myocardial infarct imaging using 99m technetium

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Med. J. Malaysia Vo!. XXXIV No. 3, March, 1980. MYOCARDIAL INFARCT IMAGING USING 99m TECHNETIUM PYROPHOSPHATE AND 99mTECHNETIUM METHYLENE DIPHOSPHONATE: . A CLINICAL EVALUATION M. PARAMSOTHY K.T. SINGHAM INTRODUCTION THE use of radionuclides in elucidating ischae- mic heart disease is a recent development. Since Bonte et al. (1974) first described the concentra- tion of 99mTechnetium labelled phosphates in acutely damaged myocardium numerous radio- pharmaceuticals, techniques, experience and data have accumulated in the non-invasive imaging methods for the direct visualisation of acute myocardial infarction. The radioisotopes may be used dynamically to provide information about the size of cardiac chambers, the ventricular ejection fraction, ventricular wall motion or regional perfusion of the myocardium. The radioisotope is injected rapidly as a bolus into a peripheral vein and its passage through the heart is recorded with a scintillation gamma camera interfaced with a data processor or computer system. Alternatively isotopes may be used for static imaging after equilibration and intracellu- lar radioactive uptake occurs, displaying areas of normal, ischaemic or infarcted myocardium. Both techniques avoids cardiac catheterisation and are non-invasive, cheap, sensitive, safe, reproducible and repeatable. If a mobile gamma. camera is available it can be done at the bedside and becomes extremely useful in the intensive care. where the physician has to continuously monitor for changing cardiac physiology in .ill cardiac patients. These techniques provide for the early diagnosis, sizing of the infarcted area, incrimination of the coronary arteries affected follow-up studies, and monitoring effect of therapy. M. Paramsothy M.B.B.S. (Mal), M.R.C.P. (UK) Division of Nuclear Medicine Department of Radiology Faculty of Medicine, University of Malaya K.T. Singham M.B.B.S. (Mal), M.Med (S'pore) M.R.C.P. (UK), F.R.A.C.P. Dept. of Medicine, University of Malaya 289 Early diagnosis of myocardial infarction may be a problem. Various clinical conditions may obscure or mimic the clinical picture. Clinical, e1ectrocardiographic and serum enzyme studies are sometimes insufficient to allow a definite appraisal; the characteristic pattern of chest pain may be absent (Papp, 1952) and atypical chest pain, so often present, only underlines the difficulties of differentiating the pain arismg from acute myocardial infarction from other non-cardiac conditions. Situations known to give to uninterpretable electrocardiographic include the presence of previous myocar- dial damage caused by infarction or cardiac surgery, abberent conduction, paced rhythms, or pre-excitation syndromes. In addition, serum enzyme measurement may be unreliable and false positive readings occur frequently (Savranoglu et al., 1959; Sobel and Shell, 1972). Borderline results may maintain rather than eliminate the diagnostic problem. Doubts of myocardial infarc- tion may also occur with ST segment changes or T-wave inversion without serum enzyme elevation or serum enzyme elevation without Q-waves especially after cardiac surgery when the serum enzyme concentrations are raised because of tissue trauma. The value of another specific and diagnostic technique which is safe, reproducible, repeatable and non-invasive is thus evident. The two main approaches to acute myocardial infarct imaging consist of (1) the utilisation of potassium analogues, mainly 201Thallium (Tl) as thallous chloride and (2) the utilisation of 99mTc- labelled radio-pharmaceuticals, mainly as 99m Tc _ pyrophosphate. 201Thallium and the other potassium analogues are taken up by the normal myocardium so that an infarct' of any duration or a region of hypoperfusion is present as an area Of absent or reduced radioactivity C'cold spot") whereas 99m phosphates are taken up by damaged tissue so that an acute infarct is shown as a

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Page 1: Myocardial infarct imaging using 99m technetium

Med. J. Malaysia Vo!. XXXIV No. 3, March, 1980.

