Atoms for better health care

Nuclear cardiologyfor developing countriesSimple devices may answer practical needs

by L.E. Feinendegen

The "power of the atom" — of radionuclides — isthe primary tool of nuclear medicine for observing thevital functions of cells and tissues. As applications anddetection devices have diversified, and especially sincethe gamma camera has become available, many havetaken up the advancement of the art of imaging as aunique possibility for describing organ structures andfunctions in a way that somewhat resembles, but cannotbe achieved by, conventional radiography. In fact,radiology departments began to call themselves imagingdepartments.

Over the past few years, imaging with ultrasound hasbeen added, and together with nuclear magneticresonance, is now gaining rapid acceptance because ofits unprecedented quality. In view of these fascinatingdevelopments, one needs to examine the role of nuclearmedical imaging in the future of clinical practice andresearch.

Currently, many physicians, administrators, andfunding groups believe that nuclear medical imaging isbeing threatened or is becoming more and more obsoletein competition with the more recent imaging techniques.No doubt this is partly true if the emphasis is placed onimaging itself, image quality, and the infrastructureneeded to produce it. This question of competitionbetween imaging techniques is of great importance,since resources are limited and one must aim to achievethe most favourable cost-benefit ratio for long-termplanning.

Attempts should be made to assess this situation, andto make suggestions for development, that are of parti-cular interest where large numbers of people lack fullmedical care, where the spectrum of diseases is quitedifferent from that in industrialized countries, and wherefunding must follow priorities set by the desire to avoid

Dr Feinendegen is the Director, Institute of Medicine, NuclearResearch Centre, Jiilich, in the Federal Republic of Germany, andprofessor at the Department of Nuclear Medicine, University ofDiisseldorf. This article is based on an invited paper presented in 1985at the IAEA/WHO symposium "Nuclear Medicine and Related Radio-nuclide Applications in Developing Countries", the proceedings ofwhich may be ordered from the IAEA Division of Publications.

as much suffering as possible with sometimes extremelylimited financial resources. The case of managingcardio-vascular disease is especially suitable as a sub-ject, and its discussion here is meant to apply to nuclearmedical imaging in general.

Assessment of imaging

Of course, nuclear medical images are a primaryexpression of the information obtained by observing thepathway of radionuclides in the body. It is this fate ofradionuclides, or more specifically of radioactivelylabelled substrates, that interests physicians most;indeed, images should be viewed as windows throughwhich one can examine this fate. One may even say thatnuclear medical images are fully exploited only whenthey unravel this fate, in the sense that radioactivelylabelled cells or metabolites can permit the observationof the cellular and molecular level of organization of thebody. In this way, nuclear medical images have thepower to make the body biochemically transparent as noother imaging technique can do. This is one importantaspect that should be stressed. It is, therefore, necessaryto first emphasize what the objectives of a diagnosticinvestigation are, and then to turn to the proper tech-niques and tools to achieve them.

If one wants to emphasize structure — or more pre-cisely, organ spaces — it does not appear to be optimalto turn to nuclear medical imaging, provided othermeans are available that are effective and cost less. Butif one wishes to investigate correlations between organspaces and time of passage of a tracer through them,then nuclear medical imaging may be the onlyalternative.

If measuring the passage of a tracer is more importantthan the resolution of the space to which it applies, thensimple, single-probe counters of radioactivity may fullysuffice without adding the luxury of an image. If pas-sages of larger masses through an organ space arerequired without the need to avoid disturbing theobserved system, nuclear medical tracer techniques mayremain the preferred method because of economy,speed, lack of hazard, and better quantification. This is

A gamma camera in use at Pakistan's Atomic Energy Medical Centre in Lahore. (Credit: Pakistan AEC)

IAEA BULLETIN, SUMMER 1986 33

Atoms for better health care

in comparison with other non-invasive approaches, suchas radiology, ultrasound, and nuclear magneticresonance imaging.

These considerations, of course, apply directly tocardio-vascular diseases.

Special case of nuclear cardiology

Primary aims of nuclear cardiology are assessmentsof (1) the pumping function of the heart, especially thatof the left ventricle; (2) myocardial perfusion; and (3)myocardial metabolism. Additional needs may arise forquantifying the capacity of the peripheral circulation toadapt especially the pulmonary circulation and reserve.*

Are these diagnostic demands very urgent in develop-ing countries?

