Pulmonary System
Report template: Ventilation/perfusion scintigraphy
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Solve questions (26) →Contents
- 17.1 Perfusion Scintigraphy (Tc-99m MAA)
- 17.2 Ventilation Scintigraphy
- 17.3 V/Q Scintigraphy and the Diagnosis of Pulmonary Embolism
- 17.4 PIOPED Criteria and Modified Criteria
- 17.5 V/Q SPECT and SPECT/CT
- 17.6 Preoperative Lung Function Assessment (Quantitative Perfusion)
- 17.7 Right-to-Left Shunt Calculation
- Key Points for the Board
- Current guidelines on this chapter's topics
Learning objectives and modules4 modules · about 2 h 25 min
Learning objectives
After this chapter you will be able to:
- Explain the principle of MAA perfusion scintigraphy, particle number and size, and the precautions in special situations.
- Compare ventilation agents (Xe-133, Kr-81m, DTPA aerosol, Technegas).
- Recognise V/Q mismatch and match patterns; interpret pulmonary embolism with the PIOPED and EANM criteria.
- Explain the advantages of V/Q SPECT and SPECT/CT over planar imaging.
- Predict postoperative lung function with quantitative perfusion and calculate a right-to-left shunt.
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 117.1 Perfusion Scintigraphy (Tc-99m MAA)25 min · 1 animation · 10 questionsAnswer the questions →
- Module 217.2–17.3 Ventilation Scintigraphy · V/Q Scintigraphy and the Diagnosis of Pulmonary Embolism50 min · 1 animation · 22 questionsAnswer the questions →
- Module 317.4–17.6 PIOPED Criteria and Modified Criteria · V/Q SPECT and SPECT/CT · Preoperative Lung Function Assessment (Quantitative Perfusion)40 min · 19 questionsAnswer the questions →
- Module 417.7 Right-to-Left Shunt Calculation · Key Points for the Board30 min · 1 animation · 10 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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Particle size: 10-90 μm (mean 20-40 μm)
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Standard particle number: 200,000-700,000
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Proportion of arterioles occluded: 0.1-0.3% → haemodynamically safe
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Injection position: Supine (to reduce the effect of gravity)
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Biological half-life: 2-9 hours
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Particle number in pulmonary hypertension: reduce to 100,000-150,000
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In right-to-left shunt: Reduce particle number (risk of cerebral embolisation)
17.1 Perfusion Scintigraphy (Tc-99m MAA)10 questions
Basic Principles
Lung perfusion scintigraphy assesses the regional distribution of the pulmonary arterial circulation. IV-injected Tc-99m MAA (macroaggregated albumin) particles are temporarily trapped in the pulmonary precapillary arterioles by mechanical embolisation and reflect the perfusion distribution. Radiopharmaceutical: Tc-99m MAA
Physical properties:
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Particle size: 10-90 μm (mean 20-40 μm)
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Precapillary arteriole diameter: ~10 μm → MAA particles are trapped here
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Particles smaller than 10 μm → pass through the capillaries → escape into the systemic circulation
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Particles larger than 150 μm → trapped in more proximal arteries → inhomogeneous distribution
Injection and distribution:
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Standard dose: 2-4 mCi (74-148 MBq). SNMMI/EANM 2026: 40-150 MBq in adults; if a Tc-99m ventilation study has been performed first, ~200-220 MBq is needed for perfusion. In children 1.1 MBq/kg (minimum 15 MBq); 2.6 MBq/kg if a Tc-99m ventilation study has been performed first
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Particle number: 200,000-700,000 (ideal: 400,000). 100,000-200,000 is regarded as the minimum required; in normal adults reducing to 100,000-200,000 does not impair image quality, while below 100,000 the distribution becomes inhomogeneous (SNMMI/EANM 2026)
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The number of particles injected depends on the volume drawn up: As the kit decays, a larger volume is drawn up for the same activity, so more particles are given
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Total number of pulmonary arterioles: ~300 million → proportion occluded by MAA: 0.1-0.3% → haemodynamically insignificant
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Particles are distributed under gravity → greater uptake in the posterior bases in the supine position
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Biological half-life: 2-9 hours → particles break down → cleared by the RES
In the first step MAA particles of different sizes travel down a narrowing pulmonary artery branch and lodge where the diameter falls to their size; very small ones pass the capillaries. In the second step, with a right-to-left shunt, some particles bypass the lung into the systemic circulation, the shunt percentage is counted and brain and kidney uptake rises on the whole-body image.
Continuous stream · no seeking
Key idea: MAA particles lodge in the precapillary arteriole that matches their size; with a right-to-left shunt particles that bypass the lung appear in brain and kidneys and the shunt fraction is systemic / total.
Source: book (17.1: 10-90 µm, mean 20-40 µm, 200,000-700,000 particles, ~300 million arterioles, 0.1-0.3%, T½ 2-9 h; 17.7: shunt formula, geometric mean, normal <5%, brain uptake). The vessel diameter model and particle size distribution are representative.
How to use: a single click on the drawing pauses and resumes; in the shunt step ↑ ↓ or the buttons below change the shunt fraction; ← → change steps.
Did this animation help you understand the topic?
Figure 17.1: Site of trapping in the pulmonary vascular bed by Tc-99m MAA particle size, and particle number/proportion of occluded arterioles (schematic).
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EANM: Adult 40-120 MBq (child at least 10 MBq; particle number adjusted to weight); 11 µSv/MBq, i.e. ~1.1 mSv for 100 MBq; breastfeeding is interrupted for 12 hours
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Pitfalls: Injection not performed supine or too few particles given (<100,000; SNMMI/EANM 2026) makes the distribution irregular; clot formation in the syringe or inadequate flushing of an indwelling catheter causes hot spots
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Other indications: Investigation of the aetiology of pulmonary HT, assessment of regional function before lung cancer surgery or RT, lung transplantation, before volume-reduction surgery in emphysema, congenital shunts, pulmonary artery stenosis and AV fistula; multiple injections may be needed in complex malformations
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Quantitative perfusion in single-lung transplantation: In primary pulmonary hypertension most of the perfusion (~90%) goes to the low-resistance graft; the shift in ventilation is more limited
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If the perfusion image is normal, PE is excluded and no ventilation study is needed; if perfusion is abnormal, ventilation is needed for interpretation
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Patency of a peritoneovenous (LeVeen/Denver) shunt: Activity in the lungs after intraperitoneal Tc-99m MAA shows the shunt is patent; no lung activity means the shunt is occluded
Injection technique:
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The patient should be injected supine (to minimise the effect of gravity)
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Slow injection: over about 30 seconds, during 3-5 normal respiratory cycles → homogeneous distribution (EANM 2019, SNMMI/EANM 2026). Not given through a catheter, port or line containing a filter; a well-flushed indwelling line may be used (excluding a Swan-Ganz catheter)
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Blood should not be drawn back into the syringe during injection → clot formation → "hot spot" artefact
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The syringe should be gently agitated before injection (particles settle)
BOARD TIP
▸
"MAA particle size?"
