digital Encyclopedia of Applied Physics || Biomedical Engineering

BIOMEDICAL ENGINEERINGJOSEPH D. BRONZINO, Trinity College/The Hartford Graduate Center, Hartford,Connecticut, U.S.A,

Introduction 5131. Evolution of the Modern

Health Care System 5142. What is Biomedical

Engineering? 5153. Present and Future

Research Directions inBiomedical Engineering 519

3.1 Systems Science andIntegrated Biology 519

3.2 Cardiovascular Assist Devices . 5213.2.1 Cardiac Pacemakers 5213.2.2 Defibrillation Techniques 5223.2.3 Artificial Heart and Cardiac

Assist Devices 5233.3 Biomaterials 5253.3.1 Metals 5253.3.2 Ceramics 525

3.3.3 Polymers 5273.4 Rehabilitation Engineering

and Prosthetic Devices 5283.5 Instrumentation and

Sensors 5293.6 Medical Imaging Technology.. 5313.6.1 Radiography 5323.6.2 Nuclear Medicine 5353.6.3 Ultrasonic Imaging 5383.6.4 Magnetic Resonance

Imaging 5403.7 Biomedical Computing 540

4. Status of BiomedicalEngineering Education 542

Glossary 546

Works Cited 547Further Reading 548

INTRODUCTION

In the 20th century, technological innova-tion has progressed at such an acceleratedpace that it has permeated almost every facetof our lives. This is especially true in recentdevelopments in the field of medicine and thedelivery of health care services. Although theart of medicine has a long history, the evolu-tion of a health care system capable of provid-ing a wide range of positive therapeutic treat-ments in the prevention and cure of illnessesis a decidedly new phenomenon. Of particu-lar importance in this evolutionary processhas been the establishment of the modernhospital as the center of a technologically so-phisticated health care system. In the processof centralizing the support and utilization ofmedical technology, it became apparent thatspecialization of a large number of healthcare professionals was also necessary. In theUnited States, the result has been the emer-gence of a technologically dominated healthcare system focused around the activities of

regional hospitals serviced by a technologi-cally sophisticated staff.

Since technology has had such a dramaticimpact on medical care, engineering profes-sionals have become intimately involved inmany medical ventures. As a result, the disci-pline of biomedical engineering has emergedas an integrating medium for two dynamicprofessions, medicine and engineering, assist-ing in the struggle against illness and diseasesby providing materials, tools, and techniques(such as imaging and artificial intelligence)that can be utilized for research, diagnosis,and treatment by health care professionals.Thus, biomedical engineers serve as relativelynew members of a health care delivery"team" seeking new solutions for the difficulthealth care problems confronting our society.The purpose of this article, therefore, is toprovide a broad overview of technology's rolein shaping our modern health care system, todiscuss the basic aspects of the field of bio-medical engineering, to review some of thecontributions made by biomedical engineersincluding cardiovascular assist devices, med-

514 Biomedical Engineering

ical imaging, and diagnostic support systems,and to present the status of biomedical engi-neering education.

1. EVOLUTION OF THE MODERNHEALTH CARE SYSTEM

Before 1900, medicine had little to offerthe average citizen, since its resources con-sisted mainly of the physician, his education,and his "little black bag." In general, physi-cians seemed to be in short supply, but theshortage had rather different causes thanmore current crises in the availability ofhealth care professionals. Although the costsof obtaining medical training were relativelylow, the demand for doctors' services wasalso very small, since many of the servicesprovided by the physician could also be ob-tained from experienced amateurs in thecommunity. The home was typically the sitefor treatment and recuperation, and relativesand neighbors constituted an able and willingnursing staff. Babies were delivered by mid-wives, and those illnesses not cured by homeremedies were left to run their natural, albeitfrequently fatal, course. The contrast withcontemporary health care practices, in whichspecialized physicians and nurses locatedwithin the hospital provide critical diagnosticand treatment services, is dramatic.

The changes that have occurred withinmedical science originated in the rapid devel-opments that took place in the applied sci-ences (chemistry, physics, engineering, mi-crobiology, physiology, pharmacology, etc.)at the turn of the century. This process of de-velopment was characterized by intense inter-disciplinary cross-fertilization, which pro-vided an environment in which medical re-search was able to take giant strides in devel-oping techniques for the diagnosis andtreatment of disease. For example, in 1903,Willem Einthoven, the Dutch physiologist, de-vised the first electrocardiograph to measurethe electrical activity of the heart. In applyingdiscoveries in the physical sciences to theanalysis of a biological process, he initiated anew age in both cardiovascular medicine andelectrical measurement techniques.

New discoveries in medical science fol-lowed one another like intermediates in achain reaction. However, the most significant

innovation for clinical medicine was the de-velopment of x rays. These "new kinds ofrays," as their discoverer W. K. Roentgen de-scribed them in 1895, opened the "inner man"to medical inspection. Initially, x rays wereused to diagnose bone fractures and disloca-tions. In the process, this "modern technol-ogy" became commonplace in most urbanhospitals. Separate departments of radiologywere established, and their influence spreadto other departments throughout the hospital.By the 1930s, x-ray visualization of practicallyall organ systems of the body had been madepossible through the use of barium salts and awide variety of radio-opaque materials.

X-ray technology gave physicians a power-ful tool that, for the first time, permitted ac-curate diagnosis of a wide variety of diseasesand injuries. Moreover, since x-ray machineswere too cumbersome and expensive for localdoctors' clinics, they had to be placed inhealth care centers or hospitals. Once there,x-ray technology essentially triggered thetransformation of the hospital from a passivereceptacle for the sick poor to an active cur-ative institution for all members of society.

For economic reasons the centralization ofhealth care services became essential becauseof many other important technological inno-vations appearing on the medical scene. How-ever, hospitals remained institutions to dread,and it was not until the introduction of sulfa-nilamide in the mid-1930s and penicillin inthe early 1940s that the main danger of hos-pitalization, i.e., cross infection among pa-tients, was significantly reduced. With thesenew drugs in their arsenals, surgeons werepermitted to perform their operations with-out the prohibitive morbidity and mortalitydue to infection. Furthermore, even thoughthe different blood groups and their incom-patibility were discovered in 1900 and so-dium citrate was used in 1913 to prevent clot-ting, full development of blood banks was notpractical until the 1930s when technologyprovided adequate refrigeration. Until thattime, "fresh" donors were bled and the bloodtransfused while it was still warm.

Once these surgical units were establishedthe employment of the available technologyassisted in further advancing the develop-ment of complex surgical procedures. For ex-ample, the Drinker respirator was introducedin 1927 and the first heart-lung bypass in1939. By the 1940s, medical procedures

Biomedical Engineering 515

FIG. 1. The operating room scene during the early1950s illustrates the invasion of medical technologyinto the clinical theater of operation. (Courtesy of Hart-ford Hospital.)

heavily dependent upon medical technologysuch as cardiac catheterization and angiogra-phy (the use of a cannula threaded throughan arm vein and into the heart with the injec-tion of radio-opaque dye for the x-ray visual-ization of lung and heart vessels and valves)were developed. As a result, accurate diag-noses of congenital and acquired heart dis-ease (mainly valve disorders due to rheu-matic fever) became possible, and a new eraof cardiac and vascular surgery was estab-lished.

Following World War II, the developmentof medical devices accelerated rapidly andthe medical profession benefited greatly fromthis rapid surge of "technological finds" (Fig.1). Consider the following examples:

1. Advances in electronics made it possible tomap the subtle electrical behavior of thefundamental unit of the central nervoussystem—the neuron—as well as to monitorvarious physiological parameters, such asthe electrocardiogram (ECG), of patients inintensive care units.

2. Nuclear medicine—an outgrowth of theatomic age—emerged as a powerful and ef-fective approach in detecting and treatingspecific physiological abnormalities.

3. Diagnostic ultrasound based on sonar tech-niques became so widely accepted that ul-trasonic studies are now part of the routinediagnostic workup in many medical spe-cialties.

4. "Spare parts" surgery also became com-monplace. Technologists were encouragedto provide prosthetic devices, such as arti-ficial heart valves and artificial blood ves-sels, and the artificial heart program waslaunched to develop a replacement for adefective or diseased human heart.

5. Computers similar to those developed tocontrol the flight plans of the Apollo cap-sule were used to store, process, and cross-check medical records, to monitor patientstatus in intensive care units, and to pro-vide sophisticated statistical diagnosis ofpotential diseases correlated with specificsets of patient symptoms (Fig. 2).

6. Development of the first computer-basedmedical instrument, the computerizedaxial tomography (CAT) scanner, revolu-tionized clinical approaches to noninvasivediagnostic imaging procedures which nowinclude magnetic resonance imaging(MRI) and positron emission tomography(PET) as well.

The impact of these discoveries and manyothers was profound. The health care systemconsisting primarily of the "horse and buggy"physician was gone forever. It was replacedby a clinical staff operating primarily in hos-pitals which began to change to accommo-date the new medical technology. The "mod-ern hospital," therefore, in its contemporary,familiar form is essentially less than sixtyyears old (Crichton, 1970; Knowles, 1973;Bronzino, 1977, 1986).

2. WHAT IS BIOMEDICALENGINEERING?

Many of the problems confronting healthprofessionals today are of extreme interest toengineers because they involve the designand practical application of medical devicesand systems—processes that are fundamentalto engineering practice. These medically re-lated design problems can range from verycomplex large-scale constructs, such as thedesign and implementation of automatedclinical laboratories, multiphasic screening


FIG. 2. Computer-based monitoring sys-tems scan the vital signs of patients inhospital intensive care units. (Courtesy ofElectronics for Medicine, Inc., WhitePlains, NY.)

facilities (i.e., centers that permit many clini-cal tests to be conducted), and hospital infor-mation systems, to the creation of relativelysmall and "simple" devices such as recordingelectrodes and transducers that may be usedto monitor the activity of specific physiologi-cal processes in either a research or clinicalsetting. They encompass the many complexi-ties of remote monitoring and telemetry, in-cluding the requirements of emergency vehi-cles, operating rooms, and intensive careunits. The American health care system,therefore, encompasses many problems thatrepresent challenges to certain members ofthe engineering profession called biomedicalengineers.

Since biomedical engineering involves ap-plying the concepts, knowledge, and ap-proaches of virtually all engineering disci-plines (e.g., electrical, mechanical, andchemical engineering) to solve specifichealth-care-related problems, the opportuni-ties for interaction between engineers andhealth professionals are many and varied.

Biomedical engineers may become in-volved, for example, in the design of a newmedical imaging modality or development ofnew medical prosthetic devices to aid thehandicapped. Although what is included inthe field of biomedical engineering is consid-ered by many to be quite clear, many con-flicting opinions concerning the field can betraced to disagreements about its definition(Plonsey, 1973; Johns, 1975). For example,consider the terms biomedical engineering,

bioengineering, and clinical (or medical) engi-neering which are defined in the Bioengineer-ing Education Directory (Pacela, 1990). WhilePacela defines "bioengineering" as the broadumbrella term used to describe this entirefield, bioengineering is usually defined as abasic-research-oriented activity closely re-lated to biotechnology and genetic engineer-ing, that is, the modification of animal orplant cells, or parts of cells, to improve plantsor animals or to develop new microorgan-isms for beneficial ends. In the food industry,for example, this has meant the improvementof strains of yeast for fermentation. In agri-culture, bioengineers may be concerned withthe improvement of crop yields by treatmentof plants with organisms to reduce frost dam-age. It is clear that bioengineers of the futurewill have a tremendous impact on the qualityof human life; the full potential of this spe-cialty is difficult to imagine. Typical pursuitsinclude the following:

• development of improved species of plantsand animals for food production;

• invention of new medical diagnostic testsfor diseases;

• production of synthetic vaccines fromclone cells;

• bioenvironmental engineering to protecthuman, animal, and plant life from toxi-cants and pollutants;

• study of protein-surface interactions;• modeling of the growth kinetics of yeast

and hybridoma cells;


• research in immobilized enzyme technol-ogy;

• development of therapeutic proteins andmonoclonal antibodies.

