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Direct deconvolution algorithms based on Laplace transforms in nuclear medicine applications.

A set of algorithms is presented for direct deconvolution of the residue signal of an organ with the input signal to the organ. The deconvolution process yields the residual impulse response from which the distribution of transit times and the important mean transit time can be readily determined. The deconvolution method is based on the Laplace transform and it requires that the input signal can be fitted with an expression consisting of one, two or three exponentials with or without a bolus term at zero time or a constant term. These types of exponential expressions for the input signal cover a wide range of the input signals encountered in nuclear medicine applications. Simulation studies of the residue signal by convolution of various input signals with a number of residual impulse response models yielded an excellent accuracy of the deconvoluted residual impulse response for a suitably small sampling time. The simulations provide an opportunity to understand further the shapes of the residue curves depending on the shape of the input signal and the distribution of transit times. Simulations with Gaussian-distributed noise and noise spikes superimposed on the residue signal were also made to investigate the robustness of the direct deconvolution algorithm using apparently real-life data.

Algorithms↗

Mean transit times without deconvolution...reconsidered.

A new deconvolution technique is described. It is based on an earlier method which used a graphical technique to analyse the early stages of organ data and blood curves to obtain the background subtraction factor and the uptake constant for tracer uptake by the organ. In that initial application, those variables were then applied to a later point on the organ and blood curves to calculate a mean transit time without first producing a retention function. This new deconvolution technique performs that later step on all points of the organ data curve to produce a function showing how the mean transit time varies with time. This considered to be the area under the retention function (i.e. the integral of the retention function), and the retention function itself is then obtained by differentiation. Modelling techniques were used to create renogram shapes by convoluting known (input) retention functions with a calculated blood curve. The new deconvolution method was then used to recover the retention function from each artificial data curve. The recovery of that input data implies that the new deconvolution technique is sufficiently successful to justify further consideration. In addition, as a demonstration, iterative deconvolution and the new method were both used on renograms from an obstructed kidney and a kidney with normal outflow. Both methods produced similar shaped retention functions.

Child, Preschool↗

Deconvolution of disoriented fiber diffraction data using iterative convolution and local regression.

Computationally efficient procedures are described for the deconvolution of disoriented fiber diffraction data to the resolution limit of measurable intensity in the patterns. The methods can be applied to diffraction data from imperfectly parallel arrays of one-dimensionally periodic rods or two-dimensionally periodic sheets, randomly rotated about their unique axes, to derive a representation of the intensity distribution corresponding to perfectly parallel orientation. With use of angular convolution and local angular regression, a set of uniform cylindrically averaged squared structure factors are iteratively adjusted, subject to a minimum-wavelength constraint, until they produce a disoriented pattern that fits the observed diffraction data. The results from this deconvolution provide a measure of the properly scaled cylindrically averaged squared structure factors, which can be used with other structural information to construct a physically plausible trial model suitable for further refinement. Sample deconvolutions of simulated X-ray patterns from partially oriented gap junction membranes are presented and the results from point-model deconvolutions are compared to those from constrained deconvolutions that began with the transform of a physically plausible trial model.

Intercellular Junctions↗

A novel approach to the 2-D blind deconvolution problem in medical ultrasound.

The finite frequency bandwidth of ultrasound transducers and the nonnegligible width of transmitted acoustic beams are the most significant factors that limit the resolution of medical ultrasound imaging. Consequently, in order to recover diagnostically important image details, obscured due to the resolution limitations, an image restoration procedure should be applied. The present study addresses the problem of ultrasound image restoration by means of the blind-deconvolution techniques. Given an acquired ultrasound image, algorithms of this kind perform either concurrent or successive estimation of the point-spread function (PSF) of the imaging system and the original image. In this paper, a blind-deconvolution algorithm is proposed, in which the PSF is recovered as a preliminary stage of the restoration problem. As the accuracy of this estimation affects all the following stages of the image restoration, it is considered as the most fundamental and important problem. The contribution of the present study is twofold. First, it introduces a novel approach to the problem of estimating the PSF, which is based on a generalization of several fundamental concepts of the homomorphic deconvolution. It is shown that a useful estimate of the spectrum of the PSF can be obtained by applying a proper smoothing operator to both log-magnitude and phase of the spectra of acquired radio-frequency (RF) images. It is demonstrated that the proposed approach performs considerably better than the existing homomorphic (cepstrum-based) deconvolution methods. Second, the study shows that given a reliable estimate of the PSF, it is possible to deconvolve it out of the RF-image and obtain an estimate of the true tissue reflectivity function, which is relatively independent of the properties of the imaging system. The deconvolution was performed using the maximum a-posteriori (MAP) estimation framework for a number of statistical priors assumed for the reflectivity function. It is shown in a series of in vivo experiments that reconstructions based on the priors, which tend to emphasize the "sparseness" of the tissue structure, result in solutions of higher resolution and contrast.