→ 10-90 μm (mean 20-40 μm).
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"Particle number?"
→ 200,000-700,000.
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"What percentage of all arterioles is occluded?"
→ 0.1-0.3% → haemodynamically safe.
▸
"Injection position?"
→ Supine (to reduce the effect of gravity).
Dose Adjustment in Special Situations
Situations requiring a reduced particle number:
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Pulmonary hypertension: Particle number should be reduced to 100,000-150,000 → vascular bed already reduced
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Right-to-left shunt: Particles pass into the systemic circulation → risk of cerebral/coronary embolisation → particle number should be reduced
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Pneumonectomy / single lung: Vascular bed reduced by 50% → particle number should be halved
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Pregnancy: Activity is reduced (1-2 mCi; e.g. ~50 MBq), but the particle number is not reduced below 100,000 (fewer particles give an inhomogeneous distribution; SNMMI/EANM 2026)
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EANM 2019: In pregnancy a perfusion-only study with low activity (50 MBq) is performed first; if perfusion is normal, ventilation is not needed. SNMMI/EANM 2026: This is an option but not the preferred approach in most pregnant patients (risk of delayed diagnosis or unnecessary anticoagulation). A reduced-dose V/Q SPECT is generally recommended, with half the standard activity of both agents and twice the acquisition time; the low-dose CT is omitted if the perfusion SPECT is definitive. Technegas is preferred for ventilation (it stays in the lungs; DTPA is excreted renally and passes the bladder close to the fetus). The main organ to protect from radiation is the maternal breast; D-dimer is of limited value because it is usually raised in pregnancy
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Paediatric patients: Particle number reduced according to age and weight (minimum 10,000-50,000)
Contraindications:
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Known MAA allergy (rare)
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Severe pulmonary hypertension → relative contraindication (can be performed with a reduced particle number)
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Tc-99m MAA → albumin-based → egg allergy is NOT a contraindication (frequently asked board question)
BOARD TIP
▸
"MAA particle number in pulmonary hypertension?"
→ Should be reduced to 100,000-150,000.
▸
"Is egg allergy a contraindication?"
→ NO → MAA is made from human albumin and has nothing to do with eggs.
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"Risk in right-to-left shunt?"
→ Particles pass into the systemic circulation → risk of cerebral embolisation.
Imaging
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Planar imaging: 8 projections (anterior, posterior, right/left lateral, right/left anterior oblique, right/left posterior oblique)
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Planar imaging is performed in 6-8 projections; 600,000-1,000,000 counts per projection are targeted for perfusion and 300,000-500,000 for ventilation (SNMMI/EANM 2026)
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SPECT or SPECT/CT: Higher sensitivity and specificity (→ see 17.5)
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Imaging can start immediately after injection
Normal Perfusion Pattern
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Homogeneous, symmetric uptake in both lungs
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Greater uptake in the bases than the apices (gravity effect → reduced in the supine position)
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Photopenic area at the cardiac silhouette and mediastinum (normal)
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Mildly reduced uptake in the hilar regions (large vessels)
Abnormal Perfusion Patterns
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Segmental defect: Loss of perfusion in one or more segments → suggests PE
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Non-segmental defect: A defect not conforming to anatomical segments → causes other than PE (tumour, effusion, cardiomegaly)
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Matched defect: Perfusion and ventilation defects in the same area → not PE (COPD, pneumonia)
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Reverse mismatch (ventilation defect larger than the perfusion defect) is seen in lobar pneumonia, atelectasis, pleural effusion, mucus plugging or bronchial obstruction; it does not suggest PE
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Mismatched defect: Perfusion defect present, ventilation normal → favours PE
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Complete loss of perfusion to one lung is rare in PE; a central tumour or compression by a hilar mass should be considered. Causes of a single-lung defect matched on ventilation: central carcinoma, aspirated foreign body, Swyer-James syndrome
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Reversal of the perfusion gradient (more perfusion in the upper than the lower zones) suggests pulmonary venous hypertension (left heart failure, mitral stenosis)
17.2 Ventilation Scintigraphy21 questions
General Principles
Ventilation scintigraphy assesses the regional distribution of lung aeration. Together with perfusion scintigraphy, as V/Q scintigraphy, it is used to diagnose pulmonary embolism.
Ventilation Agents
A) Xe-133 (Xenon-133) Gas:
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Gaseous form → administered by inhalation
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Energy: 81 keV (lower than Tc-99m → 140 keV)
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Half-life: 5.3 days
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Three-phase imaging:
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Single breath: The patient takes a deep breath and holds it → first distribution image
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Equilibrium/rebreathing: 3-5 minutes of breathing in a closed system → homogeneous distribution
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Washout: Room air is breathed → the gas clears from the lungs
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The washout phase is the most important phase → areas of air trapping clear late → diagnosis of COPD
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Disadvantages:
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Low energy (81 keV) → downscatter artefact if performed after Tc-99m perfusion
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Ventilation must be performed FIRST (low energy → high energy order)
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Only the posterior projection can be acquired (the gas distributes rapidly)
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A special ventilation system is needed (radioactive gas → environmental contamination)
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Because xenon is fat-soluble, activity may be seen in the right upper quadrant in fatty liver; swallowed gas produces activity in the stomach. The trachea and large airways are not seen with gaseous agents
BOARD TIP
▸
"Energy of Xe-133?"
→ 81 keV (lower than Tc-99m).
▸
"V/Q order if Xe-133 is used?"
→ Ventilation FIRST (low energy first).
