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Implementation and evaluation of an ordered subsets reconstruction algorithm for transmission PET studies using median root prior and inter-update median filtering.

An ordered subsets (OS) reconstruction algorithm based on the median root prior (MRP) and inter-update median filtering was implemented for the reconstruction of low count statistics transmission (TR) scans. The OS-MRP-TR algorithm was evaluated using an experimental phantom, simulating positron emission tomography (PET) whole-body (WB) studies, as well as patient data. Various experimental conditions, in terms of TR scan time (from 1 h to 1 min), covering a wide range of TR count statistics were evaluated. The performance of the algorithm was assessed by comparing the mean value of the attenuation coefficient (MVAC) of known tissue types and the coefficient of variation (CV) for low-count TR images, reconstructed with the OS-MRP-TR algorithm, with reference values obtained from high-count TR images reconstructed with a filtered back-projection (FBP) algorithm. The reconstructed OS-MRP-TR images were then used for attenuation correction of the corresponding emission (EM) data. EM images reconstructed with attenuation correction generated by OS-MRP-TR images, of low count statistics, were compared with the EM images corrected for attenuation using reference (high statistics) TR data. In all the experimental situations considered, the OS-MRP-TR algorithm showed: (1) a tendency towards a stable solution in terms of MVAC; (2) a difference in the MVAC of within 5% for a TR scan of 1 min reconstructed with the OS-MRP-TR and a TR scan of 1 h reconstructed with the FBP algorithm; (3) effectiveness in noise reduction, particularly for low count statistics data [using a specific parameter configuration the TR images reconstructed with OS-MRP-TR(1 min) had a lower CV than the corresponding TR images of a 1-h scan reconstructed with the FBP algorithm]; (4) a difference of within 3% between the mean counts in the EM images attenuation corrected using the OS-MRP-TR images of 1 min and the mean counts in the EM images attenuation corrected using the OS-MRP-TR images of 1 h; (5) preservation of "good" image quality for both TR and EM reconstructed images. In conclusion, the OS-MRP-TR algorithm is particularly suitable for WB PET studies, allowing: (1) the acquisition of a very short TR scan (within 1 min), (2) the reconstruction of such TR data in low-noise TR images and (3) the use of the reconstructed OS-MRP-TR images for attenuation correction of corresponding EM data.

Algorithms↗

Convergent incremental optimization transfer algorithms: application to tomography.

No convergent ordered subsets (OS) type image reconstruction algorithms for transmission tomography have been proposed to date. In contrast, in emission tomography, there are two known families of convergent OS algorithms: methods that use relaxation parameters, and methods based on the incremental expectation-maximization (EM) approach. This paper generalizes the incremental EM approach by introducing a general framework, "incremental optimization transfer." The proposed algorithms accelerate convergence speeds and ensure global convergence without requiring relaxation parameters. The general optimization transfer framework allows the use of a very broad family of surrogate functions, enabling the development of new algorithms. This paper provides the first convergent OS-type algorithm for (nonconcave) penalized-likelihood (PL) transmission image reconstruction by using separable paraboloidal surrogates (SPS) which yield closed-form maximization steps. We found it is very effective to achieve fast convergence rates by starting with an OS algorithm with a large number of subsets and switching to the new "transmission incremental optimization transfer (TRIOT)" algorithm. Results show that TRIOT is faster in increasing the PL objective than nonincremental ordinary SPS and even OS-SPS yet is convergent.

Algorithms↗

[UV spectrophotometry used for quantitative determination of oleanolic acid].

In order to adapt the UV spectrophotometry method to oleanolic acid dosing, absorption spectra within the range from 230 to 350 nm have been determined for both OA systems in glacial acetic acid (lambda max = 256 nm) and OA systems in ethyl alcohol (lambda max = 277 nm). The time stability of oleanolic acid in the presence of the two solvents has also been investigated in this study. Besides, the composition of etalon series and graphical representation of experimental results (n = 6) have been performed. Also, the calculation algorithm was given, the regression lines have been drawn and statistical parameters were calculated to establish the mathematical expression of OA concentration (mg%).

Algorithms↗

Likelihood maximization for list-mode emission tomographic image reconstruction.

