Liver scintigraphy of patient in Pakistan's Larkana Institute ofNuclear Medicine and Radiotherapy. (Credit: Pakistan AEC)

Nuclear imagingAdvancesand trendsDevelopments in several fieldsare influencing future directions

by Gerard van Herk

' 'One picture is worth more than a thousand words''.The validity of this expression, which is a leitmotiv

in the publicity sector, is not limited to the strategyunderlying advertisements. It certainly also applies tothe commanding role images play in diagnostic medi-cine. To draw lines of development in imaging instru-ments, one must start where the arsenal of nuclearmedicine equipment stands today. In this article, nuclearimaging instruments that are likely to be of interest to thenuclear medicine community of developing countries areemphasized.

The rectilinear scanner was the earliest instrumentwith which one created an image of a radioactive distri-bution inside the body. It still is a common — and relia-ble — piece of equipment in many nuclear medicinecentres in the Third World.

The scanner consists of a detector fitted with a leadcollimator, which focuses the radiation-sensitive field ofview to a narrow spot below it. The detector is beingmoved along a meandering path oyer the selected areawhere a radioactive tracer is distributed — for example,the organ to be imaged in the patient. The amount ofradioactivity measured at each position is simultaneouslyrecorded with a printing device attached at the other endof the moving detector assembly. After the total area hasbeen scanned, the total pattern of printed dashes, the"scan", is a life-size presentation of the tracerdistribution.

Dr van Herk is a staff member in the Medical Applications Section ofthe Division of Life Sciences.

The type of gamma camera that still is most com-monly used is the one designed by Hal Anger in 1959.In the "Anger" gamma camera, the radioactive distri-bution is projected as a whole through a parallel-holecollimator onto a thin scintillation crystal. The diameterof its field of view can range from 18 to 50 centimetres.Each scintillation event on the crystal is "seen" by anarray of photomultiplier tubes (PMTs, typically 19 to75). The relative outputs of the PMTs are analysed byan electronic positioning network, which produces twoposition signals per registered photon. When enteredinto a display monitor, the original "scintillation" isrepresented by a corresponding light dot on the screen.After accumulating several thousands of those countswith a photocamera, the resulting photograph, the"scintigram", is a projected image of the functioningorgan.

Although considered old-fashioned by comparison,the scanner does have a number of advantages over thegamma camera. By its very nature, it provides anundistorted and uniform response over the whole areaimaged; it has a satisfactory performance for higher-energy nuclides, some of which are more readily avail-able than technetium-99m, which is mostly used. Thescanner offers a superior contrast in deeper structures.Finally, it is usually less vulnerable to adverse environ-mental circumstances, to unstable power conditions, andto irregular maintenance, situations common in manydeveloping countries.

On the other hand, there are disadvantages of scan-ners: they cannot be used for dynamic studies, i.e., to

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image those tracer distributions that are not stationaryfor the duration of the study. The resolution of a scan isinferior and looks less appealing than the scintigram.The sophisticated gamma camera as such, for that mat-ter, commands more respect than the scanner, the instru-ment of the pioneer years.. Whatever the nature of the imaging instrument, it isessential to regularly assure that each piece of equipmentis functioning properly. This awareness has to translateinto a set of quality control (QC) procedures regularlyfollowed. The IAEA supports a number of programmesand projects and has published a technical document onthis subject.

Computer applications

In the early 1970s, there was widespread researchinto applying the computer for processing scintigraphimages. It resulted, within the same decade, in an expan-sive growth of commercial image processing computers.

The use of a computer for static images providesmainly a cosmetic improvement of the scintigram. Thecontrast in the image may be enhanced by subtractingbackground activity, or by emphasizing any range in theintensity scale containing significant clinical informa-tion. Distortions and artefacts, almost inherent togamma camera imaging, can be partly corrected for,with the most common corrections for deficient unifor-mity and linearity. Finally, there are numerous "filter-ing" programs to improve on the "noise" or unsharpedges of organs in the scintigram.

Apart from its usefulness for visual improvement ofimages, computer processing is indispensable for analy-sis of dynamic studies, i.e., in order to assess changesin tracer distribution over time. Immediately followinginjection of the tracer, a number of consecutive imagesare recorded in the computer memory. The activity inthe organ or selected regions of interest in it are plottedversus the time. These time-versus-activity curves arethen analysed using mathematical and physiologicalmodels. The quantitative parameters produced arerepresentative for the organ's function. Successfulmethods have been developed in nuclear medicine forthe dynamic analysis of many organ functions: notablybrain metabolism, kidney function, stomach emptying,blood flow, and heart contraction. Recent advances inthe latter have made "nuclear cardiology" virtually aseparate speciality.

