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Diffusion MRI: precision, accuracy and flow effects.

After a decade of evolution and application of diffusion imaging, a large body of literature has been accumulated. It is in this context that the accuracy and precision of diffusion-weighted and quantitative diffusion MRI are reviewed. The emphasis of the review is on practical methods for clinical human imaging, particularly in the brain. The requirements for accuracy and precision are reviewed for various clinical and basic science applications. The methods of measuring and calculating diffusion effects with MRI are reviewed. The pulse gradient spin echo (PGSE) methods are emphasized as these methods are used most commonly in the clinical setting. Processing of PGSE data is reviewed. Various PGSE encoding schemes are also reviewed in terms of the accuracy and precision of isotropic and anisotropic diffusion measurements. The broad range of factors impacting the accuracy of the PGSE methods and other encoding schemes is then considered. Firstly, system inaccuracies such as background imaging gradients, gradient linearity, refocusing RF pulses, eddy currents, image misregistration, noise and dynamic range are considered. A second class of inaccuracies is contributed by the bulk effects of the imaged object, and include sample background gradients, subject motion of cerebrospinal fluid and organs, and aperiodic organ motion. A final category of potential inaccuracies is classified as being contributed by microscopic, biophysical tissue properties and include partial volume effects, anisotropy, restriction, diffusion distance, compartmentation, exchange, multiexponential diffusion decay, T2 weighting and microvascular perfusion. Finally, the application of diffusion methods to studies of blood flow in the microvasculature (i.e. the arterioles, capillaries and venules) are reviewed in detail, particularly in terms of feasibility and the stringent accuracy and precision requirements. Recent provocative studies examining the use of PGSE approaches to suppress microvascular signals in brain functional MRI (fMRI) are also reviewed.

Animals↗

A comparative study of the accuracy of area assessment by point counting for bronchial mucous glands.

The accuracy with which areas of bronchial mucous gland on histological sections may be determined has been investigated with respect to inherent statistical variability in the point counting procedure used, and with respect to variations between the histological stains and observers employed. Very good argeement was obtained between areas determined by point counting and by planimetry. It was shown empirically that for sections of well-defined gland-like structures the accuracy (coefficient of area) of area determination was inversely proportional to the 3/4 power of the mean point count. The constant of proportionality depended on the structure's shape and on the point geometry of the grid used. Using the relationship the count needed to achieve a required accuracy of area determination could be established. It was shown that in general a smaller count was required for a given accuracy than would be the case using randomly dispersed tissue. On histological sections the accuracy of area determination is also dependent upon gland boundary definition, and our experiments showed that a recticulin Alcian Blue stain best defined mucous gland acini, and that a PBS stain gave the most accurate results for whole gland. These experiments also showed that there were small but significant differences in mean areas determined by different observers. The observers were shown to be equally consistent in their judgment of what constituted whole mucous gland and acini, but since they differed over mean counts it is recommended that studies should be designed to use either a single observer or to assign observers randomly among groups. With these considerations point counting can be made an accurate method of area determination for these or similar tissues.

Anthropometry↗

A refined accuracy index to evaluate algorithms of protein secondary structure prediction.

Nowadays even a 1% increase of the accuracy for the secondary structure prediction is considered remarkable progress. In this case, we have to consider the reasonableness of the accuracy index Q3, which is used widely. A refined accuracy index, called Q8, is proposed to evaluate algorithms of secondary structure prediction. It is shown that Q8 is superior to the widely used index Q3 in that the former carries more information of the predictive accuracy matrix than does the latter. Therefore, algorithms are evaluated more objectively by Q8 than Q3. Based on 396 nonhomologous proteins, five currently available algorithms of secondary structure prediction were evaluated and compared using the new index Q8. Of the five algorithms, PHD turned out to be the unique algorithm, with Q8 accuracy better than 70%. It is suggested that Q3 should be replaced by Q8 in evaluating secondary structure prediction in future studies.

Algorithms↗

High accuracy prediction of beta-turns and their types using propensities and multiple alignments.

