Cardiovascular System
Report template: Myocardial perfusion SPECT
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Solve questions (27) →Contents
- 14.1 Myocardial Perfusion Scintigraphy (MPI)
- 14.1.1 Radiopharmaceuticals (Tl-201, Tc-99m MIBI, Tc-99m Tetrofosmin)
- 14.1.2 Stress Protocols
- 14.1.3 Imaging Protocols (1-Day, 2-Day)
- 14.1.4 Polar Map and Segmental Analysis
- 14.1.5 Artefacts and Pitfalls
- 14.1.6 Clinical Indications and Prognostic Value
- 14.2 Assessment of Myocardial Viability
- 14.2.1 Tl-201 Rest-Redistribution and Reinjection
- 14.2.2 FDG PET Perfusion-Metabolism Mismatch
- 14.2.3 Hibernation vs Stunning vs Scar
- 14.3 MUGA (Radionuclide Ventriculography)
- 14.4 Cardiac Innervation Scintigraphy (I-123 MIBG)
- 14.4.1 H/M Ratio and Washout Rate
- 14.4.2 Prognosis in Heart Failure
- 14.4.3 Distinguishing Parkinson Disease and Dementia with Lewy Bodies
- 14.5 Cardiac Amyloidosis Scintigraphy (Tc-99m PYP/DPD/HMDP)
- 14.6 Cardiac Sarcoidosis (FDG PET)
- 14.7 Cardiac PET Perfusion and Myocardial Blood Flow Measurement
- Key Points for the Board
- Current guidelines on this chapter's topics
Learning objectives and modules5 modules · about 3 h 50 min
Learning objectives
After this chapter you will be able to:
- Compare myocardial perfusion tracers in terms of uptake mechanism, extraction and redistribution.
- Select exercise and pharmacological stress protocols, with their contraindications, and imaging protocols.
- Interpret perfusion defects with the 17-segment model and scores; distinguish artefacts from true defects.
- Assess myocardial viability from Tl-201 and FDG PET findings.
- Explain ventricular function assessment with MUGA and its use in monitoring cardiotoxicity.
- Explain the indications and interpretation criteria for cardiac innervation, amyloidosis and sarcoidosis imaging and for PET measurement of myocardial blood flow.
Modules
The chapter is divided into study modules without changing the order of the text: read, watch the animations, then answer the questions linked to those headings.
- Module 114.1.1–14.1.2 Myocardial Perfusion Scintigraphy (MPI) · Stress Protocols50 min · 1 animation · 20 questionsAnswer the questions →
- Module 214.1.3–14.1.5 Imaging Protocols (1-Day, 2-Day) · Polar Map and Segmental Analysis · Artefacts and Pitfalls55 min · 1 animation · 24 questionsAnswer the questions →
- Module 314.1.6–14.3 Clinical Indications and Prognostic Value · Assessment of Myocardial Viability · MUGA (Radionuclide Ventriculography)55 min · 1 animation · 18 questionsAnswer the questions →
- Module 414.4–14.6 Cardiac Innervation Scintigraphy (I-123 MIBG) · Cardiac Amyloidosis Scintigraphy (Tc-99m PYP/DPD/HMDP) · Cardiac Sarcoidosis (FDG PET)45 min · 21 questionsAnswer the questions →
- Module 514.7 Cardiac PET Perfusion and Myocardial Blood Flow Measurement · Key Points for the Board25 min · 6 questionsAnswer the questions →
Times are estimates: 130 words per minute, 3 min per animation, 1.5 min per question.
MOST FREQUENTLY ASKED IN THIS CHAPTER
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Tl-201: Na⁺/K⁺-ATPase, first-pass extraction 85%, redistribution present, T½ = 73 hours, low energy (69-83 keV)
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Tc-99m MIBI: Mitochondrial membrane potential, first-pass extraction 60-65%, no redistribution, marked hepatic excretion
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Tc-99m Tetrofosmin: Mitochondria, first-pass extraction 54%, faster hepatic clearance than MIBI, labelling at room temperature
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Ranking (first-pass extraction): Tl-201 > N-13 ammonia > Rb-82 > MIBI > Tetrofosmin
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Exercise is always preferred → target heart rate: (220 − age) × 0.85
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Vasodilators: Adenosine (direct A2A, T½ 10 s), dipyridamole (indirect), regadenoson (selective A2A, bolus, most widely used)
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For all vasodilators: Caffeine stopped 12-24 hours before (theophylline 48 hours); antidote = aminophylline
14.1 Myocardial Perfusion Scintigraphy (MPI)
14.1.1 Radiopharmaceuticals (Tl-201, Tc-99m MIBI, Tc-99m Tetrofosmin)8 questions
Tl-201 (Thallium-201):
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Production: Cyclotron (Tl-203 → Pb-201 → Tl-201)
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T½: 73 hours (3 days)
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Energy: 69-83 keV (mercury X-rays) → low energy → poor image quality
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Decay: Electron capture
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Uptake mechanism: Active transport via Na⁺/K⁺-ATPase → potassium analogue
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First-pass extraction: 85% (high → better linear relationship with flow)
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Redistribution: The most important property of Tl-201 → retained in myocardium after stress → redistributes between blood and myocardium over time → viable myocardium shows redistribution, scar does not
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Redistribution time: 3-4 hours (standard), 24 hours (late redistribution → viability)
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Activity: 74-111 MBq for stress (2-3 mCi; EANM), +37 MBq reinjection if needed; in the USA (ASNC) 92-130 MBq (2.5-3.5 mCi)
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Disadvantages: Low energy → more attenuation artefact; long T½ → high radiation dose; poor image quality
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Advantages: High first-pass extraction, redistribution → viability assessment
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Kinetics (EANM): ~88% is cleared from the blood on first pass; however, only ~4% of the injected activity reaches the myocardium
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Cell entry: ~60% depends on Na⁺/K⁺-ATPase; the rest is passive along the electrical gradient
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Extraction is preserved in acidosis and hypoxia; it falls with irreversible myocyte injury and fibrosis
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Uptake rises in proportion to flow up to 2-2.5 times resting flow, then plateaus
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EANM activities: 74-111 MBq for stress-redistribution, 37 MBq for reinjection. The effective dose is 140 µSv/MBq (bone surfaces and kidneys receive the highest organ doses); breastfeeding is interrupted for 48 hours
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Normal distribution of Tl-201: Myocardium, skeletal muscle, kidneys, thyroid, salivary glands and splanchnic organs; no brain uptake because it does not cross the blood-brain barrier
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Tl-201 washout: Fast in normal myocardium, slower in ischaemic myocardium (the basis of redistribution); in infarcted areas similar to normal myocardium. Tl-201 washes out of the myocardium much faster than MIBI
BOARD TIP
▸
"Most important property of Tl-201?"
→ Redistribution → viable myocardium fills in over time, scar does not.
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"Uptake mechanism?"
→ Na⁺/K⁺-ATPase (potassium analogue).
▸
"First-pass extraction?"
→ 85% (higher than Tc-99m agents).
Tc-99m Sestamibi (MIBI):
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T½: 6 hours (Tc-99m)
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Energy: 140 keV → optimal for gamma camera imaging
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Uptake mechanism: Mitochondrial membrane potential → lipophilic cationic complex → enters the cell by passive diffusion → retained by the negative mitochondrial membrane potential
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First-pass extraction: 60-65%
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Redistribution: NONE → minimal redistribution → stress and rest require separate injections
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Because there is no redistribution, MIBI can be given before reperfusion (PCI or thrombolysis) and imaged later. The defect on this image shows the 'myocardium at risk'; a subsequent rest study then shows the salvaged myocardium as the difference
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Hepatic excretion: Marked → liver activity on early images masks the inferior wall → a waiting time is needed ( 15-30 min after stress, 45-60 min after rest)
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Speeding hepatic clearance: Fatty meal or drinking water
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Dose: 1-day protocol → low dose 8-12 mCi, high dose 24-36 mCi
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Advantages: Good image quality, gating possible, EF can be calculated
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Other uses: Parathyroid scintigraphy, breast scintigraphy (→ see Chapter 13.2)
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Excretion: Mainly hepatobiliary, less by the kidneys; the gallbladder and kidneys receive the highest organ doses
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With Tc-99m perfusion agents uptake plateaus at ~2 times resting flow; at very high flow the degree of ischaemia may therefore be underestimated
BOARD TIP
▸
"Why does MIBI not show redistribution?"
→ Irreversible binding in mitochondria → no redistribution between blood and myocardium → separate injections are needed for stress and rest.
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"Why is liver activity a problem?"
→ Hepatobiliary excretion → masks the inferior wall → a waiting time is needed.
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"How to shorten the waiting time?"
→ Fatty meal or water → gallbladder contraction → faster hepatic clearance.
Tc-99m Tetrofosmin:
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T½: 6 hours (Tc-99m)
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Energy: 140 keV
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Uptake mechanism: Similar to MIBI → mitochondrial membrane potential (but partly cytoplasmic retention as well)
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First-pass extraction: 54% (slightly lower than MIBI)
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Redistribution: Minimal/none (similar to MIBI)
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Hepatic clearance: Faster than MIBI → shorter waiting time ( 10-15 min after stress may suffice)
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Advantages: Rapid hepatic clearance, easy preparation (labelling at room temperature, no heating needed)
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Dose: Similar to MIBI
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Excretion: Renal and hepatobiliary; myocardial uptake is ~1.2% of the administered dose. The gallbladder and colon receive the highest organ doses
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Effective dose coefficients: Tetrofosmin stress 6.9, rest 8.0 µSv/MBq; MIBI stress 7.9, rest 9.0 µSv/MBq
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Breastfeeding: Need not be stopped after Tc-99m agents (for safety, 4 hours or one feed may be skipped); no interruption is needed for short-lived positron emitters
A new PET perfusion agent: F-18 flurpiridaz
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A mitochondrial complex I (MC-1) inhibitor; approved by the FDA in 2024. Because it is labelled with F-18 (T½ 110 min) it is cyclotron-produced but can be distributed to distant centres; no generator or on-site cyclotron is needed
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High first-pass extraction and low positron energy give high resolution; it can also be used with exercise stress
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Flurpiridaz (FDA label, 2024): in a same-day protocol, rest 93-111 MBq, pharmacological stress 222-241 MBq, exercise stress 333-352 MBq (in a two-day protocol 93-111 MBq for both); at least 30 min (pharmacological) or 60 min (exercise) between the rest and stress injections. Acquisition starts 5 min after injection at rest and with pharmacological stress, 15-25 min after exercise, and lasts 10 min; dynamic acquisition allows myocardial blood flow quantification. Effective dose 0.019 mSv/MBq (with the maximum activities: rest 2.1, pharmacological stress 4.6, exercise 5.3 mSv). In two phase 3 trials sensitivity was higher than SPECT (74-89% and 63-77% by reader; SPECT 61-76% and 43-58%)
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SNMMI/EANM/ASNC/ACNM flurpiridaz guideline (2025): indications are the same as for other PET MPI agents; it may also be used in selected asymptomatic patients with a 10-year risk ≥20%. Absolute stress blood flow and flow reserve help to show multivessel disease, the physiological significance of a borderline stenosis and microvascular disease; the stress blood flow threshold is 1.6-1.9 mL/min/g for ≥50% stenosis and 1.6-1.7 mL/min/g for ≥70%, depending on the software. In a same-day protocol the stress study is corrected for residual activity from the rest injection
BOARD TIP
▸
"Tetrofosmin vs MIBI?"
→ Tetrofosmin → faster hepatic clearance → shorter waiting time. MIBI → requires heating (100°C, 10 min); tetrofosmin → labelling at room temperature. First-pass extraction: Tl-201 (85%) > MIBI (60-65%) > Tetrofosmin (54%).
The fraction of tracer molecules taken up by myocytes on the first pass through a capillary is shown at different flows and for six tracers. In the second step a short-axis image of a stenosed and a normal region changes as stress flow rises in the normal region; the plateau of the flow–uptake curves reduces defect contrast.
