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Applications of a general method for deconvolution using compartmental analysis.

A method of deconvolution is illustrated using compartmental models. The approach can be used to determine an arbitrary unknown input function from a measured response and the impulse response of the system. Compartmental models are constructed to specify (a) the function fitting the response data and (b) the impulse response of the system. Simulation of these models is then used to construct the unknown input function.

Alanine

Model-free deconvolution techniques for estimating vascular transport functions.

In this paper we present two methods which can be used to numerically deconvolve indicator dilution curves to obtain vascular transport functions. In the first method, direct algebraic deconvolution is made stable and practical by the damped least squares method. The second method involves a time-shift of the output curve which is based on the first and second moments of the input and output curves. This method is stable, computationally simple and can provide reasonable estimates of the transport function.

Animals

Quantitation of collagen fragments and gelatin by deconvolution of polarimetry denaturation curves.

A method for quantitating nicked or shortened molecules (fragments) in pepsinized bovine type I collagen preparations using polarimetry thermal denaturation curves is described. The shortened molecules denature about 4 degrees C lower than intact collagen molecules. The analog output of a polarimeter was digitized and stored on a microcomputer disk. A BASIC program was written which retrieves the specific rotation data from the disk, smooths the data with a boxcar average, and plots the derivative of the denaturation curve. The derivative curve was deconvoluted by fitting three Gaussian curves to the derivative curve using published algorithms. The area of the Gaussian centered at 37 degrees C was proportional to the amount of collagen fragments. A good correlation between the amount of fragments determined by polarimetry and by a trypsin sensitivity assay was observed. The overall precision of the method was about 10% RSD, and the method was repeatable by multiple analysts. Application of the method to reconstituted fibrillar collagen samples showed that more fragments are generated when pepsin digestion time is lengthened. By fitting a fourth Gaussian component to the derivative curve, the method can also be used to determine relative amounts of denatured collagen (helix partially unwound but alpha chains not nicked). The detection limit for denatured collagen is about 20%.

Algorithms

Evidence for radical anion formation during liquid secondary ion mass spectrometry analysis of oligonucleotides and synthetic oligomeric analogues: a deconvolution algorithm for molecular ion region clusters.

It is shown that one-electron reduction is a common process that occurs in negative ion liquid secondary ion mass spectrometry (LSIMS) of oligonucleotides and synthetic oligonucleosides and that this process is in competition with proton loss. Deconvolution of the molecular anion cluster reveals contributions from (M-2H).-, (M-H)-, M.-, and (M + H)-. A model based on these ionic species gives excellent agreement with the experimental data. A correlation between the concentration of species arising via one-electron reduction [M.- and (M + H)-] and the electron affinity of the matrix has been demonstrated. The relative intensity of M.- is mass-dependent; this is rationalized on the basis of base-stacking. Base sequence ion formation is theorized to arise from M.- radical anion among other possible pathways.

Algorithms

Determination of rotational correlation times from deconvoluted fluorescence anisotropy decay curves. Demonstration with 6,7-dimethyl-8-ribityllumazine and lumazine protein from Photobacterium leiognathi as fluorescent indicators.

The experimental and analytical protocols required for obtaining rotational correlation times of biological macromolecules from fluorescence anisotropy decay measurements are described. As an example, the lumazine protein from Photobacterium leiognathi was used. This stable protein (Mr 21 200) contains the noncovalently bound, natural fluorescent marker 6,7-dimethyl-8-ribityllumazine, which has in the bound state a long fluorescence lifetime (tau = 14 ns). Shortening of the fluorescence lifetime to 2.6 ns at room temperature was achieved by addition of the collisional fluorescence quencher potassium iodide. The shortening of tau had virtually no effect on the rotational correlation time of the lumazine protein (phi = 9.4 ns, 19 degrees C). The ability to measure biexponential anisotropy decay was tested by the addition of Photobacterium luciferase (Mr 80 000), which forms an equilibrium complex with lumazine protein. Under the experimental conditions used (2 degrees C) the biexponential anisotropy decay can best be described with correlation times of 20 and 60 ns, representing the uncomplexed and luciferase-associated lumazine proteins, respectively. The unbound 6,7-dimethyl-8-ribityllumazine itself (tau = 9 ns) was used as a model compound for determining correlation times in the picosecond time range. In the latter case rigorous deconvolution from the excitation profile was required to recover the correlation time, which was shorter (100-200 ps) than the measured laser excitation pulse width (500 ps).

Bacterial Proteins

The application of Fourier deconvolution to reaction time data: a cautionary note.

The Fourier transform method in conjunction with frequency domain smoothing techniques has been suggested as a powerful tool for examining components in a serial, additive reaction time model (P. L. Smith, 1990). Robustness and sensitivity to violations of the assumptions of serial model of this method are evaluated. When an incorrect distribution was used in recovering an unobserved component, results gave no information to show that an incorrect distribution was used, and the results were just as interpretable as those obtained using the correct distribution. These results demonstrate that the assumptions underlying the method cannot be assessed by the result of deconvolution, and the method cannot show that the purported component is actually from the serial combination.

