WO1992004860A1 - Systeme de simulation de reponse physiologique d'un organisme vivant - Google Patents

Systeme de simulation de reponse physiologique d'un organisme vivant Download PDF

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Publication number
WO1992004860A1
WO1992004860A1 PCT/US1991/005585 US9105585W WO9204860A1 WO 1992004860 A1 WO1992004860 A1 WO 1992004860A1 US 9105585 W US9105585 W US 9105585W WO 9204860 A1 WO9204860 A1 WO 9204860A1
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WIPO (PCT)
Prior art keywords
module
model
user
simulation
subsystems
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PCT/US1991/005585
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English (en)
Inventor
Charles G. Gray
Anthony V. Sebald
Michael Parti
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Medsim, Inc.
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Application filed by Medsim, Inc. filed Critical Medsim, Inc.
Publication of WO1992004860A1 publication Critical patent/WO1992004860A1/fr

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    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
    • G09B23/28—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B19/00—Teaching not covered by other main groups of this subclass
    • G09B19/16—Control of vehicles or other craft
    • G09B19/165—Control of aircraft
    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B5/00—Electrically-operated educational appliances
    • G09B5/08—Electrically-operated educational appliances providing for individual presentation of information to a plurality of student stations
    • G09B5/14—Electrically-operated educational appliances providing for individual presentation of information to a plurality of student stations with provision for individual teacher-student communication
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/50—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H15/00—ICT specially adapted for medical reports, e.g. generation or transmission thereof

Definitions

  • the present invention relates to a simulation system, and a method of using it.
  • the invention more particularly relates to a computer generated physiological modeling system for modeling physiological parameters relating to living organisms.
  • Background Art Simulation by modeling, presents many advantages for teaching and training of students and healthcare professionals in the study of normal and abnormal physiology in humans and other organisms. These advantages are especially valuable in teaching and training in the areas of anesthesia, physiology and other biological sciences.
  • the use of animals for research and teaching has been expensive, time consuming and inefficient.
  • only small numbers of students, at any given time can benefit from experimental work on animals.
  • only small groups of students can learn directly from experimental animal techniques.
  • the physiological status of one animal will sometimes differ from that of another and, as a result, the physiological data derived from experiments on various animals, may not be reliable, in some cases.
  • Modeling systems are known in other disciplines.
  • the cockpit simulator that is utilized in training airline pilots, has been developed to enable the pilot on the ground to learn how a particular aircraft will behave in flight. This approach, is clearly a far less expensive, and less dangerous teaching technique than it would be, if the pilot was limited to learning how to fly a very complex aircraft, only during flight.
  • anesthesia simulator-recorder has been developed by Janssen Pharmaceutica, which utilizes a personal computer to simulate responses under anesthesia.
  • the system incorporates an integrated mathematical model of cardiovascular and respiratory physiology and pharmacology in an attempt to predict a simulated patient's minute-to-minute responses to the administration of fluid and drugs, and control of the airway and ventilation in the patient.
  • the principal object of the present invention is to. provide a new and improved simulation system and method of using it.
  • a simulation system includes a computer, and provides a mathematical model of the entity under investigation, and includes input apparatus for supplying desired variable change information to the mathematical model.
  • the system generates model simulation information as modified by the variable change information, and controls the changes of the model simulation information in correspondence with real time, independently of the computer used.
  • the system includes toggling apparatus for activating and deactivating reflectively desired sub- systems of the mathematical model, and is arranged to adjust selectively the number of subsystems of the mathematical model.
  • the system allows the user to customerize the information displayed about the mathematical model while the model is running.
  • FIG. 1 is a diagrammatic view of the system of the present invention
  • FIG. 2 is a system block diagram of the main system computer program modules of the computer program forming a part of the system of FIG. 1;
  • FIGS. 3, 4 and 5 are diagrams of the computer program of FIG. 2, and are useful in understanding the present invention;
  • FIG. 6 is a flow chart of the overall system operation; and FIG. 7 is a flow chart of the operation of the connection module with the main system program.
  • the system 10 includes a set of mathematical expressions designed to simulate pulsatile cardiovascular function.
  • the form of the model allows the transport of respiratory gases (0 2 , C0 2 ) , and drugs to the various organ compartments via the blood.
  • the drugs are stored based on the specific physical characteristics of the drug and the physiological characteristics of the organ.
  • Pharmacological actions are based on the amount(s) of drug(s) present in certain organ compartments (e.g., level of anesthesia is determined by the amount of halothane in the Brain Grey Matter tissue compartment) .
