleep stages (stage 2, stage 3-4 and REM) were determined, and the EEG mean dominant frequency (MDF) was calculated in each of these stages. Results show that in cirrhotic patients, nocturnal MDF evolution discloses a clear alteration of the ultradian EEG frequency oscillations present in controls. Also, the mean value of MDF in REM episodes was larger in cirrhotics than the corresponding value in controls. CONCLUSIONS: 1) sleep EEG evidences the existence of minimal hepatic encephalopathy; 2) the spectral analysis of EEG in minimal hepatic encephalopathy showed that the changes of MDF during sleep are an early marker of cerebral dysfunction in cirrhotic patients.

Electroencephalography↗

Correlation of spectral phonoangiography and carotid angiography with gross pathology in carotid stenosis.

Spectral phonoangiography, a noninvasive method for measurement of the residual-lumen diameter of carotid stenosis by bruit analysis, was compared with x-ray angiography and direct measurement of the pathological specimen at carotid endarterectomy in 39 bifurcations from 36 patients. In six studies, the bruit was too faint to analyze. In 31 of the other 33 studies, the phonoangiogram predicted the residual-lumen diameter to within 0.5 mm of the measured value. Of the 39 contrast angiograms, 35 showed residual lumens within 0.5 mm of the value measured in the specimen, two showed lumens between 0.5 and 1 mm, and the sizes of two could not be estimated because of vessel overlap in all planes. Spectral phonoangiography and contrast angiography are both accurate methods for evaluation of carotid stenosis. Since phonoangiography is noninvasive, it may be of particular value in determining the natural history in patients with carotid bruits.

Auscultation↗

Parameterization of the voice source by combining spectral decay and amplitude features of the glottal flow.

A new method is presented for the parameterization of glottal volume velocity waveforms that have been estimated by inverse filtering acoustic speech pressure signals. The new technique, Parameter for Spectral and Amplitude Features of the Glottal Flow (PSA), combines two features of voice production, the AC value and the spectral decay of the glottal flow, both of which contribute to changes in vocal loudness. PSA yields a single parameter that characterizes the glottal flow in different loudness conditions. By analyzing voices of 8 speakers it was shown that the new parameter correlates strongly with the sound pressure level of speech.

Female↗

Intensity range based quantitative FRET data analysis to localize protein molecules in live cell nuclei.

Förster (fluorescence) resonance energy transfer (FRET) is an ideal technique to estimate the distance between interacting protein molecules in live specimens using intensity-based microscopy. The spectral overlap of donor and acceptor- essential for FRET-also generates a contamination of the FRET signal. There are a number of algorithms available to remove this spectral bleedthrough (SBT) contamination and in this paper we compare two popular algorithms to estimate the SBT element and to calculate a more precise level of energy transfer efficiency, and with that a more accurate distance estimate.

Algorithms↗

Measurement of mean velocity during pulsatile flow using time-averaged maximum frequency of Doppler ultrasound waveforms.

It has been suggested that mean velocity of flow could be estimated by the time-averaged maximum frequency over an integral number of cardiac cycles (Gill 1985). The present study verified this theory experimentally with a computer-controlled flow phantom. The effects of some parameters on the relationship between mean velocity and time-averaged maximum frequency were also studied. Parameters investigated included beam-vessel angle, diameter of tubing, pulsatility, flow rate and stenosis. The velocities measured by the Doppler system were compared with the actual velocities. A simple theoretical model was also developed to compare with the experimental results. The results showed that, in a long straight tube, the mean velocity can be estimated to within about 5% from the time-averaged maximum Doppler shift at various flow rates and pulsatilities. The error due to geometrical spectral broadening, especially for large beam-vessel angles, can be estimated to within 3% and therefore corrected.

Blood Flow Velocity↗

A radio frequency domain complex cross-correlation model to estimate blood flow velocity and tissue motion by means of ultrasound.

