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PubMed1994

Estimation of growth hormone secretory patterns in children with use of a numerical deconvolution technique: experimental design with use of computer simulation.

Growth hormone (GH) secretion rates were estimated from 24-hour plasma GH concentration profiles using a model-based numerical deconvolution method. The basic kinetic parameters describing GH distribution and elimination were obtained from studies using single intravenous injections in GH-deficient children. Computer simulation techniques were used to produce 24-hour GH secretion profiles, which could serve as reference curves for analysis of the impact of certain practical aspects of the estimation of GH secretion, such as the method of blood sampling (discrete or integrated), sampling frequency and analytical errors. The results show that sampling intervals of 20 min are acceptable even in the presence of analytical errors, and that with this sampling interval, discrete blood sampling does not seem to be preferable to continuous withdrawal of blood.

Blood Specimen Collection↗
PubMed2000

Deconvolution of event-related fMRI responses in fast-rate experimental designs: tracking amplitude variations.

Recent developments towards event-related functional magnetic resonance imaging has greatly extended the range of experimental designs. If the events occur in rapid succession, the corresponding time-locked responses overlap significantly and need to be deconvolved in order to separate the contributions of different events. Here we present a deconvolution approach, which is especially aimed at the analysis of fMRI data where sequence- or context-related responses are expected. For this purpose, we make the assumption of a hemodynamic response function (HDR) with constant yet not predefined shape but with possibly variable amplitudes. This approach reduces the number of variables to be estimated but still keeps the solutions flexible with respect to the shape. Consequently, statistical efficiency is improved. Temporal variations of the HDR strength are directly indicated by the amplitudes derived by the algorithm. Both the estimation efficiency and statistical inference are further supported by an improved estimation of the noise covariance. Using synthesized data sets, both differently shaped HDRs and varying amplitude factors were correctly identified. The gain in statistical sensitivity led to improved ratios of false- and true-positive detection rates for synthetic activations in these data. In an event-related fMRI experiment with a human subject, different HDR amplitudes could be derived corresponding to stimulation at different visual stimulus contrasts. Finally, in a visual spatial attention experiment we obtained different fMRI response amplitudes depending on the sequences of attention conditions.

Algorithms↗
PubMed1995

An information-maximization approach to blind separation and blind deconvolution.

We derive a new self-organizing learning algorithm that maximizes the information transferred in a network of nonlinear units. The algorithm does not assume any knowledge of the input distributions, and is defined here for the zero-noise limit. Under these conditions, information maximization has extra properties not found in the linear case (Linsker 1989). The nonlinearities in the transfer function are able to pick up higher-order moments of the input distributions and perform something akin to true redundancy reduction between units in the output representation. This enables the network to separate statistically independent components in the inputs: a higher-order generalization of principal components analysis. We apply the network to the source separation (or cocktail party) problem, successfully separating unknown mixtures of up to 10 speakers. We also show that a variant on the network architecture is able to perform blind deconvolution (cancellation of unknown echoes and reverberation in a speech signal). Finally, we derive dependencies of information transfer on time delays. We suggest that information maximization provides a unifying framework for problems in "blind" signal processing.

Algorithms↗
PubMed1984

Lateral deconvolution of ultrasonic beams.

A number of papers have appeared recently describing methods of lateral resolution improvement in ultrasonic images by deconvolution of the amplitude detected cross-beam characteristic. It is the intention of this paper to demonstrate that such methods of resolution improvement are appropriate only for a limited class of targets. In general, the effect of interference between the r.f. signals from multiple targets at differing distances is such that the amplitude beam width obtained for these targets cannot be considered as the linear combination of shifted replicas of the amplitude beam width for an individual target. This is a consequence of the non-linear character of the detection process. In these cases the method of deconvolving the detected responses, although capable of giving reduced spot sizes, makes errors in the position of the images and is susceptible to false images and sidelobes . The phenomenon is demonstrated with computer and experimental data on point targets.

Computers↗
PubMed1984

Range resolution improvement by a fast deconvolution method.

