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A modular framework for development and interlaboratory sharing and validation of diffusion tensor tractography algorithms.

This Technical Note describes a novel modular framework for development and interlaboratory distribution and validation of 3D tractography algorithms based on in vivo diffusion tensor imaging (DTI) measurements. The proposed framework allows individual MRI research centers to benefit from new tractography algorithms developed at other independent centers by "plugging" new tractography modules directly into their own custom DTI software tools, such as existing graphical user interfaces (GUI) for visualizing brain white matter pathways. The proposed framework is based on the Java 3D programming platform, which provides an object-oriented programming (OOP) model and independence of computer hardware configuration and operating system. To demonstrate the utility of the proposed approach, a complete GUI for interactive DTI tractography was developed, along with two separate and interchangeable modules that implement two different tractography algorithms. Although the application discussed here relates to DTI tractography, the programming concepts presented here should be of interest to anyone who wishes to develop platform-independent GUI applications for interactive 3D visualization.

Algorithms↗

Application of obesity treatment algorithms to Canadian adults.

OBJECTIVE: The purpose of this study was to apply obesity treatment algorithms to a representative sample of Canadians to determine their potential impact on the population. DESIGN: The Canadian Heart Health Surveys (1986-1992) were used to describe the prevalence of adults (18-64 y) that would be eligible for weight loss treatment according to the US NIH algorithm, which uses body mass index (BMI), waist circumference (WC), and the presence of two or more cardiovascular disease (CVD) risk factors. Similar algorithms based on CVD risk factors and a single measure of either BMI or WC alone were also evaluated. RESULTS: Using the NIH algorithm, 24% of Canadians (28% men, 19% women) would be identified for weight loss treatment. Virtually, all subjects received the same treatment recommendations when using BMI and CVD risk factors only, while 22% (23% men, 21% women) would meet the criteria for treatment using WC and CVD risk factors only. CONCLUSIONS: Approximately one in four Canadians would be eligible for weight loss treatment using the NIH obesity treatment algorithm. However, the algorithm may be improved through the incorporation of more sensitive WC thresholds.

Adolescent↗

Validation of the scanning -gamma-ray telescope for in vivo dosimetry and boron measurements during BNCT.

Gamma-ray telescope scans of a box phantom with inhomogeneous boron concentrations have proven the feasibility of in vivo measurements of different boron distributions in the head of a patient during boron neutron capture therapy (BNCT). Small structures with enhanced boron concentration can be reconstructed in a head phantom, even if the brain compartment of the phantom is surrounded by a skin layer with a ten times higher boron concentration. The motor-controlled telescope can scan the head/phantom, detecting boron and hydrogen prompt y-rays emitted at neutron capture reactions with a two-dimensional spatial resolution of 14 mm full width at half maximum. For reconstruction of the boron concentrations from the measured y-ray detection rates, a mathematical reconstruction algorithm is derived and discussed. Proper reconstruction requires position-dependent y-ray measurements combined with treatment planning programme calculations of the thermal neutron distribution. In a head phantom, in which the brain and the skull (bulk) were represented using a homogeneous boron distribution of 5.2 +/- 0.5 ppm 10B, surrounded by a skin layer with a ten times higher boron concentration, the bulk concentration was reconstructed to 4.7 +/- 0.3 ppm 10B. Telescope scans along and perpendicular to the beam axis showed the influence of inhomogeneities with a high boron concentration such as skin and a simulated blood vessel, respectively with a low boron concentration such as white matter. The profiles of the boron and hydrogen y-ray detection rates indicate how future patient measurements can be interpreted. In clinical trials, the telescope can then be used to investigate the averaged boron concentration in the bulk of a patient and local enhanced boron concentrations (e.g. in tumour tissue) in order to relate the measured boron dose distributions to the clinical effects of BNCT. Simultaneously, it can serve as quality control of the dosimetry during the irradiation.

Boron↗

GLLS for optimally sampled continuous dynamic system modeling: theory and algorithm.

