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Non-invasive measurement of microvascular permeability to a small solute in man: validation of the technique.

1. The purpose of the study was to evaluate a non-invasive technique for measurement of microvascular permeability to a small hydrophilic solute. 2. The technique measures the clearance of 99mTc-labelled diethylenetriaminepenta-acetic acid (99mTc-DTPA) from plasma into interstitial fluid in a limb after intravenous injection and uses a scintillation probe and a technique of graphical analysis called the Patlak plot, the uptake constant of which reflects 99mTc-DTPA transfer from plasma to interstitial fluid. Using deconvolution analysis, the retention function in the limb of intravenous 99mTc-DTPA was also measured. 3. The clearance values given by these two analytical techniques were compared with clearance from the same vascular bed after bolus femoral intra-arterial injection of 99mTc-DTPA. 4. Sixteen patients undergoing routine diagnostic arteriography were studied: six received sequential femoral intra-arterial injections of 99mTc-labelled human serum albumin (HSA) and 99mTc-DTPA, two received sequential intra-arterial and intravenous injections of 99mTc-HSA and eight received sequential intra-arterial and intravenous injections of 99mTc-DTPA. Tissue uptake and clearance were recorded from the limb with a scintillation probe and plasma clearance by arterial blood sampling. Tracer recirculation was addressed using a second scintillation probe over the contralateral limb. 5. After intra-arterial injection, 99mTc-HSA clearance was monoexponential, reflecting intravascular transit, and was completed by 2-5 min in seven subjects and in about 10 min in one. The corresponding 99mTc-DTPA clearance curves in the six subjects who also received intra-arterial DTPA were biexponential, analysis of which yielded a 99mTc-DTPA extraction fraction of about 0.6. By comparison with 99mTc-HSA clearance, the first exponential clearly corresponded to intravascular transit of unextracted 99mTc-DTPA. 6. In the eight patients given sequential intra-arterial and intravenous injections of 99mTc-DTPA, the second exponential recorded after intra-arterial injection, representing 99mTc-DTPA clearance from the interstitial fluid, agreed well with (a) the Patlak uptake constant recorded over the limb after intravenous injection, representing clearance from plasma into the interstitial fluid and (b) the retention function of 99mTc-DTPA in a limb calculated by deconvolution analysis. The mean clearance following intra-arterial injection (expressed in relation to extracellular fluid volume) was 9.6 (SD 2.4) ml min-1 100 ml-1, while the corresponding mean clearance after intravenous injection was 8.8 (2.1) ml min-1 100 ml-1 calculated by Patlak analysis and 10.5 (2.7) ml min-1 100 ml-1 by deconvolution analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Capillary Permeability↗

Interstudy reproducibility of quantitative perfusion cardiovascular magnetic resonance.

PURPOSE: To determine the interstudy reproducibility of quantitative first-pass perfusion cardiovascular magnetic resonance with comparison of 2 previously described analysis techniques. There is no published data on the interstudy reproducibility of perfusion cardiovascular magnetic resonance which can be used to determine the significance of longitudinal changes in myocardial perfusion after pharmacologic or therapeutic interventions with defined sample sizes. METHODS: Sixteen subjects (7 normal volunteers, 9 patients with coronary artery disease) had rest and adenosine stress perfusion cardiovascular magnetic resonance studies on two separate visits. A short axis slice was studied on each visit using a fast low-angle shot sequence. The global and regional myocardial perfusion reserve indices were calculated using 2 methods: model based constrained deconvolution with the Fermi function, and normalized upslopes. Reproducibility was defined as the standard deviation of the measurement differences, divided by the mean (coefficient of variation). RESULTS: The reproducibility of global myocardial perfusion reserve indices was 21% in normal volunteers, which was similar to that in patients with coronary artery disease (CAD) (23%, p = .88). The reproducibility of regional myocardial perfusion reserve indices was 28% (p = .45 vs. global analysis). The reproducibility of global MPRi was superior with Fermi deconvolution compared with normalized upslopes (21% vs. 41%, p = .02). CONCLUSION: At this stage of clinical development, the reproducibility of quantitative perfusion cardiovascular magnetic resonance is good, and superior using Fermi deconvolution in preference to upslope analysis.

Adenosine↗

Constrained optimisation and its application to scintigraphy.

