Nuclear cardiology methods in routine clinical practice

Lang O., Kamínek M.

Dept Nucl Med, School of Medicine, Praha, Olomouc

Materials for medical students

Nuclear cardiology

Set of non-invasive mostly imaging diagnostic methods of the cardiovascular system

Huge expansion during last 30 years, in Czech rep. during last 10 years

Examination of venous system of lower extremities and lung perfusion are included

Seminar includes

Imaging in nuclear cardiology (NC)NC methodsMyocardial perfusionMyocardial viabilityHeart functionExamination of pulmonary embolismNew trends

Ways of imaging in NC

Detectors of ionizing radiation – gamma camerasSource of radiation inside the patient body -

radiopharmaceutical, tracerWays of distribution - perfusion, metabolic

process, receptors, etc.Source of information - ionizing photon (gamma)Digital images - processing, archiving, transfer

planar, tomographic• SPECT (transversal), PET (coincidence)

Data collection by gamma cameras

PET camera

Way of tomography - SA slices

Other tomographic slices

Parts of left ventricle myocardium

Legenda:

1 - apex

2 - anterior wall

3 - lateral wall

4 - inferior wall

5 – septum

VLA SA

HLA Pollar map

Heart examination

Myocardium imaging perfusion during stress and rest (80%) viability necrosis, innervation, ischemia

Mechanical function assessment steady-state ventriculography (multigated - MUGA) Angiocardiography (first-pass) non-imaging systems

Myocardial perfusionrate of NC examinations

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CR 1999 EU 1994 EU 1998 USA 1994

Why stress?Pathophysiology of CADHemodynamic effect of coronary stenosesCollateralsIschemic cascade

Rest myocardial perfusion in CAD

Physiological compensatory arteriolar dilatation in the region supplied by narrowed artery

Blood flow remains the same as in the region supplied by normal artery

Radiopharmaceutical distribution remains homogenous

Stress myocardial perfusion in CAD

Arteriolar dilatation in the bed of normal artery for blood flow increase

Blood flow through the normal artery increasesArteriolae in the bed of narrowed artery are

already dilated - no further dilatation can occure, so blood flow remains as in the resting state

Non-homogenous perfusion (radiopharmaceutical distribution) as a result

Ischemic cascade

Type of stress

Mechanical dynamic stress ergometer (bicycle), tread-mill

Pharmacological stress vasodilators - adenosine, dipyridamole positively inotropic drugs - dobutamine,

arbutamine atropine

Combined of all mentioned above

Ergometer

Goal is to achieve at least 85% of maximal heart rate (220-age) or double-product more than 25000

Increase by 50 (25) W after every 3 (2) minutesRate of pedalling 40 to 60 per minuteRadiopharmaceutical injection at peak stress

distribution proportional to blood flow at the time of injection

Maintain this stress for at least 1 to 2 minutesWithdraw betablockers (BB), patient fasting

Dipyridamole stressActs indirectly via the adenosin (block its

removal)Dilates coronary resistant arteries - it makes

possible to assess coronary flow reserveMaximal effect is achieved 3 to 4 minutes after

stopping the 4 minutes infusionIts effect can be stopped with theophyllines

withdraw them before the test

Usually used in patients using BB, unable to exercise, with LBBB

Contraindications to perform dipyridamole stress

Patients with chronic obstructive pulmonary disease treated by theophyllines (dobutamine can be used)

Patients should avoid tee, cofee, cola before the test to prevent false negative results (insuficient or no vasodilation)

Dipyridamole stress

Side effects of dipyridamole

They occures in approximately 30% of patients headache neck tension warm feeling dizziness nausea, hypotension chest pain (very seldom)

Performance of dipy stress

Dipyridamole applied by intravenous infusionUsual dosage is 0.56 (0.75; 0.84) mg/kg Dose is diluted with saline to 50 ml

to prevent local side effects (arm pain)

Duration of infusion is 4 minutes If the patient is unable of any physical stress,

tracer is injected 3-5 min. after stopping infusion

Combined stress

Dipyridamole is infused according to previous rules to sitting or lying patient

3 to 6 min. bicycle stress follows better image quality lower frequency of side effects can be performed even in patients with hypotension

1 to 2 min. before stopping bicycle stress radiopharmaceutical is injected

Test arrangement

Right arm - tourniquet of tonometerLeft arm - infusion through the cannulaSaline is connected after stopping

dipyridamole for venous link for the case of any complication

Patient is sitting on the ergometer, ECG electrodes according to Mason and Likar

Dobutamine stress

If dipyridamole is contraindicatedDobutamine intravenously in the dose of 5 to 10

g/kg/min., increase every 3 min. up to dose of 40 g/kg/min.

