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Evaluation of oral contrast agents for abdominal magnetic resonance imaging.

We evaluated the efficacy of six available oral contrast agents in improving visualization of bowel and surrounding structures on magnetic resonance imaging of the abdomen and pelvis. Five volunteers were examined without oral contrast (baseline) and, on separate occasions, after ingestion of 600-900 cc of two positive contrasts [12.5% weight-to-volume (w/v) corn oil emulsion (COE), Redi Cat (EZ-Em Corp., Westbury, NY) mixed with 1% ferric ammonium citrate (FAC)] and four negative contrasts [220%, 105%, 85%, 60% w/v barium sulfate (Liquid HD, Liquid Polybar Plus, HD 85, reconstituted EZ Pake; EZ-Em Corp., Westbury, NY)]. Spin-echo axial and coronal T1-weighted and axial T2-weighted images were obtained in the abdomen and pelvis. Three radiologists blindly graded the images for improved visualization of bowel and surrounding structures. Data were analyzed for statistical significance using the General Linear Models algorithm. In the upper abdomen (stomach, duodenum, liver, and pancreas), COE yielded the highest mean scores (p < .0001), followed by 220% w/v barium. For the lower abdomen (ileum, colon), 220% w/v barium yielded the highest scores (p < .0001) and COE was much worse. The higher density barium preparations (220% and 105% w/v) yielded higher scores than their lower density counterparts (85% and 60%). All contrasts improved visualization of the retroperitoneum and spleen, but no one agent was best. All agents tested are superior to no agent at all. For visualization of the upper abdomen, 12.5% COE performed best. For visualization of the lower abdomen, 220% w/v barium performed best. For concurrent evaluation of both areas with one agent, 220% w/v barium performed best.

Abdomen↗

FEC (5-fluorouracil, epidoxorubicin and cyclophosphamide) versus EM (epidoxorubicin and mitomycin-C) with or without lonidamine as first-line treatment for advanced breast cancer. A multicentric randomised study. Final results.

From May 1991 to December 1996, 326 patients with advanced metastatic breast cancer were enrolled in a multicentre, randomised, phase III clinical trial with four arms. Patients were randomised to receive chemotherapy according to the FEC regimen (5-fluorouracil (5-FU) 500 mg/m2, epidoxorubicin (EPI) 75 mg/m2 and cyclophosphamide (CFA) 500 mg/m2, intravenously (i.v.). every 3 weeks) or the EM regimen (EPI 75 mg/m2, i.v. every 3 weeks; mitomycin C (MMC) 10 mg/m2, i.v. every 6 weeks) or the same regimens with the addition of lonidamine (LND) until disease progression (orally, thrice daily, 150+150+300 mg); a maximum of eight chemotherapy cycles were planned. The aim of the trial was 2-fold: to compare the EM regimen with the commonly used FEC regimen and to evaluate the possible role of the addition of LND. Patients were eligible if they had histologically proven breast carcinoma, metastatic or locoregional relapse with measurable and/or evaluable disease and were aged between 18 and 70 years: 318 patients were considered eligible. Patients with previous anthracycline-based adjuvant chemotherapy or those who relapsed within 6 months after any adjuvant chemotherapy regimen were excluded. Chemotherapy-related toxicity of grade > or = 3 was manageable and there was no significant difference between the arms in terms of haematological side-effects. The impact on heart function was mild. No increased toxicity was observed in the LND arms (apart from myalgias in 27-30% of the cases). A significant increase in the complete response rate was observed for the FEC/EM + LND group (20.4%) versus the FEC/EM group (10.8%). The median survival time and the median time to progression for the overall series were 608 days and 273 days, respectively; EM+/-LND achieved significantly improved survival and time to progression versus FEC+/-LND (P=0.01). This result was confirmed also when the analysis was restricted to patients previously treated with adjuvant CMF schedules. On the basis of these results, we conclude that EM may represent a valuable alternative to FEC for patients requiring a first-line regimen for advanced/ metastatic breast carcinoma, especially in patients previously treated with CMF in an adjuvant setting. Furthermore, we conclude that, in spite of a better complete response rate in the LND arms, as there was no clear advantage in time to progression or survival resulting from the addition of LND to the FEC or EM regimens, the routine use of LND is not warranted outside a clinical trial.