MYOCARDIAL INFARCT IMAGING USING 99mTECHNETIUM PYROPHOSPHATE AND 99mTECHNETIUMMETHYLENE DIPHOSPHONATE: .A CLINICAL EVALUATIONM. PARAMSOTHY K.T. SINGHAM

INTRODUCTION

THE use of radionuclides in elucidating ischae­mic heart disease is a recent development. SinceBonte et al. (1974) first described the concentra­tion of 99mTechnetium labelled phosphates inacutely damaged myocardium numerous radio­pharmaceuticals, techniques, experience and datahave accumulated in the non-invasive imagingmethods for the direct visualisation of acutemyocardial infarction. The radioisotopes may beused dynamically to provide information aboutthe size of cardiac chambers, the ventricularejection fraction, ventricular wall motion orregional perfusion of the myocardium. Theradioisotope is injected rapidly as a bolus into aperipheral vein and its passage through the heartis recorded with a scintillation gamma camerainterfaced with a data processor or computersystem. Alternatively isotopes may be used forstatic imaging after equilibration and intracellu­lar radioactive uptake occurs, displaying areas ofnormal, ischaemic or infarcted myocardium.Both techniques avoids cardiac catheterisationand are non-invasive, cheap, sensitive, safe,reproducible and repeatable. If a mobile gamma.camera is available it can be done at the bedsideand becomes extremely useful in the intensivecare. where the physician has to continuouslymonitor for changing cardiac physiology in .illcardiac patients. These techniques provide for theearly diagnosis, sizing of the infarcted area,incrimination of the coronary arteries affectedfollow-up studies, and monitoring effect oftherapy.

M. Paramsothy M.B.B.S. (Mal), M.R.C.P. (UK)Division of Nuclear MedicineDepartment of RadiologyFaculty of Medicine, University of Malaya

K.T. Singham M.B.B.S. (Mal), M.Med (S'pore)M.R.C.P. (UK), F.R.A.C.P.

Dept. of Medicine, University of Malaya

289

Early diagnosis of myocardial infarction maybe a problem. Various clinical conditions mayobscure or mimic the clinical picture. Clinical,e1ectrocardiographic and serum enzyme studiesare sometimes insufficient to allow a definiteappraisal; the characteristic pattern of chest painmay be absent (Papp, 1952) and atypical chestpain, so often present, only underlines thepr~~tical difficulties of differentiating the painarismg from acute myocardial infarction fromother non-cardiac conditions. Situations known togive ri~e to uninterpretable electrocardiographict~aces include the presence of previous myocar­dial damage caused by infarction or cardiacsurgery, abberent conduction, paced rhythms, orpre-excitation syndromes. In addition, serumenzyme measurement may be unreliable and falsepositive readings occur frequently (Savranoglu etal., 1959; Sobel and Shell, 1972). Borderlineresults may maintain rather than eliminate thediagnostic problem. Doubts of myocardial infarc­tion may also occur with ST segment changes orT-wave inversion without serum enzyme elevationor serum enzyme elevation without Q-wavesespecially after cardiac surgery when the serumenzyme concentrations are raised because oftissue trauma. The value of another specific anddiagnostic technique which is safe, reproducible,repeatable and non-invasive is thus evident.

The two main approaches to acute myocardialinfarct imaging consist of (1) the utilisation ofpotassium analogues, mainly 201Thallium (Tl) asthallous chloride and (2) the utilisation of99mTc­

labelled radio-pharmaceuticals, mainly as 99mTc_pyrophosphate.

201Thallium and the other potassium analoguesare taken up by the normal myocardium so thatan infarct' of any duration or a region ofhypoperfusion is present as an area Of absent orreduced radioactivity C'cold spot") whereas 99m

~c-labelled phosphates are taken up by damagedtissue so that an acute infarct is shown as a

Page 2: Myocardial infarct imaging using 99m technetium

positive image ("hot spot"). The main advantageof 201 Tl imaging is that accurate diagnosis canbe made within 6 hours of acute episode(Wackers et al; 1976). Exercise 201Thallium myo­cardial scintigraphy is very sensitive and providesprognostically significantly information aboutspecific coronary lesions providing the ability todistinguish regions of myocardial ischaemia fromfixed necrosis which is invaluable to surgeonsplanning myocardial revascularisation by corona­ry artery by-pass graft (CABG) surgery. However,it is extremely expensive and serial imaging of thepatient is undesirable because of cost, dosimetryand long biological half-life characteristics.About one' third of subendocardial lesions are notvisualized (Pittand Straus, 1976) and thenegative ("cold area") rather than positive image("hot area") of the infarct may provide somedifficulties for interpretation.

