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A polyexponential deconvolution method. Evaluation of the "gastrointestinal bioavailability" and mean in vivo dissolution time of some ibuprofen dosage forms.

A new deconvolution algorithm (DCON) suitable for pharmacokinetic applications is presented. It requires that both the impulse and input responses, typically systemic drug levels, be well described by polyexponential equations. DCON has a wider range of applications than an earlier method (DECONV) from which it is derived. A FORTRAN program is provided, making implementation of the technique a simple matter. DCON is demonstrated to evaluate the "GI bioavailability," defined as the rate and the extent of gastrointestinal drug release, of various ibuprofen dosage forms. The GI drug release kinetics exemplifies a pharmacokinetic system which cannot be evaluated using the previous deconvolution algorithm (DECONV) because of an initial zero drug level response. This limitation is not found in DCON. It is also demonstrated how the mean in vivo dissolution time MDT can be evaluated by deconvolution.

Biological Availability

Deconvolution method for accurate determination of overlapping peak areas in chromatograms.

A method is described for deconvoluting chromatograms which contain overlapping peaks. Parameters can be selected to ensure that attenuation of peak areas is uniform over any desired range of peak widths. A simple extension of the method greatly reduces the negative overshoot frequently encountered with deconvolutions. The deconvoluted chromatograms are suitable for integration by conventional methods.

Chromatography

Quantitative scintigraphy with deconvolutional analysis for the dynamic measurement of hepatic function.

A mathematical technique known as deconvolutional analysis was used to provide a critical and previously missing element in the computations required to quantitate hepatic function scintigraphically. This computer-assisted technique allowed for the determination of the time required, in minutes, of a labeled bilirubin analog (99mTc-disofenin) to enter the liver via blood and exit via bile. This interval was referred to as the mean transit time (MTT). The critical process provided for by deconvolution is the mathematical simulation of a bolus injection of tracer directly into the afferent blood supply of the liver. The raw data required for this simulation are obtained from the intravenous injection of labeled disofenin, a member of the HIDA family of radiopharmaceuticals. In this study, we perform experiments which document that the simulation process itself is accurate. We then calculate the MTT under a variety of experimental conditions involving progressive hepatic ischemia/reperfusion injury and correlate these results with the results of simultaneously performed BSP determinations and hepatic histology. The experimental group with the most pronounced histologic findings (necrosis, vacuolization, disorganization of hepatic cords) also have the most prolonged MTT and BSP half-life. However, both quantitative imaging and BSP testing are able to identify milder degrees of hepatic ischemic injury not reflected in the histologic evaluation. Quantitative imaging with deconvolutional analysis is a technique easily adaptable to the standard nuclear medicine minicomputer. It provides rapid results and appears to be a sensitive monitor of hepatic functional disturbances resulting from ischemia and reperfusion.

Animals

An iterative method for the deconvolution of microcalorimeter thermograms.

An iterative method for the deconvolution of microcalorimetry thermograms suitable for small digital computers is presented. The method employs a measured impulse response function directly as the deconvolution kernel, thus explicit system simulation is not required. Data are presented showing the performance of the method and the exchange of signal-to-noise ratio for time resolution that is made when deconvolution techniques are employed. An improvement in the system time resolution of fifty times is demonstrated with measured data.

Algorithms

Accuracy of peak deconvolution algorithms within chromatographic integrators.

The soundness of present-day algorithms to deconvolve overlapping skewed peaks was investigated. From simulated studies based on the exponentially modified Gaussian model (EMG), chromatographic peak area inaccuracies for unresolved peaks are presented for the two deconvolution methods, the tangent skim and the perpendicular drop method. These inherent inaccuracies, in many cases exceeding 50%, are much greater than those calculated from ideal Gaussian profiles. Multiple linear regression (MLR) was used to build models that predict the relative error for either peak deconvolution method. MLR also provided a means for determining influential independent variables, defining the required chromatographic relationships needed for prediction. Once forecasted errors for both methods are calculated, selection of either peak deconvolution method can be made by minimum errors. These selection boundaries are contrasted to method selection criteria of present data systems' algorithms.

Algorithms

Deconvolution in medical ultrasonics: practical considerations.

