Showing papers in "Annals of Biomedical Engineering in 1975"

Artificial intelligence and brain theory: unities and diversities.

Abstract: This review article synthesizes studies ofartificial intelligence (AI) andbrain theory (BT). In the control ofmovement, AI offers insight into overallplanning of behavior; while control theory enables BT to modelfeedback andfeedforward adjustments by the spinal cord, brainstem, and cerebellum. We stressaction-oriented perception—analyzing perception in terms of preparation for interaction with the world, and offer a new concept of aschema as the internal representation of an “object” in the sense of a domain of interaction. A schema comprises input-matching routines, action routines, and competition and cooperation routines. The internal representation of the world is then given by a “collage” of tuned and activated schemas.Segmentation of input andregion labeling are offered as two mechanisms in the activation of a suitable “collage.” We see a number of studies that offer hope of a unified theory ofcompetition and cooperation within a single subsystem: brain theory models of the reticular formation, of the frog midbrain visual system, and of segmentation on prewired features; and AI models of segmentation on ad hoc features, and of region labeling. We then turn to the modeling of a set of brain regions as acooperative computation system—a distributed structure in which each system has its own “goal structure” for selecting information to act on from its environment, and for transmitting the results to suitable receivers. We use this to describe a few findings ofneurology. We then sample AI studies of computerunderstanding of natural language, ascribing particular significance to a speech understanding system configured as a cooperative computation system. The literatures of AI and BT hardly overlap at all, and differ widely in choice of both problem and method. The aim of this article is to overcome these diversities by extracting contributions from extant AI and BT that can be melded into the creation of atop-down brain theory: the building of a coherent model of cooperative computation within which the computational roles of brain regions, and of neurons within those regions, can be analyzed.

Pulmonary surfactant: a surface chemistry viewpoint.

Abstract: In this paper, we attempt to review and evaluate pulmonary surfactant research from what is essentially a surface chemistry viewpoint. The physiological importance of the system underlies the discussion, but this is coupled with the surface chemical consideration of pulmonary surfactant as a complex multicomponent system of soluble and insoluble surfactants at a liquid-air interface. The systemin vivo is at a constant temperature (37°C) and an essentially constant bulk pressure, but is subject to large variations in surface cycling frequency and in maximum and minimum surface area. In this context, then, the present level of knowledge of the system is discussed, and areas of uncertainty or conflict which require further study are isolated. In addition, experimental or analytical approaches useful for future surface studies are given wherever possible.

Graphite fiber reinforced bone cement. An experimental feasibility investigation.

Abstract: This paper presents the results of a brief experimental investigation to determine the effects of graphite fiber additives on the flexuaral, compressive, and exothermal characteristics of surgical bone cement. The materials used in the investigation were polymethyl-methacrylate (PMM) and chopped graphite (GY70) fibers. Both fiber reinforced and unrein-forced beam and cylinder specimens were fabricated and tested. The unreinforced specimens were used to develop baseline data.

Improvement of deep body thermometer for man.

Abstract: A noninvasive method of monitoring the deep body temperature in man, originally presented by Fox and Solman, was improved The method was based on a technique of a heat flow compensation From a theoretical analysis, we found that heat insulation in the original Fox-type probe was incomplete and we modified the structure in the probe; ie, the circumference of the probe was maintained at the same temperature as the center We compared theoretically and experimentally the original Fox-type with the modified probe An improvement in accuracy was expected theoretically and that result was verified by a thermographic analysis In animal experiments, the response of the improved thermometer was accurate and rapid for a stepwise change in the internal temperature

Effective length of the arterial system

Abstract: The notions of effective length, effective reflection site, and resonance frequency of the arterial system stem from the start of the century. The effective length and effective reflection point describe a system analogous to the arterial tree by a uniform tube with one reflection point. The effective length and related effective reflection site may be obtained from the amplitudes of the various pressure harmonics measured at different locations along the aorta or from the input impedance as a function of frequency. We have studied the concept of effective length in hydraulic models of the systemic arterial tree. A uniform tube with both a frequency-independent load (resistive) and a frequency-dependent load was used. The effective length of a tube with a frequency-independent load is equal to the actual length. In the case of the frequency-dependent load (more resemblance with the arterial tree) the effective length depends on the applied method and is a function of frequency. Therefore, its application for quantitatively computing the stroke volume is doubtful.

