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A comparative analysis of preprocessing techniques of cardiac event series for the study of heart rhythm variability using simulated signals.

In the present study, using noise-free stimulated signals, we performed a comparative examination of several preprocessing techniques that are used to transform the cardiac event series in a regularly sampled time series, appropriate for spectral analysis of heart rhythm variability (HRV). First, a group of noise-free simulated point event series, which represents a time series of heartbeats, was generated by an integral pulse frequency modulation models. In order to evaluate the performance of the preprocessing methods, the differences between the spectra of the preprocessed simulated signals and the true spectrum (spectrum of the model input modulating signals) were surveyed by visual analysis and by contrasting merit indices. It is desired that estimated spectra match the true spectrum as close as possible, showing a minimum of harmonic components and other artifacts. The merit indices proposed to quantify these mismatches were the leakage rate, defined as a measure of leakage components (located outside some narrow windows centered at frequencies of model input modulating signals) with respect to the whole spectral components, and the numbers of leakage components with amplitudes greater than 1%, 5% and 10% of the total spectral components. Our data, obtained from a noise-free simulation, indicate that the utilization of heart rate values instead of heart period values in the derivation of signals representative of heart rhythm results in more accurate spectra. Furthermore, our data support the efficiency of the widely used preprocessing technique based on the convolution of inverse interval function values with a rectangular window, and suggest the preprocessing technique based on a cubic polynomial interpolation of inverse interval function values and succeeding spectral analysis as another efficient and fast method for the analysis of HRV signals.

Acoustic Stimulation↗

[Computer analysis of disturbed respiration in patients with sleep apnea].

In patients with sleep related breathing disorders parallel evaluation of respiration, blood gases and the EEG are indispensible. Computerized methods can provide a detailed analysis of the interrelation of these parameters to enlighten the disturbed central regulation of respiration in these patients. These methods also can help to achieve a better differential diagnosis in routine clinical work. A new method is presented here which evaluates the signals of nasal airflow, thoracic and abdominal movements together with oxygen saturation and heart rate in parallel. The new method is validated using a detailed visual analysis. Results prove the usefulness of the new method. To apply the method the relationship between length of apnea and oxygen desaturation is evaluated for different sleep stages separately.

Blood Gas Analysis↗

A computerized cellular imaging system for high content analysis in Monastrol suppressor screens.

In this paper, we describe a new bioimage informatics system developed for high content screening (HCS) applications with the goal to extract and analyze phenotypic features of hundreds of thousands of mitotic cells simultaneously. The system introduces the algorithm of multi-phenotypic mitotic analysis (MMA) and integrates that with algorithms of correlation analysis and compound clustering used in gene microarray studies. The HCS-MMA system combines different phenotypic information of cellular images obtained from three-channel acquisitions to distinguish and label individual cells at various phases of mitosis. The proposed system can also be used to extract and count the number of cells in each phase in cell-based assay experiments and archive the extracted data into a structured database for more sophisticated statistical and data analysis. To recognize different mitotic phases, binary patterns are set up based on a known biological mitotic spindle model to characterize cellular morphology of actin, microtubules, and DNA. To illustrate its utility, the HCS-MMA system has been applied to screen the quantitative response of 320 different drug compounds in suppressing Monastrol. The results are validated and evaluated by comparing the performance of HCS-MMA with visual analysis, as well as clustering of the drug compounds under evaluation.

Algorithms↗

The 5S rRNA gene clusters have a defined orientation toward the nucleolus in Petunia hybrida and Crepis capillaris.