Continuous stream · no seeking
Key idea: uptake is flow × extraction; extraction falls with flow, so uptake plateaus at high flow and the defect looks milder than it is; the relation is most linear for O-15 water and N-13 ammonia.
Source: book (14.1: first-pass extractions; plateau at 2-2.5× for Tl-201, ~2× for Tc-99m). Curves are fitted to these values with an extended Renkin–Crone model (PS rises with flow); representative. The 1.5× flow limit in the stenosed region is an example value.
How to use: a single click on the drawing pauses and resumes; ↑ ↓ change the flow level in the first step and the tracer in the second (you can also tap a tracer row); ← → change steps.
Did this animation help you understand the topic?
Figure 14.1: Relationship between myocardial blood flow and uptake of perfusion agents (plateau at high flow) and first-pass extraction fractions.
Comparison of the Three Agents:
| Feature | Tl-201 | Tc-99m MIBI | Tc-99m Tetrofosmin |
|---|---|---|---|
| Energy | 69-83 keV | 140 keV | 140 keV |
| T½ | 73 hours | 6 hours | 6 hours |
| Mechanism | Na⁺/K⁺-ATPase | Mitochondria | Mitochondria |
| First-pass extraction | 85% | 60-65% | 54% |
| Redistribution | YES | NO | NO |
| Hepatic clearance | Low | Moderate | Fast |
| Gating | Difficult | YES | YES |
| Viability | Redistribution | Limited | Limited |
| Radiation dose | High | Low | Low |
14.1.2 Stress Protocols12 questions
The aim of myocardial perfusion scintigraphy is to assess coronary flow reserve under stress. Normal coronary arteries can increase flow 4-5-fold under stress, whereas stenotic arteries cannot → a perfusion difference develops → seen as a defect on scintigraphy.
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Ischaemic cascade: Perfusion heterogeneity → metabolic change → diastolic, then systolic (wall motion) dysfunction → ECG change → angina. Because of this sequence MPI becomes positive before ECG and echocardiography
A) Exercise Stress Test (Treadmill / Bicycle Ergometer):
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The preferred stress method (exercise is always preferred when possible)
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Target: ≥85% of age-predicted maximal heart rate ((220 − age) × 0.85)
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The Bruce protocol is the most widely used treadmill protocol
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Radiopharmaceutical injection: At peak exercise → exercise continues for 1-2 minutes after injection
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Advantages: Physiological; ECG changes, haemodynamic response, functional capacity, prognostic information
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Contraindications: Acute MI (<2 days), unstable angina, severe aortic stenosis, decompensated heart failure, active myocarditis/pericarditis, acute pulmonary embolism, acute aortic dissection
Criteria for terminating an exercise stress test:
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Target heart rate reached
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Severe angina
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ST depression >2 mm (horizontal or downsloping)
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ST elevation >1 mm (except aVR)
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Sustained ventricular tachycardia
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Fall in systolic blood pressure >10 mmHg (from baseline)
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Hypertensive response (systolic >250 mmHg or diastolic >115 mmHg)
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Severe dyspnoea, pallor, cyanosis
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Other reasons to stop the test: Dizziness or presyncope, ataxia, claudication, new AF/SVT, 2nd or 3rd degree AV block
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Patient request
Patient preparation and adequate stress (EANM):
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β-blockers, calcium antagonists and nitrates are stopped 48 hours before the stress test (short-acting nitrates may be used up to 3 hours before the test)
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Before vasodilator stress: Dipyridamole at least 72 hours, xanthines (theophylline) at least 48 hours, caffeine at least 12 (preferably 24) hours before
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Fasting: At least 4 hours before the radiopharmaceutical; a heavy meal should be stopped 6 hours before
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Rate-pressure product (heart rate × systolic BP): >25,000 mmHg/min indicates adequate and >30,000 mmHg/min excellent hyperaemia
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High-risk findings on the exercise test: Exercise-induced hypotension, ≥2 mm ST depression at low workload, ST elevation, sustained VT and low functional capacity (Duke treadmill score)
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Other absolute contraindications to exercise: Uncontrolled hypertension (>200/110 mmHg), aortic aneurysm >50 mm, symptomatic aortic stenosis, HOCM, intraventricular thrombus and active endocarditis
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Low-level (submaximal) exercise added to pharmacological stress increases myocardial extraction and reduces background activity in the gut
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Low-level exercise also reduces vasodilator side effects (flushing, headache, hypotension, nausea); it is not added in LBBB or paced rhythm
BOARD TIP
▸
"When is the injection given in exercise stress?"
→ At peak exercise → then continue for 1-2 more min.
▸
"Target heart rate?"
→ (220 − age) × 0.85.
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"What does a submaximal test mean?"
→ Target heart rate not reached → the negative predictive value of the test falls → risk of false negatives increases.
B) Pharmacological Stress – Vasodilators: Used in patients who cannot exercise. Coronary vasodilators dilate normal arteries → dilatation is limited in stenotic arteries → coronary steal phenomenon → a perfusion difference develops.
Adenosine:
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Mechanism: A2A receptor (direct) → coronary vasodilatation
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Also activates A1 (AV block, bradycardia), A2B (bronchospasm) and A3 receptors → side effects
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Dose: 140 μg/kg/min IV infusion × 4-6 minutes
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Injection: The radiopharmaceutical is given at minute 3 of the infusion
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T½: <10 seconds (very short → side effects resolve quickly)
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Antidote: Aminophylline (50-250 mg, slow IV)
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Side effects: Flushing, chest pain, dyspnoea, headache, AV block, hypotension, bronchospasm
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Contraindications: Asthma/COPD (risk of bronchospasm), 2nd or 3rd degree AV block, systolic BP <90 mmHg, sick sinus syndrome (without pacemaker)
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Caffeine withdrawal: At least 12-24 hours before (theophylline 48 hours) → methylxanthines are adenosine receptor antagonists → block the effect of adenosine
Dipyridamole:
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Mechanism: Indirect → inhibits adenosine deaminase + blocks cellular reuptake of adenosine → accumulation of endogenous adenosine → A2A activation
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Dose: 0.56 mg/kg IV × 4 minutes
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Injection: 3-5 minutes after the end of the infusion
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T½: 30-45 minutes (much longer than adenosine → side effects last longer)
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Antidote: Aminophylline
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Side effects and contraindications: Similar to adenosine
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Caffeine withdrawal: At least 12-24 hours
Regadenoson (Lexiscan):
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Mechanism: Selective A2A receptor agonist → minimal effect on A1, A2B, A3 receptors
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Dose: 0.4 mg IV bolus (fixed dose, no weight adjustment needed)
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T½: Initial phase ~2-4 minutes, terminal phase ~2 hours
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Injection: The radiopharmaceutical is given within 10-20 seconds after the bolus
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Advantages: Fixed dose (easy administration), selective → lower risk of bronchospasm (but not completely safe), lower risk of AV block
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Contraindications: 2nd or 3rd degree AV block, sick sinus syndrome. May be used with caution in asthma/COPD (safer than adenosine/dipyridamole, but should be avoided in severe/active bronchospasm)
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Caffeine withdrawal: At least 12-24 hours
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Antidote: Aminophylline
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Currently the most widely used pharmacological stress agent (in the USA)
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Pharmacokinetics (EANM): Affinity for the A1 receptor is at least 10 times lower than for A2A; plasma level peaks at 1-4 min; half-life phases are 2-4 min, 30 min and 2 hours
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Common contraindications to vasodilators: Unstable angina, bradycardia <40/min, systolic BP <90 mmHg, severe bilateral carotid or aortic stenosis, dipyridamole use and cerebral ischaemia
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Expected haemodynamic response to vasodilators: Slight rise in heart rate and slight fall in blood pressure; unlike exercise, no target heart rate is sought
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Management of side effects: With adenosine, stopping the infusion is usually sufficient (T½ <10 s); for bronchospasm or marked ischaemia with dipyridamole or regadenoson, aminophylline (50-250 mg, slow IV) is given
BOARD TIP
▸
"Common contraindication of vasodilator stress agents?"
→ Asthma/COPD (risk of bronchospasm) and high-grade AV block.
▸
"Why should caffeine be stopped?"
→ Methylxanthine → adenosine receptor antagonist → blocks the vasodilator effect → false-negative result.
▸
"Advantage of regadenoson?"
→ Selective A2A agonist → fixed dose, lower risk of bronchospasm.
▸
"Antidote?"
→ Aminophylline for all.
▸
"Adenosine T½?"
→ 10 seconds (the shortest).
C) Pharmacological Stress – Dobutamine:
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Mechanism: β1-adrenergic agonist → increased heart rate and contractility → myocardial oxygen consumption increases → haemodynamic stress similar to exercise
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Dose: Started at 10 μg/kg/min → increased every 3 minutes → 40 μg/kg/min (maximum)
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If the target heart rate is not reached: Atropine 0.25-1 mg IV may be added
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Indication: Patients in whom vasodilators are contraindicated (asthma/COPD + unable to exercise)
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Contraindications: Severe hypertension, unstable arrhythmia, HOCM, aortic aneurysm
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Side effects: Palpitations, angina, arrhythmia, hypertension, hypotension
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Antidote: Short-acting beta-blocker (esmolol)
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Contraindications to atropine: Narrow-angle glaucoma, obstructive prostatic hypertrophy, AF with uncontrolled rate, severe ventricular arrhythmia, obstructive gastrointestinal disease or paralytic ileus; after administration there is difficulty with visual accommodation for ~2 hours
BOARD TIP
▸
"Asthmatic patient unable to exercise → which pharmacological stress?"
→ Dobutamine (vasodilators are contraindicated because of the risk of bronchospasm).
▸
"Antidote to dobutamine?"
→ Esmolol (short-acting β-blocker).
▸
"If the target heart rate is not reached with dobutamine?"
→ Add atropine.
Figure 14.2: Effects of pharmacological stress agents via adenosine receptors, methylxanthine blockade and the different pathway of dobutamine (schematic).
Did this figure help you understand the topic?
Comparison of Stress Agents:
| Feature | Adenosine | Dipyridamole | Regadenoson | Dobutamine |
|---|---|---|---|---|
| Mechanism | Direct A2A | Indirect (adenosine ↑) | Selective A2A | β1-agonist |
| Administration | Infusion | Infusion | Bolus | Infusion |
| T½ | <10 s | 30-45 min | 2-4 min (initial phase) | 2 min |
| Antidote | Aminophylline | Aminophylline | Aminophylline | Esmolol |
| In asthma | Contraindicated | Contraindicated | Caution | Safe |
| Risk of AV block | High | Moderate | Low | Low |
14.1.3 Imaging Protocols (1-Day, 2-Day)5 questions
1-Day Protocol (Tc-99m agents):
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Rest first, stress second (Rest-Stress):
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Rest: Low dose (8-12 mCi) → 45-60 min wait → imaging
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Stress: High dose (24-36 mCi) → 15-30 min wait → imaging
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Dose ratio: High dose/low dose = 3:1 (so that the high dose "overrides" the low dose)
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Advantage: If rest is normal, stress may not be needed (in some protocols)
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Stress first, rest second (Stress-Rest):
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Stress: Low dose (8-12 mCi) → imaging
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Rest: High dose (24-36 mCi) → imaging
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Advantage: If stress is normal the rest study can be cancelled → saves time and dose
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The most widely preferred 1-day protocol
BOARD TIP
▸
"Why a 3:1 dose ratio in the 1-day protocol?"
→ So that the second injection "overrides" the residual activity of the first → the high dose is given second.
▸
"Advantage of the stress-first protocol?"
→ If stress is normal, rest can be cancelled → rest is not needed in 60-70% of patients.
