Semiautomated nuclear shape analysis of prostatic carcinoma and benign prostatic hyperplasia.

Nuclear shape analysis has predicted outcome better than histologic grading in patients with clinically localized prostatic carcinoma. However, the requirement for manual nuclear contour tracing makes the method tedious and slow. Currently available image analysis systems for nuclear shape analysis using light-absorption microscopy provide nuclear boundaries of insufficient clarity for automatic segmentation. We improved image resolution using confocal laser scanning microscopy, automatically detected nuclear boundaries by a multiscale segmentation algorithm and discriminated artifacts in a semiautomated way. A manual quantitative morphometry system and our semiautomated system distinguished eight cases of prostatic carcinoma from seven cases of benign prostatic hyperplasia by nuclear roundness factor, ellipticity, nuclear area and perimeter. The ease of semiautomated nuclear shape analysis should allow evaluation of large numbers of patients with known outcomes after treatment for clinically localized prostatic carcinoma to determine whether nuclear shape analysis can be extended from research to clinical usage.

A critical review of trend-detection methodologies for biomedical monitoring systems.

Information gained through early detection of patient vital sign changes typically can be used to anticipate future difficulties. Detection of these changes through monitoring, however, can be difficult. Many of the monitored processes are random in nature. For that reason simple threshold algorithms exhibit a high incidence of false alarms, which can decrease the operator's confidence in the monitor. Many problems associated with threshold-based biological monitors can be alleviated by introducing statistical detection techniques. The purpose of this review is to develop and critique the major trend detection algorithms used in biological monitors. This review contains an evolution of trend detection through current state-of-the-art algorithms.

A Monte Carlo technique for signal level detection in implanted intracranial pressure monitoring.

Statistical monitoring techniques like CUSUM, Trigg's tracking signal and EMP filtering have a major advantage over more recent techniques, such as Kalman filtering, because of their inherent simplicity. In many biomedical applications, such as electronic implantable devices, these simpler techniques have greater utility because of the reduced requirements on power, logic complexity and sampling speed. The determination of signal means using some of the earlier techniques are reviewed in this paper, and a new Monte Carlo based method with greater capability to sparsely sample a waveform and obtain an accurate mean value is presented. This technique may find widespread use as a trend detection method when reduced power consumption is a requirement.

A nonlinear least-squares method for determining cerebrospinal fluid formation and absorption kinetics in pseudotumor cerebri.

Data from 14 patients with benign intracranial hypertension (pseudotumor cerebri) have been analyzed using a nonlinear least-squares regression model which was developed and programmed from in-hospital microcomputer use. The method of analysis permits rapid estimation of cerebrospinal fluid (CSF) formation and absorption rates as functions of pressure in individual patients using data from constant-rate infusion manometrics. The analysis predicts that prednisone therapy in pseudotumor cerebri reduces resting CSF pressure by increasing CSF absorption at all intracranial pressures studied, and decreasing CSF formation at high pressures. This result is in accordance with evidence suggesting that impaired CSF absorption plays a major role in the pathogenesis of increased intracranial pressure in pseudotumor cerebri.

Assessment of cerebrospinal fluid compliance and outflow resistance: analysis of steady-state response to sinusoidal input.

Cerebrospinal fluid dynamics have been studied in the past by analyses of responses to bolus, constant rate or constant pressure inputs. In this study, we present a method for analyzing CSF pressure responses to sinusoidal variation in the infusion rate. Infusion of artificial CSF into the cisterna magna of adult rats was modulated sinusoidally between 0 and 30 microliter/min. The resulting sinusoidal variation in intracranial pressure was recorded on a strip chart recorder simultaneously with the infusion rate signal. The two signals were analyzed for peak-to-peak variation, mean value, and phase shift for input frequencies in the range of 0.0015 to 0.01 HZ (0.00942 to 0.0628 radians/sec). The system was analyzed at each mean infusion rate as a parallel resistance and compliance with a first order linear model. The resistance to CSF outflow was determined as the change in mean steady-state pressure divided by the change in mean infusion rate. The compliance was then obtained from the frequency dependent phase shift between input and output using the first-order linear model. Resistance values were lower for higher average infusion rates consistent with our previous work, while compliance remained constant over the measured pressure range.

Responses of aortic baroreceptors to changes of aortic blood flow and pressure in rat.

To test the hypothesis that aortic baroreceptors may respond not only to changes of aortic pressure but also to changes of aortic flow, sinusoidal flow waves were applied at 1 Hz to the aorta of urethan-anesthetized rats by infusion and withdrawal of 90 microliters blood with a pump while aortic blood pressure and single baroreceptor fiber activity were monitored. Averages from 20 to 30 pressure wave forms and nerve impulse histograms were established by computer for each single fiber during control (no pump), pump instroke (I), and outstroke (O). Fiber activity increased 20 +/- 3% (mean +/- SEM, n = 28 fibers) and decreased 23 +/- 4% with respect to control during I and O, respectively, whereas estimated changes of aortic flow were +/- 21%. The number of nerve impulses increased (I) and decreased (O) mainly during late systolic pressure rise did not change significantly, but the rate of late systolic pressure fall decreased 42 +/- 7 mmHg/s (I) and increased 39 +/- 11 mmHg/s (O). These results suggest that, because of the rate sensitivity of aortic baroreceptors, changes in aortic flow are reflected in changes of nerve impulse firing patterns during the blood pressure decrease in late systole, even in the absence of significant changes in systolic, diastolic, and pulse pressure.

Cerebellar stimulation: regional effects on a thalamocortical system.

Regional effects of electrical stimulation of the cerebellar surface were quantitatively analyzed. Computer controlled stimulus sequences were delivered to ventrolateral thalamus and evoked responses recorded from ipsilateral sensorimotor cortex in the cat. Threshold and excitability profiles were produced with an on-line computer, and their modification by cerebellar stimulation was determined. The results of electrical stimulation of the cerebellar surface were: (1) depressed excitability from paramedian lobule and lobulus simplex; (2) uniquely elevated thresholds from paramedian lobule; and (3) a profound and long-lasting depression of excitability following termination of lobulus simplex stimulation. In comparison with our anticonvulsant drug studies, these data suggest that cerebellar surface stimulation has a far greater capacity to control excitability and threshold responsiveness of thalamocortical systems. Cerebellar electrode placement and temporal pattern of stimulation appear to be important factors in the production of antiepileptic effects.