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Resting membrane potentials: a student test of alternate hypotheses.
The frog sartorius muscle is a model tissue for demonstrating to physiology students the principles underlying both membrane phenomena and hypothesis testing. Myocytes can be impaled with conventional glass microelectrodes to measure membrane voltage (Vm). Further, Vm is observed as extracellular K+ is altered and a K+ channel blocker is added. After the experiment, students examine the underlying assumptions of the Nernst equilibrium and the Goldman-Hodgkin-Katz equation. They ultimately determine which of the two algorithms best predicts the measured Vm. In addition, students learn micromanipulation and impalement techniques. This experiment facilitates the student's understanding of membrane permeability, ionic gradients, and membrane voltage.
[A method for measuring QT and T duration and beat to beat variability].
The QT interval duration is an important non-invasive electrophysiological parameter that reflects ventricular depolarization and repolarization time. A knowledge of QT variability also provides specific information on the normal and pathological ventricular myocardium, and the influence of the autonomic nervous system. A numerical algorithm was developed for measuring QT interval and T-wave duration in the surface electrocardiogram. In comparison with numerous other approaches, this method calculates these durations without averaging of QRS complexes on a beat-to-beat basis. The main aim of this study was to assess the efficacy of this method for characterizing cardiac diseases. In 6 patients with hypertrophic cardiomyopathy and a control group of 5 healthy, age-matched subjects, different interval durations were calculated. In contrast to the mean QT interval duration, only the T-wave duration differed significantly between the two groups.
Computational waveform analysis and classification of auditory brainstem evoked potentials.
The widely used quantitative descriptors of amplitude and latency of evoked potentials, for peaks and troughs along the waveform, relate to only a limited number of points along the waveform, ignoring the interposed data. Moreover, these descriptors are typically determined manually, rendering them susceptible to user bias. We propose and demonstrate a machine-scoring algorithm for the identification and measurement of Auditory Brainstem Evoked Potentials (ABEP) peaks I, III and V. We further introduce an algorithm for the quantitative analysis of ABEP by waveform, and for clustering records according to waveform characteristics. The results of computerized peak identification and measurement, without user intervention, were correlated with manual measurements of the same peaks in a large number of waveforms. The waveform analysis and classification procedure differentiated waveforms to monaural left, monaural right and binaural stimulation, as well as according to the recording montage. These results underscore the advantages of using information in the waveform of ABEP, which has so far been overlooked. The automated algorithms for evaluation of ABEP by waveform hold the promise of a more comprehensive and consistent evaluation, and hence improved sensitivity.
Assessment of telomere length in hematopoietic interphase cells using in situ hybridization and digital fluorescence microscopy.
Telomeres are G/C-rich repetitive DNA sequences at the end of all eukaryotic chromosomes. The loss of telomeric repeat sequences during cell divisions has been proposed as a possible mechanism for cell senescence. The standard procedure for measurement of telomere length is Southern blot (SB) hybridization with a telomere-specific probe. However, in using this technique no information can be obtained on variation in telomeric fragments due to interchromosomal, intrachromosomal, and intercellular differences. Lansdorp et al. (Hum Mol Genet 5:685-691, 1996) developed a method to measure individual telomeres, using in situ hybridization on metaphase chromosomes, employing peptide nucleic acid (PNA) probes and digital fluorescence microscopy. In this paper we describe a method that can be used to assess telomeric length in interphase cells. An algorithm was developed to measure the total intranuclear fluorescence in situ hybridization (FISH) signal, which features accurate correction for the local autofluorescence. Application of this methodology to samples of fetal liver, umbilical cord blood, and adult bone marrow cells showed a gradual decrease of average telomeric length. Southern blot analysis and PNA FISH measurements on chromosomes in the same samples showed similar results. Advantages of interphase measurements include the possibility of studying nonproliferating cells, thus avoiding selection and cell culturing.
Acoustic pattern recognition of /s/ misarticulation by the self-organizing map.
The [s] samples of 11 women, psychoacoustically classified as acceptable/unacceptable, were studied with the self-organizing map, the neural network algorithm of Kohonen. The measurement map had been previously computed with nondisordered speech samples. Fifteen-component spectral vectors, analyzed with the map, were calculated from short-time FFT spectra at 10-ms intervals. The degree of audible acceptability correlated with the location of the sample on the map. Spectral model vectors in different map locations depicted distinguishing spectral features in the [s] samples analyzed. The results demonstrate that self-organized maps are suitable for the extraction and measurement of acoustic features underlying psychoacoustic classifications, and for on-line visual imaging of speech.