With99mTc-Iabelled pyrophosphate imagingaccurate diagnosis can be made 24 hours afterthe acute episode with a false negative rate of lessthan 4 per cent (Parkey et at; 1977).

Serial imaging of the same patient is possible,the radio-pharmaceutical being relatively cheap,and the dosimetry and biological half-life charac­teristics allow for daily images. Subendocardialinfarcts can be diagnosed though small lesionsmay be missed and the positive ("hot area")rather than negative ("cold area") images makesinterpretation less difficult: An old infarct can bedifferentiated from a recent one since only thelatter will concentrate these radiopharrnaceuti­cals. However, activity in the bony structures(99mTc-Iabelled phosphates are bone imagingagents) may cause difficulties in interpretationand false positive images occur in about 10-15per cent of patients.

A number of99mTc-labelled radiopharmaceuti­cals are now available for acute infarct scanninge.g. 99mTc-tetracycline, 99mTc-glucoheptonate,99mTc-dimercapto succinic-acid,99mTc-pyrophos­phate (99mTc_PYP) ,99mTc-methylene diphospho­nate (99mTc_MDP),99mTc-ethyl-hydroxy-diphus­phonate and 99mTc-imidodiphosphonate. 99m Tc­pyrophosphate is the most commonly used agentbut the new preparation99mTc-imidodiphospho­

nate has now been used experimentally andclinically claimed to be superior and as the agentof choice (Ell et al; 1978; Joseph et al; 1978).

In addition to the traditional means of

diagnosis of acute myocardial infarction (clinical,electrocardiography and serum enzyme changes)the value of another specific and diagnostictechnique in the early diagnosis of this conditionis evident. This paper describes experiencewith99mTc-stannous pyrophosphate (99mTc_PYP)and 99mTc-methylene diphosphonate (99mTc_MDP) myocardial imaging and its purpose is toclarify to what extent this investigation fulfils theabove mentioned criteria.

MATERIALS AND METHODS

Patients admitted to the coronary care unit. with suspected or proven myocardial infarctionwere imaged using an Ohio Nuclear Gamma.Scintillation Camera Sigma 400 with a 10 inchdiameter crystal detector and Differential Uni­form. Field Correction (DUFC). A low energy(140 Kev) high resolution 16,000 hole parallelhole collimator was used. The 'patients werebrought to the Nuclear Medicine Unit forimaging when they were clinically stable. Eachscintiscan was performed 1 hour after intravenousinjection of 15 mCi of either99mTc-PYP or99mTc_

MDP and routine anterior, left anterior oblique,and left lateral views were taken. Additional rightanterior oblique view in some patients wereobtained. For each image 400,000 counts werecollected and took about 3 to 4 minutes. Theimaging time for 3 views was approximately 15minutes. Pictorial documentation was made onpolaroid films. The images were rated ° to 4using the method of Parkey et al. (1974) and thisdepended on the activity produced by myocardialuptake of the radionuclides. ° represents noactivity; +1 questionable activity where cardiacactivity cannot be distinguished from generaltissue and blood background activity; +2 definitebut faint activity over myocardium but less thanuptake by bone; +3 and +4 represents increas­ing degrees of activity within the infarct, +3being uptake equal to the uptake observed insternum and ribs and +4 being greater thanneighbouring bone activity (sternum and ribs). Inthis study °and +1 were considered as negativeand grades + 2 to +4 as positive for myocardialdamage. No adverse reaction to the injection ofthe radiopharmaceutical or from the imagingprocess itself was noted in any patient. Inaddition every patient underwent daily 12 leadelectrocardiograms and daily estimation of creati­nine phosphokinase, aspartate transaminase andhydroxybutyric dehydrogenase.