The 3D localization of the 5S ribosomal RNA genes was studied in cells of the cortex zone of roots in the plant species Petunia hybrida inbred line V26 and in Crepis capillaris. The analysis was carried out on interphase nuclei (both species) and on prophase nuclei (C. capillaris). The 5S ribosomal RNA genes were detected by fluorescence in-situ hybridization and 3D images were obtained by confocal scanning laser microscopy. In both plant species, the 5S ribosomal genes were localized at the short arm of chromosome 2, which, in both plants, also possesses a satellite at its end. Statistical and visual analysis of interphase nuclei showed that: (1) there is a preference for an association of the 5S rRNA gene clusters of the two homologous chromosomes, and (2) the 5S rRNA gene clusters in both species had a preserved spatial position within the interphase nucleus and they tended to be polarized with respect to their neighbouring cells (i.e. a relic telophase orientation). Moreover, tracing of the chromosomal segment between the 5S loci and the active NOR revealed that the homologous chromosomes during early/mid prophase were aligned and that they entered the nucleolus side by side, at least for these chromosome segments. We interpret our data to mean that location of 5S rRNA near the nucleolus favours their functioning in ribosome biogenesis.

Asteraceae↗

DNA fingerprinting in relation to male dominance and paternity in a captive colony of tammar wallabies (Macropus eugenii).

The tammar wallaby has a polygynous mating system in which the dominant male usually controls initial access to oestrous females by mating first and then guarding the female from the advances of other subordinate males. In this study we used DNA fingerprinting with a human 3' hypervariable region (HVR) alpha globin probe to examine the paternity of pouch young progeny from 13 female tammars that were given continual access during the breeding season to a group of four sexually mature males. Constant individual-specific DNA profiles were observed for each animal. Paternity for 22 pouch young was successfully assigned using visual and computer-based analyses. However, no statistical difference was observed between the number of young sired by any of the four males (chi 2 = 2, d.f. = 3, P > 0.1). Mate guarding by the dominant male in our captive breeding group was not, therefore, sufficient to prevent successful subsequent matings by subordinates nor to enhance the genetic contribution of this male to the next generation. In each analysis, visual and computer assignments of paternity coincided, and these concurred with the results of a relatedness test which found that a large number of DNA bands were shared by sires and their progeny. The results from this paternity study show that first mating and subsequent mate guarding by the dominant male tammar wallaby in our captive group do not significantly skew the outcome of paternity towards this male and away from other males that subsequently mate with each female.

Animals↗

[Diagnosis of ischemia and survival after myocardial infarction using perfusion scintigraphy with exercise thallium-201. Relationship with electrocardiographic and angiographic findings].

OBJECTIVE: To review the experience of the laboratory on exercise-redistribution thalium-201 scintigraphy after myocardial infarction, and to compare scintigraphy results with those of exercise test and coronary angiography. DESIGN/SETTING/PATIENTS: Retrospective analysis of data from scintigraphy, exercise test and coronary angiography from all patients evaluated after myocardial infarction at Nuclear Medicine Department of Instituto do Coração with treadmill exercise-redistribution thallium-201 SPECT, if they were also submitted to cardiac catheterization. These criteria were met by 185 patients, studied between March 1988 and July 1993. MATERIAL AND METHODS: Micro-Delta system with a Siemens Orbiter gamma camera. Visual analysis of intensity and reversibility of perfusion defects in 5 segments per patient, using oblique reconstruction of images. RESULTS: Perfusion defects were found in 97% of patients and in 418/925 analysed segments. Variable degrees of reversibility were found in 78% of patients. On patients with single-vessel disease, vessel occlusion was associated with a slightly higher prevalence of reversibility (81% vs 71%; ns), and, for anterior infarcts, also with a higher prevalence of defects in areas supposed to be remote territories (44% vs 15%, p < 0.05). For 159 patients with a conclusive exercise test, ability of exercise test in diagnosing defects with reversibility was studied. Negative predictive accuracy of exercise test was poor (33%). Angina was 86% specific. Use of isolated ST depression, depression plus elevation or isolated ST elevation as criteria for a positive test result in a progressive improvement of sensitivity, but at cost of a decrease in specificity, more marked when using isolated ST elevation. CONCLUSIONS: Thallium scintigraphy revealed perfusion defects with some degree of reversibility in a large number of patients studied after myocardial infarction, even when considering single-vessel disease or occluded infarct-related artery. Electrocardiographic treadmill exercise test had a poor negative predictive accuracy, being reasonably sensible in multivessel disease, but poorer in single vessel disease. After infarction, typical angina should probably be also considered as criterion for ischemia, regardless of electrocardiographic changes. In a perspective of eventual use of revascularization after infarction, thallium-201 scintigraphy is a valuable tool, and should probably be considered in most patients.