The term biomedical engineering in this au-thor's opinion has the most comprehensivemeaning. Biomedical engineers apply electri-cal, chemical, optical, mechanical, and otherengineering principles to understand, mod-ify, or control biological (i.e., human and an-imal) systems. When a biomedical engineerworks within a hospital or clinic, he or she ismore properly called a clinical engineer.However, this theoretical distinction is not al-ways observed in practice; many profession-als working within U.S. hospitals today con-tinue to be called biomedical engineers. Inthe field of biomedical engineering there areseven major career areas which include appli-cation of engineering system analysis andmodeling (computer simulation) to biologicalproblems; measurement or monitoring ofphysiological signals; diagnostic interpreta-tion via signal processing techniques of bio-electric data; therapeutic and rehabilitationprocedures and devices; prosthetic devicesfor replacement or augmentation of bodilyfunctions; computer analysis of patient re-lated data; and medical imaging, i.e., thegraphic display of anatomical detail or phys-iological function. Typical pursuits includethe following:

• design of instrumentation for human phys-iology research;

• monitoring astronauts and maintenance oflife in space;

• research in new materials for implanted ar-tificial organs;

• development of new diagnostic instru-ments for blood analysis;

• computer modeling of the function of thehuman heart;

• writing software for analysis of medical re-search data;

• analysis of medical device hazards for theU.S. government;

• monitoring the physiological functions ofanimals;

• development of new diagnostic imagingsystems;

• design of telemetry systems for patientmonitoring;

• design of biomedical sensors for measure-

ment of human physiological systems vari-ables;

• research on artificial intelligence (AI){q.v.) and development of expert systemsfor diagnosis of diseases;

• design of closed-loop control systems fordrug administration;

• modeling of the physiological systems ofthe human body;

• design of instrumentation for sports medi-cine;

• development of new dental materials;• design of computers and communication

aids for the handicapped;• research in pulmonary fluid dynamics (see

BIORHEOLOGY);• study of the biomechanics of the human

body.

The above list is not intended to be all-inclu-sive. There are many other applications thatutilize the talents and skills of the biomedicalengineer. In fact, the list of activities of bio-medical engineers depends upon the medicalenvironment in which they work. This is es-pecially true for the "clinical engineers," bio-medical engineers employed in hospitals orclinical settings. Clinical engineers are essen-tially responsible for all the high-technologyinstruments and systems used in hospitals to-day; for the training of medical personnel inequipment use and safety; and for the design,selection, and use of technology to deliversafe and effective health care (Fig. 3).

Hospitals that have established centralizedclinical/biomedical engineering departmentsto meet these responsibilities, therefore, useclinical engineers to provide the hospital ad-ministration with an objective opinion ofequipment function, purchase, application,overall system analysis, and preventive main-tenance policies. With the in-house availabil-ity of such talent and expertise, the hospital isin a far better position to make more effectiveuse of its technological resources (Jacobs,1975; Bronzino, 1977, 1986).

In the past, industry has been reluctant tomake large investments in biomedical engi-neering research and development. The lackof a clearly defined and predictable marketfor successful technologies is the major cul-prit here. Competent clinical engineers, how-ever, as part of the health care system, canhelp create a more unified and predictablemarket. By providing health professionals


VENDORS

TECHNICALREQUIREMENTS

ANDRELIABILITY

HOSPITALADMINISTRATION

THIRD PARTYPAYORS

LEASINGAGENCIES

HUMAN ENGINEERING

ACCEPTEDMEDICAL

PRACTICES

HOSPITALENVIRONMENT

FIG. 3. Block diagram illustrating the wide range of interactions of the clinical engineer.

with needed assurance of safety, reliability,and efficiency of new and innovative equip-ment, they can, in the process, identify poor-quality and ineffective equipment much morereadily. These activities can lead to a fasterand broader acceptance of new technologyand provide a natural incentive for greater in-dustry involvement, a step that is an essentialprerequisite to widespread utilization of anytechnology (Neuman et al, 1989).

Typical pursuits of clinical engineers,therefore, include the following:

• supervision of a hospital clinical engineer-ing department;

• design, modification, or repair of sophisti-cated medical instruments or systemswithin a hospital;

• evaluation of a new noninvasive monitor-ing system during a clinical research pro-gram;

• prepurchase evaluation and planning fornew medical technology;

• cost-effective management of a medicalequipment repair service;

• safety testing of medical equipment;• risk management and liability control

within the hospital;• coordination of outside services and ven-

dors;• supervision of biomedical engineering

technicians;

• providing training for medical personnel inthe safe and effective use of medical de-vices and systems;

• custom modification of medical devices forclinical research.

Of all of the definitions discussed above,the term biomedical engineering provides thebroadest meaning (Fig. 4). Biomedical engi-neering is an interdisciplinary branch of en-gineering heavily based both in engineeringand in the life sciences. It ranges from theo-retical, nonexperimental undertakings tostate-of-the-art applications. It can encompassresearch, development, implementation, andoperation. Accordingly, like medical practiceitself, it is unlikely that any single person canacquire expertise that encompasses the entirefield. As a result, there has been an explosionof biomedical engineering specialists to coverthis broad spectrum of activity. Yet becauseof the interdisciplinary nature of this activity,there is considerable interplay and overlap-ping of interest and effort between them. Forexample, biomedical engineers engaged inthe development of biosensors may interactwith those interested in prosthetic devices todevelop a means to detect and use the samebioelectric signal to power a prosthetic de-vice. Those engaged in automating the clini-cal chemistry laboratory may collaboratewith those developing expert systems to assist


Biomedical Engineering

1Medical Instrumentationto Monitor and Measure

Physiological events,involves development

of biosensors

Rehabilitation EngineeringDesign *

and development oftherapeutic andrehabilitation

devices and procedures

Signal Processingto detect, classify

and analyzebioelectric signals

1Biomedical Computer

Analysisof patient-related data,

interpret results andassist in clinical decision

making

1Biotechnology

to create or modifybiological materialfor beneficial ends

Medical Imagingto provide graphical

displays of anatomicaldetail and physiological

function

Systems Analysis andModeling of Physiological

Systemsuse of computer simulation

to develop an understandingof physiological relationships

Prosthetic Devices*design and development

of devices for replacementor augmentation of bodily

function, includes ArtificialOrgans

Clinical Engineeringdesign and development ofclinically related facilities,

devices, systems andprocedures

* Both of these activities involve the fields of Biomechanics and Biomaterials

FIG. 4. Schematic diagram illustrating the various fields of activity within the discipline of biomedical engineering.

clinicians in making clinical decisions basedupon specific laboratory data. The possibili-ties are endless.

Perhaps a greater potential benefit occur-ring from the utilization of biomedical engi-neers is the identification of problems andneeds of our present health care delivery sys-tem that can be solved using existing engi-neering technology and systems methodol-ogy. Consequently, the field of biomedicalengineering offers hope in the continuing bat-tle to provide high-quality health care at a rea-sonable cost. If properly directed towardssolving problems related to preventative med-ical approaches, ambulatory care services,and the like, biomedical engineers can pro-vide the tools and techniques to make ourhealth care system more effective and effi-cient.

3. PRESENT AND FUTURE RESEARCHDIRECTIONS IN BIOMEDICALENGINEERINGBiomedical engineering research has

taken place in a number of important areas inthe basic life sciences and clinical medicine(Table 1). Modifying the categories of bio-medical research presented in a recent reviewby Neuman et ah (1989), we have the follow-ing:

1. systems science and integrated biology,2. cardiovascular assist devices,*3. biomaterials,4. rehabilitation engineering and prosthetic

devices,5. instrumentation and sensors,6. medical imaging technology, and7. biomedical computing.

In keeping with this classification, let us re-view some of the research activities in eachcategory.

3.1 Systems Science and IntegratedBiology

The application of engineering systemsanalysis and modeling to biological problemsis perhaps one of the earliest recognized re-search areas in biomedical engineering. Thequantification of physiological relationshipsand the building of mathematical models, i.e.,simulations, based upon these relationshipshave not only been central to the field of bio-medical engineering, but have been signifi-

*Other assist devices such as mechanical driversof limbs, etc., are covered in Sec. 3.4.


Table 1. Research areas for biomedicalengineering.8

1. Basic medical research technologiesA. Structural properties (anatomy)

1. Component (imaging techniques)2. Biomechanics (physical properties)3. Chemical composition (microscopic,

gross)B. Functional anatomy (physiology)

1. Physical factors2. Metabolic mechanisms3. Control mechanisms4. Integrated functions

C. Pathophysiology (pathology)1. Etiology of disease processes2. Sequential course of ailments3. Causes of complications

2. Clinical technologiesA. Clinical diagnosis (applications of basic

techniques)1. Anatomical alterations (imaging

methods)2. Functional factors (physical, chemical

evidence)3. Data acquisition and analysis

(computers)B. Therapeutic alternatives

1. Drug delivery systems2. Biomaterials3. Artificial sensors, tissues, and organs4. Surgical support

a. Anesthesia application and monitoringb. Least invasive surgery (e.g.,

angioplasty)C. Disease prevention

1. Lifestyles (i.e., diet, stress, exercise, etc.)2. Environmental aspects

a. Airb. Waterc. Foodd. Noise

3. Well-patient care and monitoringaTaken from Neuman et al. (1989).

cant aids to life scientists in their effort to un-derstand basic physiological mechanismsbetter.

The relevance of simulation to biologicalresearch lies in its utility, which suggests tobiological researchers the most efficient,meaningful, and creative avenues of investi-gation. Knowledge about a particular biolog-ical system is usually pieced together fromfacts gathered in a variety of laboratories, us-ing many different experimental proceduresin many different environments; in some in-stances attention is given to microscopic ex-

perimentation and in other instances to mac-roscopic experimentation. It is not surprisingthen, that comprehensive understanding doesnot necessarily correlate well with the num-ber of "facts" available about the systembeing studied.

As the various small bits of informationare synthesized into a meaningful composite,the level of complexity of the description be-comes greatly increased. The language ofmathematics, assuming the data under con-sideration are quantitative in nature, allowsthe biological investigator to contemplatecomplex interrelationships that appear to bebeyond comprehension when viewed casu-ally. In turn, modern high-speed computingmachinery can manipulate such mathematicsoften with dramatic effect which improvesunderstanding of the biological system understudy. The mathematical description (andany resultant solutions) forms a compact, ex-act language that can easily be communicatedto others.

Successful simulation demands that theexperimenter have a certain talent in modelbuilding and a grasp of the physical princi-ples that are pertinent to his field of research.It is, therefore, important that a continual in-teraction take place between experimentationand simulation (Fig. 5 suggests several modesof interaction). The ultimate objective is to in-crease the knowledge of a particular system.If we start a study by doing simulation thereare several pathways that lead to "knowl-edge." After a simulation is performed, thequestions "Has the simulation been a creativeexperience?" or "Does the solution prove newinsight into the system's performance?" mustbe answered. If the answer is "yes," then ap-propriate experimentation is in order. If theanswer is "no" the simulation activity was notcompletely successful and alterations in themodel are required. In a similar fashion, thenext step is either more experimentation ormore simulation.

Today, new modeling approaches, such asparallel processing and neural networks, areopening new horizons in enabling life scien-tists to understand complex cognitive func-tion as well as the interaction of processes oc-curring at the cellular or even subcellularlevels. At the same time further advances incomputing technology may allow investiga-tors to reduce the need of using animals in awide variety of experiments.


Or Here

ANIMALEXPERIMENT

orCLINICAL

OBSERVATION

Knowledgeabout the

system

Is the dataapplicable tothe model?

START HERE

SIMULATION OFTHE BIOLOGICAL

SYSTEM(Model building andcomputer solutions)

Does the solutionprovide new insight

into the system'sperformance?

FIG. 5. Block diagram illustrating the in-teraction between simulation and exper-imentation.

3.2 Cardiovascular Assist Devices

Biomedical engineering has played an im-portant role not only in increasing our under-standing of the cardiovascular system, butalso in the development of diagnostic andtherapeutic devices that are routinely used inthe care of cardiac patients. Since this is suchan important area of research and involvesmany biomedical engineering disciplines,such as biomaterials and instrumentation, letus explore it in more detail.

3.2.1 Cardiac Pacemakers. The use ofartificial cardiac pacemakers is well estab-lished in medical practice. Since its develop-ment in 1960, over 500 000 pacemakers havebeen implanted into patients in the UnitedStates alone, making this the most commonof all cardiovascular therapeutic procedures.The most common indication for a pace-maker is very slow heart rate or bradycardiadue to a failure of the natural pacemaker or acomponent of the conduction system. Pa-tients with bradycardia are prone to loss ofconsciousness as their hearts cannot speed inresponse to stress and their brains do not re-ceive adequate blood flow.

Modern pacemakers can sense the heart'sown electrical activity and pace appropri-ately. For patients with sinus atrium (SA)node dysfunction the pacemaker can pace theatrium directly through an atrial electrodeand allow the heart's own conduction system

to function normally. For patients with ablockage of impulse conduction between theatria and ventricles, a condition called heartblock, the heart's own atrial activity can besensed by the pacemaker and a stimulus sentdirectly to the ventricle. This type of physio-logical pacing allows the patient's own SAnode to set the rate. Many patients have wide-spread conduction system disease. At variouspoints in their conduction system, problemsmay occur and flexibility is needed to controlthe situation. These patients may initially ex-perience SA node dysfunction but subse-quently develop heart block. To deal with thisproblem of change in the status of the heart,biomedical engineers developed a dual-cham-ber programmable pacing system. After im-plantation, the functions of these units can becontrolled and reprogrammed by an externaldevice using radio-frequency commands. Thefunctions that can be controlled are the selec-tion of the chambers to be paced, the cham-bers to be sensed, and the mode of response.Furthermore, all of the above functions andbattery status are presently monitored by te-lemetry.