Monitore ECG, HR and BP, if 85% of maximal HR is not achieved, add Atropine

Radiopharmaceutical is injected 1 to 2 min. before stopping stress

Contraindications: ventricular tachycardia, severe hypertension, hypertrophic cardiomyopathy

Myocardial perfusion protocols

One-day (Tl, Tc, FDG) - two-days (Tc, FDG, Tl)

Stress - rest or rest - stress (Tc, Tl-Tc)Stress - (redistribution) - reinjection (Tl)Stress - metabolism (Tc - FDG)Stress - rest - metabolism (Tc, FDG)Rest - redistribution - (late redistribution) (Tl)Rest - metabolism (Tc - FDG)

Radiopharmaceuticals for perfusion

Tl-201 chlorid or Tc-99m MIBI for SPECT, N-13H3 or H2O-15 for PETDistribution in the myocardium rely on cells perfusion Tl-201 has redistributionTc-99m MIBI does not have redistribution

Data processing

Quantitative analysis of myocadial perfusion distribution CEqual™ - uses pollar maps for standardization and

comparison with „normals“

Gated (synchronized) tomography (QGSPECT) divides cardiac cycle into 8 periods makes possible to evaluate mechanical function of

the heart (ejection fraction - EF)

Quantification of perfusion

QGSPECT

Basic patterns of myocardial perfusion imaging (MPI)

Normal finding homogenous perfusion during stress as well as rest

Sign of ischemia perfusion defect during stress which disappears on

rest (reversible defect)

Sign of scar perfusion defect on stress and rest (fixed defect)

Sign of ischemia and scar combination of both mentioned above

Main clinical indication of MPI

Detection of ischemic heart diseaseHemodynamic effect of coronary stenosesPrognosis of patients with konwn CADEvaluation of revascularization effect and

detection of restenosisRisk stratification of patients after MIMyocardial viabilityAcute coronary syndromesCardiac risk in non-cardiac surgery

Detection of CAD

66y old pt, atypical chest pain, ECHO difuse wall motion abnormality, Ao+mi reg, sci isch. of inferior wall, EF 40%

Detection of CAD basic parameters

Planar Tl-201 scintigraphy - qualitative evaluatioin

Group of 4.678 pts - sens. 82%, spec. 88% pts without MI - sens. 85% pts after MI - sens. 99% one-vessel disease - sens. 79% two-vessel disease - sens. 88% three vessel disease - sens. 92%

Detection of CAD basic parameters

Referral bias only patients with positive scintigraphy are referred to

coronarography patients with normal scintigraphy are not catheterized higher sensitivity but decline of specificity

Normalcy rate (used instead of specificity) negative scintigraphy in patients with very low pretest

probabilty of CAD based on history, symptoms, stress ECG

Detection of CAD basic parameters

SPECT Tl-201 scintigraphyGroup of 1.527 pts - sens. 90%, spec. 70%

(more false positives due to artefacts), normalcy rate 89% pts without MI - sens. 85% pts after MI - sens. 99% one-vessel disease - sens. 83% two-vessel disease - sens. 93% three-vessel disease - sens. 95%

Detection of CAD basic parameters

SPECT Tl-201 scintigraphyGroup of 704 pts

stenosis of 50 to 70% - sens. 63% stenosis of 75 to 100% - sens. 88%

Dipyridamole stress (1.272 pts) sens. 87% spec. 81%

Detection of CAD basic parameters

SPECT Tl-201 scintigraphyAsymptomatic pts

5.000 coronarograms normal scintigraphy exclude CAD positive scintigrapy has positive predictive

value (PPV) of 50% - does not confirm CAD

Detection of CAD basic parameters

SPECT Tl-201 scintigraphyIndividual arteries (1.200 pts)SPECT is better than planar scintigraphy

(better localisation) LAD - sens. 80%, spec. 83% LCx - sens. 72%, spec. 84% RCA - sens. 83%, spec. 84%

Detection of CAD basic parameters

SPECT Tc-99m MIBI scintigraphySensitivity 87%Specificity 73% (less artefacts using