Algorithms↗

Image quality improvement via spatial deconvolution in optical tomography: time-series imaging.

We present the fourth in a series of studies devoted to the issue of improving image quality in diffuse optical tomography (DOT) by using a spatial deconvolution operation that seeks to compensate for the information-blurring property of first-order perturbation algorithms. Our earlier reports consider only static target media. Here we report spatial deconvolution applied to media with time-varying optical properties, as a model of tissue dynamics resulting from varying metabolic demand and modulation of the vascular bed. Issues under study include the influence of deconvolution on the accuracy of the recovered temporal and spatial information. The impact of noise is also explored, and techniques for ameliorating its information-degrading effects are examined. At low noise levels (i.e, < or = 5% of the time-varying signal amplitude), spatial deconvolution markedly improves the accuracy of recovered information. Temporal information is more seriously degraded by noise than is spatial information, and the impact of noise increases with the complexity of the time-varying signal. These effects, however, can be significantly reduced using simple noise suppression techniques (e.g., low-pass filtering). Results suggest that the deconvolution scheme should provide considerable enhancement of the quality of spatiotemporal information recovered from dynamic DOT techniques applied to tissue studies.

Algorithms↗

Signal-to-noise ratio and frequency analysis of continuous loop averaging deconvolution (CLAD) of overlapping evoked potentials.

In this study, a frequency domain formulation of continuous loop averaging deconvolution (CLAD) of overlapping evoked potentials is developed and applied for the extraction of transient responses from recordings obtained at high stimulation rates. This formulation allows for a faster execution of CLAD by using fast Fourier transform algorithms. The frequency characteristics of the deconvolution filter depends exclusively on the stimulus sequence and determines whether the noncoherent noise is amplified or attenuated in different frequencies. A formula for calculating the signal-to-noise ratio (SNR) achieved by the deconvolution process is developed. The newly developed theory and the methodology is applied to the extraction of the auditory brainstem and middle latency responses using various sequences. The effects of the sequence used and the number of sweeps averaged in ongoing acquisition on SNR are examined by using single sweep recordings. The results verify the deconvolution theory and the methodology and show its limitations. Depending on the frequency characteristics of the sequence, the deconvolution process can amplify or attenuate the EEG noise. Proper selection of the stimulus sequence can increase the SNR enhancement obtained with conventional averaging.

Acoustic Stimulation↗

LH and FSH secretory responses to GnRH in normal individuals: a non-parametric deconvolution approach.

OBJECTIVE: To reconstruct the instantaneous secretion rate (ISR) of LH and FSH after GnRH administration in normal volunteers using non-parametric deconvolution, and to derive a direct integration formula to evaluate the amount of LH and FSH secreted during the first 60 min after the stimulus. DESIGN AND METHODS: First, the deconvolution method was validated in vivo by reconstructing doses ranging from 7.5 IU to 75 IU injected in three healthy adult volunteers whose endogenous LH had previously been downregulated by pretreating them, 3-4 weeks earlier, with 3.75 mg GnRH agonist i.m. Then, 40 healthy adult male volunteers were tested with a single 100 microg GnRH bolus, administered at 0 min. LH and FSH concentrations were determined at -30, 0, 15, 30, 45, 60, 90, and 120 min. RESULTS AND CONCLUSIONS: The validation study, conducted over a 10-fold range of doses, demonstrated that non-parametric deconvolution provided a reasonably accurate estimate of the amount of hormone entering the circulation. Applying deconvolution to the LH and FSH responses to GnRH, the ISRs of both hormones were shown to have a similar pattern, with a clearly delimited pulse after the GnRH bolus. In conjunction with earlier analyses of estimates of GHRH-stimulated GH secretion, we conclude that secretagogues evoke discrete LH, FSH, and GH secretory bursts of about 60 min total duration, despite markedly unequal (glyco-)protein hormone half-lives (18-500 min). With respect to the assessment of total hormone release during the first 60 min after the stimulus, the integration formula provided a reliable approximation of the result obtained by deconvolution, and had a negligible dependence on the samples at times 90 and 120 min.

Adult↗

Multivariate selectivity as a metric for evaluating comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry subjected to chemometric peak deconvolution.

