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Single-trial variable model for event-related fMRI data analysis.

Most methods for fMRI data analysis assume that the hemodynamic responses (HRs) across similar experimental events are same. This assumption is not appropriate when HRs vary unpredictably from trial to trial. Here, we introduce a new method for fMRI data analysis. The main features of the proposed method are as follows: 1) The trial-to-trial variability is modeled as meaningful signal rather than assuming that the same HR is evoked in each trial; 2) Since the proposed method is a constrained optimization based general framework, it could be extended by utilizing prior knowledge of HR; 3) The traditional deconvolution method can be included into our method as a special case. A comparison of performance on simulated fMRI datasets is made using the general linear model, the deconvolution method and the proposed method with receiver operating characteristic (ROC) methodology. In addition, we examined the effectiveness and usefulness of our method on real experimental data.

Adult↗

Aperture collimation correction and maximum-likelihood image reconstruction for near-field coded aperture imaging of single photon emission computerized tomography.

Coded aperture (CA) imaging originally developed in X-ray astronomy has not been widely used in nuclear medicine due to the decoding complexity of near-field CA images. In this paper, we present a near-field CA imaging technique and image reconstruction method for high sensitivity and high resolution single photon emission computerized tomography (SPECT). Our approach makes three contributions. First, a correction method for the aperture collimation effect is used to eliminate the near-field artifacts without dual acquisitions of mask and anti-mask images. Second, a maximum-likelihood expectation-maximization (MLEM) deconvolution method is used to restore CA images. Finally, a new MLEM-based algorithm is used to partially reconstruct three-dimensional (3-D) objects from a single projection of CA images. Experiments conducted using a dual-head SPECT system equipped with a parallel-hole collimator and a CA module show a tenfold increase in count sensitivity and significant improvement in image resolution with CA collimation as compared to parallel-hole collimation. Experiments conducted using the same dual-head SPECT system equipped with a pinhole collimator show that when the object is closer to the pinhole collimator the CA image resolution is only slightly inferior to the pinhole collimated image. We found that the MLEM deconvolution method provides an inherent nonnegativity constraint on pixel values and remarkably reduces background activities of CA images. The MLEM reconstruction algorithm for CA images is capable of reconstructing 3-D objects from a single projection and can be potentially extended to full 3-D SPECT reconstruction for CA images.

Algorithms↗

Penalized-likelihood sinogram restoration for computed tomography.

We formulate computed tomography (CT) sinogram preprocessing as a statistical restoration problem in which the goal is to obtain the best estimate of the line integrals needed for reconstruction from the set of noisy, degraded measurements. CT measurement data are degraded by a number of factors-including beam hardening and off-focal radiation-that produce artifacts in reconstructed images unless properly corrected. Currently, such effects are addressed by a sequence of sinogram-preprocessing steps, including deconvolution corrections for off-focal radiation, that have the potential to amplify noise. Noise itself is generally mitigated through apodization of the reconstruction kernel, which effectively ignores the measurement statistics, although in high-noise situations adaptive filtering methods that loosely model data statistics are sometimes applied. As an alternative, we present a general imaging model relating the degraded measurements to the sinogram of ideal line integrals and propose to estimate these line integrals by iteratively optimizing a statistically based objective function. We consider three different strategies for estimating the set of ideal line integrals, one based on direct estimation of ideal "monochromatic" line integrals that have been corrected for single-material beam hardening, one based on estimation of ideal "polychromatic" line integrals that can be readily mapped to monochromatic line integrals, and one based on estimation of ideal transmitted intensities, from which ideal, monochromatic line integrals can be readily estimated. The first two approaches involve maximization of a penalized Poisson-likelihood objective function while the third involves minimization of a quadratic penalized weighted least squares (PWLS) objective applied in the transmitted intensity domain. We find that at low exposure levels typical of those being considered for screening CT, the Poisson-likelihood based approaches outperform the PWLS objective as well as a standard approach based on adaptive filtering followed by deconvolution. At higher exposure levels, the approaches all perform similarly.

Algorithms↗

Omni-directional guided wave transducer arrays for the rapid inspection of large areas of plate structures.

Omni-directional guided wave array transducers contain a circular pattern of elements that individually behave as omni-directional point transmitters or receivers. The data set acquired from such an array contains time-domain signals from each permutation of transmitter and receiver. A phased addition algorithm is developed that allows an omni-directional, B-scan image of the surrounding plate to be synthesized from any geometry of array. Numerically simulated data from a single reflector is used to test the performance of the algorithm. The results from an array containing a fully populated circular area of elements (Type I array) are found to be good, but those from an array containing a single ring of elements (Type II array) contain many large side-lobes. An enhancement to the basic-phased addition algorithm is presented that uses deconvolution to suppress these side-lobes. The deconvolution algorithm enables a Type II array to equal the performance of a Type I array of the same overall diameter. The effect of diameter on angular resolution is investigated. Experimental data obtained from a guided wave array containing electromagnetic acoustic transducers (EMAT) elements for exciting and detecting the So Lamb wave mode in a 5-mm thick aluminium plate are processed with both algorithms and the results are discussed.

