Detection of Pulmonary Embolism

• Indication Overview
• Methods
• Search Results
• Summary Table
• References
• Appendix 1
• Appendix 2
• Appendix 3

Indication Overview

Pulmonary embolism (PE) is blockage of the main artery (or a distal branch of the main artery) that supplies blood to the lungs by material (typically a thrombus, or blood clot, but may also be a tumour, air, or fat) that originates elsewhere in the body, most commonly in the leg.¹ Severe obstruction of blood flow through the lungs causes increased pressure in the lungs, which also increases the right ventricle pressure load of the heart leading to PE symptoms. The clinical presentation of PE may range from asymptomatic disease to sudden death. The most common symptoms include unexplained breathlessness, chest pain, cough, hemoptysis, syncope, palpitations, rapid breathing, increased heart rate, cyanosis (bluish discoloration of the skin and mucous membranes caused by a lack of oxygen in the blood), fever, low blood pressure, right heart failure, pulmonary hypertension, and leg swelling.² However, these clinical symptoms are non-specific.³ PE is categorized as either acute or chronic.¹ The focus of the current report is on the detection of acute PE. PE can be fatal, with a 30% mortality rate, but mortality can be significantly reduced with treatment.¹

PE usually occurs secondary to inherited or acquired predisposing factors. Active cancers, recent immobilization or surgery, extremity paresis, hormone replacement therapy, factor V Leiden mutation, and oral contraceptives are among the acquired risk factors.^2,4 In 20% of patients, PE can be found without any identified predisposing factors.⁵ Patients at risk for PE include those with deep vein thrombosis (DVT [a thrombus in a major venous system]) or patients taking medications that affect coagulation of the blood.

Imaging of PE allows for the mapping of blood flow in the lungs. The procedure allows for detection of the perfusion defect caused by the clot (embolus) but not the embolus itself.⁶ Treatment is typically with anticoagulant therapy with fractionated heparin, low-molecular-weight heparin, or warfarin.⁷

Population: Patients with suspected acute pulmonary embolism (PE).

Intervention: Ventilation-perfusion scintigraphy (V/Q scan).

The basic principle of V/Q scanning is to recognize lung segments or sub-segments without perfusion but preserved ventilation; i.e., mismatch between the amount of air and blood reaching the gas exchange units in the lung.² A V/Q scan is a combination of two nuclear tests that involve administration of inhaled and intravenous radioisotopes to measure ventilation and perfusion in all areas of the lungs. The tests can be performed simultaneously or separately. A ventilation study is performed after inhalation of tracers such as xenon-133 (^133mXe) gas, krypton (^81mKr), or technetium-99m(^99mTc)-labelled aerosols of diethylenetriamine pentaacetic acid (^99mTc-DTPA) or ^99mTc-labelled carbon microparticles (^99mTc-technegas). Perfusion studies are performed after intravenous injection of ^99mTc-labelled macroaggregated albumin (^99mTc-MAA) particles. A gamma camera acquires images of the lungs and pulmonary vessels. Any mismatches — i.e., regions with normal ventilation image and a visible defect on the perfusion image — should be considered as a site of potential PE.⁴

V/Q scans can be performed using conventional planar scintigraphy or tomographic imaging (single- photon emission computed tomography [SPECT]) techniques.²

Comparators: For this report, computed tomography pulmonary angiography (CTPA) is considered as an alternative to V/Q scan:

CTPA: CTPA is an imaging test, used for the detection of PE, that employs computed tomography (CT). This test uses an intravenous radiographic contrast agent. Images are taken using a breath-hold technique. An acute PE can be seen as a filling defect in the pulmonary artery (complete or partial closure of the vessel).⁸ Clinical signs and symptoms of PE, routine laboratory findings, chest X-rays, or cardiologic tests such as echocardiography are non-specific and their results are not always helpful in the diagnosis of PE.^4,9

Clinical signs and symptoms of PE are helpful in the estimation of the clinical likelihood of PE before any diagnostic test is undertaken (pre-test probability), and to calculate later probability of the disease (post-test probability) using the information provided by appropriate diagnostic testing.^10-13 Measurement of the plasma concentration of D-dimer has been widely used as a non-invasive diagnostic test in patients with suspected PE. However, the utility of this test in the diagnosis of PE is limited due to its low specificity and positive predictive value.⁹

