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PubMed2005

Three-dimensional IMRT verification with a flat-panel EPID.

A three-dimensional (3D) intensity-modulated radiotherapy (IMRT) pretreatment verification procedure has been developed based on the measurement of two-dimensional (2D) primary fluence profiles using an amorphous silicon flat-panel electronic portal imaging device (EPID). As described in our previous work, fluence profiles are extracted from EPID images by deconvolution with kernels that represent signal spread in the EPID due to radiation and optical scattering. The deconvolution kernels are derived using Monte Carlo simulations of dose deposition in the EPID and empirical fitting methods, for both 6 and 15 MV photon energies. In our new 3D verification technique, 2D fluence modulation profiles for each IMRT field in a treatment are used as input to a treatment planning system (TPS), which then generates 3D doses. Verification is accomplished by comparing this new EPID-based 3D dose distribution to the planned dose distribution calculated by the TPS. Thermoluminescent dosimeter (TLD) point dose measurements for an IMRT treatment of an anthropomorphic phantom were in good agreement with the EPID-based 3D doses; in contrast, the planned dose under-predicts the TLD measurement in a high-gradient region by approximately 16%. Similarly, large discrepancies between EPID-based and TPS doses were also evident in dose profiles of small fields incident on a water phantom. These results suggest that our 3D EPID-based method is effective in quantifying relevant uncertainties in the dose calculations of our TPS for IMRT treatments. For three clinical head and neck cancer IMRT treatment plans, our TPS was found to underestimate the mean EPID-based doses in the critical structures of the spinal cord and the parotids by approximately 4 Gy (11%-14%). According to radiobiological modeling calculations that were performed, such underestimates can potentially lead to clinically significant underpredictions of normal tissue complication rates.

Algorithms↗
PubMed2005

Noninvasive reflection spectra provide quantitative information about the spatial distribution of skin chromophores.

In this work, a new method of analyzing noninvasive reflection spectra is presented. The approach explicitly models the inhomogeneity of chromophore distributions in living tissues and thus extracts not only apparent chromophore concentrations but also relative chromophore distributions in tissues. Furthermore, it works with spectra obtained with short source-detector separations where the diffusion theory of light transport through turbid media is not valid, and formerly presented methods thus fail. The effect of inhomogeneously distributed chromophores in a multicompartment model of tissues on measured reflection spectra is explained and an algorithm to deconvolute tissue spectra based on this model is presented. It is evaluated using simulated spectra and measurements on phantoms, which are made up of partially printed pieces of paper to simulate inhomogeneous dye distributions. Its applicability to real tissue is proven using reflection spectra obtained with 130 microm source-detector separation from a hemoperfusion stop experiment. The proposed model accurately determines apparent chromophore concentrations and corresponding distributions in simulated spectra and phantoms. Regarding real tissue spectra, the results correspond to former publications and the spectral reconstruction yields only minimal residuals, indicating a complete and accurate spectral deconvolution. In conclusion, the presented approach is a suitable extension and amendment to existing models of light transport through inhomogeneous samples.

Algorithms↗
PubMed2005

Comprehensive Monte Carlo calculation of the point spread function for a commercial a-Si EPID.

Images produced by commercial amorphous silicon electronic portal imaging devices (a-Si EPIDs) are subject to multiple blurring processes. Implementation of these devices for fluence measurement requires that the blur be removed from the images. A standard deconvolution operation can be performed to accomplish this assuming the blur kernel is spatially invariant and accurately known. This study determines a comprehensive blur kernel for the Varian aS500 EPID. Monte Carlo techniques are used to derive a dose kernel and an optical kernel, which are then combined to yield an overall blur kernel for both 6 and 15 MV photon beams. Experimental measurement of the line spread function (LSF) is used to verify kernel shape. Kernel performance is gauged by comparing EPID image profiles with in-air dose profiles measured using a diamond detector (approximating fluence) both before and after the EPID images have been deconvolved. Quantitative comparisons are performed using the chi metric, an extension of the well-known y metric, using acceptance criteria of 0.0784 cm (1 pixel width) distance-to-agreement (deltad) and 2% of the relative central axis fluence (deltaD). Without incorporating any free parameters, acceptance was increased from 49.0% of pixels in a cross-plane profile for a 6 MV 10 x 10 cm2 open field to 92.0%. For a 10 x 10 cm2 physically wedged field, acceptance increased from 40.3% to 73.9%. The effect of the optical kernel was found to be negligible for these chi acceptance parameters, however for (deltaD= 1%, deltad = 0.0784 cm) we observed an improvement from 66.1% (without) to 78.6% (with) of chi scores <1 (from 20.6% before deconvolution). It is demonstrated that an empirical kernel having a triple exponential form or a semiempirical kernel based on a simplified model of the detector stack can match the performance of the comprehensive kernel.