  • the system 10 utilizes multiple and transport modeling strategies and incorporates augmented physiological detail and greatly enhanced tabular and graphical analytical tools.
  • the system 10 generally comprises a conventional personal computer 12 having a central processing unit 13, a pair of storage units 14 and 15 for storing database information and system software programs, respectively, a graphic interface module 16 for generating video signals indicative of character and graphic data, and a video monitor 17 for displaying character and graphic data in response to the video signals.
  • the central processing unit 13 also includes an internal memory (not shown) .
  • a cable 23A interconnects the processor unit 13 with an input keyboard 18 for entering data and commands in the internal memory of the central processing unit 13.
  • a cable 21 interconnects the graphic interface module 16 with the video monitor 17.
  • the personal computer 12 is a conventional personal computer, such as the IBM compatible ALR 80386/33MHZ Computer with a 640K Bytes of RAM, a 80387/33 math coprocessor, a Super VGA graphic board, and a VGA high resolution display.
  • IBM compatible ALR 80386/33MHZ Computer with a 640K Bytes of RAM, a 80387/33 math coprocessor, a Super VGA graphic board, and a VGA high resolution display.
  • the user-friendly model architecture enables the user to interact with and analyze the model function.
  • Command entries from the user are menu oriented and accomplished via the keyboard 18 or a mouse (not shown) .
  • the computer system 10 of the present invention is used to simulate the physiological functions and pharmacological actions of drugs in human or animal systems.
  • the system 10 is designed to enable a broad range of applications. The intent is to use the system in lieu of a living human or animal body for teaching or research applications. A variety of medical professionals can be trained on the simulator without the potential for endangering human or wasting animal lives.
  • This type of simulation serves to provide more uniform and broader training experiences as well as provide a means for performing hypothesis testing and experimental design in order to streamline live experimental procedures.
  • One can also use the system to train students in such broad areas as basic physiology and such specialized areas as pulmonary function and blood gases.
  • the overall system is composed of two main software modules, a mathematical or numerical solution model of the body module 31 and a user interface module 33.
  • the numerical solution module 31 solves the equations governing the interactions among the various bodily subsystem components.
  • the user interface module 33 provides a means through which the user interacts with the mathematical module by performing actions on the simulated system for, example, drug administration, while also providing a means for displaying results of the mathematical module's calculations. Such displayed results, for example, could be the blood pressure in the aorta and drug concentration in the brain.
  • OPERATION the first phase of the system 10 comprises a basic fact-gathering process performed under the control of a computer program executed by the central processing unit 13.
  • the information is gathered in response to computer generated images, referred to as screens, displayed on the video monitor 17.
  • the computer program for causing the generation of the screens is preferably stored on a floppy disk (not shown) which is used to store the basic data.
  • the basic data regarding a subject is stored on the same disk or in the internal memory of the central processing unit 13.
  • basic information can be gathered at a remote location and sent to the central processing unit 13 by various other techniques, such as sending by electronic messages via modems and telephone systems (not shown) .
  • the basic information is a subject profile report including the name and age of the subject, weight, height, and other pertinent information that will enable the central processing unit 13 to prepare a profile report regarding the subject.
  • a message is sent by the central processing unit 13 for display on the monitor requesting the user to input appropriate variable parameters that may or may not affect the physiological responses of the subject.
  • y arteries left and right in parallel
  • pulmonary capillaries left and right
  • pulmonary veins left and right
  • pulmonary veins left and right
  • left heart left ventricle
  • aorta for the proximal organ distribution
  • distal (leg) arteries for the distal organ distribution
  • grey matter of the brain 10) white matter of the brain; 11) myocardium (heart muscle) ; 12) muscle and skin (combined) ; 13) splanchnic organs (stomach, intestines, pancreas, spleen, liver) ; 14) kidney; and 15) other slowly perfused organs (fat, bone, connective tissue, etc.).
  • the Activation Communication Module 55 communicates the current user selection to the Numerical Solution Module 31 in the overall system defined above. Each submodule in that Numerical Module 31 regularly polls a data structure generated by module 55 in order to decide what is the currently appropriate procedure.
  • the student may decide to turn off all of the regulatory mechanisms and then turn them on one at a time, with a fixed drug admission protocol. Alternatively, the student may wish to let the system stabilize with all regulation loops intact and then turn them off one at a time to see the effect of each. Of course, it may be necessary to administer a vasodilator or a vasoconstrictor in order to push the mean arterial pressure off the nominal value and then observe the effects of turning on and off the regulatory mechanisms.