Range resolution improvement in ultrasonic echography is considered as an estimation problem which is solved using a new fast minimum variance deconvolution algorithm specially designed for a microprocessor-based on-line processing. This method is used to accurately study the lenses and fundus of the eye and to follow variations of an arterial wall thickness during the cardiac cycle.

Animals↗
PubMed1990

Temporal structure of in vivo adrenal secretory activity estimated by deconvolution analysis.

Circadian and ultradian rhythms of plasma cortisol concentrations have been documented under physiological conditions in diverse animal species. Using a novel, biophysical convolution model to remove subject-specific metabolic clearance rates, we have now estimated spontaneous adrenal secretory events in vivo. The latter were characterized by prominent ultradian rhythms of discrete secretory bursts with periodicities averaging 32, 46, 76, and 130 min. These ultradian cortisol secretory rhythms represented a 17- to 240-fold larger fraction of circadian secretory variations than did cortisol concentration rhythms. We conclude that deconvolution analysis can unmask underlying ultradian rhythms in adrenal secretory activity in vivo.

Activity Cycles↗
PubMed1984

Cytokinetics of subpopulations in mixed heteroploid tumors by television imaging. I. Deconvolution of the S-phase DNA ploidy composition. II. Analysis of the S-phase emptying profile of ploidy subpopulations.

A scheme has been developed for deciphering the cell cycle time parameters of cell subpopulations that differ in their DNA ploidy level and that coexist in mixed heteroploid tumors. The S-phase analysis is presented. The approach is coupled to an automated imaging methodology for simultaneous determination of the Feulgen-stained DNA content and grain count of 3H-thymidine-labeled cells in autoradiographs (Sklarew RJ: J Histochem Cytochem 30:35, 30:49, 1982). The experimental designs involve 3H- and 14C-thymidine double labeling and Colcemid incubation. The deconvolution of the S-phase ploidy composition is illustrated in rat sarcoma cultures comprising four major ploidy subpopulations; with G-2 and mitotic DNA contents of approximately 4C, 8C, 16C, and 32C. The components were identified by their DNA ploidy level, and their S frequencies and labeling indices were obtained. A scheme is also developed and validated for obtaining the S-phase emptying profile of component ploidy subpopulations, and their cell flux at the S/G-2 and G-2/mitosis phase boundaries. In the sarcoma cultures S mobility was found to decrease with increasing DNA ploidy level over the entire ploidy range.

Animals↗
PubMed1992

Elevated growth hormone secretory rate in premature infants: deconvolution analysis of pulsatile growth hormone secretion in the neonate.

Premature infants have higher circulating concentrations of growth hormone (GH) than term infants. Previous investigations of these differences have used sampling frequencies of every 30 min with subsequent application of pulse detection algorithms, such as the CLUSTER program, to assess serum GH pulse parameters. To determine differences in GH secretory rates or GH t1/2 values between premature and term infants, we have sampled 11 neonates at 15-min intervals. We performed deconvolution analysis of the resultant plasma GH values to estimate GH secretory and clearance parameters. Five premature infants (gestational age range 24-34 wk) and six term infants (gestational age range 38-42 wk) were sampled every 15 min for 6 h. All subjects had indwelling arterial catheters. GH was measured (in duplicate) by RIA using 10 microL of plasma. Premature infants had higher secretory burst amplitudes (2.2 +/- 0.13 micrograms/L/min versus 1.4 +/- 0.27 micrograms/L/min, p = 0.02), higher production rates (product of the total number of bursts and the mean mass of GH secreted per burst, 811 +/- 173 micrograms/L/6 h versus 283 +/- 77 micrograms/L/6 h, p = 0.03), and a higher mass of GH per secretory burst (106 +/- 25 micrograms/L versus 38 +/- 11 micrograms/L, p = 0.049) than term infants. The integrated plasma GH concentration exhibited a strong trend toward a higher value in the premature infants (18,100 +/- 800 micrograms/L versus 10,200 +/- 2,700 micrograms/L, p = 0.067).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1995

Deconvolution analysis of spontaneous nocturnal growth hormone secretion in prepubertal children with preterminal chronic renal failure and with end-stage renal disease.