Calibration↗
PubMed1998

Experimental determination of the convolution kernel for the study of the spatial response of a detector.

One of the most important parameters in the characterization of a detector is its spatial convolution kernel. This kernel contains all of the information about the influence that the detector size has on the measured beam profile. In this paper we present an experimental method for the determination of the spatial convolution kernel for commonly used detectors that are employed in the x-ray profile measurement: film + densitometer, diode, and ionization minichamber. Our work is based on first assuming a step function pattern on a photographic film is known and is a perfect step function. The kernel of the densitometer system was then derived from the deconvolution of the scanned profile to the step function. Next a film was exposed to a penumbra area of an x-ray beam from a linac. The film was scanned using the same densitometer. The "real profile" that emerges from a linear accelerator was derived by the deconvolution of the scanned profile using the now known kernel of the film densitometer. Under the same irradiation condition the x-ray profile was measured with other detectors and with this information we obtained the convolution kernels for these detectors by solving numerically their basic convolution integrals. The results show that the Gaussian convolution kernel is the most consistent with the measurements. The best numerical values for the FWHM of the kernels are 1.1 mm, 2.2 mm, and 5.4 mm for densitometer, diode, and minichamber, respectively.

Biophysical Phenomena↗
PubMed1999

Quantitative optical densitometry with scanning-laser film digitizers.

A new process for eliminating two types of artifacts inherent in commercially available transmission scanning-laser film digitizers is presented. The first kind of artifact results in nonreproducible interference-pattern fluctuations as large as 7%. The second kind results in spreading of transmitted light from low-to-high optical density (OD) in regions with rapidly varying ODs, producing errors as large as 50%. These OD artifacts cause the loss of precision for films with low-OD regions (first type) and the loss of accuracy for films with regions of high-OD near high-OD gradients (second type). Test radiochromic films, produced by uniform exposure to a 6 MV photon beam and a high dose rate 192Ir brachytherapy source, along with test radiographic films were used to characterize the artifacts of a commercially available scanning-laser film digitizer. The interference-pattern artifact was eliminated by digitizing the films on a masked diffusing ground-glass scanning bed. The light-transmission artifact was eliminated through discrete-fast-Fourier-transform (DFFT) deconvolution of transmission profiles with measured digitizer line-spread functions. Obtaining precise OD distributions after the DFFT deconvolution required prior removal of the interference-pattern artifact and application of a low-pass Wiener noise filter. Light-transmission artifacts are particularly significant for applications requiring measurement of high-gradient OD distributions, such as brachytherapy or conformal photon-beam film dosimetry and quantitation of two-dimensional electrophoresis gels. Errors as large as 15%-35% occur in OD distributions representative of these applications. The data collection and correction process developed in this study successfully removes these artifacts.

Biophysical Phenomena↗
PubMed1999

Enterococcus faecalis bearing aggregation substance is resistant to killing by human neutrophils despite phagocytosis and neutrophil activation.