2-Day Protocol (Tc-99m agents):
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Day 1: Stress → full dose (20-30 mCi) → imaging
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Day 2: Rest → full dose (20-30 mCi) → imaging
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Advantages: Full dose for both studies → best image quality; preferred in obese patients
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Disadvantages: Requires two days; higher total radiation dose
EANM activities (adult of normal weight):
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Conventional 1-day protocol: 250-400 MBq for stress; at least 3 hours later 3 times this activity is given for rest
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Conventional 2-day protocol: 350-700 MBq for each study
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CZT SPECT: 3-5 MBq/kg in the 2-day protocol; in the 1-day protocol 2.5-3.5 MBq/kg for the first injection and 7.5-10.5 MBq/kg for the second
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PET: Rb-82 1110-1480 MBq on analogue systems, 740-925 MBq on digital systems, 370-444 MBq on LAFOV; N-13 ammonia 370-925 MBq; O-15 water 400 MBq per session
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Effective dose coefficients: Rb-82 0.76, N-13 ammonia 2.0 µSv/MBq; O-15 water 0.25 mSv per session
Tl-201 Protocol:
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Stress-redistribution protocol:
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Stress: 74-111 MBq (2-3 mCi) Tl-201 injection → stress imaging 10-15 min later
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Redistribution: 3-4 hours later, repeat imaging (no new injection needed)
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If needed, late redistribution imaging at 24 hours (viability)
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Advantage: A single injection suffices (thanks to redistribution)
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Cardiac SPECT acquisition: A LEHR or LEAP collimator and a 180° arc close to the heart (from 45° RAO to 45° LPO) are used; with the low-energy photons of Tl-201 this arc gives better contrast than 360°
Dual-Isotope Protocol (now rarely used):
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Rest: Tl-201 → imaging
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Stress: Tc-99m MIBI → imaging
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Advantage: Short duration
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Disadvantage: Different energy windows → difficult comparison; high radiation dose
Figure 14.3: Timelines of Tc-99m and Tl-201 myocardial perfusion imaging protocols (schematic).
Did this figure help you understand the topic?
Gated SPECT:
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Imaging with ECG synchronisation → the cardiac cycle is divided into 8 or 16 frames
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Parameters assessed:
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LVEF (left ventricular ejection fraction)
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Wall motion
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Wall thickening
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End-diastolic and end-systolic volumes (EDV, ESV)
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Shape (sphericity) index: Shows transformation of the LV from an ellipsoid to a sphere (pathological remodelling); it rises in heart failure and ischaemic cardiomyopathy, and a high value (→1) predicts development of heart failure
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Artefact reduction: Distinguishing attenuation artefact from true defect → normal wall motion and thickening = attenuation artefact
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Wall thickening is calculated from the count increase in the systolically thickening wall (count difference between ED and ES), thanks to the partial volume effect; no geometric edge detection is needed
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With Tc-99m, stress gated SPECT is acquired under resting conditions ~30-60 min after injection; a fall in LVEF or LV dilatation lasting >60 min indicates post-stress stunning and is a sign of ischaemia
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Wall motion and thickening can be scored in 17 segments on a 5-point scale from 0 (normal) to 4 (dyskinesia); in LBBB septal motion may be abnormal while thickening is normal
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Paradoxical septal motion (septum moving towards the RV in systole) is seen in LBBB, RV-paced rhythm, after cardiac surgery (CABG/pericardiotomy) and with RV volume overload; if septal thickening is preserved it does not suggest infarction
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Because counts are low with Tl-201, interobserver variability of gated parameters is higher than with Tc-99m agents
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LVEF pitfalls in gated SPECT: In a small LV (women, children) the partial volume effect makes ESV appear small and LVEF falsely high; LVEF measured with 8 frames per cycle is ~3-4% lower than with 16 frames
BOARD TIP
▸
"Most important contribution of gated SPECT?"
→ Distinguishing attenuation artefact from true defect → normal wall motion and thickening in a fixed defect → attenuation artefact. In true scar, wall motion and thickening are reduced.
▸
"Normal LVEF?"
→ ≥50% (by gated SPECT).
14.1.4 Polar Map and Segmental Analysis3 questions
Polar Map (Bull's Eye):
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Display of the left ventricular myocardium on a 2D circular map
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Centre: Apex
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Periphery: Basal segments
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Colour coding: By perfusion intensity (normal → warm colours, defect → cold colours)
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Quantitative analysis: Comparison with a normal database → standard deviation maps
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Visual assessment is primary; quantitative analysis should not be used without visual assessment
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Display: Short-axis, vertical and horizontal long-axis slices; stress and rest images are shown side by side with a continuous colour scale. If attenuation correction was performed, the uncorrected images are also reviewed
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The reference database should match the patient's sex and body habitus, the agent, the protocol and the position
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Slices showing the walls best: Short axis and vertical long axis for the anterior and inferior walls; short axis and horizontal long axis for the septum and lateral wall; both long axes for the apex
17-Segment Model (AHA):
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The left ventricle is divided into 17 segments:
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Basal: 6 segments (anterior, anteroseptal, inferoseptal, inferior, inferolateral, anterolateral)
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Mid: 6 segments (same naming)
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Apical: 4 segments (anterior, septal, inferior, lateral)
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Apex: 1 segment (cap)
Coronary Artery Territories:
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LAD (Left Anterior Descending Artery): Anterior wall, anteroseptal, apical segments → the largest territory
•
LCx (Left Circumflex Artery): Lateral wall, inferolateral (posterolateral) segments
•
RCA (Right Coronary Artery): Inferior wall, inferoseptal basal segments
•
Dominance: Right dominant (85%) → the RCA gives the posterior descending artery → inferior and inferoseptal basal. Left dominant (8%) → the LCx gives the posterior descending artery.
•
Combined involvement of the anterior and lateral walls (LAD and LCx territories) suggests left main (or proximal multivessel) disease
•
Branches: Diagonals are branches of the LAD, obtuse marginals of the LCx; SPECT sensitivity is highest for LAD lesions and lowest for LCx lesions
Scoring Systems:
•
SSS (Summed Stress Score): Sum of the perfusion scores of all segments on stress images
•
SRS (Summed Rest Score): Total score on rest images
•
SDS (Summed Difference Score): SSS − SRS = reversibility (amount of ischaemia)
•
Each segment is scored 0-4:
–
0 = Normal
–
1 = Mildly reduced
–
2 = Moderately reduced
–
3 = Severely reduced
–
4 = Absent uptake
Prognostic value:
•
SSS <4 → normal → low risk
•
SSS 4-8 → mildly abnormal → low-to-intermediate risk
•
SSS 9-13 → moderately abnormal → intermediate risk
•
SSS >13 → severely abnormal → high risk → revascularisation should be considered
•
Ischaemic myocardium ≥10% (≈SDS ≥7) → significant ischaemia → may benefit from revascularisation
•
Converting the score to a percentage: Score/(number of segments × 4) × 100 (divided by 68 for 17 segments); e.g. in a 20-segment model an SSS of 24 means 30% of the LV is abnormal
•
Reporting: The location, size, severity and reversibility of each defect and its coronary territory are stated; LV dilatation/TID, lung uptake, gated findings and possible artefacts are also reported
•
Focal extracardiac MIBI or tetrofosmin uptake (breast, lung, mediastinum, thyroid) on raw (rotating) images must always be reviewed; it may be an incidental malignancy
BOARD TIP
▸
"What does SDS show?"
→ Reversibility = amount of ischaemia (SSS − SRS).
▸
"LAD territory?"
→ Anterior + anteroseptal + apex → the largest territory.
▸
"Prognostic value of a normal MPI?"
→ Annual cardiac event risk <1% → strong negative predictive value.
▸
"When should revascularisation be considered?"
→ Ischaemic myocardium ≥10% (≈SDS ≥7).
Short-axis slices are placed one by one from the centre (apex) to the outside (base) of the polar map, then the AHA 17-segment grid is drawn. The second step shows the segments and the LAD, LCx and RCA territories; in the third, segment scores on the stress and rest maps are added one by one to give SSS, SRS, SDS and the risk class.
Continuous stream · no seeking
Key point: the polar map gathers short-axis slices into one circle with the apex in the centre and the base outside; the sum of stress scores (SSS) gives risk and the stress–rest difference (SDS) the amount of ischaemia.
Source: book (14.1.4: polar map, AHA 17 segments, coronary territories, 0-4 score, SSS/SRS/SDS thresholds, division by 68, SDS ≥7 ≈ 10%); segment layout Cerqueira et al., Circulation 2002 (AHA). Images and scenario scores are representative (uptake ≈ 1 − 0.15 × score).
Space or the ⏸/▶ button below pauses and resumes; ← → change steps and options; double-click to enlarge; on a phone, swipe left or right to change steps.
Did this animation help you understand the topic?
Figure 14.4: AHA 17-segment polar map, coronary artery territories and risk categories by SSS.
14.1.5 Artefacts and Pitfalls16 questions
A) Attenuation Artefacts:
•
Diaphragmatic attenuation: In the inferior wall → common in men → seen as a fixed defect
•
Breast attenuation: In the anterior or anterolateral wall → common in women → fixed defect
•
Obesity: Generalised attenuation → reduced counts in all walls
•
Solution: Gated SPECT (normal wall motion = artefact), attenuation correction (CT-based), prone imaging (for inferior wall artefact)
•
Attenuation correction mainly increases specificity and the normalcy rate; its effect on sensitivity is limited, and it should be interpreted together with uncorrected images
BOARD TIP
▸
"Inferior fixed defect + normal wall motion in a man?"
→ Diaphragmatic attenuation artefact.
▸
"Anterior fixed defect + normal wall motion in a woman?"
→ Breast attenuation.
▸
"When is prone imaging used?"
→ When an inferior wall attenuation artefact is suspected → in the prone position the diaphragm moves away → the artefact resolves.
B) Patient-Related Artefacts:
•
Patient motion: The commonest cause of artefact → misregistration → artificial defects
•
Upward creep: Change in diaphragm position after exercise → inferior wall artefact
–
Upward creep is seen mostly with Tl-201 imaged immediately after exercise; it is rare with Tc-99m agents because imaging is delayed 15-30 min. It is prevented by delaying imaging
•
High subdiaphragmatic activity: Liver, bowel, stomach → scatter into the inferior wall → false hot or cold area
•
Extracardiac activity: Gallbladder, bowel loops
•
Patient motion is recognised as a break or shift on the cine display of raw projections or on the sinogram; motion correction is applied or the acquisition is repeated
•
Apical thinning: A slight count reduction due to the physiologically thin myocardium at the apex creates a false apical defect; it may become more conspicuous with attenuation correction
•
Other normal variants: Reduced counts in the basal septum due to the membranous septum (the septum looks shorter than the lateral wall on HLA) and mild count reduction at the RV insertion points
C) Technical Artefacts:
•
Centre of rotation (COR) error: Shift of the gamma camera's centre of rotation → image distortion
•
Non-uniformity: Problems with detector uniformity → ring artefact
•
Filter choice: Excessive smoothing → loss of detail; insufficient smoothing → noisy image
•
Incorrect selection of the long axis during reorientation causes artificial perfusion defects
D) Clinical Pitfalls:
•
Balanced 3-vessel disease (balanced ischaemia): Equal stenosis in all coronary arteries → equal reduction of perfusion in all segments → relatively normal appearance → false negative
•
Clues: Transient ischaemic dilatation (TID), post-stress fall in EF, widespread ST depression, increased lung uptake (Tl-201)
–
With Tl-201, globally slowed myocardial washout suggests balanced multivessel disease, whereas regionally slow washout is a sign of ischaemia (washout also slows with inadequate stress and high insulin)
•
Left bundle branch block (LBBB):
–
With exercise stress a false septal perfusion defect may develop → a defect is seen without septal ischaemia
–
Mechanism: Abnormal septal contraction during tachycardia → septal perfusion appears reduced
–
An LBBB-related false defect is confined to the septum and anteroseptal region and spares the apex and anterior wall; a defect extending to the apex or anterior wall suggests true LAD ischaemia
–
Solution: Vasodilator stress is preferred in patients with LBBB (exercise and dobutamine should be avoided) → vasodilators do not increase heart rate markedly → lower risk of a false septal defect
–
Regadenoson or adenosine is preferred
•
With a permanent pacemaker (right ventricular paced rhythm), WPW and β-blocker use, vasodilator stress is also preferred because adequate or interpretable exercise stress cannot be achieved
BOARD TIP
▸
"Which stress method in a patient with LBBB?"
