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Analysis of various beamlet sizes for IMRT with 6 MV photons.

Application of intensity modulated radiation therapy (IMRT) using multileaf collimation often requires the use of small beamlets to optimize the delivered radiation distribution. Small-beam dose distribution measurements were compared to dose distributions calculated using a commercial treatment planning system that models its data acquired using measurements from relatively large fields. We wanted to evaluate only the penumbra, percent depth-dose (PDD) and output model, so we avoided dose distribution features caused by rounded leaf ends and interleaf leakage by making measurements using the secondary collimators. We used a validated radiochromic film dosimetry system to measure high-resolution dose distributions of 6 MV photon beams. A commercial treatment planning system using the finite size pencil beam (FSPB) dose calculation algorithm was commissioned using measured central axis outputs from 4.0x4.0 to 40.0x40.0 cm2 beams and radiographic-film profile measurements of a 4.0x4.0 cm2 beam at twice the depth of maximum dose (dmax). Calculated dose distributions for square fields of 0.5x0.5 cm2, and 1.0x1.0 cm2, to 6.0x6.0 cm2, in 1.0x1.0 cm2, increments were compared against radiochromic film measurements taken with the film oriented parallel to the beam central axis in a water equivalent phantom. The PDD of the smaller field sizes exhibited behavior typical of small fields, namely a decrease in dmax with decreasing field size. The FSPB accurately modeled the depth-dose and central axis output for depths deeper than the nominal dmax of 1.5 cm plus 0.5 cm. The dose distribution in the build-up and penumbra regions was not accurately modeled for depths less than 2 cm, especially for the fields of 2.0x2.0 cm2 and smaller. Using the gamma function with 2 mm and 2% criteria, the dose model was shown to accurately predict the penumbra. While for single small beams the compared dose distributions passed the gamma function criteria, the clinical appropriateness of these criteria is not clear for a composite IMRT plan. Further investigation of the cumulative impact of the observed dose discrepancies is warranted. We speculate that the observed differences in the penumbra regions arise from some energy dependent artifact in the radiographic-film profiles used for commissioning. In the future, radiochromic film based commissioning might provide a more accurate data set for dose modeling.

Calibration↗

Design of angle-tolerant multivariate optical elements for chemical imaging.

Multivariate optical elements (MOEs) are multilayer optical interference coatings with arbitrary spectral profiles that are used in multivariate pattern recognition to perform the task of projecting magnitudes of special basis functions (regression vectors) out of optical spectra. Because MOEs depend on optical interference effects, their performance is sensitive to the angle of incidence of incident light. This angle dependence complicates their use in imaging applications. We report a method for the design of angle-insensitive MOEs based on modification of a previously described nonlinear optimization algorithm. This algorithm operates when the effects of deviant angles of incidence are simulated prior to optimization, which treats the angular deviation as an interferent in the measurement. To demonstrate the algorithm, a 13-layer imaging MOE (IMOE, with alternating layers of high-index Nb2O5 and low-index SiO2) for the determination of Bismarck Brown dye in mixtures of Bismarck Brown and Crystal Violet, was designed and its performance simulated. For angles of incidence that range from 42 degrees to 48 degrees, the IMOE has an average standard error of prediction (SEP) of 0.55 microM for Bismarck Brown. This compares with a SEP of 2.8 microM for a MOE designed by a fixed-angle algorithm.

Journal Article↗

Oblique scaling: an algorithm to correct for a non-perpendicular camera view in tendon strain measurements.

Image distortion due to a non-perpendicular camera view introduces serious errors in tendon and ligament strain measurements when data are recorded using a single camera. These errors can be corrected with the oblique scaling algorithm using two pairs of scaling markers attached to the tendon surface. Computer simulations show that application of this algorithm reduces errors over 100 times to less than 0.06%. The method is relatively insensitive to measurement errors in the scaling marker distance but sensitive to the accuracy of alignment of the scaling markers. It can be concluded that the oblique scaling algorithm eliminates the influences of a non-perpendicular camera view in single-camera tendon and ligament strain measurements.

Algorithms↗

On-line estimation of the maximum specific growth rate of nitrifiers in activated sludge systems.