Conventional scintigraphy provides an image of func-tioning organs, as a projection over the full thickness ofthe body. The activity in all planes parallel to the detec-tor are superimposed in the final image. Until recentlythe only way to view selectively a single section insidethe body was by means of surgical tomography. In thelast decade the new imaging modality of "computer-aided tomography" (CAT or CT) reached maturity as aproduct of the intimate relationship of a highly advancedimaging instrument and a high-capacity computer. Theprinciple of CT is based on the mathematical reconstruc-

Basics of nuclear imagingOriginally nuclear medicine was not concerned with imaging,

but with the quantitive assessment of a certain biomedical sub-stance at a certain time and place. The concept of tracer kineticsis that physicians "label" a biomedical compound with aradioactive "isotope" and follow the path and fate of this"tracer". Since the added substance is small in quantity andequivalent to the substance to be traced in its chemicalbehaviour, there is little interference with normal physiology.Tracers used in nuclear medicine are often called "radio-pharmaceuticals".

The close co-operation of scientists, such as biochemists,physiologists and pharmacologists, has produced a large selec-tion of radiopharmaceuticals. For most organs and for variousorgan functions there is a specific tracer that plays a particularrole in the metabolism or in transportation mechanisms. As aradioactive "label", the nuclide technetium-99m is mostly usedbecause of its convenient physical and chemical properties. It hasa short half-life, limiting the radiation dose to the patient andavoiding problems with waste management.

One characteristic advantage of nuclear medicine is that thetracers behave as "functional probes". Other diagnostic imagingmodalities, such as radiology and ultrasound, visualize the staticproperties of tissue, such as its density. Nuclear medicineimages, on the other hand, reflect the functioning biochemistry.The seemingly stationary distribution of a tracer represents themomentary uptake of the labelled compound, a snapshot of ahighly dynamic process.

Most imaging techniques apply light or other radiation in suchquantity that its intensity is measured as a total flux of radiation.The gamma radiation applied in nuclear medicine is handled inits smallest indivisible units, as single distinct packages of light,called "photons".

For the detection of gamma radiation, scintillation detectorsare widely used. In a scintillation crystal each incoming gammaray creates a tiny light flash. A photomultiplier (PMT) sub-sequently converts this scintillation into a small electronic pulse.The pulse height or amplitude is proportional to the "gammaenergy" (and inversely to the wavelength) of the incident photon.The total number of detected photons, or "counts", accumulatedin a given time represents the number of radioactive tracer, the"activity" present in the field of the detector. It is this characteris-tic of single-count measurement that makes nuclear medicinesuitable for quantitative investigations.

An inherent complication of the limited amount of photonsused, and of the random character of the radioactive disintegra-tion process in itself, is the statistical imprecision of a measure-ment. This imprecision results in irregular fluctuations of "noise"in the measured intensity and the undesired patchiness in nuclearimages.

Scintigram of brain. (Credit: CEA)

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An ECT (emission com-puterized tomography)system. (Credit: GE)

tion of three-dimensional (3-D) image information col-lected in a number of single views taken from varioussides around the object. The 3-D image informationobtained is viewed by selecting planar sections in fron-tal, lateral, and also in transversal projections from thecomputer memory. Particularly the possibility ofvisualizing structures in the latter view, perpendicular tothe body axis, has contributed to a significant wideningof the anatomical horizon.

PET and SPECT

The rapid and successful introduction of X-ray CT asa routine tool in clinical diagnosis has further stimulatedthe development of nuclear medicine CT or "emissioncomputerized tomography (ECT)". Incidentally, ECThad been conceived and developed long before X-rayCT, but was not considered a feasible standard imagingmethod for long. Two distinct modalities of ECT existin nuclear medicine: positron emission tomography(PET) and single photon ECT (SPECT).

The 3-D image information in PET is derived throughthe counting in coincidence of the two simultaneous pho-tons that accompany positrons. Positrons in turn areemitted by certain, mostly short-lived, radioactivenuclides. The imaging instrument for PET, havingdetectors at either side of the patient, allows a relativelyhigh sensitivity, i.e., detection of a large fraction of theemitted radiation. Positron ECT has been very success-ful, particularly as a research tool in physiology andmicrobiology. The atoms composing organic com-pounds have mostly radioactive isotopes that emitpositron radiation. Impressive results have been pub-lished quantifying and imaging metabolism and oxygenconsumption in the brain and the heart muscle.