  • the module 50 includes two subroutine modules, an activation/deactivation selection module 53 and an activation communication module 55.
  • the online activation/deactivation of systems and mechanism module 50 allows a user to determine and/or demonstrate significance and actions of the many physiological functions and control mechanisms employed in the model. Module 50 is useful for both analyses, understanding disease processes, and teaching. Example of Use
  • a student in anesthesiology wishes to learn how to put a patient to sleep.
  • the student would select the patient to be anesthetized by setting a variety of patient characteristics within the user interface module. For example, the student would choose the patient's sex, weight, percent body fat, age, and existing preconditions. For example,the patient may have emphysema, coronary artery disease etc.
  • the student would choose the procedure to be performed on the patient after anesthetization (eg coronary artery bypass graft) .
  • the student would then specify the drugs to be used in the anesthetization procedure. For example, the student may wish to learn how to use thiopental and halothane.
  • the student would then call up the subject display module which provides a series of life sign monitors, a ventilator and a choice of intravenous drips and airways.
  • the information displayed comes directly from the computed values of the variables contained in the model.
  • the patient appearance provides some information about his condition (i.e., skin color: such as cyconotic from hypoxia, eyes-open or closed, twitch response) .
  • User inputs i.e., I-V drugs, respiratory gases
  • mouse 'point- and-push' selections or keyboard entries.
  • the user interface module 33 enables the user to observe the state of the model at any time and to effect changes in the simulation by performing simulated actions such as injecting a drug.
  • This interface is accomplished by a series of graphic displays which represent either a physically based depiction of what the model is simulating, a set of tables and graphs which display the numerical variable computed by the model, and displays which allow the user to make changes to the characteristics of the model or input data.
  • the display interface is segmented into a simulated operation room (OR) cartoon display, and an analysis framework of tables and graphs.
  • OR simulated operation room
  • the simulated O-R includes:
  • DIGITAL MONITORS Spirometer, FI0 2 , Pulse Oximeter, End-tidal C0 2 , Mean Arterial Pressure, Mean CVP, Systolic/Diastolic pressurees and Heart Rate
  • the analytical displays provide a very useful and attractive tabular and graphic display of the values of most of the variables contained in the model. Any four of these variables can be plotted against time (over one beat or breath) simultaneously. They can also be plotted against one another (e.g., flow vs. pressure).
  • CIRCULATORY VARIABLES displayed for each circulatory compartment include:
  • RESPIRATORY VARIABLES displayed for the respiratory system include: Air volumes
  • FIG. 1 there is shown set of a flowcharts of the computer software for the system 10 as applied to a typical physiological model, such as a physiological model for teaching students how a body functions and reacts to certain stimuli or anesthetics.
  • the computer system 10 is started with a presentation of software stored on a diskette (not shown) using conventional program loading techniques.
  • operation commences at box 100.
  • operation starts in box 100 and commences to instruction box 101 where the program causes a title and protection notice to be displayed on the video monitor 17.
  • the user When the user is finished viewing the title and legal protection notice, which includes a message to press a return key on the keyboard 18 to start the program, the user presses the return key and the program advances to box 103.
  • the user is prompted to select either the instructor configuration or the training configuration and then press the return key.
  • the program advances to decision box 105. If the user selected the instructor configuration, the program goes to instruction box 107 and causes a message to be displayed on the monitor 17 instructing the user to insert an instructor program diskette in the disk memory unit 14 and press the return key. If the training configuration was selected, the program advances to instruction 120 and causes a message to be displayed on the monitor 17 instructing the user to insert a student diskette in the disk memory unit 14 and press the return key.
  • the program advances to instruction 109 which causes a menu to be displayed.
  • the program then advances to instruction 110 and prompts the user to select a module.
  • the module is then executed and the results displayed.
  • the program then advances to decision box 113 and prompts the user to indicate whether the sessions has ended. If the session has not ended, the program advances to instruction 115 prompting the user to make another module selection. The program then returns to decision box 113 and continues as previously described. If the session is to be ended, the program advances from box 113 to box 117 which ends the session.
  • the program advances to instruction 122 which causes a menu to be displayed.
  • the program then advances to instruction box 124 and prompts the user to select a module.
  • the module is then executed and the results displayed for the student.
  • the program then advances to decision box 126 and prompts the user to indicate whether the session is ended. If not ended, the program advances to instruction 128 prompting the student to make another module selection. The program then returns to decision box 126 and continues as previously described. If the session is to end, the program advances from box 126 to box 129 which ends the session.