Deconvolution can, in principle, enhance the spatial resolution of specular reflectors in medical ultrasonic imaging but, in practice, the resolution improvement offered is offset by the introduction of undesirable artefacts. In this study, several problems related to deconvolution were identified and practical suggestions for minimising artefacts were made. These include: fitting a three-dimensional surface to experimentally measured beam profiles in order to take into account the depth-dependence of the point spread function (PSF); adaptive detail-preserving noise filtering as a preprocessing tool in order to improve the quality of the data and reduce the speckle enhancement artefact; a histogram modification procedure in order to overcome the problems of ringing, over- and undershooting. Processing of a large number of A-scan data obtained from tissue-mimicking phantoms and the abdomens of normal volunteers demonstrated the efficiency of these techniques in reducing artefacts. The performance of deconvolution in terms of resolution improvement was satisfactory when data from resolution test objects were processed but poor with abdominal scans. This difference in performance raises the question as to how similar the PSF in tissue is to the experimentally measured PSF in water or even a tissue-mimicking material.

Abdomen

Ideal versus human observer for long-tailed point spread functions: does deconvolution help?

The ideal observer represents a Bayesian approach to performing detection tasks. Since such tasks are frequently used as a prototype tasks for radiological imaging systems, the detectability measured at the output of an ideal detector can be used as a figure of merit to characterize the imaging system. For the detectability achieved by the ideal observer to be a good figure of merit, it should predict the ability of the human observer to perform the same detection task. Of great general interest, especially to the medical community, are imaging devices with long-tailed point spread functions (PSFs). Such PSFs may occur due to septal penetration in collimators, veiling glare in image intensifiers or scattered radiation in the body. We have investigated the effect that this type of PSF has on human visual signal detection and whether any improvement in performance can be gained by deconvolving the tails of the PSF. For the ideal observer, it is straightforward to show that the performance is independent of any linear, invertible deconvolution filter. Our psychophysical studies show, however, that performance of the human observer is indeed improved by deconvolution. The ideal observer is, therefore, not a good predictor of human observer performance for detection of a signal imaged through a long-tailed PSF. We offer some explanations for this discrepancy by using some characteristics of the visual process and suggest a standard of comparison for the human observer that takes into account these characteristics. A look at the performance of the non-prewhitening (npw) ideal observer, before and after deconvolution, also brings some good insight into this study.

Bayes Theorem

Enhancing and accelerating cell type deconvolution of large-scale spatial transcriptomics slices with dual network model.

MOTIVATION: Cell type deconvolution deciphers spatial distribution of mRNA transcripts at single cell level by integrating single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics data to infer mixture of cell types of spots in slices. Current algorithms are criticized for neglecting connection between scRNA-seq and spatial transcriptomics data, as well as time-consuming, hampering their application to large-scale datasets. RESULTS: In this study, we propose a joint learning nonnegative matrix factorization algorithm for fast cell type deconvolution (aka jMF2D), which integrates scRNA-seq and spatial transcriptomics data with network models. To bridge scRNA-seq and spatial transcriptomics data, jMF2D jointly learns cell type similarity network to enhance quality of signatures of cell types, thereby promoting accuracy and efficiency of deconvolution. Experiments demonstrate that jMF2D outperforms state-of-the-art baselines in terms of accuracy by saving about 90% running time on various datasets generated by different platforms. Furthermore, it can also facilitates the identification of spatial domains and bio-marker genes, providing an efficient and effective model for analyzing spatial transcriptomics data. AVAILABILITY AND IMPLEMENTATION: The software is coded using python, and is free available for academic https://github.com/xkmaxidian/jMF2D.

Algorithms

Extraction of pencil beam kernels by the deconvolution method.

A method has been developed to extract pencil beam kernels from measured broad beam profiles. In theory, the convolution of a symmetric kernel with a step function will yield a function that is symmetric about the inflection point. Conversely, by deconvolution, the kernel may be extracted from a measured distribution. In practice, however, due to the uncertainties and errors associated with the measurements and due to the singularities produced in the fast Fourier transforms employed in the deconvolution process, the kernels thus obtained and the dose distributions calculated therefrom, often exhibit erratic fluctuations. We propose a method that transforms measured profiles to new, modified distributions so that they satisfy the theoretical symmetry condition. The resultant kernel from the deconvolution is then free of fluctuations. We applied this method to compute photon and electron dose distributions at various depths in water and electron fluence distributions in air. The agreement between measured and computed profiles is within 1% in dose or 1 mm in distance in high dose gradient regions.