Adult↗

Predicting severe angiographic coronary artery disease using computerization of clinical and exercise test data.

Currently the standard exercise test is shifting from being a tool for the cardiologist to utilization by the nonspecialist. This change could be facilitated by computerization similar to the interpretation programs available for the resting ECG. Therefore, we sought to determine if computerization of both exercise ECG measurements and prediction equations can substitute for visual analysis performed by cardiologists to predict which patients have severe angiographic coronary artery disease. We performed a retrospective analysis of consecutive patients referred for evaluation of possible or known coronary artery disease who underwent both exercise testing with digital recording of their exercise ECGs and coronary angiography at two university-affiliated Veteran's Affairs medical centers and a Hungarian hospital. There were 2,385 consecutive male patients with complete data who had exercise tests between 1987 and 1997. Measurements included clinical and exercise test data, and visual interpretation of the ECG paper tracings and > 100 computed measurements from the digitized ECG recordings and compilation of angiographic data from clinical reports. The computer measurements had similar diagnostic power compared with visual interpretation. Computerized ECG measurements from maximal exercise or recovery were equivalent or superior to all other measurements. Prediction equations applied by computer were only able to correctly classify two or three more patients out of 100 tested than ECG measurements alone. beta-Blockers had no effect on test characteristics while ST depression on the resting ECG decreased specificity. By setting probability limits using the scores from the equations, the population was divided into high-, intermediate-, and low-probability groups. A strategy using further testing in the intermediate group resulted in 86% sensitivity and 85% specificity for identifying patients with severe coronary disease. We conclude that computerized exercise ST measurements are comparable to visual ST measurements by a cardiologist and computerized scores only minimally improved the discriminatory power of the test. However, using these scores in a stratification algorithm allows the nonspecialist physician to improve the discriminatory characteristics of the standard exercise test even when resting ST depression is present. Computerization permitted accurate identification of patients with severe coronary disease who require referral.

Coronary Angiography↗

[Automatic computerized ECG interpretation].

The introduction of computerised interpretation of an electrocardiogram depends on the reliability of the interpretation. Previous investigations of computerised ECG diagnosis have been concerned with the diagnostic significance of selected QRST morphology changes and/or arrhythmia. In the present investigation, a full interpretation of the recorded values has been performed in terms of diagnosis and conclusions for each ECG. The investigation included 1,000 ECG's from 500 in-patients, at a Central Hospital. The ECG's were recorded on Mingograf 740 from Siemens-Elema, AB. All data from each computerised ECG were compared with the results of an ordinary visual analysis. For the rhythm diagnosis, mistakes were found in 11% of the ECG's, and in 2-3% of the mistakes the wrong diagnosis was considered of clinical significance. For the diagnosis of the QRST morphology, mistakes were found in 29% of the electrocardiograms with considered clinical significance in 20% of the ECG's. Agreement between the diagnosis "normal ECG" in the computer-based ECG interpretation and the visual analysed ECG with the diagnosis "normal ECG", was found in 99.4%. In the diagnosis of cardiac rhythm, agreement was found in 89% of the ECG's, whereas agreement concerning the QRST morphology was 71%. The differences were mainly because of too narrow boundaries in the diagnosis of normal ECG's in the investigated computerprogram. It is concluded, that the value of automatically computerised interpretation of an electrocardiogram depends to a large extent on the criteria encoded in the computerprogram employed.

Adolescent↗

Validation of a new automated method for analysis of gated-SPECT images.

