Figure 7. Single coronal SPECT image through the mid thorax demonstrates increased accumulation of 99mTc-DMP-444 (99mTc-GP IIb/IIIa antagonist) in a patient with documented PE within the right lower lobe, left main and left lower pulmonary arteries (arrows).

involves the cross-linking of fibrinogen and GPIIb/IIIa receptor on activated platelets. The Food and Drug Administration in the US has recently approved apcitide (AcuTect®), a 99mTc-labelled synthetic peptide which binds to the GPIIb/IIIa receptor, for evaluation of patients with suspected DVT. The main advantage of this agent is its ability to distinguish between acute and chronic DVT. Several 99mTc-labelled peptides directed against activated platelets are currently under investigation for the evaluation of patients with suspected PE (Fig. 7).

Diagnosis of Acute Pulmonary Embolism

Accuracy of Lung Scanning

In the Prospective Investigative Study of Acute Pulmonary embolism Diagnosis (PISA-PED), which utilized perfusion scanning alone in conjunction with the chest radiograph, the sensitivity and specificity of scintigraphy was 92% and 87%, respectively. By combining the clinical assessment of the likelihood of PE (very likely, possible or unlikely), the positive predictive value of a positive perfusion scan can be up to 99%. A perfusion scan without segmental defects combined with a low clinical likelihood of PE had a negative predictive value of 97%. It is particularly notable that these results were achieved without ventilation scanning.

To date the most comprehensive prospective study addressing the role of V/Q scanning in the diagnosis of PE has been the Prospective Investigation of Pulmonary embolism Diagnosis study (PIOPED), a multi-institutional study designed to evaluate the efficacy of various conventional methods for diagnosing acute PE. In particular, the study was designed to determine the sensitivity and specificity of V/Q lung scanning for diagnosing acute PE. In addition, the relative contributions of the clinical assessment, chest radiograph and other routine studies were assessed. The sensitivity, specificity and positive predictive value of a high probability V/Q scan interpretation for detecting acute PE were 41%, 97% and 87%, respectively. None of the patients with a normal V/Q scan had PE. The overall diagnostic performance of the V/Q scan was similar in men and women, in patients of varying ages, and among patient with or without pre-existing cardiac or pulmonary disease.

Patients with suspected pulmonary embolism can be safely managed based on pretest probability and results of V/Q scanning. One prospective study in 1239 patients with suspected pulmonary embolism examined a clinical model used to categorize pretest probability of pulmonary embolism as low, moderate, or high (Wells, 1998). V/Q scanning and bilateral deep venous ultrasonography were performed. Only 3 of the 665 patients (0.5%) with low or moderate pretest probability and a non-high-probability scan had PE or DVT during the 90-day follow-up period.

Interpretation Pitfalls

False negative lung scan interpretations (low probability despite angiographic evidence of PE) do occur and patients who have a recent history of immobilization, surgery, trauma to the lower extremities and central venous instrumentation are a particularly high risk group. In patients with low or very low probability V/Q scan interpretations and no history of immobilization, recent surgery, trauma to the lower extremities or central venous instrumentation, the prevalence of PE is only 4.5%. In contrast, when patients with a low or very low probability V/Q lung scan interpretations have one of the above mentioned risk factors, the prevalence of PE is 12%; with more than one risk factors, the prevalence rises to 21% (Table 1). Patients with false negative lung scan interpretations tend to have non-occlusive and/or subsegmental thrombi with low pulmonary clot burden. In recent years, concern has been raised that a low probability lung scan interpretation may be misleading and result in unnecessary mortality as a sequela of PE. Nevertheless, the prognostic value of a low probability scan is excellent, particularly in patients with a low clinical pre-test likelihood of disease or negative ultrasound. In a recent series of 536 consecutive patients with this finding, there was no evidence that PE was a causative or contributing factor among patients who died within six months of imaging (Rajendran, 1999).

The most common cause of V/Q mismatch in patients who do not have acute PE are related to chronic or unresolved PE. Other causes of V/Q mismatch in the absence of PE (false positive interpretation) include extrinsic compression of the pulmonary vasculature (mass lesions, adenopathy, mediastinal fibrosis), vessel wall abnormalities (pulmonary artery tumors, vasculitis), intraluminal obstruction (tumor emboli, foreign body emboli) and congenital vascular abnormalities (pulmonary artery agenesis or hypoplasia). In patients with unilateral V/Q mismatch (hypoperfusion or absent perfusion) within an entire lung or multiple contiguous segments, and normal perfusion in the contralateral lung, extrinsic compression of the pulmonary vasculature, congenital abnormalities or proximal PE all need to be considered in the differential diagnosis. These patient will often require further imaging with CT or angiography.

Interpretation Criteria

Several diagnostic criteria have been developed for the interpretation of V/Q lung scans. The original PIOPED criteria had the highest likelihood ratio for predicting the presence of PE on pulmonary angiography. However, these also had

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