Journal Article↗

Automated extraction of backbone deuteration levels from amide H/2H mass spectrometry experiments.

A Fourier deconvolution method has been developed to explicitly determine the amount of backbone amide deuterium incorporated into protein regions or segments by hydrogen/deuterium (H/D) exchange with high-resolution mass spectrometry. Determination and analysis of the level and number of backbone amide exchanging in solution provide more information about the solvent accessibility of the protein than do previous centroid methods, which only calculate the average deuterons exchanged. After exchange, a protein is digested into peptides as a way of determining the exchange within a local area of the protein. The mass of a peptide upon deuteration is a sum of the natural isotope abundance, fast exchanging side-chain hydrogens (present in MALDI-TOF H/2H data) and backbone amide exchange. Removal of the components of the isotopic distribution due to the natural isotope abundances and the fast exchanging side-chains allows for a precise quantification of the levels of backbone amide exchange, as is shown by an example from protein kinase A. The deconvoluted results are affected by overlapping peptides or inconsistent mass envelopes, and evaluation procedures for these cases are discussed. Finally, a method for determining the back exchange corrected populations is presented, and its effect on the data is discussed under various circumstances.

Amides↗

The effects of recombinant human insulin-like growth factor I on growth hormone secretion in adolescents with insulin dependent diabetes mellitus.

OBJECTIVE: It has been proposed that low IGF-I levels and reduced IGF-I bioactivity may lead to elevated GH levels in adolescents with insulin dependent diabetes (IDDM). We have therefore studied the effects of human recombinant insulin-like growth factor I (rhIGF-I) administration on GH levels and GH secretion in adolescents with IDDM. PATIENTS: Nine late pubertal adolescents (four male and five female) with IDDM. DESIGN: A double-blind placebo controlled study of rhIGF-I administered subcutaneously in a dose of 40 micrograms/kg body weight at 1800 h. MEASUREMENTS: IGF-I and GH concentrations were measured at regular intervals throughout the study. Twenty-two hour GH secretory rates were calculated by deconvolution analysis. Overnight GH profiles were analysed by distribution analysis, and Fourier transformations were performed on both overnight GH concentrations and GH secretory rates. RESULTS: Mean IGF-I levels over the 22-hour study period were significantly elevated following rhIGF-I administration (350 +/- 26 vs 205 +/- 21 micrograms/l (mean +/- SEM), P < 0.01). Mean 22-hour GH levels were reduced following rhIGF-I administration (19.4 +/- 4.0 compared with 33.6 +/- 5.8 mU/l; P = 0.01). Distribution analysis demonstrated that the reduction in GH levels was due to changes in the proportion of values at both high and low concentrations. Deconvolution analysis also revealed a significant overall reduction in GH secretory rate following IGF-I administration (1.81 +/- 0.30 vs 2.98 +/- 0.47 mU/min, P = 0.01) which was still apparent during the final 5.5 hours of the study period (1.51 +/- 0.30 vs 2.76 +/- 0.61 mU/min, P = 0.02). The dominant periodicity of GH secretory episodes as determined by Fourier transformation was between 120 and 180 minutes after both IGF-I and placebo. CONCLUSIONS: In late pubertal adolescents with IDDM the rise in IGF-I levels following rhIGF-I administration in a subcutaneous dose of 40 micrograms/kg body weight leads to a significant reduction in GH levels and GH secretory rate. The reduction in GH secretion is due to changes in pulse amplitude rather than frequency. A reduction in GH secretion was apparent at the beginning and also towards the end of the 22-hour study period.

Adolescent↗

Secondary structure and dosage of soluble and membrane proteins by attenuated total reflection Fourier-transform infrared spectroscopy on hydrated films.