Typically, a pacemaker unit will be in-stalled in a patient and programmed by a car-diologist (Fig. 6). The status of the unit will bemonitored by telemetry, increasingly via thetelephone, on a monthly basis, and periodicreprogramming of the pacemaker will takeplace as needed. Present pacemakers are so


FIG. 6. Sketch illustrating the placement of a cardiacpacemaker. (Courtesy of Medical Systems Division,General Electric Company, Milwaukee, Wl.)

durable they even can be reused. In the fu-ture, it is almost certain that more-advancedpulse generators will be developed to provideeven more flexibility.

3.2.2 Defibrillation Techniques. Thenormal heart normally contracts in a rhyth-mic fashion. In the diseased heart, especiallyin the case of coronary artery disease whenthe heart muscle does not receive adequateblood flow through the blocked coronary ar-teries, rhythm disturbances occur. These areusually limited to occasional extra beatscalled ventricular extrasystoles, but canprogress to the potentially lethal rhythmcalled ventricular fibrillation. In this state,there is no orderly beat and the ventricle isoverstimulated electrically to the point wheremechanical activity ceases and there is no ef-fective cardiac pumping. Death occurs in afew minutes if the condition persists (Fig. 7).

In 1962, Dr. Bernard Lown of Harvard, acardiologist, developed the direct current (dc)defibrillator in which a capacitor is chargedto the desired dc voltage and then dischargedthrough large metal paddles placed on the pa-tient's chest. This method is still being usedtoday.

Today the defibrillator is carried as part ofthe ambulance equipment in most areas. Theparamedical team, which arrives at the home

S-A NODE

THROMBUS

DAMAGEDMUSCLE

ELECTRICAL ACTIVITY OF DAMAGED HEART iserratic because nerve impulses can no longer flowsmoothly from the atrioventricular node throughthe pathways that feed impulses to the ventricularmuscles. Most heart-attack patients develop one ormore of the arrhythmias shown below.

1 2TIME (SECONDS)

1 2TIME (SECONDS)

1 2TIME (SECONDS)

FIRST SIGN OF ARRHYTHMIA in the heartbeat,

following a coronary heart attack, usually takes the

form of a premature ventricular beat (arrow).

MORE SERIOUS ARRHYTHMIA is tachycardia, orfast heartbeat, in which ventricular impulses occurat two or three times the normal rate. If not halted,they can cause death.

FATAL ARRHYTHMIA known as fibrillation candevelop from tachycardia or when premature beatsfall within a critical part of the T wave.

FIG. 7. Electrical activity of damaged heart. Redrawn from Lown (1968).


of a patient who is thought to be sufferingfrom a heart attack, promptly attaches elec-trocardiogram (ECG) leads to the patient, ob-serves the ECG, and sends a copy of the signalby radio to the physician at the hospital base.If ventricular fibrillation is seen, cardiopul-monary resuscitation is started and, by re-mote direction of the physician, the defibril-lator paddles are placed on the patient's chest.Ventricular fibrillation is again confirmed byanalysis of the ECG signal sensed by the pad-dles.

One paddle is placed over the upper chestand the other over the lower chest. The dis-charge switches are located in the handles ofthe paddles and both must be pressed at thesame time to allow the defibrillator to dis-charge. Within seconds, the ECG trace hope-fully reveals a return to a normal rhythm.The patient can then be safely transported tothe hospital for further care. This system ofportable monitoring, telemetry, and defibril-lation is a major reason that patients whohave heart attacks now survive in greaternumbers.

At present there also exist automatic, im-plantable defibrillators. In patients with veryunstable rhythm which is only partially con-trolled by medication, this type of device canbe used to allow them to leave the hospitaland resume a more normal lifestyle. This newelectronic device can even be programmed tomonitor cardiac electrical activity and to rec-ognize ventricular fibrillation. If ventricularfibrillation is sensed, an internal discharge ofthe device can be triggered.

3.2.3 Artificial Heart and Cardiac AssistDevices. It has always been clear to manyresearchers that many patients with heart dis-ease could not always be aided by medicationor surgical repair of their damaged hearts.The heart valves could be replaced with arti-ficial devices but the heart muscle or myocar-dium was often so damaged that it requiredreplacement or the patient would die. As a re-sult, two separate avenues of research to theproblem were begun.

First, research into cardiac transplantationwas initiated. Kidney and cornea transplantsfrom other humans had proven so successfulthat cardiac transplantation was studied. Al-though many problems such as rejection, do-nor organ procurement, and infection re-main, considerable progress has been made

and this approach has now become an ac-cepted part of cardiac therapy.

The second area of research in the area ofcardiac replacement was the development ofthe artificial heart. This effort was subdividedinto two areas: the left ventricular assist de-vice and total cardiac replacement (Bernardand LaFarge, 1969). Both approaches requireclose cooperation between the biomedical en-gineer and the surgeon. The relative successesthat have been achieved to date are testamentto the accomplishments possible from thesejoint ventures.

The first temporary use of a mechanicaldevice to sustain life while the heart was un-able to function was the pioneering effort ofJ. H. Gibbon, Jr. and C. W. Lillehei at the Uni-versity of Minnesota (Allen and Lillehei,1957). In 1953 their group began the use ofthe techniques of cardiopulmonary bypass,enabling the current practice of open-heartsurgery to evolve. The device they developedconsisted of a pump to maintain blood flowand an oxygenator to permit gas exchangewhen the heart and lungs were removed fromthe path of circulation.

The modern heart-lung machine typicallyconsists of a double-roller pump which pro-pels the blood forward by a squeezing actionand either a bubble or membrane oxygen-ator. The roller pump is quite effective as agenerator of flow, but prolonged use causesmechanical damage to the red blood cells (he-molysis). This damage can be tolerated forthe short periods (several hours) which aretypical in open-heart surgery but not for pro-longed periods as the damaged red cells re-lease hemoglobin into the bloodstream whicheventually causes kidney failure. To permitsupport for longer periods of time, pumpsthat compress the blood between the walls offlexible chambers in a way similar to the nat-ural process are more desirable. As new typesof pumps are developed they are being uti-lized.

It is important to note that the materials inthese devices are sensed as foreign to thebody. While they are not rejected as unaccept-able biological tissue (a problem that occursin the case of heart transplants), the bodydoes attempt to form clots on their surface.Such clotting is to be avoided since it couldcause the mechanism to fail. Patients withthese devices must therefore be given drugscalled anticoagulants to prevent clotting, and


the use of anticoagulants has to continue aslong as the mechanical device is sustainingcirculation. Care must be taken, however, toavoid overuse of anticoagulants since sponta-neous bleeding in such vital organs as thebrain or the gastrointestinal tract can takeplace.

Both the artificial heart and the left ven-tricular assist devices are extensions of ear-lier efforts to develop the heart-lung machinefor open-heart surgery. In many patients, theleft ventricle is damaged during an episode ofcoronary artery blockage. The left ventricle,which is the pump for the entire body, can berevascularized by coronary artery bypass, butoften requires time to heal. As the body mustbe served by the ventricle immediately aftersurgery, there can be no rest period. Whatmany patients require, therefore, is tempo-rary assistance for the left ventricular func-tion. The development of a left ventricular as-sist device (LVAD) was led by Dr. John C.Norman and colleagues (Norman and Huff-man, 1974; Norman, 1975a, 1975b). Such as-sist devices are designed to provide partial ortotal support of the circulation.

The second and more highly publicized ef-fort has been in the development and use ofthe total artificial heart. These devices are de-signed to replace completely the damagedheart and to support the circulation on a per-manent basis. Unlike the LVAD where the pa-tient's own heart can recover and the supportdevice can be removed, the artificial heart isimplanted in place of the patient's own heart,which is then discarded.

In 1963, the National Advisory HeartCouncil recommended giving priority to thistype of research, as well as the necessary fed-eral funding, focusing on such areas of re-search as biomaterials, pumping mecha-nisms, and control systems.

In 1969, sufficient progress had been madeto permit Dr. Denton Cooley of the TexasHeart Institute in Houston to implant an ar-tificial heart in a patient awaiting a hearttransplantation whose own heart had failed.The device sustained the patient for 64 h untila suitable donor heart was found and theheart transplant took place. A similar type oftemporary artificial heart was again used in asimilar circumstance by Dr. Cooley in 1981 tosustain a patient for 54 h. In both these cases,the use of the artificial heart was described astemporary, i.e., providing assistance until a

heart transplant could be performed. Thework of Dr. William C. DeVries and Dr. Rob-ert K. Jarvik, supported initially by Dr. W. J.Kolff at the University of Utah, and initiallyand subsequently by the Humana Heart Insti-tute in Louisville, Kentucky, has led to the useof a permanent artificial heart to sustain a pa-tient (DeVries et al, 1984; DeVries, 1986).

On 2 December 1987 Dr. Barney Clark be-came the first legal recipient of a permanentartificial heart—the Jarvik-7—after the U.S.Food and Drug Administration approved thedevice in 1982 (Fig. 8). Dr. Clark sufferedfrom cardiomyopathy, a disease that causesthe heart muscle to deteriorate and has noknown cure. He showed no chance of recov-ery through any heart surgery and was veryclose to death—conditions required by theFDA before approval to implant the artificialheart could be given. At 61, he was consideredtoo old to receive a transplanted heart, even ifa donor had been available.

The Federal Food and Drug Administra-tion has given the University of Utah MedicalCenter permission to implant the Jarvik-7heart and its driving system in seven patients.However, while the implantation of theJarvik-7 heart continues, the design team of

FIG. 8. The Jarvik heart being implanted.


Symbion, the firm in Salt Lake City headed byDr. Robert Jarvik, works on the successormodel, the Jarvik-8. The major problems ofthe Jarvik-7—clotting, size, durability, and"mass" production—are being addressed inthe redesign.

Both the total artificial heart and the LVADface similar engineering problems (Galioto,1986). Materials for their construction mustbe durable as they are truly life sustaining.Their mechanisms must safely pump bloodbut should not damage the delicate cellularelements of the red blood cells. Blood can beprotected by nonocclusive pumps and antico-agulants but the patient's own long-term re-sponses to such devices must be borne inmind at all times. Most important, these de-vices should allow for a reasonable and toler-able lifestyle.

3.3 Biomaterials

The use of surgical implants and invasivemedical therapies has expanded greatly in re-cent decades. Devices ranging in complexityfrom chronic infusion catheters and lens im-plants to total hip prostheses, to implantablepacemakers/defibrillators, heart-lung ma-chines, and hemodialyzer systems are nowroutinely used. These devices are employedon a vast scale: tens to hundreds of thousandsare used each year in the United States alone.On the medical horizon are numerous devices(such as the artificial heart discussed above)of increasing sophistication and complexity.Common to all these devices is the use of bio-materials.

What are these biomaterials and how dothey differ from other engineering materials?They are metals, plastics, and ceramics, someof which are merely purified forms of indus-trial materials. Some are new formulationswith specific properties found to be advanta-geous in medical applications. Others are sur-face modifications of, or bulk additives to,conventional materials. Still others are pro-cessed natural (biological) materials (Eber-hart, 1989).

Research efforts in biomaterials includeunderstanding the biological and physicalproperties of naturally occurring materials,such as bone, connective tissue, keratin, etc.,and creating new artificial materials or gener-ating "natural" materials with similar proper-ties to their natural counterparts. Since bio-

materials are used to replace or augmentnatural tissues, it is also important to under-stand and control the biology of the interfacebetween artificial and natural biomaterials inthe body.

There are three main classifications of ar-tificial biomaterials: metals, ceramics, andpolymers. Each class has specific propertiesthat make it especially suitable for some func-tion in the body, but in many cases it cannotperform today as well as its natural counter-part. It is hoped that through research, newand improved materials can be developedthat meet or even exceed the capabilities ofthe natural substances (Neuman et aL, 1989).

3.3.1 Metals. A major component ofbone and joint prostheses are metals, used be-cause of their strength and ability to absorbenergy before fracture. Table 2 presents prop-erties of some commonly used biomaterialmetals. Their major drawback, however, is as-sociated with the propensity of the elementsresponsible for their resistance to corrosion(chromium, nickel, cobalt) to induce a cell-mediated hypersensitivity. Today, work is un-der way to utilize titanium-based alloys be-cause there has yet to be any record of hy-persensitivity response from these materials.

3.3.2 Ceramics. The class of materialscalled "ceramic" includes a variety of sub-stances that are nonmetallic and inorganic innature, and generally consist of clay or othersilicates. Although ceramics are the oldestmanmade materials and plaster of Paris(CaSO4) has been used for casts in fractureimmobilization for many years, the use of ce-ramics for biomedical applications onlystarted in the mid-1960s (Saha, 1989).