We have developed a method that predicts both the presence and the type of beta-turns, using a straightforward approach based on propensities and multiple alignments. The propensities were calculated classically, but the way to use them for prediction was completely new: starting from a tetrapeptide sequence on which one wants to evaluate the presence of a beta-turn, the propensity for a given residue is modified by taking into account all the residues present in the multiple alignment at this position. The evaluation of a score is then done by weighting these propensities by the use of Position-specific score matrices generated by PSI-BLAST. The introduction of secondary structure information predicted by PSIPRED or SSPRO2 as well as taking into account the flanking residues around the tetrapeptide improved the accuracy greatly. This latter evaluated on a database of 426 reference proteins (previously used on other studies) by a sevenfold crossvalidation gave very good results with a Matthews Correlation Coefficient (MCC) of 0.42 and an overall prediction accuracy of 74.8%; this places our method among the best ones. A jackknife test was also done, which gave results within the same range. This shows that it is possible to reach neural networks accuracy with considerably less computional cost and complexity. Furthermore, propensities remain excellent descriptors of amino acid tendencies to belong to beta-turns, which can be useful for peptide or protein engineering and design. For beta-turn type prediction, we reached the best accuracy ever published in terms of MCC (except for the irregular type IV) in the range of 0.25-0.30 for types I, II, and I' and 0.13-0.15 for types VIII, II', and IV. To our knowledge, our method is the only one available on the Web that predicts types I' and II'. The accuracy evaluated on two larger databases of 547 and 823 proteins was not improved significantly. All of this was implemented into a Web server called COUDES (French acronym for: Chercher Ou Une Deviation Existe Surement), which is available at the following URL: http://bioserv.rpbs.jussieu.fr/Coudes/index.html within the new bioinformatics platform RPBS.

Amino Acid Sequence↗

Achieving 80% ten-fold cross-validated accuracy for secondary structure prediction by large-scale training.

An integrated system of neural networks, called SPINE, is established and optimized for predicting structural properties of proteins. SPINE is applied to three-state secondary-structure and residue-solvent-accessibility (RSA) prediction in this paper. The integrated neural networks are carefully trained with a large dataset of 2640 chains, sequence profiles generated from multiple sequence alignment, representative amino acid properties, a slow learning rate, overfitting protection, and an optimized sliding-widow size. More than 200,000 weights in SPINE are optimized by maximizing the accuracy measured by Q(3) (the percentage of correctly classified residues). SPINE yields a 10-fold cross-validated accuracy of 79.5% (80.0% for chains of length between 50 and 300) in secondary-structure prediction after one-month (CPU time) training on 22 processors. An accuracy of 87.5% is achieved for exposed residues (RSA >95%). The latter approaches the theoretical upper limit of 88-90% accuracy in assigning secondary structures. An accuracy of 73% for three-state solvent-accessibility prediction (25%/75% cutoff) and 79.3% for two-state prediction (25% cutoff) is also obtained.

Algorithms↗

Quantifying and comparing the accuracy of binary biomarkers when predicting a failure time outcome.

The positive and negative predictive values are standard measures used to quantify the predictive accuracy of binary biomarkers when the outcome being predicted is also binary. When the biomarkers are instead being used to predict a failure time outcome, there is no standard way of quantifying predictive accuracy. We propose a natural extension of the traditional predictive values to accommodate censored survival data. We discuss not only quantifying predictive accuracy using these extended predictive values, but also rigorously comparing the accuracy of two biomarkers in terms of their predictive values. Using a marginal regression framework, we describe how to estimate differences in predictive accuracy and how to test whether the observed difference is statistically significant.

Biomarkers↗

The influence of signal noise on the accuracy of kinetic constants measured by surface plasmon resonance experiments.