→ Vasodilator (adenosine, regadenoson, dipyridamole). Exercise and dobutamine → tachycardia → false septal defect.
▸
"Where is the false defect in LBBB?"
→ Septum.
▸
"Why a vasodilator?"
→ It does not increase heart rate markedly → lower risk of septal artefact.
•
Transient Ischaemic Dilatation (TID):
–
The LV cavity appears larger on stress images than on rest images
–
Mechanism: Widespread subendocardial ischaemia reduces subendocardial counts; the apparent endocardial border moves outwards and the cavity appears enlarged (post-stress stunned myocardium may also contribute)
–
TID ratio: Stress LV cavity / rest LV cavity → >1.22 (Tc-99m) is significant
–
Clinical significance: Marker of severe and extensive CAD → suggests multivessel or left main coronary disease
–
High-risk finding → angiography should be considered
•
Increased Lung Uptake (Tl-201):
–
Increased Tl-201 uptake in the lungs on stress images
–
Mechanism: Rise in LV filling pressure during stress → pulmonary congestion → Tl-201 accumulation in the lungs
–
Lung/heart ratio: >0.50 is significant
–
Clinical significance: Severe LV dysfunction, extensive CAD → high-risk finding
•
Prominent RV: If also prominent on the rest image, it suggests RV hypertrophy or pressure overload (pulmonary hypertension); if it becomes prominent only on the stress image, it is a relative increase due to extensive LV ischaemia (high risk)
•
Causes of perfusion defects other than CAD: LBBB or paced rhythm, coronary vasospasm, myocardial bridging, dilated or hypertrophic/hypertensive cardiomyopathy, severe aortic valve disease and infiltrative diseases (sarcoidosis)
•
Reverse redistribution: A defect that is normal or mild on the stress or early image becomes more conspicuous on the delayed (redistribution/rest) image; it is seen mostly in reperfused infarction where viable tissue and scar are mixed, and it does not indicate ischaemia
BOARD TIP
▸
"What does TID mean?"
→ Enlarged LV cavity after stress → widespread subendocardial ischaemia → severe multivessel or left main coronary disease.
▸
"Increased lung uptake (Tl-201)?"
→ Pulmonary congestion during stress → severe CAD. Both are high-risk findings → indication for angiography.
Figure 14.5: Stress-rest perfusion patterns, artefacts and clinical pitfalls on short-axis images (schematic).
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14.1.6 Clinical Indications and Prognostic Value4 questions
Indications:
•
Diagnosis of known or suspected coronary artery disease (CAD)
•
Diagnosis of CAD in patients with intermediate pretest probability
•
Risk stratification in known CAD
•
Evaluation of acute chest pain (emergency rest MPI)
–
Rest MPI when ECG and troponin are non-diagnostic: Sensitivity is highest if the injection is given during or immediately after pain; a normal result has a high negative predictive value, and the patient can be considered low risk and discharged early
•
Determining the amount of ischaemia before revascularisation
•
Assessment of residual ischaemia after revascularisation
–
Appropriate in symptomatic patients; in asymptomatic patients routine MPI is not recommended within 2 years of PCI and 5 years of CABG. False positives are common in the first weeks after PCI
–
Recurrent pain after PCI: before 1 month consider incomplete revascularisation or acute closure; between 1-6 months restenosis; after 6 months a new lesion (disease progression)
•
Preoperative cardiac risk assessment (before non-cardiac surgery)
•
Distinguishing ischaemic from non-ischaemic aetiology in heart failure
•
EANM: Symptomatic patients with a pretest probability of CAD of 15-85% and LVEF >50%; patients whose baseline ECG cannot be interpreted (e.g. LBBB)
•
Preoperatively: When more than 3 risk factors, high-risk surgery and inability to reach 6 METs on ergometry coexist
•
Other indications: Determining the functional significance of a known stenosis, Agatston score >400 and microvascular dysfunction (PET MPI is superior to SPECT)
•
Routine stress MPI screening is not recommended in asymptomatic diabetics (no reduction in events in the DIAD study); it may be considered only in selected patients at very high risk
•
Agatston coronary calcium score: The sum of calcified plaque burden (≥130 HU) in all coronary arteries; 0 indicates very low and >400 high risk. It adds most to risk stratification in the intermediate-risk group
–
Hybrid cardiovascular imaging (EANM/EACVI 2024): on hybrid systems CT is acquired for four purposes: attenuation correction, anatomical localisation, ECG-gated non-contrast coronary calcium scoring, and contrast-enhanced (~100 mL) ECG-gated coronary CT angiography; fusing perfusion with anatomy shows the functional significance of a stenosis and the culprit vessel. If no separate calcium score is acquired, the reader estimates calcium visually from the attenuation CT and states which arteries are calcified (ASNC/SNMMI 2022); in PET, perfusion, function, blood flow and calcium are reported together
Prognostic Value:
•
Normal MPI: Annual risk of cardiac events (MI or cardiac death) <1% → very strong negative predictive value
•
"Warranty period" of a normal MPI: About 2 years (shorter in diabetics)
–
The warranty period is shorter in older age, diabetes (especially in women), patients needing pharmacological stress and known CAD
•
EANM: In patients with a normal or mildly abnormal SPECT MPI the annual MACE rate is ~1% (~0.3% in women, ~2% with pharmacological stress)
•
If coronary angiography is normal but SPECT MPI is abnormal, cardiac risk increases ~4-fold
•
The sensitivity and specificity of SPECT MPI for detecting haemodynamically significant CAD are >85%
•
Because only positive or equivocal tests are referred for angiography (referral/verification bias), specificity is calculated as low; the 'normalcy rate' is therefore used in low-probability patients
•
Abnormal MPI: Risk is proportional to the extent and severity of ischaemia
–
Mild ischaemia → medical therapy
–
Extensive ischaemia (≥10% of myocardium) → revascularisation should be considered
•
High-risk findings:
–
Extensive perfusion defects (multiple coronary territories)
–
TID (transient ischaemic dilatation)
–
Post-stress fall in EF
–
Increased lung uptake (Tl-201)
–
Large reversible defect (LAD territory)
–
ST depression during stress + perfusion defect
•
Gated SPECT: Post-stress LVEF (<45%) and ESV (>70 mL) best predict cardiac death, whereas perfusion findings (SDS/SSS) best predict MI; with LVEF <45% annual cardiac death is >7% even if the defect is mild
14.2 Assessment of Myocardial Viability
14.2.1 Tl-201 Rest-Redistribution and Reinjection3 questions
Concept of viability:
Determining whether dysfunctional myocardium in chronic ischaemic heart disease is viable → viable myocardium can recover function after revascularisation, scar tissue cannot.
Viability assessment with Tl-201:
A) Stress-Redistribution Protocol:
•
Stress → imaging → 3-4 hours redistribution → repeat imaging
•
Reversible defect → ischaemia (viable)
•
Fixed defect → scar or severe hypoperfusion (may be viable → delayed imaging may be needed)
B) Rest-Redistribution Protocol:
•
Rest injection → early imaging → 3-4 hours redistribution → delayed imaging
•
Early defect + late fill-in → viable myocardium (redistribution positive)
•
Fixed defect in both phases → scar (but 30-50% may still be viable)
C) Reinjection Protocol:
•
Stress → redistribution → if a fixed defect is present → additional 1 mCi Tl-201 reinjection → repeat imaging 15-20 min later
•
Fill-in after reinjection → viable myocardium (shows viability not detected by redistribution)
•
40-50% of fixed defects show fill-in after reinjection → viability
BOARD TIP
▸
"A fixed defect on Tl-201 redistribution → definitely scar?"
→ No! 30-50% of fixed defects may still be viable → viability can be shown by reinjection or 24-hour delayed imaging.
▸
"When is reinjection performed?"
→ If there is a fixed defect on redistribution images → additional 1 mCi Tl-201 → fill-in = viable.
D) 24-Hour Late Redistribution:
•
Fixed defect on standard 3-4-hour redistribution → repeat imaging 24 hours later
•
Late fill-in → severely hypoperfused but viable myocardium
•
Disadvantage: at 24 hours counts are very low → poor image quality
On a short-axis image the Tl-201 distribution at stress and as time passes is shown with the time–count curves of normal, ischaemic and scarred regions. In the second step a defect that looks fixed at 4 h is separated into scar or slowly redistributing viable tissue with reinjection and a 24 h late image.
Continuous stream · no seeking
Key idea: viable ischaemic myocardium keeps taking up Tl-201 from the blood, so the defect fills with time; some defects that look fixed at 4 h prove viable with reinjection or a 24 h late image.
Source: book (14.1.1, 14.2.1: stress image at 10-15 min, redistribution at 3-4 h, 24 h late image, reinjection 37 MBq with imaging 15-20 min later, 30-50% of fixed defects viable). The kinetic model is representative; physical decay is not shown and each image is scaled to its own maximum.
How to use: a single click on the drawing pauses and resumes; in the second step ↑ ↓ or the buttons below change the scenario; ← → change steps.
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Figure 14.6: Time-activity behaviour of normal, ischaemic (viable) and scarred myocardium on Tl-201 stress-redistribution (schematic).
14.2.2 FDG PET Perfusion-Metabolism Mismatch4 questions
Principle:
•
Normal myocardium: Uses fatty acids as an energy source in the fasting state and glucose in the fed state
•
Ischaemic/hibernating myocardium: Oxidative metabolism impaired → dependent on glucose → FDG uptake increases
•
Scar tissue: Neither perfusion nor metabolism → no FDG uptake
•
Agents showing fatty acid metabolism: C-11 palmitate (PET) and I-123 BMIPP (SPECT). BMIPP uptake remains reduced for days after an ischaemic episode, allowing imaging of 'ischaemic memory'
•
C-11 acetate: Oxidised in the myocardium in the TCA cycle; its clearance rate reflects oxidative metabolism (MVO₂) and its early uptake reflects perfusion. Both can thus be assessed in a single study
Perfusion-Metabolism Patterns:
•
Normal: Normal perfusion + normal FDG → healthy myocardium
•
Mismatch: Reduced perfusion + preserved/increased FDG → HIBERNATION → viable → benefits from revascularisation
•
Match (matched defect): Reduced perfusion + reduced FDG → SCAR → does not benefit from revascularisation
–
Mild match (mild concordant reduction of perfusion and FDG): A mixture of non-transmural scar and viable myocytes
•
Reverse mismatch: Normal perfusion + reduced FDG → non-transmural MI, stunning or LBBB
Patient preparation:
•
Glucose loading protocol: 50-75 g oral glucose → insulin secretion → myocardial glucose utilisation increases → FDG uptake increases
•
In diabetic patients: Insulin-glucose clamp or acipimox (nicotinic acid derivative → inhibition of fatty acids)
•
Aim: Shift the myocardium to glucose utilisation → optimise FDG uptake
•
Fasting protocol: Used for cardiac sarcoidosis (→ see 14.6), not for viability
FDG PET viability → gold standard:
•
Highest sensitivity and specificity for viability assessment
•
Perfusion agent: Rb-82, N-13 ammonia or Tc-99m MIBI/tetrofosmin (SPECT)
•
Mismatch area ≥7-10% of myocardium → benefit from revascularisation is expected
•
EANM: FDG 185-400 MBq (at least 26 MBq in children); 19 µSv/MBq, i.e. 3.5-7.6 mSv; breastfeeding interrupted for 3-6 hours
•
If perfusion and metabolism are normal, the myocardium is normal, stunned or remodelled; all of these are viable
•
Causes of reverse mismatch: LBBB, early revascularisation after MI, non-ischaemic cardiomyopathy and diabetes; the tissue is considered viable because perfusion is preserved
•
Pitfalls (ASNC/SNMMI 2016): FDG and perfusion images are normalised to the same normally perfused region; in LBBB the septum takes up FDG spuriously low and is not used for normalisation, so the ECG is reviewed as well. If FDG uptake in a mismatch region is very high it is set to 100% at normalisation and remote regions may falsely appear reduced. Misregistration between emission and attenuation images creates spurious defects or hot spots; perfusion and FDG should be acquired in the same session with identical positioning and correction
–
In diabetes and insulin resistance, oral glucose loading may give poor image quality; insulin supplementation, a hyperinsulinaemic euglycaemic clamp or acipimox is used. With impaired left ventricular function blood pool activity clears slowly and may make perfusion defects appear milder and FDG uptake higher. Absolute glucose utilisation is not used for the viability decision
•
Guideline recommendation: If viable myocardium is present, revascularisation should be considered (Class IIa, level of evidence B)
•
Allman meta-analysis: In patients with viable myocardium, annual mortality is 3.2% with revascularisation and 16% with medical therapy; without viable myocardium there is no difference between the two (7.7% vs 6.2%)
•
Report content (ASNC/SNMMI 2016): in addition to the common items (see 27), metabolic preparation (glucose loading, insulin, acipimox) and blood glucose at FDG injection, perfusion agent used. Findings: site, extent and severity of rest perfusion defects; FDG uptake and pattern in normally perfused and hypoperfused myocardium (mismatch, match, reverse mismatch); extent of mismatch and match as a percentage of the left ventricle (small <10%, moderate 10-20%, large >20%) and severity of match defects (mild, moderate, severe; non-transmural versus transmural scar); if stress perfusion is available, ischaemia in regions with normal rest perfusion; interpretation of the septum in LBBB
BOARD TIP
▸
"Gold standard for viability assessment?"