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"Most important phase of Xe-133?"
→ Washout phase → shows air trapping.
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"Disadvantage of Xe-133?"
→ Posterior projection only, special ventilation system needed.
On a posterior lung image the distribution of Xe-133 gas in the single-breath, equilibrium and washout phases is shown, with activity curves for a normal region and an air-trapping region; the air-trapping region is faint on single breath, fills at equilibrium and clears late on washout.
Continuous stream · no seeking
Key idea: air trapping shows reduced filling on single breath, filling at equilibrium and delayed clearance on washout; washout is the key phase.
Source: book (17.2: single breath, equilibrium 3-5 min, washout; washout phase most important; posterior only; 81 keV, ventilation first). Curves and time constants are representative.
How to use: a single click on the drawing pauses and resumes; drag the time bar below to any moment; ← → change phases (single breath, equilibrium, washout).
Did this animation help you understand the topic?
Figure 17.2: Single-breath, equilibrium and washout phases of a Xe-133 ventilation study; delayed washout in an area of air trapping (schematic).
B) Tc-99m DTPA Aerosol:
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Aerosol form → inhaled through a nebuliser
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Particle size: 0.5-2 μm (must be <2 μm to reach the alveoli)
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Energy: 140 keV (Tc-99m)
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Half-life: 6 hours (Tc-99m)
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Advantages:
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Tc-99m energy → same energy as perfusion → order not critical (although ventilation is usually first)
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The activity of the second study with the same radionuclide must be markedly higher (SNMMI/EANM 2026: perfusion count rate at least 4 and ideally 5 times that of ventilation; target ventilation count rate 1.0-1.5 kcps)
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Imaging can be performed in all projections (does not distribute rapidly like a gas)
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No special ventilation system needed
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Easy to administer, widely available
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Disadvantages:
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Central airway deposition → in areas of turbulent flow (COPD, bronchiectasis) → "clumping" artefact
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The washout phase cannot be assessed (aerosol → does not behave like a gas)
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Central deposition in smokers and COPD → image quality falls
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EANM: The most commonly used radioaerosol for ventilation; the nebuliser should preferably produce particles with a mass median aerodynamic diameter of 1-3 µm. SNMMI/EANM 2026: 900-1300 MBq is placed in the nebuliser and ~20-40 MBq reaches the lungs
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It is inhaled with slow tidal breathing and the particles are deposited by sedimentation
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Only ~5-10% of the activity in the nebuliser reaches the lungs. Normally the trachea and main bronchi, the stomach (swallowed aerosol), and the kidneys and bladder (absorbed DTPA) may be seen
BOARD TIP
▸
"Problem with Tc-99m DTPA aerosol in a COPD patient?"
→ Central airway deposition (clumping) → turbulent flow → homogeneous distribution disrupted.
▸
"Aerosol particle size?"
→ 0.5-2 μm (to reach the alveoli).
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"Advantage of DTPA aerosol?"
→ Imaging in all projections, no special ventilation system needed.
C) Tc-99m Technegas:
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Tc-99m bound to ultrafine carbon particles → "pseudo-gas"
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Particle size: 0.1 μm (very small → behaves like a gas)
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Advantages:
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Homogeneous gas-like distribution → good image quality even in COPD
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Very little central deposition (clumping) (superior to DTPA aerosol)
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Imaging in all projections
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Washout can be partly assessed
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Disadvantages:
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A special generator device is required
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FDA approval in the USA was obtained in 2023 (long widely used in Europe and Australia)
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Must not be produced in an oxygen atmosphere (Pertechnegas forms → clears rapidly from the alveoli, unsuitable for ventilation)
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EANM: Obtained by burning pertechnetate in a graphite crucible in an argon atmosphere at high temperature; particle size is 5-200 nm
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Inhaled with 1-3 slow breaths; deposits evenly by diffusion in the small airways and alveoli. The particles remain in the lung for days. Normal tidal breathing is recommended rather than deep inspiration, which accentuates the posterior 'rind' artefact on SPECT (SNMMI/EANM 2026)
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The activity reaching the patient is 20-30 MBq (EANM 2019; at least 100 MBq is placed in the nebuliser). SNMMI/EANM 2026: 400-900 MBq of pertechnetate is placed in the graphite crucible (a standard crucible holds 0.12-0.17 mL) and ~20-40 MBq reaches the lungs; it is used within 10 minutes of generation because the particles aggregate over time. Where available it is the preferred ventilation agent for most indications, including PE; 15 µSv/MBq, i.e. ~0.45 mSv for 30 MBq
BOARD TIP
▸
"Best ventilation agent in a COPD patient?"
→ Technegas (ultrafine particles, minimal central deposition).
▸
"Can Technegas be used in the USA?"
→ YES (FDA approval 2023).
▸
"Technegas particle size?"
→ ~0.1 μm (5-200 nm).
Figure 17.3: Particle size of ventilation agents and, in a COPD patient, central deposition of DTPA aerosol versus homogeneous distribution of Technegas (schematic).
Did this figure help you understand the topic?
D) Kr-81m (Krypton-81m) Gas:
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Energy: 190 keV
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Half-life: 13 seconds (ultra-short)
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Obtained from an Rb-81/Kr-81m generator
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Advantages:
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Ultra-short half-life → imaging during continuous inhalation → equilibrium image
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Simultaneous imaging with Tc-99m is possible (different energy window: 190 keV vs 140 keV)
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Imaging in all projections
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Requires little patient cooperation
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Disadvantages:
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The generator is very expensive and short-lived (Rb-81 half-life: 4.6 hours)
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Cyclotron production required
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Washout cannot be assessed (very short half-life)
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Not widely available
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EANM: The ventilation agent with the lowest radiation exposure: 27 nSv/MBq (~0.16 mSv for 6 GBq); the critical organ is the lung
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If breathing is very rapid, a steady state may not be reached and the distribution may not reflect true ventilation
BOARD TIP
▸
"Agent allowing ventilation imaging simultaneously with perfusion?"
→ Kr-81m (190 keV, different energy window from Tc-99m).
▸
"Half-life of Kr-81m?"
→ 13 seconds.
▸
"Disadvantage of Kr-81m?"
→ Very expensive, cyclotron needed, washout cannot be assessed.