290

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TABLE 11

99mTc_PYP AND 99mTc_MDP SCAN RESULTS FROM18 INVESTIGATED PATIENTS

Diagnosis No. Cases Positive Negative SensitivityScan Scan

) PYP 7(390/0) 6 1 850/0Transmural infarction )

) MDP 2010/0) 1 1 500/0

) PYP 1 (60/0) 1 0 1000/0Subendocardial infarction)

) MDP o (00/0) 0 0 -

) PYP 306"10) 2 1 660/0

Unstable angina )) MDP 2(110/0) 0 2 -

) PYP 1 (60/0) 1 0 -Doubtful diagnosisDoubtful diagnosis )

) MDP 2(110/0) 2 1

) PYP 12Patient total )

) MDP 6

TABLE ill

ANALYSIS OF 99mTc_PYP AND 99mTc_MDP SCANS ANDENZYME RESULTS IN PATIENTS STUDIED

Diagnosis [ECG] 99mTc- 99mTc_ Total No. Positive BorderUne Negativepyp MDP of Cases Enzymes Enzymes Enzymes

) +ve scan 6 1 7 6 1 0Transmural infarction )

) -ve scan 1 1 2 2 0 0

) +ve scan 1 0 1 0 1 0Subendocardial infarction)

) -ve scan 0 0 0 0 0 0

Unstable angina ) +ve scan 2 0 2 0 2 0(accelerated angina )preinfarction syndrome ) -ve scan 1 2 3 2 1 0

) +ve scan 1 1 2 0 1 1Previously abnormal )

electrocardiogramelectrocardiogram ) -ve scan 0 0 0 0 0 0

) §ve scan 0 0 0 0 0 0Normal electrocardio-gram ) -ve scan 0 1 1 0 1 0

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Page 6: Myocardial infarct imaging using 99m technetium

To investigate the possibility of false positivemyocardial imaging SO patients referred for wholebody bone scanning with a variety of non-cardiacconditions also underwent myocardial imaging 1hour after intravenous injection of the same doseof the radionuclides. The patients' clinical data,serum enzyme result, electrocardiogram and theside and grading of radioactivity and intervalbetween chest pain and imaging is summarized inTable I. Patient population consisted of 13 malesand 5 females with age ranging from 27 to 76years old. The mean time from onset of acutechest pain to imaging is 6 days (range = 1-19days). In 12 patients99mTc-PYP while in 6patients99mTc-MDP were used.

9 patients (SO per cent of all admissions) werediagnosed on the basis of the electrocardiogramto have transmural myocardial infarction (McCo­nahay et al; 1970). Of these 7 patients had apositive scan and 2 patients had a negative scan:sensitivity of detection - 78 per cent (Table II).The 2 patients with negative scans were imagedat 17 and 19 days after infarction, and it ispossible that earlier imaging would have beenpositive. 1 patient (6 per cent of admissions) wasjudged to have subendocardial infarction (TableI). She had a positive scan: sensitivity ofdetection - 100 per cent and borderline enzymerise. Of the 9 patients with transmural infarction8 had positive enzyme rises while 1 hadborderline enzyme rise. •

5 patients (28 per cent of admissions) wereconsidered to have unstable angina (acceleratedangina, preinfarction syndrome). Of these only 2had positive scans with imaging done at 3 daysafter onset of acute chest pain: sensitivity ofdetection - 40 per cent. Both had borderlineenzyme rises. Of the remainder 3 patients withnegative scans, 2 had positive enzymes rises with

imaging done at 3 and 6 days from onset of chestpain; 1 patient had borderline enzyme rise withimaging done at 14 days from onset of chestpain.