The original generalized linear least squares (GLLS) algorithm was developed for non-uniformly sampled biomedical system parameter estimation using finely sampled instantaneous measurements (D. Feng, S.C. Huang, Z. Wang, D. Ho, An unbiased parametric imaging algorithm for non-uniformly sampled biomedical system parameter estimation, IEEE Trans. Med. Imag. 15 (1996) 512-518). This algorithm is particularly useful for image-wide generation of parametric images with positron emission tomography (PET), as it is computationally efficient and statistically reliable (D. Feng, D. Ho, Chen, K., L.C. Wu, J.K. Wang, R.S. Liu, S.H. Yeh, An evaluation of the algorithms for determining local cerebral metabolic rates of glucose using positron emission tomography dynamic data, IEEE Trans. Med. Imag. 14 (1995) 697-710). However, when dynamic PET image data are sampled according to the optimal image sampling schedule (OISS) to reduce memory and storage space (X. Li, D. Feng, K. Chen, Optimal image sampling schedule: A new effective way to reduce dynamic image storage space and functional image processing time, IEEE Trans. Med. Imag. 15 (1996) 710-718), only a few temporal image frames are recorded (e.g. only four images are recorded for the four parameter fluoro-deoxy-glucose (FDG) model). These image frames are recorded in terms of accumulated radio-activity counts and as a result, the direct application of GLLS is not reliable as instantaneous measurement samples can no longer be approximated by averaging of accumulated measurements over the sampling intervals. In this paper, we extend GLLS to OISS-GLLS which deals with the fewer accumulated measurement samples obtained from OISS dynamic systems. The theory and algorithm of this new technique are formulated and studied extensively. To investigate statistical reliability and computational efficiency of OISS-GLLS, a simulation study using dynamic PET data was performed. OISS-GLLS using 4-measurement samples was compared to the non-linear least squares (NLS) method using 22-measurement samples, GLLS using 22-measurement samples and OISS-NLS using 4-measurement samples. Results demonstrated that OISS-GLLS was able to achieve parameter estimates of equivalent accuracy and reliability in comparison to NLS or GLLS using finely sampled measurements (22-measurement samples), or OISS-NLS using optimally sampled measurements (4-measurement samples). Further more, as fewer measurement samples are used in OISS-GLLS, this algorithm is computationally faster than NLS or GLLS. Therefore, OISS-GLLS is well-suited for image-wide parameter estimation when PET image data are recorded according to the optimal image sampling schedule.

Algorithms↗

Automated identification of Fos expression.

The concentration of Fos, a protein encoded by the immediate-early gene c-fos, provides a measure of synaptic activity that may not parallel the electrical activity of neurons. Such a measure is important for the difficult problem of identifying dynamic properties of neuronal circuitries activated by a variety of stimuli and behaviours. We employ two-stage statistical pattern recognition to identify cellular nuclei that express Fos in two-dimensional sections of rat forebrain after administration of antipsychotic drugs. In stage one, we distinguish dark-stained candidate nuclei from image background by a thresholding algorithm and record size and shape measurements of these objects. In stage two, we compare performance of linear and quadratic discriminants, nearest-neighbour and artificial neural network classifiers that employ functions of these measurements to label candidate objects as either Fos nuclei, two touching Fos nuclei or irrelevant background material. New images of neighbouring brain tissue serve as test sets to assess generalizability of the best derived classification rule, as determined by lowest cross-validation misclassification rate. Three experts, two internal and one external, compare manual and automated results for accuracy assessment. Analyses of a subset of images on two separate occasions provide quantitative measures of inter- and intra-expert consistency. We conclude that our automated procedure yields results that compare favourably with those of the experts and thus has potential to remove much of the tedium, subjectivity and irreproducibility of current Fos identification methods in digital microscopy.

Journal Article↗

3D PET using a conventional multislice tomograph without septa.

A conventional multislice positron emission tomography scanner was modified to operate without interplane septa to evaluate its performance in collecting and reconstructing data in a three-dimensional (3D) format, thereby significantly increasing system sensitivity. A 3D filtered backprojection algorithm was implemented and tested, using both computer simulations and phantom measurements. No artifacts were apparent in the test images, although the algorithm was shown to lead to a 11% degradation in transaxial resolution in the outer planes. Following septa removal, sensitivity was found to increase by a factor of 7 with an increase in scatter fraction from 16 to 41%. Axial resolution degraded from 6.9 to 7.7 mm full width at half maximum at the center of the field of view. The maximum count rate without septa was 2.4 x 10(5) cps, at a concentration of 0.4 microCi/ml, compared with 1.3 x 10(5) cps at 1.5 microCi/ml with septa. Brain studies were performed with volunteers using 18F-fluorodeoxyglucose, 18F-fluorodopa, and H2 15O to compare noise-equivalent count rates and qualitatively assess image quality over a wide range of imaging conditions.

Algorithms↗

Degree of modiolar coiling, electrical thresholds, and speech perception after cochlear implantation.