Figure 17.4: Ventilation agent energy and V/Q order: Tc-99m scatter into the Xe-133 window (downscatter) and simultaneous imaging in separate windows with Kr-81m (schematic).
Did this figure help you understand the topic?
Comparison of Ventilation Agents:
| Feature | Xe-133 | Tc-99m DTPA Aerosol | Technegas | Kr-81m |
|---|---|---|---|---|
| Form | Gas | Aerosol | Pseudo-gas | Gas |
| Energy (keV) | 81 | 140 | 140 | 190 |
| Half-life | 5.3 days | 6 hours | 6 hours | 13 seconds |
| Particle size | Gas | 0.5-2 μm | ~0.1 μm (5-200 nm) | Gas |
| Projections | Posterior only | All | All | All |
| Quality in COPD | Good (washout) | Poor (clumping) | Very good | Good |
| Washout | YES (best) | NO | Partly | NO |
| Simultaneous V/Q | NO | NO | NO | YES |
| Availability | Moderate | Widespread | Limited | Rare |
Indications
Primary indication: Suspected pulmonary embolism (PE)
Situations in which V/Q scintigraphy is preferred to CT pulmonary angiography (CTPA):
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Contrast allergy
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Renal failure (risk of contrast nephropathy)
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Pregnancy (lower breast radiation dose)
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Young women (concern about breast radiation)
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Patients with a normal chest radiograph (V/Q has higher diagnostic accuracy)
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Situations in which CTPA is non-diagnostic
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Suspected CTEPH (V/Q is more sensitive). SNMMI/EANM 2026: V/Q (preferably SPECT) is also preferred in premenopausal women, pregnant patients, moderate-severe renal impairment and when iodinated contrast is contraindicated; the ATS and ACOG guidelines prefer V/Q to CTPA in pregnancy when the chest radiograph is normal
Situations in which CTPA is preferred:
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Abnormal chest radiograph (COPD, effusion, infiltrate)
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When an alternative diagnosis is sought
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Haemodynamic instability (rapid result needed)
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Generally more readily accessible
BOARD TIP
▸
"Preferred test for suspected PE in a pregnant patient?"
→ V/Q scintigraphy (breast dose lower than CTPA).
▸
"Suspected PE with a normal chest radiograph?"
→ V/Q scintigraphy has higher diagnostic accuracy.
▸
"Suspected PE in a COPD patient?"
→ CTPA preferred (high rate of intermediate probability on V/Q).
Alveolocapillary Permeability and Mucociliary Clearance (EANM)
Tc-99m DTPA aerosol clearance:
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Specific indication: Assessment of alveolocapillary permeability (interstitial lung disease, gas or particle exposure, pulmonary infection)
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In a healthy non-smoker clearance is <2% per minute; in an active smoker it is 2-5 times faster and early renal activity is seen
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Situations with markedly increased permeability: Active pulmonary fibrosis, sarcoidosis, pneumonitis, ARDS, Pneumocystis pneumonia, smoke or ozone exposure
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Situations with mildly reduced permeability: Primary ciliary dyskinesia, RAI treatment of lung metastases, diabetes with vascular complications, advanced age
Mucociliary clearance (Tc-99m nanocolloid):
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Nasal mucociliary clearance (NMC): 2 MBq is dropped onto the floor of the nose and the speed at which the activity moves to the pharynx is measured; normal mean 6 mm/min (2-12), in PCD ~0.2 mm/min (0-0.7)
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Pulmonary radioaerosol mucociliary clearance (PRMC): 2-10 MBq is inhaled; normal tracheobronchial speed ~4 mm/min (2-6); can be performed from 5 years of age
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Used as a screening test before biopsy when primary ciliary dyskinesia (PCD) is suspected; a normal PRMC result excludes PCD with great certainty (negative predictive value ~100%). An abnormal result alone, however, is not diagnostic; false positives are common and further tests are needed
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Non-absorbable particles (Tc-99m sulphur colloid or nanocolloid, albumin) are used to measure mucociliary clearance; because DTPA is absorbed from the alveoli, it measures alveolocapillary permeability, not mucociliary clearance
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More objective than the saccharin test; should be performed 3-6 weeks after an acute airway infection
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Ventilation scintigraphy can also show the presence of a bronchopleural fistula
BOARD TIP
▸
"What is DTPA aerosol clearance like in a smoker?"
→ 2-5 times faster (alveolocapillary permeability is increased).
▸
"Which nuclear medicine test is performed when PCD is suspected?"
→ Nasal or pulmonary mucociliary clearance measurement with Tc-99m nanocolloid.
17.3 V/Q Scintigraphy and the Diagnosis of Pulmonary Embolism1 questions
Principle of V/Q Mismatch
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Pulmonary embolism → occludes a pulmonary artery branch → perfusion is cut off but ventilation is preserved
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Result: Perfusion defect + Normal ventilation = MISMATCH → favours PE
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COPD, pneumonia, atelectasis → both perfusion and ventilation affected → MATCH → not PE
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Mortality in untreated PE is ~30%; because of the lung's dual blood supply (bronchial arteries), only ~10-15% of emboli progress to infarction, and infarction produces an opacity on the radiograph
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The chest radiograph is non-specific in PE (atelectasis and effusion are most common). The Westermark sign is regional oligaemia, Hampton's hump a pleura-based wedge-shaped infarct opacity, and the Fleischner sign enlargement of the central pulmonary artery
Defect size classification:
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Large: >75% of a segment
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Moderate: 25-75% of a segment
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Small: <25% of a segment
Stripe Sign
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A thin rim of perfusion seen at the periphery of a perfusion defect
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Not expected in PE (embolus → complete segmental occlusion)
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Stripe sign positive → low probability of PE → usually a non-embolic cause (COPD, fibrosis)
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Fissure sign: A linear perfusion defect along a fissure caused by pleural fluid in the fissure; it is not due to PE. In a supine patient a large effusion causes diffuse attenuation on posterior images
BOARD TIP
▸
"What does the stripe sign mean?"
→ A rim of perfusion at the periphery of a perfusion defect → low probability of PE → think of a non-embolic cause.
Figure 17.5: Mismatched and matched defect and stripe sign patterns on V/Q scintigraphy, anterior image (schematic).
Did this figure help you understand the topic?