Attenuated total reflection Fourier-transform infrared spectroscopy of thin hydrated films of soluble and membrane protein included in a phospholipid bilayer is shown to provide useful information as to the secondary structure of the protein. The analysis of the amide I band of deuterated samples by Fourier self-deconvolution followed by a curve fitting was performed by a new procedure in which all the input parameters are generated by the computer rather than by the investigator. The results of this analysis provide a correct estimation of the alpha-helix and beta-sheet structure content with a standard deviation of 8.6% when X-ray structures are taken as a reference. We also show that the orientation of the different secondary structures resolved by the Fourier self-deconvolution/curve-fitting procedure and of the phospholipid acyl chains can be simultaneously evaluated for membrane proteins reconstituted in a lipid bilayer. Of special interest for reconstitution of membrane proteins, the lipid/protein ratio can be accurately and quickly determined from the infrared spectrum.

Electronic Data Processing↗

Simulation of the electrochemical behavior of multi-redox systems. Current potential studies on multiheme cytochromes.

The direct unmediated electrochemical response of the tetrahemic cytochrome c3 isolated from sulfate reducers Desulfovibrio baculatus (DSM 1743) and D. vulgaris (strain Hildenborough), was evaluated using different electrode systems [graphite (edge cut), gold, semiconductor (InO2) and mercury)] and different electrochemical methods (cyclic voltammetry and differential pulse voltammetry). A computer program was developed for the theoretical simulation of a complete cyclic voltammetry curve, based on the method proposed by Nicholson and Shain [Nicholson, R.S. & Shain, I. (1964) Anal. Chem. 36, 706-723], using the Gauss-Legendre method for calculation of the integral equations. The experimental data obtained for this multi-redox center protein was deconvoluted in to the four redox components using theoretically generated cyclic voltammetry curves and the four mid-point reduction potentials determined. The pH dependence of the four reduction potentials was evaluated using the deconvolution method described.

Carbon↗

Differentiation of the maturity of cataractous human lens capsules according to changes in protein secondary structures determined by Fourier-transformed infrared spectroscopy.

PURPOSE: Cataract-induced alterations in the protein secondary structure of human lens capsules in different maturity of cataractous patients was investigated. METHODS: Fourier-transformed infrared (FT-IR) spectroscopy with Fourier self-deconvolution and curve-fitting algorithms was used. Twenty-seven immature and four mature cataractous patients (previously classified through observations of the depth of the shadow cast by the iris on oblique illumination) were investigated in the present study. RESULTS: Two groups with progressive cataract formation could be effectively redifferentiated and re-arranged. In the first group, all the peak positions were the same and the peak at 1651 cm-1 assigned to the alpha-helix structure was predominant, but the structural compositions of the beta-sheet and beta-turn changed with progressive cataractogenesis. In the second group, in which cataract formation was more advanced, the peak at 1651 cm-1 assigned to the alpha-helix structure shifted to 1658 cm-1 and a new peak appeared at 1647 cm-1, due to random coil structure; the structural compositions of triple helix significantly decreased but the compositions of the beta-sheet and beta-turn slightly increased. Amides II and III of the IR spectra seemed to be less changed in secondary structures. CONCLUSIONS: These results suggest that FT-IR spectroscopy with Fourier self-deconvolution and curve-fitting programs can be used as a diagnostic tool for the determination of the cataractous maturity of human lens capsules.

Aged↗

The obstructed kidney: correlation between renal function and urodynamic assessment.

In 20 patients with pelvi-ureteric junction obstruction the results of quantification of the change in renal pelvis size during high-dose intravenous urography with a diuretic, pressure/flow studies, standard renography and deconvolution analysis of the gamma camera renogram have been compared. The results of high-dose intravenous urography and pressure/flow studies correlated well. Renography was unreliable in diagnosing obstruction unless deconvolution analysis of the gamma camera renogram was used to differentiate those showing an obstructive uropathy from those with an obstructing nephropathy.

Humans↗

Left ventricular unloading with an assist device results in receptor relocalization as well as increased beta-adrenergic receptor numbers: are these changes indications for outcome?

BACKGROUND: The use of left ventricular (LV) assist devices (LVADs) can improve performance and recovery of failing human hearts. AIM: Following our alpha-adrenergic receptor work, we hypothesized that mechanical unloading in patients with low output syndrome and LV failure would yield similar results with beta-adrenergic receptors ((beta)AR), that being increased numbers and intra-myocytic relocalization. METHODS: (beta)AR density and localization were investigated by fluorescence deconvolution microscopy and compared at LVAD insertion and removal in 13 heart failure patients, the patients therefore acting as their own control. (beta)AR densities and distribution were determined in snap frozen sections of human core biopsy left ventricular apical tissue. Samples were probed with tagged CGP 12177 for visualization of (beta)AR and challenged with cold agonists and antagonists. (beta)AR density was measured by two independent methods. Localization of receptors was examined in reconstructed, deconvoluted, stacked section images. RESULTS: There was an increase in (beta)AR density following ventricular unloading in most of the patients, and also significant normalization in the location of the receptors in the myocardium comparing pre- and post-LVAD tissue. CONCLUSIONS: These findings suggest that supporting an ailing heart via unloading initiates mechanisms and pathways responsible for myocardial recovery and repair. With appropriate pharmacological support, patients with LVAD might recover to the point where they no longer depend on eventual organ transplantation, and (beta)AR number, type, and distribution in pre-LVAD myocardial tissue, could predict outcome with regard to recovery, repair, and improvement in cardiac function.