We sought to determine whether elevated circulating growth hormone (GH) concentrations in uremic prepubertal children are due to an increase in GH secretory activity by the pituitary gland or a decrease in the metabolic clearance of GH consequent to reduced GFR. Deconvolution analysis was applied to the nighttime plasma GH profiles of 1) 11 children with preterminal chronic renal failure, 2) 12 children with end-stage renal disease (ESRD), and 3) a control group of matched children with idiopathic short stature (n = 12). Mean (+/- SEM) half-life of endogenous GH in children with ESRD (27.5 +/- 2.7 min) and preterminal chronic renal failure (23.1 +/- 2.1 min) was significantly higher than in controls (14.8 +/- 1.6 min; p < 0.001). GH half-life correlated inversely with GFR (r = -0.65, p < 0.001). The number of GH secretory bursts/10 h in ESRD (8.1 +/- 0.4) was amplified compared with preterminal chronic renal failure (6.4 +/- 0.5) and with controls (5.9 +/- 0.4; p < 0.005). GH production rate varied over a broad range in the three groups: It was highest in ESRD (202 +/- 56.6 microgm/L/10 h; range 36-683), mainly as a result of an increased number of GH secretory bursts, and not statistically different in preterminal chronic renal failure (66.2 +/- 11.4 microgm/L/10 h; range 25-168) and in controls (129 +/- 27.7 microgm/L/10 h; range 39-392). Increased GH half-life, in concert with an increased GH production in some individuals with ESRD, leads to a 2.5-fold increase in the mean plasma GH concentration in ESRD compared with the two other groups (p < 0.005) [corrected].(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1996

Overnight growth hormone secretion in achondroplasia: deconvolution analysis, correlation with sleep state, and changes after treatment of obstructive sleep apnea.

The normal profile for overnight GH secretion in achondroplasia has not been previously studied. Factors that have been shown to influence GH secretion include age, obesity, sleep state, and the presence of obstructive sleep apnea (OSA). We assessed GH levels in a group of subjects with achondroplasia, during overnight polysomnography. Nineteen subjects with achondroplasia were studied at 11.3 y of age (median 6.7, range 1.8-30.9). Levels of GH were measured using time-resolved immunofluorometric assay (DELFIA, Pharmacia Biotech Inc.) and analyzed by a deconvolution method. Five subjects were restudied after treatment for OSA. Secretion rates of GH were greater in slow wave (SWS) and rapid eye movement (REM) sleep than in stage one and two (SI-II = light non-REM) sleep (p < 0.01). Total overnight GH secretion decreased with increasing age (r2 = 0.22 p < 0.04). Neither the frequency of arousals, frequency of sleep state transitions nor the severity of OSA correlated with measures of GH secretion. Levels of IGF-I correlated independently with age, body weight (percent ideal), and GH secretion rate (r2 = 0.76, p < 0.001). In a group of five subjects treated for OSA, improved respiratory distress index and reduced sleep state transitions were not associated with significant changes in GH secretion rate by sleep stage; SWS [from 0.62 +/- 0.28 mIU/L/min to 1.02 +/- 0.25 mIU/L/min (NS)] and SI-II sleep [from 0.26 +/- 0.07 mIU/L/min to 0.60 +/- 0.16 mIU/L/min (NS)]. However, in those five subjects, a GH secretion peak during the first 2 h of SWS was initially absent, appearing only after treatment of OSA (1.09 +/- 0.38 mIU/L/min) compared with (2.40 +/- 0.59 mIU/L/min (p = 0.01). A profile of overnight GH secretion is presented for subjects with achondroplasia.

Achondroplasia↗
PubMed1992

Endogenous growth hormone secretion and clearance rates in normal boys, as determined by deconvolution analysis: relationship to age, pubertal status, and body mass.