The on-line estimation of the maximum specific growth rate of autotrophic biomass is addressed in this article. A general nitrification process model, which is valid for any realistic flow pattern, is used to develop the estimation algorithm. Depending on the measurements available, two estimation equations are derived. While both require measuring the nitrification activity of the activated sludge, one requires the additional measurement of the nitrifiable nitrogen concentrations at the two ends of the bioreactor, and the other requires the nitrate nitrogen concentrations at the same locations. The algorithm also requires some stoichiometric and kinetic parameters. However, sensitivity analysis shows that the estimate is insensitive to the parameters other than the autotrophic decay rate. Compared to the existing algorithms, the algorithm developed in this article does not rely on the assumption of ideal flow pattern in the plant and does not require an error-prone estimate of the autotrophic biomass concentration. Experimental and simulation studies show that the algorithm performs well and is robust to influent variations and accidental sludge losses.

Algorithms↗

Senescent changes in scotopic contrast sensitivity.

Scotopic contrast sensitivity functions (CSFs) were measured for 50 observers between the ages of 20 and 88 years. Using a maximum-likelihood, 2-alternative, temporal forced-choice threshold-estimation algorithm, scotopic CSFs were measured at 7 spatial frequencies ranging from 0.2 to 3.0 cpd, with mean retinal illuminance equated for observers at -0.85 log scotopic Trolands. For each stimulus condition, eight cycles of a horizontal sinusoidal grating were presented within +/- 1 S.D. of a 2-D Gaussian-spatial envelope and within a 1-s Gaussian-temporal envelope. Stimuli were centered on the nasal retina along the horizontal meridian 6 degrees from the fovea. Scotopic CSFs were found to be low-pass. Statistically significant age-related declines in contrast sensitivities were found for spatial frequencies at or below 1.2 cpd. There was also a statistically significant decrease in the high frequency cut-off with age (P < 0.01). An explanation of these results in terms of optical factors is rejected, while the results are consistent with age-related changes in the magnocellular pathway.

Adult↗

Comparing the continuous representation of time-series expression profiles to identify differentially expressed genes.

We present a general algorithm to detect genes differentially expressed between two nonhomogeneous time-series data sets. As increasing amounts of high-throughput biological data become available, a major challenge in genomic and computational biology is to develop methods for comparing data from different experimental sources. Time-series whole-genome expression data are a particularly valuable source of information because they can describe an unfolding biological process such as the cell cycle or immune response. However, comparisons of time-series expression data sets are hindered by biological and experimental inconsistencies such as differences in sampling rate, variations in the timing of biological processes, and the lack of repeats. Our algorithm overcomes these difficulties by using a continuous representation for time-series data and combining a noise model for individual samples with a global difference measure. We introduce a corresponding statistical method for computing the significance of this differential expression measure. We used our algorithm to compare cell-cycle-dependent gene expression in wild-type and knockout yeast strains. Our algorithm identified a set of 56 differentially expressed genes, and these results were validated by using independent protein-DNA-binding data. Unlike previous methods, our algorithm was also able to identify 22 non-cell-cycle-regulated genes as differentially expressed. This set of genes is significantly correlated in a set of independent expression experiments, suggesting additional roles for the transcription factors Fkh1 and Fkh2 in controlling cellular activity in yeast.

Algorithms↗

Measuring portal venous perfusion with contrast-enhanced CT: comparison of direct and indirect methods.

RATIONALE AND OBJECTIVES: Two algorithms can be used to measure portal venous perfusion (PVP) with contrast material-enhanced single-level liver computed tomography. The "direct" and "indirect" algorithms use data from the portal vein and aorta, respectively. This study compared PVP values obtained with direct and with indirect algorithms in a series of patients. MATERIALS AND METHODS: Both techniques were applied in 27 patients with cirrhosis (14 men and 13 women; mean age, 56.1 years +/- 9.4) and 18 control patients (seven men and 11 women; 52.8 years +/- 12.3). A single section through the liver was scanned after intravenous injection of ioversol (40-mL bolus; 320 mg of iodine per milliliter). RESULTS: Both techniques showed reduced PVP in patients with cirrhosis (0.63 for direct and 0.17 for indirect method) compared with control patients (1.06 and 0.26, respectively), but only the direct method agreed with physiologic expectations based on animal and human studies. In separating cirrhotic and control patients, the area under the receiver operating characteristic curve was significantly greater for the direct method (0.91 vs 0.78; P = .03). CONCLUSION: Both direct and indirect methods are feasible and distinguish well between cirrhotic and control patients, but the direct method is more physiologic and is preferable if portal venous data are available.