A simulation model of extracellular glucose distribution in the human body.

Abstract: A model of the human circulation, devised for use in computer simulation studies of the dynamics of glucose-insulin interactions, is presented. The circulation is modeled as a branched circuit, with separate branches representing the major circulation paths in which distinctly different processes, important in glucose-insulin dynamics, occur. Individual processes are formulated directly, in more explicit detail than that possible in conventional “compartment” models, and are subject to experimental verification. Initial studies of circulatory distribution responses to glucose injections of various sizes have yielded quantitative estimates of the parameters governing glucose diffusion between the circulation and various major interstitial beds. This model provides solute-concentration response simulations in more realistic form and more comprehensive structure than has been reported in previous work on this subject. It is believed that such improvements will be useful in the investigation of rapid-response modes observed in insulin secretory responses to glucose.

Two models of glomerular filtration rate and renal blood flow in the rat.

Abstract: Two mathematical models of glomerular filtration and blood flow are derived. The first is based on principles of fluid and mass conservation in individual capillaries. The model explains why the filtration rate (GFR) is strongly dependent on local hydrostatic and protein oncotic pressures, and on plasma flow rate (GCPF), but only weakly dependent on exact numbers, lengths, radii, or filtration coefficient of glomerular capillaries. The model shows that much of the increased GFR in both isooncotic plasma loading and isotonic Ringer's loading is due to increased GCPF caused by diluting erythrocytes. The second model uses several approximations and reduces to a quadratic in afferent arteriolar blood flow. When arterial pressure, hematocrit, plasma protein concentration, and afferent and efferent arteriolar resistances are specified, the model predicts GFR, afferent arteriolar blood flow, and filtration fraction. Alternatively, if any two of these three variables are known, the model predicts segmental arteriolar resistances. The model indicates that GFR and blood flow regulation must be located in the afferent arteriole, despite the strong dependence of GFR on GCPF.

A permutation test for periodicities in short, noisy time series

Abstract: We developed a distribution-free, nonparametric statistical test (the permutation-rank test) for verifying the exiscence of significant peaks in power spectral ordinates calculated on noisy, short, time series. In this paper, we demonstrate the application of the test in the case of periodic series generated by the in numero perturbation of the amplitude of a cosine wave of known, single, constant frequency. The test was able to detect the underlying oscillation when it was amplitude-corrupted by noise generated by a standard uniform distribution, with a noise-to-signal ratio of 1 or less.

Dynamic vagal control of atrial-ventricular condition: theoretical and experimental studies.

Abstract: The dynamic effects of vagal stimulation on atrial-ventricular conduction were studied with paced canine hearts under β-adrenergic blockade. An analog/hybrid computer was used to precisely control the intensity and timing of a vagal stimulus burst given to the cervical vagosympathetic trunk, and to measure the atrial-ventricular response. On-line digital techniques were used to generate a composite “vagal effect curve” which is a dynamic representation of nerve-ending process dynamics. It was clearly seen that the magnitude of the AV conduction response is critically dependent upon the time in the cardiac cycle at which the vagal stimulus is given. A functionally isomorphic mathematical model, consisting of independent but coupled AV nodal and vagal-acetylcholine subsystems, was derived and used to simulate and predict the specific characteristics of a variety of vagal effect curves. These predictions were subsequently confirmed under experimental conditions. For example, the peak amplitude of an experimental vagal effect curve increases with increasing vagal stimulus intensity in the precise nonlinear fashion predicted by the model. It was further concluded that certain changes in the shape characteristics of vagal effect curves are more likely related to changes in the state of the AV node itself, rather than to changes in the processes which govern the release, diffusion, and inactivation of acetylcholine. It was also demonstrated for the AV node that the time course of a vagal effect curve need not exactly coincide with the computed time course of ACh concentration at the affected nodal cell membrane, as has been assumed previously for the SA node.