We recently presented a new method for quantification of CArdiac FUnction--denoted CAFU--as the first step in the development of an automated method for integrated interpretation of gated myocardial perfusion single photon emission computed tomography (SPECT) images. The aim of this study was to validate CAFU in the assessment of global and regional function of the left ventricle. Quantitative gated-SPECT (QGS), the most widely used software package for quantification of gated-SPECT images, was used as reference method for the measurements of ejection fraction (EF) and ventricular volumes, and visual analysis by an experienced physician was used as reference method for the measurements of regional wall motion and thickening. Two different groups of consecutive patients referred for myocardial perfusion scintigraphy were studied. Global function was evaluated in 316 patients and regional function in 49 other patients. The studies were performed using a 2-day stress/rest 99 m-Tc-sestamibi protocol. A good correlation was found between EF values from QGS and CAFU (EF CAFU = 0.84 EF QGS + 13, r = 0.94), but CAFU values were on average 4 EF points higher than QGS values. With CAFU the segments with normal thickening according to the physician showed significantly higher thickening values (in all parts of the myocardium) compared to the segments classified as having abnormal thickening. In conclusion, this study demonstrates that CAFU can be used to quantify global and regional function in gated-SPECT images. This is an important step in our development of an automated method for integrated interpretation of gated-SPECT myocardial perfusion scintigraphy studies.

Adenosine↗

Proliferating cell nuclear antigen expression in brain tumors, and its prognostic role in ependymomas: an immunohistochemical study.

Proliferating cell nuclear antigen (PCNA)/cyclin is currently often investigated immunohistochemically in tumors as a marker of cell proliferation, but many problems remain open concerning its reliability as a prognostic factor. PCNA has been studied in a series of 123 brain tumors using the monoclonal antibody PC10. A clear intra- and inter-tumor variability of PCNA-positive nuclei has been found, but taking into account the tumor areas with the highest number of positive nuclei, a positive correlation between this number and the histological malignancy of tumors has been demonstrated. The staining intensity of nuclei was variable; very-intensely positive nuclei, counted separately, are hypothesized to represent nuclei in S-phase of the cell cycle. In ependymomas the investigation included a quantitative statistical analysis. The number of PCNA-positive nuclei correlated with cell density and mitotic index, but only very intensely positive nuclei showed a significant statistical correlation with survival. In spite of the many possibilities of wrong interpretation of PCNA expression, the most important of which is its deregulation, the method is useful in the practice for prognostic purposes. Its important advantages are the possibility of a retrospective application and a visual analysis of the proliferation potential of tumors.

Antigens, Neoplasm↗

Evaluation of 3 dimensional space and time filtering on ECG gated 201Tl myocardial images.

Stress 201Tl myocardial images were obtained using a standard ECG gated acquisition protocol for 10 min per view. These images were filtered using a three dimensional space and time filter. The effects of filtering were evaluated by sectorial analysis. Comparing raw and filtered dynamic images, quantification demonstrated that filtering did not produce artefacts. A conventional static image was also obtained as the sum of the series of unfiltered dynamic images. Comparison of raw static and filtered diastolic images indicated that the latter demonstrated myocardial abnormalities more clearly (P less than 0.01) in 33 patients. Improvement in the signal to noise ratio produced by filtering made cinematic display and visual analysis possible which was not feasible with raw gated images. Clinical evaluation is in progress.

Diastole↗

Quantification and measurement of human lens opacities using the lens opacity meter.

Lens opacity was quantified in 85 cataractous patients, using a new instrument: the lens opacity meter 701 (LOM; Interzeag, Schlieren, Switzerland). Cataracts were classified as nuclear, cortical, subcapsular and mixed forms. Sensitivity, specificity and reproducibility of the results were evaluated by statistical analysis. Visual acuity was correlated with LOM values in patients with nuclear and mixed cataracts. Moreover, the instrument gave a good degree of reproducibility only in patients who presented these forms of lens opacities. Our findings demonstrate that the LOM 701 is able to detect and to measure only lens opacities which affect the central area of the lens.