An analysis is carried out to investigate the accuracy of kinetic parameters obtained using surface plasmon resonance methodology with a BIAcore instrument. The Cramer Rao lower bound for the least possible variance of an estimator of the kinetic parameters is determined. Using simulations it is shown that the standard least-squares estimation technique provides estimates that achieve this bound. The theoretical and simulation results are compared with experimental data obtained from an analysis of the interaction of the myc peptide with the anti-myc antibody, 9E10. This investigation indicates that the accuracy of the results depends on the signal level which has particular relevance to the design of experiments with low signal levels. It is shown how the accuracy of the estimates of the kinetic constants depends on the kinetic constants themselves and how the accuracy of the association constants depends on the concentration of the analyte that is used in the experiment. In addition, the effects of increasing the number of data points in the analysis of dissociation data on the accuracy of the estimates are quantitated. It is also demonstrated that signal averaging of data derived from repeat sensorgrams can result in a significant decrease in the standard deviation of the estimates.

Animals↗

The credibility of children's testimony: can children control the accuracy of their memory reports?

In previous work with adults (A. Koriat & M. Goldsmith, 1994, 1996c), it was shown that people can enhance the accuracy of their testimony substantially when they (a) are effective in monitoring the correctness of their answers, (b) are free to control their reporting accordingly (i.e., to decide which pieces of information to volunteer and which to withhold), and (c) are given incentives for accurate reporting. A theoretical model was developed, which specifies the critical role of metacognitive monitoring and control processes in mediating free-report memory accuracy. The present study applies that model to examine the strategic regulation of memory accuracy by children. Three experiments indicate that both younger (ages 7 to 9) and older (ages 10 to 12) children can enhance the accuracy of their testimony by screening out wrong answers under free-report conditions but suggest a developmental trend in the level of memory accuracy that is thereby achieved. The implications of the results for the dependability of children's testimony in legal settings are discussed.

Age Factors↗

An assessment of the precision and accuracy of protein structures determined by NMR. Dependence on distance errors.

We tested the dependence of the accuracy and precision of calculated NMR structures on the errors of the distance constraints using sequential simulated annealing and found that: (1) the accuracy of the family of structures depends mainly on the quality of the data, but is no better than about 1 A even if the errors in distance constraints are smaller than +/- 1 A. (2) The precision of the calculated structures, on the other hand, is nearly insensitive to the quality of the data. With present methods, the accuracy of NMR structures is at best of the order of 1 to 2 A, although a precision of 0.4 to 0.7 A is readily attainable. Comparisons with recent studies of this problem also brought out the importance of distinguishing between correct and incorrect definitions of accuracy when reporting numerical estimates. Using an incorrect definition of the term accuracy can lead to an artificially favorable estimate of its numerical value.

Evaluation Studies as Topic↗

The complexity and accuracy of discrete state models of protein structure.

The prediction of protein structure depends on the quality of the models used. In this paper, we examine the relationship between the complexity and accuracy of representation of various models of protein alpha-carbon backbone structure. First, we develop an efficient algorithm for the near optimal fitting of arbitrary lattice and off-lattice models of polypeptide chains to their true X-ray structures. Using this, we show that the relationship between the complexity of a model, taken as the number of possible conformational states per residue, and the simplest measure of accuracy, the root-mean-square deviation from the X-ray structure, is approximately (Accuracy) varies; is directly proportional to (Complexity)-1/2. This relationship is insensitive to the particularities of individual models, i.e. lattice and off-lattice models of the same complexity tend to have similar average root-mean-square deviations, and this also implies that improvements in model accuracy with increasing complexity are very small. However, other measures of model accuracy, such as the preservation of X-ray residue-residue contacts and the alpha-helix, do distinguish among models. In addition, we show that low complexity models, which take into account the uneven distribution of residue conformations in real proteins, can represent X-ray structures as accurately as more complex models, which do not: a selected 6-state model can represent protein structures almost as accurately (1.7 A root-mean-square) as a 17-state lattice model (1.6 A root-mean-square). Finally, we use a novel optimization procedure to generate eight 4-state models, which fit native proteins to an average of 2.4 A, and preserve 85% of native residue-residue contacts. We discuss the implications of these findings for protein folding and the prediction of protein conformation.

Algorithms↗

Effects of experimentally achievable improvements in the quality of NMR distance constraints on the accuracy of calculated protein structures.