Two-dimensional gas chromatography (GC x GC) coupled to time-of-flight mass spectrometry (TOFMS) [GC x GC-TOFMS)] is a highly selective technique well suited to analyzing complex mixtures. The data generated is information-rich, making it applicable to multivariate quantitative analysis and pattern recognition. One separation on a GC x GC-TOFMS provides retention times on two chromatographic columns and a complete mass spectrum for each component within the mixture. In this report, we demonstrate how GC x GC-TOFMS combined with trilinear chemometric techniques, specifically parallel factor analysis (PARAFAC) initiated by trilinear decomposition (TLD), results in a powerful analytical methodology for multivariate deconvolution. Using PARAFAC, partially resolved components in complex mixtures can be deconvoluted and identified without requiring a standard data set, signal shape assumptions or any fully selective mass signals. A set of four isomers (iso-butyl, sec-butyl, tert-butyl, and n-butyl benzenes) is used to investigate the practical limitations of PARAFAC for the deconvolution of isomers at varying degrees of chromatographic resolution and mass spectral selectivity. In this report, multivariate selectivity was tested as a metric for evaluating GC x GC-TOFMS data that is subjected to PARAFAC peak deconvolution. It was found that deconvolution results were best with multivariate selectivities over 0.18. Furthermore, the application of GC x GC-TOFMS followed by TLD/PARAFAC is demonstrated for a plant metabolite sample. A region of GC x GC-TOFMS data from a complex natural sample of a derivatized metabolic plant extract from Huilmo (Sisyrinchium striatum) was analyzed using TLD/PARAFAC, demonstrating the utility of this analytical technique on a natural sample containing overlapped analytes without selective ions or peak shape assumptions.

Evaluation Studies as Topic↗

Absorption profiles of rectally administered midazolam estimated by deconvolution.

UNLABELLED: An algebraic deconvolution procedure adopted from the literature has been used to estimate the absorption profiles of rectally administered midazolam (0.3 mg/kg) in 8 healthy subjects. The extent of absorption estimated by the conventional AUC approach has previously been published and was compared to the deconvolution results. In the original study the sampling period was 840 min. When a deconvolution approach is used there may be no need to sample after the absorption is completed. Thus in this communication only samples drawn within the first 120 min and 300 min were used. The bioavailability estimated by the AUC ratio (mean 0.52 +/- SDrel 16%) is compared to the deconvolution results obtained using only data points within 120 (0.46 +/- 22%) (p = 0.02) and 300 min (0.51 +/- 20%) (p = 0.6) after drug administration. The absorption is almost complete after 120 min. Regarding the absorption rates 40% (range 27.55%) of the dose is absorbed after 60 min. The relative (normalised) absorption profiles showed that 79% (range 63-90%) of the maximum absorbed amount is absorbed within 60 min. IN CONCLUSION: Information regarding the rectal absorption of midazolam can be obtained from a sampling period of approximately 5 hours using the deconvolution approach. The algorithm used is relative easy to implement and is very easy to use with polyexponential parameters obtained by curve fitting as input.

Administration, Rectal↗

Deconvolution analysis in radionuclide quantitation of left-to-right cardiac shunts.

A poor bolus injection results in an unsatisfactory quantitative radionuclide angiocardiogram in as many as 20% of children with possible, left-to-right (L-R) cardiac shunts. Deconvolution analysis was applied to similar studies in experimental animals to determine whether dependence on the input bolus could be minimized. Repeated good-bolus, prolonged (greater than 2.5 sec), or multiple-peak injections were made in four normal dogs and seven dogs with surgically created atrial septal defects (ASD). QP/QS was determined using the gamma function. The mean QP/QS from ten good-bolus studies in each animal was used as the standard for comparison. In five trials in normal animals, where a prolonged or double-peak bolus led to a shunt calculation (QP/QS greater than 1.2 : 1), deconvolution resulted in QP/QS = 1.0. Deconvolution improved shunt quantitation in eight of ten trials in animals that received a prolonged bolus. The correlation between the reference QP/QS and the QP/QS calculated from uncorrected bad bolus studies was only 0.39 (p greater than 0.20). After deconvolution using a low pass filter, the correlation improved significantly (r = 0.77, p less than 0.01). The technique gave inconsistent results with multiple-peak bolus injections. Deconvolution analysis in these studies is useful in preventing normals from being classified as shunts, and in improving shunt quantitation after a prolonged bolus. Clinical testing of this technique in children with suspected L-R shunts seems warranted.