17.4 PIOPED Criteria and Modified Criteria11 questions
Original PIOPED Criteria (1990)
The PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) study is the landmark study that assessed the accuracy of V/Q scintigraphy in the diagnosis of PE.
High Probability:
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≥2 large segmental mismatched perfusion defects (normal ventilation or normal chest radiograph)
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Or: 1 large + ≥2 moderate segmental mismatched defects
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Or: ≥4 moderate segmental mismatched defects
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Probability of PE: ~80-90%
Intermediate Probability:
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Findings that do not fit the high or low category
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1 moderate-to-large mismatched defect
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A single matched V/Q defect with a normal chest radiograph (defined as "borderline low" in revised PIOPED and assessed in the intermediate category)
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Probability of PE: ~20-30%
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The most problematic category → high rate of non-diagnostic results → further tests needed
Low Probability:
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Small perfusion defects
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Non-segmental defects (cardiomegaly, effusion, hilar enlargement)
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Triple match in the upper/middle zone (V/Q defect + matching opacity on the radiograph)
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Perfusion defect markedly smaller than the lesion on the chest radiograph
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Multiple or widespread matched V/Q defects with a normal chest radiograph (if perfusion remains normal in other areas)
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Probability of PE: ~10-15%
Normal / Very Low Probability:
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No perfusion defect or very small non-segmental defects
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Probability of PE: <5%
BOARD TIP
▸
"High-probability criterion in PIOPED?"
→ ≥2 large segmental mismatched defects.
▸
"Most problematic category?"
→ Intermediate probability → high non-diagnostic rate.
▸
"Does a normal V/Q exclude PE?"
→ YES, the negative predictive value is very high (~97%).
Figure 17.6: Perfusion defect size classes, original PIOPED high-probability combinations and probability of PE by category (schematic).
Did this figure help you understand the topic?
Modified PIOPED II Criteria
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Combined assessment of clinical probability (Wells score) and the V/Q result is recommended
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Low clinical probability + low V/Q probability → PE excluded (NPV ~96%)
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High clinical probability + high V/Q probability → PE diagnosed (PPV ~96%)
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Discordant results (low clinical + high V/Q or vice versa) → further tests needed (CTPA, lower limb Doppler)
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Wells score: <2 low, 2-6 intermediate, >6 high probability. If the Wells score is low and D-dimer negative, PE is excluded (NPV ~99%) and imaging is not needed; a positive D-dimer is non-specific
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PIOPED II "very low probability" (PE <10%): Non-segmental defect, defect smaller than the radiographic lesion, 1-3 small segmental defects, triple match involving a single segment in the middle or upper zone, stripe sign, large effusion without other defects
Simplified Interpretation by Modified Criteria
In current practice many centres use a simplified three-category interpretation:
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Normal: PE excluded
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Consistent with PE (positive): ≥1 segmental or ≥2 subsegmental mismatches → treatment
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Non-diagnostic: No definite interpretation possible → further tests
Figure 17.7: V/Q interpretation flow according to EANM criteria and combined assessment with clinical probability (modified PIOPED II).
Did this figure help you understand the topic?
EANM V/Q Interpretation Criteria:
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"PE present": V/Q mismatch of at least 1 segment or 2 subsegments conforming to pulmonary vascular anatomy
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"No PE": Normal perfusion; matched or reverse-mismatched (V > Q) defects of any number, size and shape; mismatch not showing a segmental, subsegmental or lobar pattern
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"Non-diagnostic for PE": Multiple V/Q abnormalities not typical of a specific disease
•
SNMMI/EANM 2026: this trinary reporting (PE present / PE absent / non-diagnostic) is used for SPECT; probabilistic (PIOPED) reporting has not been validated for SPECT and is not recommended. Trinary reporting is also preferred to probabilistic reports for planar studies. A single small mismatched defect is reported as negative on EANM criteria because its clinical significance is uncertain; the thromboembolism rate during follow-up is very low in patients reported negative with these criteria (<0.4% in one series)
•
Causes of V/Q mismatch other than PE: Chronic PE, obstruction by tumour, radiotherapy, vasculitis, vascular agenesis
•
CTEPH: If dyspnoea or PH persists after acute PE despite at least 3 months of anticoagulation, the screening test is V/Q scintigraphy (more sensitive than CTPA); a normal V/Q excludes CTEPH. In idiopathic PAH perfusion is normal or shows a non-segmental patchy distribution, whereas CTEPH shows segmental mismatch
•
The commonest cause of a false-positive mismatch is unresolved old PE. Emboli (especially small ones, and in young patients without comorbidity) may resolve within a day or persist; a proximal clot may fragment and move peripherally. A follow-up V/Q after treatment therefore provides a new baseline
•
A V/Q performed 3-6 months after anticoagulation provides a new baseline. Residual pulmonary vascular obstruction persists in 30-40% of patients after six months of anticoagulation and is associated with a 2-3-fold higher risk of recurrent venous thromboembolism. CTEPH develops in ~3% of PE survivors; up to 25% of patients with CTEPH have no documented history of PE (SNMMI/EANM 2026)
•
Other causes of mismatch: Vascular compression by bronchogenic carcinoma or hilar LAP, fibrosing mediastinitis, sarcoidosis, old TB, non-thrombotic embolism, AV malformation, pulmonary hypertension
•
Using the PIOPED criteria, up to 73% of studies were indeterminate
Triple-Match Finding
•
Perfusion defect + ventilation defect + opacity on the chest radiograph → triple match
•
Triple match in the lower lobes → probability of PE ~33% → should be assessed as intermediate
•
Triple match in the upper/middle lobes → low probability of PE
BOARD TIP
▸
"Triple match in a lower lobe?"
→ Probability of PE ~33% → intermediate category.
▸
"Triple match in an upper lobe?"
→ Low probability of PE.
▸
"Why is the lower lobe different?"
→ PE is most common in the lower lobes.