Adult↗

Comparative pharmacodynamic analysis of Q-T interval prolongation induced by the macrolides clarithromycin, roxithromycin, and azithromycin in rats.

In order to evaluate the arrhythmogenic potency of macrolide antibiotics in a quantitative manner, we analyzed the influence of clarithromycin (CAM), roxithromycin (RXM), and azithromycin (AZM) on Q-T intervals from pharmacokinetic and pharmacodynamic points of view and in comparison with the potency of erythromycin (EM) previously reported by us for rats. Male Sprague-Dawley rats were anesthetized, and CAM (6.6, 21.6, and 43.2 mg/kg of body weight/h), RXM (20 and 40 mg/kg/h), and AZM (40 and 100 mg/kg/h) were intravenously injected for 90 min to obtain the time courses of drug concentrations in plasma and the changes in the Q-T intervals during and after the drug injections. Distinct Q-T interval prolongation of up to 10 ms was observed with CAM at its clinical concentrations. RXM and AZM evoked Q-T interval prolongation at concentrations higher than their clinical ranges. The potencies for Q-T interval prolongation, assessed as the slope of the concentration-response relationship, were 6.09, 0.536, and 0.989 ms. ml/microg for CAM, RXM, and AZM, respectively. There was hysteresis between the change in the Q-T intervals and the time course of the plasma concentration of each drug. The rank order of clinical arrhythmogenicity was estimated to be EM > CAM > RXM > AZM, as assessed from the present results and our previous report for EM. In conclusion, RXM and AZM were estimated to be less potent at provoking arrhythmia than EM and CAM. These results should be useful for making a safer choice of an appropriate agent for patients with electrocardiographic risk factors.

Algorithms↗

United snakes.

Since their debut in 1987, snakes (active contour models) have become a standard image analysis technique with several variants now in common use. We present a framework called "United Snakes", which has two key features. First, it unifies the most popular snake variants, including finite difference, B-spline, and Hermite polynomial snakes in a consistent finite element formulation, thus expanding the range of object modeling capabilities within a uniform snake construction process. Second, it embodies the idea that the heretofore presumed competing technique known as "live wire" or "intelligent scissors" is in fact complementary to snakes and that the two techniques can advantageously be combined by introducing an effective hard constraint mechanism. The United Snakes framework amplifies the efficiency and reproducibility of the component techniques, and it offers more flexible interactive control while further minimizing user interactions. We apply United Snakes to several different medical image analysis tasks, including the segmentation of neuronal dendrites in EM images, dynamic chest image analysis, the quantification of growth plates in MR images and the isolation of the breast region in mammograms, demonstrating the generality, accuracy and robustness of the tool.

Algorithms↗

Pathway selection by pulsed field gradients.

A method for pathway selection in a multiple spin-echo pulse sequence applying crusher gradients before and after each pi pulse, to dephase unwanted pathways, is described. This method selects the only pathway that would contribute to the measurable signal if the pi pulses were perfect (1,-1,1,-1, em leader ). Good pathway selection is essential in pulse programming, especially when the CPMG condition is not met. An interactive applet was also developed to deal with these calculations.

Algorithms↗

Is it possible to safely triage callers to EMS dispatch centers to alternative resources?