OBJECTIVE: Perimodiolar electrode arrays were developed to improve stimulation of specific neural populations and to decrease power consumption. Postoperative radiographs suggest that some arrays are more tightly coiled than others. The purpose of this study was to evaluate whether the degree of modiolar coil correlates with electrical threshold and/or performance measures postimplantation with the Nucleus CI24RCS (Contour) device. STUDY DESIGN: Retrospective review. SETTING: Cochlear implant center and a tertiary care hospital. PATIENTS: Twenty-eight adult cochlear implant recipients with normal cochlear anatomy who underwent implantation with the Nucleus C124RCS perimodiolar electrode and are at least 1 year postimplantation. INTERVENTIONS: Therapeutic. MAIN OUTCOME MEASURES: Radiologic degree of perimodiolar electrode placement (determined by a computer algorithmic analysis) compared with electrical thresholds and standard speech perception outcome measures at 1 year postcochlear implantation. RESULTS: No significant correlations were found between the degree of modiolar coiling of the electrode array and electrical thresholds and speech perception outcome measures at 1 year postcochlear implantation. CONCLUSIONS: The degree of coiling of a modiolar hugging electrode array was not directly correlated with the level of electrical thresholds or postoperative speech perception outcome measures. Appearance of coil tightness on postoperative radiographs could reflect either differences in array placement or intrinsic variations in cochlear anatomy, and variations in speech perception performance can be influenced by other factors, including length of deafness.

Adult↗

A noninvasive technique for detecting hypernasal speech using a nonlinear operator.

Speakers with a defective velopharyngeal mechanism produce speech with inappropriate nasal resonance (hypernasal speech). It is of clinical interest to detect hypernasality as it is indicative of an anatomical, neurological, or peripheral nervous system problem. There are various clinical techniques used to determine hypernasality. The current techniques are physically invasive or intrusive to some extent. A preferred approach for detecting hypernasality, would be noninvasive to maximize patient comfort and naturalness of speaking. In this study, a noninvasive technique based on the Teager Energy operator is proposed. Utilizing a property of the Teager Energy operator and a model for normal and nasalized speech, a significant difference between the Teager Energy profile for lowpass and bandpass filtered nasalized speech is shown. This difference is shown to be nonexistent for normal speech. A classification algorithm is formulated that detects the presence of hypernasality using a measure of the difference in the Teager Energy profiles. The classification algorithm was evaluated using a native English speaker population producing front (/i/) and mid (/A/) vowels. Results show that the presence of hypernasality in speech can be reliably detected using the proposed classification algorithm.

Algorithms↗

External ocular hyperemia: a quantifiable indicator of spacecraft air quality.

BACKGROUND: Eye irritation consistently ranks as a top astronaut complaint but is difficult to measure. Exposure to internal air pollution hypothetically disrupts the eye's tear film, thereby exposing the crewmembers' conjunctivae to the irritating effects of the recirculated, contaminant-laden atmosphere of the space vehicle. Causes elude engineers and toxicologists, who report that measured irritants remain below established Spacecraft Maximum Allowable Concentrations. Lack of objective ocular endpoints stymies efforts to identify etiologies. HYPOTHESIS: Computers offer a practical means of analyzing ocular hyperemia in space. METHODS: We use computer analysis to quantify redness and blood vessels of digitized images of bulbar conjunctivae in near real time. Custom software masks artifacts, lids and lashes for each photographic or telemedicine ocular image, Algorithms then generate semi-independent measurements of hyperemia. Computed difference scores between 34 pairs of images were compared with subjective difference scores as voted on by a panel of ophthalmology residents. RESULTS: Objective data were reliably extracted from ocular images and significantly correlated (r = 0.583, p < 0.05) with subjective scores. CONCLUSIONS: This ground-based methodology generates accurate and reliable ocular endpoint data without mass, volume, or power penalty. To assist in identifying and eliminating onboard ocular irritants, these objective data can be regressed against independent variables such as mission elapsed time, subjective astronaut complaints, levels of chemical and electromagnetic contaminants, nephthelometric and barothermal data. As missions lengthen, sensitive tools such as hyperemia quantification will become increasingly important for assessing and optimizing spacecraft environments.

Adult↗

Bayesian decision making based on measurements containing errors.

The paper presents a Bayesian approach to the construction of diagnostic and prognostic algorithms, based on the use of several diagnostic factors (tests) in combination. With this approach, the simultaneous use of dichotomous, discrete, categoric, and continuous factors is easy and the resulting algorithms are more efficient than those of other known methods. Moreover, each factor value that is available for use is assumed to represent an estimate (the result of an imperfect measurement) of some (unknown) true value. The proposed method of accounting for measurement errors is advantageous as regards efficiency for users of the algorithm (physicians) if the accuracy of the factor-measurement techniques at their disposal differs from that of the constructor of the algorithm (the scientist). The approach is illustrated by an example, and possible error models and methods of collecting statistical data are discussed.

