(Radiographics. 2000;20:99-105.)
© RSNA, 2000
Review of Criteria Appropriate for a Very Low Probability of Pulmonary Embolism on Ventilation-Perfusion Lung Scans: A Position Paper1
Paul D. Stein, MD and
Alexander Gottschalk, MD
1 From the Henry Ford Heart and Vascular Institute, Detroit, Mich (P.D.S.), and Michigan State University, East Lansing (A.G.). Received July 31, 1998; revision requested February 8, 1999 and final revision received May 17; accepted May 17. Address reprint requests to P.D.S., Henry Ford Cardiac Wellness Center, 6525 Second Ave, Detroit, MI 48202-3006.
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Abstract
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The "low-probability" interpretation of ventilation-perfusion lung scans has been characterized as misleading or even dangerous because of the high prevalence of pulmonary embolism associated with such an interpretation. Since the completion of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study, analyses of the PIOPED database have allowed identification of several abnormalities seen on ventilation-perfusion scans that have a positive predictive value (PPV) for pulmonary embolism of less than 10%. These include nonsegmental perfusion abnormalities (PPV = 8%), perfusion defects smaller than the corresponding areas of increased opacity at chest radiography (PPV = 8%), matched ventilation-perfusion abnormalities in two or three zones of a single lung (PPV = 3%), one to three small segmental perfusion defects (PPV = 1%), triple matched defects in the upper or middle lung zone (PPV = 4%), and the stripe sign (PPV = 7%). Use of these abnormalities as interpretative criteria constitutes "very low probability" interpretation and will reduce the number of low-probability interpretations of ventilation-perfusion lung scans, which may be considered nondiagnostic because of the unacceptably high rate of false-negative results. This will enhance the utility of the ventilation-perfusion lung scan for screening patients with suspected pulmonary embolism.
Index Terms: Embolism, pulmonary, 60.72 • Lung, perfusion, 60.12171 • Lung, ventilation, 60.12174
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Introduction
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The "low-probability" interpretation of ventilation-perfusion lung scans has been characterized as misleading or even dangerous because of the unacceptably high prevalence of pulmonary embolism associated with this interpretation (1). In the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study, pulmonary angiography revealed pulmonary embolism in 14% of patients with low-probability ventilation-perfusion lung scans (2). Hull and Raskob (1) demonstrated pulmonary embolism in 23% of patients with low-probability ventilation-perfusion scans using the criteria proposed by Biello et al (3) and in 26% of patients using the criteria proposed by McNeil (4). The authors suggested that the low-probability interpretation of a ventilation-perfusion lung scan is no longer clinically helpful because it is frequently misinterpreted by the clinician as ruling out pulmonary embolism (1). Moser (5) suggested that ventilation-perfusion lung scan findings be reported as either normal, high-probability, or nondiagnostic. However, it is possible to identify abnormalities on a ventilation-perfusion lung scan that indicate a truly low probability for pulmonary embolism ("very low probability" interpretation). Use of these findings as interpretative criteria is associated with a positive predictive value (PPV) of less than 10%. Therefore, very low probability interpretation has the same diagnostic reliability as high-probability interpretation.
The original PIOPED criteria defined a very low probability ventilation-perfusion scan as one having three or fewer small segmental perfusion defects and accompanied by normal chest radiographic findings (2). A small segmental perfusion defect was defined as one involving less than 25% of a segment (2).
In this article, we review data published after the PIOPED study that permit formulation of criteria for very low probability interpretation of ventilation-perfusion lung scans.
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Criteria for Very Low Probability Interpretation
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Following the completion of the PIOPED study, the Nuclear Medicine Working Group reassessed the original criteria used for low-probability interpretation of ventilation-perfusion lung scans and made recommendations for modifying the criteria (6). Low probability was defined as a 0%–19% likelihood of pulmonary embolism (6). Other investigators prospectively tested the modified PIOPED criteria in a community hospital (7) and demonstrated pulmonary embolism in 6% of patients with low-probability scans (7). This represented a lower prevalence than was seen in the PIOPED study (14%). However, the patient population at the community hospital differed significantly from that in the PIOPED study (2,7): The overall prevalence of pulmonary embolism was 10% in the former group compared with 28% in the latter group.
