99mTc-labelled macro-aggregated human albumin (99mTc-MAA) particles are used to assess the regional distribution of the lung perfusion. 99mTc-MAA is injected intravenously and passes through the pulmonary arteries to the lung capillaries and arterioles, where the 99mTc-MAA particles are trapped due to their relatively large size (10-100 µm). If there is no obstruction of the flow, then there is a uniform lung capillaries and arterioles, where the 99mTc-MAA particles are trapped due to their relatively large size (10-100 µm). If there is no obstruction of the flow, then there is a uniform lung perfusion distribution. Perfusion defects are seen peripherally to obstructions of flow from e.g. pulmonary embolism (PE). Since primary ventilation abnormalities with associated hypoxic vasoconstriction can also create perfusion defects, combined ventilation and perfusion (V/Q) scintigraphy is often performed to better diagnose the disease.
Indications for lung perfusion scintigraphy include but are not limited to:
Diagnosis and follow-up of pulmonary embolism (PE);
Evaluate the cause of pulmonary hypertension;
Quantify regional pulmonary function before surgery/radiation therapy for lung cancer;
Evaluate lung transplants;
Evaluate emphysema for lung volume reduction intervention;
Evaluate congenital heart or lung disease such as cardiac shunts, pulmonary arterial stenosis, and arteriovenous fistulae and their treatment;
Evaluate chronic pulmonary parenchymal disorders;
Evaluate shunts or arteriovenous fistulae.
Hypersensitivity to the active substance or to any of the excipients and in case of severe pulmonary hypertension.
Precaution:
Breast feeding should be interrupted for 12 h following the examination [3,91].
In case of pulmonary hypertension or right-to-left shunt, a reduced number of injected particles should be considered. Multiple injections are required in some complex malformations, depending on anatomy and surgery (i.e. persistent left superior vena cava, cavo-pulmonaryu anastomosis) [92].
Most 99mTc-MAA perfusion studies are used for PE work-up. A normal scan excludes PE. If the perfusion scan is abnormal, then a ventilation scan is needed for the interpretation. So, in many cases a V/Q scintigraphy is performed. Using the prospective investigation of pulmonary embolism diagnosis (PIOPED) criteria, up to 73% of studies were indeterminate. Hence, instead of planar V/Q scintigraphy and PIOPED interpretation criteria, V/Q SPECT or V/Q SPECT/CT with trinary interpretation are often used. Many studies demonstrate enhanced sensitivity and specificity as well as reduction in the non-diagnostic rate in favour of V/Q SPECT and V/Q SPECT/CT. In clinical head-to-head comparisons of V/Q SPECT and planar scintigraphy, more and smaller defects were seen on SPECT, and higher sensitivity (21% in median), specificity (6%), and accuracy (7%) were found. Moreover, V/Q SPECT is diagnostic in ≥95% of cases and feasible in almost all patients. The negative predictive value of V/Q SPECT for PE is ≥97%, and long-term outcome of with-holding anti-thrombotic treatment after a negative SPECT has been studied in over 1600 patients with ≤1.5% false negatives, which is similar to reported values for planar V/Q studies and CT pulmonary angiogram studies.
The diagnostic value can be increased further by V/Q SPECT/CT, because the low dose CT gives information about the lung parenchyma, which could provide alternative explanations and allow attenuation correction. In a prospective head-to-head study, simultaneously obtained V/Q SPECT, V/Q SPECT/CT, and CT pulmonary angiography were compared. Adding CT to V/Q SPECT increased specificity (from 88 to 100%) by reducing false positive readings (from 18 to 0%) without hampering sensitivity (still 97%) and reduced inconclusive tests (from 5 to 0%). The highest diagnostic accuracy was obtained by V/Q SPECT/CT.
The use of V/Q SPECT and SPECT/CT over planar imaging in indications other than PE is not evidence based, but it is likely valuable, if identification of smaller perfusion defects is clinically relevant.
The suggested activities to administer for adults range from 40 MBq to 120 MBq.
In paediatric nuclear medicine, the particle number should be adjusted to the patient’s weight and the activities should be modified according to the EANM paediatric dosage card (https://www.eanm.org/publications/dosage-calculator/). The minimum recommended activity is 10 MBq.
The effective dose per administered activity is 11 µSv/MBq [3]. The effective dose for a reference activity of 100 MBq is 1.1 mSv.
Caveat
“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."
Interpretation of PE using the EANM guidelines: “PE” is reported if there is V/Q mismatch of ≥1 segment or 2 subsegments that conforms to the pulmonary vascular anatomy.
“No PE” is reported if there is a normal perfusion pattern conforming to the anatomic boundaries of the lung, if there are matched or reversed mismatch V/Q defects (any number, size, shape), or a V/Q mismatch that does not have a subsegmental, segmental, or lobar pattern. “Non-diagnostic for PE” is reported if there are multiple V/Q abnormalities not typical of specific disease.
Other interpretations: V/Q mismatch can result from any cause of pulmonary arterial blood flow obstruction as acute and chronic PE, tumour obstruction, radiation therapy, vasculitis, agenesia of vessels, etc.
V/Q match or even inverse V/Q mismatch (V defects >Q defects) result from primary ventilation abnormalities with associated hypoxic vasoconstriction as seen in COPD, asthma, cystic fibrosis, lung fibrosis, atelectasis, tumour, pneumonia, pleura effusion, etc.
The major pitfalls include:
A recent standard chest radiograph or a CT scan can help in the interpretation. However, this is not needed if a CT scan is performed as part of a SPECT/CT procedure.
The detailed recommendations are available in the EANM Plumonary Embolism Guidelines. Further information can be found in the published literature [93].