Angiocardiography↗

Estimating the diagnostic yields resulting from renography and deconvolution parameters: a logistic regression analysis.

METHODS: Seventy patients with established diagnoses of normal, parenchymally insufficient or acutely obstructed kidneys were subjected to gamma camera renography. Deconvolution was then performed using three main techniques subdivided into six variants. Parameters from time-activity curves as well as retention curves were calculated. Logistic regression analysis was performed to assess the ability of renography and deconvolution methods to differentiate between kidney groups. RESULTS: Discrimination between the groups was achieved by standard renography using six of 17 tested renogram parameters. Based on a set of six curve parameters, the correct classification rates ranged 86%-100%. Five of the six variants of the deconvolution technique used produced similar results. None, however, produced results which were as robust as those from renography. The sixth deconvolution method was consistently worse than the others. CONCLUSION: Standard renography was consistently better than any of the deconvolution techniques used in the separation of the kidney groups. Conceptually, the results of a logistic regression analysis of renogram parameters may raise possibilities in the field of computer-aided diagnosis.

Adolescent↗

An evaluation of two-photon excitation versus confocal and digital deconvolution fluorescence microscopy imaging in Xenopus morphogenesis.

The ability to visualize cell motility occurring deep in the context of opaque tissues will allow many currently intractable issues in developmental biology and organogenesis to be addressed. In this study, we compare two-photon excitation with laser scanning confocal and conventional digital deconvolution fluorescence microscopy, using the same optical configuration, for their ability to resolve cell shape deep in Xenopus gastrula and neurula tissues. The two-photon microscope offers better depth penetration and less autofluorescence compared to confocal and conventional deconvolution imaging. Both two-photon excitation and confocal microscopy also provide improved rejection of "out-of-focus" noise and better lateral and axial resolution than conventional digital deconvolution microscopy. Deep Xenopus cells are best resolved by applying the digital deconvolution method on the two-photon images. We have also found that the two-photon has better depth penetration without any degradation in the image quality of interior sections compared to the other two techniques. Also, we have demonstrated that the quality of the image changes at different depths for various excitation powers.

Animals↗

Visualization of synaptic markers in the optic neuropils of Drosophila using a new constrained deconvolution method.

The fruitfly Drosophila melanogaster offers compelling genetic advantages for the analysis of its nervous system, but cell size precludes immunocytochemical analysis of wild-type structure and mutant phenotypes beyond the level of neuronal arborizations. For many antibodies, especially when immunoelectron microscopy is not feasible, it would therefore be desirable to extend the resolution limit of confocal microscopy as far as possible. Because high-resolution confocal microscopy suffers from considerable blurring, so-called deconvolution algorithms are needed to remove, at least partially, the blur introduced by the microscope and by the specimen itself. Here, we present the establishment and application of a new deconvolution method to visualize synaptic markers in Drosophila optic neuropils at the resolution limit of light. We ascertained all necessary parameters experimentally and verified them by deconvolving injected fluorescent microspheres in immunostained optic lobe tissue. The resulting deconvolution method was used to analyze colocalization between the synaptic vesicle marker neuronal synaptobrevin and synaptic and putative synaptic markers in photoreceptor terminals. We report differential localization of these near the resolution limit of light, which could not be distinguished without deconvolution.

Animals↗

Dermal absorption of pesticides calculated by deconvolution.

Using published human data on skin-to-urine and blood-to-urine transfer of 12 pesticides and herbicides, the skin-to-blood transfer rates for each compound were estimated by two numerical deconvolution techniques. Regular constrained deconvolution produced an estimated upper limit on cumulative dermal absorption of the radiolabel, while minimized deconvolution produced an upper bound on cumulative dermal absorption of parent compound. Dermal absorption rate was largest within 8 h of dosing for all pesticides examined. Only carbaryl showed a lag (3.5 h) in penetration. This may indicate a prolonged transit time through skin or a chemical transformation in skin has occurred. After onset, absorption occurred rapidly with 45% of the 120 h cumulative absorption occurring in 8 h. For parathion and dieldrin, over 50% of the 120 h total absorption occurred in the first 4 h. The deconvolution technique described here permits the calculation of the temporal aspect of dermal absorption for linear systems.

Humans↗

Deconvolution of mass spectra measured with a non-uniform detector array to give accurate ion abundances.