OBJECTIVES: To develop guidelines allowing emergency medical services (EMS) dispatchers to safely match callers to an EMS response or, alternatively, to a nontraditional resource. METHODS: This was a prospective cohort study of callers to an urban EMS dispatch center and an associated review of EMS patient care forms and emergency department (ED) patient care records. The following five "nature codes" (patient chief complaints) were included: back pain, fall, bleeding or laceration, sick, and trauma. Callers included in the study had been assigned the lowest severity level (Alpha), according to existing dispatch criteria. An a priori list of EMS and ED "important findings," indicating need for an EMS response, was used as the outcome variable. Classification and regression tree (CART) analysis was used to develop a decision rule to further identify a low-risk subgroup of patients who could potentially be served by alternative resources. RESULTS: From November 1, 1998, to May 31, 1999, 656 subjects were entered into the study, including 263 males (40%) and 389 females (59%). The mean age was 51 years (range, 0-101 years). One hundred twenty-five (19%) callers had an important EMS finding, including the administration of comfort medications, morphine, benzodiazepines, and droperidol. Forty-six subjects (7%) had an important ED finding. When EMS and ED findings were combined, 158 subjects (24%) had an "important finding." Using CART analysis, having an age <12 years predicted a subset of patients who did not have an important finding suggesting the need for an EMS response. Using cross-validation, this decision rule had a 99% sensitivity, 13% specificity, and 98% negative predictive value. CONCLUSION: The authors were able to use a demographic variable (age) to predict a population of callers to a 911 dispatch center triaged to the lowest acuity category, who have a very low risk of having an EMS or ED important finding. The decision rule developed here is preliminary, requiring further validation.

Adolescent↗

Iterative three-dimensional expectation maximization restoration of single photon emission computed tomography images: application in striatal imaging.

Single photon emission computed tomography imaging suffers from poor spatial resolution and high statistical noise. Consequently, the contrast of small structures is reduced, the visual detection of defects is limited and precise quantification is difficult. To improve the contrast, it is possible to include the spatially variant point spread function of the detection system into the iterative reconstruction algorithm. This kind of method is well known to be effective, but time consuming. We have developed a faster method to account for the spatial resolution loss in three dimensions, based on a postreconstruction restoration method. The method uses two steps. First, a noncorrected iterative ordered subsets expectation maximization (OSEM) reconstruction is performed and, in the second step, a three-dimensional (3D) iterative maximum likelihood expectation maximization (ML-EM) a posteriori spatial restoration of the reconstructed volume is done. In this paper, we compare to the standard OSEM-3D method, in three studies (two in simulation and one from experimental data). In the two first studies, contrast, noise, and visual detection of defects are studied. In the third study, a quantitative analysis is performed from data obtained with an anthropomorphic striatal phantom filled with 123-I. From the simulations, we demonstrate that contrast as a function of noise and lesion detectability are very similar for both OSEM-3D and OSEM-R methods. In the experimental study, we obtained very similar values of activity-quantification ratios for different regions in the brain. The advantage of OSEM-R compared to OSEM-3D is a substantial gain of processing time. This gain depends on several factors. In a typical situation, for a 128 x 128 acquisition of 120 projections, OSEM-R is 13 or 25 times faster than OSEM-3D, depending on the calculation method used in the iterative restoration. In this paper, the OSEM-R method is tested with the approximation of depth independent resolution. For the striatum this approximation is appropriate, but for other clinical situations we will need to include a spatially varying response. Such a response is already included in OSEM-3D.

Algorithms↗

Collaborative EM image processing with the IPLT image processing library and toolbox.

We present the Image Processing Library and Toolbox, IPLT, in the context of a collaborative electron microscopy processing effort, which has driven the evolution of our software architecture over the last years. The high-level interface design as well as the underlying implementations are described to demonstrate the flexibility of the IPLT framework. It aims to support the wide range of skills and interests of methodologically oriented scientists who wish to implement their ideas and algorithms as processing code.

Algorithms↗

Non-Gaussian smoothing of low-count transmission scans for PET whole-body studies.

