SPECIAL CONTRIBUTION

Myocardial Perfusion Imaging with PET

Markus Schwaiger

Nuklearmedizinische Klinik und Poliklini/çDer Technischen Universitdt Munchen, Klini/wm Rechts der Isar, Munich, Germany

SPEC!' (5). PET spatial resolution is superior to that of AlthoughSPECThas become an acceptedimagingtechnique SPECT, resulting in superior image quality and less partial formyocardialperfusionstudies,thereare severaladvantages volume effect (5). Most PET images are processed with a to evaluatingcoronaryarterydisease (CAD)withPET.CADis a spatial resolution of about 6—10mm, as compared with complex, dynamic disease and quantitativemeasurements of 10—15mm for SPECF image reconstruction. myocardialbloodflowby PET can improvethe fUnCtiOnalchar The majoradvantageof PET is its ability to correct for acterizationof CAD.The majoradvantage of PET over SPECT attenuation.Traditionalmyocardialperfusionimagingwith is @rtsabilityto provideattenuation-correctedimages, whichde single-photon radiotracers such as 201'flposes significant creases incidenceof attenuation artifactsand increases spea challenges in avoiding or identifying and correcting for flcfty.Myocardialpertusion imagingwithPET can also provide moreaccurateinformationon localizationofdisease, as wellas attenuation artifacts, particularly those that involve the quantitativeassessment, inabsolutevalues, ofmyocardialblood inferior wall in male patients and the anterior wall in female flow.The measurement ofregionalflowreserve allowsforphys patients (6,7). iologiccharacterizationof stenosis severity, and may provide Unquestionably, attenuation correction provides more earn, detection of CAD as well as prognostic information. The homogeneous radiotracerdistribution in normal myocar disadvantage of PET, compared to SPECT, is that the equip dium, andimprovedcharacterizationof relativedifferences ment and operationsare more expensive.As more accurate in regional perfusion (8). In addition, attenuation correc diagnosticand prognosticdata lead to improvedpatient man tion improves the accuracy of quantitativeanalysis of de agement,the cost-to-benefitratiosof PETand SPECTin the fect severity since variation within normal segments is clinicalsetting need to be furtheranalyzed to determine which reduced (8). Thus, PET can provide reliable, quantitative diagnostictest is most effiaent in the work-upof patients with assessment of myocardialradiotracerdistribution;whereas suspected orknownCAD. SPECT, without attenuation correction, provides a more KeyWords:myocardialperfusionimaging;coronaryarterydis variable reflection of regional myocardial radiotracerdis ease; SPECT; PET tribution.Such improvement in image quality is expected J NucIMed1994;35:693-698 to result in enhanced diagnostic performance. Validation As new medical technology is introduced,several issues must be addressed. t is well established that tomographicmyocardialperfu One challenge is to validate a new diagnostictechnology sion images provide higher spatial resolution than planar with established tests that are accepted as gold standards. images for evaluatingpatientswith coronaryarterydisease If, for example, coronaty is used to confirm (CAD) (1,2). SPECT is used routinely in the clinical set results of myocardialperfusion studies with PET, referral ting. There are three commercially available radiotracers bias becomes a problembecause only patientswith abnor for myocardial perfusion SPEC!' which have been em mal myocardial perfusion scans are referred for cardiac ployed successfully for the detection and localization of catheterization (9). The selected study population, there CAD (1—4):20―fl,9@9'c-sestamibi and @‘@Tc-teboroxime.fore, may not representthe general patientpopulationthat is referred for myocardial perfusion studies. PET VERSUS SPECT Secondly, it is important to consider which diagnostic In comparison to SPECT, PET can detect radiotracer accuracy is necessary to affect patient management dcci activity with 10 times the sensitivity of state-of-the-art sions. Clinicalexperience shows, for example, that a nor mal201'flstudy, even in the presence of CAD, is associated ReceivedJan.7, 1994;revisIonacceptedJan. 18,1994. with a vety good prognosis (10—12).Therefore, the sensi This paper was presented in part at the AnnualMeetingof the Societyof NudearMedicineon June8, 1993as partof a ContinuingMed@siEducation tivity of 20111 SPEC!' for detection of CAD may be ade Seminarorganizedbythe CardiOvascUlarCouncil quate. However, the specificity of @°@Tlstudies is not suf For correspondence or repñntscont@ Prof. Dr. Maalws Schwaiger, Nuklear medizinischeKilnikundPolknik,DerTechnischenUniversitátMUnchen,KJin@umficiently high, resulting in a reported false-positive rate Rechtsder Isar,IsmaningerStrasse 22, 8000MUnchen80, Germany. ranging from 20% to 50% (13—15).As a consequence, pa