Array detectors are under active development since they offer large improvements in the efficiency of mass spectrum measurements. High quality is always a requirement whether array detectors are used for ions, electrons, UV, x-rays, etc., but in mass spectrometry the very high accuracy frequently needed in ion abundance measurements for isotope ratios is unique. These demands necessitate modelling the measurement process and careful deconvolution of the measured data. A linear model in terms of matrix algebra is presented in which the incident spectrum (unknown) and the measured spectrum are represented by column matrices and the action of the detector array on the incident spectrum is represented by an experimentally measurable square 'A' matrix. Residual noise in this matrix can be minimized following a singular value decomposition procedure and its use in 'forward deconvolution' of measured spectra is discussed. The random error in the incident ion counts is accounted for after the deconvolution since this is not an error from the perspective of the detector. The microchannel plate electron multiplier gain distribution is an important feature of the deconvolution.

Algorithms↗

Bioavailability of hydroxychloroquine tablets assessed with deconvolution techniques.

Four deconvolution methods (staircase, delta function, and least squares methods using single and sequential first-order input functions) were used to assess the absolute bioavailability of hydroxychloroquine tablets in nine healthy fasting volunteers. The volunteers received, in a random crossover design, a 155-mg oral tablet and a 155-mg iv infusion of racemic hydroxychloroquine. The mean fractions of the dose absorbed, calculated using the four deconvolution methods, were not statistically different (p = 0.70). The mean fraction absorbed (+/- SD) was 0.67 +/- 0.12, which was not significantly different from that reported previously in a conventional bioavailability study (p = 0.22). The mean absorption half-life was calculated to be 4.0 +/- 1.3 h. The mean lag time before absorption commenced was 0.57 +/- 0.30 h. The fraction of the dose absorbed ranged from 0.44 to 0.86. Low and/or variable bioavailability of hydroxychloroquine may be a cause of therapeutic failure in some patients. Validation of the deconvolution methods means that these techniques may now be used to assess the bioavailability of hydroxychloroquine in patients. An advantage of these methods is that samples need only be collected over the expected time period of absorption, rather than the whole time drug can be detected in the body, as is required in conventional area under the concentration-time curve ratio methods. Deconvolution studies may be completed in 2 weeks rather than the 10 months required for a conventional bioavailability study of hydroxychloroquine.

Adult↗

An algorithm for constrained deconvolution based on reparameterization.

The method of deconvolution is the most general method of evaluating drug absorption. Deconvolution does not normally subscribe to a particular structured model for the input function that would ensure non-negativity of the calculated input rate. Unfortunately, the increased flexibility gained by this "model independence" sometimes results in a calculated input rate that becomes negative in the late absorption phase. A method for constrained deconvolution is proposed to overcome this deficiency. The method is based on a reparameterization of the input function in a "model-free" context. The reparameterization schemes proposed are optimal in the sense that they give the input function its maximum flexibility possible while at the same time ensuring non-negativity. The method makes use of "deconvolution through convolution." The basic procedure of this technique is, during the curve fitting, to iteratively adjust the input function so that when it is convolved with the unit impulse response function it results in a curve that best fits the data from the extravascular administration. Cimetidine data from oral and iv administrations are deconvolved by the proposed method to demonstrate the basic procedures involved. The proposed method is easy to implement since it relies on simple curve-fitting procedures as routinely performed in pharmacokinetics. The procedure can be carried out using any of the many curve-fitting programs available that allow the user to supply the function to be fitted and allow simple bounds to be specified for the fitted parameters. The convolution required by the method can be done analytically using a previously published computer program.

Algorithms↗

Improved cell typing by charge-state deconvolution of matrix-assisted laser desorption/ionization mass spectra.

Robust, specific, and rapid identification of toxic strains of bacteria and viruses, to guide the mitigation of their adverse health effects and optimum implementation of other response actions, remains a major analytical challenge. This need has driven the development of methods for classification of microorganisms using mass spectrometry, particularly matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), that allows high-throughput analyses with minimum sample preparation. We describe a novel approach to cell typing based on pattern recognition of MALDI mass spectra, which involves charge-state deconvolution in conjunction with a new correlation analysis procedure. The method is applicable to both prokaryotic and eukaryotic cells. Charge-state deconvolution improves the quantitative reproducibility of spectra because multiply charged ions resulting from the same biomarker attaching a different number of protons are recognized and their abundances are combined. This allows a clearer distinction of bacterial strains or of cancerous and normal liver cells. Improved class distinction provided by charge-state deconvolution was demonstrated by cluster spacing on canonical variate score charts and by correlation analyses. Deconvolution may enhance detection of early disease state or therapy progress markers in various tissues analyzed by MALDI-MS.

Algorithms↗