  • the user would select the patient to be anesthetized by setting a variety of patient characteristics within the user interface module. For example, the user would choose the patients, sex weight, percent body fat, age, and existing preconditions. For example, the patent may have emphysema, coronary artery disease etc. Finally, the user would choose the procedure to be performed on the patient after anesthetization (e.g., coronary artery bypass graft). Once the patient has been specified, the user would then specify the drugs to be used in the anesthetization procedure.
  • anesthetization e.g., coronary artery bypass graft
  • the user may wish to learn how to use thiopental and halothane.
  • the user will then call up the patient display module which provides a series of life sign monitors, a ventilator and a choice of IV solutions and airways. From this screen, the user would then perform the entire anesthization including drug introduction, intubation and ventilation.
  • the mathematical module would be accepting user interventions, continually computing all appropriate variable values and delivering results to the screen according to the instructions of the user.
  • users may be particularly interested in pulmonary function and only desire a summary view of the rest of the body.
  • the user may be a novice anesthesia student only interested in overall summary variables like end tidal C02, percent 02 saturation etc.
  • the user may want to look at long term plots of a variety of variables like acid base variables in the muscles, fat and brain.
  • the solution proposed in this patent application is to provide an interface module structured in such a way that the user can easily configure the display at any time in any desired format with display of only those variables of interest at the time. Furthermore, formats for the screens of interest can be stored on disk for retrieval by name. Each user would then have at their disposal a collection of previously defined displays for use at any time in their particular application interest areas.
  • a second issue is that of traffic control in displays.
  • this speed control must be instantly available to the user and, at a minimum, must include the ability to freeze the simulation in order to carefully study the tabular data on various screens and the ability to step through the simulation one step at a time.
  • the module in this patent application requires a single keystroke or mouse click to freeze or to enter step action mode. In the latter, the simulation is advanced one step each time a key is depressed or the mouse is clicked.
  • the numerical module 31 is of the general class of models called a physiological pharmacokinetic model, combined with functions of transport of multiple components.
  • the transported components would include: 1) physiological factors, such as hemoglobin in the blood or air (oxygen + carbon dioxide +nitrogen) through air passages into the lungs; and 2) effector agents, such as drugs being carried by the blood to the various organs where stored or where certain drug effects occur.
  • the module 31 is subdivided into subsystem components arranged in a combination of series, parallel, and tangential elements which mimic the actual organization in the real physiological system. These components of this compartmental model are shared by all mammalian systems with some species and individual variations.
  • the cardiovascular system is the "heart" of the model. It allows the distribution of blood and blood borne agents to the organs of the body where many of the various simulated actions occur.
  • the cardiovascular system is driven by a pulsetide heart. Since this is a closed system, the description of the components will begin at an arbitrary point, the venous side of the circulation.
  • the vascular compartments are 1) vena cava; (in series with) 2) right heart (right ventricle) ; (in series with) 3) the pulmonarete the circuit.
  • each vascular compartment has a defined capacitance which determines the pressure in that compartment as a function of the volume of blood instantaneously present in a compartment.
  • the pressure differentials between sequential or parallel compartments combined with the resistances to flow between compartments determines the magnitude and direction of blood flow just as in the real physiological system. Therefore each compartment maintains a dynamic balance of blood flow from the compartment(s) preceding it in the scheme and out to the compartment(s) following it in the circulatory scheme.
  • the blood carries its various fractions with this fluid flow around to the organs.
  • the fractions (or components) which can be carried or transported by the blood include red blood cells, electrolytes and other chemical components (ie. sodium, potassium, chloride, bicarbonate, oxygen, carbon dioxide, proteins, and H + ) , hormones,and drugs.
  • red blood cells include red blood cells, electrolytes and other chemical components (ie. sodium, potassium, chloride, bicarbonate, oxygen, carbon dioxide, proteins, and H + ) , hormones,and drugs.
  • Some of the components of the blood can bind other substances with high affinity and increase the amount which can be carried in the blood. Examples of these binding substances included in this model are hemoglobin and plasma proteins. Hemoglobin binds oxygen, carbon dioxide,and H + ion, whereas plasma proteins can bind drugs to varying degrees, depending on the specific drug.
  • the binding affinity of hemoglobin and plasma proteins can be affected by computed physiological factors, such as lood pH, the presence of modifiers to
  • the lungs are subdivided into the left and right lungs.
  • the sequential compartments, beginning with the mouth are: 1) mouth and trachea; (in series with) 2) bronchi (left and right, in parallel) ; (in series with) 3) bronchioles and small airways (left and right in parallel) ; (in series with) 4) alveoli (left and right in parallel) .