Any instrument that records data will produce a distorted or degraded version of the input signal. For example, imaging equipment will produce a blurred image of the object, and in the case of scintigraphic imaging the blurs may be comparable to the size of the physiological structures being investigated. The process of refocusing is called, in mathematical terms, deconvolution. In scintigraphy most workers have implemented deconvolution based on Wiener filtering. The shortcomings of the Wiener method when applied to scintigraphy are identified and an alternative approach to deconvolution using constrained optimisation is presented. The mathematical derivation of the new restoring filter is given in terms of the discrete Fourier transform. The practical implementation of the method on a digital computer is described and, as an example, the result of deconvolving a brain scan is presented.

Brain↗

The inverse problem of a Gaussian convolution and its application to the finite size of the measurement chambers/detectors in photon and proton dosimetry.

A Gaussian convolution kernel K is deduced as a Green's function of a Lie operator series. The deconvolution of a Gaussian kernel is developed by the inverse Green's function K(-1). A practical application is the deconvolution of measured profiles Dm(x) of photons and protons with finite detector size to determine the profiles Dp(x) of point-detectors or Monte Carlo Bragg curves of protons. The presented algorithms work if Dm(x) is either an analytical function or only given in a numerical form. Some approximation methods of the deconvolution are compared (differential operator expansion to analytical adaptations of 2 x 2 cm2 and 4 x 4 cm2 profiles, Hermite expansions to measured 6 x 6 cm2 and 20 x 20 cm2 profiles and Bragg curves of 80/180 MeV protons, FFT to an analytical 4 x 4 cm2 profile). The inverse problem may imply ill-posed problems, and, in particular, the use of FFT may be susceptible to them.

Algorithms↗

Functional CT in lung with a conventional scanner: simulations and sampling considerations.

Due to rapid transit times, motion artefacts from breathing and the low signal intensity, functional computed tomography (f-CT) studies in lung tissue remain challenging with conventional CT scanners. The purpose of this study is to examine the accuracy of parameter estimates when performing deconvolution analysis with signals from lung tissue. The effects of partial volume averaging in lung tissue, differing transit times, variable vascular and capillary responses, expected noise levels, differing sampling rate and durations were simulated on a computer. Deconvolution using singular-value decomposition (SVD) analysis was performed for realistic lung signals using published and measured values of the arterial input and noise levels. The accuracy, bias and variance of the estimated residue functions and their associated parameter estimates were evaluated. We find that f-CT signals may be measured and analysed using SVD and other deconvolution approaches. Functional CT signals in the lung may be analysed provided that the rise and fall of the tissue and input curves are well sampled (regardless of sampling rate) and noise levels in the lung ROI tissue are approximately 20 HU or less, even for regions of interest that are mostly occupied by air. Estimates of the mean tissue transit time (MTT) are insensitive to air volume. Other decovolution methods such as fast Fourier transform methods provide more accurate estimates of PBF, whereas SVD approaches provide more accurate estimates of pulmonary blood volume and MTT. F-CT of the lung with a conventional scanner should be possible, when the extra dose is not a consideration.

Computer Simulation↗

Analytical reconstruction of deconvolved Fourier rebinned PET sinograms.

Fully 3D PET data are often rebinned into 2D data sets in order to avoid computationally intensive fully 3D reconstruction. Then, conventional 2D reconstruction techniques are employed to obtain images from the rebinned data. In a common scenario, 2D filtered back projection (FBP) is applied to Fourier rebinned (FORE) data. This approach is suboptimal because FBP is based on an idealized mathematical model of the data and cannot account for the statistical structure of data and noise. FORE data contain some blur in all three dimensions in comparison to conventional 2D PET data. In this work, we propose methods for approximating this blur in the sinogram domain due to FORE through its point spread function (PSF). We also explore simple methods for deconvolving the rebinned data with this PSF to restore it to a more ideal state prior to FBP. Our results show that deconvolution of the approximate transaxial PSF yields no improvement. When low image noise levels are required for detection tasks, the deconvolution of the axial PSF does not provide adequate resolution or quantitative benefits to justify its application. When accurate quantitation is required and higher noise levels are acceptable, the deconvolution of the axial PSF leads to considerable gains (30%) in accuracy over conventional FORE+FBP at matched noise levels.