We subsequently attempted to develop criteria for very low probability interpretation that would be valid in all patient populations, including those in tertiary referral centers. We evaluated the features, both singly and in combination, of low-probability ventilation-perfusion lung scans with a PPV for pulmonary embolism of less than 10% (8–11). These features included nonsegmental perfusion abnormalities, perfusion defects smaller than the corresponding radiographic defects, matching ventilation-perfusion defects in two or three zones of a single lung accompanied by normal radiographic findings, one to three small segmental perfusion defects, triple matched defects in the upper or middle lung zone, and the stripe sign (Table). The available data on the various features were numerically limited even though PIOPED has the largest database on this subject. However, in some instances we were able to make optimal use of the PIOPED database by evaluating individual lungs or lung zones rather than individual patients. In addition, in some instances we evaluated the arm of PIOPED that included patients who were referred for pulmonary angiography as well as patients randomized for pulmonary angiography.
Nonsegmental Perfusion Abnormalities
Nonsegmental perfusion abnormalities with a low PPV for pulmonary embolism included enlargement of the heart, hila, or mediastinum and an elevated hemidiaphragm (Fig 1). As shown in the Table, these abnormalities demonstrated a PPV for pulmonary embolism of 8% (8).
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Figure 1a. Nonsegmental perfusion abnormality. Pulmonary angiography showed no pulmonary embolism. (a) Chest radiograph shows a prominent right hilum. (b) Posterior and right posterior oblique (RPO) images from a perfusion lung scan show enlargement of the right hilum (arrowheads).
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Figure 1b. Nonsegmental perfusion abnormality. Pulmonary angiography showed no pulmonary embolism. (a) Chest radiograph shows a prominent right hilum. (b) Posterior and right posterior oblique (RPO) images from a perfusion lung scan show enlargement of the right hilum (arrowheads).
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Perfusion Defect Smaller than Corresponding Radiographic Defect
A perfusion defect smaller than the corresponding radiographic defect, regardless of findings on the ventilation scan, demonstrated a PPV for pulmonary embolism of 8% (Fig 2) (8).
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Figure 2a. Perfusion defect smaller than a corresponding radiographic defect. Pulmonary angiography showed no pulmonary embolism. (a) Chest radiograph shows a retrocardiac area of increased opacity with faint depiction of air bronchograms. (b) Anterior and posterior images from a perfusion scan only vaguely suggest a perfusion defect in the left lung base. No ventilation scan was performed in this case.
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Figure 2b. Perfusion defect smaller than a corresponding radiographic defect. Pulmonary angiography showed no pulmonary embolism. (a) Chest radiograph shows a retrocardiac area of increased opacity with faint depiction of air bronchograms. (b) Anterior and posterior images from a perfusion scan only vaguely suggest a perfusion defect in the left lung base. No ventilation scan was performed in this case.
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Matched Ventilation-Perfusion Defects in Two or Three Zones of a Single Lung
Matched ventilation-perfusion defects that represented the only type of perfusion defect in two or three zones of a single lung and were accompanied by regionally normal findings at chest radiography demonstrated a PPV for pulmonary embolism of 3% (Fig 3) (8).
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Figure 3a. Matched ventilation-perfusion scan defects. No areas of increased opacity were seen at chest radiography, and pulmonary angiography showed no pulmonary embolism. (a) Left posterior oblique (LPO) and posterior images from a perfusion scan show multiple areas of diminished perfusion that are especially prominent in the lung bases. Note the irregular lung margins; these are not artifactual but represent diminished perfusion. (b) Images from a xenon-133 ventilation scan demonstrate matched ventilation-perfusion defects in all three zones of both lungs. The equilibrium image was obtained over a 2-minute period at the end of the 4-minute equilibration period. Note the relatively sharp lung margins (especially at the bases) compared with the perfusion scan (cf a). The posterior image was obtained over a 45-second period that ended 90 seconds after the start of washout. Procurement of the left posterior oblique (LPO) image ended 180 seconds after the start of washout. The focal areas of increased activity represent abnormal ventilation (slow washout). Matched basilar perfusion and ventilation abnormalities are particularly well visualized on left posterior oblique images.