Mean plasma GH concentrations increase in normal boys during mid- to late-puberty. To investigate the nature of the pituitary secretory events and/or altered metabolic clearance responsible for these serum GH concentration changes, we performed multiple-parameter deconvolution analysis of 46 24-h serum GH concentration-time series obtained from normal boys at various stages of puberty and young adulthood. The subjects ranged in chronological age from 7-27 yr. The height and weight of each subject were between the 5th and 95th percentile for age. The calculated daily mass of GH secreted was greatest (P less than 0.001) in late pubertal boys (mean +/- SE, 1810 +/- 250 micrograms/24 h) and was triple the value in prepubertal boys (610 +/- 65 micrograms/24 h). When the values were normalized and expressed as mass of GH secreted per unit (m2) body surface area or per L distribution volume, GH secretion in late pubertal boys was still significantly greater than that in any other group (P less than 0.05). These values for late pubertal boys were nearly double the corresponding values for prepubertal boys (1160 +/- 160 vs. 600 +/- 58 micrograms GH/m2.24 h and 440 +/- 63 vs. 270 +/- 25 micrograms GH/L vol.24 h, respectively). When the effect of clearance mechanics on serum GH concentrations was removed mathematically, the primary change in predicted GH secretory burst parameters during pubertal development was an increase in GH mass released per burst resulting from an increase in the maximal rate of GH secretion attained within the bursts. These changes in the amplitude of GH release events were specific, in that they were largely independent of any accompanying alterations in duration or frequency of the GH secretory bursts or in serum GH half-life. Correlation analysis revealed that the 24-h GH secretion rate varied inversely with the subjects' body mass index SD score (r = -0.65; P less than 0.01), suggesting that differences in body mass, even within the normal range, contribute to the wide variability in daily GH secretion rates among normally growing children. The plasma insulin-like growth factor-I concentrations of all subjects correlated positively with the calculated 24-h GH secretion rate (r = 0.51; P less than 0.001). In summary, the primary neuroendocrine alteration responsible for the augmented serum GH concentrations characterizing mid- to late-puberty in boys is an increased mass of GH released per pituitary secretory episode resulting from an increased maximal rate of GH secretion within each burst.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Pulsatile secretion of parathyroid hormone in normal young subjects: assessment by deconvolution analysis.

Preliminary reports suggest that PTH is secreted in a pulsatile fashion. However, available studies have not attempted to calculate actual PTH secretion rates in healthy individuals. To accurately characterize PTH secretory dynamics in healthy subjects, we studied seven young women and six young men, all of whom had hip and spine bone densities by dual photon densitometry in the upper tertile for age-matched control subjects. PTH concentrations were measured by immunoradiometric assay in blood sampled every 2 min over 6 h. Ionized calcium levels were obtained during the second and third hours of the study. Plasma PTH profiles were subjected to deconvolution analysis, which resolves measured hormone levels into secretion and clearance components. Cross-correlation analysis was performed to assess direct or inverse correlations between serum PTH and ionized calcium concentrations at various time lags. In these subjects, PTH was secreted in a dual fashion, with significant basal (tonic) secretion and PTH pulses approximately every 20 min. Pulsatile PTH secretion accounted for approximately 25% of the total secreted PTH. There were no differences in PTH secretory parameters between men and women, nor were there any significant correlations between PTH and ionized calcium concentrations. We conclude that in normal subjects, the predominant mode of PTH secretion is tonic, with superimposed PTH pulses of small amplitude but high frequency. The clinical significance of this complex physiological pattern of secretion awaits further study.

Adult↗
PubMed1996

Alterations in pulsatile luteinizing hormone and follicle-stimulating hormone secretion in idiopathic oligoasthenospermic men: assessment by deconvolution analysis--a clinical research center study.