The success of PET in turn has stimulated the questfor a tomography instrument, with which conventional— single photon — nuclides could be applied. At least

three categories of instruments for SPECT may be dis-tinguished. These collect necessary views from differentangles through a multi-pinhole collimator, a rotatingslant hole collimator, and a rotating camera respec-tively. The latter one has been most promising becauseit is least affected by unwanted artefacts and allowsimaging in the transversal planes, too.

The additional efforts spent for SPECT over conven-tional scintigraphy are repaid by a modest but significantimprovement of diagnostic accuracy. The tomographicimage offers a superior contrast because it eliminatesoverprojection of overlying structures. Thus, deeperstructures are visualized with better contrast.

It was only after the first wave of enthusiasm overSPECT had subsided that the image artefacts were disco-vered. The artefacts could be hot spots, streaks or circlesin the final image. It appeared that they were causedeither by significant activity that remains partly outsidethe field of view, or by maladjustments of the gammacamera. Defects in uniformity, non-linearities and mis-alignment of the rotating camera, while insignificant forconventional scintigraphy, are blown up in the recon-struction process and may suggest serious abnormalitiesin the final tomographic image. Rigorous QC proce-dures for test and calibration are essential if the advan-tages of ECT are not to be turned into drawbacks.

Trends in imaging instrumentation

The thrust of the development in nuclear medicineimaging equipment comes, at least partly, from whatcommercial suppliers of instruments select to manufac-ture. Research in nuclear medicine is characterized byrapid innovation, particularly in the field of instrumenta-tion. The process of actually implementing these appearsto have slowed down recently, due to a number of fac-tors. While engineers and physicists are ready to embarkon ever new designs, the medical world sometimes

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shows much more inertia in its acceptance of newmethods and instruments into clinical routine.

That may explain the typical two-stage growth andacceptance shown with new developments, such as withnuclear cardiology and emission tomography recently.First there is an enthusiastic wave of innovative ideas,published and presented at annual scientific meetings.This high time is followed by a comparative lull on thesubject, which may last as much as half a decade. Then,a sudden rise in general acceptance, supported byfinished products marketed by industry, indicates thatthe new development has matured and will serve as anew tool for clinical imaging studies.

With the impressive expansion of other imagingmodalities, and the generally tightening budgets forresearch and development, industrial innovation inimaging instruments for nuclear medicine has lost someof its impetus in recent years. For instance, a significantnumber of companies marketing computers for nuclearmedicine have discontinued their business in the lastyears. Furthermore, the market in the developed worldis reaching a saturation level. An estimated 10 000gamma cameras are presently installed all over theworld with a turnover rate of roughly 1000 per year.

Electronic developments

Development of new instruments is facilitated andstimulated to a great extent by advances in electronics.A recent trend is miniaturization, leading to increasinglylarge-scale integration of components, and consequentlya dramatic fall in the costs of those "chips". Theintroduction of microprocessors in place of hardwarecircuits is rendering instruments more powerful andmore versatile, but for a lower price. The emphasis ofdesign efforts appears to be shifting away from hard-ware towards software development. Extensive process-ing power can now be stored into ever more compactchips. Software so condensed is sometimes referred toas "firmware".

Trends in gamma cameras and SPECT

The principle of the Anger camera has its inherentlimitations, which forces the designer into some com-promise between, for instance, sensitivity and spatialresolution (resolving power in the image). Comparedwith other imaging methods, such as X-ray radiologyand nuclear magnetic resonance (NMRI), nuclear medi-cine is constrained by the limited number of photonsavailable, since radiation exposure to the patient has tobe restricted.

Any approach to improve spatial resolution (by usinga thinner crystal or a finer collimator) is paid for by aloss in sensitivity and consequently an image with more"noise". Some research is done in applying other scin-tillation crystals, such as caesium-iodine or pure ger-manium, instead of sodium-iodine, which is generallyused. However, this has not yet resulted in a viable newproduct. The use of more photomultipliers on the crystal

has pushed the spatial resolution only slightly moretowards its theoretical limit. At the same time, however,the instrument becomes more susceptible to breakdown,since every added component contributes to the proba-bility of instrument failure.