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Figure 3b. Matched ventilation-perfusion scan defects. No areas of increased opacity were seen at chest radiography, and pulmonary angiography showed no pulmonary embolism. (a) Left posterior oblique (LPO) and posterior images from a perfusion scan show multiple areas of diminished perfusion that are especially prominent in the lung bases. Note the irregular lung margins; these are not artifactual but represent diminished perfusion. (b) Images from a xenon-133 ventilation scan demonstrate matched ventilation-perfusion defects in all three zones of both lungs. The equilibrium image was obtained over a 2-minute period at the end of the 4-minute equilibration period. Note the relatively sharp lung margins (especially at the bases) compared with the perfusion scan (cf a). The posterior image was obtained over a 45-second period that ended 90 seconds after the start of washout. Procurement of the left posterior oblique (LPO) image ended 180 seconds after the start of washout. The focal areas of increased activity represent abnormal ventilation (slow washout). Matched basilar perfusion and ventilation abnormalities are particularly well visualized on left posterior oblique images.
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A matched ventilation-perfusion defect that represented the only type of perfusion defect in one zone of a single lung tended to demonstrate a higher PPV for pulmonary embolism (12% [four of 34 cases]) than matched ventilation-perfusion defects in two (5% [one of 20]) or three (0% [zero of 10]) zones. A matched ventilation-perfusion defect in only one zone was not used as a criterion for very low probability interpretation (8).
One to Three Small Segmental Perfusion Defects
A finding of one to three small segmental perfusion defects (ie, those involving <25% of a segment) accompanied by a regionally normal chest radiograph demonstrated a PPV for pulmonary embolism of 1%–3% depending on whether pulmonary embolism was diagnosed or excluded entirely with pulmonary angiography or with pulmonary angiography and follow-up (Fig 4) (9). Evaluation of this criterion was independent of findings on the ventilation scan. This low PPV for pulmonary embolism is comparable to that reported by Silberstein et al (13). Pulmonary embolism was seen in only one of 68 patients (1%) in whom pulmonary embolism was diagnosed or excluded at pulmonary angiography or follow-up (9).
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Figure 4. One to three small segmental perfusion defects. Pulmonary angiography showed no pulmonary embolism. Posterior image from a perfusion scan shows small, round lesions in the left apex (top arrow) and retrocardiac left lung base (bottom arrow). (Reprinted, with permission, from reference 12.)
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Triple Matched Defects in the Upper or Middle Lung Zone
A matched ventilation-perfusion defect with an associated matching area of increased opacity at chest radiography is defined as a triple matched defect. This defect may be caused by pulmonary embolism creating a pulmonary "infarction" (usually pulmonary hemorrhage). Worsley et al (14) showed that pulmonary embolism was more frequently seen with triple matched defects in the lower zone of the lung than in the upper or middle zone. The authors also demonstrated that matching ventilation-perfusion defects and chest radiographic areas of increased opacity isolated to the upper and middle zones indicate a low probability of pulmonary embolism (<20% PPV), whereas triple matched defects in the lower zone indicate an intermediate probability of pulmonary embolism (20%–79% PPV) (14).
We further explored the diagnostic value of triple matched defects (10). Lungs with mismatched perfusion defects were excluded. Lungs with triple matched defects and a pleural effusion were also excluded because small pleural effusions that caused blunting of the costophrenic angle were associated with pulmonary embolism in over 20% of patients (8). Pulmonary embolism was seen with triple matched defects in the upper or middle lung zone in only one of 27 cases (4%) (Fig 5) (10).
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Figure 5a. Triple matched defect in the right midlung zone. Pulmonary angiography showed no pulmonary embolism. (a) Portable chest radiograph shows an area of increased opacity in the right midlung. The right lung base is not well visualized. (b) Posterior single-breath (left) and equilibrium (right) images from a xenon-133 ventilation scan show a ventilation defect in the right midlung zone. (c) Posterior (left) and right posterior oblique (right) images from a perfusion scan show a perfusion defect in the right midlung zone in the apical segment of the right lower lobe (arrows).