The maximum a posteriori (MAP) Bayesian iterative algorithm using priors that are gamma distributed, due to Lange, Bahn and Little, is extended to include parameter choices that fall outside the gamma distribution model. Special cases of the resulting iterative method include the expectation maximization maximum likelihood (EMML) method based on the Poisson model in emission tomography, as well as algorithms obtained by Parra and Barrett and by Huesman et al. that converge to maximum likelihood and maximum conditional likelihood estimates of radionuclide intensities for list-mode emission tomography. The approach taken here is optimization-theoretic and does not rely on the usual expectation maximization (EM) formalism. Block-iterative variants of the algorithms are presented. A self-contained, elementary proof of convergence of the algorithm is included.

Algorithms↗

Iterative image reconstruction for clinical PET using ordered subsets, median root prior, and a web-based interface.

PURPOSE: The development, implementation and validation of simple, flexible and efficient iterative image reconstruction (IIR) methods for their take-up in routine clinical positron emission tomography (PET) static or dynamic studies. PROCEDURES: The ordered subsets (OS) technique applied for the acceleration of the maximum likelihood expectation maximization (MLEM) IIR algorithm is here extended to include the weighted least-squares (WLS), image space reconstruction algorithm (ISRA) and the space alternating generalized EM (SAGE). The median root prior (MRP) has been successfully applied as a Bayesian regularization to control the noise level in the reconstructed images. All methods are implemented on distributed Pentium systems and tested using simulated PET data from a brain phantom. A Javascript is used for the initiation of the reconstruction. RESULTS: Taking into consideration the image quality and the time required for the reconstruction, the MRP-OSEM (ordered subsets expectation maximization) seems to provide best results after four to eight iterations, with four subsets and a MRP coefficient of 0.2-0.4. Iterative reconstruction of the transmission images with OS-acceleration and MRP regularization with subsequent calculation of the attenuation correction factors (ACFs) is shown to effectively remove streak artifacts in the emission images, especially along paths of high attenuation. CONCLUSIONS: An efficient implementation using distributed processing principles and a web-based interface allows the reconstruction of one frame (with 63 cross-section slices) from a dynamic determination in few minutes. This work showed that regular PC systems can provide fast execution and produce results in clinically meaningful times. This eradicates the argument of the computational burden of the method that prevented the extensive use of IIR in today's modern PET systems.

Journal Article↗

Mixture models, robustness, and the weighted likelihood methodology.

Problems associated with the analysis of data from a mixture of distributions include the presence of outliers in the sample, the fact that a component may not be well represented in the data, and the problem of biases that occur when the model is slightly misspecified. We study the performance of weighted likelihood in this context. The method produces estimates with low bias and mean squared error, and it is useful in that it unearths data substructures in the form of multiple roots. This in turn indicates multiple potential mixture model fits due to the presence of more components than originally specified in the model. To compute the weighted likelihood estimates, we use as starting values the method of moment estimates computed on bootstrap subsamples drawn from the data. We address a number of important practical issues involving bootstrap sample size selection, the role of starting values, and the behavior of the roots. The algorithm used to compute the weighted likelihood estimates is competitive with EM, and it is similar to EM when the components are not well separated. Moreover, we propose a new statistical stopping rule for the termination of the algorithm. An example and a small simulation study illustrate the above points.

Animals↗

Triage accuracy at a multiple casualty incident disaster drill: the Emergency Medical Service, Fire Department of New York City experience.

We sought to evaluate the accuracy and speed for the triage of multiple patients during a disaster drill by Emergency Medical Service (EMS) personnel. During a disaster drill (train collision with blast injury and chemical release), the accuracy and speed of triage of 130 patient-actors by the Fire Department of New York City (FDNY) EMS personnel was evaluated using the Simple Triage and Rapid Treatment (START) triage system. All EMS personnel had been previously trained in START, but refresher training was not administered before the drill. Overall triage accuracy was 78%. In patients that had additional changes in their status during the triage process (injects), 62% were retriaged appropriately. Because of security and decontamination procedures, triage at the triage/treatment area began 40 minutes after the drill commenced. It took 2 hours and 38 minutes to completely clear the scene of all patients. On average, the time from the start of triage to transport was 1 hour and 2 minutes. Despite the fact that triage is a skill practiced by every EMS system in the country on a daily basis, few studies regarding triage accuracy are available. Limited data suggest that the triage accuracy rates using different triage strategy algorithms are approximately 45% to 55%. During this drill, FDNY-EMS triage accuracy using the START system exceeded these expectations. This study provides insight as to the triage experience of a large urban EMS system operating at a disaster drill.