Compared to the large number of differentceramic materials that are used for industrialpurposes, only a few classes of these materi-als have been found suitable for implantationand clinical use, in spite of the fact that theyare highly inert and elicit a minimumforeign-body reaction. These classes include

1. oxide ceramics and ceramics of calciumphosphate salts,

2. various types of glass or enamel, and3. crystalline or glassy forms of carbon and

its compounds (Heimke, 1986).

The oxide ceramics are known by themetals from which they are formed. Alumina

Tab

le 2

. Pro

pert

ies

of c

omm

only

use

d bi

omed

ical

met

als.

a

N> i o W (TQ

Sta

inle

ssst

eel

No.

316

LT

itan

ium

MP

35N

Elg

iloy

Pla

tinu

mN

itin

ol/T

inel

Com

posi

tion

App

lica

tion

Den

sity

(g/

cm3)

Ele

ctri

cal

resi

stiv

ity

(/xft

cm)

The

rmal

cond

ucti

vity

(W/c

m °

C)

Spec

ific

heat

(cal

/g°C

)

The

rmal

expa

nsio

nco

effi

cien

t(1

0~6/°

C)

Fe,

Cr,

Ni,

Mo,

Si,

Mn

Impl

ant

case

;el

ectr

ode

lead 7.

9

74 0.15

0.5

16

Ti Im

plan

tca

se 4.5

48-6

0

0.16

0.52

9.2-

9.9

Co

35%

, N

i 35%

,C

r 20

%, M

n 10

%

Ele

ctro

de

8.3

101 15

.7

Co

40%

, Cr

20%

,F

e 16

%, N

i 15

%,

Mo

7%, M

n 2%

,C

o 0.

001%

, B

e 0.

04%

Ele

ctro

de

8.2

99.5 0.13

15.8

Pt Ele

ctro

de

21.4 9.8

0.73

0.12

8.8

50 N

i, 50

Ti

Spec

ial

(sha

pe m

emor

y)

6.5

100 80 0.

180.

086

0.84

11 8.6

(hig

h-te

mp.

)(l

ow-t

emp.

)

(hig

h-te

mp.

)(l

ow-t

emp.

)

(hig

h-te

mp.

)(l

ow-t

emp.

)

aFro

m T

arja

n an

d G

old

(198

8).


(A12O3) is the most commonly used andmost biocompatible ceramic material for or-thopedic implants. Other oxides of calciumand phosphorus, such as hydroxyapatite[Ca10(PO4)6(OH)2] and hydroxylapatite[Ca4H(PO4)3OH] have also been used. Amongthese, hydroxyapatite (HA) is of particular in-terest as its chemical composition is very sim-ilar to that of the mineral content of bone.

The glasses that have been studied for im-plantation are based on silica (SiO2) andsometimes contain a small amount of othercrystalline phases. Bioglass, developed byHench and co-workers (1988), is perhaps themost common among these types of ceram-ics.

The carbons that are primarily used inprosthetic devices include low-temperatureisotropic (LTI) pyrolitic carbon (Pyrolite), bi-otite carbon, and carbon or graphite fibers.LTI pyrolitic carbon has been used in theDeBakey heart valve since 1969 and has alsobeen used to make coatings for other valves,vascular access devices, and dental implants.Carbon fibers are being used to replace oraugment ligaments and tendons. Carbon-fiber-based composites are also being devel-oped to manufacture orthopedic implants.

During the last twenty years, ceramicshave also been used as a material for totaljoint-replacement implants as well as a coat-ing on metal implants for improved biologi-cal fixation with the host bone (Christel,Meunier, and Lu, 1986).

Total joint replacement is one of the greatorthopedic advances of this century. Sir JohnCharnley introduced the metal-on-plastictotal hip replacement in the mid-1950s, andsince then this orthopedic procedure has rev-olutionized the treatment of painful arthritichip disorders. This procedure is highly suc-cessful with rates of success between 80% and98%, depending upon the type of implant,surgical technique, patient selection, and,particularly, follow-up time. In long-term fol-low-up studies, it has been found that asepticloosening is the significant cause of failure oftotal hip replacement. This failure rate is es-timated to be 7%-24% for a 5-10 yr follow-up(Russotti, Coventry, and Stouffer, 1988). Theenormity of the problem is evident from thefact that in the United States alone, over120 000 total hip replacement arthroplasties

are performed each year. Worldwide, over2.5 million people are estimated to have arti-ficial hip joints.

To improve the long-term results of totalhip replacement (THR), a large number ofnew prosthesis designs have been proposed.These include use of a low-modulus metalsuch as titanium alloy to reduce the stressshearing effect on bone. Ceramics have alsobeen used to make the whole or parts of aTHR and in coating on metal implants to ob-tain a chemical bond between the implantand surrounding bone.

In the future, it is anticipated that ceram-ics will become a major component for her-metic sealing of implantable microelectronicdevices and sensors because of a combinationof their properties. Of major importance istheir transparency to electromagnetic radia-tion, as well as their impermeability to water.It has been suggested that sealing processesusing laser technology will solve the problemof packaging implantable electronic deviceswithout damage and that modification of thesurface charge on such ceramic packages willhelp to control their thrombogenicity, thus al-lowing their use in packages for sensing ap-plications in blood.

3.3.3 Polymers. Polyurethanes are gen-erally formed by the addition of a polyglycolto an isocyanate. Typically, the isocyanate ispart of an aromatic molecule that gives rigid-ity or hardness to this portion of the polymerchain, while the polyglycol is the part of an al-iphatic molecule that produces a less rigid orsoft portion of the polymer chain. Most poly-urethanes, therefore, have hard and soft seg-ments and are called segmented polyure-thanes (McMillin, 1989).

Polyurethanes can be readily tailored formany biomedical applications by eitherchanging the chemical used in any of thecomponents or by changing the length of theprepolymer or extended chains of the poly-urethane. Thus, polyurethanes are in them-selves a wide class of materials. Ether-basedpolyurethanes are known to be less suscepti-ble to hydrolytic cleavage than ester-basedpolyurethanes and have therefore been usedfor most biomedical applications. Polyure-thanes are usually strong, flexible, transpar-ent, or translucent, tissue compatible, andreasonably blood compatible, and are usedfor a variety of applications requiring these


properties, such as peristaltic pump tubing,parenteral solution tubing, balloon pumps,and catheters.

Much of the research on biomedical poly-urethanes focuses on a relatively few com-mercial polymers. For competitive reasons,the chemical composition of these polyure-thanes are sometimes trade secrets. Theknown compositions of some urethanes areshown in Table 3.

Polymers of biological origin such as col-lagen and elastin appear to be a logical solu-tion for implant applications. The majorproblem is how to remove their antigenicproperties while maintaining their desirableproperties. It is important to make progressin using materials of biological origin as scaf-folds for the reconstruction of certain tissues.Probably the major advance in this area willbe in the use of synthetic polymers as scaf-folding structures that will degrade, andtherefore be repopulated by body cells, toconstruct the appropriate collagen network togive structural integrity to the system as awhole.

A major limitation in the use of syntheticpolymers as biological materials is their ten-dency to fatigue. More fatigue-resistant poly-mers with isotropic mechanical propertiesneed to be developed. These materials areneeded as the basis of the diaphragms forpumps in total artificial heart and heart assist

systems, as well as polymeric valves that willreplace the artificial heart valves used today.

3.4 Rehabilitation Engineering andProsthetic Devices

Engineering devices have been applied tohelping disabled individuals return to moreuseful lives. The design of prosthetic devicesand artificial organs frequently involves me-chanical principles, and therefore these areaslie partly in the province of biomechanics.

Biomechanics has traditionally been con-cerned with the analysis of macroscopic bio-logical structures such as bones, blood ves-sels, other soft tissues, and blood and otherbiological fluids. In the past, computer mod-eling techniques have been applied to helpunderstand not only normal function but alsothe pathophysiology of various diseases andconditions. For example, computer simula-tions have provided great insights into themechanics of lifting as it applies to lowerback pain, optimization of athletic perfor-mance, mechanics of bone healing, and trans-port processes in various organ systems. Bio-mechanics has also led to the development ofprocedures in diagnostic medicine, such asgait analysis, and the design of various pros-thetic devices ranging from joint replace-ments to artificial organs. This field has con-tributed to the design and optimization of

Table 3. Composition

Trade name/supplier

or some polyurethane

PTMEG

biomedical

MDI

elastomers. Modified from McMillan

Urethane components8

ED BD PD HMDI

(1989).

PDMS

Biomer/Ethicon Inc.,Somerville, NJ

Surethane/Cardiac ControlSystems, Palm Coast, FL

Pellethane/Dow Chemical Co.,Midland, MI

Corplex/Corvita,Miami, FL

Toyobo TM5/Toyobo Co.,Osaka, Japan

Tecoflex HR/Thermedics, Inc.,Woburn, MA

Cardiothane-51/KontronInstitute, Everett, MA

(X) posttreatment

aPTMEG, polytetramethylene ether glycol; MDI, methylene diisocyanate; ED, ethylenediamine; BD, 1,4-butanediol; PD, propylenediamine; HMDI, hydrogenated MDI; PDMS, polydimethylsiloxane.


man-machine interfaces, such as improvedsports equipment, safety of automobiles andaircraft, and specialized equipment for spaceexploration.

As physiologists and other biological scien-tists increasingly turn their attention to stud-ies at the cellular and molecular levels, it be-comes clear that mechanics has importantapplications in these areas as well. Athero-sclerosis remains a major clinical problem,and only preliminary exploration of the ef-fects of blood fluid mechanics on endothelialcells has been done. Other cellular and molec-ular aspects of biomechanics remain rela-tively unexplored. There are many phenom-ena at the microscopic level in which me-chanics is likely to play a role. Among theseare

1. atrophy and hypertrophy of muscle,2. regulation of blood pressure,3. the origin of atherosclerosis,4. microscopic processes in bone healing,

and5. bone remodeling and osteoporosis.

The roots of rehabilitation originate in thehistorical use of prosthetic devices (woodenlimb substitutes) and orthotic devices (crutch-like aids) (see PROSTHETICS AND ARTIFICIALORGANS). In modern times, visual orthoses(eyeglasses) have become ubiquitous. Tech-nological advances in medical treatmentwere developed during World War II at thesame time as technological applications toweaponry leaped forward. Thus, society be-lieved that the people maimed by the war andsaved by medicine had to be helped to leadfuller lives.

After the war, the Veterans Administration(VA) was founded and began to apply engi-neering solutions to some of the physicallydisabling problems which patients in VA hos-pitals presented—principally in the areas ofwheelchair development and prostheticlimbs. Around 1970, several RehabilitativeEngineering Centers were funded by the U.S.government to increase the application of en-gineering techniques in the solution of prob-lems related to rehabilitation. However, itwas not until about 1980 that the idea devel-oped, in major centers of rehabilitation, thatengineers could be useful in direct service topatients along with the more usual deliverersof patient care.

Recently, the idea that people with techni-cal training in engineering can help in the pa-tient care process has spread outside of themajor rehabilitation hospitals to smaller hos-pitals with rehabilitation departments. TheRehabilitative Engineer, trained in engineer-ing and biology, has a capacity to act as theinterface between the patient, the rehabilita-tive team, and technology.

Although many orthotic and prosthetic de-vices have been developed to help individualsregain some form of functionality, many op-portunities remain for future research. In thefuture, rehabilitation research will probablybe more in the direction of utilizing existingbut nonfunctional biological structures, suchas a paralyzed limb, to regain function ratherthan by employing external orthoses. Func-tional electrical stimulation of intact nervesand muscles will allow patients to controlcontraction of paralyzed muscles. To controlsuch motor prostheses effectively, it will benecessary to obtain a better understanding ofthe body's natural control systems and to de-termine what constitutes minimal processingto regain particular functions. Sensory inputto such systems will be important, and re-search into making use of intact but discon-nected natural sensors, as well as the develop-ment of implantable artificial sensors, willcontinue to be important research areas.

The computer has already played an im-portant role in helping individuals with dis-abilities to be viably employed and to per-form tasks that were once thought to be im-possible. The interface between the patientand the computer, however, still remainscrude. Research is needed to develop more ef-fective interfaces, as well as processing algo-rithms for these interfaces. Advances in theneural sciences should help to establish con-nections between a patient's nervous systemand external electronic devices. By under-standing natural signal processing in the ner-vous system, it should be possible for comput-ers to emulate this human function and tocontrol both internal body structures and ex-ternal devices.