Algorithms↗

In vivo evaluation of a noninvasive method to measure the retinal thickness in primates.

To diagnose certain macular diseases earlier and monitor their therapy more sensitively, we are developing a noninvasive method to measure the retinal thickness. The new instrument, which is an extension of slit-lamp biomicroscopy, was used to obtain the data, which were analyzed with an algorithm to yield thickness measurements. The measurements performed in monkeys indicated that the retinal thickness can be visualized in a region extending from the optic disc to the fovea and that quantitative results can be obtained. The retinal thickness reproducibility was 6% for the same location on the same day, 15% for the same location on different days, and 12% for the same location in different eyes. The average retinal thickness in these areas was 335 microns, indicating that the reproducibility was between 20 and 50 microns. Measurements across the foveola illustrated that retinal thicknesses as low as 80 microns could be obtained.

Animals↗

Bedside assessment of intravascular volume status in patients undergoing coronary bypass surgery.

BACKGROUND: Management of intravascular volume is crucial in patients after cardiopulmonary bypass as myocardial dysfunction is common. The purpose of this study was to validate a novel bedside technique for real-time assessment of intravascular volumes. METHODS: Eleven patients undergoing cardiopulmonary bypass were studied. In addition to standard monitors, a fiberoptic thermistor catheter was placed in the descending aorta and central venous injections of 10 ml ice-cold indocyanine green dye were performed. Total blood volume was measured by a standard in vitro technique. Circulating and central blood volume were calculated by using cardiac output, mean transit times, and a newly developed recursive convolution algorithm that models recirculation. Measurements were performed after induction of anesthesia and at 1, 6, and 24 h after surgery. RESULTS: A two-compartment model of the circulation was required for adequate fit of the data. We found a significant correlation between total and circulating blood volumes (r = 0.87). One hour after surgery, central blood volume was decreased by 10% (P < 0.05). At 6 and 24 h after surgery, circulating blood volumes were significantly increased by 29% and 20%, respectively (P < 0.01), although central blood volume was similar to control values. Before surgery stroke volume index correlated with circulating blood volume (r = 0.87) but not with pulmonary capillary wedge and central venous pressures. CONCLUSIONS: This study shows that bedside determinations of intravascular blood volumes are feasible and that these measurements are more indicative of intravascular volume status than are either pulmonary capillary wedge or central venous pressures in the post-cardiopulmonary bypass period. Our data also demonstrate that despite a normal central blood volume both circulating and total blood volume are significantly increased in the immediate post-cardiopulmonary bypass period.

Aged↗

Morphological measurement of the SEP using a dynamic time warping algorithm.

A dynamic time warping technique was created to align the components of digitally high-pass (300 Hz-2500 Hz) filtered somatosensory evoked potentials evoked by median nerve stimulation recorded with a bipolar cephalic montage. A cost function was assigned related to the amount of warping necessary to match a standard wave derived from 24 normal subjects. Its value ranged from 0.525 to 2.456 (mean 1.305 +/- 0.501). This contrasted with a mean of 5.089 +/- 4.277 (range 0.701-13.972) derived from 25 patients with definite (n = 24) or possible (n = 1) multiple sclerosis chosen on the basis of having few or no clinical abnormalities at the time of testing. Fourteen (56%) of the patients had cost functions that were 3 or more S.D.s above the normal mean as compared to 3 (12%) having prolonged latency of the N19 peak. When used in combination, the cost function and latency yielded 60% abnormalities; 5 times higher than latency measurement alone.

Adult↗

The clinical value of assessing left ventricular function from gated SPECT perfusion studies.

Gated myocardial perfusion SPECT is a technique that is rapidly becoming widespread in the nuclear cardiology arena, and it currently accounts for a majority of all perfusion SPECT acquisitions performed in the USA. Its main advantage is that of providing important incremental clinical information over SPECT perfusion assessment alone, at essentially no extra cost. With respect to the diagnosis of cardiac disease, gated SPECT has been demonstrated to improve specificity by helping identify attenuation artifacts in patients with suspected coronary artery disease, and is also key in identifying patients with non-ischemic cardiomyopathies. In prognostic assessment, gated SPECT-derived measurements of ejection fraction achieve substantial incremental stratification of patients at risk for cardiac death or myocardial infarction, compared to perfusion scores, and volume measurements further improve risk stratification. New quantitative algorithms allow the fast, accurate and reproducible measurement of parameters of global cardiac function (ejection fraction, end-systolic and end-diastolic volume) as well as regional cardiac function (myocardial wall motion and thickening), all of which have been validated against a wide variety of gold standards.