Algorithms↗

Algorithm for ventricular capture verification based on the mechanical evoked response.

Automatic pacemaker capture verification is important for maintaining safety and low energy consumption in pacemaker patients. A new algorithm was developed, based on impedance measurement between pacing electrode poles, which reflects the distribution of the conducting medium between the poles and changes with effective contraction. Data acquired during pacemaker implant in 17 subjects were analysed, with intracardiac impedance recorded while pacing was performed in the ventricle at varying energies, resulting in multiple-captured and non-captured beats. The impedance signals of all captured/non-captured beats were analysed using three different algorithms, based on the morphology of the impedance signal. The algorithm decision for each beat was compared with an actual capture or non-capture, as determined from the simultaneous recording of surface ECG. Two of the three algorithms (Z1 and Zn) were based on impedance values, and one (Z'n) was based on the first derivative of the impedance. Z1 was based on a single sample, whereas Z'n and Z'n were based on several samples in each beat. The total accuracy for each was Z1: 43%, Zn: 87%, Z'n: 92%. It was concluded that impedance-based capture verification is feasible, that a multiple rather than single sample approach for signal classification is both feasible and superior, and that first derivative analysis with multiple samples (Z'n) provides the best results.

Aged↗

Algorithms for large-scale genotyping microarrays.

MOTIVATION: Analysis of many thousands of single nucleotide polymorphisms (SNPs) across whole genome is crucial to efficiently map disease genes and understanding susceptibility to diseases, drug efficacy and side effects for different populations and individuals. High density oligonucleotide microarrays provide the possibility for such analysis with reasonable cost. Such analysis requires accurate, reliable methods for feature extraction, classification, statistical modeling and filtering. RESULTS: We propose the modified partitioning around medoids as a classification method for relative allele signals. We use the average silhouette width, separation and other quantities as quality measures for genotyping classification. We form robust statistical models based on the classification results and use these models to make genotype calls and calculate quality measures of calls. We apply our algorithms to several different genotyping microarrays. We use reference types, informative Mendelian relationship in families, and leave-one-out cross validation to verify our results. The concordance rates with the single base extension reference types are 99.36% for the SNPs on autosomes and 99.64% for the SNPs on sex chromosomes. The concordance of the leave-one-out test is over 99.5% and is 99.9% higher for AA, AB and BB cells. We also provide a method to determine the gender of a sample based on the heterozygous call rate of SNPs on the X chromosome. See http://www.affymetrix.com for further information. The microarray data will also be available from the Affymetrix web site. AVAILABILITY: The algorithms will be available commercially in the Affymetrix software package.

Algorithms↗

A geometric algorithm for medical image correlations.

An automatic image correlation algorithm is discussed for the cranial region which is based on the geometric properties of the second moment tensor associated with a volume. The second moment tensor of two identical volumes represented in two different coordinate frames is evaluated to obtain the set of translations, rotations, and anisotropic scaling operators which relate the two coordinate frames. The theory is presented along with a discussion of quantitative error analysis to measure the usefulness of such an algorithm in the clinical setting.

Algorithms↗

Modification of sonic boom wave forms during propagation from the source to the ground.

A number of physical processes work to modify the shape of sonic boom wave forms as the wave form propagates from the aircraft to a receiver on the ground. These include frequency-dependent absorption, nonlinear steepening, and scattering by atmospheric turbulence. In the past two decades, each of these effects has been introduced into numerical prediction algorithms and results compared to experimental measurements. There is still some disagreement between measurements and prediction, but those differences are now in the range of tens of percent. The processes seem to be understood. The present understanding of sonic boom evolution will be presented along with experimental justification.

Aircraft↗

Comparison insight bone measurements by histomorphometry and microCT.