3.5 Instrumentation and Sensors

Instrumentation is involved throughoutthe field of biomedical engineering. This cer-tainly becomes clear when one reviews thenumber and diversity of biomedical quanti-


ties measured by biomedical instruments inTable 4. In practice, however, the transducerswhich convert signals in one form of energyinto signals in another form of energy are in-corporated in an instrumentation package orsystem. The most general instrumentationsystem then consists of the transducer orbiosensor, a signal processing component

which amplifies and filters the signal and per-forms some preprocessing to permit the mea-sured quantity to be stored, to be displayed, toactivate some device, or to be processed fur-ther.

The biosensor, therefore, serves as the in-terface between the biological system beingmeasured and the electronic system of the in-

Table 4. Biomedical electronic measurements.3

Measured quantity Principle or devices used Biomedical applications

A. Physical parameters

Electricalpotential

Impedance

Temperature

Sound

Light

Magnet

Force and pressure

Displacement, velocity,acceleration

Voltage

Z bridge

Thermistor, p-njunction, infrared

Microphones

Transmission, refractionabsorption

Permeability, field

Piezoresistance, capaci-tance deformation

Capacitive, magnetic, la-ser, ultrasound, accel-eration force

Flow: blood, fluid, air

Volume

Time

Electromagnetic, opticalultrasonic Doppler,pressure drop, stream-ing potential

Displaced volume, dyedilution

Delay, response time

Nerve and muscle activity, ECG, EEG,EMG, EOG, etc.

Skin condition, respiration rate, peripheralblood flow

Inflammation, cancer location, blockedcirculation

Heart and breathing sounds, blood pressuremeasurement, fluid flow

Physiology research, clinical laboratory, gasand ion sensors

Blood flow, heart activity, proximity

Pressure of blood, CSF, urine, etc.;locomotion

Body movement, physiology research,orthopedics

Blood, air, body fluid; heart, lung, kidneyfunction

Physiology research, cardiac output

Alertness, nerve signal transmission, signaltransmission in heart and other organs

B. Chemical parameters

Gas concentration

Humidity

Ions

Biomolecules

Gas-sensitive electrodes,chromatography,chemical analysis

Dew-point temperature,resistance and capaci-tance change due tocondensation or absorption

Ion-selective electrodes,ISFET, chemical analysis

Enzyme electrodes,chemical analysis

Blood gas (H+, O2, CO2, O2 saturation),respiration, perfusion, anesthesia, hospitaloperations, clinical laboratory

Pediatric, respiratory research, intensive care

Clinical laboratory, intensive care unit,acid-base balance

Clinical laboratory, research laboratory,patient monitoring

aModified from Ko (1988).


strumentation. Work during this century hasbeen devoted to developing new types of sen-sors of physical and chemical variables andincorporating these sensors into instrumenta-tion systems. The application of technologiessuch as microelectronics and optoelectronicsto biomedical sensor problems has shownthat imaginative solutions are possible. Forexample, a few years ago transducers formeasuring biomedical pressures were basedon handmade, unbonded strain gauge tech-nology. These devices were expensive andhad to be individually calibrated for the elec-tronic system with which they were used. To-day, semiconductor electronics allows massproduced biomedical pressure transducers tobe sold at less than 5% of the price of the ear-lier devices. This makes it possible to havedisposable pressure sensors for clinical appli-cations at a cost that would have been impos-sible in the past (Neuman et al, 1989).

Future research in sensors will certainlyfollow corresponding improvements in tech-nology, as well as the feasibility of developingbioanalytical sensors for complex biochemi-cal substances that are found in the body inonly very small concentrations. Substancessuch as neurotransmitters, tumor markers,and local and systemic hormones are impor-tant analytes for future biomedical sensors.The availability of such sensors would makeit possible to measure these biochemicals di-rectly and continuously within the body it-self.

It is important to note that creative ways topresent and summarize large amounts of pa-tient-related data for busy physicians andnurses need to be incorporated into moderninstrumentation systems. Furthermore, pro-viding instrumentation packages to monitorpatients in their homes will become more andmore important as health care becomes de-centralized and the need for larger data sam-ples becomes important. Coupled with theseefforts is the need to develop communicationsystems to tie such monitoring devices intocentral facilities.

3.6 Medical Imaging Technology

Developing noninvasive tools that can"look into" the human body while posingminimal risks for the patient has been givenan extremely high priority in the post 19thcentury scientific era of medical research and

practice (see IMAGING TECHNIQUES, BIOMEDI-CAL). Diagnostic and therapeutic techniquesthat remove the need for invasive (surgical)exploration often both reduce patient riskand lower the costs of health care. However,until recently the health care profession"black bag" has contained only a relativelysmall number of noninvasive diagnostic toolsthat provided images of the body. None wereavailable until the end of the 19th century.

We now know that x rays

1. are part of the electromagnetic spectrum,that have relatively short wavelengths,

2. are generated by collision of atomic parti-cles,

3. travel in straight lines in all directionsfrom the point of origin, and

4. are capable of penetrating many forms ofmatter opaque to ordinary light.

Therefore, the classical medical imaging tech-nique, radiology, uses high-energy electro-magnetic waves or x rays as a tool to "look"into the patient to view certain anatomicalstructures. During the early part of the 20thcentury additional improvements in the fieldof radiography involved advances in technol-ogy related to particular components of thesystem including intensifying screens and ro-tating anode tubes.

It is interesting to note that after 1930, pro-found improvements in radiology wereachieved by developing procedures for selec-tively opacifying regions of interest in thebody. These developments were achievedthrough a variety of approaches, such as theinjection of dyes, often invasive to the body,to facilitate visual representation of other-wise invisible organs.

Since 1960, through the marriage of com-puters and sophisticated imaging processingtechniques, medical imagery has been able topursue totally new directions. Images of theinternal structures of the body are now cre-ated that are often of startling clarity, signif-icantly enhancing the ability of the clinicianto arrive at an appropriate diagnosis.

Although modern medical imaging takesmany forms, systems of most practical inter-est today include the following: nuclear med-icine, diagnostic ultrasound, computerized to-mography, and magnetic-resonance imaging.These imaging devices enable doctors toavoid exploratory surgery and still watch vi-


tal organs at work, identify blockages andgrowths, and detect the warning signs of pos-sible future disorders. Since these techniques,for the most part, do not involve penetratingthe skin, they have been classified as nonin-vasive. However, patients may face other con-sequences of their use (e.g., the possible de-struction of body tissue caused by the radio-active materials used in nuclear medicine, orthe increase in tissue temperature as a resultof high-frequency ultrasound). Bearing thisin mind, it may be more precise to considerthe relative degree of direct surgical interven-tion that certain devices entail. Thus the termnoninvasive will be used here to refer only tospecific techniques developed in radiology,nuclear medicine, and ultrasound.

Major advances in medical diagnostic pro-cedures were made during the 1980s thatgreatly enhanced image quality and ex-panded the types of tissues that could be visu-alized with good resolution. Even with thisadvanced technology and the integration ofcomputer and image processing techniquesinto medical imaging devices, problems andopportunities remain for biomedical engi-neering researchers. These include instru-mentation not only for visualizing internalstructures but for assessing their function.

3.6.1 Radiography. Radiography, theclassical medical imaging technique routinelyapplied to nearly all hospitalized patientswhether or not there is a direct need, useshigh-energy electromagnetic waves or pho-tons (x rays), as a tool to "look" through thepatient to obtain information on anatomicalstructures (Fig. 9). The propagation of x rays,characterized by wavelengths that are shorterthan the atomic diameters of the penetratedmatter, is dominated by corpuscular rayproperties rather than by the wave characterof light. The velocity of propagation is essen-tially constant for all kinds of biological tis-sue; thus the refractive index of all such struc-tures is unity. As a consequence, the onlymechanisms of interaction are absorptionand scattering; no reflection or diffractiontakes place. So, unlike ultrasonic waves, xrays travel in straight lines through the body,unaffected by tissue interfaces, and provideundistorted images of high resolution (seeBIOMEDICAL USES OF RADIATION).

The term radiography is sometimes mis-leading because it applies to various x-ray

CONVENTIONAL X-RAY PICTURE is made by al-lowing the X rays to diverge from a source, pass throughthe body of the subject and then fall on a sheet of photo-graphic film.

TOMOGRAM is made by having the X-ray source movein one direction during the exposure and film in the otherdirection. In projected image only one plane in body re-mains stationary with respect to moving film. In the pic-ture all other planes in body are blurred.

RECONSTRUCTION FROM PROJECTIONS is madeby mounting the X-ray source and an X-ray detector on ayoke and moving them past the body. The yoke is alsorotated through a series of angles around the body. Datarecorded by detector are processed by a special computeralgorithm, or program. Computer generates picture on acathode-ray screen.

FIG. 9. Image reconstruction from x-ray projections.

techniques. Its original definition referredonly to the recording of x-ray projection im-ages on photographic film. Use of a fluoro-scopic screen as the x-ray detector (instead offilm), called fluoroscopy, provided the abilityfor continuous x-ray monitoring. The use ofTV systems for electronically monitoring thefluoroscopic screen is called x-ray television.Because all of these systems, including film


recording, use fluoroscopic screens as imageconverters, and all of them are based on thesame physical principle of imaging (i.e., theprojection of body absorption onto a singleplane), the terminology is illogical and arbi-trary. So, with the development of an imagingprinciple called computed tomography (CT)(Ledley, 1976), a renaming took place, inwhich all possible imaging techniques using xrays are called radiography (Nagel, 1988).

Since its introduction, computed tomogra-phy has undergone continuous refinementand development. Significant improvementshave been made in

1. x-ray tube performance,2. reduction of scan times,3. reduction of image reconstruction time,4. reduction and, in some cases, elimination

of image artifacts,5. reduction of patient dose.

Present CT scanners are usually integratedunits consisting of three major elements (Fig.10):

1. the scanning gantry, which takes the read-ings in a suitable form and quantity for apicture to be reconstructed;

2. the data handling unit, which convertsthese readings into intelligible picture in-formation, presents this picture informa-tion in a visual format, and provides vari-ous manipulative aids to enhance theimage and thereby assist the doctor informing a diagnosis, and

3. a storage facility, which enables the infor-mation to be examined or reexamined atany time subsequent to the actual scan(Walmsley, 1979).

The objective of the scanning system is toobtain enough information to reconstruct animage of the cross section of interest. All theinformation obtained must be relevant andaccurate, and there must be enough indepen-dent readings to reconstruct a picture withsufficient spatial resolution and density dis-crimination to permit an accurate diagnosis.The operation of the scanning system is there-fore extremely important.

During the past decade, the CT scanner hasundergone several design changes. The earli-est generation of gantries used a systemknown as "traverse and index." In these sys-tems, the tube and detector were mounted ona frame and a single beam of x rays traversedthe slice linearly, thereby providing absorp-tion measurements along one profile. At theend of the traverse, the frame indexedthrough 1° and the traverse was repeated.This procedure continued until 180 singletraverses were made and 180 profiles weremeasured. Using the "traverse and index" ap-proach, the entire scanning procedure tookapproximately 4-5 min. The images it pro-vided had excellent picture quality and hencehigh diagnostic utility. However, this ap-proach had several disadvantages. First of allit was relatively slow, resulting in relativelylow patient throughput. Second, streak arti-

Control and ViewingConsole

Line Printer

X-Ray Tube

ScanDetectors

Monitor

X-RayControl

Keyboard

ReferenceDetector

Computer

Disc Store FIG. 10. Basic components of a CTscanner.


facts, i.e., lines in the image, were common,and although these artifacts normally werenot diagnostically confusing, the image qual-ity did suffer. Finally, perhaps the biggestdrawback was that since the patient had to re-main absolutely still during the scan, its usewas restricted solely to brain scans.

In an attempt to solve these problems, sev-eral generations of gantries have evolved overthe past 15 years (Fig. 11). Initially new scan-ning procedures included a translation stepas in the first generation but permitted thescanning gantry to go around the patient(180°) in 10° steps. With use of this 10° fanbeam, it is possible to obtain a full set of 180°profiles by making only 18 traverses. At therate of approximately 1 s for each traverse,

scanning systems of this type usually operatein the range of 18-20 s while still retainingpicture quality.

However, very shortly a major redesignensued and a third generation of gantriesevolved consisting of a pure rotational sys-tem. In these systems the source/detectorunit, with a pulsing, highly collimated wide-angle (typically 20°-50°) fan beam and a mul-tiple detector array, is rotated 360° around thepatient. This single 360° smoothly rotatingmovement decreases scan time to approxi-mately 3 s, increases appreciably the reliabil-ity of the data since it is taken twice, and in-creases the quality of the reconstructedimage. A by-product of this design is that thepulsing x-ray source can be synchronizedwith physiological parameters enabling

SCANNING GANTRY DESIGNS

FIRST GENERATION

X-RAY SOURCE

O 120 th SCAN

DETECTOR

I DETECTORSCAN T IME; 4 - 5 MINUTES

SECOND GENERATION

x X-RAY\ SOURCE

'' MULTIPLEDETECTORS

30 DETECTORSSCAN TIME ; 18 -20 SECONDS

THIRD GENERATION FOURTH GENERATION

NON-PULSEDFAN BEAM

DETECTORARRAY

360° DETECTORRING

3 0 0 DETECTORSSCAN TIME ; 2 - 4 SECONDS

700 STATIONARY DETECTORSSCAN TIME; 2 - 4 SECONDS

FIG. 11. Four generations of CT scanners.


rhythmically moving structures, such as theheart, to be accurately imaged.