MyocardialPerfusionImagingwithPET•Schwaiger 693 tient care may not suffer, but unnecessary additional diag Copper-62-PTSM nostic procedures will be performed, affecting the cost of Copper-62-pyruvaldehyde bin(n-methy-thio-semicarba patient care. zonado) (PThM)is currentlybeing validated as an alterna Thirdly, as diagnostic imaging technology advances, it tive to 82Rbfor myocardialperfusionimaging(24). As with provides new approaches to more sophisticated diagnostic 82Rb,the relation between 62Cu-PTSMand blood flow is challenges. Althoughthe presence of CAD can be detected nonlinear and may therefore lead to an underestimation of adequately with a variety of diagnostic tests, other ques coronaiy flow reserve estimates. Direct comparison of tions—suchas the exact location of stenoses and their 82Rb and 62Cu-PTSM studies are necessaiy to define the hemodynamic significance—requiremore advanced quan future clinical role of this new radiotracer. titative measurements of regionalblood flow. Over recent years, internists and cardiologists have become more ag IMAGEQUALITY gressive in treating CAD and more demanding of docu mented outcomes. The need for noninvasive techniques to Excellent PET image quality is obtainable with 82Rb, monitor therapy is well appreciated. Quantitative measure ‘3N-ammoniaand 6@Cu-VFSM,with a high contrast be ments of regional flow reserve, which PET can provide, tween myocardium and underlying lung tissue or blood may be able to monitor the progression or regression of pool (24,25). Because 82Rb emits a high-energy positron CAD and, thus, allow for guided therapy in patients with a that travels a longer distance before collidingwith an elec high risk for accelerated atherosclerotic disease processes tron to produce two gamma photons, 82RbPET images in primaryand secondary prevention (16). have a lower intrinsic resolution. Figure 1 shows images and polar maps representing the normal distribution of all PET MYOCARDIAL PERFUSION TRACERS three tracers (13). PET images with 82Rbdemonstrate homogeneous dintri There are several positron-emittingradiotracersuseful bution, reflectingthe effect of attenuationcorrection; ‘3N- for myocardialperfusion imaging. ammonia distribution is slightly nonhomogeneous, with re Rubldlum-82 duced radiotraceractivity in the lateralwall (Fig. 1); and Rubidium-82 in a convenient radiotracer because it can 62@p@'5M maps demonstrate some scatter in the inferior be produced by a radionucide generatorsystem (17). Any wall, resulting from its high liver uptake. The low uptake of nuclear facility with PET, therefore, can ‘3N-anunoniain the lateralwall is a reproduciblefindingin provide 82Rbstudies without the need for an on-site cyclo both rest and stress images. Although the mechanism is tron. With a half-life of 76 5cc, 82Rballows for repeated unknown, it appears to be a regional metabolic alteration in blood flow measurements in short time intervals. The re ‘3N-ammoniatissue retention (26). lation between 82Rbuptake and blood flow is nonlinear with decreasingmyocardialextraction at higherflow rates, PROTOCOLS however, the practicality of the radiotracer offsets thin As a rule, PET studies are obtainedwith short scanning physiologic limitation. Several studies have shown that times. A typical myocardialperfusion study with 82Rbcan 82Rb, in combination with pharmacologic stress, allows be completed in 1 hr. After injection of 82Rb,the protocol accurate detection of CAD (18—21). entails:a 15-mintransmissionscan, a 5-mmrest flow study, Nftrogen-13-Ammonia injection of a pharmacologic stress agent, a second dose of Nitrogen-13-ammonia incyclotron-produced. Its half-life 82Rb and a 5-mm stress study acquisition (17). Similar of 10min requiresa 30- to 40-mmwaiting periodbefore the protocols are followed for myocardial perfusion PET im rest and second stress injection (21). With respect to the aging with ‘3N-ammonia,which requires a waiting period relation between blood flow and radiotraceruptake, ‘3N-for ‘3Ndecay, but can be completed within 1.5 to 2.0 hr ammonia behaves similarly to @°‘Tlin that its uptake is less (8). The short completion times of these PET protocols affected by high flow rates as compared with 82Rb. This offer a distinct advantage over myocardial perfusion stud radiotracerexcels by the excellent image quality and con ies with 20111or @Fc-sestamibi. venient use in a clinical setting (8). Oxygen-15-Water DIAGNOSTiC AOCURACY Oxygen-15-water is used primarily in the research envi Myocardial perfusion studies with PET have been ronment (22,23). Theoretically, this radiotracer is ideal for shown to provide a higher diagnostic accuracy than those quantitativeflow measurementsby PET for two reasons: it with SPEC!' (Table 1) (18—2Z27,28).The reported sensi diffuses freely across the myocyte membranes, and the tivities of PET for CAD detection are in the range of tissue retention of ‘50-wateruptake is not affected by 80%—95%;whereasreportedspecificity valuesof PET are metabolic factors. However, the technical requirements of 80%—95%.Although there are only two studies comparing ‘50-waterstudies limit its clinical application. This tech PET and SPECT in the same patient populations, and nique involves dynamic imaging procedures and subtrac although these studies have been criticized for referral tion methods for removal of blood tracer activity (22). bias, the results consistently find that PET provides about