Can the same edge-detection algorithm be applied to on-line and off-line analysis systems? Validation of a new cinefilm-based geometric coronary measurement software.
In the Cardiovascular Measurement System (CMS) the edge-detection algorithm, which was primarily designed for the Philips digital cardiac imaging system (DCI), is applied to cinefilms. Comparative validation of CMS and DCI was performed in vitro and in vivo with intracoronary insertion of stenosis phantoms in anesthetized pigs. The "obstruction diameter" (OD) was measured at the artificial stenoses visualized by angiography with calibration at the isocenter (ISO) and catheter calibration (CATH) and compared with the true phantom diameters. A clinical comparison of OD, reference diameter (RD), and percentage diameter stenosis (DS) was performed on 70 corresponding images from post-PTCA angiograms. In vitro, OD (CMS) yielded an accuracy of 0.18 +/- 0.14 mm with 100% (correlation coefficient: r = 0.97, y = 0.06 + 0.75x, standard error of estimate [SEE] = 0.09) and 0.19 +/- 0.15 mm with 50% contrast (r = 0.94, y = 0.02 + 0.81 x). OD (DCI) yielded an accuracy of 0.11 +/- 0.06 mm with 100% (r = 0.99, y = -0.03 + 0.91 x, SEE = 0.05) and 0.24 +/- 0.13 mm with 50% contrast (r = 0.94, y = 0.29 + 6.69 x, SEE = 0.12). In vivo, OD (CMS) yielded an accuracy of 0.18 +/- 0.23 mm with ISO (r = 0.89, y = 0.02 + 0.83 x, SEE = 0.22) and 0.26 +/- 0.24 mm with CATH (r = 0.89, y = 0.06 + 0.72 x, SEE = 0.19). OD (DCI) yielded an accuracy of 0.08 +/- 0.15 mm with ISO (r = 0.96, y = 0.08 + 0.86 x, SEE = 0.14) and 0.18 +/- 0.21 mm with CATH (r = 0.92, y = 0.09 + 0.76 x, SEE = 0.17). The clinical comparison showed reasonable agreement for OD only (r = 0.81, y = 0.26 + 0.81 x, SEE = 0.29). Transformation of an edge-detection algorithm from a digital to a cinefilm-based system can lead to impairment of measurement reliability.
Beam profiles along the nonwedged direction for large wedged fields.
Beam profiles along the nonwedged direction of a wedged field produced by a linear accelerator exhibit more "sagging" than that of an open field at the same depth. For large fields, the profiles of open and wedged fields can differ by as much as 7%. The extra "sagging" of wedged profiles is mainly due to the difference in penetration between on- and off-axis rays caused by the variation of beam quality across the field. An algorithm was developed to estimate an "effective" depth such that the profile of a wedged field can be approximated by the open-field profile at the effective depth. The algorithm was verified by measured beam profiles for 6- and 15-MV x-ray beams for 15 degree, 30 degree, 45 degree, and 60 degree wedges.
Estimation of peripheral dose from two linacs: Mevatron MX6700 and Mevatron KDS.
An empirical calculation method for high-energy beam peripheral dose estimation is described. The peripheral dose has been measured for a Siemens Mevatron MX6700 (6 MV) and a Siemens Mevatron KDS (6 and 18 MV) linear accelerators. The dose distribution is parameterized for each beam energy as a function of depth, distance from the edge of the field, and field size. A simple algorithm has been developed for dose calculation up to 100 cm from the field central axes. Predictions by this algorithm are compared with measurements in an Alderson phantom.
The use of urinary hormonal assessments in human studies.