→ FDG PET perfusion-metabolism mismatch.
▸
"What does mismatch mean?"
→ Perfusion ↓ + FDG ↑ = hibernation = viable = benefits from revascularisation.
▸
"What does match mean?"
→ Perfusion ↓ + FDG ↓ = scar = does not benefit from revascularisation.
▸
"Patient preparation for viability?"
→ Glucose loading (not fasting!). Fasting → cardiac sarcoidosis protocol.
Figure 14.7: Perfusion-metabolism patterns and their interpretation in an FDG PET viability study (schematic).
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14.2.3 Hibernation vs Stunning vs Scar2 questions
Hibernation (Hibernating Myocardium):
•
Chronic hypoperfusion → the myocardium reduces energy consumption by reducing contractility → "sleep mode"
•
Perfusion: Reduced (chronic)
•
Function: Reduced (chronic)
•
Metabolism: Glucose-dependent → FDG uptake preserved/increased
•
Cell: Viable (but structural changes may have begun)
•
Revascularisation: Function recovers (within weeks-months)
•
Diagnosis: FDG PET mismatch, Tl-201 redistribution/reinjection, low-dose dobutamine echo
•
Viability with Tc-99m MIBI/tetrofosmin: A rest injection after sublingual nitrate increases uptake in viable hypoperfused regions; regional uptake exceeding ~50-60% of maximal counts supports viability
•
Other methods showing viability: Late gadolinium enhancement (LGE) on cardiac MRI shows scar (if transmural extent is >50%, recovery of function is unlikely); a biphasic response on dobutamine echocardiography suggests hibernation
Stunning (Stunned Myocardium):
•
After an acute ischaemic event, perfusion has recovered but function is transiently impaired
•
Perfusion: Normal (reperfusion achieved)
•
Function: Reduced (transient)
•
Metabolism: Normal or increased FDG uptake
•
Cell: Viable
•
Revascularisation: Function recovers spontaneously (days-weeks)
•
Example: Transient wall motion abnormality after successful primary PCI
Scar:
•
Irreversible myocardial injury → necrosis → fibrosis
•
Perfusion: Reduced/absent
•
Function: Reduced/absent (permanent)
•
Metabolism: No FDG uptake
•
Cell: Dead → fibrotic tissue
•
Revascularisation: Function does not recover
| Feature | Hibernation | Stunning | Scar |
|---|---|---|---|
| Perfusion | Reduced (chronic) | Normal | Reduced/absent |
| Function | Reduced | Reduced (transient) | Reduced (permanent) |
| FDG uptake | Preserved/increased | Normal/increased | Absent |
| Cell viability | Viable | Viable | Dead |
| Revascularisation | Beneficial | Recovers spontaneously | No benefit |
| PET pattern | Mismatch | Normal or reverse mismatch | Match |
BOARD TIP
▸
"Reduced perfusion + increased FDG?"
→ Hibernation → revascularisation indicated.
▸
"Normal perfusion + impaired function?"
→ Stunning → recovers spontaneously.
▸
"Reduced perfusion + reduced FDG?"
→ Scar → irreversible.
▸
"Hibernation vs stunning?"
→ In hibernation perfusion is chronically reduced; in stunning perfusion has recovered but function is transiently impaired.
14.3 MUGA (Radionuclide Ventriculography)6 questions
Definition and Principle:
•
MUGA = Multi-Gated Acquisition = radionuclide ventriculography (RNV)
•
Blood pool imaging with Tc-99m labelled red cells
•
ECG-gated → the cardiac cycle is divided into 16-24 frames → ventricular counts are measured in each frame
•
LVEF calculation: (EDV − ESV) / EDV × 100
–
EDV: End-diastolic counts (highest)
–
ESV: End-systolic counts (lowest)
–
Background correction is applied
•
Acquisition: Triggered by the R wave of the ECG; 16-24 frames (each ~40-50 ms) and ~250 thousand counts per frame are collected. As the number of frames increases, temporal resolution increases but counts per frame fall
•
Views: Anterior; LAO at the angle where the septum best separates the two ventricles ("best septal", ~30-60°; LVEF is calculated from this view) and LPO
•
Gated blood pool SPECT: The cardiac chambers are seen separately without overlap; RV volume and EF and regional wall motion are therefore assessed better than with planar ERNA
•
Sources of error in LVEF: Overestimation of background makes LVEF falsely high, whereas inclusion of the left atrium in the end-systolic LV ROI makes it falsely low
•
An LPO or left lateral view best shows the left atrium and the inferior-posterolateral walls of the LV; on the LAO view the left atrium lies behind the LV
•
Normal LVEF is ≥50% (usually 55-75%); because the RV end-diastolic volume is larger, normal RVEF is lower than LVEF (≥~40-45%)
•
Parametric images: The Fourier amplitude image shows the magnitude of contraction (reduced in hypokinesia/akinesia); the phase image shows the timing of contraction (~180° opposite phase to the ventricle in dyskinesia/aneurysm, early phase at the pre-excitation site in WPW)
•
Phase analysis gives the contraction time of each pixel relative to the R wave; it shows conduction disorders (bundle branch blocks, pre-excitation, ectopic focus) and dyssynchrony. In RV apical pacing, contraction spreads from the apex to the base
•
Functional images: Stroke volume image = ED − ES; EF image = (ED − ES)/ED, akinetic region appears faint; paradox image = ES − ED, dyskinetic region appears bright
•
Wall motion: Hypokinesia (reduced), akinesia (absent), dyskinesia (paradoxical outward motion in systole; aneurysm) and tardokinesia (delayed contraction). Both scar and ischaemia cause hypokinesia or akinesia
•
Blood pool findings: A photopenic halo around all cardiac chambers suggests pericardial effusion, whereas a photopenic band around the LV only suggests LV hypertrophy
Red cell labelling methods:
•
In vivo: Stannous pyrophosphate (tin) IV → 20-30 min later Tc-99m pertechnetate IV → binds to red cells. Labelling efficiency: 75-80%
•
In vitro (best method): Blood is drawn and incubated with tin (stannous chloride/citrate); extracellular tin is oxidised with sodium hypochlorite, then Tc-99m pertechnetate is added and the blood is reinjected. Labelling efficiency is >97%
•
UltraTag® (commercial in vitro kit): Does not require centrifugation. As an alternative to red cells, Tc-99m labelled human serum albumin (HSA) may also be used
•
Breastfeeding: Interrupted for 12 hours after ERNA (milk may be expressed in advance)
•
Modified in vivo (in vivtro): Stannous pyrophosphate IV → blood drawn → Tc-99m added → reinjection. Labelling efficiency: 85-90%
•
After reduction by tin inside the red cell, Tc-99m binds to the β chain of haemoglobin
•
Causes of poor labelling: Drugs (heparin, iodinated contrast, doxorubicin, methyldopa, hydralazine, quinidine), circulating antibodies, inappropriate amount of tin and excess carrier Tc-99m; activity is then seen in the stomach, thyroid and soft tissue
Indications:
•
Monitoring of chemotherapy cardiotoxicity (the most important indication)
–
Doxorubicin (adriamycin) → cumulative dose-dependent cardiotoxicity
–
Baseline LVEF measurement → repeated before each cycle
–
Absolute fall ≥10% from baseline + LVEF <50% → stop/change chemotherapy
•
Cumulative dose limit: 550 mg/m² (450 mg/m² after mediastinal RT)
•
Anthracycline cardiotoxicity (type I) results from cumulative dose-dependent myocyte loss and is largely irreversible; dexrazoxane (ICRF-187) is protective. Trastuzumab toxicity (type II) is usually reversible; 5-FU can cause coronary vasospasm
•
If baseline LVEF is <50%, the drug is stopped with an absolute fall of ≥10% or when LVEF falls to ≤30% (treatment is not started if baseline LVEF is ≤30%). RNV is performed at cumulative doses of 250-300 and 400-450 mg/m², then before each dose and ≥3 weeks after the last dose
•
Measurement of left and right ventricular EF
•
Wall motion analysis
•
Shunt calculation (Qp/Qs) can only be done with a first-pass study; the equilibrium (MUGA) study does not show an intracardiac shunt
•
Assessment of diastolic function (peak filling rate)
–
Diastolic parameters require ≥32 frames per cycle (or list mode); combining forward and backward gating samples late diastole more accurately. Normal PFR is >2.5 EDV/s and TTPF <180 ms
•
Acute MI: ~75% of patients have regional wall motion abnormality and reduced global EF; the lower the EF, the worse the prognosis. Inferior MI may be accompanied by RV wall motion abnormality (RCA)
•
Signs of ischaemia on exercise RNV: Failure of EF to rise with stress (it normally rises by ≥5%) and a new wall motion abnormality. Specificity is low; cardiomyopathy, valve disease, myocarditis and drug toxicity give a similar response
–
Because images are acquired during exercise in exercise ERNA, a supine or semi-supine bicycle ergometer is used; a treadmill is not suitable
•
Dilated cardiomyopathy: LV dilated, globally hypokinetic, with low EF (basal and septal segments may be relatively preserved). In cor pulmonale the RV is dilated with low RVEF and the LV is preserved
•
Hypertrophic cardiomyopathy: Asymmetric septal hypertrophy, small LV cavity, hyperdynamic LV (high LVEF) and impaired diastolic filling (low PFR, prolonged TTPF). On MPI the septal/lateral count ratio is increased (also increased in hypertensive LVH)
–
Ischaemic cardiomyopathy: Large defects corresponding to coronary territories, regional wall motion abnormality and usually LV dilatation. Non-ischaemic dilated cardiomyopathy: Heterogeneous uptake, no large defects, global hypokinesia and often biventricular dilatation
Advantages:
•
The most reproducible method of LVEF measurement → gold standard for serial follow-up
•
The reference (gold) standard for ventricular volumes and EF is cardiac MRI; because MUGA is count-based, its reproducibility is close to that of MRI
•
Operator-independent
•
Requires no geometric assumptions (count-based)
Disadvantages:
•
Limited anatomical information
•
Reduced accuracy in arrhythmias (especially AF) → irregular R-R intervals → gating is degraded
•
In arrhythmia, counts fall markedly in the last frames; the solution is beat rejection of outlier cycles or list-mode acquisition
•
Radiation exposure
First-pass radionuclide angiography (FPRNA):
•
Agents: Tc-99m DTPA, pertechnetate, labelled red cells/HSA and MIBI/tetrofosmin; if a perfusion agent is used, MPI can also be acquired afterwards
•
Indications: RV and LV EF, wall motion, quantification of left-to-right shunt (Qp/Qs), cardiac output and diastolic function (peak filling rate and time to peak filling rate)
•
Activity: 555-1110 MBq in adults (any Tc-99m agent); the most commonly used position is semi-supine, straight anterior
•
Its use has declined with the spread of echocardiography, but it remains valuable for assessing RV function and intracardiac shunts
•
FPRNA technique: A compact bolus (medial antecubital or basilic vein; the cephalic vein is avoided), 15-30 frames per second, ~30 s acquisition, anterior or ~20° RAO position. Advantages are its short duration (can be acquired at peak exercise) and ability to measure RVEF; the disadvantage is poor count statistics
•
Camera and collimator: Because count rates are high in FPRNA, a high-sensitivity collimator (preferably a multicrystal camera suited to high count rates) is required; for ERNA a single-crystal camera and LEAP/LEHR collimator suffice
•
Report content (SNMMI/EANM 2020): in addition to the common items (see 27), height, weight and body surface area, red cell labelling method, rhythm, heart rate and beat rejection window, study quality; LV size, regional wall motion (normal, mild, moderate or severe hypokinesis, akinesis, dyskinesis), LVEF (normal ≥50%), diastolic function (qualitative; PFR if possible), RV size and, with SPECT ERNA, RVEF (lower limit ~40%). Comparison with the prior study is stated: reproducibility is ~5%, so a change greater than 5 EF units is significant, and serial monitoring uses the same technique; during chemotherapy a fall of ≥10 EF units from baseline to below 50% is the cardiotoxicity criterion
BOARD TIP
▸
"Most reproducible method of LVEF measurement?"