Algorithms↗

Classical detection theory and the cryo-EM particle selection problem.

Particle selection is an essential but tedious step in the determination of macromolecular structures by single particle reconstruction. This paper presents an automatic, multi-reference particle detection scheme that is based on the classical matched filter principle. It makes use of a pre-whitening filter to standardize the noise, a reduced representation of the references by means of principal component analysis, and a statistic for distinguishing particles from image artifacts. Standardizing the noise allows the noise-induced false-positive frequency to be estimated, and also allows the distribution of the discrimination statistic to be calculated a priori. The method is demonstrated with an annotated dataset of cryo-EM images.

Algorithms↗

Common conventions for interchange and archiving of three-dimensional electron microscopy information in structural biology.

Three-dimensional electron microscopy (3DEM) has made significant contributions to structural biology. To accomplish this feat, many image-processing software packages were developed by various laboratories. The independent development of methods naturally implied the adoption of dissimilar conventions-penalizing users who want to take advantage of the wealth of algorithms from different packages. In addition, a public repository of 3DEM research results, the EM Data Bank, is now established. In an era where information exchange is important, standardizing conventions is a necessity. The 3DEM field requires a consistent set of conventions. We propose a set of common conventions named the "3DEM Image Conventions." They are designed as a standardized approach to image interpretation and presentation. In this regard, the conventions serve as a first step on which to build data-exchange solutions among existing software packages and as a vehicle for homogenous data representation in data archives, such as the EM Data Bank.

Algorithms↗

A fast image reconstruction algorithm based on penalized-likelihood estimate.

Statistical iterative methods for image reconstruction like maximum likelihood expectation maximization (ML-EM) are more robust and flexible than analytical inversion methods and allow for accurately modeling the counting statistics and the photon transport during acquisition. They are rapidly becoming the standard for image reconstruction in emission computed tomography. The maximum likelihood approach provides images with superior noise characteristics compared to the conventional filtered back projection algorithm. But a major drawback of the statistical iterative image reconstruction is its high computational cost. In this paper, a fast algorithm is proposed as a modified OS-EM (MOS-EM) using a penalized function, which is applied to the least squares merit function to accelerate image reconstruction and to achieve better convergence. The experimental results show that the algorithm can provide high quality reconstructed images with a small number of iterations.

Algorithms↗

CARTOS II semi-automated nerve tracing: three-dimensional reconstruction from serial section micrographs.

The paper describes the history of tracing activities in the Levinthal lab from 1965 to the present. It also focuses on the evolution of electron micrograph (EM) tracing from early hand tracing reconstruction to the current, nearly fully automated CARTOS II tracing system. The present hardware systems and tracing algorithms are described in detail. Also presented are the partial tracing results of one EM data set in two and three dimensions.

Algorithms↗

Prehospital management of pediatric SVT.

Accurate prehospital diagnosis and early initiation of emergency medical treatment for pediatric patients found to have supraventricular tachycardia is a reasonable task to accomplish and one that does not have to be anxiety-provoking. The most important point to remember is that the standard approach to resuscitation and stabilization for pediatric patients with narrow complex tachycardias (and those with aberrant or wide complexes identifiable as WPW) applies to all variations of SVT; thus, it is not necessary to precisely diagnose the variant prior to initiation of treatment, except for WPW, in which adenosine administration is contraindicated. Once the dysrhythmia is identified as SVT, the patient must rapidly be categorized as stable or unstable, which will then lead the EMS provider down the correct branch of the treatment algorithm. Every attempt should be made to perform a 12-lead ECG pre- and post-resuscitation, as well at to administer sedation prior to emergent synchronized cardioversion. Dosages of medications need not be memorized, provided that a readily available guide, such as a Broselow tape or regional tertiary care center laminated resuscitation card, is at hand. Finally, while termination of pediatric SVT, whether spontaneous or by EMS intervention, will also likely terminate the EMS provider's own palpitations, it is essential that these patients be seen in an emergency department immediately in order to accurately diagnose their medical condition and provide the patient and family with an appropriate disposition based on the events surrounding the incident.

Cardiovascular Agents↗

Subsets and overrelaxation in iterative image reconstruction.