The collection and analysis of urine samples provides a practical method for monitoring female reproductive events in non-laboratory and non-clinic populations. Collection of biologic samples permits objective assessment of reproductive health endpoints in epidemiologic studies and for epidemiologic research purposes can provide validation of information provided by the subjects, especially outcomes which are usually concealed and thus unknown to the participant. Urine sampling has several advantages over the collection of blood samples, such as simplicity, non-invasiveness, and cost efficiency. Several studies have shown that endocrine information similar to that obtained in blood samples can be obtained from assays of daily urine samples. The measurement of human chorionic gonadotropin in daily and selected urine samples has been incorporated into several recent epidemiologic studies focusing on early fetal loss, and ovarian and pituitary hormone metabolites have been measured in daily urine samples to evaluate ovarian function in studies focusing on women's reproductive health. As the strategy of urinary monitoring becomes more accepted as a legitimate research tool, laboratory methods are being modified to improve performance, reduce costs and adapted to sophisticated algorithms using multiple hormonal measurements to identify a number of end-points.
A method for dose calculation for high energy photon beams based on measurements performed at reference depth.
An algorithm is proposed to calculate the dose per monitor unit at any point along the beam axis for blocked or unblocked fields. The proposed formalism takes into consideration the beam measurements performed at the reference depth as recommended by most dosimetry protocols (5 cm or 10 cm depending on the beam quality). The only parameters which cannot be measured at the reference depth are the peak scatter factors, but they appear only as a ratio of two peak scatter factors for two slightly different field sizes. A correction factor is proposed when the distance of one shielding block to the beam axis is smaller than 5 cm. An agreement better than 1% has been obtained between calculations and measurements in the range of beam qualities, distances to the source and field sizes defined by typical collimators or shielding blocks, usually encountered in clinical practice.
Development of an advanced digital image processor for real-time speckle suppression in routine ultrasonic scanning.
This paper describes a digital image processor for ultrasonic speckle suppression that was explicitly designed to satisfy the requirements of detail preservation, adequate smoothing and real-time operation. The first two of these requirements were addressed by selecting a nonlinear adaptive algorithm, which uses a measure of local homogeneity to adjust the amount of smoothing performed at each point of the scan, and employing a large (9 x 9 pixels) filtering window. Real-time operation was achieved by developing a highly concurrent systolic architecture that allowed the efficient mapping of the algorithm into low-cost high-density hardware. Initial experience, obtained by interfacing the processor to a scanner, suggests that this type of processing is capable of enhancing the visibility of subtle differences in echogenicity while retaining genuine image detail, as judged by the preservation of the small vessels and ducts. In addition to its impact on contrast resolution, this form of real-time speckle suppression should also prove valuable as a preprocessing stage before performing other digital image processing operations that are sensitive to noise, such as segmentation and three-dimensional rendering.
Thermoluminescence dosimetry applied to in vivo dose measurements for total body irradiation techniques.
BACKGROUND AND PURPOSE: In total body irradiation (TBI) treatments in vivo dosimetry is recommended because it makes it possible to ensure the accuracy and quality control of dose delivery. The aim of this work is to set up an in vivo thermoluminescence dosimetry (TLD) system to measure the dose distribution during the TBI technique used prior to bone marrow transplant. Some technical problems due to the presence of lung shielding blocks are discussed. MATERIALS AND METHODS: Irradiations were performed in the Hospital de la Santa Creu i Sant Pau by means of a Varian Clinac-1800 linear accelerator with 18 MV X-ray beams. Different TLD calibration experiments were set up to optimize in vivo dose assessment and to analyze the influence on dose measurement of shielding blocks. An algorithm to estimate midplane doses from entrance and exit doses is proposed and the estimated dose in critical organs is compared to internal dose measurements performed in an Alderson anthropomorphic phantom. RESULTS: The predictions of the dose algorithm, even in heterogeneous zones of the body such as the lungs, are in good agreement with the experimental results obtained with and without shielding blocks. The differences between measured and predicted values are in all cases lower than 2%. CONCLUSIONS: The TLD system described in this work has been proven to be appropriate for in vivo dosimetry in TBI irradiations. The described calibration experiments point out the difficulty of calibrating an in vivo dosimetry system when lung shielding blocks are used.
A two-dimensional pencil-beam algorithm for calculation of arc electron dose distributions.