The remannng 3 patients (16 per cent ofadmissions) presented with doubtful diagnosisand 2 had abnormal electrocardiograms resultingfrom conduction defects or previous ischaemicdamage rendering electrocardiographic diagnosisimpossible. These two had positive scans withnegative or borderline enzyme rises and repeatscans 7 days later were negative; one of them hadprevious massive infarction and resection ofventricular aneurysm 3 years previously presentedwith mild left ventricular failure but had no chestpain. The remaining 1 patient who had anginapectoris for past 18 years and myocardialinfarction 8 years ago presented with chest painbut had a normal ECG and borderline enzymerise. The scan was negative but was done at 8days after the onset of chest pain and it ispossible that an earlier imaging would have beenpositive. Further analysis of these results ispresented in Table Ill.

One of the patients with acute transmuralinfarction had primary arteritis for the past 10years, angina pectoris for the past 5 months andaccelerated angina for 1 month prior toadmission. She presented with severe retrosternalpain, and electrocardiogram indicated acuteanteroseptal infarction. Positive enzyme rise and+4 positive scan were obtained. Repeat electro­cardiograms 6 months later showed persistence ofST elevation in Vl-V5 leads and a repeat scan atthis time still showed +3 positive anteroseptalactivity indicating a ventricular aneurysm.

Table IV shows the results of myocardialimages obtained with the group of 50 patients

TABLE IV

SO PATIENTS WITH NON CARDIAC PATHOLOGY REFERREDFOR WHOLE BODY BONE SCANNING

Isotope No. of +4 activity +3 activity +2 activity +1 activity 0Patients image Image image image activity

99mTc-PYP 25 0 0 0 2 23

99mTc_MOP 25 0 0 0 1 24

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Anterior Left Lateral

Figure 1. M. Paramsothy et al. Nonnal 99mTc.PYP Scan.

Left Anterior Oblique

Figure 2. M. Paramsothy et al. 99mTc.MDP Scintigram [anteriorview] of anteroseptal infarct.

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Figure 3. M. Param80thy et al. A typical 99mTc.PYP Scan of apatient with an inferior myocardial infarction.

Figure 4. M. Paramsothy et al. Serial 99mTc·PYp Scan.

Figure 5. M. Param80thy et al. Typical Scan of a subendocardialinfarct.

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with no history of heart disease referred for wholebody scanning for a variety of reasons but mainlyfor the detection of bony metastasis.

In our study with99mTc-PYP

and99mTc-MDP

the apparent low sensitivity of detection with99mTc-MDP is probably due to the fact that mostof the. patients imaged with this radiopharmaceu­tical had a long interval time between chest painand imaging (varied from 3 to 19 days). Inrelation to quality of images both radiopharma­ceutical 'appeared to be similar in their ability.

Fig. 1 to 5 represents the spectrum ofscintiscans obtained with this technique in thisseries of patients.

DISCUSSION

Imaging of acute myocardial infarct can beperformed both with radiopharmaceuticals thatvisualize the normal myocardium (42K, 43K,81Rb, 86Rb, 129Cs, 131Cs, 201Tl) and withthose that visualize the abnormal myocardium(99mTc-tetracycline,99mTc-glucoheptonate,99m Tc~phosphates). Each group of radiopharmaceuticalshas advantages and disadvantages and has beendiscussed previously.

201Thallium (201Tl) with its 74-hr half life and81-Kev x-ray and high myocardial extractionefficiency (greater than 80 per cent) and moresuitable imaging properties has now becomeestablished as the imaging agent of choice 'in. theevaluation of patients with ischaemic heartdisease. Exercise 201 Tl myocardial scintigraphyprovides prognostically significant informationabout specific coronary lesions and the necessaryfunctional equivalent to coronary arteriogram andis probably the most sensitive method for thedetection of myocardial ischaemia. It is moresensitive than S-T segment depression on theexercise ECG (Wainwright and Maisey, 1978).