A non-Gaussian smoothing (NGS) technique is developed for filtering low count transmission (TR) data to be used for attenuation correction (AC) of positron emission tomography (PET) studies. The method is based on a statistical technique known as the generalized linear mixed model that allows an inverse link function that avoids the inversion of the observed transmission data. The NGS technique has been implemented in the sinogram domain in one-dimensional mode as angle-by-angle computation. To make it adaptive as a function of the TR count statistics we also develop and validate an objective procedure to choose an optimal smoothing parameter. The technique is assessed using experimental phantoms, simulating PET whole-body studies, and applied to real patient data. Different experimental conditions, in terms of TR scan time (from 1 h to 1 min), covering a wide range of TR counting statistic are considered. The method is evaluated, in terms of mean squared error (MSE), by comparing pixel by pixel the distribution for high counts statistics TR scan (1 h) with the corresponding counts distribution for low count statistics TR scans (e.g., 1 min). The smoothing parameter selection is shown to have high efficiency, meaning that it tends to choose values close to the unknown best value. Furthermore, the counts distribution of emission (EM) images, reconstructed with AC generated using low count TR data (1 min), are within 5% of the corresponding EM images reconstructed with AC generated using the high count statistics TR data (1 h). An application to a real patient whole-body PET study shows the promise of the technique for routine use.

Algorithms↗

Evaluation of the number of SPECT projections in the ordered subsets-expectation maximization image reconstruction method.

Filtered back projection (FBP) method, maximum likelihood-expectation maximization(ML-EM) method, and ordered subsets-expectation maximization (OS-EM) method are currently used for reconstruction of SPECT images in clinical studies. In the ML-EM method, images of good quality can be reconstructed even with a small sampling number of projection data, when compared with FBP. Shorter acquisition time and less radionuclide dose are preferable in the clinical setting if image quality is the same. In this study, we attempted to find optimal conditions for reconstruction of OS-EM images with commonly used sampling numbers of 30, 60 and 120 (step angles: 12 degrees, 6 degrees, and 3 degrees, respectively), with acquisition counts/projection of 30, 60, 120 and 240 each. We adjusted the pixel counts of reconstructed images to be constant, by setting combination of sampling number and counts/projection (120 sampling number for 30 counts/projection, 60 for 60, and 30 for 120). Among the 3 acquisition conditions, the small sampling number of 30 had large acquisition counts per direction, resulting in low signal to noise ratio. Under this condition, the resolution was slightly low, but the uniformity of images was high. The combination of OS-EM and smaller sampling projection number may be clinically useful with reduction of the examination time, which is also beneficial to reduce dead time for gamma-camera rotation.

Adult↗

Comparison of termination-of-resuscitation guidelines for basic life support: defibrillator providers in out-of-hospital cardiac arrest.

STUDY OBJECTIVE: Termination of resuscitation in the field for out-of-hospital cardiac arrest can reduce unnecessary transport to hospital and associated road hazards and increase availability of emergency medical services (EMS) and emergency department resources for other patients. We compare the performance of 3 termination-of-resuscitation guidelines for basic life support-defibrillator (BLS) providers when applied to cardiac arrest patients in the Ontario Prehospital Advanced Life Support study. METHODS: This prospective cohort study involved all out-of-hospital cardiac arrest patients attended by BLS defibrillator providers in 21 Ontario urban or suburban communities. The data analyses were conducted secondarily on these prospectively collected data. Three termination-of-resuscitation guidelines (referred to as Marsden, Petrie, and Verbeek rules) were applied and contingency tables calculated to show the relationship between the rule and actual survival. RESULTS: From 1988 to 2003, 13,684 cardiac arrest patients were attended by BLS defibrillator providers. Six hundred thirty-six (4.7%) patients survived to hospital discharge. For the 3 termination-of-resuscitation rules, sensitivity was 99.8% (95% confidence interval [CI] 99.5% to 100.0%) (Petrie rules), 99.5% (95% CI 99.0% to 100.0%) (Verbeek rules), and 99.8% (95% CI 99.5% to 100.0%) (Marsden rules). Specificity was 9.9% (95% CI 9.4% to 10.4%) (Petrie rules), 52.9% (95% CI 52.1% to 53.8%) (Verbeek rules), and 19.4 % (95% CI 18.8% to 20.1%) (Marsden rules). Negative predictive value was 99.9% (95% CI 99.8% to 100.0%) (Petrie rules), 100.0% (95% CI 99.9% to 100.0%) (Verbeek rules), and 100.0% (95% CI 99.9% to 100.0%) (Marsden rules). These rules would have resulted in field termination of resuscitation in 9.4% (Petrie rules), 50.5% (Verbeek rules), and 18.5 % (Marsden rules) of cases. Termination of resuscitation was recommended for 1 patient (Petrie rules), 3 patients (Verbeek rules), and 1 patient (Marsden rules), who survived. CONCLUSION: We found all 3 termination-of-resuscitation rules to have high sensitivity and negative predictive value. However, the specificity and transport rates varied greatly. The results of this study will be useful for EMS providers considering adoption of termination of resuscitation in BLS defibrillator systems for out-of-hospital cardiac arrest.