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Figure 5b. Triple matched defect in the right midlung zone. Pulmonary angiography showed no pulmonary embolism. (a) Portable chest radiograph shows an area of increased opacity in the right midlung. The right lung base is not well visualized. (b) Posterior single-breath (left) and equilibrium (right) images from a xenon-133 ventilation scan show a ventilation defect in the right midlung zone. (c) Posterior (left) and right posterior oblique (right) images from a perfusion scan show a perfusion defect in the right midlung zone in the apical segment of the right lower lobe (arrows).
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Figure 5c. Triple matched defect in the right midlung zone. Pulmonary angiography showed no pulmonary embolism. (a) Portable chest radiograph shows an area of increased opacity in the right midlung. The right lung base is not well visualized. (b) Posterior single-breath (left) and equilibrium (right) images from a xenon-133 ventilation scan show a ventilation defect in the right midlung zone. (c) Posterior (left) and right posterior oblique (right) images from a perfusion scan show a perfusion defect in the right midlung zone in the apical segment of the right lower lobe (arrows).
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Stripe Sign
The stripe sign on perfusion scans consists of a stripe of perfused lung tissue between a perfusion defect and the adjacent pleural surface (Fig 6) (15). In the PIOPED study, the stripe sign demonstrated a PPV for pulmonary embolism of only 7% (six of 85 cases) (11). Therefore, when present, the stripe sign indicated a very low probability of pulmonary embolism in the affected region.
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Figure 6a. Stripe sign. Pulmonary angiography showed no pulmonary embolism. (a) Chest radiograph shows no area of increased opacity in the right midlung zone. The right midlung demonstrated normal findings on a xenon-133 ventilation scan. (b) Posterior (left) and right posterior oblique (right) images from a perfusion scan demonstrate a possible perfusion mismatch in the apical segment of the right lower lobe (posterior image) and a peripheral rim of increased activity, or stripe sign (arrows on right posterior oblique image). The stripe sign indicates a very low probability that this lesion was caused by pulmonary embolism.
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Figure 6b. Stripe sign. Pulmonary angiography showed no pulmonary embolism. (a) Chest radiograph shows no area of increased opacity in the right midlung zone. The right midlung demonstrated normal findings on a xenon-133 ventilation scan. (b) Posterior (left) and right posterior oblique (right) images from a perfusion scan demonstrate a possible perfusion mismatch in the apical segment of the right lower lobe (posterior image) and a peripheral rim of increased activity, or stripe sign (arrows on right posterior oblique image). The stripe sign indicates a very low probability that this lesion was caused by pulmonary embolism.
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Discussion
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The criteria for very low probability interpretation of a ventilation-perfusion lung scan are based on data from the PIOPED study (8–11), which involved patients in tertiary care hospitals. The prevalence of pulmonary embolism is likely to be lower among patients in community hospitals than in patients in tertiary care hospitals (2,7). Because the PPV associated with a ventilation-perfusion lung scan depends on the prevalence of pulmonary embolism, findings on a very low probability lung scan should have an even lower PPV in patients in a community hospital than in patients in a tertiary care hospital.
Stratification of patients according to the presence or absence of prior cardiopulmonary disease suggests that some criteria suited to the general population as "very low probability" might be better suited to one or the other subgroup (8). These criteria, either singly or in combination, and their relevance in patients who are stratified on the basis of prior cardiopulmonary disease will be strengthened by further prospective testing.
Use of very low probability interpretation of ventilation-perfusion scans will reduce the number of low-probability interpretations, which may be considered nondiagnostic because of the high rate of false-negative results. This will enhance the utility of the ventilation-perfusion lung scan for screening patients with suspected pulmonary embolism.
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Footnotes
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Abbreviations: PIOPED = Prospective Investigation of Pulmonary Embolism Diagnosis
PPV = positive predictive value
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References
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Abstract
Introduction