Algorithms↗

Input characteristics and bioavailability after administration of immediate and a new extended-release formulation of hydromorphone in healthy volunteers.

BACKGROUND: To compare the pharmacokinetics of intravenous, oral immediate-release (IR), and oral extended-release (OROS ) formulations of hydromorphone. METHODS: In this randomized, six-session, crossover-design study, 12 subjects received hydromorphone 8-mg intravenous, 8-mg IR oral, and 8-, 16-, and 32-mg OROS formulations or placebo orally followed by plasma sampling for hydromorphone determination. Pharmacokinetic analysis was performed using NONMEM. Using the disposition of hydromorphone from the intravenous administration, deconvolution was used to estimate the input rate function (release rate from the gut to the blood) for the IR and OROS formulations. A linear spline was used to describe the drug input rate function. RESULTS: The deconvolution using linear splines described the release characteristics of both the IR and OROS formulations. The mean absolute bioavailability for the 8-mg OROS formulation was significantly larger ( = 0.025) than for the 8-mg IR formulation: 0.24 (SD 0.059) versus 0.19 (SD 0.054), respectively. The bioavailability was the same for the three doses of the OROS formulation. Predicted degree of fluctuation of plasma concentrations would be expected to be 130% and 39% for the IR and OROS 8-mg doses, respectively. CONCLUSIONS: The OROS formulation of hydromorphone produced continued release of medication over 24 h, which should allow for once-daily oral dosing. The extended release of hydromorphone will produce less fluctuation of plasma concentrations compared with IR formulations, which should provide for more constant pain control. The in vivo release of hydromorphone from both IR and OROS formulations were adequately described using a linear spline deconvolution approach. The increased bioavailability from the OROS formulation may be related to decreased metabolism by a first-pass effect or enterohepatic recycling of hydromorphone.

Administration, Oral↗

Accurate analysis of blood vessel sizes and stenotic lesions using stereoscopic DSA system.

We have developed a technique to determine accurately the magnification factor and three-dimensional orientation of a vessel segment from a stereoscopic pair of digital subtraction angiograms (DSA). Our DSA system includes a stereoscopic x-ray tube with a 25-mm focal spot shift. The magnification and orientation of a selected vessel segment are determined from the distance and direction of the focal spot shift and the stereoscopic discrepancy in image positions for that segment. Our results indicate that the accuracies of determining the magnification and orientation are less than 1% and approximately 5 degrees, respectively. After the magnification and orientation are determined accurately, an iterative deconvolution technique for the measurement of vessel image size is applied to the selected vessel segment. This iterative deconvolution technique provides the best estimate of vessel image size by taking into account the unsharpness of the digital system. With this technique, the vessel image size can be determined to an accuracy of approximately 1.0 mm, which corresponds to one third the pixel size of our DSA system. Information derived from stereoscopic analysis and iterative deconvolution thus allows accurate calculation of actual vascular dimensions from DSA images.

Angiography↗

An adaptive Gaussian model for satellite image deblurring.

The deconvolution of blurred and noisy satellite images is an ill-posed inverse problem, which can be regularized within a Bayesian context by using an a priori model of the reconstructed solution. Since real satellite data show spatially variant characteristics, we propose here to use an inhomogeneous model. We use the maximum likelihood estimator (MLE) to estimate its parameters and we show that the MLE computed on the corrupted image is not suitable for image deconvolution because it is not robust to noise. We then show that the estimation is correct only if it is made from the original image. Since this image is unknown, we need to compute an approximation of sufficiently good quality to provide useful estimation results. Such an approximation is provided by a wavelet-based deconvolution algorithm. Thus, a hybrid method is first used to estimate the space-variant parameters from this image and then to compute the regularized solution. The obtained results on high resolution satellite images simultaneously exhibit sharp edges, correctly restored textures, and a high SNR in homogeneous areas, since the proposed technique adapts to the local characteristics of the data.

Algorithms↗

A non-invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses.