694 TheJournalof NuclearMediane•Vol.35 •No.4 •APnI1994 A QUANTITATIVEANALYSIS LOCALIZATIONOF DISEASE N = 35; NO Ml C-)

C.) N@3AMMON@ C.) C.) I- Cl) 0 z C, 4 @m @mu 0 LAD RCA LCX

PET @SPECT

FiGURE 2. Dlagnosticaccurecy indetectionof reg@nalCADby LAT quantftath@eevaluation of @°@11SPECT and @RbPET in patients withoutpriorMI.Reprintedwithpermis@onfromReference29.

mine when PET should replace SPECT for myocardial perfusion studies in patients with suspected CAD. Localization of Dlseae• The quantitative assessment of PET radiotracerdintn bution can provide a significantadvantageover SPECT in cases where attenuation artifacts pose limitations in the localization ofdisease (8). Automated programs can objec FIGURE 1. PETimages ofmyocardlalbloodflow,mid-ventricular tively determine the extent and severity of perfusion de short-ads plane (A),and polarmaps of radlotracerdistribution(B) fects by comparison with normal databases with sensitivi with @Rb,13N-ammonsaand °@Cu-PTSM.Reprintedwithpermis slonfromC.V.Mosby,St Louis,MO(Amerk@anHeaatJoumaIl989; ties and specificities of approximately 85% and 80%, 13:600-612). respectively, for both 50% and 75% stenoses (28). A study of 35 patients who underwent both @°‘TlSPECT and 82RbPET perfusionstudies demonstrateda diagnostic 10%higherdiagnostic accuracy than SPECT for detection gain in accurate localization of regional disease with the of CAD (19,20). 82Rbstudies. Quantitative analysis was performed for both More data are needed to define the diagnostic differ the @°@Tlstudies and 82Rbstudies (Fig. 2) (29). ences in large patient populations, and to calculate the In another study of 34 patients without previous myo cost-to-benefit ratios of various clinical situations to deter cardial infarction (MI), ‘3N-ammoniaPET provided high