Enterococcus faecalis aggregation substance (AS) mediates efficient bacterium-bacterium contact to facilitate plasmid exchange as part of a bacterial sex pheromone system. We have previously determined that AS promotes direct, opsonin-independent binding of E. faecalis to human neutrophils (PMNs) via complement receptor type 3 and other receptors on the PMN surface. We have now examined the functional consequences of this bacterium-host cell interaction. AS-bearing E. faecalis was phagocytosed and internalized by PMNs, as determined by deconvolution fluorescence microscopy. However, these bacteria were not killed by PMNs, and internalized bacteria excluded propidium iodide, indicating intact bacterial membranes. Resistance to killing occurred despite activation of PMNs, as indicated by an increase in both functional and total surface Mac-1 expression, shedding of L-selectin, and an increase in PMN extracellular superoxide and phagosomal oxidant production. Deconvolution fluorescence microscopy also revealed that phagosomes containing AS-bearing bacteria were markedly larger than phagosomes containing opsonized E. faecalis, suggesting that some modification of phagosomal maturation may be involved in AS-induced resistance to killing. PMN phagosomal pH was significantly higher after ingestion of nonopsonized AS-bearing E. faecalis than after that of opsonized bacteria. The novel ability of AS to promote intracellular survival of E. faecalis inside PMNs suggests that AS may be a virulence factor used by strains of E. faecalis.

Animals↗
PubMed2002

Which MR-derived perfusion parameters are the best predictors of infarct growth in hyperacute stroke? Comparative study between relative and quantitative measurements.

PURPOSE: To compare predictors of infarct growth in hyperacute stroke from a retrospective review of various relative and quantitative parameters calculated at perfusion-weighted magnetic resonance (MR) imaging performed within 6 hours after ictus. MATERIALS AND METHODS: Fluid-attenuated inversion recovery and diffusion- and perfusion-weighted images were obtained in 66 patients. The initial infarct was delineated on diffusion-weighted images; the hemodynamic disturbance, on apparent mean transit time (MTT) maps; and the final infarct, on follow-up fluid-attenuated inversion recovery images. Relative (without and with deconvolution) and quantitative values of the bolus arrival time, time to peak (TTP), apparent MTT or MTT, cerebral blood volume (CBV), peak height, and cerebral blood flow (CBF) index or CBF were calculated for initial infarct, infarct growth (final minus initial infarct contour), viable hemodynamic disturbance (apparent MTT minus final infarct contour), and contralateral mirror regions. Univariate and multivariate analyses (receiver operating characteristic curves and discriminant analysis) were performed to compare the diagnostic performance of these parameters for predicting infarct growth. RESULTS: At univariate analysis, relative peak height and quantitative CBF were the best predictors of infarct growth; at multivariate analysis, a function of peak height and TTP for relative measurements and CBF alone for quantitative measurements. Quantitative and relative measurements (without or with deconvolution) worked equally well. A combined relative peak height or TTP threshold (<54% or >5.2 seconds, respectively) had a sensitivity of 71% and a specificity of 98%. A quantitative CBF threshold (<35 mL/min/100 g) had a sensitivity of 69% and a specificity of 85%. CONCLUSION: A combination of relative peak height and TTP measurements allowed the best prediction of infarct growth, which obviates more complex quantitative calculation.

Acute Disease↗
PubMed1991

Nuclear calcium gradients in cultured rat hepatocytes.

Ca2+ concentrations ([Ca2+]) in cytosol and nucleus in fura-2-loaded cultured rat hepatocytes were determined by three-dimensional (3-D) optical-sectioning microscopy. After determining the empirical 3-D point spread function of the fluorescence microscope-coupled digital video imaging system, contaminating light arising from optical planes above and below the plane of interest was removed by deconvolution using the nearest-neighboring approach (NNA) algorithm. Although deconvolution resulted in substantial improvement in accuracy of fluorescence intensity determinations in single-wavelength excitation images as well as sharper delineation of boundaries between cellular compartments, the complicated mathematical process did not significantly enhance the precision of [Ca2+] values derived from ratiometric (ratio of dual-wavelength excitation) images. In resting hepatocytes, cytosolic Ca2+ (210 +/- 15 nM) was 1.6- to 2-fold higher than nuclear Ca2+ (128 +/- 12 nM). This difference in Ca2+ between the two compartments was detected both in raw ratiometric images and in those processed with NNA algorithm. Addition of arginine vasopressin or epidermal growth factor resulted in significant increases (2- to 3-fold) in both cytosolic and nuclear Ca2+; however, the nuclear-to-cytosolic Ca2+ gradient was preserved in hepatocytes stimulated with mitogens. We conclude that the hepatocyte nuclear membrane contains Ca2+ permeability barriers and Ca2+ transport mechanisms that may be hormonally sensitive. We postulate that the increase in nuclear Ca2+ may be important in regulation of cell proliferation induced by mitogens, possibly by activating Ca(2+)-dependent endonucleases, nuclear calmodulin, or nuclear protein kinase C.