→ MUGA.
▸
"For monitoring doxorubicin cardiotoxicity?"
→ Serial LVEF measurement with MUGA.
▸
"Fall ≥10% with LVEF <50%?"
→ Stop chemotherapy.
▸
"Best efficiency in red cell labelling?"
→ In vitro (>97%).
▸
"Cause of artefact on MUGA?"
→ Atrial fibrillation → irregular R-R → gating is degraded.
Figure 14.8: LVEF calculation from the ECG-gated left ventricular count curve on MUGA and the stopping criterion in monitoring doxorubicin cardiotoxicity (schematic).
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14.4 Cardiac Innervation Scintigraphy (I-123 MIBG)
14.4.1 H/M Ratio and Washout Rate1 questions
I-123 MIBG (Metaiodobenzylguanidine):
•
Norepinephrine (NE) analogue → taken up by uptake-1 (NET) at presynaptic sympathetic nerve terminals
•
Assesses the density and function of sympathetic innervation in the myocardium
•
Dose: 5-10 mCi (185-370 MBq) IV
•
Thyroid blockade: Potassium iodide or Lugol's solution (protection against free I-123)
•
MIBG is retained in nerve terminals because it is not degraded by MAO or COMT
•
EANM: 111-185 MBq for planar imaging (slow IV over 1-2 min), 370 MBq for SPECT in systolic heart failure; 0.013 mSv/MBq
•
Thyroid blockade is started ≥30 min before injection and continued for 2-3 days; breastfeeding is interrupted for ≥24 hours. Clearance falls in renal failure, and MIBG cannot be removed by dialysis
•
Substances affecting uptake: Tricyclic antidepressants, sympathomimetics, antipsychotics, some antihypertensives, tramadol, opioids, cocaine and foods containing catecholamine-like compounds (chocolate, blue cheese)
•
PET innervation agents: C-11 hydroxyephedrine (uptake-1), C-11 epinephrine (requires vesicular storage), C-11 phenylephrine and F-18 meta-fluorobenzylguanidine, whose kinetics resemble MIBG
Imaging protocol:
•
Early imaging: 15-20 minutes after injection → planar anterior chest
•
Delayed imaging: 3-4 hours after injection → planar anterior chest
•
SPECT imaging can also be performed (regional assessment of innervation)
•
EANM: Early image at 15 minutes, delayed image at 4 hours; LEHR collimator, 159 keV ±20% window; anterior planar image 10 min, 128×128 or 256×256 matrix
•
The mediastinal ROI is drawn in the upper mediastinum, away from the thyroid; the delayed H/M ratio falls with age and WR rises with age
H/M Ratio (Heart-to-Mediastinum Ratio):
•
Heart ROI counts / mediastinum ROI counts
•
Mediastinum → non-specific uptake → reference region
•
Early H/M: Reflects uptake-1 function
•
Delayed H/M: Reflects neuronal retention and vesicular storage function → more important
•
Normal delayed H/M: ≥~1.8-2.0 with LEHR (ADMIRE-HF threshold 1.6); values are higher with an ME collimator
•
Low H/M → sympathetic denervation → poor prognosis
Washout Rate (WR):
•
Rate of MIBG washout between early and delayed images
•
WR = [(Early H/M − Delayed H/M) / Early H/M] × 100
•
Normal: low (usually <20%)
•
Increased WR → increased sympathetic activity → increased NE turnover → poor prognosis
BOARD TIP
▸
"Most important parameter on cardiac MIBG?"
→ The delayed H/M ratio.
▸
"What does H/M <1.6 mean?"
→ Sympathetic denervation → poor prognosis.
▸
"Increased washout rate?"
→ Increased sympathetic activity → high NE turnover → poor prognosis.
14.4.2 Prognosis in Heart Failure4 questions
ADMIRE-HF Trial:
•
Prognostic value of I-123 MIBG in patients with chronic heart failure (NYHA II-III, LVEF ≤35%)
•
Delayed H/M ≥1.6: Low event risk → good prognosis
•
Delayed H/M <1.6: High event risk (cardiac death, arrhythmic event, HF progression)
•
The H/M ratio carries prognostic value independent of LVEF
•
May help in assessing the indication for an ICD (implantable cardioverter-defibrillator)
–
ADMIRE-HF: 961 patients, 2-year follow-up. The 2-year event rate was 15% with H/M ≥1.60 and 37% with <1.60 (HR 0.40); arrhythmic events were most frequent in the group with H/M 1.30-1.39
–
Innervation/perfusion mismatch: Perfused but denervated viable myocardium (adjacent to scar) shows denervation supersensitivity; it may be the source of lethal arrhythmias and a target for ablation
–
H/M ≥1.6 → low arrhythmic risk → may not benefit from an ICD
–
H/M <1.6 → high arrhythmic risk → may benefit from an ICD
Clinical use:
•
Risk stratification in heart failure
•
Aid in decisions on ICD implantation
•
Evaluation of heart transplant candidates
•
In the transplanted (denervated) heart MIBG uptake is absent or very low; partial reinnervation over the years begins in the basal anterior and anterolateral walls
•
Monitoring of treatment response (rise in H/M after beta-blocker therapy → favourable response)
–
With ACE inhibitor/ARB and β-blocker therapy H/M rises and WR falls; a high WR may predict response to β-blockers
14.4.3 Distinguishing Parkinson Disease and Dementia with Lewy Bodies3 questions
Principle:
•
Parkinson disease and dementia with Lewy bodies (DLB): Cardiac sympathetic denervation → reduced MIBG uptake (low H/M)
•
Essential tremor, drug-induced parkinsonism, vascular parkinsonism: Cardiac innervation preserved → normal MIBG uptake
•
Multiple system atrophy (MSA): Variable → usually preserved or mildly reduced (preganglionic lesion)
Clinical use:
•
Parkinson vs essential tremor → assessed together with DaTscan (→ see Chapter 19.6)
•
DLB vs Alzheimer → MIBG reduced in DLB, normal in Alzheimer
•
MSA vs Parkinson → MIBG usually preserved in MSA, reduced in Parkinson
•
EANM: Cardiac MIBG uptake is reduced in ~80-90% of Lewy body diseases; it is preserved in MSA, PSP and Alzheimer disease
•
A meta-analysis found a delayed H/M threshold of ~1.77 for identifying Parkinson disease/DLB
•
Report content (EANM 2010 standardisation proposal; EACVI/EANM 2021): in addition to the common items (see 27), drugs affecting MIBG uptake (tricyclic antidepressants, labetalol, sympathomimetics), thyroid blockade; collimator used (medium-energy is recommended because the H/M ratio depends on the collimator), early (~15 minutes) and late (~3-4 hours) imaging times, ROI method. Findings: early and late H/M ratio, washout rate and its calculation (background and decay correction); regional defects if SPECT was performed. As there is no universal H/M cut-off, the threshold used and the collimator-specific reference value are stated
BOARD TIP
▸
"Cardiac MIBG in Parkinson disease?"
→ Reduced (postganglionic sympathetic denervation).
▸
"MIBG in DLB vs Alzheimer?"
→ DLB → MIBG reduced; Alzheimer → MIBG normal.
▸
"MSA vs Parkinson?"
→ MSA → MIBG usually preserved (preganglionic); Parkinson → MIBG reduced (postganglionic).
Figure 14.9: H/M measurement, washout, ADMIRE-HF event rates and neurological differential diagnosis on cardiac I-123 MIBG (schematic).
