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Simultaneous analysis of multiple fluorescence decay curves by Laplace transforms. Deconvolution with reference or excitation profiles.

The properties and potentials of the noniterative Laplace deconvolution (LAP2) (M. Ameloot and H. Hendrickx, Biophys. J. 44 (1983) 27) are further investigated. It is shown that LAP2 is exact and that no extrapolations have to be calculated or assumed for the data measured in the actual time window if the impulse response function of the investigated system can be described by a sum of exponentials. The formulas for the LAP2 deconvolution against the measured decay of a reference compound instead of the recorded excitation profile are derived. The procedure for the simultaneous analysis of multiple fluorescence decay curves by LAP2 is described in detail. This global analysis allows one to link any decay parameter, is fast and compares favorably with the nonlinear least-squares iterative reconvolution methods. Because of its short computation time the global analysis by LAP2 provides an efficient way to analyze the fluorescence decay surface in terms of decay associated spectra.

Anthracenes

X-ray small angle scattering. A new deconvolution method for evaluating electron density distributions from small angle scattering diagrams.

The direct determination of the electron density distributions of multilayered specimens with a small number of unit cells from X-ray small angle scattering experiments via the Q-function method of Hosemann and Bagchi includes the deconvolution of the so-called Q(o)-function, the generalized Patterson function of one unit cell. In this paper a new and direct deconvolution method on the basis of Fourier series is presented which is suitable for one-dimensional centrosymmetrical (or antisymmetrical) density distributions. A FORTRAN-program has been written which has an execution time of ca. 20 s on an UNIVAC 1106-computer. The procedure has been successfully tested on some convolution functions generated by membrane-type electron density distributions.

Computers

Quantitative deconvolution of heavily fused chromatographic peaks of biological components using a multi-wavelength UV detector.

Quantitative deconvolution of a chromatographic peak with extremely low UV absorption (less than 0.005 A.U.) is demonstrated for the analysis of an anaesthetic (ketamine) in rabbit serum. One ketamine metabolite, nor-ketamine, was deconvoluted from a completely fused peak in the three-dimensional chromatogram by using a highly sensitive multi-wavelength UV detector. After injection of ketamine, the nor-ketamine level in the serum increased to 3 micrograms/ml, calculated as ketamine, in 120 min.

Animals

Multiple oral administration of a ketoprofen-dextran ester prodrug in pigs: assessment of gastrointestinal bioavailability by deconvolution.

Deconvolution has been applied to estimate the in vivo dissolution/release process of ketoprofen from a ketoprofen-dextran ester prodrug in pigs. The prodrug was given to three pigs at intervals of 12 hr and in seven doses corresponding to 4 mg ketoprofen/kg body weight. Frequent blood sampling was carried out at the first, third, and seventh intervals. Plasma steady-state concentrations of ketoprofen following the prodrug administration were between 2 and 4 micrograms/ml. The reference consisted of a single p.o. dose of parent ketoprofen (4 mg/kg body weight). For each pig the response following the multiple dosing was deconvolved with the reference response using an algebraic deconvolution procedure adopted from the literature. The obtained cumulated in vivo dissolution/release profiles revealed similar release rates for the three pigs and similar extents of release (59, 70, and 65%). The mean in vivo dissolution/release times (MDT) were calculated to be 5.4, 6.1, and 5.7 hr, respectively. In conclusion, following administration of the dextran prodrug the plasma concentration curves and the dissolution/release profiles are uniform, with small interindividual variations.

Administration, Oral

Theoretical aspects of multiple deconvolution analysis for quantification of left to right cardiac shunts.

A new method for quantification of left to right cardiac shunts by Bourguignon et al based on multiple deconvolution analysis is critically analysed within the framework of a simple mathematical model. Underlying assumptions are explicitly stated and their validity discussed. It turns out that some reinterpretation of the method is necessary. Using the same ideas as in multiple deconvolution analysis, a new relation for the pulmonary to systemic flow ratio is proposed on a theoretical basis. This technique may be useful when diagnosing left to right cardiac shunts with radiocardiographic methods.