New methods for collecting cross-relaxation data from proteins and nucleic acids make it possible to improve the accuracy and precision of interproton distance measurements used as input for NMR solution structure determinations. It thus is of interest to determine whether such experimentally achievable improvements in input distance constraints have significant effects on the precision and accuracy of the resulting structures. To answer this question, we have turned to a computational procedure involving the use of data simulated from a known structure, in order to allow unambiguous assessments of accuracy. The approach to improved distances evaluated here is that afforded by magnetization exchange network editing (MENE); MENE pulse sequences break the network of cross-relaxation interactions into regions that are manipulated so as to defeat certain spin-diffusion terms. A target structure was prepared from the X-ray structure of a small protein, turkey ovomucoid third domain (OMTKY3). A normal NOESY spectrum and two varieties of MENE spectra, BD-NOESY and CBD-NOESY, were simulated by means of complete relaxation matrix analysis. These results were used to create different input data sets with the same number of constraints (perfectly accurate distances derived from the target structure, more accurate distances derived from the MENE simulations, and less accurate distances derived from the NOESY simulation), and these, interpreted at different levels of precision, were used as input for solution structure calculations. The results showed that the use of more precise input data measurably improves the local precision and accuracy of calculated structures, but only if the more precise data include the actual target distance. Incorporation of the experimentally achievable, accurate distances with higher precision afforded by the MENE pulse sequences into the set of input distances was found to improve the accuracy of the resulting structures, particularly in terms of side-chain conformation.

Animals↗

The influence of efferent, proprioceptive, and timing factors on the accuracy of eye-hand tracking.

Oculomotor tracking of one's moving hand is considerably more accurate than tracking of an external target undergoing comparable motion. To identify the factors contributing to this enhancement of tracking accuracy, the influence of visual, proprioceptive, and efferent cues on tracking performance was assessed. Related observations were made on the influence both of linear and topological transformations between target and hand position on tracking accuracy. The experimental findings indicate that if a target light is attached to one's hand, a) the target can be tracked with comparable accuracy for active and passive limb movements, and b) when the entire hand rather than just the target light is visible, pursuit velocity is higher and more closely matches target velocity. If a linear transformation is introduced between hand and target positions, nearly identical tracking accuracy is found with voluntary and involuntary limb movements. By contrast, topological transformations degrade target tracking accuracy for passive but not for voluntary limb movements. The implications of this finding are discussed.

Adult↗

Accuracy and precision study in vitro for peripheral quantitative computed tomography.

We evaluated the accuracy and precision of a peripheral quantitative computed tomography (pQCT) scanner, the Stratec XCT-960, using 12 human cadaveric forearms. The accuracy was determined by comparing the total bone mineral content (BMC) with the ash weight (AW). We scanned and ashed three consecutive slices (thickness 2.5 mm) at the standard position (s-position) and at 2.5 mm both proximal and distal to the s-position. The correlation coefficient between the AW and total BMC using slices at the s-position was r = 0.87 with an accuracy error (random component) of 15.5%. The correlation coefficient using all slices was r = 0.90 with an accuracy error of 14.3%. The correlation coefficient improved to r = 0.95 with an accuracy error of 9.7% after averaging the results of all three slices for each forearm. The short-term precision error expressed as the coefficient of variation (CV) of bone mineral density (BMD) and BMC was determined by measuring the forearms five times either with repositioning or without repositioning. The CVs with repositioning were 2.77 and 1.15 for total BMD and BMC, 1.85 for trabecular BMD; without repositioning they were 0.29, 0.58 and 0.69 respectively. To further evaluate the influence of positioning, additional scans were performed at 1, 2 and 5 mm proximal, and 1 and 2 mm distal to the s-position. BMD and BMC were greatly influenced by the scan location; for example, the percentage differences in trabecular BMD 1 mm distal and proximal relative to the s-position were 2.5% +/- 5.1% and 0.18% +/- 6.3%, respectively. The Stratec XCT-960 appears to be a moderately accurate and highly precise scanner with potential usefulness for evaluating BMC and BMD of ultradistal radius.