Algorithms↗
PubMed2000

High-frequency oscillations in circulating amylin concentrations in healthy humans.

Amylin is stored in the pancreatic beta-cell granules and cosecreted with insulin in response to nutrient stimuli. To gain further insight into control of hormonal release in beta-cell physiology, we examined whether amylin, like insulin, circulates in a high-frequency oscillatory pattern, and if it does, to compare the secretory patterns of the two hormones. Eight overnight-fasted healthy individuals were studied during intravenous glucose infusion (2.0 mg. kg(-1). min(-1)). Blood was collected every minute for 90 min and analyzed in triplicate for amylin, total amylin immunoreactivity (TAI), and insulin. Mean plasma concentrations of amylin (nonglycosylated), TAI (nonglycosylated plus glycosylated), insulin, and glucose were 2.77 +/- 1.21 pmol/l, 7.60 +/- 1.73 pmol/l, 50.4 +/- 17.5 pmol/l, and 5.9 +/- 0.3 mmol/l, respectively. The 90-min time series of amylin, TAI, and insulin were analyzed for periodicity (by spectral analysis, autocorrelation analysis, and deconvolution analysis) and regularity [by approximate entropy (ApEn)]. Significant spectral density peaks were demonstrated by a random shuffling technique in 7 (out of 7), 8 (out of 8), and 8 (out of 8) time series, respectively, whereas autocorrelation analysis revealed significant pulsatility in 5 (out of 7), 7 (out of 8), and 5 (out of 8), respectively. The dominant periodicity of oscillations determined by spectral analysis was 4.6 +/- 0.3, 4.6 +/- 0.4, and 6. 5 +/- 1.1 min/pulse, respectively (amylin vs. insulin, P = 0.017, TAI vs. insulin, P = 0.018). By deconvolution analysis, amylin and insulin periodicities were, respectively, 6.3 +/- 1.0 and 5.5 +/- 0. 6 min. By application of the regularity statistic, ApEn, 6 (out of 7), 7 (out of 8), and 6 (out of 8), respectively, were found to be significantly different from random. In conclusion, like several other hormones, circulating amylin concentrations exhibit oscillations in the secretory patterns for nonglycosylated as well as glycosylated forms. Whether the high-frequency pulsatile release of amylin is disturbed in diabetes is not known.

Adult↗
PubMed1987

A model-free method for mass spectrometer response correction.

A new method for correction of mass spectrometer output signals is described. Response-time distortion is reduced independently of any model of mass spectrometer behavior. The delay of the system is found first from the cross-correlation function of a step change and its response. A two-sided time-domain digital correction filter (deconvolution filter) is generated next from the same step response data using a regression procedure. Other data are corrected using the filter and delay. The mean squared error between a step response and a step is reduced considerably more after the use of a deconvolution filter than after the application of a second-order model correction. O2 consumption and CO2 production values calculated from data corrupted by a simulated dynamic process return to near the uncorrupted values after correction. Although a clean step response or the ensemble average of several responses contaminated with noise is needed for the generation of the filter, random noise of magnitude less than or equal to 0.5% added to the response to be corrected does not impair the correction severely.

Cardiac Output↗
PubMed2026

Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma.