To investigate the nature of neuroendocrine disturbances of the hypothalamo-pituitary-gonadal axis in idiopathic male infertility, we studied 14 infertile men with oligoasthenozoospermia (OLIGO) and 15 age-, body mass index-, and community-matched euspermic controls by blood withdrawal at 10-min intervals for 12 h to encompass basal (8-h) and exogenous GnRH-stimulated (4-h) pulsatile release of LH and FSH (by immunoradiometric assay) as well as testosterone (by RIA). Deconvolution analysis was used to estimate endogenous LH and FSH half-lives, secretory burst frequency, amplitude, duration, and mass. OLIGO men exhibited normal serum concentrations of total, free, and percent dialyzable testosterone and estradiol, but distinct dynamic alterations within the LH and FSH axes; namely (P < 0.05), 1) a prolonged half-life of LH (OLIGO, 95 +/- 19 min; control, 80 +/- 9.3 min) and a reduced half-life of FSH (OLIGO, 260 +/- 79 min; control, 320 +/- 93 min); 2) a low LH, but normal FSH, secretory burst frequency (OLIGO, 12 +/- 3.4; control, 15 +/- 3.0 LH pulses/day); 3) a decreased serum testosterone peak frequency (OLIGO, 16 +/- 4.3; control, 21 +/- 3.2 peaks/day); and 4) an amplified mass of LH (1.1- to 1.3-fold higher in OLIGO) and FSH (2.4- to 2.7-fold higher in OLIGO) secreted per burst basally as well as after GnRH injection. These disturbances were readily distinguishable from the neuroendocrine dysregulation described in other states of male hypogonadotropism (e.g. uremia, fasting, and aging).

Adult↗
PubMed1996

Ontogeny of pulsatile gonadotropin releasing hormone secretion from midchildhood, through puberty, to adulthood in the human male: a study using deconvolution analysis and an ultrasensitive immunofluorometric assay.

The ontogeny of gonadotropin releasing hormone pulse generator activity underlying pubertal development in the human male is incompletely defined because of the limitations of assay sensitivity in measurements and the inaccuracies attendant upon the analyses of pulsatile secretion of circulating gonadotropins. Using an ultrasensitive immunofluorometric assay (DELFIA) to measure plasma LH and deconvolution analysis to depict LH secretory characteristics, we compared nocturnal (2000-0800 h) pulsatile LH secretion cross-sectionally in 16 boys in midchildhood (mean +/- SD age 6.6 +/- 0.3 yr), 8 prepubertal boys (12.0 +/- 0.3 yr), 8 early pubertal boys (14.3 +/- 0.4 yr), and in 8 young fertile adult men (32.6 +/- 1.6 yr) as an indirect in vivo assessment of hypothalamic GnRH pulse generator activity over the entire span of pubertal development in the human male. We confirmed that sleep-entrained GnRH/LH burst secretory activity was present in midchildhood. The first increase in sleep-entrained GnRH/LH secretion occurred some 2 yr before the clinical onset of puberty. From midchildhood to sexual maturity, LH production rate increased 39-fold. However, GnRH/LH pulse frequency showed only a relatively small (1.8-fold) increment from midchildhood to the clinical onset of puberty, with no subsequent changes to continuing development towards adulthood. Thus 91.7% of the increment in LH plasma concentration from childhood to sexual maturity could be accounted for by an amplification of a pre-existing ultradian rhythm of secretion with a steadily and markedly increasing mass of LH secreted per burst. The duration of secretory burst and apparent half-life of plasma LH disappearance remained constant from midchildhood, through puberty, to adulthood. The nyctohemeral rhythm-and sleep-associated LH/GnRH secretion was eventually lost in young adulthood. We conclude that the onset of puberty in man is heralded by the reawakening of a partially quiescent GnRH pulse generator. This predominantly involves an amplification of a pre-existing pattern of hypothalamic GnRH secretion leading to a major augmentation of the total quantity of LH molecules released per burst. The almost two-fold increment in GnRH pulse frequency contributed synergistically to the pubertal process, before the clinical onset of puberty, possibly by enhancing gonadotropic sensitivity to increase the mass of LH produced per burst. The relative constancy of GnRH pulse frequency in the gonad-intact hypothalamic-pituitary-testicular axis from pubertal onset to adulthood implies that testicular steroidal feedback plays a role in restraining the burst frequency of the GnRH pulse generator during pubertal development and adulthood.

Adolescent↗
PubMed1997

Differential sex steroid negative feedback regulation of pulsatile follicle-stimulating hormone secretion in healthy older men: deconvolution analysis and steady-state sex-steroid hormone infusions in frequently sampled healthy older individuals.