Bone Density↗

Accuracy and reliability of transanal ultrasound for anterior anal sphincter injury.

INTRODUCTION: Although transanal ultrasound has rapidly become the test of choice for the diagnosis of anal sphincter injury, the accuracy and reliability of this technique are unknown. This study evaluates the accuracy and reliability of transanal ultrasound for anterior (obstetric-related) anal sphincter injury. METHODS: Sixty-two women underwent transanal ultrasound with hard-copy images obtained at 0.5-cm intervals from the anal verge to 2.5 cm into the anal canal. All transanal ultrasound procedures were also recorded on videotape. Two experienced ultrasonographers blinded as to the patients' clinical history and examination independently reviewed the images and videotape recordings for the presence or absence of anal sphincter injury. RESULTS: The accuracy of transanal ultrasound in 22 incontinent women with known anal sphincter injury was 100 percent. The accuracy of transanal ultrasound in 20 nulliparous women with intact anal sphincters was only 35 percent but improved to 50 percent after the "real time" videotape was reviewed (P = 0.16) and further improved to 85 percent when interpretation was limited to the distal 1.5 cm of the anal canal (P = 0.004). In these nulliparous women, intact internal sphincters were more accurately predicted than intact external sphincters (95 vs. 85 percent; P = 0.24). Measurement agreement between the two ultrasonographers was 68 percent (fair; kappa, 0.26) but significantly improved to 78 percent (moderate; kappa, 0.48; P = 0.0001) when interpretation was limited to the distal 1.5 cm of the anal canal. Overall clinical agreement (final scan interpretation) was good (81 percent agreement; kappa, 0.61). Agreement was better for the internal sphincter (74 percent; fair; kappa, 0.36) than the external sphincter (61 percent; poor; kappa, 0.17; P = 0.0002). CONCLUSIONS: Although transanal ultrasound can accurately identify anterior anal sphincter injury when present, transanal ultrasound falsely identifies sphincter injury in at least 5 to 25 percent of normal anal sphincters. Only fair agreement in the interpretation of transanal ultrasound exists between experienced ultrasonographers. Both the accuracy and reliability of transanal ultrasound are significantly improved by limiting transanal ultrasound to the distal 1.5 cm of the anal canal.

Adult↗

Static and dynamic accuracy required of gas concentration measuring instruments.

The dynamic and static accuracy required of gas concentration measuring instruments for the measurement of physiological parameters is discussed. Static accuracy is examined using error sensitivity analysis of a range of physiological measurements requiring gas concentration information. From this an acceptable static accuracy of +/- 0.1 per cent volume/volume is established as an acceptable accuracy. Dynamic accuracy is examined using an idealised exhaled carbon dioxide curve. By considering the contribution of various features in the curve to the power spectrum of the curve a 'rule of thumb' for acceptable dynamic bandwidth of acceptable bandwidth = 4 (heart rate/60) + 5 Hz where heart rate is in beats min-1, is developed.

Biomedical Engineering↗

Brain perfusion SPECT study with 99mTc-bicisate: clinical pitfalls and improved diagnostic accuracy with a combination of linearization and scatter-attenuation correction.

To evaluate the usefulness of a combination of linearization and scatter-attenuation correction on 99mTc-bicisate (ECD)-single photon emission tomographic (SPECT) images, both cerebral blood flow (CBF)-positron emission tomographic (PET) images and ECD-SPECT images from fifteen patients with chronic cerebral infarction were acquired. We measured radioactivity counts in regions of interest (ROIs) on all sets of both images and obtained a 2D scattered graph between ECD-SPECT and CBF-PET data. To evaluate diagnostic accuracy, the sensitivity, specificity and accuracy of ECD-SPECT images were calculated by means of discriminant analysis. The same analysis was also performed on the ECD-SPECT images corrected by a combination of linearization and scatter-attenuation correction. An overall nonlinear relationship was observed between ECD-SPECT and CBF-PET. The sensitivity, specificity, and accuracy of ECD-SPECT images were 69.6%, 91.4% and 73.0%, and those of ECD images corrected by the combination of linearization and scatter-attenuation correction were 79.5%, 95.7% and 82.0% respectively. The clinically diagnostic accuracy of ECD-SPECT images corrected by the combined method apparently increased. So that the linearization with the scatter-attenuation method is useful for improving the diagnostic accuracy of ECD-SPECT images.