Dipole moment of the hearts of various species.

Abstract: Methods which have been used for finding the resultant dipole moment of the hearts of various species are described. These include both isolated perfused hearts and heartsin vivo. A table of numerical values is given together with equations relating heart weight, body weight and dipole moment. Very high correlations between these variables, when plotted on a log-log basis, were obtained.

Dynamic control of hepatic glucose metabolism: Studies by experiment and computer simulation.

Abstract: The rates of storage and release of carbohydrate by the liver are deterined by the plasma concentrations of several bloodborne signals; most important are the concentrations of glucose, and the hormones insulin and glucagon. To understand the complex control relationships of these three signals as they affect the liver, their individual dynamic influences have been determined experimentally, and they have been integrated by means of a computer simulation of the pathways of hepatic glycogen metabolism. The simulation studies have led to specific hypotheses about the biochemical effects of glucose and insulin on the liver. The simulation studies have also led to the conclusion that glucose exerts a rapid moment-to-moment influence on the rate of uptake of glucose by the liver. Insulin, however, by exerting a slower influence on the sensitivity of the liver to glucose, is very effective in “optimizing” the amount of glucogen with the liver stores during food intake. Thus, integrated experimental and simulation studies can lead to a view of a physiological regulating system which does not emerge from either approach used alone.

Application of control theory to endocrine regulation and control.

Abstract: This paper considers some aspects of the application of control theory to endocrine regulation and control. Consideration is given to both the structural and functional aspects of various control concepts and ideas in this context. For single-input, single-output feedback control structures, emphasis is placed on loop gain and its importance in establishing the functional capability of such structures. Examples are given of both functional and nonfunctional feedback structures proposed by endocrinologists. For multi-input, multi-output structures, emphasis is placed on the concept of input and output decoupling, and the possible applicability of these concepts to hormonal control system interrelationships is illustrated. Finally, the possible application of optimal control theory to endocrine regulation and control is illustrated by means of a naive and highly simplified example involving control of the thyroid gland by the pituitary gland, and several surprising and interesting implications are shown to be implicit in the resulting control structure.

On nature, man, and society: a basis for scientific modeling.

Abstract: A physical basis for the modeling of autonomous systems is presented. Namely the thesis is unfolded that irreversible thermodynamics is presently capable of describing nature, man, and society. Four fragments of the theme are presented. The first is a description of how thermodynamics orders all of nature. The second illustrates how the dynamics of fluid fields (mobile atomisms) is developed. The third begins the formulation of a social physics. The fourth provides a primitive notion why all autonomous systems are described by the same formal set of equations of state and change.

Critique of a large-scale organ system model: Guytonian cardiovascular model.

Abstract: This paper reviews Guyton's model, which is large not only in the number of its components but also in the time scale that it spans. The evolution of this model is explained in three stages. To explain short-term regulations of cardiac output Guyton started with a drastically simplified model of the entire cardiovascular system, which emphasized the role of blood volume and the vascular capacity. Guyton's group then directed its efforts toward the analysis of long-term regulation of arterial pressure. Two slow-acting mechanisms were added to the model: (1) the marked increase or decrease of urinary output with only slight increase or decrease in arterial pressure (the renal function curve in the Guytonian model), and (2) long-term vascular autoregulation. This second-stage model explained the transient dynamics and steady equilibrium in renal hypertension. The current version of Guyton's model incorporates a variety of additional endocrine and neural mechanisms that parametrically control the renal function curve. The Guytonian model is a unique venture in modern cardiovascular physiology because of its size and the investigators' incessant efforts to test it against the real system behaviors.

Optimization of materials for a user-formed mouthguard.