The main advantages of this type of systemare its simplicity and its speed; however, itsfixed geometry system with a fan beam, usu-ally established for the largest patient, makesit inefficient for smaller objects, in particularhead scanning. Consequently a fourth gener-ation gantry system consisting of a continu-ous ring of fixed detectors (usually number-ing between 500 and 700) was developed. Inthis system the x-ray source rotates as before,but the detectors remain stationary, arrangedin a full circle around the gantry. The fanbeam is increased slightly so that the detec-tors on the leading and trailing edge of thefan can be continuously monitored andthereby adjust the data in case of shifts in de-tector performance (Maravilla and Pastel,1978).

Recently the bulky, noisy electromechani-cal rotation mechanism has been eliminatedand, in its place, a magnetic induction systemis employed to rotate the source. This has en-abled designers to attain a long sought goal:the 1-s scan.

The whole purpose of the scanning proce-dure is to take thousands of accurate absorp-tion measurements through the body. Takenat all angles through the cross section of in-terest, these measurements provide an enor-mous amount of information about the com-position of the section of the body beingscanned.

In conjunction with the operation of thescanning and detection system, the data ob-tained must be processed rapidly to permitproducing and viewing an image or scan asquickly as possible. The first stage of thiscomputation process is to analyze all of thisraw data and convert it into the set of profiles,normally 180 or more, and then convert theseprofiles into information which can be dis-played as a picture and used for diagnosis.Here we have the heart of the operation of aCT scanner, that element which makes CT to-tally different from conventional x-ray tech-niques and most other imaging techniques.The algorithms or computer programs for re-constructing tissue x-ray absorption presentlyfall into one of the following categories: sim-ple back projection (sometimes called sum-mation), Fourier transforms, integral equa-tions, and series expansions. The choice of an

algorithm for a CT scanner depends upon itsspeed and accuracy (Nagel, 1988).

To facilitate the utilization of these compu-tational processes significant advances hadbeen made in the development of data acqui-sition and conversion systems by the late1970s. One of the most important of these de-velopments was the design of the array pro-cessor which has become an integral part ofthe data acquisition and conversion systemsused in the most recent CT systems.

Once the image is displayed and initiallyreviewed, it is often important that this infor-mation be retained. Consequently, present CTsystems have a variety of storage media suchas floppy disks or magnetic tape available.The type of storage facility employed dependsto a large extent on the length of time the in-formation is required to be held.

The availability of various storage media,therefore, provides a means of recording,storing, and viewing patient scans indepen-dently of the scanning system's operationalviewing unit. Consequently, health profes-sionals are provided with around-the-clockaccess to existing patient scans, irrespectiveof the in-use status of the basic scanner. Withpresent CT systems, patient records can bestored on floppy disks or magnetic tape in lessthan 1 min. These magnetic storage devicescan serve as a means of permanent storage ofpatients' records or may be erased and thenused again.

Although there have been technologicalimprovements of methods for generating xrays during this century, for the most partmedical x-ray sources are basically the sametoday as they were in the early years. There isa need to develop new methods of generatingx rays, including tunable, steerable, and co-herent beams. Improved detectors are alsoneeded. Photographic film will no longer beused for detection and archiving in medicalimaging systems of the next century. High-resolution, two-dimensional detectors withhigh sensitivity and capable of rapid se-quence imaging and energy resolution areneeded. New methods of practical and effi-cient picture archiving, image communica-tion, and three-dimensional image displaywill also be important areas for significantwork to be done.

3.6.2 Nuclear Medicine. Nuclear medi-cine has been defined as the application of ra-


dioactive materials (tracers) to medical diag-nosis and treatment (see NUCLEAR MEDICINE).It is a classic example of a medical disciplinethat has embraced and utilized concepts de-veloped in the physical sciences. Conceived asa "joint venture" between the clinician andphysical scientist, nuclear medicine hasevolved into a science with its own body ofknowledge and techniques. In the process,the domain of nuclear medicine has grown toinclude studies pertaining to

1. the creation and proper utilization of ra-dioactive tracers (or radiopharmaceuti-cals),

2. the design and application of appropriatenuclear instrumentation to detect and dis-play the activity of these radioactive ele-ments, and

3. the determination of the relationship be-tween the activity of the radioactive tracerand specific physiological processes (Wag-ner, 1975).

The gamma camera system, one of themost basic instruments for diagnostic nuclearmedicine (Spencer and Hosain, 1986), con-verts the radioactive emissions into an image(Fig. 12). Interfacing this device with a digitalcomputer enables clinicians to perform datacollection, storage, and analyses.

The gamma camera systems are large andheavy and cannot be moved easily. They areregarded as stationary cameras. However,

relatively mobile versions are available withcomputer interface especially for cardiacstudies. Gamma cameras often have capabili-ties for obtaining whole-body images by lin-early moving the camera head or the patientbed. Often called scanning cameras, theyhave replaced rectilinear scanner systems. Amajor innovation in gamma camera designhas been the addition of an extra camerahead with rotational capabilities which isused with a computer system known assingle-photon-emission computed tomogra-phy (SPECT) for carrying out optional tomog-raphic work. The technique is known as com-puter-assisted reconstruction tomography(CT) scanning. Tomograms represent the im-ages of isolated cross-sectional slices of thebody. They facilitate identification of abnor-malities that are otherwise difficult or impos-sible to identify in a two-dimensional imagecovering overlying and underlying tissues(Spencer and Hosain, 1986).

With the discovery of artificial radionu-clides, the "modern era" of nuclear medicinebegan. The availability of these radioactive el-ements increasingly encouraged pioneers inthis discipline to employ radioactive tracertechniques to gain information regarding bi-ological and physiological systems. One of thefirst physiological systems to be studied inboth animal and man was the metabolism ofphosphorus. Using the cyclotron-producedtracer 32P, several investigators observed the

Gamma Rays

Kidneys

DirectedGamma Rays

Oscilloscope Display

GOXy

LightPhotons Photons Converted

to volts

ImagePosition

Electronics

Collimator SodiumIodide

Crystal

PhotomultiplierTubes

Display Output

FIG. 12. Basic steps in obtaining an image in nuclear medicine.


great efficiency with which the body absorbedinorganic phosphorus and preferentially uti-lized it in rapidly multiplying tissues, such asthose associated with malignancies. In 1936,John Lawrence, recognizing the therapeuticimplications of these findings, acted. He used32P in the treatment of leukemia, and in theprocess inaugurated the therapeutic employ-ment of artificial radionuclides (Wagner,1975).

Although the early uses of radioactive ma-terials in medicine were chiefly in radiationtherapy, today most radioactive materials areused to provide useful diagnostic informa-tion. These radionuclides can be monitoredwithin the patient (in vivo) or in variousbodily fluids removed from the patient (invitro). For example, it is possible to inject apatient with a radioactive substance that is"taken up" by a particular organ such as thekidney. By placing a detector over the kid-neys, the amount of radioactive material ac-cumulated by the kidney can actually be mea-sured. This uptake test allows the clinician tomonitor the activity of specific organs and de-termine whether they are functioning prop-erly. Another example of an in vivo study in-volves imaging the distribution of a radionu-clide within an organ. This can be very im-portant, especially since it has beendemonstrated that abnormal tissue tends toaccumulate more or less of the radionuclideadministered than the normal tissue sur-rounding it. In this way, in vivo measurementcan help the clinician delineate the presenceof these tissue abnormalities.

The in vitro category, on the other hand,includes tests made outside the body. Thesetests are used to study various chemical, aswell as physiological, processes. Today, invitro tests are capable of detecting extremelysmall amounts of various hormones andchemicals in the blood and have been used todetermine

1. insulin dosage in diabetics,2. whether individuals are immune to specific

diseases such as hepatitis, and even3. the proper dosage of digitalis required by

cardiac patients.

Recent developments in this area have indi-cated that this is an area of application thatwill continue to grow in importance over thenext decade.

The major thrust of the current applicationin nuclear medicine lies primarily in the useof radioactive tracers in both in vivo and invitro studies to evaluate various physiologicalsystems within a patient. The key to successin this application is the specificity of the ra-dioactive material utilized (Bronzino, 1977).That is, the more closely the radionuclide canbe tied to a specific function, then the easier itis to examine the dynamic physiological sys-tem under study. Clearly, it is beyond thescope of this text to provide a complete out-line of all the possible applications presentlybeing utilized. However, some of the mostcommon clinical applications of nuclear tech-nology in studying major organs are summa-rized in Table 5. Obviously, these applicationsare only representative of the type of infor-mation available using nuclear instrumenta-tion techniques.

Although the initial notion of developingradioactive "magic bullets" capable of seekingout and destroying diseased tissue in the hu-man body has not been realized, it is increas-ingly evident that the techniques embodied incurrent nuclear medicine (NM) clearly allowthe acquisition of quantitative informationnot available by other means (Spencer andHosain, 1986). The utilization of radio-nuclides makes possible the measurementand visualization of the regional function. Asa result, it is possible to use nuclear technol-ogy to determine both the site and activity(rate of change) of essential biological pro-cesses, thereby permitting abnormalities, i.e.,regions of dysfunction, to be detected.

Since most physiological processes withinthe body are usually in a dynamic state inso-far as they exhibit continual change, radioac-tive tracer techniques have enabled the clini-cian to monitor accurately the activity of avariety of different physiological systems.These systems range from the pulmonary andcardiovascular systems, to renal function, tothe microvascular circulation of the eye. To-day, several of these procedures are widelyused in clinical medicine, whereas others areconducted only in research laboratories. Ashas been the case in other fields of medicine,procedures that are presently being viewed as"ancillary" may become an essential part ofthe routine medical examination conductedin the future.

Although NM will continue to be an impor-tant imaging modality, improved radiation


Table 5. Clinical application of nuclear medicineimaging technology.

1. Brain scanninga. Detection of intracerebral-space-

occupying disease: primary or secondaryneoplasms, abscesses, arteriovenousmalformations

b. Evaluation of cerebrovascular diseasec. Detection and localization of intracranial

injury after trauma2. Lung scanning

a. Diagnosis and management of pulmonaryembolism

b. Evaluation of regional function inemphysema and other forms of chronicobstructive lung disease

c. Evaluation of pulmonary venoushypertension

3. Thyroid scanninga. Evaluation of thyroid size, position, and

functionb. Functional assessment of thyroid nodulesc. Diagnosis of functioning metastatic lesions

in patients with known carcinoma4. Liver scanning

a. Evaluation of liver size, configuration, andposition

b. Preoperative search for metastatic diseasewhen a primary neoplasm exists elsewhere

c. Functional evaluation of cirrhosis andother diffuse parenchymal processes

5. Spleen scanninga. Evaluation of spleen size, shape, and

positionb. Evaluation of spleen functionc. Detection of intrasplenic-space-

occupying disease6. Pancreas scanning

a. Carcinoma of the pancreasb. Pancreatitisc. Miscellaneous pancreatic problems such as

pseudocysts

sources and detectors with higher resolutionneed to be developed. The development of nu-clear probes for use in the operating roomduring surgery would also be of extreme as-sistance to the surgeon to visualize structuresduring complex operations.

3.6.3 Ultrasonic Imaging. The applica-tion of ultrasound as a noninvasive diagnos-tic tool is presently widely accepted withinthe medical community (see IMAGING TECH-NIQUES, BIOMEDICAL). AS a matter of fact, di-agnostic ultrasound studies are often themethod of choice because they provide infor-mation otherwise not available. The term ul-trasound is used to describe sound waves

(mechanical vibrations) that are beyond therange of human hearing, that is, above 20 000Hz. Since sound waves of any frequency areessentially vibratory phenomena, their trans-mission from one point to another requiresthe presence of matter. As a result, substancesbest suited for transmission of sound wavesare those with a significant number of mole-cules. Consequently, solids are better trans-mitters of sound waves than gases, in whichthere are fewer molecules. In a vacuumwhere there are no molecules present, theconduction of sound waves becomes impossi-ble.