Adolescent↗

BASIC programs to compute source densities from autoradiographic cross-fire matrices.

Two different mathematical procedures to compute source densities from cross-fire matrices in quantitative EM autoradiography are reported. BASIC programs for a desk-top microcomputer were written to fit the hypothetical silver grain distribution to the observed real silver grain distribution using a non-iterative linear process (least-squares procedure) and an iterative method, which minimizes the chi-square component between the observed and computed silver grain distributions. The latter procedure uses a Gauss-Newton algorithm.

Autoradiography↗

Quantitative comparison of anti-fading mounting media for confocal laser scanning microscopy.

Fading is one of the major obstacles to reliable observation in fluorescence microscopy. Using a confocal laser scanning microscope (CLSM) coupled to a computer, we quantitatively measured fading of fluorescence to formulate an equation, evaluated the anti-fading ability of several anti-fading media, and restored the faded images to the original level according to this equation. NIH 3T3 cells were stained with fluorescein isothiocyanate (FITC)-phalloidin, mounted with several commercial and homemade anti-fade media, and observed with CLSM under repeated illumination. With any mounting medium, attenuation of fluorescence intensity at a certain pixel occurred stepwise and the decrease was proportional to the intensity of the previous scan. From these results, we formulated an equation that has three coefficients: anti-fading factor (A), indicating the ability to retard fading; fluorescent intensity at the first scan (EM(1)); and background fluorescence (B). The fluorescent intensity at a certain point following nth scan is given as EM(n) = EM(1) * A ((n-1)). This equation was available for restoring faded images to their original states, even after the image had faded to only 60% of its original intensity.

3T3 Cells↗

Determination of spin-label orientation within the myosin head.

Current methods of analyzing EPR spectra of spin-labeled muscle fibers allow the determination of spin-label orientation within the fiber, rather than the orientation of the myosin head itself. In order to describe the orientational distribution of spin labeled myosin heads within the muscle fibers, the orientation of the spin label within the myosin head must be known. The iodoacetamide label orientation in the myosin head was determined to be (16.8 degrees, 28.3 degrees, 4.2 degrees) or (16.6 degrees, 72.0 degrees, 4.3 degrees). These Eulerian angles were obtained from the analysis of EPR spectra of fibers decorated with labeled myosin heads in the absence of ATP, with the assumption that the head's tilt angle is 40 degrees, as observed in a recent EM study [Pollard, T., Bhandari, D., Maupin, P., Wachsstock, D., Weeds, A. & Zot, H. (1993) Biophys. J. 64, 454-471]. Knowledge of spin-label orientation will allow for quantitative determination of myosin head orientation in the various states of the contractile cycle.

Algorithms↗

Effectiveness of interactive videodisc instruction for the continuing education of paramedics.