Abstract: A mouthguard that can be custom formed by the user at the time of need to achieve optimum fit and protection is required for sports and clinical applications. This study has evaluated two silicone-based polymer systems found sufficiently workable to be molded to the user's mouth. Compositions were optimized for setting time and mechanical properties by varying the proportions of catalyst, cross-linking agent, and filler. Mechanical tests showed the optimized silicones to have lower tensile and tear strengths and higher penetration and rebound than most present mouthguard materials. Detailed measurements of compressive stress-strain, coupled with a stress analysis of conditions in actual mouthguard use, indicate that the optimized silicone polymers possess more than adequate strength and durability for a user-formed mouthguard.

Estimation of parameters affecting rapid fluid transfers in the whole body. I. Isotonic infusions.

Abstract: The whole body capillary filtration coefficient (Lp), and tissue compliance (γi) were estimated using a mathematical model of transcapillary water and solute exchange and transient data from experiments. The model describes the dynamic exchanges of water and a generalized solute between the plasma and interstitial compartments as a result of isotonic infusions. An optimization procedure was used to estimate the values of the parameters which gave a “best fit” of the model to transient plasma volume data measured in nephrectomized dogs during and after isotonic infusions. The meanLp for all the experiments ranged from 0.114±0.015 (SEM) ml/min/mm Hg/kg to 0.135±0.019 (SEM) depending upon whether the γi was considered to be constant or to vary in a nonlinear manner. These values are similar to those measured by others in isolated hind limb experiments. The mean γi at normal tissue volume was found to range between 2 and 3 ml/mm Hg/kg. These values indicate that overall tissue compliance is low in agreement with the conclusion of Guyton and thus at variance with the results of others.

Modes of operation in continuous flow sedimentation of erythrocytes.

Abstract: The Kynch theory of hindered sedimentation is used to investigate all possible modes of operation of a continuous flow gravitational settling chamber. The investigation is then extended to centrifugal sedimentation. An application to blood cell separation is suggested.

Videodensitometric determination of left ventricular ejection and filling characteristics.

Abstract: Left ventricular ejection fraction and values proportional to mitral and aortic flow were measured throughout the cardiac cycle by videodensitometric analysis of left ventricular roentgen angiograms. The technique was used simultaneously with measurement of the dimensions of the ventricle to provide absolute values for comparison. Sensitivity of the technique was tested by the ability to detect the atrial contribution to mitral flow and left ventricular chamber volume. Roentgen videodensitometry has the advantages that much information can be extracted from videoangiograms in real-time (on-line, if need be), it requires relatively low concentration of contrast medium, and it is self-calibrating.

A comparative study of nonlinear equivalent cardiac generators.

Abstract: In a previous paper, the theoretical development of several advanced nonlinear models of equivalent cardiac generators was presented. The present communication compares the salient quantitative and qualitative aspects of these models in an idealized mathematical environment.

An intravascular test device for thromboresistant materials: analysis and preliminary experimental evaluation.

Abstract: The interaction of artificial materials with the process of thrombus formation in blood depends on geometric and fluid-mechanical factors as well as the proximity of even slightly injured tissue. A test device that takes account of these factors and is suitable for intravascular implantation is described. The device effects a division of total flow between a tube oriented on the vessel axis, whose diameter is less than that of the vessel, and the annular space between the tube and vessel. Dimensions are chosen to effect thrombogenesis preferentially within the tube. The division of flow is calculated as a function of dimensional ratios and Reynolds number. Other aspects of the fluid dynamical performance of the device are discussed. Results of experimental evaluations in an extracorporeal shunt are reported; they show preferential deposition where expected, small variations among similar experiments, and good ability to distinguish among different materials.

A simulation study of transient changes in splanchnic and peripheral blood flows in the dog after a volume load.

Abstract: Using a two-compartment model of the systemic circulation the responses of dogs subjected to small volume loads were simulated on a digital computer under conditions where cardiac output (Q) was held constant. A 200 ml volume load produced a rapid increase in vena caval pressure (Pvc) during infusion, but this slowly decreased to a new steady state. The transient change in Pvc was the result of an intravascular redistribution of blood volume between parallel vascular compartments of unequal time constants for venous drainage. Apparent compliance, calculated as the ratio of the volume added to the change in Pve, increased with time as Pro decreased. Since the compliance parameters were held constant throughout the entire simulation, the change in apparent compliance reflects the intravascular redistribution of blood volume and bears no relation to the elastic properties of the system. Similar changes in Pve at constant Q have been observed in animal experiments. When the results of these animal studies were interpreted using a model with a single-flow channel the data suggested an increase in compliance or fluid loss from the capillaries. The simulation of the two-compartment model suggests that such animal data may be explicable in terms of an intravascular redistribution of blood volume between vascular compartments of unequal venous time constants.