GSPECT)Normalcy rate 92%Optimal indication for detection of CAD

pretest probability 0.15 to 0.50 + pos. stress ECG pretest probability 0.50 to 0.85

Detection of CAD basic parameters

Difference was not confirmed Tl-201 vs Tc-99m MIBI MIBI vs Myoview physical vs pharmacological stress men vs women

Improvement of accuracy was confirmed SPECT vs planar scintigraphy GSPECT, quantification, prone projection

Pts prognosis

Prognosis of pts with known CADbasic parameters

Good prognosis - normal scintigraphy 2.825 pts without MI

• annual increment of death 0.24%

• annual increment of MI 0.53%

Signs of poor prognosis more perfusion defects in more arterial territories increased uptake in lungs and transient LV dilatation reversible defects, large and severe defects

Pts after revascularizationdetection of culprit lesion

56 y old pt, typical AP, positive stress ECG

SCG arteries stenoses, way of treatmen:

1. CABG RIA, RMS I, III a IV

2. PTCA RMS III a IV

Pts after revascularizationassessment of the result moderate ischemia of the lateral wall, after PTCA LCx: perfusion and wall motion improvement, EF from 56% to 63%, stress ECG positive in both

Pts after revascularizationprognosis

8

2540

90

10

20

30

40

positive negative

yes

no

MPI

Cardiac events

chi - square = 26.76p = 0.00000023RR = 3.15

Pts after revascularizationsummary

Early after the procedure negative scintigraphy - good prognosis positive scintigraphy - no predictive value

Ability of long-term prognosisRestenosis detection

in symptomatic patients in asymptomatic patients with positive stress ECG

Pts after MI

Definition of infarct sizeAssessment of salvaged myocardium thanks

to different ways of therapyEvaluation of myocardial viability in

location of wall motion abnormalityRisk stratification using stress perfusion

scintigraphy

Pts after MIscintigrapnic findings

Group of 55 pts pos 38 (69%), borderline 3 (5%), neg 14 (26%)

Group after QMI (32 pts) pos 23 (72%), borderline 2 (6%), neg 7 (22%)

Group after nQMI (23 pts) pos 15 (65%), borderline 1 (4%), neg 7 (31%)

Group with positive enzymes kinetics (35 pts) pos 25 (71%), borderline 3 (9%), neg 7 (20%)

Pts after MI with positive scintitypes of impairment

Group of 41 pts scar 6 (15%), scar + ischemia 9 (22%), isch 26 (63%)

Group after QMI (25 pts) scar 5 (20%), scar + ischemia 7 (28%), isch 13 (52%)

Group after nQMI (16 pts) scar 1 (6%), scar + ischemia 2 (13%), isch 13 (81%)

Group with positive enzymes kinetics (25 pts) scar 4 (16%), scar + ischemia 8 (32%), isch 13 (52%)

74y old pt, nQIM 9/98, left - scinti before PTCA 2.11.98, then PTCA LAD and OM with stents, right - scinti after PTCA 17.12.98

Pts after MIsummary

High risk pts (shock, failure, persistent AP, previous MI) - coronarography

Without failure with EF < 40% - scintigraphy viability and residual ischemia

Moderate risk - stress scintigraphy conservative vs invasive therapy

Low risk - stress ECG

Myocardial viabilityclinical significance

Important before revascularization prediction of cardiac function improvement (>

25% of myocardium should be viable)

Patients with cardiac failure decline of mortality but increase of cardiac

failure due to CAD nowadays high prevalence of viable myocardium among

pts in waiting list for heart transplantation

Myocardial viabilitycharacteristics

Defined by perfusion, metabolism and functionStunned myocardium

wall motion abnormality but normal perfusion and preserved metabolism

Hibernating myocardium wall motion and perfusion abnormality but

preserved metabolism

Scar abnormality of all characteristics

Myocardial viabilityPET examination (mismatch = hibernation)

Myocardial viabilityprinciple of the assessment

Preserved function of ATP-ase late accumulation of Tl-201

Preserved glucose metabolism accumulation of F-18 FDG

Preserved mitochondrial function accumulation of Tc-99m MIBI

Preserved answer to dobutamine dobutamine echocardiography

50y old woman, QMI of anterior wall treated by rescue PTCA LAD with stent implant. 6/99, ECHO anterior wall motion abnorm., stress scinti 7/99 apico-antero-septal scar,

examination by Tl-201 9/99, F-18 FDG 10/99201Tl

rest

redistribution

VLA

99mTc MIBI rest

18F FDG

restVLA

50y old woman, QMI antero-septal 1995, after PTCA LAD 1997, recurrent AP, stress scinti 11/98 antero-septal scar, Tl-