The ability to distinguish regions of myocardialischaemia from fixed necrosis using 201\TI-scinti­graphy is invaluable to surgeon planning myocar­dial revascularization by CABG surgery and thiscan be accomplished more .economically byabandoning separate rest and stress injectionsand instead re-imaging the myocardium severalhours after initial administration of 201'TI whensignificant intramyocardial redistribution of tra-

,cer has occurred. At present the three most

clinically relevant uses of this. technique 'ar~ (1)Detection of specific coronary artery: .disease e.g.left anterior descending (LAD) disease; .especiallyin public transport personnel such as airlinepilots and in patients without symptoms: butstrongly positive exercise electrocardiograms, (2)Distinction of myocardial necrosis from myocar­dial ischaemia e.g. in the preoperative assessment

'of CABG patients.' (3) Follow up of CABGpatients - non-invasive detection of graft closure.There are other valuable and potential applica­tions but remain to be completely explored.201Thallium myocardial scintigraphy should be

the initialmethod of choice in the assessment ofischaemic heart disease if this technique isavailable. It can be suitably combinedwith'PwTc­multiple gated acquisition (MUGA) scintigraphyas one sequential procedure- .in individual pa-tients. The information obtained by both '., me­thods is complimentary as perfusion defects causeventricular wall motion and resulting pumpfunction abnormalities. It is invaluable in thecoronary care unit where the cardiologist need tomonitor patient's cardiac function continuously,and evaluate therapy instituted., The chief dis­advantages of 201T1 are its cost and its restrictedavailability. (201 Tl) is cyclotron produced and hasa half life of 74-hrs). Daily serial imaging of thesame patient is undesirable because of high cost,dosimetry and long biological .half-life characte­ristics. An old infarct cannot be distinguishedfrom a recent one.

99mThe advantage of Tc-labelled phosphates

imaging are accurate diagnosis can be" made 24hours after the acute episode with a false negativerate of less than 4 per cent (Parkey et al. 1977) .Serial daily imaging of the ,-,same patient iseminently possible as the radiopharmaceutical isrelatively cheap, and the dosimetry and biologicalhalf-life characteristics allow for daily -images (70mRad for 2011Tl against lSmRad/mCi, for'99mTc

whole body). An old infarct can be distinguishedfrom a .recent one since only the .Iatter willconcentrate these radiopharmaceuticals. Thesesubstances are thought to be .bound vwith thecalcium ion of hydroxyapatite-crystals in or. nearthe mitochondria of damaged 'cells and accumu­late mainly in the tissue at the edge -of- theinfarct. However, the sub-cellular distributionexperiments by Dewanjee and ~ Kahn (1976) .didnot substantiate this theory and suggested thatthe uptake of technetium chelates in myocardialinfarcts may be due to the formation of

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polynuclear complexes with denatured macro­molecules rather than to the deposition ofcalcium in mitochondria. This would also explainwhy other technetium chelates such a§9mTc-Iabel_led tetracycline and glucoheptonate have someability to concentrate in myocardial infarctalthough they are in no way considered bonescanning agents. The uptake of these radiophar­maceuticals by damaged myocardial tissue pro­duce a positive image ("hot spot") withoutinterference from the normal myocardium.Images of high technical quality are obtained byusing radiopharmaceuticals of high signal tonoise ratio (uptake in infarcted myocardium/uptake in normal myocardium). The signal tonoise ratio for99mTc-pyrophosphate and99mTc­

methylene diphosphonate is S:1. Recently a newbone imaging agent99mTc-imidodiphosphonate

(99mTc_IOP) with a signal to noise ratio of 20:1has been used experimentally and clinically andclaimed as the agent of choice (Ell et al, 1978and Joseph et al, 1978). Minimum interferencefrom the blood pool background activity isimportant in producing high quality images, andthis is dependent on the blood clearance rates ofthe radiopharmaceuticals.· The percentage of5-minute post-injection sample at 1 hr for 99mTc­MOP = 2S%;99mTc-PYP = 39%; and 99mTc_lOP = 30% (Ell et al, 1978). Activity in thebony structures is minimized if imaging isperformed 1 hr after intravenous injection.Contrast enhancement by computer processingwith background and rib subtraction techniquesmake the image even better seen. This may benecessary in about 10% of cases especially ofinfarctions in the posterior wall which havesuperimposed rib structure seen. However uptakein normal bone is not considered a disadvantagefor it allows exact location of the sternum andxyphoid and the rib arches, this being anexcellent anatomical reference system for theinterpreting observer. Throughout this investiga­tion it was consistently felt that both for thenuclear medicine physician and the cardiologistthe interpretation of these images is much easierand perhaps, therefore, more accurate.