Coronary Circulation

Error analysis by simulation studies in renography deconvolution.

The renogram, defined as the time-activity curve obtained from measurements with a gamma detector over the kidneys after a prior injection of a radioactive tracer, can be quantified using the deconvolution method. Essentially all the inherent information in the renogram, the estimated relative renal uptake function and transit time spectrum through the kidney, can be derived from the computed renal retention function. This study shows how statistical and physiological noise and different backgrounds affect the accuracy of the derived parameters. Confidence intervals for the estimated relative renal function and mean transit time (MTT) are presented. The principal source of error in relative renal function was due to extrarenal background. It was found that the error in mean transit time due to statistical noise was proportional to MTT, that the presence of extrarenal background strongly affected the accuracy of the MTT, whereas the vascular background in the renogram was of minor importance. Physiological noise, interpreted as periodic changes in transit times does, strictly speaking, invalidate the deconvolution principle, but it was possible to calculate a valid mean value of the different actual transit times. The transit time spectrum, measured by differentiation of the computed retention function, was found to be of no practical value with use of the unconstrained matrix method. The signal to noise ratio and consequently the need for smoothing can be estimated from the sum of the squared second derivatives of the renogram itself. The plateau levels in the renal retention function provide a more reliable estimate for the relative function ratio than the relative amplitude of a renogram in which extrarenal background only has been subtracted.

Algorithms

Constrained least-squares restoration and renogram deconvolution: a comparison by simulation.

Before deconvolution can be used in renography, it is necessary to decide whether the renal function is sufficiently good to allow it. To see if this decision can be circumvented, an iterative constrained least-squares restoration (CLSR) method was implemented in which the point of termination of the iteration occurs when a residual vector has a value less than an estimate of the noise in the original renogram curve. The technique was compared with the matrix algorithm and with direct FFT division. The comparison was achieved by deconvolving simulated renogram data with differing transit time spectra and statistics. As expected, the FFT technique produced results of little value whereas the CLSR and matrix methods produced values of mean transit time (MTT) that differed slightly from the expected results. Analysis indicated that the matrix approach was superior when the percentage noise component was less than 6% and vice versa. No technique produced useful transit time spectra. As the CLSR technique produced better results than the matrix method in simulations with relatively long MTTs and high noise, it seems reasonable to suggest that it might be used for renogram deconvolution without the need for previous inspection of the curves.

Humans

Deconvolution of chemical shift spectra in two- or three-dimensional [19F] MR imaging.

The chemical shift spectra of 19F in perfluorinated compounds (PFCs) present a nontrivial impulse response function for magnetic resonance (MR) imaging. The 19F images of organs containing PFCs can be degraded by blurring and ghost image artifacts. Two methods (noise masked deconvolution and maximum entropy deconvolution) are presented that allow the chemical shift spectra of 19F in PFCs to be used to extract high quality MR images free of chemical shift artifact. Both techniques rely on postprocessing of either the raw data or the original image to produce images that are not degraded by the chemical shift spectra of the compound being imaged and that exhibit a signal-to-noise ratio equal to or better than that observed in the original image. The techniques are general in that they can be used with many PFC spectra. Using MR imaging data obtained from phantoms filled with cis/transperfluorodecalin and perfluorotributylamine (FC-43), the methods are compared in terms of their (a) ability to eliminate the chemical shift artifact associated with the PFC spectrum; (b) signal-to-noise performance; and (c) ability to preserve information related to the density and the longitudinal relaxation rate of the resonant nuclei. The utility of these techniques is demonstrated by a series of three-dimensional Fourier transform in vivo images of FC-43 emulsion in a mouse liver.

Algorithms

The individual kidney function. A comparison between frame summation and deconvolution.