PURPOSE: Liquid biopsy monitoring in pediatric solid tumors is limited by low mutational burden and lack of trackable genomic drivers. We sought to develop a mutation-agnostic, methylation-based liquid biopsy framework enabling universal molecular surveillance of high-risk neuroblastoma. EXPERIMENTAL DESIGN: Using whole-genome Oxford Nanopore Technologies sequencing of high-risk neuroblastoma tumors, we compared tumor-derived methylation profiles with a comprehensive atlas of normal human cell types and identified 72 neuroblastoma-specific differentially methylated regions (meNBL) that were reliably detectable in cell-free DNA (cfDNA). Marker robustness and specificity were validated using independent neuroblastoma methylation datasets and assessed against methylation profiles from other cancer types. We established neuroblastoma as a distinct methylation entity within the reference atlas by integrating a panel of 25 meNBLs, enabling quantitative estimation of tumor-derived cfDNA. Assay performance was evaluated across diagnostic, remission, relapse, and healthy control samples and compared with mutation-based and copy number-based approaches. RESULTS: Neuroblastoma-derived cfDNA was consistently detected at diagnosis and relapse but was absent in healthy controls and during confirmed remission. Methylation-based deconvolution demonstrated high specificity, with no detectable background signal in controls, and improved performance relative to copy number-based tumor fraction estimation. Longitudinal profiling enabled early molecular detection of relapse and reliable disease monitoring. CONCLUSIONS: We establish a robust, mutation-independent methylation-based liquid biopsy strategy for neuroblastoma that enables accurate, quantitative disease monitoring across all high-risk patients, including those lacking trackable genomic alterations. This approach supports the clinical translation of methylation-based cfDNA deconvolution as a broadly applicable platform for pediatric precision oncology.

Humans↗
PubMed2006

Towards many colors in FISH on 3D-preserved interphase nuclei.

The article reviews the existing methods of multicolor FISH on nuclear targets, first of all, interphase chromosomes. FISH proper and image acquisition are considered as two related components of a single process. We discuss (1) M-FISH (combinatorial labeling + deconvolution + wide-field microscopy); (2) multicolor labeling + SIM (structured illumination microscopy); (3) the standard approach to multicolor FISH + CLSM (confocal laser scanning microscopy; one fluorochrome - one color channel); (4) combinatorial labeling + CLSM; (5) non-combinatorial labeling + CLSM + linear unmixing. Two related issues, deconvolution of images acquired with CLSM and correction of data for chromatic Z-shift, are also discussed. All methods are illustrated with practical examples. Finally, several rules of thumb helping to choose an optimal labeling + microscopy combination for the planned experiment are suggested.

Cell Nucleus↗
PubMed1992

Comparison of four computerized models to estimate 24-hour growth hormone secretion in girls with Turner's syndrome.

Daily pituitary growth hormone (GH) secretion can be estimated from a 24-hour GH profile by various methods. We have used four methods to assess GH secretion in 36 girls with Turner's syndrome: the method described by Thompson et al., the Pulsar algorithm combined with the method of Hellman et al. and two deconvolution techniques. The number of detected peaks varied considerably among the methods. The mean (+/- SD) total daily secretion per square meter body surface was 0.53 (0.19) U/m2.day by deconvolution, in contrast to 0.31 (0.17) with the Hellman method and 1.06 (0.37) according to Thompson. The differences are explained by different assumptions about the metabolic clearance rate and various methodological aspects. Assuming a degradation rate of 50%, the growth hormone substitution dosage would be 1-2 IU/m2.day in GH-deficient children. The usual dosage in girls with Turner's syndrome is expected to lead to serum GH levels approximately 4 times higher than in the untreated state.

Adolescent↗
PubMed1989

High-resolution, reflection mode tomographic imaging. Part I: Principles and methods.

A general method for improving image resolution is derived and applied to ultrasound signals; it combines the principles of both reflection mode tomography and deconvolution. The different possibilities of applying these principles allow two types of approaches to be defined, depending upon whether image reconstruction is achieved on radiofrequency or detected signals. A thorough description of three methods that are of particular interest due to their lower computation costs is presented, and their results quantified. They permit a gain in resolution of the order of ten with respect to two-dimensional deconvolution of images, as well as an improvement of the S/N ratio, which is related to the square root of the number of projections used in the reconstruction process, and a decrease of about four in computation time.

Humans↗
PubMed1989

High-resolution, reflection mode tomographic imaging. Part II: Application to echography.