17.5 V/Q SPECT and SPECT/CT3 questions
V/Q SPECT
•
Higher sensitivity and specificity than planar V/Q
•
Three-dimensional assessment → detection of small subsegmental defects increases
•
The intermediate (non-diagnostic) rate falls markedly: usually <5%, and 1-3% in several large series (30-40% for planar; SNMMI/EANM 2026)
•
SNMMI/EANM 2026: V/Q SPECT is the preferred technique for most lung conditions, including PE, and adding a low-dose CT should be considered in most cases; planar V/Q is used when SPECT is unavailable (the EANM 2019 guideline also recommends SPECT)
V/Q SPECT/CT
•
Low-dose CT added to SPECT → anatomical correlation
•
Advantages:
–
Attenuation correction → fewer artefacts
–
Anatomical reference → localisation and characterisation of defects
–
Alternative diagnoses can be detected (pneumonia, effusion, tumour)
–
The non-diagnostic rate falls further
•
Disadvantage: Additional radiation dose (low-dose CT; ~1-2 mSv)
•
V/Q PET/CT: Performed with Ga-68 MAA (perfusion) and Ga-68 carbon nanoparticles (Galligas, ventilation); it offers better resolution and quantification, but is mostly still investigational
•
EANM: V/Q SPECT is diagnostic in at least 95% of cases; NPV for PE is ≥97%. In more than 1600 patients with a negative SPECT followed up without treatment, the false-negative rate was ≤1.5%
•
SPECT is well suited to quantifying PE burden: mismatched segments and subsegments are counted and expressed as a percentage of the total lung parenchyma; a low PE burden in a haemodynamically stable patient supports outpatient management. V/Q quotient images derived from the ratio of ventilation and perfusion counts show the location and extent of the defects (SNMMI/EANM 2026)
•
In direct comparison with planar imaging, the median sensitivity of SPECT is 21%, specificity 6% and accuracy 7% higher
•
With the addition of CT, specificity rose from 88% to 100% and false-positive reads fell from 18% to 0%
•
False mismatches accentuated by SPECT (none has a segmental pattern): the 'rind' effect (a band of ventilation in the dependent posterior lung of a supine patient; increased by deep breathing), linear reduction of perfusion along the fissures, and anterior shift of perfusion in left heart failure (antigravitational distribution; 5-15% of patients, mismatch mostly dorsal). Ventilation trapped in bullae in emphysema can also mimic a mismatch (SNMMI/EANM 2026)
•
Report content (SNMMI/EANM 2026): in addition to the common items (see 27), ventilation agent and perfusion activity, SPECT or planar technique and patient position; type and date of the chest radiograph, CT or CTPA used for comparison. Findings: distribution of ventilation and perfusion, site and number of mismatched defects at segmental or subsegmental level (extent has prognostic value); the conclusion is given as three categories rather than probabilities (PE present, PE absent, non-diagnostic; EANM criteria for SPECT). Pre- and post-test probability may be added; with SPECT/CT, lung and incidental findings on CT are reported, but a low-dose CT acquired only for attenuation correction is used cautiously for structural interpretation
BOARD TIP
▸
"Advantage of V/Q SPECT over planar V/Q?"
→ Higher sensitivity/specificity, the intermediate rate falls markedly.
▸
"Advantage of V/Q SPECT/CT?"
→ Attenuation correction + anatomical correlation + alternative diagnosis.
17.6 Preoperative Lung Function Assessment (Quantitative Perfusion)5 questions
Indication
•
Patients in whom lung resection is planned (lung cancer, bronchiectasis)
•
Postoperative predicted FEV1 calculation (predicted postoperative FEV1 – ppoFEV1)
•
Assessment of whether surgery is safe
Method
•
Tc-99m MAA perfusion scintigraphy → quantitative regional perfusion distribution
•
The contribution of each lung and each lobe to total perfusion is calculated as a percentage (%)
•
The contribution of the right and left lung is calculated from the mean of anterior and posterior counts (preferably the geometric mean)
•
Assessed together with preoperative spirometry (FEV1)
•
SNMMI/EANM 2026: lobar and segmental contributions are calculated most accurately with SPECT/CT (lobes are defined on CT). On planar imaging, usually three rectangular ROIs are drawn per lung; accuracy is limited because lobes and segments overlap. Either ventilation or perfusion images predict postoperative function well; in emphysema they show non-functional, hyperinflated regions before lung volume reduction therapy
•
Pitfalls: planar rectangular ROIs (three regions per lung) measure upper, middle and lower lung zones, not lobes; because of oblique fissures and lobar overlap they underestimate the right upper and lower lobes and overestimate the middle zone compared with SPECT/CT (differences may exceed 10-20%), whereas the right-left split is similar. Planar measurement can include extrapulmonary activity (stomach and thyroid from free pertechnetate, vascular activity) and lung crossing the midline. In a borderline patient planned for lobectomy, ppoFEV1 should therefore be calculated with SPECT/CT (SNMMI/EANM 2026)
Calculation of Predicted Postoperative FEV1 (ppoFEV1)
For pneumonectomy:
ppoFEV1 = Preoperative FEV1 × (1 − perfusion fraction of the lung to be resected)
Example: Preoperative FEV1 = 2.0 L, right lung perfusion contribution = 55%
ppoFEV1 = 2.0 × (1 − 0.55) = 2.0 × 0.45 = 0.90 L
For lobectomy:
ppoFEV1 = Preoperative FEV1 × [1 − (number of segments in the lobe to be resected / total number of functional segments) × perfusion fraction of the lung]
Surgical Safety Criteria
•
ppoFEV1 > 40% (predicted) or >0.8 L → surgery generally safe
•
ppoFEV1 30-40% → increased risk, further assessment needed (DLCO, exercise testing)
•
ppoFEV1 < 30% or <0.8 L → high risk, surgery generally contraindicated
•
ppoDLCO is calculated and assessed in the same way
BOARD TIP
▸
"Why is quantitative perfusion scintigraphy performed before pneumonectomy?"
→ ppoFEV1 calculation → to predict postoperative respiratory function.
▸
"ppoFEV1 safety limit?"
→ >40% predicted or >0.8 L.
▸
"Calculation formula?"
→ ppoFEV1 = Preop FEV1 × (1 − perfusion fraction of the lung to be resected).
Figure 17.8: ppoFEV1 calculation with quantitative perfusion scintigraphy: lobar segment numbers, a pneumonectomy example and surgical risk thresholds (schematic).