TABLE 1 DiagnOSfiC Performance of PET vs. SPECT in Detection of CAD

(%)SchelbertAuthorStressPETSPECTTracerNSen (%)Spec (%)Ace (%)NSen (%)Spec (%)Ace (22)•Dipyridamole1@NH3359710098————Demeret al. (18)Dipyridamole13NH3,@Rb193829588————Stewartetal(19)Dipyridamole@Rb8185848581845379Goat ai. (20)D@yridamoIe@Rb135958292135797678Tamakiat al. (27)Exerclse*13NH34898——4896——Total492919092264866578*B@y@et al.

ergometer.Sen = sensitivitySpee = specificity;Ace= accuracy;NH3 =ammonia.

Myocardial Perfualon Imaging with PET •Schwaiger 695 ROCAnalysis N-13AmmoniaPET Localization of Disease N=34

LAD RCA LCX S 1.0 1.0 1.0 0.8 1@—0.8 0.8 0.6 0.6 0.6 0.4 0.4 0.4 0.2 0.2 0.2 FiGURE 3. ROC curves for detection and localizationofCAD usingquantitative @ 0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0 0.0 0:2 0.4 •0.6 •0.8 1@0 evaluationof 13N-ammonlaPET images in patientswithoutpriorMI.Reprintedwithper False-Positive Fraction misalonfromReference28.

sensitivity and specificity in localizing disease in the left incidence of abnormalcoronary reserve (34). On the other anterior descending (lAD) artery and the right coronaiy hand, a more moderate degree of stenosis (50%—70%)was artery (RCA) (Fig. 3) (28). PET was somewhat less suc associated with considerable scatter of coronary reserve cessful in localizing disease of the circumflex artery. values, suggesting complementary information provided Quantification of Blood Flow by functional characterizationwith PET. PET quantification of myocardial blood flow is more The surprisingobservation, however, was that patients difficult than diagnosis and localization of CAD because of with angiographically normal myocardial regions, espe the technical requirementsof data acquisition; it is neces cially in the presence of coronary stenosis in remote yes sary to process dynamic data acquisition, which is sensi sels, had significantlyreduced coronary reserve. Thinfind tive to patient motion. A kinetic model of radiotracerbio ing indicates that normal angiographicresults in patients distribution, validated in animal models, as well as with CAD are not always associated with functionallynor sophisticated computerprocessing, are necessary to trans mal vasculature. late scintigraphic information into absolute blood flow Based on these results, we investigatedwhether quanti measurements. However, several approaches have been tative assessment of blood flow reserve can identify early shown to provide reproducibleblood flow measurements atherosclerosis in asymptomatic subjects at high risk for in ml/min/100g ofleft ventricular tissue Table 2(24,30—33). CAD. A study compared age-matched male patients with a In a study of healthy volunteers, quantitative regional strong family history of premature CAD with a second data presented in polar maps demonstrated that resting group of asymptomatic male subjects without risk factors blood flow averaged 70 cc/min/100 g, with little variation for CAD (35). The results showed that coronary flow re within the left ventricularmyocardium (8). After pharma serve was significantlylow in the patients with high risk. cologic stress, blood flow increased four to five times, The degree of impaired flow reserve correlated with the which correlatedwith the expected coronary flow reserve severity of lipid abnormality.These data suggest a poten in normalmyocardial tissue. tial application of quantitative PET blood flow measure Are these PET blood flow measurements clinically use ments in the early detection of CAD in high-riskpopula ful? In a study that compared blood flow estimates with tions. Furthermore, the monitoring of flow reserve may quantitative angiography, results showed that a high de serve as a useful endpoint in the assessment of therapy gree of stenosis (70%—90%)correlated with a very high designed to prevent the progression of CAD.