The healthy aging male reproductive axis tends to exhibit a progressive decline in serum concentrations of biologically available testosterone with gradual concomitant reciprocal increases in both LH and FSH concentrations. However, relatively little is known about the sex steroid-mediated negative feedback regulation of physiologically pulsatile gonadotropin release in general, and episodic FSH release in particular, in older males. To examine the steroid hormone negative feedback control of pulsatile FSH secretion in healthy older men, we applied multiparameter deconvolution analysis to serum FSH (immunoradiometric assay) profiles obtained by sampling every 10 min over 24 h during steady state (4.5-day) infusions of estradiol (E2; 48 micrograms/day), 5 alpha-dihydrotestosterone (DHT; 7.0 mg/day), or 5% dextrose in water in five healthy older men, aged 60-73 yr. We observed the following principal responses: 1) both E2 and DHT significantly suppressed mean and 24-h integrated serum FSH concentrations (P < 0.032); 2) the calculated daily secretion rate of FSH fell significantly in all five individuals during DHT infusion; 3) the apparent half-life of FSH decreased during E2 (but not DHT) infusion; 4) DHT infusion reduced the mass and frequency of FSH secretory bursts significantly; 5) neither E2 nor DHT treatment significantly attenuated the release of FSH stimulated by consecutive iv injections of GnRH (10 and 100 micrograms); and 6) integrated 24-h serum LH (immunoradiometric assay) concentrations decreased significantly during both DHT and E2 infusions, whereas mean LH release after the serial GnRH injections was not altered. Compared to younger men studied earlier in an identical fashion, older men had significantly reduced FSH intersecretory burst intervals, reflecting a higher FSH pulse frequency at baseline and during the steroid infusions and a significantly lower mass of FSH secreted per burst during E2 infusion. We conclude that healthy older men maintain intact negative feedback responsiveness of the hypothalamo-pituitary gonadotroph unit to exogenously delivered sex steroid hormones, and that individual sex steroid hormones differentially regulate specific features of pulsatile FSH release and half-life in older men.

Aged↗
PubMed1992

Determination of the arterial flow fraction in normal and diseased livers using constrained deconvolution.

There is some evidence that the ratio of the blood flow to the liver through the hepatic artery to the total flow to the liver through the hepatic artery and portal vein (the hepatic arterial flow fraction, AFF) is altered in the presence of cirrhosis. Several methods have been published that seek to provide an index of this ratio. These indices are dependent on factors other than the AFF and cannot provide a true measure of it. The impulse retention function of the liver has two components and these may be derived using a model-driven deconvolution of the arterial tracer concentration curve and the curve of tracer concentration in the liver. The AFF may then be obtained from the relative heights of these two components. Simulation studies show that the AFF calculated using this method is reasonably accurate and a small clinical series shows that it is capable of appropriate clinical classification of patients into cirrhotic and non-cirrhotic groups.

Colloids↗
PubMed1975

Deconvolution analysis of the scintillation camera renogram.

A scintillation camera with digital data store has been used to assess renal function. Analysis of the renogram by deconvolution, using an on-line digital computer, shows promise as a means of expressing renal function in terms of tubular transit times for 123I-Hippuran.

Computers↗
PubMed1982

A co-operative study on the clinical value of dynamic renal scanning with deconvolution analysis.

An international project was set up to study the clinical usefulness of intrarenal transit times derived from the renogram by deconvolution. A common data sheet, to collect clinical, biochemical, radiological and isotopic information, was completed by the centres. Five hundred and ninety-one patients were studied and the results analysed. The mean transit time (MTT) in normal kidneys was found to be 3.6 +/- 1.1 min. If the MTT is greater than 7.6 min, a kidney is likely to be obstructed. In vesico-ureteric reflux, the transit times are prolonged, but they are normal in infection, hypertension, parenchymal disease and minimally irradiated kidneys. In transplantation, when the kidney is normal, the transit times are shorter than in the natural kidney; in acute rejection, transit time are prolonged.

Adult↗