Aged↗

Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers.

To establish test specific normal limits for quantitative analysis of uptake and washout of 201Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as less than or equal to 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the 201Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37% +/- 2.11%. The regional washout in the 70 degrees LAO view (46.65% +/- 1.10%) was significantly higher than in the anterior and 30 degrees LAO views (43.44% +/- 1.50% and 43.02% +/- 1.45%, respectively). Profiles of uptake and washout of 201Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of 201Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of 201Tl derived from healthy volunteers who underwent the same combined protocol.

Adult↗

Bladder cancer diagnosis by computer image analysis of cells in the sediment of voided urine using a video scanning system.

A video-based computerized semiautomated image analysis system was applied to the diagnostic evaluation of 119 sediments of voided urine: 103 from patients with a broad variety of neoplastic and nonneoplastic disorders of the lower urinary tract and 16 normal controls. Each specimen was presented to the machine as a single cytocentrifuge preparation, preserved in 2% Carbowax in 50% ethanol and stained-by the Papanicolaou method. Five hundred sequential "objects" were scanned within an area of 9 sq mm on each slide. "Objects" of no diagnostic value, such as dirt, debris, inflammatory cells, cell clusters, poorly preserved cells, etc., were eliminated from the final diagnostic analysis by a computer-based hierarchic triage system. The final specimen classifier was based on the cell images identified by the computer as well-preserved normal (NEG), atypical (ATY I), suspicious (ATY II) and malignant (POS) cells. For specimen classification by computer, the four categories of "abnormal," "inadequate," "acellular" and "negative" were defined. For high-grade tumors, the performance of the specimen classifier was generally comparable to the visual diagnosis. The specimen classifier unexpectedly identified twice as many low-grade papillary urothelial tumors as abnormal than did the visual analysis. Several false "alarms" were recorded by computer in patients with benign prostatic hypertrophy and prostatic carcinoma, some of whom had atypical urothelium. One of the 16 negative controls was misdiagnosed by the computer as abnormal. The possibility that the video system recognizes nuclear abnormalities not perceived by the human eye is being investigated further. The details of the computer analysis are reported, and the value of the system is discussed. The system appears to be promising as a future laboratory instrument, although it requires further extensive testing.

Adenocarcinoma↗

A new digital electronic caliper for measurement of coronary arterial stenosis: comparison with visual estimates and computer-assisted measurements.

Visual analysis of the severity of coronary stenosis is limited by observer variability. However, more complex techniques of proved accuracy are tedious and costly. Therefore, a new digital electronic caliper (DEC) was evaluated as a potentially more accurate, rapid and less costly alternative for measuring stenosis severity. Stenosis minimum diameter (Dmin) and percent diameter reduction (% S) were measured from the screen of the cine projector using a DEC. These measurements were compared with visual estimates (VIS) by 4 experienced angiographers and with measurements made by a computer-assisted method (QCA) of proved accuracy. In routine cineangiograms from 7 patients, 10 lesions were significant (greater than 50% S) and 8 were mild (less than 50% S). Variability, the standard deviation of multiple estimates of Dmin and % S, averaged 0.09 mm and 3.1% for QCA; 0.18 mm and 5.9% for DEC; and 0.26 mm and 7.4% for VIS. Compared with QCA, the visual determination of % S significantly underestimates (-5%; p less than 0.02) mild and overestimates (+11%; p less than 0.002) significant stenosis. VIS underestimates Dmin in significant lesions by 20% (p less than 0.04). In contrast, the mean error for DEC measurement of Dmin and % S was not significantly different from 0 in either lesion group. For the entire group of lesions, and particularly in significant lesions, the mean error for measurement of these 2 indexes of disease was significantly less with DEC than with VIS. Thus, variability and error with DEC are acceptably low for clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

Cineangiography↗

Speechreading in the akinetopsic patient, L.M.