The present study was undertaken to measure the weight of muscle destroyed by an intramuscular injection of phenylbutazone (PBZ) in horses. In six horses, CK disposition parameters were evaluated after intravenous (i.v.) and intramuscular (i.m.) administration of a CK horse preparation. The same horses received PBZ, a potentially irritating agent, by i.v. and i.m. (neck and hindquarter) routes. Data were analysed using compartmental approaches and instantaneous CK flux was calculated using a discrete deconvolution method. For a 150 U/kg CK dose, the steady-state volume of distribution was 0.050 +/- 0.0115 L/kg and the plasma half-life was 112 +/- 18 min. After CK i.m. administration, the half-life of the terminal phase was 11.8 +/- 5.3 h indicating a flip-flop process and the mean bioavailability of CK was close to 100%. After PBZ i.m. administration, the CK activity was significantly increased with peak values of 508 +/- 109 U/L after the neck administration and 873 +/- 365 U/L after the gluteal administration. By measuring the total amount of CK released from injured muscle, it was calculated that an equivalent of 0.044 +/- 0.029 g/kg of muscle was destroyed after PBZ administration in the neck. The corresponding figure was 0.118 +/- 0.048 g/kg after intragluteal PBZ administration. By deconvoluting plasma CK activity, it was shown that the CK entry rate was maximum for the first 30-60 min following PBZ administration, which then decreased slowly to return to the control value after a delay of 24-48 h after PBZ administration. It was concluded that the CK release pattern following a controlled muscular damage was a non-invasive approach useful for quantifying the amount of damaged muscle, and that the calculation of CK input rate by deconvolution was of potential interest in describing events at the muscle cell level.

Animals↗

Study of polynucleotide conformation by resolution-enhanced ultraviolet spectroscopy poly(rC) and poly(dC).

Self-deconvolution and the fourth derivative of ultraviolet absorption spectra have been used to study stacked single-stranded and double-helix structures of different cytosine-containing polynucleotides for the first time. These compounds were studied under different solution conditions (pH and organic solvents) and at low temperatures. The red shift of the lower band (B2u band plus possibly some n-->pi* transition) of the absorption spectra in the cytosine-containing polynucleotides and the appearance of new peaks in the deconvoluted and derivative spectra in the 280-310 nm region are attributed mainly to cytosine-cytosine stacking interactions. In particular, the fourth-derivative peaks at wavelengths higher than 290 nm can be associated to coupling of electronic transitions of cytosine bases. The nature of the electronic transitions producing the absorption bands which are resolved in the aforementioned fourth-derivative peaks is discussed. It is concluded that the resolution-enhancement techniques used in this work, i.e. self-deconvolution and fourth derivative, complement each other and are useful methods to study structural changes of single-stranded and double-stranded polynucleotides allowing, at the same time, more information to be obtained about specific stacking interactions than classical absorption spectrophotometry.

Cytidine↗

Simple peak shift analysis of time-of-flight data with a slow instrumental response function.

Analysis of time-of-flight (TOF) data is sometimes limited by the instrumental response function, and optical parameters are extracted from the observed response curve by several mathematical methods, such as deconvolution. In contrast to this, we demonstrate that a method using shifts of the peak time of the response curve with different source-detector separations can yield the average path length of the light traveling in a tissue-like sample without deconvolution. In addition, combining the intensity information allows us to separate the scattering and absorption coefficients. This simple method is more robust in signal-to-noise ratio than the moment analysis, which also does not require the deconvolution procedure, because the peak position is not significantly dependent on the baseline fluctuation and the contamination of the scattering. The analysis is demonstrated by TOF measurements of an Intralipid solution at 800 nm, and is applied to the measurements at 1.29 microm, where the temporal response of photomultiplier tubes is not sufficiently good.

Fat Emulsions, Intravenous↗

Experimental evaluation of a simple algorithm to enhance the spatial resolution in scanned radiographic systems.

In order to ensure an early diagnosis of breast cancer, an imaging system must fulfil extremely stringent requirements in terms of dynamic range, contrast resolution and spatial resolution. Furthermore, in order to reduce the dose delivered to the patient, a high efficiency of the detector device should be provided. In this paper the SYRMEP/FRONTRAD (SYnchrotron Radiation for MEdical Physics/FRONTier RADiology) mammography project, based on synchroton radiation and a novel solid state pixel detector, is briefly described. Particular relevance is given to the fact that the radiographic image is obtained by means of a scanning technique, which allows the possibility of utilizing a scanning step smaller than the pixel size. With this procedure, a convolution between the real image and the detector point spread function (PSF) is actually acquired: by carefully measuring the detector PSF, it is possible to apply a post-processing procedure (filtered deconvolution), which reconstructs images with enhanced spatial resolution. The image acquisition modality and the deconvolution algorithm are herein described, and some test object images, with spatial resolution enhanced by means of the filtered deconvolution procedure, are presented. As discussed in detail in this paper, this procedure allows us to obtain a spatial resolution determined by the scanning step, rather than by the pixel size.