OBJECTIVES: To evaluate the effectiveness of interactive videodisc (IVD) instruction of paramedics through the use of computer analysis of trip sheets. DESIGN/SETTING: Prospective, controlled, in an urban 9-1-1, paramedic, emergency medical services (EMS) system with total call volume of 62,000/year; 15,000 advanced life support (ALS). INTERVENTIONS: All 150 paramedics in the system received eight hours of IVD instruction covering five subject areas: 1) airway; 2) head/cervical trauma; 3) chest; 4) shock; and 5) cardiac arrest. Trip sheets from 9,943 runs in the pre-IVD period were subjected to computer analysis, and a compliance score was generated using previously developed algorithms that assigned a weight to each omission and commission. After a nine-month IVD training period, 4,303 cases were collected and analyzed in the post-IVD period. Statistical analyses were made using "Student's" t-test and Chi-square with alpha set at 0.05. EXCLUSIONS: Only those records of adult patients who fit one of the five protocols were eligible for computer analysis. Of the 9,943 cases in the pre-IVD group, 480 (4.8%) were excluded, all due to inadequate data recording by the paramedics. A statistically similar portion, 233 (5.4%) of the 4,303 post-IVD instruction cases were excluded (p = .15). RESULTS: Overall the mean compliance score of the pre-IVD group was 0.65 +/-0.19 (+/-SD). The post-IVD group score was 0.65 +/-0.19 (p = 0.99). Analysis of scores for each algorithm also showed no significant differences. This study had an observed power of .94 to detect a difference in compliance as small as 0.030. CONCLUSION: (ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Effectiveness of interactive videodisc instruction for the continuing education of paramedics.

OBJECTIVES: To evaluate the effectiveness of interactive videodisc (IVD) instruction of paramedics through the use of computer analysis of trip sheets. DESIGN/SETTING: Prospective, controlled, in an urban 9-1-1, paramedic, emergency medical services (EMS) system with total call volume of 62,000/year; 15,000 advanced life support (ALS). INTERVENTIONS: All 150 paramedics in the system received eight hours of IVD instruction covering five subject areas: 1) airway; 2) head/cervical trauma; 3) chest; 4) shock; and 5) cardiac arrest. Trip sheets from 9,943 runs in the pre-IVD period were subjected to computer analysis, and a compliance score was generated using previously developed algorithms that assigned a weight to each omission and commission. After a nine-month IVD training period, 4,303 cases were collected and analyzed in the post-IVD period. Statistical analyses were made using "Student's" t-test and Chi-square with alpha set at 0.05. EXCLUSIONS: Only those records of adult patients who fit one of the five protocols were eligible for computer analysis. Of the 9,943 cases in the pre-IVD group, 480 (4.8%) were excluded, all due to inadequate data recording by the paramedics. A statistically similar portion, 233 (5.4%) of the 4,303 post-IVD instruction cases were excluded (p = .15). RESULTS: Overall the mean compliance score of the pre-IVD group was 0.65 +/- 0.19 (+/- SD). The post-IVD group score was 0.65 +/- 0.19 (p = 0.99). Analysis of scores for each algorithm also showed no significant differences. This study had an observed power of .94 to detect a difference in compliance as small as 0.030. CONCLUSION: Eight hours of IVD instruction did not result in improved paramedic performance as judged by computer analysis of trip sheets.

Adult↗

TYSON: robust searching, sorting, and selecting of single particles in electron micrographs.

We here present TYSON, a new program for automatic and semi-automatic particle selection from electron micrographs. TYSON employs a three-step strategy of searching, sorting and selecting single particles. In the first step, TYSON finds the positions of potential particles by one of three different methods: local averaging, template matching or local variance. The practical merits and drawbacks of these methods are discussed. In the second step, these potential particles are automatically sorted according to their probability of being true positives. Many criteria are provided for this sort. In the final -interactive- step, whole categories of poorly fitting false positives can be removed with a single mouse-click. We present results obtained using cryo-EM micrographs of both spherical virus particles and asymmetric particles. The procedures are fast and use of TYSON allowed, for example, some 20,000 particles to be selected in a single working day.

Algorithms↗