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Lung Segment Numbers
•
Right lung: 10 segments (upper lobe: 3, middle lobe: 2, lower lobe: 5)
•
Left lung: 8-9 segments (upper lobe: 4-5 [including lingula], lower lobe: 4)
•
Total: 18-19 segments
•
Report content (SNMMI/EANM 2026): in addition to the common items (see 27), position at administration of the perfusion (and, if used, ventilation) agent (upright or supine), planar or SPECT/CT technique and ROI method (rectangular ROIs or lobes defined on CT); contribution of the right and left lungs and, if requested, of each lobe to total perfusion as percentages; if requested, the ppoFEV1 and ppoDLCO calculation and the formula used. If lobar values were derived from planar images, it is stated that they are zonal (upper, middle, lower) values and may not reflect true lobar contribution
17.7 Right-to-Left Shunt Calculation10 questions
Principle
•
Normally all Tc-99m MAA particles are trapped in the pulmonary capillaries → do not enter the systemic circulation
•
With a right-to-left shunt → some particles bypass the lung capillaries → enter the systemic circulation
•
MAA uptake in systemic organs (brain, kidneys) → shows the presence of a shunt
•
Differential diagnosis of systemic activity: Right-to-left shunt (brain uptake is the most reliable indicator), free Tc-99m pertechnetate (thyroid and stomach seen, brain not seen) and particles <10 µm in size
•
Liver and spleen uptake in an MAA study: Due to RES uptake of small particles or of colloidal (reduced-hydrolysed) Tc-99m impurity
Indications
•
Congenital heart disease (ASD, VSD, tetralogy of Fallot, Eisenmenger syndrome)
•
Pulmonary arteriovenous malformation (AVM) → Osler-Weber-Rendu syndrome (HHT)
•
Hepatopulmonary syndrome → liver cirrhosis + intrapulmonary shunt
Calculation Method
•
Whole-body imaging after Tc-99m MAA injection
•
Activity in the lungs and in systemic organs (brain, kidneys, whole body) is measured
Shunt Percentage (%) = Systemic Activity / (Systemic Activity + Lung Activity) × 100
•
Systemic activity = Whole-body activity − Lung activity
•
The geometric mean is used (square root of the anterior × posterior product)
Normal values:
•
Normal right-to-left shunt: <5% (physiological, due to bronchial artery → pulmonary vein connections)
•
>5% → pathological shunt
•
As the shunt increases → MAA uptake in systemic organs (especially brain and kidneys) increases
In the first step MAA particles of different sizes travel down a narrowing pulmonary artery branch and lodge where the diameter falls to their size; very small ones pass the capillaries. In the second step, with a right-to-left shunt, some particles bypass the lung into the systemic circulation, the shunt percentage is counted and brain and kidney uptake rises on the whole-body image.
Continuous stream · no seeking
Key idea: MAA particles lodge in the precapillary arteriole that matches their size; with a right-to-left shunt particles that bypass the lung appear in brain and kidneys and the shunt fraction is systemic / total.
Source: book (17.1: 10-90 µm, mean 20-40 µm, 200,000-700,000 particles, ~300 million arterioles, 0.1-0.3%, T½ 2-9 h; 17.7: shunt formula, geometric mean, normal <5%, brain uptake). The vessel diameter model and particle size distribution are representative.
How to use: a single click on the drawing pauses and resumes; in the shunt step ↑ ↓ or the buttons below change the shunt fraction; ← → change steps.
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Figure 17.9: Right-to-left shunt assessment with Tc-99m MAA: particle path, shunt calculation and brain/kidney uptake in a shunt (schematic).
Clinical Importance
•
Pulmonary AVM: Shunt fraction usually between 5-30%
•
Osler-Weber-Rendu syndrome (HHT): Multiple pulmonary AVMs → high shunt fraction
•
Hepatopulmonary syndrome: Intrapulmonary vascular dilatation in liver cirrhosis → right-to-left shunt
•
Shunt fraction >5% → embolisation or surgical treatment should be considered
BOARD TIP
▸
"Normal right-to-left shunt fraction?"
→ <5%.
▸
"Which agent is used for shunt calculation?"
→ Tc-99m MAA.
▸
"Syndrome associated with pulmonary AVM?"
→ Osler-Weber-Rendu (HHT).
▸
"Shunt mechanism in hepatopulmonary syndrome?"
→ Intrapulmonary vascular dilatation → MAA particles pass through the capillaries.
Right-to-Left vs Left-to-Right Shunt
•
Right-to-left shunt: Assessed with MAA → particles enter the systemic circulation
•
Left-to-right shunt: Cannot be assessed with MAA → particles are trapped in the lungs anyway
•
Assessment of left-to-right shunt: The Qp/Qs ratio is calculated with radionuclide angiocardiography (first-pass study)
Qp/Qs Calculation (Left-to-Right Shunt):
•
A pulmonary time-activity curve is obtained with first-pass radionuclide angiocardiography
•
A gamma-variate fit is applied → first pass and recirculation are separated
•
In a left-to-right shunt the descending limb of the pulmonary curve is interrupted or slowed by early pulmonary recirculation and activity remains in the lung; normally recirculation is late and systemic
•
Qp/Qs > 1 → left-to-right shunt (pulmonary flow > systemic flow)
•
Qp/Qs = 1 → no shunt
•
Qp/Qs < 1 → right-to-left shunt (systemic flow > pulmonary flow)
•
Qp/Qs = A1/(A1−A2) (areas under the gamma-variate curves); the reliable measurement range is ~1.2-3.0. It cannot be calculated if the bolus is poor or there is tricuspid regurgitation (reflux into the IVC and hepatic veins). In a right-to-left shunt (Fallot) the left heart and aorta appear early
•
Normal: Qp/Qs = 1.0 ± 0.2
BOARD TIP
▸
"How is a left-to-right shunt assessed?"
→ Qp/Qs ratio with first-pass radionuclide angiocardiography.
▸
"Qp/Qs > 1.5 — what does it mean?"
→ Haemodynamically significant left-to-right shunt → surgical correction should be considered.
▸
"Can a left-to-right shunt be assessed with MAA?"
→ NO → particles are trapped in the lungs anyway.
Figure 17.10: Pulmonary time-activity curve on first-pass radionuclide angiocardiography and Qp/Qs calculation with gamma-variate analysis (schematic).