Since the composition of each substancevaries, these ultrasonic or high-frequencysound waves travel through each of them atdifferent velocities. Thus it is possible to in-vestigate the internal composition of manymaterials simply by studying the transmis-sion of ultrasound through them. In addition,just as audible sound under correct condi-tions produces echoes that can be heard, ul-trasound, also under the correct conditions,produces echoes that can be detected with ap-propriate instruments, and then processedand displayed. The application of these basicconcepts of ultrasound transmission andecho-ranging led to the development of non-destructive testing techniques in industry andeventually to the utilization of ultrasonictechniques in the conduction of noninvasivetesting in medicine today. However, althoughthe discovery of ultrasound preceded the dis-covery of x rays by 12 years, x rays found al-most immediate clinical application, whilethe use of ultrasound did not become wide-spread until much later. The primary reasonfor this delay is that the application of ultra-sound had to await the development of appro-priate technologies to detect the presence ofechoes and display the information in ameaningful manner.

Real-time ultrasonic examinations are be-ing used diagnostically to characterize nor-mal and abnormal anatomical structures ac-curately in many areas of the body (Peura,1986). Ultrasonic images of the fetus, for ex-ample, are especially useful in fetal examina-tions since there is no electromagnetic radia-tion danger, and they can be used to guide aneedle to harvest ovary material for patholog-ical tests. Today, it is estimated that from one-half to two-thirds of the pregnant women inthe United States have at least one fetal ultra-


sound scan, while in Great Britain and Ger-many fetal examination by ultrasound is re-quired by law.

Fetal ultrasound scans are used to view thefetus and to determine whether the fetus isnormal. Fetal anatomical features includingthe width of the fetal head, size of brain ven-tricles to monitor possible hydrocephalus,crown-to-rump length to determine the age ofthe fetus, spinal examination to check for ab-normalities, the femur length to correlatewith biparietal diameter to assess properphysical development of the fetus, and detect-able fetal anomalies can be determined.

Real-time ultrasound has been used to per-form interventional therapeutic techniqueson the fetus in utero. Fetal transfusions havebeen performed using real-time ultrasonic vi-sualization. Also, ultrasonic guidance hasbeen used to drain hydrocephalus, posteriorurethral valves, and chylothorax in utero.

The introduction of ultrasonic examina-tions of the heart (Fig. 13) has had great im-

B

FIG. 13. (A) Diagnostic ultrasound being used to as-sess cardiac function. (B) Once trained, the physiciancan interpret the ultrasonic images shown here to de-tect the presence of any abnormalities. (Courtesy ofPecker Corporation, Cleveland, OH.)

pact on the field of cardiology since thepresent real-time two-dimensional ultra-sound images or echocardiograms provide analmost unlimited number of cross-sectionalimage planes. Furthermore, using real-timescanners, additional spatial resolutions of thevalve morphology as well as the cardiacchambers is now possible. The recent addi-tion of Doppler flow measurements toechocardiography imaging also holds greatpromise for the future, since the cardiologistwill be able not only to visualize the move-ment of cardiac structures but also to mea-sure the blood-flow velocity in the heartchambers and great vessels as well.

Superficial structures, located less than 5cm from the skin surface, can also be imagedin real time using ultrasound techniques.Since depth penetration is not a requirement,high-frequency transducers with resultantsubmillimeter anatomic resolution are used,thereby permitting very small lesions (2-3mm) to be observed. Superficial anatomicalstructures which can be imaged include thethyroid, carotid arteries, eye, scrotum, breast,and subcutaneous tissue.

Ultrasonic examinations of the eye are im-portant especially when an ophthalmologistcannot visually examine the eye (in situationsin which opaque material such as blood ispresent or when the patient has cataracts). Itwould be unfortunate to have a situation inwhich a cataract was removed only to findthat the patient had a retinal detachment or alarge melanoma. The major application of ul-trasonic examinations of the eye is in theevaluation of nonmetallic foreign bodies, ret-inal detachment, and intraocular tumors. Theavailability of high-frequency transducersmakes evaluating the eye for periorbital andintraorbital disorders possible.

The future of the medical applications ofdiagnostic ultrasound is tied to the progressof electronic and computer technology. Aselectronic and computer circuits becomemore powerful for the same hardware vol-ume and cost, more sophisticated ultrasonicimagers will be developed and new medicalapplications will be found. Furthermore, thefuture of diagnostic ultrasonic applications inmedicine is contingent on the development ofimproved digital processing of the ultrasonicdata. New image processing algorithms willhandle and quantify the large amounts of ul-trasonic data. In present-day systems, once


the data are stored in relatively inexpensivedigital memory devices, they can be manipu-lated to improve the image quality and tomake simple calculations of tissue dimen-sions. Further work remains in terms of im-proving the image quality, extracting infor-mation about the nature of the tissue, andmaking accurate calculations of tissue dimen-sion, including volumes, from three-dimensional measurements.

Perhaps one of the most exciting and chal-lenging areas of ultrasonic imaging dealswith tissue characterization. Wells (1977) re-viewed the early work in this area and indi-cated that the ultrasonic signal (or signature)can distinguish between normal or abnormaltissue. A number of ultrasound parametershave been investigated, including attenua-tion, scattering, and velocity of propagation.These parameters now need to be tested to de-termine, e.g., from an appropriate ultrasonicscan of the heart, whether a myocardial infarc-tion has taken place, and if so, how severe itwas. Similar questions need to be posed forbenign and cancerous tissue.

Another area of future development dealswith the development of specialized transduc-ers that would be placed inside the body forbetter imaging of a specific organ. For in-stance, approximately 30% of all men aged 50or over have prostate cancer. It has been pro-posed that a high-resolution ultrasonic trans-ducer operating at 10 MHz, when placed inthe rectum, could provide high-resolution ul-trasound images of prostate cancer. Thisshould give more definitive results than thoseavailable with the normal digital examinationfor prostate cancer.

3.6.4 Magnetic Resonance Imaging. Tis-sue variations can be measured by methodsother than those using x rays. For example,protons, neutrons, high-frequency soundwaves, or nuclear magnetic resonance canalso be employed. Each of these energy-con-taining sources can be used to generate sets ofmeasurements or projections at different an-gles across the body, and, in a similar man-ner, a picture can be reconstructed fromthem.

In recent years, attention has focused onbody-scanning devices capable of providinginformation on specific chemicals as well asstructural information about soft tissues. Em-ploying magnetic resonance imaging {q.v.)

(MRI) techniques instead of x-ray radiation,several systems have produced images thatpermit the detection of healthy bone, organs,and tissue, as well as areas of chemical andstructural irregularity (Lauterbur, 1973). Thismethod is noninvasive, penetrates bony struc-tures without attenuation, does not use ioniz-ing radiation, and appears to be without haz-ard. As a result, MRI has become an essentialand well-established technique for analytic,structural, and dynamic investigations ofmatter in many disciplines, especially chem-istry and physics, and in recent years hasmade significant inroads in the field of medi-cine (Taylor, 1986).

Although MRI is still a relatively new tech-nology, it has already changed the definitionof optimal diagnostic care in several clinicalareas, particularly the brain, spinal cord, andmusculoskeletal system. Thus, many radiolo-gists, neurosurgeons, neurologists, and ortho-pedists are incorporating MRI scanning intotheir practices, either as a single diagnostictest or as a complement to other modalitiessuch as computed tomography (CT).

3.7 Biomedical Computing

During the past two decades, the expan-sion of the use of computer technology hasbeen explosive, involving almost every facetof human activity. Today computers arenearly everywhere, and yet these devices arestill considered to be in their infancy. This ob-servation is especially true in the utilizationof computer technology in the clinical envi-ronment. In recent years, the introduction ofcomputerized systems into the medical envi-ronment has greatly accelerated, and there isevery indication that this will continue. In thefuture, it is almost certain that computer sys-tems will be even more extensively utilized byhealth care systems than they are today. Ma-jor areas that have been and will continue tobe important include patient care and the de-velopment of medical expert systems to assistclinicians in the diagnosis and treatment oftheir patients. As a result, these evolving com-puter technologies will have significant im-pact on U.S. health care procedures and poli-cies into the 21st century.

The digital computer is clearly the linch-pin for modern state-of-the-art informationprocessing systems. This is especially true inmodern health care institutions. The tech-


niques actually used to collect, store, retrieve,and analyze data on the status of a patient,however, have been until recently quite slowand inefficient, even rudimentary. Since thequality of patient management and care de-pends on the rapid processing of accurate in-formation about the patient's status, compre-hensive computer-based health care informa-tion management systems have been increas-ingly used for these purposes. In spite of theprogress to date, it is still the case that inmany hospital and other health care facilities,patient management and care could be fur-ther enhanced by the adoption of currenthardware and software data processing sys-tems. Moreover, in the future, the types of in-formation processing tasks that could be car-ried out by health care professionals will beeven further expanded as new applications ofcomputer-based technologies are developed.

Since the early 1960s, health care technol-ogies based on the digital computer have be-come more and more pervasive. Advances inalmost all types of medical research havecome to depend heavily on computer-basedtechnologies, either through the acquisitionof accurate data from experimentation or the

analysis of that data. Efficient financial man-agement of health care facilities has also be-come increasingly dependent on high-speeddata collection and retrieval of patient-relatedinformation. Only with such systems is it pos-sible to achieve economic management ofhospital inventories of drugs and equipmentand provide accurate accounting of patientcare costs and billing.

Since the 1970s, patient care computingsystems have been developed to provide com-prehensive information about the health carestatus of the patient (Fig. 14). These systemsutilize computer hardware and software tocollect, retrieve, and present clearly a widevariety of patient-related information (Jen-kins, 1978; Bronzino, 1982). The developmentof such patient care systems has significantlyaltered and improved the way in which healthcare professionals utilize information aboutthe patient's health care status. For example,patient care computing systems do the follow-ing:

1. provide clinicians with access to sophisti-cated and often widely dispersed re-sources,

Medical History

Physical Exam

X-ray 8 Lab Report

Physiological Measurements

Physician's Orders

Procedures

Therapy 8 Medication

Progress Notes

Diagnosis

Therapeutic Decision

Assurance of Quality Care

Teaching

Clinical Research

Epidemiological Studies

Medical Audit

Accounting 8t Administration

FIG. 14. Block diagram of medical information systems.


2. simplify the assembly of patient-relateddata for review by all types of health careprofessionals, and

3. assist health care professionals in makingfundamental decisions about patienthealth care strategies.

As current systems are more widelyadopted, the scope of the services they pro-vide expands, and patient care computingwill enhance both clinical performance andpatient care.

Specific patient-care-related computer ap-plications can be (approximately) allocated tothe following categories (Bronzino, 1982):

• clinical laboratory analysis;• acquisition of patient data and the evolu-

tion of automated multiphasic testing sys-tems;

• computer-based medical-record data col-lection, storage, and information retrievalsystems for patient management;

• automated patient monitoring;• diagnostic support systems (such as electro-

cardiographic interpretive systems);• medical imaging;• artificial intelligence and expert systems.

The application of computers in biologyand medicine has been important, and therehave been many advances in applying com-puter technology to problems in the basic lifesciences and clinical medicine. Even so, prob-lems remain where computer technology canhave a significant effect.

One class of these problems revolvesaround record keeping in clinical medicine. Ahospital chart today does not look much dif-ferent from what it did ten or twenty yearsago, with the exception that it is thicker be-cause of additional diagnostic proceduresand patient monitoring data available. Tryingto extract information from one of theserecords remains a problem for anyone otherthan those intimately involved in the patient'scare and the production of the record in thefirst place. There is little standardization, andstorage and retrieval techniques are not at thefrontiers of technology. Yet the medical chartis becoming increasingly important in the pa-tient's care, as well as for medical-legal rea-sons. Change in this feature of clinical medi-cine has been slow and will probably con-tinue to be slow until such time that truly

useful systems are developed and cliniciansbecome more comfortable with computertechnology. It is anticipated that these condi-tions will evolve in the 1990s, and opportuni-ties for developing new methods of medicalrecord keeping on a national and perhapseven an international basis will be best at thebeginning of the next century. Such computersystems will have to incorporate advances incomputer science such as artificial intelli-gence and expert systems, high-density datastorage, more direct input and output fromhuman beings (such as computer recognitionof speech), and a combination of alpha-numeric and pictorial data.

Computers will continue to play an impor-tant role in medical instrumentation, as theyhave begun to do in the late 1980s. No longerwill instruments be concerned only with datagathering. Signal processing, including spe-cific pattern recognition, self-calibration, pre-ventative maintenance, data transmission,and multiple instrument control, will con-tinue to offer research opportunities. As in-strumentation and computer technology bothbecome more complex, it will be important todevelop software to keep the technologywithin reasonable bounds for human usersand to optimize the application of the hard-ware to medical problems.

While computer engineers are just begin-ning to find the value of electronic systemsfor parallel processing as a means of speedingup complex computer operations, biologicalsystems have been using this technique allalong. Complex pattern recognition routinesplay an important role in biochemical reac-tions, such as between enzyme and substrateor antigen and antibody. Although investiga-tors have explored the possibility of harness-ing these complex processes into computa-tional hardware, this field still remains at thefrontier of technology, and many problemswill need to be solved before techniques canbe demonstrated and applied.

