Biomedical subjects

Harrison H Barrett

Publications and source records attributed to Harrison H Barrett.

At least 19 recordsLinked to original sources

PubMed2007

Maximum-likelihood methods in wavefront sensing: stochastic models and likelihood functions.

Maximum-likelihood (ML) estimation in wavefront sensing requires careful attention to all noise sources and all factors that influence the sensor data. We present detailed probability density functions for the output of the image detector in a wavefront sensor, conditional not only on wavefront parameters but also on various nuisance parameters. Practical ways of dealing with nuisance parameters are described, and final expressions for likelihoods and Fisher information matrices are derived. The theory is illustrated by discussing Shack-Hartmann sensors, and computational requirements are discussed. Simulation results show that ML estimation can significantly increase the dynamic range of a Shack-Hartmann sensor with four detectors and that it can reduce the residual wavefront error when compared with traditional methods.

Electrons↗

PubMed2006

Comparing cardiac ejection fraction estimation algorithms without a gold standard.

RATIONALE AND OBJECTIVES: Imaging and estimation of left ventricular function have major diagnostic and prognostic importance in patients with coronary artery disease. It is vital that the method used to estimate cardiac ejection fraction (EF) allows the observer to best perform this task. To measure task-based performance, one must clearly define the task in question, the observer performing the task, and the patient population being imaged. In this report, the task is to accurately and precisely measure cardiac EF, and the observers are human-assisted computer algorithms that analyze the images and estimate cardiac EF. It is very difficult to measure the performance of an observer by using clinical data because estimation tasks typically lack a gold standard. A solution to this "no-gold-standard" problem recently was proposed, called regression without truth (RWT). MATERIALS AND METHODS: Results of three different software packages used to analyze gated, cardiac, and nuclear medicine images, each of which uses a different algorithm to estimate a patient's cardiac EF, are compared. The three methods are the Emory method, Quantitative Gated Single-Photon Emission Computed Tomographic method, and the Wackers-Liu Circumferential Quantification method. The same set of images is used as input to each of the three algorithms. Data were analyzed from the three different algorithms by using RWT to determine which produces the best estimates of cardiac EF in terms of accuracy and precision. RESULTS AND DISCUSSION: In performing this study, three different consistency checks were developed to ensure that the RWT method is working properly. The Emory method of estimating EF slightly outperformed the other two methods. In addition, the RWT method passed all three consistency checks, garnering confidence in the method and its application to clinical data.

Algorithms↗

PubMed2006

A probabilistic model for the MRMC method, part 2: validation and applications.

RATIONALE AND OBJECTIVES: We have previously described a probabilistic model for the multiple-reader, multiple-case paradigm for receiver operating characteristic analysis. When the figure of merit is the Wilcoxon statistic, this model returns a seven-term expansion for the variance of this statistic as a function of the numbers of cases and readers. This probabilistic model also provides expressions for the coefficients in the seven-term expansion in terms of expectations over the internal noise, readers, and cases. Finally, this probabilistic model sets bounds on both the overall variance of the Wilcoxon statistic and the individual coefficients. MATERIALS AND METHODS: In this article, we will first validate the probabilistic model by comparing variances determined by direct computation of the expansion coefficients to empirical estimates of the variance using independent sampling. Validation of the probabilistic model will enable us to use the direct estimates of the expansion coefficients as a gold standard to compare other coefficient-estimation techniques. Next, we develop a coefficient-estimation technique that employs bootstrapping to estimate the Wilcoxon statistic variance for different numbers of readers and cases. We then employ constrained, least-squares fitting techniques to estimate the expansion coefficients. The constraints used in this fitting are derived directly from the probabilistic model. RESULTS: Using two different simulation studies, we show that the novel (and practical) bootstrapping/fitting technique returns estimates of the coefficients that are consistent with the gold standard. CONCLUSION: The results presented also serve to validate the seven-term expansion for the variance of the Wilcoxon statistic.

Analysis of Variance↗

PubMed2006

A probabilistic model for the MRMC method, part 1: theoretical development.