TABLE 2 MyocardialBlood-RowEstimatesinHumansDeterminedby PET flow flow stressBergmannAuthorTracerRest (mt/laO9/mm)Stress (mI/1009/mm)Exercise/RestType of 123.94DipyridamoleHutchinset al. (24)1@O-water90 ±22355 ±1 124.74DipyridamoleKrivokapichat al. (31)13N-ammonia88 ±17417 ±I .97Exerdse*Czeminat al.(33)13N-ammonia70 ±17132 ±221 803.00Dipyridamole*B@y@@Jeet al. (32)13N-ammonia76 ±17300 ±

ergometer.

696 TheJoumal ofNuclear Medicine'Vol. 35•No.4•ApnI1994 Assessment of Endothellal Function sioncomputedtomographyoverplanarimaginginthediagnosisofcoronary Cold-pressor testing is considered a specific test for en artery disease:a receiveroperatingcharacteristicanalysis.JAm CoilCar. diol 1989;13:600—612. dothelial function of coronary arteries. We have recently 3. Kiat H, MaddahiJ, RoyLT, et al. Comparisonof technetium99mmethoxy explored the feasibility of myocardial perfusion imaging in isobutylisonitrileandthallium-201forevaluationof coronaryarterydisease combination with cold-pressor testing (36). During PET by planarandtomographicmethods.AmHeartl 1989;117:1-I1. 4. SeldinDW,JohnsonLL, BloodDK, et al. Myocardialperfusionimaging scanning, the patient's foot is immersed in ice-cold water; withtechnetium-99mSQ30217:comparisonwiththallium-201andcornnaiy coronary blood flow is measured before and during this anatomy.JNuclMed 1989;30:312-319. stress procedure. Results showed that all patients with 5. KoeppeRA,HutchinsGD. Instrumentationforpositronemissiontomog raphy: tomographs and data processing and display systems. Semin Nucl angiographically normal CAD had increased myocardial Med 1992;22:162—181. blood flow in response to the cold-pressor test, whereas 6. FriedmanJ, Van Train K, MaddhiJ, et al. “Upwardcreep―of theheart:a patientswith minimalCAD had a wide rangeof responses; frequent source of false positive reversible defects during thailium-201 in contrast, patients with severe CAD demonstrateda de stress-redistributiontomographicmyocardial .I Nuci Med 1989;30:1718—1722. crease ofbboodflow. These preliminaryresultssuggest that 7. Eisner RI, Tamas MJ, aoninger K, et al. Normal SPECF thallium-201 an abnormalresponse to cold-pressor testing may identify bulls-eye display: gender differences. I NuciMed 1988;29:1901—1909. endothelial dysfunction associated with early CAD, and 8. SchwaigerM, Muzik 0. Assessmentof myocardialperfusionby positron emissiontomography.AmI Cardiol1991;67:35D-43D. may provide a noninvasive technique (with PET imaging) 9. RozanskiA. Referralbias and the efficacyof radionuclidestress tests: to define endothelial pathology. problemsand solutions.I NuciMed 1992;33:2074—2078. From these data, hypotheses on prognostic indicators 10.WackersFJT,RussoDJ,RussoD,ClementaJP.Prognosticsignificanceof normal quantitative planar thailium-201 stress scintigraphy in patients with from quantitative myocardial perfusion PET in patients chest pain. JAm Coil Cardiol 1985;6:27-30. with CAD can be derived and subsequently tested in pro 11.PameliaFX, GibsonRS,WatsonDD, CraddockGB, SirnwatkaJ, Belier spective studies. GA. Prognosiswith chest painand normalthallium-201exercisescinti grams. Am I Caidiol 1992;55:920-926. 12. WahI JM, Hakki A-H, IskandrianAS. Prognosticimplicationsof normal CONCLUSION exercise thalhium-201 images. Arch Intern Med 1985;145:253—256. Several positron-emitting radiotracers are useful for 13.AilmanK, BerryJ,SucharkskiL. Howwelldoesadenosinethalliumscm tigraphycharacterizeextent and locationof cornnaryartery disease?JAm myocardialperfusion PET, including82Rband ‘3N-ammo Coil Cardiol 1992;19:311. nia. The use of 62Cu-PTSMis still being validated and 14. SchwartzRS, JacksonWG, CelioPV, HickmanJR. Exercisethailium-201 ‘5O-wateris mainlyused in the researchenvironment.PET scintigraphyfor detectingcoronaryartery diseasein