The answer appears to be "yes" and "no" at thesame time: "Yes" for those many individuals who needthe diagnostic work-up, and "no" for those manyindividuals who, because of other serious illnesses, donot, or very rarely do, develop cardio-vascular disease.

The next question then is: Can the specified diagnos-tic demands be met? Here are the main problems:Finances are limited; training is often not sufficient;maintenance of equipment is most difficult for infra-structural and climatic reasons; supply of radiophar-maceuticals is constantly in jeopardy. Nevertheless, thisdoes not advise taking these difficulties as justification toabstain from nuclear medical investigations whereverthey are uniquely in demand.

There are two reasons for this statement: The first isthe need for evolution, from which no one should beexcluded. This demands openness, motivation to engageoneself and to be efficient in a team with colleagues,administrators, and society as a whole. The second rea-son is a psychological one: It would be disastrous towiden the gap between developing and industrialized, orwealthy and poor, countries. Planning should be helpfulhere to co-ordinate investments so efficiently thatcentres of excellence can be maintained. On the onehand, these are a source of pride, and on the other hand,they are an opportunity for training in self-sufficiency asdemands arise and can be financed.

Nuclear cardiology, because of its diversity and itsparticular role in clinical practice, poses a challenge forthe good.

Examining cardiac function

Examinations of cardiac function may resort to com-plex imaging procedures, such as parametric imaging ofthe left ventricular ejection fraction and of wall motion.Both of these, however, can now be analysed to somedegree by ultrasound, even if quantification still leavesmuch to be desired. Cardiac functional assessment bythe fastest flow times and the minimal transit times is

relatively simple and precise as well. The latter investi-gation does not necessarily demand complex imaging;single-probe devices may be quite useful, or even betterfor this purpose.

A single-probe device for specifically measuring theleft ventricular performance (in terms of the ejectionfraction, time and rate, and the filling time and rate) isthe "nuclear stethoscope".* It will be referred to brieflylater in this article, when a new simple device isexplained that may answer a practical need in developingcountries.

Imaging agents

There is no doubt that the diagnosis of coronaryartery disease has immensely profited from the use ofthallium-201 myocardial perfusion imaging. Differentia-tion between the images obtained immediately after aproper exercise load and after a 2 to 3 hour rest periodhas fully proved its clinical significance. It has a sensi-tivity of close to 90% for the practically risk-free andtime-saving diagnosis of coronary artery disease, whenconventional methods, excepting angiography, havefailed to clarify the suspicion.

However, thallium-201 is not only expensive, butalso hampered by a gamma energy emission that is notquite optimal for conventional gamma cameras. Newtracers are actively sought. Recently it was found (firstannounced at a nuclear medicine conference in Kuwaitfrom 17 to 21 February 1985) that iodinatedorthophenyl-pentadecanoic acid is a superb myocardialimaging agent. It is easily prepared and, when labelledwith iodine-123, gives image qualities superior tothallium-201. It is avidly incorporated by the well-perfused myocardium and then becomes trapped there,so that images may be repeated for hours. This com-pound is hardly, if at all, catabolized, in contrast toothers.**

* Clinical nuclear cardiology, edited by D.S. Bergman andD.T. Mason (Grune & Stratum, New York, London, Toronto,Sydney, San Francisco, 1981).

* "The nuclear stethoscope: A simple device for generation of leftventricular volume curves", by H.N. Wagner, R. Wake, andE. Nicholoff, Journal of Cardiology, 38, 747 (1976).