In vivo and in vitro comparative studies of animal articular surfaces.

Abstract: The contours in the articular surfaces of rabbit and canine knee joints were measuredin vivo andin vitro using the scanning electron microscope (SEM), replication, and light-microscopy techniques. Using the light microscope, patterns of highlights of the order 10 μm were observed when the living joint-surfaces were exposed. Replicas were made of these surface contours using Xantopren, a light-bodied dental silicone impression-material. More than 50% of the replicas were discarded because of defects. In the SEM, a crazing phenomenom was sometimes evident on the replicated surfaces which may have been attributable to distortion of the silicone medium, possiblyin vacuo.

A comment on models of ion transport across cell membranes.

Abstract: One usually thinks of ionic flow across membranes as controlled by modulation of the energies needed by an ion to get into a membrane. Examination of these energies shows that they are not only large enough to perturb the ionic distribution but also sufficient to deform a thin membrane. The deformability of a cell membrane may then be related to its control of ionic current.

Control processes in development: Pattern formation in chick limb morphogenesis.

Abstract: Pattern formation is the process in development whereby cells acquire different states and can thus differentiate to form well-defined patterns of cell types. The development of the pattern of cartilage differentiation in the chick wing is chosen as a model and it is suggested that it can be viewed in terms of positional information. This suggests that cells are assigned positional values as in a coordinate system and this is interpreted by appropriate cytodifferentiation. There is reason to believe that the program for generating complex patterns may be simple.

On the description of physiological systems: Epistemological considerations

Abstract: Various points of view concerning what is required for a description to be adequate have appeard in the history of physiology since mathematics began to be used for that description. Three main themes are described in the present paper, and the criteria underlying them are examined. Certain additional criteria are considered for judging among the descriptive themes. The proposition is advanced that questions of heuristic value and questions of relevance to major current themes in the discipline tend to dominate consideration. Judged by these criteria, the suggestion is made that an instrumentalist position may be the most satis-factory epistemological one, and that the application to physiology of finite level models may represent a successful example of the application of this position to physiological description.

The mechanics of dual-control above-elbow prostheses.

Abstract: A computer model of a cable-operated dual-control above-elbow prosthesis is presented and used to show the effect of certain geometric parameters on the force and excursion characteristics of the limb. The resulting data can be used to fabricate a prosthesis with operating characteristics which match an individual amputee's capabilities.

A mathematical model of the sympathetic-heart period system in the cat.

Abstract: The dynamic behavior of changes in heart period in response to changes in frequency of supramaximal electrical stimulation of either pre- or postganglionic cardiac sympathetic nerves in five chloralosed cats pretreated with methyl atropine was investigated using time domain techniques. The typical response to step changes in frequency of stimulation (range 1–10 Hz) was found to be a decrease in heart period which reached a steady value after a short delay and was followed, after the stimulus was removed, by a slower return to prestimulus values. No significant difference was found between the responses to pre- and postganglionic stimulation although the strength of the stimuli required to achieve the same response was greater for postganglionic stimulation. Both the observed dynamic and steadystate responses were described to a good approximation by a first-order nonlinear system. The asymmetry in the response was accounted for by including in the model a second-order chemical reaction. The observed delay was accounted for by including a pure time delay. These results suggest that models proposed by previous investigators were unnecessarily complex.

A calibration system for a Holter pump for hyperalimentation infusion.

Abstract: Pumps are being used for precise, constant fluid delivery. Many pumps of reasonable cost require tedious calibration by serial changing of dial-settings, observing with a stopwatch the time for delivery of a certain volume of fluid, and then calculating the rate for each setting.