Patient L.M. has a well-documented, long-standing and profound deficit in the perception of visual movement, following bilateral lesions of area V5 (visual movement cortex). Speechreading was explored in this patient in order to clarify the extent to which the extraction of dynamic information from facial actions is necessary for speechreading. Since L.M. is able to identify biological motion from point-light displays to whole-body forms and has some limited visual motion capabilities, we expected that some speechreading of faces in action would be possible in this patient. L.M.'s reading of natural speech was severely impaired, despite unimpaired ability to recognize speech-patterns from face photographs and reasonable identification of monosyllables produced in isolation. She was unable to track multisyllabic utterances reliably and was insensitive to vision when incongruent audiovisual speech syllables were shown. Point-light displays of speech were as poorly read as whole face displays. Rate of presentation was critical to her performance. With speech, as with other visual events, including tracking the direction of gaze and of hand-movement sequences, she could report actions that unfolded slowly (approximately one event per 2 s). In line with this, she was poor at reporting whether seen speech rate was normal, fast (double-speed) or slow (half-speed). L.M.'s debility is the converse of that reported for a patient with lesions primarily to V4 (H.J.A.), who is unable to speechread photographs of faces but can speechread moving faces. The visual analysis of both form and motion is required for speechreading; the neural systems that support these analyses are discussed.

Aged↗

Cavernous hemangioma of the liver: assessment of MR tissue specificity with a simplified T2 index.

This is a comparison of the ability of two quantitative magnetic resonance (MR) indices: (a) the second echo signal drop (SESD) (a simplified index of T2 relaxation times that we have developed); and (b) the previously described lesion/liver signal intensity ratio (LLR) to provide histologic diagnosis in hepatic lesions greater than 2 cm in diameter. In 55 patients 108 hepatic masses [31 cavernous hemangiomas (CH), 68 metastases, and 9 hepatocellular carcinomas] were scanned at 0.5 T. Statistically significant differences between CH and malignant lesions were obtained in mean SESD (p = 0.0006) and LLR (p = 0.0008) using repetition time (TR) 2,100/echo time (TE) 35, 60 ms. Application of cutoff values derived from receiver-operator characteristic analysis led to a correct diagnosis in 100 and 94% of lesions, respectively. Using TR 2,100/TE 35, 90 ms in a different patient population, CH and malignancies again displayed significantly different mean values, using the SESD (p = 0.0090) and LLR (p = 0.0024) methods. These measurements provided a correct diagnosis in 74 and 81%, respectively. Accuracy was increased in those cases in which the diagnosis by SESD and LLR were concordant. When compared with visual analysis, these quantitative methods appear to achieve near 100% accuracy in the differentiation of hepatic CH from malignancies.

Adult↗

Analysis of the statistical methods used to detect submaximal effort with the five-rung grip strength test.

Controversy exists in the literature concerning the ability of the five-rung grip test to identify submaximal effort. The purpose of this study was to analyze four methods commonly used to evaluate the shape of the curve generated by maximal versus submaximal efforts. Thirty hand therapy patients performed the five-rung grip test maximally and submaximally with both their injured and uninjured hands. Grip strength scores were recorded at each of the five-rung positions. Next, four methods were used to analyze the data 1) visual analysis, 2) analysis of variance, 3) normalization, and 4) calculation of the standard deviation across the five strength scores. Analysis by all methods demonstrated that there were no differences between the injured hand exerting maximal effort and the uninjured hand exerting submaximal effort. In all four methods, the five-rung grip strength test was unable to distinguish between the injured hand exerting maximal effort and the uninjured hand exerting submaximal effort. The results suggest that the five-rung grip strength test should not be used to determine sincerity of effort in people with hand injuries, and that the shape of the curve generated by the five-rung grip strength test may not be related to level of effort but rather to the amount of force generated by the gripping hand.

Adolescent↗