Today, technetium-99m-labelled macroaggregated albumin (^99mTc-MAA) has replaced the iodine-based perfusion tracers, but otherwise the technique has remained virtually unchanged since 1964. Usually, 200,000–500,000 particles are injected intravenously with the patient in the supine position to limit the effect of gravity on regional pulmonary arterial blood flow. The particles mix uniformly with venous blood and are subsequently distributed homogenously in the pulmonary circulation. The caliber of precapillary arterioles is usually < 15 μm, while ^99mTc MAA particles measure between 10 and 90 μm. They cause transient blockage of about 0.1 % of the capillary bed; the biologic half-life of the particles is usually 3–4 h before they are hydrolyzed to smaller particles by enzymatic hydrolysis and cleared by phagocytosis. The administered dose of radioactivity is usually 100–200 MBq yielding an effective dose of 2–3 mSv (mean annual background radiation constitutes ca. 3 mSv worldwide). The dose should be reduced in pregnant women, while the number of particles should be reduced according to weight in children (<35 kg) and may be reduced in patients suspected of right-to-left shunt (to minimize the risk of systemic emboli) or pulmonary hypertension (to reduce the risk of severe pulmonary deterioration as the particles lodge more centrally due to reduced lumen) (Bajc et al. 2009a; Ciofetta et al. 2007).

Ventilation tracers are either gaseous or aerosols. Of the former, the preferred tracer is krypton-81m, a noble gas with a 13 s physical half-life. Thus, is has to be breathed continuously by mask during image acquisition which most patients with impaired respiration can accommodate. However, krypton-81m is produced from rubidium-81 with a physical half-life of 4.7 h, and the generator lifetime is therefore only 1 day which may limit availability due to relatively high costs. Particularly in Europe, an aerosol labelled with technetium-99m (^99mTc-Technegas®) is now replacing krypton-81m. It is produced by nebulizing the radiopharmaceutical into a fine mist for inhalation. In contrast to krypton-81m, technetium-99m is widely available and relatively inexpensive. Both have ideal energies for gamma camera imaging, but the aerosols are not always uniformly distributed as their regional distribution in the lungs reflects local ventilation. Furthermore, the ultrafine particles may be caught in mucus in the central airways of COPD patients, and not all patients can cooperate to the relatively deep inhalations required (Bajc et al. 2009a, 2010).

In suspected PE, most centers routinely combine perfusion and ventilation images in corresponding projections (Figs. 3, 4, and 5).

Images may be acquired as planar (two-dimensional) in which case they should include 4–8 views of the lungs, i.e. anterior and posterior views, right and left lateral views, and right and left posterior oblique views. However, despite numerous projections, planar perfusion imaging may not be sufficient to clearly visualize all segments of the lungs; especially solitary segmental defects in the basal medial segments of the right lower lobe may go undetected. Segments devoid of radioactivity in these regions will be obscured by the radioactivity in the surrounding segments that completely encompass it. Thus, in recent years single photon emission computed tomography (SPECT) imaging has become much more widespread: SPECT enables three-dimensional image acquisition by rotation of the gamma camera around the patient. Images are subsequently reconstructed to be displayed in three projections (i.e. transaxial, sagittal, and coronal), much like conventional CT (Fig. 6).

SPECT images may even be co-registered with CT (SPECT/CT) to combine the physiological data from the radiotracer distribution with the radiological (structural) information from CT. The downside of SPECT is longer acquisition time of ca. 30 min for a complete ventilation/perfusion scintigraphy, which may be rather lengthy to lay still and flat for patients with respiratory impairment. The CT acquisition only takes a few minutes.

To date, the comprehensive multicenter Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study from 1990 remains the landmark study on combined V/Q-scan in suspected PE (PIOPED Investigators 1990). It included 933 consecutive patients of which 755 underwent both V/Q-scan and the reference standard pulmonary angiography. V/Q-scans were reported probabilistic, i.e. scan results were divided into four categories based on comprehensive, but somewhat cumbersome interpretation criteria, i.e. high, intermediate, or low probability for PE or normal scans (Table 1).

The results clearly stated that, in conclusive cases, sensitivity and specificity was high: If all abnormal scans (high, intermediate, or low) were considered indicative of PE, sensitivity was 98 %, but specificity only 10 %; which means all PE would be diagnosed and a normal scan would safely rule out the diagnosis. If on the other hand only high probability scans were considered diagnostic for PE, sensitivity was only 41 %, but specificity increased to 98 %; which means not all PE would be diagnosed but a positive scan would be very specific for PE. Thus, a high probability scan accurately diagnoses PE, whereas normal scans safely rules out the diagnosis. Unfortunately, less than half of the scans were in either category with the remainder being intermediate or low probability scans, and both categories are considered non-diagnostic as PE is present in 31 % and 12 % of cases, respectively. The combination of clinical pretest probability and V/Q-scan results could to some extent mitigate these numbers, i.e. in patients with low-probability V/Q-scans and low clinical pretest probability of PE, the negative predictive value was 96 %, but this combination only occurred in a minority of patients. Thus, the conclusions of the study, which still stands today at its 25-years anniversary, were those already mentioned, i.e. in conclusive patients V/Q-scans reliably established and ruled out PE, but in many patients further imaging is necessary. Some additional shortcomings of PIOPED study need to be mentioned. First and foremost, the interpretation criteria are themselves relatively complicated and may therefore seem cumbersome to use in daily clinical practice. They are not based solely on mismatched defects, but a rather intricate assessment which to some extent seems arbitrarily outlined and prone to subjectivity. This is to some extent evident from the inter-observer variability in scan interpretation. As expected, agreement among readers was excellent for normal and high probability scans (92–95 %), but not as good for intermediate and low probability studies. Furthermore, since pulmonary angiography (PA) was omitted for ethical reasons in 176 patients with low probability or normal V/Q-scans, selection bias may have been introduced towards patients with intermediate or high probability scans leading to overestimation of sensitivity and underestimation of specificity (Stein and Gottschalk 1994).