Principles of high-resolution, ultrasonic imaging using data acquisition by a compound scanning with a sector echograph are presented. The signal processing is based on both deconvolution and reflection mode tomography. Three of the methods that can be derived from these principles are selected due to their lower computation costs. Applications of these methods to synthetic data and test targets demonstrate that, with respect to 2D deconvolution, they offer: a gain in computation time of more than 8, an improvement in resolution of the order of 10 and an increase of S/N ratio of the order of 4. Finally, both the effects of limited acquisition angular window and of a variable propagation speed are illustrated.

Humans↗
PubMed1997

High resolution low frequency ultrasonic tomography.

Ultrasonic reflection tomography results from a linearization of the inverse acoustic scattering problem, named the inverse Born approximation. The goal of ultrasonic reflection tomography is to obtain reflectivity images from backscattered measurements. This is a Fourier synthesis problem and the first step is to correctly cover the frequency space of the object. For this inverse problem, we use the classical algorithm of tomographic reconstruction by summation of filtered backprojections. In practice, only a limited number of views are available with our mechanical rig, typically 180, and the frequency bandwidth of the pulses is very limited, typically one octave. The resolving power of the system is them limited by the bandwidth of the pulse. Low and high frequencies can be restored by use of a deconvolution algorithm that enhances resolution. We used a deconvolution technique based on the Papoulis method. The advantage of this technique is conservation of the overall frequency information content of the signals. The enhancement procedure was tested by imaging a square aluminium rod with a cross-section less than the wavelength. In this application, the central frequency of the transducer was 250 kHz so that the central wavelength was 6 mm whereas the cross-section of the rod was 4 mm. Although the Born approximation was not theoretically valid in this case (high contrast), a good reconstruction was obtained.

Computer Simulation↗
PubMed1996

Susceptibility contrast imaging of CO2-induced changes in the blood volume of the human brain.

PURPOSE: To investigate changes in the regional cerebral blood volume (rCBV) in human subjects during rest and hypercapnia by MR imaging, and to compare the results from contrast-enhanced and noncontrast-enhanced susceptibility-weighted imaging. MATERIAL AND METHODS: Five healthy volunteers (aged 24-29 years) were studied during inhalation of atmospheric air and 7% CO2. A bolus injection of Gd-DTPA was given during the acquisition of a series of susceptibility-weighted, fast gradient echo images (TR/TE = 27/22 ms). The images were converted to delta R2* maps, and CBV was calculated pixelwise by fitting a gamma-variate function to the data. The tissue concentration vs time curves were deconvoluted using an input function obtained by arterial sampling. RESULTS: The ratio of gray to white matter CBV (1.9-2.5) as well as the fractional increase in rCBV during hypercapnia (about 30%) was found to be in accordance with results obtained by other methods. Noncontrast functional MR (fMR) imaging showed signal increases in gray matter, but also inconsistent changes in some white matter regions. CONCLUSION: In this experiment, contrast-enhanced imaging seemed to show a somewhat higher sensitivity towards changes in cerebral hemodynamics than noncontrast-enhanced imaging. The results of the deconvolution analysis suggested that perfusion calculation by conventional tracer kinetic methods may be impracticable because of nonlinear effects in contrast-enhanced MR imaging.

Administration, Inhalation↗
PubMed2005

Isotropic component trace analysis.

A new method for analyzing diffusion tensor imaging (DTI) of the brain, based on a recently introduced algorithm, lambda chart analysis (LCA), is presented. Pre-treatment of a given DTI data set with LCA, which effectively segregates isotropic and anisotropic components, allows for total removal of the anisotropic component from the DTI data set. The remaining pure isotropic component can therefore be subjected to further analysis similar to that applied in the trace histogram method. Deconvolution of the trace function yielded 3 Gaussian elements. Remapping of these 3 deconvoluted isotropic elements back onto the 2-dimensional image plane provided anatomical correlates of each element. The algorithm, referred to here as isotropic component trace analysis, can be used as a pictorial analytic tool, as well as a numerical analytical tool, for the noninvasive assessment of isotropic parenchymal components. The presented method provides quantitative indices of certain parenchymal parameters with better clarity than currently available methods. A ready-to-use program, EZ-LCA, for this powerful method is provided (available at http://coe.bri.niigata-u.ac.jp).

Algorithms↗