  • the alveoli are functionally and numerically tangential to the circulatory system at the point of the pulmonary capillaries (left and right) .
  • the air in the lungs contains major amounts of nitrogen, oxygen, and carbon dioxide.
  • This air can also carry relatively small amounts of other gas vapors, such as inhaled anesthetics, or other gases, such as xenon.
  • the sequential airway compartments interact with each other as the air passes through (alternating bidirectional flow) causing mixing.
  • the airway is either open to the outside world at the mouth (open system) or it can be semi-closed by the imposition of a ventilator which can force the air flow.
  • the air is only tangentially connected to the circulation through the alveoli/pulmonary capillaries (left and right) , which is where all of the simulated exchange processes occur.
  • a tangential component is one which is connected to the periphery of the circulatory system, but is not actually within the stream of flow.
  • Examples of tangential components are the actual organ compartments (separate from the blood compartment which flows through the organ) and the air in the alveoli of the lungs (discussed above) . These tangential sites represent the simulated capillaries of the body where the circulatory/end organ interactions occur.
  • the organs can represent tangential sites of closed system storage of components, such as drugs, or semi-open system effects of metabolism, such as drug deactivation by the liver or the respiratory conversion of oxygen to carbon dioxide by the cells comprising the organs.
  • the organ subsystems have some common features. Transfers of components carried by the blood are determined by a concentration gradient from the blood to the tangential organ compartments. Oxygen is taken up and carbon dioxide released by the organ as a function of the metabolic requirements of the tissue and the oxygen availability in the blood. Electrolytes may be exchanged with the blood dependent on changes in conditions in the blood and organs. Drugs which are circulated by the blood may be stored in the organ tissue compartment or released from the tissue to the blood, if the reverse gradient exists. The rate of storage in (or release from) the tissues depends on any limitations to passage through membranes. The maximal amount of drug which can be stored is dependent on the relative solubilities of the drug in water and fat (or lipid) .
  • a measure of this relative solubility is the blood/tissue partition coefficient.
  • the amount of relatively fat soluble drugs which can be stored in the organ tissues is more dependent on the amount of fat in the tissue.
  • the amount of relatively water soluble drugs which can be stored in the organ tissues is more dependent on tissue water content.
  • the amount of drug delivered to the tissue, and therefore available for storage in the tissue is dependent on the blood flow to the compartment and the amount or concentration of the drug contained in that blood.
  • Each organ compartment has different drug storage characteristics (different specific values for these parameters) determined by measurements in laboratory experiments.
  • the combination of drug distribution by the blood, uptake by the organs, and elimination by single or combinations of mechanisms describes the pharmacokinetic behavior of a drug.
  • the effects of the drugs on the various components of the system are determined by dose- response relationships for specific sites of action, such as the blood or brain tissue.
  • dose- response relationships for specific sites of action, such as the blood or brain tissue.
  • the combination of the physical properties of pharmacokinetics with the dose-response relationships yields the overall pharmacodynamic characterization of a drug.
  • a parallel and separate nervous system which operates much the same way as a real nervous system.
  • This system senses the state or condition of certain parameters and makes a change in the system.
  • An example is the mean systolic pressure in the aorta. If the pressure is lower than a predetermined "setpoint", the system uses an algorithm to increase the heart rate. If the difference cannot be maintained by minor adjustments in heart rate, there may also be increases in resistance to blood flow into some of the organ systems. There may also be a change (decrease) in compliance of some components of the venous system.
  • These various responses to altered blood pressure are implemented by feedback control loops, are non-linear, and unevenly applied to the various organ subsystems.
  • feedback control sensors include arterial pressure, venous pressure, arterial oxygen content, arterial pH, and arterial carbon dioxide content. These sensors feed information to an integrated control algorithm for each reflex which controls parameters such as respiratory rate, tidal volume, heart rate, stroke volume, and venous compliance.
  • the computations which comprise the numerical model are performed using iterative and closed form solution techniques to solve a system of differential and algebraic equations.
  • the state of the model is recomputed at regular time intervals.
  • the state of the system is defined by a computed assignment of values to every variable within the system.
  • the overall design of the system allows the user to turn on or off many of the physiological components of the system. Examples of mechanisms which can be on-off manipulated include gas exchange between the alveoli and blood, organ metabolism ,blood pressure control loops, transport of drugs, actions of drugs, etc. These manipulations can be accomplished by a special screen displayed by a keystroke as an easy to use part of the user interface. Many other components of the numerical system which are displayed by the user interface can also control features or parameters of the model, such as physical characteristics of a drug, the compliance of a vascular compartment, or resistance to blood flow into an organ.