RATIONALE AND OBJECTIVES: Current approaches to receiver operating characteristic (ROC) analysis use the MRMC (multiple-reader, multiple-case) paradigm in which several readers read each case and their ratings (or scores) are used to construct an estimate of the area under the ROC curve or some other ROC-related parameter. Standard practice is to decompose the parameter of interest according to a linear model into terms that depend in various ways on the readers, cases, and modalities. Though the methodologic aspects of MRMC analysis have been studied in detail, the literature on the probabilistic basis of the individual terms is sparse. In particular, few articles state what probability law applies to each term and what underlying assumptions are needed for the assumed independence. When probability distributions are specified for these terms, these distributions are assumed to be Gaussians. MATERIALS AND METHODS: This article approaches the MRMC problem from a mechanistic perspective. For a single modality, three sources of randomness are included: the images, the reader skill, and the reader uncertainty. The probability law on the reader scores is written in terms of three nested conditional probabilities, and random variables associated with this probability are referred to as triply stochastic. RESULTS: In this article, we present the probabilistic MRMC model and apply this model to the Wilcoxon statistic. The result is a seven-term expansion for the variance of the figure of merit. CONCLUSION: We relate the terms in this expansion to those in the standard, linear MRMC model. Finally, we use the probabilistic model to derive constraints on the coefficients in the seven-term expansion.

Analysis of Variance↗

PubMed2006

SemiSPECT: a small-animal single-photon emission computed tomography (SPECT) imager based on eight cadmium zinc telluride (CZT) detector arrays.

The first full single-photon emission computed tomography (SPECT) imager to exploit eight compact high-intrinsic-resolution cadmium zinc telluride (CZT) detectors, called SemiSPECT, has been completed. Each detector consists of a CZT crystal and a customized application-specific integrated circuit (ASIC). The CZT crystal is a 2.7 cm x 2.7 cm x -0.2 cm slab with a continuous top electrode and a bottom electrode patterned into a 64 x 64 pixel array by photolithography. The ASIC is attached to the bottom of the CZT crystal by indium-bump bonding. A bias voltage of -180 V is applied to the continuous electrode. The eight detectors are arranged in an octagonal lead-shielded ring. Each pinhole in the eight-pinhole aperture placed at the center of the ring is matched to each individual detector array. An object is imaged onto each detector through a pinhole, and each detector is operated independently with list-mode acquisition. The imaging subject can be rotated about a vertical axis to obtain additional angular projections. The performance of SemiSPECT was characterized using 99mTc. When a 0.5 mm diameter pinhole is used, the spatial resolution on each axis is about 1.4 mm as estimated by the Fourier crosstalk matrix, which provides an algorithm-independent average resolution over the field of view. The energy resolution achieved by summing neighboring pixel signals in a 3 x 3 window is about 10% full-width-at-half-maximum of the photopeak. The overall system sensitivity is about 0.5 x 10(-4) with the energy window of +/-10% from the photopeak. Line-phantom images are presented to visualize the spatial resolution provided by SemiSPECT, and images of bone, myocardium, and human tumor xenografts in mice demonstrate the feasibility of preclinical small-animal studies with SemiSPECT.

Animals↗

PubMed2006

Singular-value decomposition for through-focus imaging systems.

Singular-value decomposition (SVD) of a linear imaging system gives information on the null and measurement components of object and image and provides a method for object reconstruction from image data. We apply SVD to through-focus imaging systems that produce several two-dimensional images of a three-dimensional object. Analytical expressions for the singular functions are derived in the geometrical approximation for a telecentric, laterally shift-invariant system linear in intensity. The modes are evaluated numerically, and their accuracy confirmed. Similarly, the modes are derived and evaluated for a continuous image representing the limit of a large number of image planes.

Journal Article↗

PubMed2006

Information content of data types in time-domain optical tomography.

The information content of data types in time-domain optical tomography is quantified by studying the detectability of signals in the attenuation and reduced scatter coefficients. Detection in both uniform and structured backgrounds is considered, and our results show a complex dependence of spatial detectability maps on the type of signal, data type, and background. In terms of the detectability of lesions, the mean time of arrival of photons and the total number of counts effectively summarize the information content of the full temporal waveform. A methodology for quantifying information content prior to reconstruction without assumptions of linearity is established, and the importance of signal and background characterization is highlighted.