Fourier Analysis

Reconstructing the rate of appearance of subcutaneous insulin by deconvolution.

In this paper a deconvolution scheme is presented to reconstruct the rate of appearance of subcutaneously injected insulin. Relevant aspects of experiment design are briefly described. Intravenous insulin kinetics are modeled to determine the impulse response of the system. The deconvolution problem is not ill conditioned and is solved using a least-squares method without imposing constraints on the input. An estimate of the error of the reconstructed input is provided. The reliability of the deconvolution scheme is tested by means of an independent validation study. Finally, the different sources of error that affect the method are discussed, and a figure of the global error is derived.

Humans

Hydrocortisone secretion: production rate and pulse characterization by numerical deconvolution.

Based on serial blood sampling over 24 h, hydrocortisone was shown to be secreted episodically in the horse. The purpose of the present experiment was to characterize peaks and troughs by analyzing the instantaneous secretion rate profile obtained by a deconvolution technique rather than from the plasma concentration time profile. Kinetic parameters of hydrocortisone were determined following intravenous bolus and intravenous perfusion of hydrocortisone. Stationary and nonlinearity of hydrocortisone disposition were demonstrated. With the use of clearance values calculated from constant perfusion administration, the 24-h hydrocortisone production rate was estimated at 0.46 +/- 0.08 mg.kg-1.24 h-1. The instantaneous secretory profile was reconstituted by deconvoluting the plasma concentration profile using structural parameters determined from the bolus hydrocortisone administration. When this secretory profile was subjected to a pulse analysis program, the number of detected peaks was found to be 17.25 +/- 1.26 and the mean peak duration 34.01 +/- 5.52 min. The total duration of secretory activity was estimated at 582.5 +/- 63.97 min. By comparison, when the plasma concentration profile was analyzed directly, the number of peaks was only 10.0 +/- 1.41 but their mean duration was much longer, i.e., 105.25 +/- 21.24 min. The origin of these differences and the advantages and limits of deconvolution analysis are discussed.

Animals

Porcine and human insulin absorption from subcutaneous tissues in normal and insulin-dependent diabetic subjects: a deconvolution-based approach.

The mechanisms of sc insulin absorption are not understood, and models for interpreting in vivo data cannot be developed without gross simplification. To overcome this difficulty we developed a new approach which makes use of deconvolution analysis and does not require any model of the sc tissue. In five normal subjects and seven insulin-dependent diabetic (IDDM) patients endogenous insulin secretion was suppressed by means of a hypoglycemic glucose clamp procedure (approximately 2.8 mmol/L) sustained by a continuous insulin infusion (approximately 4 pmol/min.kg). A bolus injection of insulin (5.4 nmol) was administered iv, and plasma insulin concentrations were measured frequently for 2 h to assess iv insulin kinetics. Insulin then was injected sc in the abdominal region, and plasma insulin concentrations were measured for 8 h. Each subject was studied twice, with porcine and semisynthetic human insulin (Actrapid, Novo). The rate of insulin absorption was reconstructed by deconvolution from the plasma concentrations and iv insulin kinetic data. Linearity of the iv insulin kinetics, essential for deconvolution analysis, was confirmed by a dose-response study in the range of the measured concentrations (150-1800 pmol/L). In most instances, a two-compartment model was adequate to describe the iv response. The mean plasma insulin clearance rates were 15.5 +/- 1.9 (+/- SD) mL/min.kg (porcine) and 17.2 +/- 6.0 (human) in normal subjects and 20.7 +/- 8.8 (porcine) and 20.9 +/- 9.1 (human) in the IDDM patients. The rate of appearance of human insulin from sc tissue was faster than that of porcine insulin in both normal and IDDM subjects, but no significant differences were found in bioavailability, which was 55 +/- 12% (+/- SD; porcine) and 61 +/- 34% (human) in the normal subjects, and 84 +/- 28% (porcine) and 86 +/- 23% (human) in the IDDM patients. The rate of absorption and bioavailability were higher in the IDDM patients than in the normal subjects, a difference possibly related to increased sc blood flow in the IDDM patients. No differences were found with regard to glucose requirement values, normalized to plasma insulin concentrations, in agreement with the finding that the bioavailability of the two insulin species was similar.

Adolescent

Deconvolution of emission tomographic data: a clinical evaluation.