  • a variety of disease conditions can also be simulated. Examples of these disease conditions would be heart failure, emphysema, or anemia.
  • the separation of components, such as red blood cells from plasma, also allows an adequate means of simulating a wide variety of treatment modalities in addition to drugs. Examples of these variations in treatments would be the administration of blood components, such as packed red blood cells or whole blood or normal saline solution, or alteration of inspired gas mixtures.
  • system 10 in the preferred embodiment includes only those features described, a variety of enhancements of the model would be known by one skilled in the art.
  • enhancements include an embellishment of physiological function; an increase in the variety of patient selection; additional drugs selections of various types; and enlarged I-V fluid selection; an improved analytical capabilities.
  • the user interface module 33 allows a user to individualize, the output displays that will be displayed on the monitor 17.
  • different purposes and user bias can require variation in data organization and display to better understand or demonstrate the many detailed characteristics of the model simulation.
  • the user interface module includes two subroutine modules, the display selection subroutine module 41 and the display activation subroutine module 43. These form part of the user interface module 33 specified above.
  • the user interface module also includes a set of submodules including a mouse controller module 42, a display control module 44, a screen object drivers module 46 and a screen format data base module 48. Each of these modules will be described hereinafter in greater detail.
  • the user interface module 33 enables the user to have maximum freedom in choosing (and/or change) the data being displayed. There is quite a bit of complexity involved in these choices. One must choose what data (if any) to display in tabular form on the screen. A user must choose what data are to be graphed and in what format. For example, a user could choose pie charts for distributional information, bar charts, time plots or x-y plots. The latter are plots in which both the horizontal and vertical axes correspond to non-time variables (e.g left ventricular pressure vs left ventricular volume) . Typically, a user may wish the time and X-Y plots to have more than one curve (e.g. all heart pressures simultaneously vs time.)
  • the Display Selection subroutine 44 includes a Display Repertoire subroutine module 45, and a User Choice 1 data function subroutine module 47.
  • the Display Repertoire, subroutine module 45 includes the building blocks for the various display objects in the display interface.
  • These blocks comprise both data and subroutines necessary for the actual on-screen display generation.
  • data associated with the display object itself e.g titles, size of window, colors etc
  • actual data being displayed e.g. pressures, flows, concentrations
  • the display objects in the display repertoire subroutine module 45 include routines for tables, pie charts, bar charts, time plots and x-y plots, all of which are capable of displaying many variables simultaneously.
  • the user choice identification subroutine module 45 contains the routines for providing an efficient means for the user to choose data to be displayed along with the type of display desired.
  • one of the hard-wired display screens is a kind of cartoon of the actual subject environment including a depiction of the subject and a variety of appropriate equipment, e.g. monitors and perhaps a ventilator. The user is permitted to select variables for display by pointing to the appropriate place on the cartoon and following a simple selection procedure.
  • the display activation subroutine module 43 obtains data from the Numerical Solution Module 31 and combines it with selections made by the user choice identification module 47 and actually puts the chosen displayed information on the screen using routines and information from the display repertoire subroutine module 45.
  • the user interface module 33 permits a user to monitor the experiment described in the example discussed below in the section on real time activation/deactivation.
  • the user is a student trying to understand the control of mean arterial pressure in the body.
  • this pressure is affected by the bar or receptor loops, the renin-angiotensin loop some drugs hypovolemia and systemic anomalies) .
  • the student is interested in the effects of baroreceptors, renin-angiotensin and a single vasodilator and a single vasoconstrictor. There are very many combinations of these effects which could be observed.
  • the student may decide to turn off all of the regulatory mechanisms and then turn them on one at a time, with a fixed drug admission protocol.
  • the student may wish to let the system stabilize with all regulation loops intact and then turn them off one at a time to see the effect of each.
  • it may be necessary to administer a vasodilator or a vasoconstrictor in order to push the mean arterial pressure off the nominal value and then observe the effects of turning on and off the regulatory mechanisms.
  • the student may wish to concentrate on cardiovascular variables such as pressures and flows in the artery and venous compartments (aorta, peripheral arteries, and all organ compartments) .
  • cardiovascular variables such as pressures and flows in the artery and venous compartments (aorta, peripheral arteries, and all organ compartments) .
  • the user may choose to display drug concentrations in the blood or in the brain in order to note the effect of drugs on the pressure.
  • the user would also probably choose to monitor mean arterial pressure, systemic vascular resistance, total blood volume and perhaps cardiac output, heart rate and stroke volume.