If high sensitivity of detection of myocardialinfarction is to be achieved with this techniqueserial scanning is mandatory. Two patients hadclinical and electrocardiographic evidence oftransmural infarction and positive enzymes risesbut negative scans. Both patients, however were

scanned at 17 days and'!9 days after the acuteevent, clearly too late and these two cases shouldnot be counted as true false negatives. Theoptimal time for imaging is between 24 and 48hrs after the acute event. A positive result with atechnetium scan may usually be obtained up to 6days after acute episode; after this the imagebegins to fade and this is a most useful feature ofpositive myocardial infarct imaging as it allowsthe differentiation of an old infarct from a recentone (Ell et at, 1978). In our series one patienthad previous myocardial infarction withaneurysm from anterolateral wall resected andpresented with mild left ventricular failure but nochest pain; and another patient with previousinfarction presented with chest pain. Both pa­tients had persistent electrocardiographic changessince the previous episode and negative orborderline enzyme rise in this episode andelectrocardiographic diagnosis of recent infarctionwas problematic. Both patients had +3 positivescans and repeat scans 7 days later were negative,confirming recent reinfarction. (Fig. 4). Infre­quently the positive image persists for weeks ormonths and could be a problem in interpretatingsubsequent scintiscans in these patients who areat risk of reinfarction. (Parkey et al, 1977).Persistent S-T elevation in Vi-VS electrocardio­graphic leads and persistent positive scans couldsuggest ventricular aneurysm. One patient in ourseries who had a 10 year history of primaryarteritis, S months history of angina pectoris, and1 month history. of accelerated angine had anacute anteroseptal infarction with ECG changesand a +4 positive scintiscan. Repeat studies 6months later showed persistent ST elevation onVl-VS leads and + 3 positive anteroseptal activityscintiscans indicating an anteroseptal ventricularaneurysm. Thus meaningful interpretation ispossible by correlation with the clinical statusand comparison with previous scintiscans. Base­line myocardial scans should be considered forpatients with symptomatic coronary arterydisease.

Assessing the image is subjective and thegrading 0 to +4 using the method of Parkey et al(1974) refers to visibility of the image and not toits size. Assessing the size of an infarct bytechnetium scans is not reliable as uptakedepends on blood flow and is not proportional tothe volume of the infarct. Recent work indicateincreased localization of the phosphate com-

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pounds in areas of reduced coronary flowimplying that some perfusion is required for thetracer to be extracted and positive uptake doesnot necessarily mean cell death or irreversibleinjury. In our series out of the 5 patientsdiagnosed to have unstable or accelerated angina2 had +3 positive scintiscans at 3 days after theonset of acute chest pain. Of the remaining 3patients with negative scans 2 had initial scansdone at 6 and 14 days after onset of acute chestpain and this delay could possibly have affectedthe imaging. Radioactive uptake in unstableangina has been also documented elsewhere(Donsky et al, 1976). Myocardial uptake has alsobeen observed in patients with stable angina,

.valve calcification, cardiomyopathy, after directcurrent transthoracic shock therapy and ondialysis with secondary hyperparathyroidism anduremic pericarditis.