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Key Points for the Board
Perfusion Scintigraphy (Tc-99m MAA):
•
Particle size: 10-90 μm (mean 20-40 μm)
•
Standard particle number: 200,000-700,000
•
Proportion of arterioles occluded: 0.1-0.3% → haemodynamically safe
•
Injection position: Supine (to reduce the effect of gravity)
•
Biological half-life: 2-9 hours
•
Particle number in pulmonary hypertension: reduce to 100,000-150,000
•
In right-to-left shunt: Reduce particle number (risk of cerebral embolisation)
•
In pregnancy: Reduce activity (1-2 mCi); the particle number does not go below 100,000
•
Egg allergy → NOT a contraindication (MAA is made from human albumin)
•
If blood is drawn into the syringe → clot → "hot spot" artefact
Ventilation Agents – Comparison:
•
Xe-133: 81 keV, washout phase most important (air trapping), posterior projection only, ventilation must be performed FIRST
•
Tc-99m DTPA aerosol: 140 keV, 0.5-2 μm, clumping problem in COPD, all projections, most widely used
•
Technegas: 140 keV, FDA-approved (2023)
•
Kr-81m: 190 keV, 13 s half-life, simultaneous imaging with Tc-99m, very expensive
Principle of V/Q Mismatch:
•
Mismatch = perfusion defect + normal ventilation → favours PE
•
Match = perfusion + ventilation defect in the same area → not PE (COPD, pneumonia)
•
Reverse mismatch = ventilation defect + normal perfusion → mucus plug, bronchial obstruction
•
Stripe sign = rim of perfusion at the periphery of a perfusion defect → low probability of PE
•
Complete loss of perfusion to one lung is rare in PE → central tumour/compression by a hilar mass (if matched on ventilation: central carcinoma, foreign body, Swyer-James)
•
Reversal of the perfusion gradient (upper zone > lower zone) → pulmonary venous hypertension (left heart failure, mitral stenosis)
PIOPED Criteria:
•
High probability: ≥2 large segmental mismatches (probability of PE ~80-90%)
•
Intermediate: The most problematic category → high non-diagnostic rate
•
Low probability: Small defects, non-segmental defects, matched defects (probability of PE ~ 10-15%)
•
Triple match in a lower lobe: Probability of PE ~33% → intermediate
•
Normal: Probability of PE <5% → PE excluded
•
Triple match in an upper/middle lobe: Low probability of PE
•
Clinical probability (Wells score) and the V/Q result should be assessed together
•
PIOPED II very low probability (<10%): Non-segmental defect, 1-3 small segmental defects, single-segment triple match in the middle/upper zone, stripe sign, large effusion without other defects
•
V/Q is more sensitive than CTPA for CTEPH screening; a normal V/Q excludes CTEPH
Defect Size Classification:
•
Large: >75% of a segment
•
Moderate: 25-75% of a segment
•
Small: <25% of a segment
V/Q Scintigraphy vs CTPA:
•
V/Q preferred: Contrast allergy, renal failure, pregnancy, young woman, normal chest radiograph
•
CTPA preferred: Abnormal chest radiograph (COPD), alternative diagnosis sought, haemodynamic instability
V/Q SPECT and SPECT/CT:
•
SPECT → intermediate rate falls from 30-40% to <5% (SNMMI/EANM 2026)
•
SPECT/CT → attenuation correction + anatomical correlation + alternative diagnosis
Quantitative Perfusion (Preoperative):
•
ppoFEV1 = Preop FEV1 × (1 − perfusion fraction of the lung to be resected)
•
ppoFEV1 >40% or >0.8 L → surgery generally safe
•
ppoFEV1 30-40% → increased risk, further assessment
•
ppoFEV1 <30% or <0.8 L → high risk, generally contraindicated
•
Right lung segment number: 10, Left lung: 8-9, Total: 18-19
Shunt Calculation:
•
Right-to-left shunt: With Tc-99m MAA → uptake in systemic organs → normal <5%
•
Systemic activity after MAA: Brain uptake → right-to-left shunt; thyroid/stomach (no brain) → free pertechnetate
•
Left-to-right shunt: First-pass radionuclide angiocardiography → Qp/Qs ratio
•
Qp/Qs = 1.0 → normal
•
Qp/Qs > 1 → left-to-right shunt
•
Qp/Qs < 1 → right-to-left shunt
•
Qp/Qs > 1.5 → haemodynamically significant → consider surgical correction
•
Pulmonary AVM → Osler-Weber-Rendu syndrome (HHT)
•
Hepatopulmonary syndrome → cirrhosis + intrapulmonary vascular dilatation
Frequently Asked Board Themes:
•
"Preferred test for suspected PE in a pregnant patient?" → V/Q scintigraphy (low breast dose)
•
"Best ventilation agent in COPD?" → Technegas
•
"V/Q order with Xe-133?" → Ventilation FIRST (low energy first)
•
"Agent allowing simultaneous V/Q?" → Kr-81m (190 keV)
•
"PIOPED high-probability criterion?" → ≥2 large segmental mismatches
•
"Stripe sign?" → Low probability of PE
•
"Triple match in a lower lobe?" → Probability of PE ~33% (intermediate)
•
"ppoFEV1 safety limit?" → >0.8 L or >40%
•
"Normal right-to-left shunt?" → <5%
•
"How is a left-to-right shunt assessed?" → First-pass angiocardiography, Qp/Qs
•
"Can a left-to-right shunt be assessed with MAA?" → NO
Additional Notes from EANM Guidelines:
•
MAA: 40-120 MBq, 11 µSv/MBq, breastfeeding 12 hours; <100,000 particles (SNMMI/EANM 2026) or non-supine injection → irregular distribution
•
EANM PE criterion: ≥1 segment or ≥2 subsegment mismatch; V/Q SPECT ≥95% diagnostic, NPV ≥97%; with CT specificity 88% → 100%
•
Ventilation doses: Kr-81m lowest (27 nSv/MBq); Technegas 20-30 MBq (15 µSv/MBq); DTPA aerosol 900-1300 MBq in the nebuliser (SNMMI/EANM 2026)
•
DTPA aerosol clearance: Normal <2%/min; 2-5 times faster in smokers; increased in fibrosis, sarcoidosis, ARDS, PCP
•
Mucociliary clearance: Normal nasal ~6 mm/min, tracheobronchial ~4 mm/min; ~0.2 mm/min in PCD
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.
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