Algorithms↗

Physiological attributes of endogenous bioactive luteinizing hormone secretory bursts in man.

The exact nature of glandular secretory events is difficult to discern in vivo, since underlying patterns of hormone release are confounded by metabolic clearance. Moreover, conventional immunoassay does not always agree with bioassay. Here, we have used the rat interstitial cell testosterone in vitro bioassay of luteinizing hormone (LH) to measure serial LH concentrations in the normal adult human male. The resultant bioactive LH time series were analyzed by a deconvolution model in which circulating hormone concentrations are controlled by the operation of four finite, nonzero, and determinable parameters: 1) the location(s); 2) the amplitude(s), and 3) the half-duration(s) of underlying secretory bursts, acted on by 4) endogenous exponential clearance kinetics. A macroscopic secretory burst was modeled in the algebraic form of a Gaussian distribution of instantaneous molecular secretory rates. The physiological implications of this model were examined by analyzing bioactive LH pulsatility in eight men sampled every 10 min for 6 h. Multiple-parameter deconvolution disclosed endogenous bioactive LH half-lives of 53 +/- 5.4 min (range 38-76 min), in agreement with earlier independent estimates of 65 +/- 4.9 (42-87) min in four LH-deficient men given a 35 micrograms iv bolus of human LH. Calculated endogenous production rates of bioactive LH (0.48 +/- 0.06 mIU.min-1.ml-1) were also in accord with values estimated previously from steady-state infusions of LH. Deconvolution further indicated that underlying bioactive LH secretory bursts had half-durations of only 12.2 +/- 1.5 min, occurred at intervals of 56 +/- 1.3 min, and achieved amplitudes of 2.1 +/- 0.26 mIU.min-1.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pulsatile insulin secretion accounts for 70% of total insulin secretion during fasting.

The purpose of the present study was to determine the contributions of discrete insulin secretory bursts vs. basal insulin release to total insulin secretion in vivo. Quantification of the partitioning of pulsatile and basal insulin secretion is complicated by physiological delivery of these pulses into the portal vein and the absence of validated methods of measuring the rates of pulsatile and basal insulin secretion in vivo. We therefore 1) developed a canine model with chronically implanted portal vein catheters, 2) validated an established deconvolution technique as well as a novel direct catheterization technique (Clustcath) for measurement of pulsatile and nonpulsatile insulin secretion rates in this model, and 3) applied these methods to study insulin secretion in the overnight-fasted dog in vivo to determine the contribution of pulsatile vs. basal insulin secretion to total rates of endogenous insulin secretion. Rates of total, pulsatile, and nonpulsatile endogenous insulin secretion measured by Cluscath closely parallel those measured by deconvolution analysis (54 +/- 15 vs. 51 +/- 11, 38 +/- 12 vs. 36 +/- 11, and 16 +/- 4 vs. 14 +/- 4 pmol/min, respectively). Clustcath and deconvolution indicated that the majority of insulin was secreted as pulses (70 +/- 6 and 66 +/- 7%, respectively). These data infer that any process that selectively decreases the pulsatile component of insulin secretion (e.g., diabetes mellitus) will likely have a major impact on total insulin secretion.

Animals↗

Estimation of growth hormone secretion rate: impact of kinetic assumptions intrinsic to the analytical approach.

We compared four common mathematical techniques to determine daily endogenous growth hormone (GH) secretion rates from diurnal plasma GH concentration profiles in 24 women (16 upper- or lower-body obese and 8 normal-weight individuals). Two forms of deconvolution analysis and two techniques based on a priori determined GH clearance estimates were employed. Deconvolution analyses revealed significant differences in the 24-h GH secretion rate between normal-weight and upper-body obese women, whereas the other two techniques did not. Moreover, deconvolution analyses predicted that the reduction in mean plasma GH concentrations in upper-body obese women was accounted for by impaired GH secretion, whereas the other methods suggested that obesity increases GH metabolic clearance. Thus we infer that disparate conclusions concerning GH secretion can be drawn from the same primary data set. The different inferences likely reflect dissimilar kinetic assumptions and the particular limitations intrinsic to each analytical approach. Accordingly, we urge caution in the facile comparison of calculated GH secretion data in humans, especially when kinetic and secretion measurements are performed under different conditions. The most appropriate way to determine the GH secretion rate in humans must be balanced by the exact intent of the experiment and the acceptability of different assumptions in that context.