Lower limb compression ultrasonography is also indicated as a non-invasive diagnostic test in patients with suspected PE. This test is used for direct assessment of deep venous thrombosis (DVT) which can be associated with a higher risk of PE.^14,15 Thus, a positive test result can justify anticoagulant therapy and prevent the need for further investigation. However, because PE can occur in the absence of DVT, a negative test result does not necessarily exclude PE.¹⁶ The accuracy of magnetic resonance imaging (MRI) techniques (e.g., real time MRI, MR angiography, MR perfusion imaging) for the diagnosis of PE has also been studied.^17,18 This modality is considered a safe and useful tool in patients with allergic reactions to iodine contrast materials (used for CTPA) or in patients for whom the radiation risk is a concern.¹⁷ Various diagnostic algorithms have been developed to guide the use of combinations of multiple diagnostic tests to confirm or exclude PE.¹⁹

Outcomes: Eleven outcomes (referred to as criteria) are considered in this report:

• Criterion 1: Size of the affected population
• Criterion 2 : Timeliness and urgency of test results in planning patient management
• Criterion 3: Impact of not performing a diagnostic imaging test on mortality related to the underlying condition
• Criterion 4: Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition
• Criterion 5: Relative impact on health disparities
• Criterion 6: Relative acceptability of the test to patients
• Criterion 7: Relative diagnostic accuracy of the test
• Criterion 8: Relative risks associated with the test
• Criterion 9: Relative availability of personnel with expertise and experience required for the test
• Criterion 10: Accessibility of alternative tests (equipment and wait times)
• Criterion 11: Relative cost of the test.

Definitions of the criteria are in Appendix 1.

Methods

The literature search was performed by an information specialist using a peer-reviewed search strategy.

Published literature was identified by searching the following bibliographic databases: MEDLINE with In-Process records via Ovid; The Cochrane Library (2011, Issue 1) via Wiley; PubMed; and University of York Centre for Reviews and Dissemination (CRD) databases. The search strategy was comprised of both controlled vocabulary, such as the National Library of Medicine's MeSH (Medical Subject Headings), and keywords. The main search concepts were radionuclide imaging and pulmonary embolism.

Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses (HTA/SR/MA), randomized controlled trials, and non-randomized studies, including diagnostic accuracy studies. No date or human limits were applied to the HTA/SR/MA search. For primary studies, the retrieval was limited to documents published between January 1, 2006 and January 28, 2011, and the human population. Both searches were also limited to English language documents. Regular alerts were established to update the search until October 2011. Detailed search strategies are located in Appendix 2.

Grey literature (literature that is not commercially published) was identified by searching relevant sections of the Our Grey Matters checklist. Google was used to search for additional web-based materials. The searches were supplemented by reviewing the bibliographies of key papers. See Appendix 2 for more information on the grey literature search strategy.

Targeted searches were done as required for the criteria, using the aforementioned databases and Internet search engines. When no literature was identified addressing specific criteria, experts were consulted.

Search Results

There were 31 potential clinical articles identified through the MA/SR/HTA filtered search and 15 were subjected to full-text review. Of these, six reported on the relative diagnostic accuracy of V/Q scanning and CTPA in diagnosis of PE.^20-25 Two reviews^22,23 were excluded because they did not report summary estimates of diagnostic accuracy (i.e., sensitivity, specificity), and two^21,25 were excluded because they included older technologies. The two included analyses^20,24 were published in 2005. Different techniques (i.e., V/Q SPECT and V/Q planar and products (i.e., ¹³³Xe, ^81mKr, ^99mTc-DTPA, ^99mTc-labelled technegas, ^99mTc-MAA) may have been combined in some of the published analyses.