** Iodinated para-phenyl-pentadecanoic acid or iodinated omega-heptadecanoic acid, both of which were found to be most useful forevaluating myocardial metabolism. See "Myocardial imaging andmetabolic studies with (17-123-1) iodo-heptadecanoic acid in patientswith idiopathic congestive cardiomyopathy", by A. Hock,Chr.Freundlieb, K.Vyska, B.Losse, R.Erbel, and L.E.Feinendegen,Journal of Nuclear Medicine, 24, 22-28 (1983); "Kinetics of different123-1- and 14-C-labelled fatty acids in normal and diabetic ratmyocardium in vivo", by T.E. Beckurts, W.W. Shreeve, R. Schieren,and L.E. Feinendegen, Nuclear Medicine Comm., 6, 415—424(1985); and "15-(ortho-123-I-phenyl)-pentadecanoic acid, a newmyocardial imaging agent for clinical use", by M.A. Antar, G. Spohr,H.H. Herzog, K.P. Kaiser, G. Notohamiprodjo, E. Vester,B. Schwartzkopf, B. Losse, H.-J. Machulla, W.W. Shreeve, andL.E. Feinendegen, Nuclear Medicine Comm. (in press).Myocardial metabolism can be assessed by planar scintigraphy andlong-chain fatty acids (such as I-omega-heptadecanoic acid) labelledwith iodine-123, if the labelled catabolites are corrected for by theproper image-substraction technique. Results are practically identicalto those obtained by positron emission tomography and "C-palmiticacid.

34 IAEA BULLETIN, SUMMER 1986

Atoms for better health care

One special advantage of metabolic imaging of themyocardium appears to be the differential diagnosisbetween coronary artery disease and cardiomyopathy,even in an early stage of development. Even subtle,induced changes in myocardial metabolism — • forexample, by alcohol or insulin — have been easilyobserved. Even though metabolic imaging of themyocardium is at present a special test reserved for solv-ing difficult diagnostic problems, it appears thatcardiomyopathies are more common than so far gener-ally believed.

There are challenging questions here, especially inregard to malnutrition, vitamin deficiencies, trace ele-ment deficiencies or overburdens, and to changesinduced by drugs, toxic chemicals, or infections.Particularly in poor countries, one knows little of theeffects of living conditions on myocardial metabolism.Are there at least certain minimal requirements for nor-mal cardio-vascular performance? These are researchquestions with potentially great practical consequences.

A simplified nuclear cardiology

As previously mentioned, there is a need for evolu-tion, response, and adaptation to practical needs. Sucha response is the suggestion of a compact radiocardio-graph that was developed by the Institute of Medicine atthe Nuclear Research Centre, Jiilich, in the FederalRepublic of Germany. Named the parametric gamma-scope, the instrument combines the performance of thenuclear stethoscope with the capacity to measure thecardiac minimal transit time, and to observe changes incardiac, pulmonary, and hepatic blood volume, both atrest and during graded exercise. These three cardio-vascular tests are made in one examination.They measure sequentially the left ventricular perfor-mance, the entire central circulation from the rightatrium to the aortic root including the pulmonary seg-ment, and finally the response of the cardiac-pulmonary-hepatic blood volume distribution during graded exer-cise. The equipment is compact, robust, easily movable,and electronically designed to withstand considerablealterations in room temperature, humidity, and changesin electrical current. The device relies on single-probemeasurements; curves are produced and evaluated by asmall computer with currently available hardware.*

* For further technical information, see the author's paper in NuclearMedicine and Related Radionuclide Applications in DevelopingCountries, proceedings of the IAEA/WHO symposium, IAEASTI/PUB/699, Vienna (1986). Also see "A compact radiocardiographfor simultaneous measurement of left ventricular function and cardio-pulmonary minimal transit time", by V. Becker, M. Schittek,M. Rosen, and L.E. Feinendegen, and "Multiple non-gated bloodpool analysis for measuring central hemodynamics at rest and exer-cise", by G. Spohr, A. Hock, A. Schmid, and L.E. Feinendegen,Nuklearmedizin — Darstellung von Metabolismen und Organ-Funktionen, edited by H.A.E. Schmidt, W.E. Adam; F.K. SchattauerVerlag, Stuttgart, New York (1984); and "The minimal transittimes", by L.E. Feinendegen, K. Vyska, H. Schicha, V. Becker,Chr. Freundlieb, Der Nuklearmediziner (Supplement 1979).

Overall view of parametric gamma scope and one of its probes.

Challenges and needs

The role of nuclear medicine in developing countriesmust be oriented to local needs for clinical practice, thehealth care of .large populations, and the demands forresearch with, sometimes extremely limited resources.To help define the locally different needs, it should bereiterated that nuclear medicine provides the uniqueopportunity to observe the body at the molecular level oforganization and, thus, makes the body biochemicallytransparent.