Adult↗

An anatomic and physiological model of hepatic vascular system.

Hepatic function can be characterized by the activity/time curves obtained by imaging the aorta, spleen, and liver. Nonparametric deconvolution of the activity/time curves is clinically useful as a diagnostic tool in determining organ transit times and flow fractions. The use of this technique is limited, however, because of numerical and noise problems in performing deconvolution. Furthermore, the interaction of part of the tracer with the spleen and gastrointestinal tract, before it enters the liver, further obscures physiological information in the deconvolved liver curve. In this paper, a mathematical relationship is derived relating the liver activity/time curve to portal and hepatic behavior. The mathematical relationship is derived by using transit time spectrum/residence time density theory. Based on this theory, it is shown that the deconvolution of liver activity/time curves gives rise to a complex combination of splenic, gastrointestinal, and liver dependencies. An anatomically and physiologically plausible parametric model of the hepatic vascular system has been developed. This model is used in conjunction with experimental data to estimate portal, splenic, and hepatic physiological blood flow parameters for eight normal volunteers. These calculated parameters, which include the portal flow fraction, the splenic blood flow fraction, and blood transit times are shown to adequately correspond to published values. In particular, the model of the hepatic vascular system identifies the portal flow fraction as 0.752 +/- 0.022, the splenic blood flow fraction as 0.180 +/- 0.023, and the liver mean transit time as 13.4 +/- 1.71 s. The model has also been applied to two portal hypertensive patients. The variation in some of the model parameters is beyond normal limits and is consistent with the observed pathology.

Blood Flow Velocity↗

Interaction of baseline synaptic noise and Ia EPSPs: evidence for appreciable negative correlation under physiological conditions.

1. In the anesthetized cat, simultaneous intracellular recordings from pairs of spinal motoneurons were undertaken to see whether the amplitude of single-fiber excitatory postsynaptic potentials (EPSPs) in both cells fluctuated in a coordinated manner that would indicate correlative mechanisms at either pre- or post-synaptic level. Although these recordings revealed correlated fluctuations in the baseline, the single-fiber Ia/EPSPs recorded with the spike-triggered averaging technique exhibited no correlated fluctuations and, unexpectedly, virtually no increase in baseline variance associated with the EPSP. However, the fact that these experiments were carried out under conditions of high baseline synaptic noise (i.e., with muscle stretch) may have influenced the outcome because of interaction between EPSP and synaptic noise, and this possibility was evaluated explicitly. 2. A given connection was studied under low noise by electrically stimulating a single Ia fiber in the absence of muscle stretch. The same connection was analyzed under conditions of high noise by activating the fiber and all other stretch receptor afferents with muscle stretch and by using spike-triggered averaging to extract the EPSP. The differences in mean EPSP amplitude at a given connection under conditions of low noise and high noise were minimal. 3. Fluctuations in EPSP amplitude were then determined to see whether these were influenced by presence of baseline synaptic noise and whether the interaction was nonlinear. Two methods were used to measure EPSP fluctuations: measurement of the variance associated with the EPSP, and determination by the use of deconvolution methods of the discrete amplitude components associated with the EPSP. 4. An increase in baseline variance was observed during the EPSP evoked under low noise conditions at all six connections studied in this way. This increase disappeared at two of these connections when examined under high noise. This may help to explain the results obtained in pairs of motoneurons. 5. The deconvolution results were used to calculate the variance of the noise-free EPSP. This was found to differ from the variance of the EPSP amplitude distribution measured directly from the change in baseline variance associated with the EPSP. Analytic techniques suggested that this difference could be explained in most cases by negative correlation between the EPSP and baseline synaptic noise. These considerations led to an analytic method to assess the reliability of the deconvolution result. 6. Simulation studies revealed that the baseline variance increase associated with the EPSP is also highly dependent on the correlation between signal and noise.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