Algorithms↗

PubMed2006

Objective assessment of image quality. IV. Application to adaptive optics.

The methodology of objective assessment, which defines image quality in terms of the performance of specific observers on specific tasks of interest, is extended to temporal sequences of images with random point spread functions and applied to adaptive imaging in astronomy. The tasks considered include both detection and estimation, and the observers are the optimal linear discriminant (Hotelling observer) and the optimal linear estimator (Wiener). A general theory of first- and second-order spatiotemporal statistics in adaptive optics is developed. It is shown that the covariance matrix can be rigorously decomposed into three terms representing the effect of measurement noise, random point spread function, and random nature of the astronomical scene. Figures of merit are developed, and computational methods are discussed.

Algorithms↗

PubMed2005

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin.

BACKGROUND: (99m)Tc-sestamibi (MIBI) and (99m)Tc-tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging. METHODS: Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session. RESULTS: MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62+/-0.15 vs. 0.55+/-0.05, P<.05) for TF and 1.9-fold (1.21+/-0.04 vs. 0.64+/-0.05, P<.05) for MIBI but did not affect MCF7/WT. CONCLUSIONS: The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Efficiency of the human observer detecting random signals in random backgrounds.

The efficiencies of the human observer and the channelized-Hotelling observer relative to the ideal observer for signal-detection tasks are discussed. Both signal-known-exactly (SKE) tasks and signal-known-statistically (SKS) tasks are considered. Signal location is uncertain for the SKS tasks, and lumpy backgrounds are used for background uncertainty in both cases. Markov chain Monte Carlo methods are employed to determine ideal-observer performance on the detection tasks. Psychophysical studies are conducted to compute human-observer performance on the same tasks. Efficiency is computed as the squared ratio of the detectabilities of the observer of interest to the ideal observer. Human efficiencies are approximately 2.1% and 24%, respectively, for the SKE and SKS tasks. The results imply that human observers are not affected as much as the ideal observer by signal-location uncertainty even though the ideal observer outperforms the human observer for both tasks. Three different simplified pinhole imaging systems are simulated, and the humans and the model observers rank the systems in the same order for both the SKE and the SKS tasks.

Algorithms↗

PubMed2005

Task-based lens design with application to digital mammography.

Recent advances in model observers that predict human perceptual performance now make it possible to optimize medical imaging systems for human task performance. We illustrate the procedure by considering the design of a lens for use in an optically coupled digital mammography system. The channelized Hotelling observer is used to model human performance, and the channels chosen are differences of Gaussians. The task performed by the model observer is detection of a lesion at a random but known location in a clustered lumpy background mimicking breast tissue. The entire system is simulated with a Monte Carlo application according to physics principles, and the main system component under study is the imaging lens that couples a fluorescent screen to a CCD detector. The signal-to-noise ratio (SNR) of the channelized Hotelling observer is used to quantify this detectability of the simulated lesion (signal) on the simulated mammographic background. Plots of channelized Hotelling SNR versus signal location for various lens apertures, various working distances, and various focusing places are presented. These plots thus illustrate the trade-off between coupling efficiency and blur in a task-based manner. In this way, the channelized Hotelling SNR is used as a merit function for lens design.

Algorithms↗

PubMed2004

Imaging recognition of multidrug resistance in human breast tumors using 99mTc-labeled monocationic agents and a high-resolution stationary SPECT system.

Imaging recognition of multidrug-resistance by 99mTc-labeled sestamibi, tetrofosmin and furifosmin in mice bearing human breast tumors was evaluated using a high-resolution SPECT, FASTSPECT. Imaging results showed that the washout rates in drug-resistant MCF7/D40 tumors were significantly greater than that in drug-sensitive MCF7/S tumors. Furifosmin exhibited greater washout from both MCF7/S and MCF7/D40 than sestamibi, while tetrofosmin washout was greater than sestamibi in MCF7/D40 only. Feasibility of the monocationic agents for characterizing MDR expression was well clarified with FASTSPECT imaging.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice.