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14.5 Cardiac Amyloidosis Scintigraphy (Tc-99m PYP/DPD/HMDP)5 questions
Types of Cardiac Amyloidosis:
•
ATTR (transthyretin): Wild-type (senile) or hereditary (mutant) → detected with bone agents
•
AL (light chain): Plasma cell dyscrasia → usually not detected with bone agents
Radiopharmaceuticals:
•
Tc-99m PYP (pyrophosphate): Most widely used in the USA
•
Tc-99m DPD (3,3-diphosphono-1,2-propanodicarboxylic acid): Widely used in Europe
•
Tc-99m HMDP (hydroxymethylene diphosphonate): Alternative
•
These are bone scintigraphy agents → bind to ATTR amyloid fibrils
•
The mechanism of cardiac uptake is not definitely known; it may relate to the propensity of the amyloid type to support calcium deposition
•
DPD and HMDP may also show amyloid infiltration in extracardiac tissues such as skeletal muscle and lung
•
Commonest causes of cardiac amyloidosis: AL, hereditary ATTR (ATTRv/ATTRh) and wild-type ATTR (ATTRwt)
•
EANM activity: ~740 MBq (15-25 mCi); effective dose 3.3-4.4 mSv. Pregnancy is a relative contraindication; breastfeeding need not be interrupted
–
No preparation and no fasting are needed (2021 consensus). The activity is 370-740 MBq (10-20 mCi) for all three agents; the diagnostic acquisition is at 2 or 3 hours with SPECT including the heart (preferably SPECT/CT); a 1-hour image is optional for PYP only and is repeated at 3 hours if blood pool activity is excessive
Imaging protocol:
•
Tc-99m PYP: 10-25 mCi IV → planar + SPECT/CT after 1 hour (and/or 3 hours)
•
Planar imaging: Anterior chest → heart/contralateral chest (H/CL) ratio
Assessment – Perugini Score (Visual Grading):
•
Grade 0: No cardiac uptake → no ATTR amyloidosis
•
Grade 1: Cardiac uptake less than bone → equivocal
•
Grade 2: Cardiac uptake equal to bone → consistent with ATTR amyloidosis
•
Grade 3: Cardiac uptake greater than bone (bone uptake appears reduced) → consistent with ATTR amyloidosis
H/CL Ratio:
•
≥1.5 (at 1 hour) or ≥1.3 (at 3 hours) → consistent with ATTR amyloidosis
–
Current recommendation: the addendum to the consensus removed H/CL ≥1.5 as a "strongly positive" criterion; the diagnosis rests on the visual grade of diffuse myocardial uptake on SPECT or SPECT/CT (ASNC 2023: interpretation based on planar images increases errors; 1-hour planar-only imaging is not recommended). H/CL is a complementary measurement
Importance of SPECT/CT:
•
Critical for excluding blood pool activity
•
On planar imaging, blood pool activity may cause false positives
•
SPECT/CT → distinguishes myocardial uptake from blood pool
Diagnostic algorithm:
•
Grade 2-3 uptake + negative monoclonal protein (serum/urine immunofixation + normal free light chains) → ATTR can be diagnosed without biopsy (PPV close to 100%)
•
Grade 2-3 uptake + positive monoclonal protein → biopsy required (may be AL)
•
Grade 0 → ATTR unlikely; Grade 1 → equivocal (AL not excluded)
•
EANM: After AL has been excluded, a score ≥2 on planar or SPECT images at 3 hours is a strong finding for ATTR cardiac amyloidosis
•
Pitfall: Marked cardiac uptake (including grade 2-3) may also be seen in >20% of patients with AL cardiac amyloidosis; screening for monoclonal protein is therefore essential
–
Other causes of false positives: excessive blood pool activity, recent myocardial injury (myocardial infarction, pericarditis; PYP uptake may persist up to 6 months after infarction), a rib fracture or metastasis overlying the heart, breast tissue and lung parenchymal uptake, hydroxychloroquine cardiotoxicity, rare amyloid types (apolipoprotein A-I). Causes of false negatives: early disease, TTR variants with low sensitivity (p.Phe84Leu [formerly Phe64Leu], p.Val50Met [Val30Met], Ser77Tyr), type B fibrils only, imaging too early or too late; with a large infarct scar, uptake is seen only in the intact segments (ACC 2025; ASNC 2023)
•
Uptake must be in the myocardial wall and should not be confused with intravascular blood pool activity
•
Report content (multisociety consensus 2020): in addition to the common items (see 27), agent used (PYP, DPD or HMDP) and imaging time, that SPECT (preferably SPECT/CT) was performed. Findings: visual grade of myocardial uptake relative to rib (0-3) and confirmation on SPECT that the uptake is myocardial rather than blood pool; if measured, the H/CL ratio as supporting information only. The conclusion states that grade 2-3 uptake indicates ATTR cardiac amyloidosis only when a monoclonal protein has been excluded (serum free light chains, serum and urine immunofixation); if these results are unknown, the report says so explicitly
BOARD TIP
▸
"Which type of amyloidosis does Tc-99m PYP detect?"
→ ATTR (transthyretin). AL amyloidosis is usually not detected.
▸
"Perugini Grade 2-3 + negative monoclonal protein?"
→ ATTR can be diagnosed without biopsy.
▸
"Why is SPECT/CT needed?"
→ To exclude blood pool activity → to prevent false positives.
▸
"What does Grade 1 mean?"
→ Equivocal → further evaluation needed.
Figure 14.10: Perugini visual score in cardiac amyloidosis with bone agents and the ATTR diagnostic algorithm (schematic).
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14.6 Cardiac Sarcoidosis (FDG PET)8 questions
Principle:
•
Sarcoidosis → non-caseating granulomas → inflammation in the myocardium
•
Active inflammatory cells (macrophages) → high glucose metabolism → FDG uptake
•
Normal myocardium also uses glucose → physiological myocardial FDG uptake must be suppressed
Patient preparation – Suppressing physiological myocardial uptake:
•
Prolonged fasting: At least 12-18 hours (preferably ≥18 hours)
•
High-fat, low-carbohydrate diet: The day before and the morning of imaging → shifts the myocardium to fatty acid utilisation
•
Heparin protocol (optional): IV heparin (50 IU/kg) → increases free fatty acids → myocardium uses fatty acids → FDG uptake falls
•
Aim: Suppress FDG uptake in normal myocardium → reveal inflammatory uptake
•
EANM: A fat-rich, carbohydrate-poor diet for 24 hours before imaging; FDG 185-400 MBq (2-4 MBq/kg)
•
CAD must be excluded before FDG is interpreted; perfusion imaging (MIBI/tetrofosmin SPECT or Rb-82/N-13 ammonia PET) is recommended for this purpose
•
Rest perfusion defect: Microvascular compression by inflammation, or scar
•
Pregnancy is a relative contraindication; interruption of breastfeeding is not recommended
BOARD TIP
▸
"Patient preparation in cardiac sarcoidosis?"
→ Prolonged fasting (≥12-18 hours) + high-fat/low-carbohydrate diet → suppress physiological myocardial FDG uptake.
▸
"Patient preparation for a viability study?"
→ Glucose loading (the exact opposite!). Do not confuse these two protocols!
Imaging and Assessment:
•
FDG PET/CT → focal or focal-on-diffuse myocardial FDG uptake → active cardiac sarcoidosis
•
Assessed together with a perfusion study (Rb-82 or N-13 ammonia)
•
Uptake is usually patchy and particularly prominent in the basal septum and basal lateral wall of the LV
•
Perfusion-Metabolism Patterns (Sarcoidosis):
–
Normal perfusion + focally increased FDG → early/active inflammation (no scar yet)
–
Reduced perfusion + increased FDG → active inflammation + scar (mismatch)
–
Reduced perfusion + reduced FDG → scar (burned-out, inactive disease)
–
Normal perfusion + normal FDG → normal (no active cardiac sarcoidosis)
Clinical indications:
•
Diagnosis of cardiac sarcoidosis (clinical suspicion + echocardiography/MRI findings)
•
Monitoring of treatment response (fall in FDG uptake after immunosuppressive therapy → favourable response)
•
Simultaneous assessment of extracardiac sarcoidosis activity
•
Guiding biopsy site
•
The diagnostic yield of endomyocardial biopsy (EMB) is low; it rises to ~50% when guided by voltage mapping, FDG PET or cardiac MRI
•
Differential diagnosis: Other granulomatous diseases, infections and tumours may also take up FDG
Clinical significance of cardiac sarcoidosis:
•
Risk of AV block, ventricular arrhythmia and sudden cardiac death
•
Dilated cardiomyopathy
•
Heart failure
•
Early diagnosis and treatment → improved prognosis
•
Report content (EANM/EACVI/ASNC 2018): in addition to the common items (see 27), preparation to suppress myocardial glucose use (high-fat, low-carbohydrate diet and fasting duration) and blood glucose, uptake interval, perfusion agent. Findings: myocardial FDG pattern (none, diffuse, focal, focal on diffuse; diffuse uptake may reflect inadequate suppression), segments and sites of foci, SUV values; combined pattern with perfusion (FDG positive only, FDG and perfusion defect in the same or different segments, perfusion defect only); extracardiac uptake (e.g. mediastinal and hilar nodes as biopsy targets) and change from the previous study at follow-up
BOARD TIP
▸
"Two main indications for FDG PET in cardiac sarcoidosis?"
→ 1) Diagnosis, 2) Monitoring of treatment response.
▸
"Diffuse homogeneous myocardial FDG uptake?"
→ Most likely inadequate patient preparation (physiological uptake not suppressed) → repeat the study.
▸
"Focal or focal-on-diffuse uptake?"
→ Pathological → consistent with sarcoidosis.
Figure 14.11: Comparison of patient preparation for viability and cardiac sarcoidosis FDG PET, and myocardial FDG patterns in sarcoidosis (schematic).
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14.7 Cardiac PET Perfusion and Myocardial Blood Flow Measurement6 questions
Rb-82 (Rubidium-82)
•
Production: Sr-82/Rb-82 generator (no cyclotron needed → advantage for PET centres)
•
T½: 75 seconds (very short → rapid protocol)
•
Decay: Positron emission (95%) + electron capture (5%)
•
Positron energy: 3.35 MeV (high → long positron range → spatial resolution slightly lower)
•
Uptake mechanism: Na⁺/K⁺-ATPase → potassium analogue (similar to Tl-201)
•
First-pass extraction: 65% (falls as flow increases → plateaus → underestimation at high flow)
•
Activity: 1480-2220 MBq (40-60 mCi) on older 2D systems; 1110-1480 MBq on current 3D/analogue PET and 740-925 MBq on digital PET (EANM). Separate injections are given for rest and stress
•
Imaging: Starts 90 seconds after injection → lasts 5-7 min
•
Stress agent: Vasodilator (regadenoson, adenosine, dipyridamole) → exercise is unsuitable because of the short T½ (injected during exercise → decays before imaging)
–
Preparation is the same as for pharmacological stress: caffeine is stopped at least 12 (preferably 24) hours, theophylline 48 hours and dipyridamole 72 hours before (see 14.1)
•
Generator life: Sr-82 T½ = 25.4 days → the generator can be used for ~4-8 weeks
•
Quality control: Daily Sr-82 and Sr-85 breakthrough testing is mandatory → Sr-82 limit: 0.02 μCi Sr-82 / mCi Rb-82
•
Rb-82 PET MPI: Sensitivity similar to or slightly higher than SPECT, with markedly higher specificity (~90%); fewer artefacts thanks to reliable attenuation correction and high counts
•
PET MPI is preferred to SPECT especially in obese patients, women with large breasts and patients with equivocal or uninterpretable SPECT
BOARD TIP
▸
"Production of Rb-82?"
→ Sr-82/Rb-82 generator (no cyclotron needed).
▸
"T½?"
→ 75 seconds.
▸
"Uptake mechanism?"
→ Na⁺/K⁺-ATPase (potassium analogue, like Tl-201).
▸
"Can exercise stress be done with Rb-82?"
→ No → very short T½ → vasodilator stress is mandatory.
▸
"Generator quality control?"
→ Daily Sr-82 breakthrough test.
N-13 Ammonia
•
Production: Cyclotron (on-site production required)
•
T½: 10 minutes
•
Decay: Positron emission
•
Positron energy: 1.19 MeV (lower than Rb-82 → better spatial resolution)
•
Uptake mechanism: Converted to glutamine by glutamine synthetase in the myocyte → retained in the cell
•
First-pass extraction: 80% (high → more linear relationship with flow)
•
Dose: 10-20 mCi (370-740 MBq)
•
Imaging: Starts 3-5 minutes after injection
•
Stress agent: Vasodilator or exercise (T½ long enough)
•
Advantage: Better image quality than Rb-82 (low positron energy → better resolution)
•
Disadvantage: Requires a cyclotron → limited access
BOARD TIP
▸
"Uptake mechanism of N-13 ammonia?"
→ Metabolic trapping by glutamine synthetase.
▸
"Rb-82 vs N-13 ammonia → which has better resolution?"
→ N-13 ammonia (low positron energy).
▸
"Disadvantage of N-13 ammonia?"
→ Requires a cyclotron.
O-15 Water
•
T½: 2 minutes (very short)
•
Uptake mechanism: Diffuses freely → no metabolic trapping
•
First-pass extraction: 100% (complete diffusion → fully linear with flow)
•
Gold standard for MBF measurement (absolute myocardial blood flow)
•
Disadvantage: Very short T½ → on-site cyclotron required; does not produce a perfusion image (no static image → dynamic acquisition only)
•
O-15 water is given IV or as inhaled C¹⁵O₂ (converted to water by carbonic anhydrase). Because blood pool activity is high, blood pool subtraction (with C¹⁵O/¹¹CO-labelled red cells) or parametric imaging is needed
•
Rarely used in clinical practice → research use
BOARD TIP
▸
"Gold standard for MBF measurement?"
→ O-15 water (first-pass extraction 100%, fully linear with flow).
▸
"Why is it not used in clinical practice?"
→ T½ = 2 min → on-site cyclotron; does not produce a perfusion image.