Aged↗

Does myocardial thallium-201 SPECT combined with electron beam computed tomography improve the detectability of coronary artery disease?--comparative study of diagnostic accuracy.

OBJECTIVE: The aim of this study is to evaluate the diagnostic accuracy of myocardial 201Tl SPECT combined with EBT for detecting CAD. METHODS: The study was based on 34 patients with suspected CAD, who had EBT and myocardial 201Tl SPECT. The CAD was diagnosed by the findings of coronary arteriography. Sensitivity, specificity and accuracy of EBT, myocardial 201Tl SPECT and the combined diagnosis on a per vessel basis and a per-patient basis were studied. RESULTS: The sensitivity for detecting CAD of myocardial 201Tl SPECT, EBT and the combined diagnosis was 85%, 77%, and 62%, respectively. No significant difference in the accuracy of myocardial 201Tl SPECT, EBT and the combined diagnosis was observed on a patient basis and per vessel basis. In the over 70 yr age subgroup, the sensitivity and accuracy of EBT for detecting LAD lesion were significantly superior to those of myocardial 201Tl SPECT. Regardless of age-based subgroups and gender, the combined diagnosis did not contribute to an improvement in diagnostic accuracy. CONCLUSION: Although the sensitivity of EBT for detecting LAD lesion in patients over 70 yr of age was significantly higher than that of myocardial 201Tl SPECT, in the detectability of CAD, combined use of myocardial 201Tl SPECT and EBT offers no improvement.

Adult↗

Additive deficits in the choice accuracy of rats in the delayed non-matching to position task after cholinolytics and serotonergic lesions are non-mnemonic in nature.

The role of serotonin (5-HT) and its interaction with the muscarinic or nicotinic receptor-mediated mechanisms in the modulation of working memory and motor activity was investigated by assessing the effects of 5-HT lesion and cholinergic receptor blockade on the performance of rats in a working memory (delayed non-matching to position, DNMTP) task. A global serotonergic lesion was induced by the intracerebroventricular administration of 5,7-dihydroxytryptamine (5,7-DHT). Post-mortem neurochemical analysis revealed that serotonin and 5-hydroxyindoleacetic acid (5-HIAA) levels were reduced in frontal and parieto-occipital cortices and in hippocampi of 5,7-DHT lesioned rats. 5-HIAA levels were also reduced in striatum. 5,7-DHT lesion slightly impaired choice accuracy of rats in the DNMTP task and also transiently reduced motor activity in rats. Even the lower dose of scopolamine (0.075 mg/kg), a muscarinic receptor antagonist, impaired the choice accuracy already at the shortest delay (i.e. not indicative of a working memory impairment per se), and caused a marked disruption of motor activity (lengthened response latencies, increased probability of omissions and decreased trials completed). Furthermore, the quaternary analogue, N-methylscopolamine (0.150 mg/kg), affected the motor activity of rats to the same extent as scopolamine. Mecamylamine (1.0; 3.0 mg/kg) also interfered with motor activity and it slightly decreased the choice accuracy, which was not dependent on the delay. Although mecamylamine disrupted the performance of rats in the DNMTP task, the disruption was not as severe as that seen with scopolamine. Moreover, both scopolamine and mecamylamine augmented the slight impairment on the choice accuracy of 5,7-DHT lesioned rats, but this was non-mnemonic in character. We conclude that there is no evidence for any major interaction between the serotonergic system and muscarinic or nicotinic cholinergic mechanisms in working memory per se, but muscarinic and nicotinic receptor antagonists may act additively with the 5,7-DHT lesion to disrupt the choice accuracy of rats.

5,7-Dihydroxytryptamine↗