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V/Q scanning in CTEPH

This ventilation/perfusion (V/Q) scan primer has been prepared by Dr Richard Channick, Associate Professor of Medicine at Harvard Medical School, Boston, Massachusetts, based on the 2009 European Association of Nuclear Medicine guidelines for ventilation perfusion scintigraphy.1

 

Context

Pulmonary embolism (PE) can only be diagnosed with imaging techniques.1 These include:

  • Multidetector computed tomography (CT) of the pulmonary arteries, which has become the screening tool of choice for acute PE1,2

    • A good-quality CT pulmonary angiogram that is negative for acute PE effectively rules that diagnosis out2

  • V/Q scintigraphy1

    • A normal V/Q scan also rules out PE2

 

The V/Q scan, however, is the preferred and recommended screening test for chronic thromboembolic pulmonary hypertension (CTEPH), a severe, long-term complication of acute PE that can potentially be cured only with pulmonary thromboendarterectomy (PTE) surgery.3-5

 

  • V/Q scan has >96% sensitivity for CTEPH6

  • While a normal V/Q scan effectively rules out the presence of CTEPH, the use of CT pulmonary angiography for CTEPH screening may lead to underdiagnosis of CTEPH3,6

 

Basic principles of the V/Q scan

  • Each bronchopulmonary segment is supplied by a single end artery, and V/Q scanning makes use of this unique characteristic of pulmonary arterial segmental anatomy1

  • In principle, conical bronchopulmonary segments have their apexes toward the hilum, while their bases project onto the pleural surface1

  • Occlusive thrombi that affect individual pulmonary arteries produce characteristic lobar, segmental, or subsegmental peripheral, wedge-shaped defects with the bases projecting to the lung periphery1

 

Anatomy

This map shows the lungs as frontal slices from anterior (upper left) to posterior (upper right) and sagittal slices from right periphery (lower left) to left periphery (lower right).

lung anatomy graphic

Segmental map

segmental map image

Ventilation component

The ventilation scan maps regional ventilation and helps define lung borders. It may also provide information about non-PE cardiopulmonary disorders1:

  • In chronic obstructive pulmonary disease (COPD), distribution of ventilation is uneven, and in aerosol studies, focal deposition is often seen in central or peripheral airways

  • Pneumonias cause regional ventilation defects, which are usually more extensive than associated perfusion defects. Preserved perfusion along the pleural border—called the “stripe sign”—may be seen

 

Ventilation materials

  • 133Xe has historically been the agent of choice for ventilation studies, including in PIOPED I.7 Its half-life is 5 days, and it allows studies of regional ventilation1

  • 133Xe is less commonly used now due to cost and availability. However, it may be preferable to reduce deposition problems with aerosols

 

Aerosols

  • For ventilation scintigraphy, radioaerosols are now commonly used. Aerosols are relatively time-stable, two-phase systems consisting of particles suspended in air1

  • The radiolabeled particles may be liquid, solid, or a combination of the two. The proportion of particles remaining in the lung after inhalation, called the deposition fraction, depends on the aerodynamic properties, mainly their size, of the particles1

    • The deposition fraction can be up to 50% with ultrafine nanoparticles of diameter 0.02 nm

 

99mTc-DTPA

  • 99mTc-DTPA is the most commonly used aerosol1

    • It’s cleared from the alveolar region by transepithelial diffusion

    • Its half-life ranges from about 80 minutes in healthy nonsmokers to 24 minutes in healthy smokers

    • Resorbed 99mTc-DTPA is excreted via glomerular filtration in the kidneys1

 

Technegas

  • Technegas is an aerosol made up of extremely small (about 0.005 to 0.2 μm in diameter) 99mTc-labelled solid graphite particles generated at high temperature1

    • Technegas particles are hydrophobic but tend to grow by aggregation

    • They should be used within 10 minutes of generation

  • Hot spots are rarely seen with 99mTc-Technegas in patients with airway obstruction1

 

Perfusion component

  • Radiolabeled particles (between 15 and 100 μm in diameter) are injected into a peripheral vein to achieve microembolization1

    • The commercially used particles are microaggregated albumin (MAA), which are labelled with 99mTc

    • Particles lodge in the pulmonary capillaries and in the precapillary arterioles

    • Particle distribution defines regional lung perfusion

  • An important factor in the success of the study is the number of particles injected1

    • At minimum, 60,000 particles must be injected to obtain uniform distribution of activity reflecting regional perfusion

    • Typically, though, about 400,000 radiolabeled particles are injected for the scan

    • There are more than 280 billion pulmonary capillaries and 300 million precapillary arterioles, so injecting up to 400,000 particles will result in obstruction of only a very small fraction of pulmonary vessels

      • Still, a reduction to between 100,000 and 200,000 particles injected is recommended for patients who have confirmed pulmonary hypertension

 

Protocol

  • In most cases, ventilation and perfusion should both be done in a single day1

    • Among elderly patients, up to 60% of perfusion-only scans may result in false-positive findings, since prevalence of obstructive airway disease increases significantly with age

    • On the other hand, ventilation scans are often normal in healthy younger persons

    • To cut down on radiation exposure, a ventilation scan can be avoided in most patients with suspected PE during the first trimester of pregnancy