A variety of methods have been developed to estimate the individual kidney function. Many methods use a scintillation camera the data from which are processed in a computer system. To compare two of these methods, the principles of which are completely different, such as the 'Oberhausen' method of frame summation and background subtraction and a method that uses deconvolution, the scintillation camera data of 121 patients have been collected. A computer program was written to calculate the individual kidney function by which both methods were used. It is often asserted that specific techniques of frame summation and background subtraction are not suitable to define the individual kidney function. To see if this assertion is true, two different methods have been compared using the contribution of the left kidney to the individual kidney function. An excellent correlation between the two methods was found (R = 0.9808, n = 121) which proves the ability of both the 'Oberhausen' method and the method that uses deconvolution. However, it is also seen that the 'Oberhausen' method may give false results, caused by an increasing background count outside the kidneys in patients with a large difference in function between the two kidneys.

Humans

Mössbauer characterization of the tetraheme cytochrome c3 from Desulfovibrio baculatus (DSM 1743). Spectral deconvolution of the heme components.

Mössbauer spectroscopy was used to study the tetraheme cytochrome c3 from Desulfovibrio baculatus (DSM 1743). Samples with different degrees of reduction were prepared using a redoxtitration technique. In the reduced cytochrome c3, all four hemes are reduced and exhibit diamagnetic Mössbauer spectra typical for low-spin ferrous hemes (S = 0). In the oxidized protein, the hemes are low-spin ferric (S = 1/2) and exhibit overlapping magnetic Mössbauer spectra. A method of differential spectroscopy was applied to deconvolute the four overlapping heme spectra and a crystal-field model was used for data analysis. Characteristic Mössbauer spectral components for each heme group are obtained. Hyperfine and crystal-field parameters for all four hemes are determined from these deconvoluted spectra.

Cytochrome c Group

Measurement of hepatocellular function with deconvolutional analysis: application in the differential diagnosis of acute jaundice.

A direct, noninvasive technique was developed to quantitate hepatocyte function with computer assessment of scintiscans obtained after administration of technetium-99m disofenin in 53 patients with acute jaundice: 32 patients with normal livers, 10 patients with acute biliary obstruction, and 11 patients with acute hepatocellular dysfunction. In all patients a final clinical diagnosis was obtained with follow-up for a minimum of 4 months and, in most patients with obstruction or dysfunction, with surgery, intraoperative cholangiography, ultrasound, and/or computed tomography. Heart (blood pool) and liver time-activity curves were generated for 32 minutes after intravenous injection of 5-15 mCi (185-555 MBq) of Tc-99m disofenin and were subjected to deconvolutional analysis to determine the first-pass hepatocyte extraction fraction (HEF) of the tracer. The difference in HEF between patients with obstruction and those with dysfunction was highly significant (P = 3.3 X 10(-19)). Deconvolutional analysis eliminates the effects of tracer recirculation, thus permitting direct measurement of hepatic disofenin extraction, and appears to provide functional information useful in evaluation of the patient with acute jaundice.

Acute Disease

Thermal recovery after passage of the pulmonary circulation assessed by deconvolution.

For indicator-dilution studies, complete thermal recovery after passage of heat through the pulmonary circulation would be desirable. However, the results in the literature obtained by extrapolation techniques are inconsistent. To overcome problems of the extrapolation approach, transport functions of the pulmonary circulation (including the left heart) were computed by deconvolution of pulmonary arterial and aortic pairs of thermodilution curves after central venous indicator injection (10 ml of an ice-cold blood indocyanine green dye mixture). Thermal recovery was determined as the finite integral of the transport function. Thirteen mongrel dogs under piritramid-N2O anesthesia were examined under base-line conditions, in orthostasis to alter the distribution of pulmonary blood flow (9 dogs), and in oleic acid edema (8 dogs). Using the deconvolution approach, thermal recovery was 0.97 +/- 0.04 under base-line conditions, 0.96 +/- 0.03 in orthostasis, and 0.96 +/- 0.05 in pulmonary edema. Thermal recovery determined from extrapolated dilution curves was greater than 100% in all groups, a physically impossible finding. It is concluded that thermal recovery is incomplete but insensitive with respect to the distribution of blood flow and to the size of the extravascular compartment. Monoexponential extrapolation is unsuited for the determination of thermal recovery.