  • the user selects the kind of display to be used.
  • Some of the variables e.g. mean arterial pressure, systemic vascular resistance and heart rate
  • the user may wish long range plots of these variables as well as the drug concentrations.
  • Short term (beat to beat) plots may be appropriate for the aortic and venous compartment pressures.
  • An alternate mode available to the user is to simply make a table including all of the important data and then use the mouse to select which variables are to be included in which plots.
  • the mouse controller module 42 handles all mouse functions.
  • the display control module 44 performs traffic control to interleave requests for action from the user and determine the need to update information displayed on the screen.
  • the screen object drivers module 46 contains all drivers for objects to be displayed on the screen.
  • the screen format data base module 48 contains all data pertinent to objects to be drawn on the screen. It also contains information relevant to the user's current preferences regarding what data is currently of interest and should be displayed.
  • the numerical solution module 31 includes seven submodules: a timing and control module 32, a circulation module 34, an agent effect module 35, a hardware module 36, an agent transport module 37, a lung module 38 and a trunk to display module 39. Each of these submodules will be described hereinafter in greater detail.
  • the timing and control module 32 is responsible for traffic control of the entire system. It determines when it is appropriate to perform each computation made by the simulation.
  • the circulation module 34 computes blood circulation around the system. It updates all of the relevant pressures, flows and quantities.
  • the agent effect module 35 computes the effect on all systems of all agents present in the body being simulated.
  • the hardware module 36 simulates any required hardware attached to the body being simulated. For example, if the simulation pertains to anesthesia, the hardware module would contain a ventilator.
  • the agent transport module 37 computes the flow of all agents contained in the blood. This includes standard elements such as 0 2 and C0 2 as well as any injected or inhaled agents.
  • the lung module 38 computes the flow of all gases into and out of the lungs.
  • the trunk to display module 39 is the channel between the numerical solution module and the interface module. This is a bidirectional channel.
  • the module under discussion in this section is designed to make such switching very simple to accomplish.
  • the activation/deactivation selection subroutine module 53 gives the user the ability to select which modes are to be active for the next period of the simulation. It is assumed that a given set of choices will be in force until the user decides to change them.
  • the activation/deactivation selection module 53 contains a set of all available options which can be made active or inactive.
  • connection module 72 functions to keep track of the connections among all the components of the model. As we increase or decrease the number of body elements that are modeled, the connection module allows the system to automatically to keep track of the details of regularly occurring mechanisms for which the model must account.
  • connection module 72 greatly decreases the cost (time) required for improving the model (increasing its complexity) or for simplifying the model to customize it for less sophisticated markets. The importance of the scheme may be seen if we consider the alternatives. 1) The Alternatives:
  • connection module provides a central place for keeping track of all connections and sequences in the model so that decisions about the sequences of all types of events in the model can be made conveniently with minimal risk of introducing errors.
  • connection module 72 includes a main program 73 that must make decisions about where execution is to take place.
  • the main program 73 calls the connection module 72 which sets up an initial model connection array 74 which is passed back to the main program 73.
  • the main program 73 uses a second model connection array 75 to decide which model component to execute next.
  • model component A 76 might represent the blood flow, pressure and volume calculations for the vena cava
  • model component B 77 might represent the corresponding calculations for the heart
  • model component C 78 might represent the corresponding calculations for the aorta. The model must decide which to execute next.
  • connection module takes account of the fact that the modules would have to be executed in a different order.
  • the main module may detect that the current machine is operating too slowly for the fully detailed model to operate in real time. In this case, a message 80 can be sent to the connection module to disconnect some of the components of the module to speed the model's execution.

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Abstract

Un système de simulation comprend un ordinateur (12), produit un modèle mathématique devant être étudié, et comprend un appareil d'introduction de données pour fournir des informations relatives à des changements variables souhaités au modèle mathématique. Le système produit des informations se rapportant à la simulation du modèle en fonction des modifications apportées par les informations de changements variables, et commande les changements des informations se rapportant à la simulation du modèle en correspondance avec le temps réel, indépendamment de l'ordinateur utilisé. Le système comprend un appareil de bascule (18) servant à activer et à désactiver respectivement des sous-systèmes souhatiés du modèle mathématique, et est agencé pour régler de manière sélective le nombre de sous-systèmes du modèle mathématique.