  • Planar imaging is performed with at least four views, including anterior, posterior, left and right posterior oblique1

    • More commonly, 6 to 8 views are now done

    • The recommended matrix size is 256×256, used with a high-resolution, low-energy collimator

      • 500 to 1,000 kcounts per view is recommended

  • To minimize vertical ventilation and perfusion gradients, inhalation of aerosols and IV injections of MAA should be performed with the patient in the supine position1

 

V/Q mismatch

  • Ventilation is usually preserved within the bronchopulmonary segments affected by PE, while perfusion is absent1

    • This pattern of preserved ventilation with no perfusion within a lung segment is called V/Q mismatch, and it provides the basis for PE diagnosis using V/Q scanning

  • A normal pulmonary perfusion pattern effectively excludes PE1

  • V/Q mismatches can be caused by conditions other than PE, including1:

    • Congenital pulmonary vascular abnormalities, veno-occlusive disease, vasculitis, lung cancer, or mediastinal adenopathy

 

Typical defect

Below is a sagittal slice of the left lung in a patient with PE. The perfusion defect is wedge-shaped (arrow). Ventilation is preserved. The abnormality is highlighted in the V/Q quotient image (arrow).

PE defect image

Interpretation of V/Q scans

  • Probabilistic interpretation based on simplistic criteria were promoted through the PIOPED I study: high, intermediate, low, and very low probability scans and indeterminate (ie, nondiagnostic) examinations were the terms used1,7

  • However, that may not be the best method. According to Bayes’ theorem, probability cannot be defined from a single test without taking into account prior probability1

  • In fact, such a technique can be misleading—for example, low probability interpretation when a patient likely has PE

 

Basic criteria for reading images

  • Interpreter’s knowledge and experience, according to the principle of “gestalt,” must be applied

  • Pretest probability must be in accordance with the principle of “holistic” interpretation; that is, it must take into account all available data1

  • In other words, the clinician should be interpreting the scan

 

A V/Q Scan

V/Q scan image

Interpretation of V/Q scans

No PE is reported if there is/are:

  • Normal perfusion pattern conforming to the anatomic boundaries of the lungs

  • Matched or reversed mismatch V/Q defects of any size, shape, or number in the absence of mismatch

  • Mismatch that does not have a lobar, segmental, or subsegmental pattern

 

PE is reported if there is:

  • V/Q mismatch of at least one segment or two subsegments that conforms to the pulmonary vascular anatomy

 

Nondiagnostic for PE is reported if there are:

  • Multiple V/Q abnormalities not typical of specific diseases

 

Typical examples of V/Q findings

 

“Chronic” PE missed on CT scan but clearly evident on V/Q scan1

scan image

PE can be diagnosed in COPD with V/Q scan1

COPD scan image

Heart failure: redistribution of perfusion1

heart failure scan image

Pneumonia, showing “stripe sign” (arrow)1

pneumonia scan image

Technical issues

Technical artifacts may arise from how the 99mTc-MAA was handled prior to injection.1

  • If blood is drawn into the syringe containing the 99mTc-MAA, aggregation of the particles may result, creating hot spots in the images1

  • Failure to resuspend 99mTc-MAA particles prior to administration may also result in hot spots1

  • Planar imaging may underestimate the presence or extent of perfusion abnormalities because of superposition of lung regions with normal perfusion1

    • This circumstance is reflected as “shine-through” masking of embolized regions

    • It is essential to look at all projections to rule out shine-through

 

Unilateral absence of perfusion in a whole lung with preserved ventilation and without any V/Q mismatch in the other lung is generally not due to PE. 1

  • In such cases, a CT scan of the thorax may reveal the presence of other pathologies, such as tumor and other mediastinal processes, congenital pulmonary vascular abnormalities, or aortic aneurysm1

 

Shine-through seen on left lateral (arrow)

Shine-through image
See the first case study

References:

1. Bajc M, Neilly JB, Miniati M, et al. EANM guidelines for ventilation/perfusion scintigraphy: part 1. pulmonary imaging with ventilation/perfusion single photon emission tomography. Eur J Nucl Med Mol Imaging. 2009;36(8):1356-1370. 2. Tapson VF. Advances in the diagnosis and treatment of acute pulmonary embolism. F1000 Med Rep. 2012;4:9. 3. Kim NH, Delcroix M, Jenkins DP, et al. Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol. 2013;62(suppl D):D92-D99. 4. Klok FA, van der Hulle T, den Exter PL, et al. The post-PE syndrome: a new concept for chronic complications of pulmonary embolism. Blood Rev. 2014;28(6):221-226. 5. Keogh AM, Mayer E, Benza RL, et al. Interventional and surgical modalities of treatment in pulmonary hypertension. J Am Coll Cardiol. 2009;54(suppl 1):S67-S77. 6. Tunariu N, Gibbs SJR, Win Z, et al. Ventilation–perfusion scintigraphy is more sensitive than multidetector CTPA in detecting chronic thromboembolic pulmonary disease as a treatable cause of pulmonary hypertension. J Nucl Med. 2007;48(5):680-684. 7. PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263(20):2753-2759.

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