Animals

The practical significance of two-dimensional deconvolution in echography.

This paper evaluates deconvolution (inverse filtering) as applied to ultrasonic imaging systems, and discusses the obstacles which are encountered employing the technique in practice. A minicomputer is used to generate artificial echo signals, simulating rf signals resulting from a set of point reflectors in a homogeneous medium, as recorded by an electronically focused group-steered linear array scanner. Two-dimensional deconvolution in combination with a Wiener noise reduction filter (i.e., a Wiener-Inverse filter) is applied to these simulated rf signals, which were contaminated with white noise. The efficacy of the Wiener-Inverse filter is defined in terms of its ability to resolve two point reflectors with a lateral spacing equal to the local -6 dB width of the ultrasonic beam. In favorable circumstances, the targets are resolved at signal-to-noise ratios (SNR) better than 20 dB, where SNR is defined as the maximum signal power divided by the average noise power level. Nonlinear effects due to quantization or signal clipping are investigated. In order to improve the resolution of an rf signal with a dynamic range of 40 dB, the input signal should be digitized at a minimum of 12 bits. The problem of signal clipping can be circumvented by oversampling. The two-dimensional Wiener-Inverse filter is defined in terms of both temporal and spatial properties of the insonification. Effects of wave diffraction give rise to a depth-dependent ultrasonic beam. As a result of a misfit of the Wiener-Inverse filter and the local properties of the ultrasonic beam, erroneous noisy texture arises in the image. Adaptation of the Wiener-Inverse filter with respect to the beam properties gives acceptable results, at the expense of a rather large computational effort.

Computer Simulation

[Usefulness of radioisotope (RI) deconvolution analysis with Tc-99m-DTPA in transplanted kidney].

In 50 renal transplant recipients, we performed radioisotope (RI) deconvolution analysis, as reported by O'Reilly, in 179 renograms from dynamic renal scanning with Tc-99m-DTPA and obtained MTT (mean transit time) and H0 (initial height) values. We found characteristic features of various graft conditions using the combination of MTT and H0. The mean H0 value was greater in normally functioning grafted kidneys than in kidneys with other states. The mean MTT in the normal group was about 2 min. In the acute rejection group, the mean H0 value was lower and the mean MTT was more prolonged compared with the normal group. In ATN group, the mean MTT was similar to that in the acute rejection group, whereas the mean H0 value was lower. In the chronic rejection group, the mean MTT was similar to that in the normal group, but the mean H0 value showed a lower one. The hydronephrosis group had an extremely prolonged MTT. This study indicated that the combination of H0 and MTT obtained from RI deconvolution analysis is a valuable means of understanding the condition of renal grafts.

Graft Rejection

[An experimental study of liver perfusion using non-diffusible radiotracers: differentiation of the arterial and portal venous components by deconvolution analysis of first-pass time-activity curves].

The transfer function of the liver perfusion is an idealized time-activity curve that could be registered over the liver if a non-diffusible tracer would be injected directly into the abdominal aorta and no tracer recirculation would occur. The reproducibility of the transfer function was experimentally investigated in foxhounds. Both the routes of tracer application and the modes of data evaluation were varied and the perfusion was investigated under physiological and pathological conditions. The transfer function was calculated by deconvolution analysis of first-pass time-activity curves using the matrix regularization method. The transfer function showed clearly distinguishable arterial and portal-venous components. Repeated peripheral venous and central aortic applications resulted in reproducible curves. In addition to the arterial and portal-venous components the subcomponents of the portal-venous component could also be identified in the transfer function after ligation of the appropriate vessels. The accuracy of the mathematical procedure was tested by computer simulations. The simulation studies demonstrated also that the matrix regularization technique is suitable for deconvolution analysis of time-activity curves even when they are significantly contaminated by statistical noise. Calculation of the transfer function of liver perfusion and of its quantitative parameters seems thus to be a reliable method for non-invasive investigation of liver hemodynamics under physiological and pathological conditions.