Fourier Analysis

Cell cycle-dependent protein dynamics in budding yeast resolved by deconvolution of bulk proteomics.

The cell division cycle is characterised by oscillatory dynamics in regulatory mechanisms and biosynthesis, coordinated with genome replication and segregation. To understand these dynamics, quantitative cell cycle-dependent protein concentration data are essential. Unfortunately, accurately resolving cell cycle-dependent protein dynamics is challenging because single-cell proteomics is currently infeasible and bulk proteomics requires - inherently imperfect - cell synchronisation. Here, we developed a computational method to deconvolve cell cycle-dependent protein concentration dynamics and applied it to new budding yeast bulk proteome data. Key to this method was a yeast population model, parameterised with experimental cell cycle progression and volume growth data, for quantifying the desynchronisation in sampled populations. We performed deconvolution on 3272 proteins, using cross-validation to determine regularisation parameters, and identified 539 proteins with cell cycle-dependent dynamics. Many of these dynamics were consistent with known yeast biology and dynamic proteins were enriched for several metabolic process, extending previous observations and supporting the emerging picture of metabolic activity as varying substantially over cell cycle phases. We consider the generated cell cycle-resolved budding yeast proteome data a key resource.

Journal Article

Rates of plasma protein synthesis by deconvolution.

The plasma specific radioactivity of arginine guanidine (14)C-labelled protein has been measured at various times after the injection of labelled protein precursor (Na(2) (14)CO(3)). The resulting ;appearance' curve is a balance between the rate of synthesis and delivery of new protein and the rate of destruction and distribution of new plus existing protein. The measured appearance curve can be corrected to give a measure solely of the rate of synthesis of the plasma protein concerned, if the amplitude of the curve at every point is increased by an amount that compensates for the destruction and distribution processes. The decrease of plasma specific radioactivity of labelled plasma protein after an injection of exogenously labelled protein is termed the ;disappearance' curve, and the method of correcting the appearance curve by using the disappearance curve is shown to take the form of a deconvolution.

Arginine

The pituitary gland secretes in bursts: appraising the nature of glandular secretory impulses by simultaneous multiple-parameter deconvolution of plasma hormone concentrations.

To investigate patterns of endogenous hormone release, we have proposed a biophysical model in which measured hormone concentrations at any given instant reflect the operation of a suitable cumulation function (secretory input) convolved with an appropriate elimination mechanism (metabolic clearance). The cumulation function underlying a macroscopic hormone secretory burst can be represented by a random (Gaussian) distribution of instantaneous molecular secretory rates, which are centered with some finite and determinable standard deviation about a particular moment in time. The hormone elimination mechanism is described by a mono- or biexponential clearance function. The resultant convolution integral is solved by iterative nonlinear least-squares parameter estimation, in which all plasma hormone concentrations and their variances are considered simultaneously. Experiments with human endocrine time series revealed that the spontaneous secretory patterns of any of multiple distinct anterior pituitary hormones (luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, thyrotropin, and adrenocorticotropic hormone) can be described effectively by this parsimonious model. In addition, endogenous hormone disappearance rates determined by deconvolution agreed well with those reported earlier that were determined after exogenous hormone injections. Moreover, this model predicted that durations of underlying secretory impulses are extremely brief; i.e., the standard deviations of the Gaussian distributions of instantaneous secretory rates range from 4.5 min (luteinizing hormone) to 16 min (growth hormone) compared to plasma hormone concentration peaks of 90-140 min in duration. Accordingly, we conclude that observed physiological patterns of fluctuating plasma hormone concentrations can be accounted for by distinct, highly delimited, random bursts of hormone release separated by intervals of secretory quiescence.

Adrenocorticotropic Hormone

A study of the application of a deconvolution method to scintigraphy.

It is shown that an Anger-type gamma camera can be considered as a linear filter. The image is therefore the convolution of the object by the camera point spread function. An important property of the objects is the fact that they are basically positive (count-rates as a function of space variables). The proposed deconvolution method (due to Biraud) is shown to work satisfactorily on a 1-D scintigraphic signal which is a particular cross-section of a 2-D image. This is a preliminary study of the enhancement of real scintigraphic images.

Image Enhancement

On the deconvolution of exponential response functions.

The deconvolution or unfolding of exponential response functions from experimental data has been examined through the use of a Bayesian based algorithm. The algorithm, which is founded upon the concepts of probability, ensures positivity of solution. This constraint leads to a significant reduction in the growth of statistical noise in deconvolved data when compared with the more common linear unfolding techniques. The algorithm is an iterative procedure which, in the absence of statistical noise, can ultimately result in complete signal recovery. When noise is present one must balance the degree with which the response function is removed against the growth in the noise and, at some point, terminate the iterative process. Criteria for determining the point at which this 'best estimate' is attained are examined and an operationally realisable test is given. Comparison of results is made with the inverse filter solution which, for an exponential response function, is shown to consist of the sum of the observed data and its first derivative.

Mathematics

On the possibility of obtaining non-diffused proximity functions from cloud-chamber data: I. Fourier deconvolution.