A number of iterative image reconstruction algorithms were integrated into one formula characterizing each algorithm by only two parameters: overrelaxation and number of subsets. From the formula it follows that the ordered-subsets iteration (OS-EM) is equivalent to iteration with overrelaxation, where the OS level corresponds to the overrelaxation parameter. Algorithms represented by the formula were studied with respect to speed of convergence and image characteristics. In particular, OS-EM was compared with a single-projection iteration procedure using an optimized sequence of overrelaxation parameters (HOSP) which combines rapid convergence with reduced storage requirements. As a result, OS-EM with a constant number of subsets either needed more iteration steps than HOSP or provoked additional noise, depending on the number of subsets used during iteration. OS-EM can be improved by using decreasing OS levels, imitating the decreasing overrelaxation parameters used for HOSP. The resulting OS-EM may be slightly more rapid than HOSP, due to the increasing number of projections used simultaneously.

Algorithms↗

Time-resolved fluorescence studies of dityrosine in the outer layer of intact yeast ascospores.

The (time-resolved) fluorescence properties of dityrosine in the outermost layer of the spore wall of Saccharomyces cerevisiae were investigated. Steady-state spectra revealed an emission maximum at 404 nm and a corresponding excitation maximum at 326 nm. The relative fluorescence quantum yield decreased with increasing proton concentration. The fluorescence decay of yeast spores was found to be nonexponential and differed pronouncedly from that of unbound dityrosine in water. Analysis of the spore decay recorded at lambda ex = 323 nm and lambda em = 404 nm by an exponential series (ESM) algorithm revealed a bimodal lifetime distribution with maxima centered at tau 1C = 0.5 ns and tau 2C = 2.6 ns. The relative amplitudes of the two distributions are shown to depend on the emission wavelength, indicating contributions from spectrally different dityrosine chromophores. On quenching the spore fluorescence with acrylamide, a downward curvature of the Stern-Volmer plot was obtained. A multitude of chromophores more or less shielded from solvent in the spore wall is proposed to account for the nonlinear quenching of the total spore fluorescence. Analysis of the fluorescence anisotropy decay revealed two rotational correlation times (phi 1 = 0.9 ns and phi 2 = 30.6 ns) or a bimodal distribution of rotational correlation times (centers at 0.7 ns and 40 ns) when the data were analyzed by the maximum entropy method (MEM). We present a model that accounts for the differences between unbound (aqueous) and bound (incorporated in the spore wall) dityrosine fluorescence. The main feature of the photophysical model for yeast spores is the presence of at least two species of dityrosine chromophores differing in their chemical environments. A hypothetical photobiological role of these fluorophores in the spore wall is discussed: the protection of the spore genome from mutagenic UV light.

Cell Membrane↗

Expert opinion elicitation for assisting deep learning based Lyme disease classifier with patient data.

BACKGROUND: Diagnosing erythema migrans (EM) skin lesion, the most common early symptom of Lyme disease, using deep learning techniques can be effective to prevent long-term complications. Existing works on deep learning based EM recognition only utilizes lesion image due to the lack of a dataset of Lyme disease related images with associated patient data. Doctors rely on patient information about the background of the skin lesion to confirm their diagnosis. To assist deep learning model with a probability score calculated from patient data, this study elicited opinions from fifteen expert doctors. To the best of our knowledge, this is the first expert elicitation work to calculate Lyme disease probability from patient data. METHODS: For the elicitation process, a questionnaire with questions and possible answers related to EM was prepared. Doctors provided relative weights to different answers to the questions. We converted doctors' evaluations to probability scores using Gaussian mixture based density estimation. We exploited formal concept analysis and decision tree for elicited model validation and explanation. We also proposed an algorithm for combining independent probability estimates from multiple modalities, such as merging the EM probability score from a deep learning image classifier with the elicited score from patient data. RESULTS: We successfully elicited opinions from fifteen expert doctors to create a model for obtaining EM probability scores from patient data. CONCLUSIONS: The elicited probability score and the proposed algorithm can be utilized to make image based deep learning Lyme disease pre-scanners robust. The proposed elicitation and validation process is easy for doctors to follow and can help address related medical diagnosis problems where it is challenging to collect patient data.

Humans↗

A novel neural network technique for analysis and classification of EM single-particle images.