Animals

Hepatocyte versus biliary disease: a distinction by deconvolutional analysis of technetium-99m IDA time-activity curves.

A combination of quantitative hepatobiliary imaging techniques was developed to study normal control subjects and patients with 3 categories of hepatobiliary disease: 1) alcoholic cirrhosis; 2) sclerosing cholangitis; and 3) isolated common bile duct obstruction. Scintigraphic images were supplemented by quantitative measurement of hepatic extraction fraction by deconvolutional analysis and liver excretion T 1/2 by a nonlinear least squares method. In diseases confined primarily to the biliary tract (isolated common bile duct obstruction and sclerosing cholangitis), the mean hepatic extraction fraction as measured by deconvolutional analysis was not different from that in normal controls. In severe alcoholic cirrhosis, considered primarily a hepatocyte disease, the hepatic extraction fraction was markedly reduced. The T 1/2 excretion, compared to normal subjects, was prolonged in all three liver disease categories. We conclude that these quantitative parameters were able to detect hepatobiliary disease and to separate severe hepatocyte disease from biliary tract disease.

Biliary Tract Diseases

Biokinetics of bone tracers by means of deconvolution analysis--comparison of 99mTc MDP, 99mTc DPD and 99mTc EHDP.

Transfer functions of 99mTc methylene diphosphonate (MDP), 99mTc 2,3-dicarboxypropane-1,1-diphosphonate (DPD) and 99mTc ethane-1-hydroxy-1,1-diphosphonate (EHDP) into bone and extravascular fluid of soft tissues were determined in 5 dogs by deconvolution analysis of the time-course of plasma, soft tissue and bone radioactivity. The transfer rates 5 min after injection--indicating the rapid exchange of the tracer between plasma and the extravascular fluid--decrease in the order MDP greater than EHDP greater than DPD (P less than 0.05). The transfer rates into bone--determined from transfer rates between 30 and 60 min--decreased in a different order, i.e. MDP greater than DPD greater than EHDP (P less than 0.05). The fractional bone uptake of diphosphonates estimated from the ratio of early to late transfer rates was slightly greater for DPD than for MDP and EHDP respectively. The difference between DPD and MDP was not significant (P greater than 0.05). The average bone and soft tissue concentrations of DPD 60 min after injection were greater than that of MDP and EHDP due to different plasma concentrations (DPD greater than EHDP greater than MDP), whereas the bone-to-soft tissue ratios decreased in the sequence MDP greater than DPD greater than EHDP (P less than 0.05).--Our results reveal different biokinetics of MDP, DPD and EHDP explaining variations in osseous and soft tissue uptake suggesting that deconvolution analysis could play an important role in bone scan interpretation.

Animals

Drug absorption evaluation in the presence of changes in clearance: an algorithm and computer program for deconvolution with exact clearance correction.

Most commonly drug absorption is evaluated with a reference dosing given on separate occasions. The assumption that no change in drug disposition is taking place between the drug administrations is often violated resulting in errors in the calculations. A novel deconvolution method is presented which exactly compensates for a change in drug clearance. The method is based on a model independent disposition decomposition-recomposition technique. The distribution function is obtained from an i.v. administration by disposition decomposition. This distribution function is assembled together with the elimination kinetics containing the perturbed clearance to construct the perturbed disposition function in the subsequent disposition recomposition operation. The perturbed absorption response is finally deconvolved using the corresponding perturbed disposition function. It is shown that the perturbed clearance can be obtained from the log-linear terminal disposition phase once the distribution function has been obtained from an i.v. administration. The proposed method is implemented in an algorithm and computer program DCONB and demonstrated using human cimetidine drug level data from an i.v. and oral administration. The usage of DCONB is identical to DECONV previously published. It requires only regular sums of exponentials to be fitted to drug level data. Such fittings are routinely done in pharmacokinetics thereby enabling DCONB to be implemented very simply.

Algorithms