Female↗

The kinetics of short-lived indium-111 radiolabelled platelets.

We have studied the kinetics of autologous 111In-labelled platelets in patients with reduced platelet life span (less than 4.5 d), most of whom were thrombocytopenic, and of homologous 111In-labelled platelets in patients with severe thrombocytopenia. Intrasplenic platelet transit time (t) was calculated by compartmental and deconvolution analysis. In patients with a mean platelet life span of less than a few h, compartmental analysis may not be valid and so only deconvolution analysis was applied. There was a close correlation between values of t given by the two approaches (r = 0.88, n = 18, P less than 0.001). In some patients with severely reduced mean platelet life span (MPLS), the deconvolved splenic platelet clearance curves appeared to approach an asymptote, the relative magnitude of which was indicative of the irreversible extraction fraction by the spleen of incoming platelets. In other patients with severely reduced MPLS resulting from abnormal intra-hepatic platelet destruction, the deconvolved splenic curves resembled the normal. The intrasplenic platelet transit time showed no clear relationship with other parameters. It was concluded that platelet pooling within the spleen is normal in patients with reduced platelet life span, including idiopathic thrombocytopenic purpura, even when the predominant site of destruction is the spleen, and that platelets are not delayed in transit through the spleen in preparation for their removal from the circulation and ultimate destruction.

Blood Platelets↗

Linear dichroism study of metalloporphyrin transition moments in view of radiationless interactions with tryptophan in hemoproteins.

We measured the linear dichroism of several metalloporphyrins embedded in stretched polyvinyl alcohol (PVA) films to estimate the orientation of the absorption transition moments, which in hemoproteins are relevant to the radiationless energy transfer between tryptophan and heme. The metalloporphyrins were derivatives of protoporphyrin IX (PPIX), namely Fe(3+)-PPIX (ferric-heme) and Fe2+CO-PPIX (CO-heme), Mg-PPIX (Mg-heme) and Zn-PPIX (Zn-heme). Measurements were conducted between 300 and 700 nm. In all cases the linear dichroism was wavelength dependent, indicating the presence of several transition moments with different orientations. We focused our attention on the near-UV (300-380 nm) and Soret (380-450 nm) absorption bands. Deconvolution in terms of Gaussian components gave three components between 380 and 450 nm and only one in the 300-380 nm region. Deconvolution of the near-UV and Soret spectra of oxy-, deoxy- and carbonmonoxyhemoglobin gave very similar results, suggesting a very similar orientation of the various transition moments in the free and protein-embedded hemes. It should be stressed that the single 300-380 nm band is the only one responsible for the overlap integral that regulates the energy transfer from tryptophan to heme in hemoproteins (Gryczynski et al., Biophys. J. 63, 648-653, 1992). The dichroism of this single band indicated that its transition moment is oriented at about 60 degrees from the alpha-gamma meso-axis of the heme moiety. We conclude that the heme should be considered a linear oscillator when it acts as acceptor of energy transfer from tryptophans.

Binding Sites↗

Estimating the timing of quantal releases during end-plate currents at the frog neuromuscular junction.

1. Following motor nerve stimulation there is a period of greatly enhanced quantal release, called the early release period or ERP (Barrett & Stevens, 1972b). Until now, measurements of the probability of quantal releases at different points in the ERP have come from experiments in which quantal output was greatly reduced, so that the time of release of individual quanta could be detected or so that the latency to the release of the first quantum could be measured. 2. A method has been developed to estimate the timing of quantal release during the ERP that can be used at much higher levels of quantal output. The assumption is made that each quantal release generates an end-plate current (EPC) that rises instantaneously and then decays exponentially. The peak amplitude of the quantal currents and the time constant for their decay are measured from miniature end-plate currents (MEPCs). Then a number of EPCs are averaged, and the times of release of the individual quanta during the ERP estimated by a simple mathematical method for deconvolution derived by Cohen, Van der Kloot & Attwell (1981). 3. The deconvolution method was tested using data from preparations in high-Mg2+ low-Ca2+ solution. One test was to reconstitute the averaged EPCs from the estimated times of quantal release and the quantal currents, by using Fourier convolution. The reconstructions fit well to the originals. 4. Reconstructions were also made from averaged MEPCs which do not rise instantaneously and the estimated times of quantal release.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

The kinetics of quantal releases during end-plate currents at the frog neuromuscular junction.