asymptomaticyoung men.JAm CoilCan'Jiol1988;11:80A. technology can provide improved diagnostic accuracy, 15. Gould ICL, Goldstein RA, Mullani NA, et al. Noninvasive assessment of comparedwith SPECT, in evaluatingpatientswith known cornnarystenosesby myocardialperfusionimagingduringpharmacologic or suspected CAD. The major advantage of PET over coronaryvasodilation.VIII. clinicalfeasibilityof positroncardiac imaging withouta cyclotronusinggenerator-producedrubidium-82.JAm CoilCar SPEC!' is its ability to provide attenuation-corrected im dial 1986;7:775—789. ages, which increases the specificity (decreasingthe false 16. OrnishDM, Scherwitz1W, BrownSE, et al. Canlifestylechangesreverse positive rate) of the diagnostic test. As improvedmethods atherosclernsis?CÜVUlatiOn1988;78:II-11. 17. GouldKL. How accurateis thalliumexercisetesting?JAm Coil Cardiol of attenuation correction for SPEC'T—suchas transmis 1989;14:1487—1490. sion/emission acquisition—progress, SPECT will become 18. DemerL, GouldK, GoldsteinR, et al. Assessmentof cornnaryartery more competitive with PET for myocardial perfusion im disease severity by positron emission : comparison with quan titativearteriographyin 193patients.CirculatiOn1989;79:825—835. aging. The cost-to-benefit ratios of using myocardial per 19. StewartR, SchwaigerM, MolinaE, et al. Comparisonof rubidium-82 fusion PET in the clinical setting are as yet undefined. positrnnemissiontomographyand thallium-201SPED' imagingfor detec In additionto diagnosticevaluationof CAD, myocardial tionof coronaryarterydisease.AmJ Cardiol1991;67:1303-1310. 20. Go RI, MarwickTH, McintyreWi, et al. A prnspectivecomparisonof perfusion imaging with PET can provide quantitative as rubidium.82 PET and thailium-201 SPECI' myocardial perfusion imaging sessment of myocardial blood flow. The quantitative as utilizinga singledipyridamolestress in the diagnosisof coronary artery sessment of regional flow reserve allows for physiologic disease.JNuclMed 1990;31:1899-1905. 21. WffliamsB,JansenD,WongL, etal.Positrnnemissiontomographyforthe characterizationof CAD, which may enhance the under diagnosis of : a non-university experience and cor standing of CAD and provide additionalprognostic infor relationwithcoronaryangiography[Abstractj.JNucl Med 1989;30:845. mation. 22. SchelbertHR.WisenbergG, PhelpsME,etal.Noninvasiveassessmentof coronary stenoses by myocardial imaging during pharmacologic coronary vasodilation. VI. Detection ofcornnaiy artery disease in man with intrave ACKNOWLEDGMENTS nous N-13 ammonia and positron computed tomography. Am I Cardiol 1982;49:1197—1207. Financial support for this work was provided by NIH grants 23. Walsh MN, BergmannSR. Steele RL, et al. Delineationof impairedre ROlHL41047andROIHL4743.Theworkwasperformedunder gional myocardial perfusion by positron emission tomography with H2150. thetenureof anestablishedinvestigatorshipby theAMA. Circulation 1988;78:612-620. 24. BergmannSR,HerrernP, MarkhamJ, WeinheimerCJ,WalshMN.Non REFERENCES invasive quantitation of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography. I Am Coil 1. Maddahi J, KVT, PrigentF, et al. Quantitativesinglephotonemission Canliol1989;14:639—652. computedthallium-201tomographyfor detectionand localizationof corn 25. BeanlandsR,MuZikO,MintunM,etal.Thekineticsofcopper-62-PTSMin naryarterydisease:optimizationandprospectivevalidationof a newtech thenormalhumanheart.JNuclMed 1992;33:684-690. nique. JAm CoIl Cardiol 1989;14:1689—1699. 26. HutchinsGD, BeanlandsRSB,Muzik0, SchwaigerM. Quantitativevs. 2. FintelDJ, LinksJM, BrinkerJA, FrankIL, ParkerM, BeckerLC. Im semi-quantitativePETmyocardialbloodflow:influenceof regionalammo prnved diagnostic performance ofexercise thailium-201 single photon emis nia kinetics. Circulation 1992;86:I-710.