Unequivocally positive scans are present inabout 90-95% of ECG proved transmural in­farcts; where a localised area of uptake is seen(Fig. 2, 3); in subendocardial infarction theimages are less intense and usually diffuse (Fig.5), so that necrosis can seldom be localisedanatomically. In our series positive scans in ECGproved transmural infarcts were obtained in 780/0of cases. However this does not reflect the truesensitivity of detection as in both patients withnegative scans the imaging were done at 17 and19 days after the acute event. Fewer than 4%false negative results occur with optimal timing ofimaging (1-3 days after the onset of infarction)and performance of serial imaging (Parkey et al,1977). A localised zone of intense activity in theanterior wall is seen on anterior infarction (Fig.2) and plate-like or band-shaped activity alongthe inferior or diaphragmatic wall of myocardiumoccurs in inferior wall infarction (Fig. 3). In ourseries the lower rate of positive scans using 99mTc_MDP as compared t099mTc-PYP does not reflectits true sensitivity of detection as many of thepatients imaged wth this radiopharmaceuticalhad long time intervals between onset of event,and time of imaging; in addition lesser numberof patients were scanned with99mTc-MDP than99mTc-PYP. Both the imaging agents havesimilar signal to noise ratio (5:1) though99mTc_MDP images at 1 hr have significantly lessbackground activity. In majority of patients, thediagnosis of myocardial infarction could be madeon the basis of well established criteria. A highsensitivity (85%) was achieved with99mTc_PYP

scanning in patients considered to have transmu­ral infarction. The one patient with subendocar­dial infarction (100%) had positive scan. 2 of the9 patients with transmural infarction and the 1patient with subendocardial necrosis had onlyborderline enzyme increases and may representthe hinterland between infarction. and ischaemiawithout infarction, and illustrates the use oftechnetium scans being sufficiently sensitive toshow myocardial damage undetected by enzymeelevation. In these 3 cases the technetium scanswere considered to be of special diagnostic value.

3 patients (16%) presented with a doubtfuldiagnosis either because of previous abnormaland uninterpretable electrocardiograms orbecause of normal electrocardiogram (Table Ill).The 2 patients with previous abnormal electrocar­diograms had positive scans with normal orborderline enzyme levels. Repeat scans 7 dayslater were negative and it was consideredjustifiable to classify these patients as infarcted orhaving severe ischaemia. In the 1 patient withnormal electrocardiogram and borderline enzymelevels the negative scintiscan was of value inexcluding infarction. Thus in all -these 3 casesthe 99mTc-phosphates scans were of considerablediagnostic value. False positive images occur inabout 10-15% of patients and may be secondaryto delayed clearance of radiotracer from cardiacblood pool e.g. in renal diseases; breast tumours;functioning breast parenchyma in premenopausalfemales; healing rib fractures or other ribabnormalities, and carcinoma. In our group of SOpatients with noncardiac pathology none hadpositive myocardial images (Table IV).

CONCLUSION

In assessing the role of technetium-labelledphosphates myocardial scanning the conventionalmethods of diagnosis of infarction has to beconsidered. Doubt whether infarction has occurr­ed arises most often in patients with oldinfarction with persistent ECG changes, leftbundle branch block, subendocardial infarctionand after cardiac operation when the serumenzymes concentration are raised because oftissue trauma. It will be in these cases thephysicians could find the scintigram useful inestablishing myocardial ischaemic necrosis. It is asafe, simple, cheap, reproducible, repeatable,non-invasive, and sensitive test (95% sensitivity ofdetection). Gamma cameras are expensive and

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few medical units have them. For reliable resultscare in technique and caution in interpretationshould be exercised. 201Thallium myocardial per­fusion scintigraphy is probably the most sensitivetest for ischaemic heart disease and whencombined with99mTc-MUGA scintigraphy whichprovides information about wall motion, cardiacchambers, ejection fraction is invaluable incoronary care unit. However, 99mTc-Iabelled phos­phates myocardial scintigraphy is still the morewidely used method.

SUMMARY

Radioisotope detection and localisation ofmyocardial infarction is discussed. Its clinicalvalue and pitfalls are also discussed. The clinicalapplication of this safe, simple, sensitive, repeat­able, reproducible and non-invasive method inMalaysian patients performed during the periodOctober 1978 to April 1979 at the UniversityHospital is reviewed. The main value of

99mTc­

labelled phosphate scan is in the demonstrationand localisation of recent myocardial infarctionsin patients where the electrocardiogram or serumenzymes changes are unhelpful.

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