A method of improving the quality of images in single photon emission computed tomography (SPECT) is demonstrated using transaxial images of the liver and brain. Deconvolution of the nuclear medicine data by a point source response function (PSRF) acquired previously in a scattering medium attempts to compensate for scattered radiation within the patient. The average geometric response of the collimator of the gamma camera is also compensated for with this technique. Three patients with known metastatic lesions in the liver and three with primary lesions in the brain were imaged. Clinical assessment of reconstructed slices both before and after deconvolution demonstrates that compensating for the effects of scatter and of collimator blurring leads to enhanced detail of pathological lesions. In all cases, cold lesions seen prior to deconvolution were enhanced in detail and, in addition, new lesions were seen with this technique.

Adult

Deconvolution study of the absorption rate and disposition kinetic values of lindane in sheep.

Absorption rate and plasma and fat disposition of lindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 micrograms/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 micrograms/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 micrograms/g (ie, lower than the generally accepted tolerance level of 2 micrograms/g).

Adipose Tissue

An overview of computer algorithms for deconvolution-based assessment of in vivo neuroendocrine secretory events.

The availability of increasingly efficient computational systems has made feasible the otherwise burdensome analysis of complex neurobiological data, such as in vivo neuroendocrine glandular secretory activity. Neuroendocrine data sets are typically sparse, noisy and generated by combined processes (such as secretion and metabolic clearance) operating simultaneously over both short and long time spans. The concept of a convolution integral to describe the impact of two or more processes acting jointly has offered an informative mathematical construct with which to dissect (deconvolve) specific quantitative features of in vivo neuroendocrine phenomena. Appropriate computer-based deconvolution algorithms are capable of solving families of 100-300 simultaneous integral equations for a large number of secretion and/or clearance parameters of interest. For example, one application of computer technology allows investigators to deconvolve the number, amplitude and duration of statistically significant underlying secretory episodes of algebraically specifiable waveform and simultaneously estimate subject- and condition-specific neurohormone metabolic clearance rates using all observed data and their experimental variances considered simultaneously. Here, we will provide a definition of selected deconvolution techniques, review their conceptual basis, illustrate their applicability to biological data and discuss new perspectives in the arena of computer-based deconvolution methodologies for evaluating complex biological events.

Algorithms

Deconvolution of Compton scatter in SPECT.

A deconvolution algorithm has been developed which compensates for Compton scattering in SPECT images. Compton scatter is modeled as a convolution of the nonscattered projection data with an exponential function. Deconvolution of the total (scatter + nonscatter) projection data yields compensated true projection. Using Monte Carlo methods, the scattered and nonscattered components of a SPECT image are simulated thus allowing a comparison of scatter compensated results with direct nonscatter results. The quality of the compensation is evaluated by comparing the ratio of total to direct counts with the ratio of compensated to direct counts. This deconvolution technique has been developed and evaluated for experimentally acquired SPECT data as well as for simulated data.

Filtration

Continuous DNA Methylation Deconvolution-Based Surrogate for B-Cell Differentiation State in CLL.

Chronic Lymphocytic Leukemia (CLL) is clinically divided into IGHV mutated (M-CLL) and IGHV unmutated (U-CLL) subtypes, which are thought to arise from distinct cells of origin along the B-cell differentiation pathway. We measured genome-scale DNA methylation in purified CLL samples ( n = 89) and utilized reference-based cell deconvolution techniques to develop a continuous metric of epigenetic similarity across a B-naive-like to B-memory-like scale (B-Index). B-Index accurately classifies CLL into clinical subtypes (98.8%), has a stronger epigenetic signal than IGHV gene percent identity, and demonstrates additional epigenetic signal within the M-CLL subgroup. We demonstrate that U-CLL is epigenetically more similar to B-memory than B-naive cells and reconcile previous reports of a B-naive-like epigenetic signal. The B-memory-like program of U-CLL is enriched for binding sites of transcription factors related to the germinal center activation pathway. Our findings provide epigenetic evidence for discerning CLL mechanisms of initiation and cell of origin. We also identified an epigenetic signal associated with tumor burden, which may have some relation to viral infections such as Epstein-Barr-Virus. Our cell-type deconvolution-based approach to developing a continuous metric for CLL epigenetic differentiation state can be applied to other tumors with multiple subtypes across differentiation stages.

B-memory-like