A two-dimensional pencil-beam algorithm is presented for the calculation of arc electron dose distributions in any plane that is perpendicular to the axis of rotation. The dose distributions are calculated by modelling the arced beam as a single broad beam defined by the irradiated surface of the patient. The algorithm is two-dimensional in that the anatomical cross section of the patient and the skin collimators are assumed identical in parallel planes outside the plane of calculation. The broad beam is modelled as a collection of strip beams, each strip beam being characterised by its planar fluence, mean projected angular direction and a root-mean-square spread about the mean direction. Using these parameters, the dose distribution is calculated using pencil-beam theory. Examples of strip-beam parameters and resulting dose distributions for patient geometries are presented. Features of the algorithm, which include (1) incorporation of pencil-beam theory for the calculation of dose in heterogeneous tissue, (2) run times of only about twice that of comparable-sized fixed electron fields and (3) the input requirement of only a single depth dose and four off-axis dose profiles of measured data, make the algorithm practical for clinical use.
Internal tissue displacement measurement based on ultrasonic wave Doppler signal digital detection and its application to fetal movement monitoring.
We have developed a fetal movement monitoring system based on small displacement measurement of internal tissues. When ultrasonic pulses are transmitted to the fetus, the reflected ultrasonic waves which have a Doppler frequency shift due to the fetal movements are detected by using an ultrasonic pulsed Doppler technique. In this paper, we propose a displacement measurement method for internal tissues which is based on the Doppler signal digital detection technique. In the method, the received ultrasonic RF signals are sampled with a sampling frequency of four times higher than the centre frequency of the ultrasonic waves; the Doppler frequency shift signals are derived using digital signal processing. From the detected signals, the internal displacements are estimated using the arc-tangent method. The basic algorithm of the detection method has already been used in the area of blood flow sensing, however, we apply the algorithm to the displacement measurement of internal tissues. The comparison between the proposed method and the conventional method is presented. The fetal movement quantitative monitoring system based on the method which has been constructed is shown.
[The choice of the treatment procedure in complicated forms of gallstones].
The article is devoted to an assessment of results of treatment of patients with complicated forms of cholelithiasis. Results of the treatment with active surgical measures and use of the endoscopic surgery methods are compared. Advantages of using endoscopy in algorithm of diagnostic and medical measures are shown. Recommendations are given concerning the terms and consequence of using the endoscopic methods of treatment.
Quantification of diabetic maculopathy by digital imaging of the fundus.
Measurement of the extent of diabetic retinopathy is an essential part of assessing the efficacy of local or systemic treatment regimens. Current clinical studies use empirical grading of retinopathy which is performed by a trained observer using standard photographs. This method is relatively arbitrary, as well as time consuming and vulnerable to observer error. We have developed a digital fundus imaging system and image processing programs which provide objective, quantitative measures of macular oedema, retinal exudates, and microaneurysms in diabetic retinopathy. Using fluorescein angiograms, the degree of macular oedema is quantified both in terms of area of fundus involved and severity of oedema by analysis of the temporal changes in intensity of fluorescence. Fluorescein angiograms are also used for the detection and counting of microaneurysms, by a combination of shade correction, matched filtering, and shape algorithms. For detection and measurement of retinal exudates, a colour transparency projected through a red free filter is analysed using a combination of shade correction and thresholding techniques. The system described is in clinical use, and has potential for a wide variety of applications. With further development, digital analysis of fundus images should supercede the currently used manual semi-quantitative methods, providing faster, more accurate, objective quantitative results.
Screening for peripheral arterial disease: the sensitivity, specificity, and predictive value of noninvasive tests in a defined population.
Large vessel peripheral arterial disease (LV-PAD) is a common condition that causes significant morbidity and disability. The authors evaluated the individual components of a comprehensive noninvasive vascular examination to identify the most sensitive and specific measurements for diagnosing LV-PAD. This cohort, initially screened between 1979 and 1981 in Rancho Bernardo, California, included 421 normal subjects and 63 subjects with LV-PAD. Segmental blood pressure ratios and flow velocities by Doppler ultrasound were used to define cases of LV-PAD. The sensitivity, specificity, positive predictive value, and negative predictive value of each individual component of the diagnostic algorithm were determined. Overall, measurements of posterior tibial flow showed the highest sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy. In addition, an absent or non-recordable posterior tibial peak forward flow, occurring in 96% of all limbs with isolated posterior tibial disease, or an ankle ratio < or = 0.8 considered in parallel yielded a test with sensitivity of 89%, specificity of 99%, positive predictive value of 90%, negative predictive value of 99%, and overall accuracy of 98%. These results indicate that the vast majority of LV-PAD cases can be detected with a single measurement using a handheld Doppler flowmeter employed at the ankle.