BACKGROUND AND AIM: Previous studies have showed that 99mTc labelled glucarate (GLA) might be an agent for non-invasive detection of breast tumours. In xenografted BT20 breast tumours, GLA was found to have higher uptake than 99mTc sestamibi (MIBI). It is unclear whether GLA can localize in all cell line breast cancer xenografts, as well as breast tumours with multidrug resistance (MDR). The present study aimed to investigate the properties of GLA in detecting drug sensitive and drug resistant MCF7 breast cancer xenografts in mice by using dynamic single photon emission computed tomography (SPECT) imaging. METHODS: MCF7/S cells are drug sensitive breast carcinoma cells. MCF7/D40 cells are 40-fold more resistant to doxorubicin compared to MCF7/S. Subcutaneous tumours were grown in SCID mice for 10-14 days after injection of 1 x 10(6) cells into the right thigh. Anaesthetized mice with MCF7/S (MIBI, n=9; GLA, n=8) and MCF7/D40 (MIBI, n=6; GLA, n=5) tumours were imaged using a high-resolution SPECT system called FASTSPECT. Dynamic images were acquired for 2 h after intravenous injection of GLA or MIBI. Expression of MDR P-glycoprotein (Pgp) in the tumours was demonstrated in the MCF7/D40 tumours by western blotting, not in the MCF7/S tumours. RESULTS: The xenografted tumours were visualized unequivocally within 10-30 min in GLA images and remained detectable for at least 2 h after injection. Drug resistant tumours, from which MIBI was rapidly expelled, retained GLA as readily as did drug sensitive tumours. The biodistribution data of GLA demonstrated significantly higher accumulation (%ID/g) compared to MIBI. CONCLUSION: MCF7 tumour xenografts can be detected by 99mTc glucarate imaging. More importantly, 99mTc glucarate can potentially localize drug resistant breast tumours.

Animals↗

PubMed2004

Figures of merit for detectors in digital radiography. I. Flat background and deterministic blurring.

Digital radiography systems can be thought of as continuous linear shift-invariant systems followed by sampling. This view, along with the large number of pixels used for flat-panel systems, has motivated much of the work which attempts to extend figures of merit developed for analog systems, in particular noise equivalent quanta (NEQ) and detective quantum efficiency (DQE). A more general approach looks at the system as a continuous-to-discrete mapping and evaluates the signal-to-noise ratio (SNR) completely from the discrete data. In this paper, we study the effect of presampling blur on these figures of merit for a simple model that assumes that the background fluence is constant and that the blurring of the signal is deterministic. We find that for small signals, even in this idealized model, commonly used DQE/NEQ formulations do not accurately track the behavior of the fully digital SNR. Using these NEQ-based figures of merit would lead to different design decisions than using the ideal SNR. This study is meant to bring attention to the assumptions implicitly made when using Fourier methods.

Algorithms↗

PubMed2004

Figures of merit for detectors in digital radiography. II. Finite number of secondaries and structured backgrounds.

The current paradigm for evaluating detectors in digital radiography relies on Fourier methods. Fourier methods rely on a shift-invariant and statistically stationary description of the imaging system. The theoretical justification for the use of Fourier methods is based on a uniform background fluence and an infinite detector. In practice, the background fluence is not uniform and detector size is finite. We study the effect of stochastic blurring and structured backgrounds on the correlation between Fourier-based figures of merit and Hotelling detectability. A stochastic model of the blurring leads to behavior similar to what is observed by adding electronic noise to the deterministic blurring model. Background structure does away with the shift invariance. Anatomical variation makes the covariance matrix of the data less amenable to Fourier methods by introducing long-range correlations. It is desirable to have figures of merit that can account for all the sources of variation, some of which are not stationary. For such cases, we show that the commonly used figures of merit based on the discrete Fourier transform can provide an inaccurate estimate of Hotelling detectability.