UNLABELLED: Morphometric analysis of 70 bone biopsies was done in parallel by microCT and histomorphometry. microCT provided higher results for trabecular thickness and separation because of the 3D shape of these anatomical objects. INTRODUCTION: Bone histomorphometry is used to explore the various metabolic bone diseases. The technique is done on microscopic 2D sections, and several methods have been proposed to extrapolate 2D measurements to the 3D dimension. X-ray microCT is a recently developed imaging tool to appreciate 3D architecture. Recently the use of 2D histomorphometric measurements have been shown to provide discordant results compared with 3D values obtained directly. MATERIAL AND METHODS: Seventy human bone biopsies were removed from patients presenting with metabolic bone diseases. Complete bone biopsies were examined by microCT. Bone volume (BV/TV), Tb.Th, and Tb.Sp were measured on the 3D models. Tb.Th and Tb.Sp were measured by a method based on the sphere algorithm. In addition, six images were resliced and transferred to an image analyzer: bone volume and trabecular characteristics were measured after thresholding of the images. Bone cores were embedded undecalcified; histological sections were prepared and measured by routine histomorphometric methods providing another set of values for bone volume and trabecular characteristics. Comparison between the different methods was done by using regression analysis, Bland-Altman, Passing-Bablock, and Mountain plots. RESULTS: Correlations between all parameters were highly significant, but microCT overestimated bone volume. The osteoid volume had no influence in this series. Overestimation may have been caused by a double threshold used in microCT, giving trabecular boundaries less well defined than on histological sections. Correlations between Tb.Th and Tb.Sp values obtained by 3D or 2D measurements were lower, and 3D analysis always overestimated thickness by approximately 50%. These increases could be attributed to the 3D shape of the object because the number of nodes and the size of the marrow cavities were correlated with 3D values. CONCLUSION: In clinical practice, microCT seems to be an interesting method providing reliable morphometric results in less time than conventional histomorphometry. The correlation coefficient is not sufficient to study the agreement between techniques in histomorphometry. The architectural descriptors are influenced by the algorithms used in 3D.

Biopsy↗

Temperature field estimation using electrical impedance profiling methods. I. Reconstruction algorithm and simulated results.

Algorithmic methods for estimating complete temperature fields during hyperthermia treatments based on surface and internal electrical measurements are presented. The techniques utilized draw upon impedance imaging concepts, but rather than limit the measurements to positions on the body surface, internal impedance recording sites are allowed. Theoretical simulations show that this strategy improves the reconstructed image in the target region when either internal measurement locations are added to a given number of external recording sites or some external measurement locations are replaced by internal recording positions. The algorithms developed are tested on a set of problems with increasing levels of complexity. The culmination of these investigations is a complete simulation of a hyperthermia treatment and reconstruction of a thermal image for a body cross-section of an actual cancer patient. The results of this work suggest that the surface plus internal measurement approach holds some promise as a method for estimating temperature distributions during hyperthermia treatments. However, the simulations while promising are idealizations in that they are two-dimensional with modest levels of additive noise. In a companion paper, we explore the viability of this approach in several laboratory phantom experiments which include both static and heat-induced transient electrical property profiles.

Algorithms↗

Prediction of IgE(Lb4)-ligand complex structures by automated docking.

A mouse monoclonal anti-2,4,6-trinitrophenyl IgE (clone Lb4) was screened with a random set of over 2000 compounds, and several ligands were found to bind with affinities comparable to that of the immunizing hapten (KD in the microM range). An automated docking algorithm was used for the prediction of complex structures formed by 2,4-dinitrophenyl (DNP) and non-DNP ligands in the fragment variable region of IgE(Lb4). All ligands were found to dock in an L-shaped cavity of 15 x 16 x 10 A, surrounded by complementary-determining regions L1, L3, H2 and H3. The ligands were found to occupy the same binding site in different orientations. For rigid ligands the most stable orientation could be predicted with high probability, based on the calculated energy of binding and the occurrence frequencies of identical complexes obtained by repeated simulations. The localization of a flexible ligand (cycrimine-R) was more ambiguous, but it still docked in the same site. The results support a model for heteroligating antibody (Ab) binding sites, where different ligands utilize the total set of available contacts in different combinations. It is suggested that although pseudoenergies calculated by the docking algorithm do not correlate with experimentally measured binding energies, the screening-and-docking procedure can be useful for the mapping of Ab and other receptor binding sites ligating small molecules.

2,4-Dinitrophenol↗

Image analysis techniques for automatic evaluation of two-dimensional electrophoresis.

Techniques for automatic analysis of two-dimensional electrophoresis gels by computer-aided image analysis are described. Original gels or photographic films are scanned using a laser scanner and the files are transferred to a microcomputer. The program package first performs a compression and preevaluation of the files. Spot identification and quantification is performed by the chain code algorithm after appropriate zooming and cutting. Labeling facilitates spot identification and quantification in numerical and graphical (pseudocolor) representation on peripheral devices for camera ready output. Interpolation between measured basepoints is performed by cubic spline algorithms which are automatically switched on and off, depending on the need by the program. High speed analysis and graphic representation is achieved using fast Assembler language routines rather than high level languages. One-dimensional gels can be analyzed using the same software. Spot matching between parallel two-dimensional gels has not yet been implemented.

Electrophoresis, Gel, Two-Dimensional↗