# Ventilation-Perfusion Scintigraphy

## Introduction

Ventilation-perfusion (V/Q) scintigraphy remains a valuable diagnostic tool for the evaluation of **pulmonary embolism (PE)**, particularly in patients with contraindications to CT pulmonary angiography (CTPA).

## Radiopharmaceuticals

### Perfusion Agents

**Technetium-99m macroaggregated albumin (Tc-99m MAA)** is the standard perfusion agent. The particles range from **10-90 micrometers** in diameter and lodge in precapillary arterioles. Approximately **200,000-700,000 particles** are injected, occluding less than 0.1% of pulmonary arterioles. The patient should be **supine during injection** to ensure uniform distribution, as upright injection causes a gradient artifact. In patients with known **right-to-left shunts**, the particle count should be reduced to approximately 100,000-150,000. In pregnancy, both particle count and activity are reduced.

### Ventilation Agents

**Xenon-133 gas** provides single-breath, equilibrium, and washout phases that detect air trapping. Its 81 keV energy is lower than Tc-99m, so ventilation must be performed first. **Technetium-99m DTPA aerosol** is widely available but may show central deposition (clumping artifact) in patients with obstructive airway disease. **Technetium-99m Technegas** consists of ultrafine carbon particles labeled with Tc-99m that achieve excellent peripheral penetration and are less affected by obstructive airways disease, though it is not available in the US. **Krypton-81m gas** has a 13-second half-life and allows simultaneous V/Q imaging but has limited availability.

## Acquisition Protocol

### Perfusion Imaging

**Eight standard views** are acquired: anterior, posterior, right lateral, left lateral, right posterior oblique, left posterior oblique, right anterior oblique, and left anterior oblique. Each view is acquired for approximately 500,000-750,000 counts. SPECT/CT acquisition is increasingly used for improved sensitivity and specificity.

### Ventilation Imaging

Ventilation imaging is performed before or after perfusion depending on the agent. Xenon-133 is acquired in a single posterior projection through single-breath, equilibrium (3-5 minutes), and washout (2-3 minutes) phases. Tc-99m aerosol or Technegas allows multiple projections matching the perfusion views.

### Chest Radiograph Correlation

A **recent chest radiograph** (within 12-24 hours) is essential for interpretation because parenchymal opacities can cause matched V/Q defects that mimic PE. A normal chest radiograph increases the diagnostic value of the V/Q scan.

## Interpretation Criteria

### PIOPED II Modified Criteria

| PIOPED II Category | Findings | PE Likelihood |
|-------------------|----------|---------------|
| Normal | No perfusion defects | Excludes PE |
| Very low probability | Non-segmental defects (cardiomegaly, elevated diaphragm) | <10% |
| Low probability | Small subsegmental defects or matched V/Q with CXR abnormality | ~15% |
| Intermediate probability | Difficult to categorize; 1 moderate mismatched defect | ~30% |
| High probability | >=2 large segmental mismatched defects | ~97% specificity |

A **normal** scan shows no perfusion defects and excludes PE. A **very low probability** scan shows non-segmental perfusion defects such as those from cardiomegaly, elevated hemidiaphragm, or costophrenic angle defects. A **low probability** scan shows small subsegmental perfusion defects or matched V/Q defects with a corresponding chest radiograph abnormality. An **intermediate probability** scan is difficult to categorize and often requires further workup. A **high probability** scan shows **two or more large segmental perfusion defects** (or equivalent) with normal ventilation (mismatch), with a specificity for PE of approximately 97%.

### PISAPED Criteria (Perfusion-Only Interpretation)

The PISAPED criteria focus on the **shape and distribution** of perfusion defects. **Wedge-shaped, segmental perfusion defects** are considered PE-positive, while non-wedge-shaped defects (such as the stripe sign or non-segmental defects) are considered PE-negative. This approach eliminates the need for ventilation imaging in some protocols.

### Key Interpretive Signs

The **stripe sign** is a stripe of preserved perfusion between the defect and the pleural surface, which argues against PE and suggests parenchymal disease. Only **segmental defects** conforming to pulmonary arterial anatomy suggest PE, while non-segmental defects do not. A **triple match** -- matched ventilation, perfusion, and chest radiograph abnormality in the lower lobes -- is classified as intermediate probability because it could represent PE or atelectasis/pneumonia.

## SPECT V/Q Imaging

SPECT and SPECT/CT improve sensitivity and specificity compared to planar imaging. They reduce the proportion of **indeterminate studies** from approximately 30-40% to less than 5%. The CT component provides anatomic correlation and may identify alternative diagnoses. European guidelines recommend SPECT V/Q as first-line, and it is increasingly adopted in North America. Automated quantitative analysis software is available for standardized reporting.

## Clinical Applications Beyond PE

### Quantitative Lung Perfusion

Quantitative lung perfusion is used for **pre-operative assessment** before lung resection (pneumonectomy or lobectomy). Differential perfusion to each lung is calculated as a percentage of total counts. **Predicted post-operative FEV1** is calculated by multiplying the pre-operative FEV1 by the percentage of perfusion to the remaining lung. A minimum predicted post-operative FEV1 of greater than 800 mL or greater than 40% predicted is generally required for surgery.

### Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

The V/Q scan is the **screening test of choice** for CTEPH. One or more **segmental or larger mismatched perfusion defects** are highly sensitive for CTEPH, and a normal V/Q scan effectively excludes it. CTPA may miss subsegmental chronic thrombi that V/Q scintigraphy detects.

### Right-to-Left Shunt Quantification

Tc-99m MAA particles that traverse a right-to-left shunt lodge in systemic capillary beds. **Brain and kidney uptake** on whole-body images quantifies the shunt fraction, which is normally less than 5%.

## Clinical Pearls

**Two or more large segmental mismatched perfusion defects** constitute a high-probability scan with approximately 97% specificity for PE. V/Q scan is preferred over CTPA in patients with **contrast allergy, renal insufficiency, or pregnancy** (though institutional protocols vary for pregnancy). SPECT V/Q significantly reduces indeterminate results compared to planar imaging. V/Q scintigraphy is the **screening test of choice for CTEPH** and is more sensitive than CTPA for this diagnosis.

## References

1. PIOPED II Investigators: Diagnostic Pathways in Acute Pulmonary Embolism. *JAMA*. 2006;295(2):172-179.
2. EANM Guidelines for Ventilation/Perfusion Scintigraphy. *Eur J Nucl Med Mol Imaging*. 2019;46(12):2429-2451.
3. V/Q SPECT and SPECT/CT in the Diagnosis of Pulmonary Embolism. *Semin Nucl Med*. 2017;47(6):584-598.
4. Chronic Thromboembolic Pulmonary Hypertension: Role of Imaging. *Radiographics*. 2020;40(4):1046-1068.