4. STATUS OF BIOMEDICALENGINEERING EDUCATION

The first undergraduate programs in bio-medical engineering were initially organizedas options in the traditional engineering un-dergraduate departments (such as electrical


and mechanical engineering). As the field ofbiomedical engineering matured, separatelyaccredited programs in biomedical engineer-ing emerged. Today there are 18 organizedundergraduate programs which have been ac-credited by the Accreditation Board for Engi-neering and Technology (ABET). A list of thepresently accredited programs with the yearof initial accreditation is shown in Table 6.

A significant number of undergraduate"option" programs, however, have not movedto separate department status. Since growthin enrollments and in the demographic pro-jections for college-age youth has nearlyceased, it is expected that few, if any, new de-partments will be formed (Pilkington et al.,1989).

The first formal programs in biomedicalengineering began at the master's level, theprogram at Drexel which began in 1959 beinga prime example; Johns Hopkins and the Uni-versity of Pennsylvania began Ph.D. pro-grams shortly thereafter. Graduate programs,because they are either research oriented orin some cases clinically oriented, are verymuch cast in the "image" of the particular fac-ulty forming the program. In this respect,graduate programs often have different direc-tions, and thus offer very different areas ofspecialization to the student. For example,some institutions have a basic research effortin physiological system modeling, others em-phasize instrumentation and devices, whilestill others may have a clinically based pro-gram or one that emphasizes rehabilitation

Table 6. Bioengineering group accreditedprograms (IEEE Lead Society, with AIChE, ASAE,ASME, and NICE). (Programs in this group areaccredited according to the program criteria forbioengineering and similarly named engineeringprograms. Year of accreditation is shown.a)

BioengineeringArizona State University, 1985University of Illinois at Chicago, 1976University of Pennsylvania, 1982Texas A&M University, 1977

Biomedical engineeringBoston University, 1983Brown University, 1973University of California at San Diego, 1987Case Western Reserve University, 1977Duke University, 1972University of Iowa, 1985Johns Hopkins University, 1983Louisiana Tech University, 1978Marquette University, 1983Northwestern University, 1982University of Pennsylvania, 1986Rensselaer Polytechnic Institute, 1972Tulane University, 1981Wright State University, 1988

aFrom Pilkington et al (1989).

engineering. This diversity is appropriate be-cause no one program can possibly providethe depth of education and training requiredto be competent in all fields (Pilkington et al,1989).

In Table 7, the actual number of students

Table 7. Total engineering and biomedical engineering.

Fall (yr)

197519761977197819791980198119821983198419851986

AverageaFrom

B.S.-BME

161019542355265427243252342034786747370135183627

Pilkington

Full-time enrollments (total for indicated degree)

B.S.-Eng.

231 300257 800289 300311200340 500365 100387 600403 400406 144394 635384 191369 520

etal (1989).

Percent

0.700.760.810.850.800.890.880.860.920.940.920.98

0.81

M.S.-BME M.S.-A11

341302452451464481459510679693641660

26 00425 51626 10725 36024 34928 57130 67932 70937 76937 71838 49942 664

Percent Ph.D.-BME

1.311.181.734.781.911.681.501.561.801.841.661.55

1.61

233210294243279256287287300283348423

Ph.D.-All ]

11281 :10 96312 359 ;12 32113 461 :14 465 115 47216 44218 54019 5592149424 227 1

1

^rcent

>.O71.92>.38L.97>.O7L.77L.85L.75L.62L.45L.62L.75

L.93


enrolled both in engineering and in biomedi-cal engineering (BME) for the B.S., M.S., andPh.D. is shown. It will be noted that at the un-dergraduate level, the total engineering en-rollment peaked in 1983, and that biomedicalengineering represents 1% of the total num-ber. On the other hand, the percentage ofBME students has remained fairly steady inrecent years on both the graduate and under-graduate levels, and on this basis the expecta-

tion is for BME to follow engineering enroll-ments as a whole.

Finally, in Table 8 are listed the biomedi-cal engineering undergraduate and graduateprograms by state (Browneller, 1986a-f). Itwill be noted that the field of biomedical engi-neering is represented in almost every stateand has indeed become an important compo-nent of the engineering profession.

Table 8. Bioengineering education. Types of programs offered: B.S./B.A., Bachelor of Science andBachelor of Arts; M.S., Master of Science; Ph.D., Doctor of Philosophy; M.D./Ph.D., M.D. and Ph.D.combined.

State

ArizonaArizona State Univ.Univ. of Arizona, Tucson

ArkansasUniv. of Arkansas, Fayetteville

CaliforniaCalifornia State Univ., SacramentoStanford Univ.Univ. of California, BerkeleyUniv. of California, DavisUniv. of California, Los AngelesUniv. of California, Santa Barbara

ColoradoColorado Technical CollegeUniv. of Colorado, Boulder

ConnecticutHartford Graduate CenterTrinity CollegeUniv. of BridgeportUniv. of Connecticut

District of ColumbiaCatholic Univ. of AmericaGeorge Washington Univ.

HawaiiUniv. of Hawaii, Manoa

IllinoisNorthwestern Univ.Univ. of Illinois, ChicagoUniv. of Illinois,Urbana/Champaign

IndianaPurdue Univ.

IowaIowa State Univ., AmesUniv. of Iowa, Iowa City

KansasKansas State Univ.

B.S./B.A.

XX

X

X

XX

XX

XX

X

X

X

X

X

M.S.

X

X

XXXXXX

X

X

XX

X

XXX

X

X

XX

X

Ph.D. M.D./Ph.D.

X

X

XXXXX

X

XX

X

XX X

X

X

XX

X

(continued)


Table 8. (continued).

State B.S./B.A. M.S. Ph.D. M.D./Ph.D.

MarylandThe Johns Hopkins Univ.

MassachussettsBoston Univ.MITNortheastern Univ.Western New England College

MichiganMichigan State Univ.Michigan Technological Univ.Univ. of MichiganWayne State Univ.

MinnesotaUniv. of Minnesota

NevadaUniv. of Nevada, Renoa

New HampshireDartmouth College(Thayer School of Engineering)

Univ. of New Hampshire

X

XX

XX

X

XX

XX

X

X

New JerseyFairleigh Dickinson Univ.New Jersey Institute of TechnologyRutgers Univ.

XXX

XX

New MexicoUniv. of New Mexico

New YorkColumbia Univ.Hofstra Univ.New York Institute of TechnologyRensselaer Polytechnic InstituteUniv. of RochesterSyracuse Univ.

OhioAir Force Institute of TechnologyCase Western Reserve Univ.Ohio State Univ.Univ. of AkronUniv. of ToledoWright State Univ.

OklahomaUniv. of Oklahoma

PennsylvaniaCarnegie Mellon Univ.Drexel Univ.Univ. of Pennsylvania

Rhode IslandBrown Univ.

South DakotaSouth Dakota State Univ.

X

XXXXXX

X

X

X

X

X

XX

XXXXXX

X

XXX

X

X

XX

XXXXX

X

XXX

X

XX

X

(continued)


Table 8. Bioengineering education. Types of programs offered: B.S./B.A., Bachelor of Science andBachelor of Arts; M.S., Master of Science; Ph.D., Doctor of Philosophy; M.D./Ph.D., M.D. and Ph.D.combined, (continued.)

State

TexasSouthern Meth. Univ.Texas A&M Univ.Univ. of Texas, ArlingtonUniv. of Texas, AustinUniv. of Texas Health Science Center

VermontUniv. of Vermont

VirginiaUniv. of VirginiaVirginia Commonwealth Univ.Virginia Polytechnic Institute

& State Univ.Washington

Walla Walla CollegeUniv. of Washington, Seattle

West VirginiaWest Virginia Univ.

B.S./B.A.

XX

X

X

M.S.

XXXXX

X

XX

X

X

X

Ph.D.

XXXXX

X

X

X

X

M.D./Ph.D.

X

X

WisconsinMarquette Univ. XMilwaukee School of Engineering XUniv. of Wisconsin, Madison

WyomingUniv. of Wyoming XaDetails not received in time for publication.

X

X

XX

GLOSSARY

Aliphatic Molecule: A molecule belong-ing to that series of compounds characterizedby open chains of carbon atoms rather thanby rings.

Artificial Intelligence: The science ofmaking machines do things that would re-quire intelligence if done by men.

Atherosclerosis: A form of arteriosclero-sis characterized by a variable combinationof changes to the intima of arteries, not arte-rioles, consisting of the focal accumulation oflipids, complex carbohydrates, blood andblood products, fibrous tissue, and calciumdeposits; associated with changes in themedia of the arteries.

Digitalis: The dried leaves of the Digitalispurpurea plant which are powdered into tab-lets or capsules. Cardiotonic glycosides, espe-cially digitoxin and digoxin, are obtainedfrom various species of the Digitalis plant.

Use of these glycosides increases cardiac out-put and results in diuresis.

Etiology: The study of the causes of dis-ease.

Hemodialyzer: Instrument for removalof chemical substances from the blood bypassing it through tubes made of semiperme-able membranes.

Hemolysis: The destruction of red bloodcells with the liberation of hemoglobin whichdiffuses into the fluid surrounding them.

Hermetic: Airtight.Hydrolytic Cleavage: The splitting of a

molecule into two or more simpler onesthrough the addition of water.

Isotropic: 1. Possessing similar qualitiesin every direction. 2. Having equal refraction.

Left Ventricular Assist Device(LVAD): Implantable device used to assistin those instances where the major contrac-


tual muscle of the heart, the left ventricle, isnot performing satisfactorily.

Morbidity: 1. State of being diseased. 2.The number of sick persons or cases of dis-ease in relationship to a specific population.

Morphology: Science of structure andform without regard to function.

Mortality: 1. State of being mortal. 2.The death rate; ratio of number of deaths to agiven population.

Multiphasic Screening: A battery of clin-ical tests to which a patient is subjected in or-der to evaluate his or her medical status.

Orthotic Device: A device for straighten-ing or correcting a deformity or disability.

Osteoporosis: Increased porosity ofbone, seen most often in the elderly.

Periorbital: Surrounding the socket ofthe eye.

Picture Archiving: The use of computersto digitize and store images.

Prosthetic Devices: Devices designed toreplace missing parts (limbs, etc.)—artificialsubstitutes.

Rehabilitation Engineering: A sub spe-cialty of biomedical engineering concernedwith the development of devices to assist thedisabled.

SA (Sino-Atrial) Node: Node at junctionof superior vena cava and right cardiacatrium, regarded as the site of initiation of theheartbeat.

Scintillation: The photoeffect caused bycollision of particles emitted by radioactivesubstances and a detector surface.

Streak Artifacts: Blurs which occur oncomputed tomographic (CT) images.

Sulfanilamide (Para-aminobenzenesul-fonamide): White, slightly bitter, crystallinesubstance derived from coal tar, the parent ofthe azo family of dyes. Formerly widely usedin the treatment of a number of infections,due to its toxic effects its use has been super-ceded by more effective and less toxic sulfon-amides.

Tomography: Any of several noninvasivespecial techniques of roentgenography de-signed to show detailed images of structuresin a selected plane of tissue by blurring im-ages of structures in all other planes.

Thrombogenuity: Producing or tendingto produce a clot.

Ultrasound: Inaudible sound in the fre-quency range of approximately 20 kHz to 10GHz. Ultrasound waves have different veloci-

ties in tissues of different densities and elas-ticity. This property permits the use of ultra-sound in outlining the shape of various tis-sues and organs in the body.

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Further Reading

Anbar, M. (1987), Computers in Medicine, Rock-ville, MD: Computer Science.

Boretos, J. W., Eded, M. (1984), ContemporaryBiomaterials, San Francisco: Noyes.

Bronzino, J. D. (1986), Biomedical Engineeringand Instrumentation, Boston, MA: PWS.

Christensen, D. A. (1988), Ultrasonic Bioinstru-mentation, New York: Wiley.

Feinborg, B. N. (1986), Applied Clinical Engi-neering, Englewood Cliffs, NJ: Prentice-Hall.

Fung, Y. C. (1981), Biomechanics: MechanicalProperties of Living Tissue, New York: Springer-Verlag.

Gedder, L. A. (1986), Cardiovascular Devices,New York: Wiley.

Kline, J. (1988), Handbook of Biomedical Engi-neering, New York: Academic.

Macovski, A. (1983), Medical Imaging Systems,Englewood Cliffs, NJ: Prentice-Hall.

Park, J. B. (1979), Biomaterials: An Introduction,New York: Plenum.

Webster, J. G. (1988), Encyclopedia of MedicalDevices and Instrumentation, New York: Wiley.

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