MyocardialPerfusionImagingwithPET•Schwaiger 697 27. Tamaki N, Yonekura Y, Yamashita K, et al. Value ofrest-stress myocardial 32. czernin J, Muller P, Chan 5, et al. Influence of age and hemodynamics on positron tomography using nitrogen.13 ammonia for the preoperative pre myocardial blood flow and flow reserve. Cfrculation 1993;88:62-69. diction of reversible asynergy. JNuclMed 1989;30:1302—1310. 33. Krivokapich J, Stevenson LW, Kobashigawa J, et al. Quantification of 28. LaubenbacherC, RothleyJ, SitomerJ, et al. An automatedanalysispm absolutemyocardialperfusionat rest and duringexercisewith positron gram for the evaluation of cardiac PET studies: initial results in the detec emissiontomographyafter humancardiactransplantation.JAm CoilCar tionandlocalizationof coronaryarterydiseaseusingnitrogen-13ammonia. did 1991;18:512—517. JNucIMed 1993;34:%8—978. 34. BeanlandsRSB,MelonPG.Muzik0, et al.N-13ammoniaPETidentifies 29. AllmannCJ,RothleyJM,Yang5, etal.QuantitativeanalysisofRb-82PET reduced perfusionreserve in angiographicallynormal regionsof patients images: intra- and internbservervariability [Ahstractl.JNuclMed Technol withCAD.Circulation1992;86:I-184. 1992;20:1O1. 35. DayanikliF, GrambowD, Muzik0, MoscaL, RubenfireM,SchwaigerM. 30. lidaH, KannoI, TakahashiA, et aLMeasurementof absolutemyocardial Evaluationof coronaryflowreserve in asymptomaticmaleswith hyperlip bloodflowwith H2150anddynamicpositron emission tomography strategy idemiaand f@y historyof coronary artery disease (CAD)[Abstracti.I forquantificationin relationto thepartial-volumeeffect.Circulation1988; NuclMed 1993;34:115. 78:104—115. 36. GrambowD, DayanikliF, Muzik0, etal.Assessmentof endotheialfunc 31. HutchinsGD,SchwaigerM, RosenspireKC,KrivokapichJ, SchelbertH, tionwithPETcoldpressortest inpatientswithvariousdegreesofcoronary Kuhi DE. Noninvasive quantification of regional blood flow in the human atherosclerosis [Abstractj. INucIMed 1993;34:36P. using N-13-ammoniaand dynamic positron emission tomographic 37. SchwaigerM, HutchinsGD. Evaluationof coronaryarterydiseasewith imaging. JAm Coil Cwviiol 1990;15:1032—1042. positronemissiontomography.SeminNuclMed 1992;12:210-223.

698 TheJournalof NudearMedicine•Vol.35 •No.4 •Apnl1994