Coronary Disease↗

Development of an evidence-based algorithm for the management of cervical cancer.

OBJECTIVE: To develop a description of the management of cervical cancer to support locally developed, regional guidelines and to identify the level of primary research evidence to support it. DESIGN: Development of a flow-charted algorithm, using regional guidelines and clinician consensus. A Medline literature search for primary research was done to validate the algorithm and selection of papers, to verify if they were valid according to pre-defined criteria and to compare algorithm management with an alternative. MAIN OUTCOME MEASURE: The highest level of evidence for algorithm management was based on the design of the supporting research. RESULTS: Twenty percent of the algorithm is supported by level I evidence (randomised controlled trials), 70% by level II evidence (cohort studies) and 10% by level IV evidence (expert opinion or case series). Level II evidence supports the management of Stage Ia, squamous cell carcinoma by cone biopsy or a simple hysterectomy. This level of evidence also applies to research on the management of Stages Ib-IIa, by radical hysterectomy and pelvic lymphadenectomy followed by radiotherapy, if the lymph nodes are positive. Radiotherapy to treat Stages IIb-IV cervical cancer is supported by level I evidence. The management of Stage I adenocarcinoma is supported by level II evidence. CONCLUSIONS: Evaluations of the effect of informing clinicians of the strengths of the proposed management are now required, as constructing evidence-based algorithms is worthwhile, only if they are likely to affect clinical practice.

Adenocarcinoma↗

Automated determination of the magnitude and time delay ("phase") of the cardiac cycle dependent variation of myocardial ultrasonic integrated backscatter.

An algorithm for quantitative description of cardiac cycle dependent variation of integrated backscatter (cyclic variation) has been developed and is shown to be suitable for analysis of nonsinusoidal data typical of ultrasonic tissue characterization measurements from myocardium in vivo. The algorithm produces estimates of the magnitude of variation and of the time delay relative to the electrocardiographically recorded QRS-complex. To validate the algorithm, 246 integrated backscatter measurements were analyzed both manually and by the automated method. The magnitude and time delay estimates from the two methods correlated closely. With a separate set of data, the algorithm produced reasonable descriptions of the cyclic variation for 89 of 101 integrated backscatter measurements. Only modest computational power is required for effective implementation of this algorithm, facilitating inclusion of online automated analysis capabilities in quantitative ultrasonic tissue characterization systems.

Algorithms↗

A method of calculating peripheral dose distributions of photon beams below 10 MV.

The radiation dose outside the radiotherapy treatment field can be of clinical concern and, therefore, a method of accurately predicting the peripheral doses received by tissues would be beneficial. This paper describes a semiempirical method developed for calculating the peripheral dose received at points outside the collimated field edge for incident photon beams with energies below neutron production thresholds (less than 10 MV). The dependence of the peripheral dose upon depth, distance, field shape and size, azimuthal angle about the central axis, external contour variations, and tissue heterogeneities are accounted for by this calculation. Predictions by this algorithm are compared with measurements and it is shown that the method is capable of reproducing the measured peripheral dose values usually to within the statistical uncertainties of the data.

Algorithms↗

Three-dimensional optical measurement of instantaneous pressure.

Local perturbations in material density induced in a material by a compressional wave give rise to local perturbations in refractive index. Accurate, high-resolution, three-dimensional, optical measurements of an instantaneous refractive index perturbation in a homogeneous, optically transparent medium may be obtained from measurements of scattered optical intensity alone. The method of generalized projections allows incorporation of optical intensity measurements into an iterative algorithm for computing the phase of the interrogating optical pulse as the solution of a fixed point equation. The complex optical field amplitude, computed in this manner, is unique up to a constant unit magnitude complex coefficient. The three-dimensional refractive index distribution may be computed via the Fourier slice reconstruction algorithm from the optical phase data under the assumption of weak optical scattering. The refractive index perturbation is related to local instantaneous pressure under a linear, small-displacement model for the mechanical wave. A numerical simulation of the measurement experiment, phase recovery, and reconstruction process for a plane piston ultrasound transducer with a semicircular aperture and center frequency of 1.5 MHz is described and corresponds very well with experiment. Experimental data obtained using an 810-nm laser source are used to reconstruct the three-dimensional pressure field from two elements of a 2.5-MHz linear array. Comparison with a measurement obtained via a 500-microm needle hydrophone shows excellent agreement.