A mathematical procedure, using Fourier deconvolution, is described whereby diffusion-free proximity functions can be obtained from cloud-chamber data. Such non-diffused distributions can be used to obtain further microdosimetric and nanodosimetric quantities hitherto not available from experiments, thus making the cloud chamber an almost ideal nanodosimeter.

Fourier Analysis

Optimal filtering values in renogram deconvolution.

The evaluation of the isotopic renogram by means of the renal retention function (RRF) is a technique that supplies valuable information about renal function. It is not unusual to perform a smoothing of the data because of the sensitivity of the deconvolution algorithms with respect to noise. The purpose of this work is to confirm the existence of an optimal smoothing which minimises the error between the calculated RRF and the theoretical value for two filters (linear and non-linear). In order to test the effectiveness of these optimal smoothing values, some parameters of the calculated RRF were considered using this optimal smoothing. The comparison of these parameters with the theoretical ones revealed a better result in the case of the linear filter than in the non-linear case. The study was carried out simulating the input and output curves which would be obtained when using hippuran and DTPA as tracers.

Humans

Extravascular background subtraction using deconvolution analysis of the renogram.

The effect of the intravascular background in the renogram on the calculated renal retention function is known and can be removed. However, the effect of the extravascular background (EVB) has not been thoroughly investigated using patient data. By varying the size of the region of interest containing a single kidney and by deconvolving the 131I-hippuran and 99Tcm-DTPA renograms so generated, the following has been found: (a) the effect of EVB on the mean transit time (MTT) is negligible and EVB subtraction is not necessary, (b) the EVB overestimates the lower relative kidney function (RKF) and underestimates the higher RKF, so that EVB subtraction should be performed if the RKFs are asymmetric. A new method is described in which the correction for EVB is performed following deconvolution. If the RKFs are greater than about 30%, the correction can be performed using a regression equation between the RKFs corrected for EVB and those that are not corrected. When the RKFs are asymmetric to a greater extent, the correction should be performed for each study separately. The proposed method includes a small systematic error due to the inherent limitations of nuclear medicine equipment.

Adult

Perfect-mixer retention function by analytical deconvolution of tracer histograms: application to evaluation of left-ventricular contractility and competence.

The analytical solution for the perfect-mixer retention function, r(t), was developed from tracer histograms sampled at the system input, i(t), and its output, y(t), linked by the convolution integral y = i * r. Theories were developed for both continuous-output mixer and pulsatile, discrete mixer. The latter method was applied in first-pass radioangiography (FPRA) to calculate the forward ejection fraction of the left ventricle (LVFEF). Curves generated over the lungs and the ventricle provided system input and output respectively. LVFEF correlated strongly with the reference values obtained with simultaneously acquired gated FPRA(LVGEF) in 32 non-regurgitant patients: LVGEF = 0.90LVFEF + 5.93, r = 0.96, SEE = 3.98, p less than 0.001. In 14 patients with left-side valvular incompetence LVFEF values (0.41 +/- 0.13) were consistently lower than the corresponding LVGEF values (0.63 +/- 0.11). The method is free from instability inherent in numerical deconvolution. Applied in FPRA it yielded accurate estimates of LV contractility and competence. The continuous-mixer theory may apply to arbitrary compartmental models studied via tracer kinetics.

Adolescent

Scatter compensation in digital chest radiography using Fourier deconvolution.

The authors present a numerical deconvolution technique to compensate for image degrading effects caused by scattered photons in radiographic chest images. Fourier transform techniques are used to deconvolve a shift invariant model of the two dimensional point spread response functions of the scattered radiation. This approach uses a digitized radiograph acquired with a standard chest imaging protocol, so no specialized imaging equipment is required. While the shift variant shape of the scatter model is optimized for the lung field, effective compensation is provided when this model shape is applied to other chest regions. Preliminary evaluation suggests that this technique can provide improved image contrast over the entire chest region.

Computer Simulation

99Tcm-TDG renography with deconvolution analysis: a comparative study with 99Tcm-DTPA and 123I-hippuran.

TDG has been compared with hippuran and DTPA in normal subjects and the derived gamma camera renograms of both the whole kidney and parenchymal regions subjected to deconvolution analysis using the matrix algorithm. The transit time of TDG was found to be longer than both hippuran and DTPA. The parenchymal mean transit time of TDG was 3.0 +/- 0.6 min (mean +/- S.D.). That of hippuran was 2.2 +/- 0.7 min and DTPA, 2.6 +/- 0.5 min. It is thought that a small fraction of the TDG is bound to the renal parenchyma thus prolonging both the mean and maximum transit times.

Adult

The reduction of renogram deconvolution to a direct method of transit time determination.

It is known that the intrarenal mean transit time (MTT) can be determined using renography by first deconvoluing the kidney retention function from the obtained time-activity curve and then integrating the retention function. A direct and approximate calculational method, based on an integral mathematical model, has also been employed to estimate the MTT. In this work it is shown that the direct approximate method is equivalent to the standard deconvolution method applied with the assumption of a time independent retention function. Potential errors incurred using the direct method are thus quantified and assessed over a range of representative decay parameters.

Humans