201 1/99, F-18 FDG 2/99, ECHO unable to evaluate

99mTc MIBI rest

201Tl

redistribution

VLA

99mTc MIBI rest

18F FDG

restVLA

72y old woman, MI 4/00, PTCA LAD 5/00, exam. 7/00, viab. 8/00, PTCA LAD 9/00, follow up exam. 10/00 – perfusion improv. about 7% of myocardium of LV, EF as well as wall motion the same

Myocardial viabilityaccuracy of different methods

Acute coronary syndromes

Imaging of jeopardized myocardium injection on admission, imaging after stabilization PPV of perfusion defect 90% NPV of no defect 100%

Infarction size measurement examination before leaving (correlates with histology)

ViabilityRisk stratification

Acute coronary syndromes

Examination rest SPECT perfusion with Tc-99m MIBI

Indication non-diagnostic ECG

Limitation availability

Benefit cost

Cardiac risk assessment in non-coronary surgery

Separates group of pts with higher riskGroup of 2020 pts

perfusion defect - perioperative events in 20% of pts

no perfusion defect - perioperative events in 2% of pts

Radionuclide ventriculography(MUGA)

Information about regional and global ventricular function

Excellent reproducibility of the resultsIndications

cardiotoxicity of cytostatics alternative in pts non-evaluable with ECHO

Radionuclide angiocardiography

First-pass evaluation of right ventricle function quantification of central circulation shunts

Non-imaging devices can monitore EF on CCU can be used for ambulatory EF monitoring

Non-imaging devices

Post-stress ventriculography

Imaging of myocardial sympathetic receptor densityI-123 MIBG

Tracer accumulates in postganglionic praesynaptic vesicules

Non-invasive assessment of myocardial sympathetic tone prognosis of pts with cardiac failure

Rational treatment of cardiac failure with beta-blockers

New trends

New tracers for myocardial perfusion imaging

Imaging of myocardial ischemiaImaging of myocardial necrosisImaging of cells apoptosisImaging of endothellin receptorsImaging of gene expression

Conclusion Nuclear cardiology tests can display non-

invasively myocardial perfusion distribution during different pathophysiological conditions above all

They contribute to myocardial viability assessment in acute and chronic forms of CAD

Cooperation of cardiologists with nuclear medicine physicians is essential for proper use of this methods in favour of our patients

Radionuclide venography and lung scintigraphyMain clinical indication is suspicion of

pulmonary embolismMain clinical significance is negative finding

- can exclude embolismWidely available is perfusion scintigraphyCorrelation with chest radiograph is essentialVentilation scintigraphy is useful in embolism

of less than 50% of pulmonary circulation

Lung perfusion scintigraphy

Tc-99m MAA as a tracer capillary microembolism display pulmonary blood flow distribution

It does not increase pulmonary pressure Injection in supine positionPlanar or SPECT imagingProcedure takes approximately 30 min.Interpretation is visual - PIOPED criteria

Lung perfusion scintigraphypatient imaging

Lung perfusion scintigraphyplanar images - normal

Lung perfusion scintigraphy planar and SPECT slices - embolism

Lung perfusion and ventilationpulmonary embolism

anterior view, left - perfusion, right - ventilation

Lung perfusion and ventilation pulmonary embolism

ANT POST RPO LPO

perfusion

ventilation

Radionuclide venography

Displays patency/abrupt cutoff of lower limbs deep venous system

Displays abnormal collateralizationDisplays irregular or asymmetric fillingDoes not display thrombusInjection of Tc-99m MAA into dorsal pedal

veins - lung perfusion scintigraphy followsProcedure takes approx. 40 to 60 minutes

Radionuclide venography

injection and imaging

Radionuclide venography

left without, right with tourniquets

Radionuclide venography

pathological findings

New trends

Thrombi imagingLabeled thrombocytes

not readily available

Receptors imaging Acutect - not registered in the Czech rep.

• peptide binding to receptors of activated thrombocytes labelled with Tc-99m

Result available in the order of 4 to 6 hours