Acoustics↗

An adaptive control algorithm for optimization of intensity modulated radiotherapy considering uncertainties in beam profiles, patient set-up and internal organ motion.

A new general beam optimization algorithm for inverse treatment planning is presented. It utilizes a new formulation of the probability to achieve complication-free tumour control. The new formulation explicitly describes the dependence of the treatment outcome on the incident fluence distribution, the patient geometry, the radiobiological properties of the patient and the fractionation schedule. In order to account for both measured and non-measured positioning uncertainties, the algorithm is based on a combination of dynamic and stochastic optimization techniques. Because of the difficulty in measuring all aspects of the intra- and interfractional variations in the patient geometry, such as internal organ displacements and deformations, these uncertainties are primarily accounted for in the treatment planning process by intensity modulation using stochastic optimization. The information about the deviations from the nominal fluence profiles and the nominal position of the patient relative to the beam that is obtained by portal imaging during treatment delivery, is used in a feedback loop to automatically adjust the profiles and the location of the patient for all subsequent treatments. Based on the treatment delivered in previous fractions, the algorithm furnishes optimal corrections for the remaining dose delivery both with regard to the fluence profile and its position relative to the patient. By dynamically refining the beam configuration from fraction to fraction, the algorithm generates an optimal sequence of treatments that very effectively reduces the influence of systematic and random set-up uncertainties to minimize and almost eliminate their overall effect on the treatment. Computer simulations have shown that the present algorithm leads to a significant increase in the probability of uncomplicated tumour control compared with the simple classical approach of adding fixed set-up margins to the internal target volume.

Algorithms↗

[A device for studying respiratory mechanics by the forced oscillation technique].

A new compact device for measuring respiratory impedance is designed. Input respiratory impedance, an impedance of upper airways and respiratory impedance corrected for upper airways shunt can be measured in 2 minutes. The space-condition requirements are complied by integrating an oscillation generator, sensors, a mouthpiece with a screen and a reference resistor in the measuring head. The oscillation generator produces small-amplitude forced oscillations (with a tidal volume of about 1 ml) at frequencies f = 7, 10, 13, 16, and 19 Hz. Algorithms of calibration and measurement provide impedance calculation. For 55 different external impedances, complex transmission factors are measured for each of the five frequencies. The standard deviation of amount and phase of complex transmission factors are less than 5% and 0.06, respectively.

Humans↗

Experimental evaluation of leaky least-mean-square algorithms for active noise reduction in communication headsets.

An adaptive leaky normalized least-mean-square (NLMS) algorithm has been developed to optimize stability and performance of active noise cancellation systems. The research addresses LMS filter performance issues related to insufficient excitation, nonstationary noise fields, and time-varying signal-to-noise ratio. The adaptive leaky NLMS algorithm is based on a Lyapunov tuning approach in which three candidate algorithms, each of which is a function of the instantaneous measured reference input, measurement noise variance, and filter length, are shown to provide varying degrees of tradeoff between stability and noise reduction performance. Each algorithm is evaluated experimentally for reduction of low frequency noise in communication headsets, and stability and noise reduction performance are compared with that of traditional NLMS and fixed-leakage NLMS algorithms. Acoustic measurements are made in a specially designed acoustic test cell which is based on the original work of Ryan et al. ["Enclosure for low frequency assessment of active noise reducing circumaural headsets and hearing protection," Can. Acoust. 21, 19-20 (1993)] and which provides a highly controlled and uniform acoustic environment. The stability and performance of the active noise reduction system, including a prototype communication headset, are investigated for a variety of noise sources ranging from stationary tonal noise to highly nonstationary measured F-16 aircraft noise over a 20 dB dynamic range. Results demonstrate significant improvements in stability of Lyapunov-tuned LMS algorithms over traditional leaky or nonleaky normalized algorithms, while providing noise reduction performance equivalent to that of the NLMS algorithm for idealized noise fields.

Journal Article↗