Considering its price and relative reliability,however, the Anger camera is likely to remain theaccepted and practical imaging instrument for nuclearmedicine.

Rather than significant changes in gamma cameradesign as such, there is a definite trend toward speciali-zation. The inevitable trade-off in camera design may betailored to the specific clinical application, leading todedicated systems. There are, for instance, small field-of-view cameras capable of handling high count rates,applied for nuclear cardiology; there are camera sys-tems, rotating very closely around the body, designed tooptimize tomographic imaging; cameras are specializedfor mobile use, and others for whole-body scanning.

SPECT is likely to become more important in thenear future. This is helped by a concomitant rapidimprovement in computer hardware and software,together with an increasing number of accepted clinicalapplications. Along with PET, its more sophisticatedcounterpart, SPECT is developing to allow quantifica-tion of tracer distribution. A crucial condition to quan-tify reliably is accurate correction for tissue attenuation.This is generally achieved by measuring the actualattenuation with a transmission scan. A drawback of anyimage correction using measured radioactivity is theincrease of the "noise" or statistical fluctuations, andconsequent degradation of the resulting image. Anotherapproach is to determine the body contour or assume anallipsoid shape and apply a theoretical correction. Thisdoes not degrade the image quality, but may representa less accurate approximation of the real situation.

Improving visualization of depth

However attractive insight may be into deeper sec-tions cut through deeper planes within the body, thedrawback is that one ends up with a multitude of selec-tive pictures. Much of the advantage of tomographicimaging depends on the visualization of the 3-D imagein a compact and comprehensible way. There are a num-ber of methods presently being explored by which theimpression of depth is added to the display oftomograms.

Normal photographs that only suggest a 3-D structurehave the advantage of being practical and transportable.They are obtained from the screen, whereby successivedeeper sections are displayed with decreasing contrast orwith edges removed, thus having the same effect as thewings on a theatrical stage. Other, more elaboratemethods are stereoscopic pictures, holograms, and the"vibrating mirror", where the three. dimensions areclearly "seen" when one is seated at the display stationof the image-processor computer. A simpler way to sug-gest depth at the computer screen is to display all origi-

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Competitive imaging systems, such as computer-aided tomography,are influencing the future of nuclear medical imaging. (Credit:Tech-Ops)

nal views in rapid succession, just as they were takenfrom around the patient. This "rotating view in moviemode" leaves it to the observer's perception system tosmooth out the noise in images and to visualize threedimensions in body organs.

A number of different designs of cameras for PET arebeing developed. Some have become available commer-cially. However, the world of PET seems to dissociateitself further from the SPECT imaging field. PETrequires the availability of a nearby cyclotron and a staffof highly skilled scientists, whereas SPECT uses con-ventional radiopharmaceuticals. Moreover, the benefitof clinical applications using PET have turned out to belimited, in relation with the costs involved. While a verysophisticated tool per se, positron tomography is beingapplied predominantly in advanced physiologicalresearch.

Integrating computers and cameras

The trend towards more compact, more powerful,and less expensive computer hardware, combined withthe need for fast signal and image correction, has led toan integration of the computer with the camera. The ana-logue position signals, originating from the PMTs on thedetector crystal, are converted to digital data at anearlier stage, thus reducing the distortion of the imageinformation. These so-called "digital cameras" have amore stable performance, since they are less susceptibleto disturbances or a gradual drift of the analogue signals.

On the other hand, since the gamma camera is controlledby the digital electronics, any failure of the computerwould cripple operation of the whole system.

For the reconstruction algorithms in ECT and, forexample, Fourier filtering in nuclear cardiology, exten-sive "number crunching" has to be carried out, nor-mally consuming considerable computer time. Parallelprocessors, such as the array processor, can perform anumber of operations simultaneously. With the price forhardware falling, array processors may well become anintegral part of computer systems for image processing.

In general, a major contribution to nuclear medicinesoon will come from the development of software.Together with the trend to "freeze" computer programsinto chips, this may indicate that more image analysisprotocols will become standard features of the imaginginstruments. Presently software is freely accessible forpersonal and customized modifications, which hampersthe standardization of procedures. One attractive appli-cation that deserves mentioning is the "functionalimage". In the functional or "parametric" image theintensity or colour of each picture element ("pixel")represents the value of a parameter, e.g., the result ofthe mathematical analysis of a dynamic study for thatparticular point of the image. Functional images of thephase and amplitude of the heart contraction, afterFourier analysis, and of kidney function, after "factoranalysis", are gradually gaining acceptance.