Absolute Myocardial Blood Flow (MBF) and Coronary Flow Reserve (CFR)
MBF (Myocardial Blood Flow):
•
Calculated from dynamic PET acquisition (mL/min/g)
•
Normal rest MBF: 0.6-1.0 mL/min/g
•
Normal stress MBF: 2.5-4.0 mL/min/g
•
Calculated using compartmental models
–
O-15 water and Rb-82: A one-tissue compartment model suffices; N-13 ammonia: A second, irreversible compartment (k3 > 0, k4 = 0) is needed
•
Advantages of PET MPI: Higher spatial and temporal resolution, depth-independent attenuation correction
•
CZT cameras allow quantification of myocardial blood flow and flow reserve with dynamic SPECT
CFR (Coronary Flow Reserve):
•
CFR = Stress MBF / Rest MBF
•
Normal: ≥2.0 (usually 2.5-4.0)
•
CFR <1.5 → severely abnormal → high risk of cardiac events
•
CFR <2.0 → abnormal → epicardial stenosis and/or microvascular dysfunction
Clinical significance:
•
Balanced 3-vessel disease: Relative perfusion images may be normal → detected by MBF/CFR
•
Microvascular disease: Epicardial arteries normal → low CFR → microvascular dysfunction
•
Prognostic value: Low CFR → increased risk of cardiac events (independent of LVEF and perfusion defect)
•
Global vs regional CFR: Low global CFR + no regional difference → microvascular disease or balanced 3-vessel disease. Regional CFR difference → epicardial stenosis
•
Report content (EANM 2020 quantitative PET MPI): in addition to the common items (see 27), indication (which determines the emphasis), tracer, stress agent, software and kinetic model used; visually, the number of ischaemic and necrotic segments (17-segment model), SSS/SRS/SDS and percentage ischaemic burden, rest and stress LVEF, wall motion, TID and additional findings such as right ventricle and lung uptake. Quantitatively, stress and rest MBF and myocardial flow reserve (global and per coronary territory) with the normal/abnormal thresholds used and their source; calcium score in hybrid studies. The conclusion discusses homogeneous diffuse MBF reduction (microvascular disease) versus heterogeneous reduction (balanced three-vessel ischaemia)
BOARD TIP
▸
"Normal MPI in balanced 3-vessel disease → what should be done?"
→ Absolute MBF/CFR measurement with PET → global CFR will be low.
▸
"CFR <2.0?"
→ Abnormal.
▸
"Normal CFR but a perfusion defect?"
→ Possible artefact.
▸
"Gold-standard agent for MBF measurement?"
→ O-15 water.
▸
"MBF measurement in clinical practice?"
→ Dynamic PET with Rb-82 or N-13 ammonia.
Figure 14.12: Coronary flow reserve (CFR) thresholds based on rest and stress myocardial blood flow, with clinical examples (schematic).
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Comparison of PET Perfusion Agents:
| Feature | Rb-82 | N-13 Ammonia | O-15 Water |
|---|---|---|---|
| T½ | 75 s | 10 min | 2 min |
| Production | Generator | Cyclotron | Cyclotron |
| First-pass extraction | 65% | 80% | 100% |
| Mechanism | Na⁺/K⁺-ATPase | Glutamine synthetase | Free diffusion |
| Positron energy | 3.35 MeV | 1.19 MeV | 1.73 MeV |
| Spatial resolution | Moderate | Good | Moderate |
| Exercise stress | NO | YES | NO |
| MBF measurement | YES | YES | Gold standard |
| Clinical use | Widespread | Moderate | Rare (research) |
Key Points for the Board
MPI Radiopharmaceuticals:
•
Tl-201: Na⁺/K⁺-ATPase, first-pass extraction 85%, redistribution present, T½ = 73 hours, low energy (69-83 keV)
•
Tc-99m MIBI: Mitochondrial membrane potential, first-pass extraction 60-65%, no redistribution, marked hepatic excretion
•
Tc-99m Tetrofosmin: Mitochondria, first-pass extraction 54%, faster hepatic clearance than MIBI, labelling at room temperature
•
Ranking (first-pass extraction): Tl-201 > N-13 ammonia > Rb-82 > MIBI > Tetrofosmin
Stress Protocols:
•
Exercise is always preferred → target heart rate: (220 − age) × 0.85
•
Vasodilators: Adenosine (direct A2A, T½ 10 s), dipyridamole (indirect), regadenoson (selective A2A, bolus, most widely used)
•
For all vasodilators: Caffeine stopped 12-24 hours before (theophylline 48 hours); antidote = aminophylline
•
Asthma/COPD → vasodilators contraindicated → dobutamine (antidote: esmolol)
•
LBBB → vasodilator preferred (exercise/dobutamine → false septal defect)
Artefacts and High-Risk Findings:
•
Diaphragmatic attenuation: Male, inferior, fixed defect, normal wall motion → prone imaging
•
Breast attenuation: Female, anterior/anterolateral, fixed defect, normal wall motion
•
Gated SPECT: Attenuation artefact vs true defect → normal motion = artefact
•
TID: Severe multivessel / left main disease → high risk
•
Increased lung uptake (Tl-201): Severe LV dysfunction → high risk
•
Balanced 3-vessel disease: Normal-looking MPI → MBF/CFR measurement with PET
•
Reverse redistribution (defect becoming more conspicuous on the delayed image): Mostly reperfused infarction, not ischaemia
•
The LBBB false defect is confined to the septum and spares the apex; extension to the apex/anterior wall indicates true LAD ischaemia
Viability:
•
Hibernation: Perfusion ↓ + FDG ↑ (mismatch) → benefits from revascularisation
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Stunning: Normal perfusion + transiently impaired function → recovers spontaneously
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Scar: Perfusion ↓ + FDG ↓ (match) → irreversible
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FDG PET mismatch → gold standard for viability
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Tl-201 reinjection: 40-50% of fixed defects show fill-in
•
Allman meta-analysis: In viable myocardium revascularisation reduces annual mortality from 16% to 3.2%; no difference without viable myocardium
•
Viability preparation: Glucose loading (the exact opposite of sarcoidosis preparation!)
MUGA:
•
The most reproducible method of LVEF measurement
•
Doxorubicin monitoring: Fall ≥10% + LVEF <50% → stop chemotherapy
•
If baseline LVEF <50%: fall ≥10% or LVEF ≤30% → stop; baseline ≤30% → do not start
•
Phase analysis: Dyskinesia/aneurysm ~180° opposite phase to the ventricle; WPW pre-excitation site early phase
•
Red cell labelling: In vitro >97% (best), in vivo 75-80% (lowest)
•
AF → gating degraded → reduced accuracy
Cardiac MIBG:
•
Delayed H/M ≥1.6 → low risk → good prognosis (normal ≥~1.8-2.0)
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Delayed H/M <1.6 → sympathetic denervation → poor prognosis, high arrhythmic risk
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DLB → MIBG reduced; Alzheimer → MIBG normal
•
Parkinson → MIBG reduced (postganglionic); MSA → MIBG preserved (preganglionic)
Cardiac Amyloidosis (Tc-99m PYP/DPD/HMDP):
•
Detects ATTR amyloidosis (AL not detected)
•
Perugini Grade 2-3 + negative monoclonal protein → ATTR diagnosis without biopsy
•
SPECT/CT → mandatory to exclude blood pool activity
Cardiac Sarcoidosis (FDG PET):
•
Patient preparation: ≥12-18 hours fasting + high-fat/low-carbohydrate (suppress physiological uptake)
•
Focal/focal-on-diffuse FDG → pathological; diffuse homogeneous → inadequate preparation
•
Normal perfusion + focal FDG ↑ → early active inflammation
•
Used to monitor treatment response
PET Perfusion:
•
Rb-82: Generator, T½ = 75 s, Na⁺/K⁺-ATPase, vasodilator stress mandatory, daily Sr-82 breakthrough test
•
N-13 ammonia: Cyclotron, T½ = 10 min, glutamine synthetase, exercise stress possible, best resolution
•
O-15 water: Cyclotron, T½ = 2 min, free diffusion, first-pass extraction 100%, gold standard for MBF, rare in clinical practice
•
CFR = Stress MBF / Rest MBF → normal ≥2.0 → <2.0 abnormal → <1.5 severely abnormal
•
Balanced 3-vessel disease → detected by MBF/CFR
Scoring and Prognosis:
•
SSS: Total stress score; SRS: total rest score; SDS = SSS − SRS (amount of ischaemia)
•
Normal MPI → annual cardiac event risk <1% (warranty period ~2 years)
•
Ischaemic myocardium ≥10% → revascularisation should be considered
•
17-segment model (AHA): LAD → anterior + anteroseptal + apex (largest territory)
Additional Notes (EANM guidelines):
•
Tl-201: ~4% reaches the myocardium; extraction preserved in acidosis/hypoxia, reduced in fibrosis; plateau at 2-2.5 × resting flow; 74-111 MBq (+37 MBq reinjection); breastfeeding interrupted for 48 hours
•
Tc-99m agents: Plateau at ~2 × resting flow; 1-day protocol stress 250-400 MBq + 3 times that for rest ≥3 hours later; breastfeeding not interrupted
•
Withdrawal: β-blocker/Ca antagonist/nitrate 48 hours, dipyridamole 72 hours, theophylline 48 hours, caffeine ≥12 (preferably 24) hours
•
Rate-pressure product >25,000 adequate, >30,000 excellent; target heart rate >85%
•
Normal MPI annual MACE ~1% (women ~0.3%, pharmacological stress ~2%); post-stress stunning: EF fall lasting >60 min
•
Reverse mismatch: LBBB, early revascularised MI, non-ischaemic CMP, diabetes → considered viable
•
FPRNA: Shunt (Qp/Qs), RV function, cardiac output; 555-1110 MBq
•
Cardiac MIBG: 15 min and 4 hours, LEHR; ADMIRE-HF 2-year events 15% (H/M ≥1.6) vs 37%; 80-90% reduction in Lewy body diseases; PD/DLB threshold ~1.77
•
Amyloidosis: score ≥2 at 3 hours + AL excluded → ATTR; marked uptake may occur in >20% of AL
•
Cardiac sarcoidosis: 24-hour high-fat/low-carbohydrate diet; CAD should be excluded by perfusion
Current guidelines on this chapter's topics
The latest guidelines and consensus documents on the procedures covered in this chapter (official EANM index and primary sources, November 2026). Comparison of the text with these versions is in progress; consult the guideline itself for details.
- 2025SNMMI/EANM/ASNC/ACNM Procedure Standard/Practice Guideline for 18F-Flurpiridaz PET Myocardial Perfusion Imaging and Blood Flow Quantitation (opens in a new tab)
- 2024Hybrid cardiovascular imaging. A clinical consensus statement of the european association of nuclear medicine (EANM) and the european association of cardiovascular imaging (EACVI) of the ESC. (opens in a new tab)
- 2022Nuclear medicine in the assessment and prevention of cancer therapy-related cardiotoxicity: prospects and proposal of use by the European Association of Nuclear Medicine (EANM) (opens in a new tab)
- 2021The role of myocardial innervation imaging in different clinical scenarios: an expert document of the European Association of Cardiovascular Imaging and Cardiovascular Committee of the European Association of Nuclear Medicine (opens in a new tab)
- 2020EANM procedural guidelines for PET/CT quantitative myocardial perfusion imaging (opens in a new tab)
- 2020SNMMI Procedure Standard/EANM Guideline for Gated Equilibrium Radionuclide Angiography (opens in a new tab)
- 2020ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2—Diagnostic criteria and appropriate utilization (opens in a new tab)
- 2020Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM (opens in a new tab)
- 2019EANM procedural guidelines for myocardial perfusion scintigraphy using cardiac-centered gamma cameras (opens in a new tab)
- 2018A joint procedural position statement on imaging in cardiac sarcoidosis: from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology (opens in a new tab)
- 2015EANM procedural guidelines for radionuclide myocardial perfusion imaging with SPECT and SPECT/CT (opens in a new tab)
- 2015Reporting nuclear cardiology: A joint position paper by the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI) (opens in a new tab)
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