1. The preceding paper (Van der Kloot, 1988) described a method for estimating the timing of quantal releases during an end-plate current. This period of elevated quantal release is called the early release period or ERP (Barrett & Stevens, 1972b). In the present paper, this deconvolution method is used to study the effects of varying quantal output by extracellular ions, stimulus patterns and drugs. 2. The data were obtained by voltage clamping end-plates in low-Ca2+ high-Mg2+ solutions, or in solutions containing tubocurarine (measuring the decay of the miniature end-plate currents (MEPCs) before curarization and assuming a value for MEPC amplitude after curarization). Data were also obtained by extracellular recording in Ca2+-free solution, using a recording pipette filled with CaCl2 and regulating Ca2+ release with a bias current. The three approaches led to similar conclusions. 3. Quantal release rose during the ERP along a sigmoid curve and reached a maximum after about 1.4 ms at 10 degrees C. This is called the time to peak. Quantal release then fell, following an exponential time course with a time constant of about 1.2 ms (10 degrees C). This is called the time constant for decline. 4. The ERP was followed by further, elevated quantal release, at a much lower rate, which declined over a longer time course. This is called late release. The magnitude of late release appears to be almost independent of the magnitude of release during the ERP, although the deconvolution method is a poor one for determining late release. The remainder of the results therefore focus on the ERP. 5. Increasing [Ca2+]o increased quantal output, and the rate of quantal output. It did not change the time to peak or the time constant of decline. Similarly, replacing Ca2+ with Sr2+ did not alter the time course of the ERP. 6. Two-pulse facilitation increased quantal output without changing the time to peak or the time constant of decline. 7. Quantal output was enhanced still more following a brief series of repetitive nerve stimulations. There was a lengthening of the time to peak; there was no change in the decline. The depression produced by longer series of repetitive stimulations did not change the time course of the ERP. 8. 4-Aminopyridine (4-AP) and dimethylsulphoxide (DMSO) increased quantal output and lengthened the time to peak, without altering the time constant for decline. 9. Adenosine decreased quantal output without altering the time course of the ERP.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗

Stimulated secretion of pituitary hormones in normal humans: a novel direct assessment from blood concentrations.

Gland responsiveness is usually assessed by administering suitable secretagogues and measuring the resulting hormone concentration in blood after the specific stimulus. Such response-to-stimulus tests are routinely conducted for the clinical diagnosis of pathologies involving the pituitary hormones growth hormone, prolactin, luteinizing hormone, follicle stimulating hormone, adrenocorticotropic hormone, and thyrotropin hormone. However, the current evaluation approaches, based on the maximum peak value or the (normalized) area under the curve, are inadequate under several respects. A more physiologically based index of responsiveness is the amount of released hormone. This is not directly accessible but is typically estimated by (computationally expensive) deconvolution analysis. The present work derives a simple formula yielding the amount of released hormone as a linear combination of blood concentrations through proper weights depending on hormone kinetics and sampling protocol. The weights are derived and reported for all six pituitary hormones and the more common sampling protocols. A validation study involving 174 test experiments has been carried out. The use of the formula shows excellent agreement with the cumulative secretion estimates obtained through deconvolution analysis.

Adolescent↗

Insulin secretion rate during glucose stimuli: alternative analyses of C-peptide data.

The ability to evaluate the pancreatic insulin secretion rate (ISR) is essential for a quantitative understanding of the glucose regulation system in man. Various approaches have been developed for evaluation of the ISR in vivo. The aim of this study was to compare input/output and compartmental models of C-peptide to reconstruct the ISR in response to both physiological and nonphysiological glucose stimuli in healthy humans. In particular we applied the nonparametric stochastic deconvolution and the C-peptide minimal model approaches to the graded up&down glucose infusion protocol, where glucose was infused at progressively increasing and then decreasing rates, and to the intravenous glucose tolerance test (IVGTT), where an impulse dose of glucose was administered. Our results show that the two models give virtually identical results when glucose and C-peptide (and thus ISR) profiles are smooth and regular, but when vigorous nonstationarities are present, like during the first 4 min of the IVGTT, the two ISR profiles are different (but not their areas under the curve). The C-peptide minimal model, albeit requiring, at variance with deconvolution, the knowledge of glucose data, has the advantage of providing quantitative indices of the beta-cell function, which is important in the parametric definition of different physiopathological states.

Adult↗

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions.

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Algorithms↗