Radiopharmaceutical developments

Since nuclear medicine is an intimately multidiscipli-nary endeavour, its future is not only determined byinstrument trends, but also by developments inradiopharmacy. Ultra-short-lived radionuclides, in com-bination with gamma cameras capable of handling highcount rates, will lead to new applications in blood flowstudies and nuclear angiography.

The present trend in development of tracers that aremore organ- or function-specific may open up a wholenew area of functional imaging. Particular mentionshould be made of monoclonal antibodies, highlytumour-specific compounds presently used in radioim-munoassay. If this application would expand into the invivo field, a totally new imaging modality could evolve("radioimmuno-imaging"). If these antibodies were tobe labelled with the widely available technetium-99m,the nuclear medicine physician would have a new andpowerful tool in his combat against cancer.

Growing competition

Apart from these developments, there is significantexternal influence on the future of nuclear medicine —increasing competition of other imaging modalities, suchas (digital) radiology, ultrasound, and NMRI. This com-petition, together with the growing similarity amongtheir needs for image processing and computer use, maydictate establishment of integrated imaging departments

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in hospitals of the future. Similar to the development inthe in vitro laboratory, this may even lead to a gradualend to isolated nuclear medicine departments as such.

For the developing world it may take 5 to 10 yearslonger before a new development in nuclear medicinebecomes commonplace. Among other causes, this isinevitably due to the shortage of financial resources.

Administrative procedures and political pressuressometimes appear to set the time-frame for the transferof technology. The generally extensive bureaucraticprocedures add a considerable delay to the procurementof new equipment. In addition to all this, there are perti-nent problems in coping with the more adverse circum-stances in many developing countries. Notablyinsufficient climatic- and power-conditioning create anunsuitable environment for increasingly sophisticatedand vulnerable equipment. An inadequate infrastructureand lack of foreign currency hamper the regular supplyof short-lived radiopharmaceuticals and the promptavailability of repair and maintenance services. And lastof all, insufficient pay and training of engineers,together with a considerable "brain drain" does notstimulate growth of motivation, knowledge, andexperience. On the whole, for the developing world, thepace of development is much slower than in the deve-loped world, and consequently the gap in accepted(nuclear medicine) technology continues to widengradually.

Future directions

Trends in nuclear medicine and imaging instrumentsseem to lead to different futures for the developingworld and for developed countries. There are significantdifferences in the disease patterns and clinical questionsin both worlds. Moreover, resources available forsophisticated medical facilities differ in absolute andrelative terms. It is a risky and unrealistic endeavour toeven try and predict the future of a development, which,in its short history, has proved to be capricious, rapid,and directed by unexpected events and inventions.

In more advanced parts of the world the rate ofexpansion and innovative designs in nuclear medicine

equipment may well slow down in the years to come.The competition with other imaging modalities involvedin clinical diagnosis and the changing public attitudetowards nuclear applications may dampen the forcewhich drove nuclear medicine to its present level ofsophistication.

Integration of more powerful computers in the Angergamma camera is likely to continue, allowing on-lineimage optimization and efficient analysis of dynamicstudies. With the further implementation of fast arrayprocessors, single photon tomography may mature to aroutine and accurate imaging modality. A major contri-bution to new clinical studies will come from thedevelopment of highly organ-specific radio-pharmaceuticals.

While rectilinear scanners are gradually beingreplaced by gamma cameras in the developing countries,there is a definite trend towards attaching computers toexisting gamma cameras. This will allow access to newapplications, such as nuclear cardiology. SPECT sys-tems are only beginning to be installed among the moreadvanced of the nuclear medicine centres in that part ofthe world.

The acquisition of new equipment is, in general, agoal aspired with much more fervour than the main-tenance of existing instruments. Nevertheless well-organized repair and maintenance facilities will prove ofprime importance both for a continued development ofclinical nuclear medicine services and as a means oftraining for electronics engineers. Apart from the obvi-ous saving of financial resources, the strengthening oflocal expertise will help countries to become moreself-supporting.

However challenging nuclear medicine developmentsmay appear, it is important to justify spending the man-power and other valuable resources in view of thespecific clinical questions posed and of their contributionto public health in general. Only when the quality of theinvestigations is constantly and rigorously assured, andwhen the expenditures are evaluated against their socialimpact, may nuclear medicine imaging maintain its roleas a useful and attractive application of atoms for peace.

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