We propose a novel self-organizing neural network for the unsupervised classification of electron microscopy (EM) images of biological macromolecules. The radical novelty of the algorithm lies in its rigorous mathematical formulation that, starting from a large set of possibly very noisy input data, finds a set of "representative" data items, organized onto an ordered output map, such that the probability density of this set of representative items resembles at its possible best the probability density of the input data. In a way, it summarizes large amounts of information into a concise description that rigorously keeps the basic pattern of the input data distribution. In this application to the field of three-dimensional EM of single particles, two different data sets have been used; one comprised 2458 rotational power spectra of individual negative stain images of the G40P helicase of Bacillus subtilis bacteriophage SPP1, and the other contained 2822 cryoelectron images of SV40 large T-antigen. Our experimental results prove that this technique is indeed very successful, providing the user with the capability of exploring complex patterns in a succinct, informative, and objective manner. The above facts, together with the consideration that the integration of this new algorithm with commonly used software packages is immediate, prompt us to propose it as a valuable new tool in the analysis of large collections of noisy data.

Algorithms↗

Estimation of pharmacokinetic parameters of sodium tungstate after multiple-dose during preclinical studies in beagle dogs.

In this paper, an empirical Bayes methodology was used to determine the pharmacokinetic profile of sodium tungstate in beagle dogs after multiple oral dosing using the P-PHARM computer program. The population estimation algorithm used in P-PHARM is an EM-type procedure. Sodium tungstate was administered orally, three times a day, (i) for 11 days (21 and 42 mg/kg per day) to 18 dogs (nine males and nine females) and (ii) for 13 weeks (15, 30 and 60 mg/kg per day) to 28 dogs (14 males, 14 females). Six other dogs received the compound intravenously (25 and 50 mg/kg). Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. After oral administration, F (0.61+/-0.086 vs. 0.48+/-0.093), and normalized (to a 7-mg/kg dose of sodium tungstate) AUC (54+/-8.4 vs. 41.2+/-8.5 mg/l x h), C(max) (10.6+/-0.49 vs. 8.5+/-0.57 microg/ml) and C(min) (3.04+/-0.23 vs. 2.04+/-0.22 microg/ml), were higher in male than in female dogs. However, the introduction of the gender in the final model did not contribute statistically to an improvement of the fit of the population pharmacokinetic model. In males, t(1/2) elimination averaged 3.1+/-0.56 vs. 2.6+/-0.18 h in females. The duration of treatment did not modify statistically the pharmacokinetic parameters. After repeated multiple oral administration of 15-60 mg/kg per day of sodium tungstate, tungsten plasma concentrations increased in proportion to dose. No dose-dependent changes in pharmacokinetic parameters occurred.

Administration, Oral↗

The use of electron microscopy to refine diagnoses in the daily practice of cytopathology.

Conceived as a screening tool, cytology is a field that since the 1980s has become more diagnostic in its scope. The advent of the fine-needle aspiration biopsy (FNAB) is responsible for cytology's new place in pathology. In the everyday practice of cytopathology, about 85-90% of the nongynecologic cases can be diagnosed with the use of routine stains (i.e., Papanicolaou and Diff Quik). The other 10-15% of the cases require the use of ancillary diagnostic techniques for a precise diagnosis. Immunohistochemistry helps solve approximately 50% of these cases, and the other half of these challenging cases are best approached and diagnosed by using electron microscopy (EM). In their practice, the authors obtain cytologic samples for EM routinely in difficult cases. Unfortunately, a percentage of these cases collected for ultrastructural evaluation do not have enough cells after processing, and others only have a few diagnostic cells available. In the cases in which at least a handful of cells are available, EM is almost invariably helpful in one way or another, either making a definitive diagnosis or refining the diagnosis. A sampling of FNAB cases from the authors' everyday practice is prevented to illustrate the use of EM in the practice of cytopathology. The cases have been selected from among the most common diagnostic challenges to highlight the important role that ultrastructural evaluation plays in a busy cytology practice. In our practice ultrastructural evaluation is a piece of the puzzle, which, along with the clinical history, clinical impression, light microscopic/cytologic features, and other ancillary techniques (IHC, flow cytometry, and molecular pathology), help compile an accurate diagnosis. Many times EM is the most important component of the diagnostic algorithm.

Adolescent↗