PCT/US1991/005585 1990-09-21 1991-08-06 Systeme de simulation de reponse physiologique d'un organisme vivant WO1992004860A1 (fr)

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Cited By (7)

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WO1997044752A1 (fr) * 1996-05-22 1997-11-27 Medical Science Systems, Inc. Systeme de saisie et d'analyse de donnees relatives a des processus pharmaceutiques
EP0992915A1 (fr) * 1993-08-25 2000-04-12 Casio Computer Co., Ltd. Appareil d'affichage d'images
US6108635A (en) * 1996-05-22 2000-08-22 Interleukin Genetics, Inc. Integrated disease information system
WO2001098935A2 (fr) * 2000-06-22 2001-12-27 Physiome Sciences, Inc. Systeme informatique permettant la modelisation de l'expression d'une proteine dans un organe
WO2002054370A1 (fr) * 2001-01-08 2002-07-11 Simsurgery As Procede et systeme de simulation d'un fil dans des simulations graphiques informatiques
WO2001085230A3 (fr) * 2000-05-08 2003-01-16 Image Guided Neurologics Inc Procede et appareil permettant de cibler une distribution de materiau a un tissu
EP2255843A1 (fr) * 2009-05-29 2010-12-01 FluiDA Respi Procédé pour déterminer les traitements en utilisant des modèles de poumon spécifiques aux patients et procédés informatiques

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US4437469A (en) * 1980-09-29 1984-03-20 Rush-Presbyterian-St. Luke's Medical Center System for determining characteristics of blood flow
US4665285A (en) * 1984-10-04 1987-05-12 Nifco, Inc. Automobile door switch bumper
US4676253A (en) * 1985-07-18 1987-06-30 Doll Medical Research, Inc. Method and apparatus for noninvasive determination of cardiac output
US4679144A (en) * 1984-08-21 1987-07-07 Q-Med, Inc. Cardiac signal real time monitor and method of analysis
US4736322A (en) * 1985-07-12 1988-04-05 Clifford Ralph D Cardiological simulator

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Publication number Priority date Publication date Assignee Title
US3736363A (en) * 1971-11-09 1973-05-29 Humetrics Corp Physiologic function simulator
US4437469A (en) * 1980-09-29 1984-03-20 Rush-Presbyterian-St. Luke's Medical Center System for determining characteristics of blood flow
US4679144A (en) * 1984-08-21 1987-07-07 Q-Med, Inc. Cardiac signal real time monitor and method of analysis
US4665285A (en) * 1984-10-04 1987-05-12 Nifco, Inc. Automobile door switch bumper
US4736322A (en) * 1985-07-12 1988-04-05 Clifford Ralph D Cardiological simulator
US4676253A (en) * 1985-07-18 1987-06-30 Doll Medical Research, Inc. Method and apparatus for noninvasive determination of cardiac output

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0992915A1 (fr) * 1993-08-25 2000-04-12 Casio Computer Co., Ltd. Appareil d'affichage d'images
US6633295B1 (en) 1993-08-25 2003-10-14 Casio Computer Co., Ltd. Image displaying apparatus
WO1997044752A1 (fr) * 1996-05-22 1997-11-27 Medical Science Systems, Inc. Systeme de saisie et d'analyse de donnees relatives a des processus pharmaceutiques
US6108635A (en) * 1996-05-22 2000-08-22 Interleukin Genetics, Inc. Integrated disease information system
WO2001085230A3 (fr) * 2000-05-08 2003-01-16 Image Guided Neurologics Inc Procede et appareil permettant de cibler une distribution de materiau a un tissu
WO2001098935A2 (fr) * 2000-06-22 2001-12-27 Physiome Sciences, Inc. Systeme informatique permettant la modelisation de l'expression d'une proteine dans un organe
WO2001098935A3 (fr) * 2000-06-22 2003-03-13 Physiome Sciences Inc Systeme informatique permettant la modelisation de l'expression d'une proteine dans un organe
WO2002054370A1 (fr) * 2001-01-08 2002-07-11 Simsurgery As Procede et systeme de simulation d'un fil dans des simulations graphiques informatiques
US7375726B2 (en) 2001-01-08 2008-05-20 Simsurgery As Method and system for simulation of a thread in computer graphics simulations
EP2255843A1 (fr) * 2009-05-29 2010-12-01 FluiDA Respi Procédé pour déterminer les traitements en utilisant des modèles de poumon spécifiques aux patients et procédés informatiques
WO2010136528A1 (fr) * 2009-05-29 2010-12-02 Fluidda Respi Procédé utilisant des modèles de poumon spécifiques de patient pour déterminer des traitements, et procédés informatiques
US8886500B2 (en) 2009-05-29 2014-11-11 Fluidda Respi Method for determining treatments using patient-specific lung models and computer methods

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