This article introduces a mean frequency estimator based on a radio frequency (RF) domain complex cross-correlation model (C3M). The C3M estimator differs from the real cross-correlation model (CCM) estimator in two respects; it is an unbiased estimator of blood flow velocity and/or tissue motion independent of the bandwidth of the RF ultrasound signals, and it provides an estimate of the spatial bandwidth of the RF-signal. The estimators derived from the complex cross-correlation model (mean spatial frequency, mean temporal frequency, spatial bandwidth and signal-to-noise ratio) are based on three complex cross-correlation coefficients. A full derivation and mathematical description of both estimators (C3M and CCM), starting from a Gaussian model of the complex power spectral density distribution of sampled RF signals, are presented. In addition, a thorough performance evaluation of the C3M estimator in comparison with the CCM estimator is carried out by means of simulations to document the effect of signal-to-noise ratio, bandwidth and sample frequency. In the context of the specific simulation conditions considered, the quality of the C3M estimator is shown to offer the best performance (no bias, low standard deviation of the estimate). Taking into account the computational load and the robustness of the C3M estimator, it may be concluded that the C3M estimator combines high quality and modest complexity.

Blood Flow Velocity↗

Spectral calibration of hyperspectral imagery using atmospheric absorption features.

One of the initial steps in the preprocessing of remote sensing data is the atmospheric correction of the at-sensor radiance images, i.e., radiances recorded at the sensor aperture. Apart from the accuracy in the estimation of the concentrations of the main atmospheric species, the retrieved surface reflectance is also influenced by the spectral calibration of the sensor, especially in those wavelengths mostly affected by gaseous absorptions. In particular, errors in the surface reflectance appear when a systematic shift in the nominal channel positions occurs. A method to assess the spectral calibration of hyperspectral imaging spectrometers from the acquired imagery is presented in this paper. The fundamental basis of the method is the calculation of the value of the spectral shift that minimizes the error in the estimates of surface reflectance. This is performed by an optimization procedure that minimizes the deviation between a surface reflectance spectrum and a smoothed one resulting from the application of a low-pass filter. A sensitivity analysis was performed using synthetic data generated with the MODTRAN4 radiative transfer code for several values of the spectral shift and the water vapor column content. The error detected in the retrieval is less than +/- 0.2 nm for spectral shifts smaller than 2 nm, and less than +/- 1.0 nm for extreme spectral shifts of 5 nm. A low sensitivity to uncertainties in the estimation of water vapor content was found, which reinforces the robustness of the algorithm. The method was successfully applied to data acquired by different hyperspectral sensors.

Journal Article↗

A new method for estimation of nerve conduction velocity distribution in the frequency domain.

Nerve conduction velocity (NCV) measurements have been widely used to assess the electrophysiological properties of peripheral nerves and to detect neuropathies at a subclinical stage. Conventional NCVs are usually expressed as the NCV for the fastest conducting fibers and the current standard methods do neither supply information about slower conducting fibers, nor detect information about individual fiber groups. We present a new analytical method, to estimate the distribution of conduction velocity (DCV), based upon spectral analysis of the wave forms of two compound action potentials (CAPs) recorded by surface electrodes from a nerve bundle. If the spectra of the two CAPs recorded at two different sites in response to supramaximal electrical stimulation at distances l1 and l2 are given as G11(omega) and G12(omega), the spectral representation of the latency distribution P12(omega) for the propagation distance l2 is expressed as follows: P12(l1 omega/l2) = [G11(omega)/G12(omega)]P12(omega), where omega is an angular frequency. We developed an algorithm that computes P12(omega) successively without using iterative calculation methods. Our estimation method is theoretically based upon the principle that the CAPs are recorded monopolarly to estimate the DCV, but in practical use, it is almost impossible to obtain appropriate CAP wave forms by monopolar recording methods, because of stimulation and muscle artefacts. In order to evaluate the efficacy of bipolarly recorded CAP wave forms for this computation algorithm, we examined the two CAP wave forms reconstructed by simulation techniques. We found that the difference between the monopolar and bipolar recording methods was reflected in the wave form extracted for the single fiber action potentials but not in the latency distribution. The distance between the bipolarly recorded electrodes (1.5 cm was the minimal distance used) did not affect the reproducibility of estimating the latency distribution. This new method is non-invasive and could be used for evaluation of peripheral neuropathies.

Action Potentials↗

Interobserver variability of cerebral blood flow measurements obtained using spectral analysis and technetium-99m labeled compounds.

Radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or technetium-99m ethyl cysteinate dimer (99mTc-ECD) enables the non-invasive estimation of absolute cerebral blood flow (CBF) to be determined by using spectral analysis (SA). We previously demonstrated the clinical use of SA; however, this method involves a few manual steps. The aim of this study was to evaluate the interobserver variability of CBF estimations made using SA and compare these results with those obtained by using graphical analysis (GA). In twenty patients with various brain diseases (27-74 years old), radionuclide angiography examinations were performed using 99mTc-labeled compounds (10 patients, 99mTc-HMPAO; 10 patients, 99mTc-ECD). Bilateral cerebral hemispheres were studied in all patients, and the brain perfusion index (BPI) values were estimated using SA and GA. The interobserver variability between two observers was then assessed. A good correlation between the BPI values assessed using both SA (BPI(S)) and GA (BPI(G)) was obtained. The correlation coefficient for BPI(S) (r = 0.987) was almost the same as that for BPI(G) (r = 0.982). The degree of interobserver variability was not affected by the measurement of elevated BPI values. Measurements carried out by two observers using both SA and GA exhibited a similar degree of interobserver variability. SA appears to have a satisfactory interobserver variability and may be more suitable for clinical applications.

Algorithms↗

Can electroencephalographic analysis be used to determine sedation levels in critically ill patients?

UNLABELLED: Prolonged use of sedative drugs frequently leads to oversedation of intensive care patients. Clinical assessment scales are not reliable in deeply sedated patients. Parameters obtained from spectral and bispectral analysis of electroencephalogram (EEG) records have been combined to create an index (BIS) to monitor anesthesia depth. The role of such parameters in monitoring the depth of the sedation in intensive care unit (ICU) patients has yet to be determined. We designed the present prospective study to redefine and calculate available spectral and bispectral parameters from raw EEG records and estimate their clinical relevance for the diagnosis of under- or oversedation levels in ICU patients. Forty adult patients receiving continuous midazolam and morphine sedation were included. We obtained 167 clinical evaluations of sedation level using Ramsay and COMFORT scales along with an EEG record of 300 s. Six spectral parameters-relative power of 4 frequency bands (beta, alpha, Theta, and delta), 95th percentile of the power spectrum (SEF95), and 50th percentile of the power spectrum (SEF50) and four bispectral parameters, real triple product, bispectrum (Bispectrum), bicoherence, and ratio 10-were calculated. The relevance of each of these parameters and combinations in predicting too light (Ramsay 1 and 2) or deep (Ramsay 5 and 6) sedation levels was assessed. These calculations were performed before and after exclusion of the agitated patients, whose COMFORT 4 score was above 2. The most relevant parameters for predicting levels of deep sedation (Ramsay 5 and 6) were ratio 10 (area under the curve = 0.763; 95% confidence interval, 0.679-0.833) and SEF95 (area under the curve = 0.687; 95% confidence interval, 0.597-0.767). The most relevant parameters for predicting light levels of sedation (Ramsay 1 and 2) were also ratio 10 (area under the curve = 0.829; 95% confidence interval, 0.695-0.917) and SEF95 (area under the curve = 0.798; 95% confidence interval, 0.650-0.898). There is a modest improvement in relevance of their linear combination in predicting sedation level. Results were similar after exclusion of agitated patients. We conclude that various calculated EEG descriptive parameters exhibited large interindividual variability. There was a strong correlation between EEG spectral and bispectral parameters. Bispectral analysis slightly improves the predictive power of simple spectral analysis in distinguishing too light or deep sedation levels in ICU patients. IMPLICATIONS: Spectral edge frequency 95 and Ratio 10 are the most relevant electroencephalogram (EEG) indexes for monitoring the level of sedation in intensive care unit patients but calculated EEG values exhibited large interindividual variability. Bispectral analysis of EEG provides a slight improvement over simple spectral analysis.

Adult↗

Predictor-corrector with cubic spline method for spectrum estimation in Compton scatter correction of SPECT.

In single photon emission computed tomography (SPECT), Compton scattered photons degrade image contrast and cause erroneous regional activity quantification. A predictor-corrector and cubic spline (PCCS) method for the compensation of Compton scatter in SPECT is proposed. Using spectral information recorded at four energy windows, the PCCS method estimates scatter counts at each window and constructs the scatter spectrum with cubic spline interpolation. We have shown in simulated noise-free situations that this method provides accurate estimation of scatter fractions. A scatter correction employing PCCS method can be implemented on many existing SPECT systems without hardware modification and complicated calibration.

Computer Simulation↗