Depending on the particular diagnostic demands,complex computer-assisted imaging with gamma-camera scintigraphy or emission tomography may be theonly method of choice in some instances, but for theothers it may be an unnecessary luxury. Nuclear cardiol-ogy) with the purpose of non-invasively assessingcardiac function, myocardial perfusion, and myocardialmetabolism, is a particular challenge in both respects fordeveloping countries. Given such requirements, single-probe devices with multiple purpose application are lessexpensive than gamma cameras and promise advanceddiagnostic uses.

Developing countries should be encouraged toparticipate in nuclear medicine's evolution and to assurethat centres of excellence are maintained, not .only fortreatment, but also for the purpose of training.

IAEA BULLETIN, SUMMER 1986 35

Special

IAEA's role in the field

Agency programmes continue to attach a great deal ofimportance to appropriate development and dissemination of cur-rent technical know-how for radiation sterilization, in particularwith regard to health and welfare interests of technologically lessadvanced developing Member States. Particular emphasis hasbeen given to helping development of suitable practices pertinentto indigenous medical and pharmaceutical items, with regard tolocal conditions and environment. Action plans are developedand implemented through periodic panels, expert advisorygroups, topical symposia, research support, and co-ordinationprogrammes, publications, and, primarily, through an elaboratetechnical co-operation and support service to Member States.

Encouraging results are noticeable, particularly in somedeveloping countries of Asia and the Pacific region in implemen-tation of various integral steps for radiation sterilization practicesof medical supplies (see accompanying map). Following success-ful commissioning of two cobalt-60 irradiation facilities in India, in1974, and in the Republic of Korea, in 1975, a spurt of interest inthis nuclear technology was evident in most other countries in theregion.

Today in the region, large-scale cobalt-60 irradiation facilitiesare operating in Bangladesh, Indonesia, Malaysia, Singapore,and Thailand, while smaller pilot gamma-cell facilities are inresearch and development stages in Burma, Pakistan,Philippines, and, more recently, in Sri Lanka. Since 1985, Chinesecobalt-60 facilities, respectively in Beijing and Shanghai, havesought and received IAEA assistance in research support, as wellas in provision of microbiological standard preparations fordosimetry and process calibration. Through these recentdevelopments, the "radiation sterilization map" in Asia and the

' Pacific region has better bridged the gap between Japan andAustralia. Further progress is expected in the region.

The map also gives an overview of the status in developingregions of Europe, the Middle East, Africa, and Latin America.Africa, the Middle East, and Latin America are marked by a highdegree of heterogeneity and inadequacy, leaving much scope forfuture development. In the African region, Egypt and SaudiArabia have already commissioned and are operating cobalt-60facilities producing sterile medical supplies for indigenous healthcare. In striking contrast, many other countries in the region donot even have at the elementary level a technical and manpowerinfrastructure, while some others (e.g., Algeria, Ghana, Morocco,Zaire, and Zambia) are in an advanced planning stage. A promo-tion of regional co-operation is desired.

Recently some countries in Latin America have been con-sidering possible regional co-operation in industrial uses of radia-tion processing, for which medical supply sterilization is a likelycandidate.

Almost all cobalt-60 facilities installed in developing MemberStates through IAEA support are located administratively in therespective governmental establishments, such as the AtomicEnergy Commission or the Ministry of Science and Technology.Consequently, their operation involves the "service sterilization"of medical products derived from local manufacturers. Thisimplies that a close co-operation be maintained with facility cus-tomers at all stages, including education and technical guidancefor specifications, compatibility, and standardization throughgood manufacturing practices and national regulation. Advisorygroup meetings and workshops, including one in Sri Lanka laterthis year, and regional co-operative projects for Member Stateshelp fulfil such promotional objectives and development of radia-tion technology well suited to upgrading local health care.

Nearly half of medical supplies and devices such as these are beingsterilized by radiation in some countries. (Credit: Isomedix)

Legend:

0 Gamma irradiator for medical suppliesand/or food irradiation

A Research, technical assistance, and/ortraining

36 IAEA BULLETIN, SUMMER 1986