Algorithms↗

PubMed2004

High-resolution imaging with (99m)Tc-glucarate for assessing myocardial injury in rat heart models exposed to different durations of ischemia with reperfusion.

UNLABELLED: (99m)Tc-Glucarate ((99m)Tc-GLA) is a novel infarct-avid imaging agent. The aim of this study was to evaluate the role of (99m)Tc-GLA for assessing the severity of myocardial ischemia-reperfusion injury in rat heart models exposed to varied durations of left coronary artery (LCA) occlusion with reperfusion using a high-resolution SPECT system, FASTSPECT. We also wanted to clarify whether a rapid sequence of 3-dimensional imaging with FASTSPECT can quantify uptake and washout kinetics of cardiovascular imaging agents in small-animal heart models. METHODS: The ischemic-reperfused rat heart models were created by ligating the LCA for 30 min (IR30, n = 12) or 90 min (IR90, n = 6) (IR = ischemia-reperfusion) and releasing the ligature for 30 min. Dynamic images were acquired over a 2-h period after (99m)Tc-GLA was intravenously injected. The ischemic area at risk (IAR) was determined by Evans blue staining. Necrosis was assessed with triphenyltetrazolium chloride (TTC) staining and a transmission electron microscope (TEM). RESULTS: The infarct size of the left ventricle (% IAR) on TTC staining was smaller in IR30 (49.2 +/- 4.3) than in IR90 (73.4 +/- 4.7, P < 0.05), which exhibited evidence of more severe irreversible injury than the IR30 heart on TEM. FASTSPECT images demonstrated hot spot accumulations of (99m)Tc-GLA in all hearts. The washout of (99m)Tc-GLA from the ischemic-reperfused area in IR90 was significantly slower than that in IR30. The ratio of the hot spot to normal myocardial activity was 4.1 +/- 0.3 in IR30 and 7.1 +/- 1.1 in IR90 (P < 0.05). The hot spot size (% IAR) (58.4 +/- 2.7 in IR30 vs. 75.9 +/- 2.7 in IR90, P < 0.05) related significantly to the infarct size. CONCLUSION: The severity of myocardial injury induced by ischemia-reperfusion can be assessed by FASTSPECT imaging with (99m)Tc-GLA. The results suggest that (99m)Tc-GLA will be clinically useful in detecting and quantifying acute necrotic myocardium. The FASTSPECT imaging with the rat heart models provides a solution-specific approach with high-resolution and fast dynamic acquisition for kinetic studies of new myocardial imaging agents.

Animals↗

PubMed2003

Experimental determination of object statistics from noisy images.

Modern imaging systems rely on complicated hardware and sophisticated image-processing methods to produce images. Owing to this complexity in the imaging chain, there are numerous variables in both the hardware and the software that need to be determined. We advocate a task-based approach to measuring and optimizing image quality in which one analyzes the ability of an observer to perform a task. Ideally, a task-based measure of image quality would account for all sources of variation in the imaging system, including object variability. Often, researchers ignore object variability even though it is known to have a large effect on task performance. The more accurate the statistical description of the objects, the more believable the task-based results will be. We have developed methods to fit statistical models of objects, using only noisy image data and a well-characterized imaging system. The results of these techniques could eventually be used to optimize both the hardware and the software components of imaging systems.

Artifacts↗

PubMed2003

Ideal-observer computation in medical imaging with use of Markov-chain Monte Carlo techniques.

The ideal observer sets an upper limit on the performance of an observer on a detection or classification task. The performance of the ideal observer can be used to optimize hardware components of imaging systems and also to determine another observer's relative performance in comparison with the best possible observer. The ideal observer employs complete knowledge of the statistics of the imaging system, including the noise and object variability. Thus computing the ideal observer for images (large-dimensional vectors) is burdensome without severely restricting the randomness in the imaging system, e.g., assuming a flat object. We present a method for computing the ideal-observer test statistic and performance by using Markov-chain Monte Carlo techniques when we have a well-characterized imaging system, knowledge of the noise statistics, and a stochastic object model. We demonstrate the method by comparing three different parallel-hole collimator imaging systems in simulation.

Diagnostic Imaging↗