Four primary studies are included in the diagnostic accuracy section of this report; one comparing planar V/Q scintigraphy with V/Q SPECT²⁶ and three comparing V/Q scanning with CTPA.^27-29

Finally, our search of the grey literature identified three guidelines on the prevention, diagnosis, and treatment of PE: those of the Institute for Clinical Systems Improvement (ICSI), the Scottish Intercollegiate Guidelines Network (SIGN), and the European Association of Nuclear Medicine (EANM).^2,30

Summary table

Table 1: Summary of Criterion Evidence

Domain 1: Criteria Related to the Underlying Health Condition
Criterion		Synthesized Information
1	Size of the affected population	Each year, approximately 600,000 patients in the United States are diagnosed with a PE.31,32 Of note, many more scans are performed to check for PE than the number of PE cases identified. Assuming the incidence rate in Canada is similar to that in the US, the size of the affected population is more than 1 in 1,000 (0.1%), and less than 1 in 100 (1%).
2	Timeliness and urgency of test results in planning patient management	Patients with suspected PE should be evaluated using appropriate diagnostic tests within the first 24 hours (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011) and receive anticoagulant therapy or installation of a central venous filter if the diagnosis is confirmed.32 Not performing imaging can have a significant impact on patient management. The target time frame for performing the test is in 24 hours or less and obtaining the test results in a timely manner has significant impact on the management of the condition or the effective use of heath care resources.
3	Impact of not performing a diagnostic imaging test on mortality related to the underlying condition	The mortality rate of undiagnosed and untreated PE is 30%. However, a timely diagnosis and adequate treatment can reduce the mortality rate to 2% to 8%.4,33 Diagnostic imaging test results can have significant impact on mortality.
4	Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition	Undiagnosed and untreated PE may lead to disabling morbidity from pulmonary hypertension (4% to 5%) and right ventricular failure,4,34,35 and predispose patients to recurrent venous thromboembolism (2.5% for the first year following PE and 0.5% in successive years).36,37 Diagnostic imaging test results can have moderate impact on morbidity or quality of life.

 

 

Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses
Criterion		Synthesized Information
5	Relative impact on health disparities	To be scored locally.
6	Relative acceptability of the test to patients	Patients having a V/Q scan are required to hold their breath for several seconds, which may be difficult. In addition, they are required to lie on their backs for up to 25 minutes. Patients undergoing CTPA are also required to hold their breath. The length of the CTPA procedure is shorter than a V/Q scan. One study evaluated patients' satisfaction for V/Q scan and CTPA. The proportion of the patients who rated their satisfaction as "good" or "very good" was 85.7% for spiral CT, compared to 14.3% for V/Q scanning.38 The authors described the V/Q scans as being obtained using standard techniques; however, these techniques and the radiopharmaceutical used were not described in the study publication. Although it is recognized that patient acceptability of V/Q scanning can vary depending on the techniques and the radiopharmaceutical used, it is assumed that V/Q scanning is minimally less acceptable to patients than CTPA.
7	Relative diagnostic accuracy of the test	The most recent data on the relative diagnostic accuracy of V/Q scanning versus CT were found in four primary studies: one comparing planar V/Q scintigraphy with V/Q SPECT26 and three comparing V/Q scanning to CTPA.27-29 Study Modality Sensitivity (%) Specificity (%) Gutte et al., 201026 V/Q SPECT 100 (79–100) 87 (78–87) Planar V/Q 64 (40–83) 72 (61–80) Gutte et al., 200927 V/Q SPECT 97 (82–100) 88 (75–95) CTPA 68 (49–83) 100 (93–100) Miles et al., 200928 V/Q SPECT 83 (61–95) 98 (92–100) CTPA NR NR Wang et al., 200929 Planar V/Q 91.7 92.9 CTPA 100 92.9 CTPA = computed tomography pulmonary angiography; NR = not reported; SPECT = single-photon emission computed tomography; V/Q = ventilation-perfusion scintigraphy. The discussion from MIIMAC members highlighted issues including location of the embolus and the lack of a gold standard. In large arteries, both V/Q and CTPA are able to detect PE; however, in smaller arteries, V/Q scan is typically better. Based on these results and expert opinion from MIIMAC members, V/Q SPECT and CTPA have similar diagnostic accuracies.
8	Relative risks associated with the test	Non–radiation-related Risks  V/Q scanning has been reported to be safe to use and few adverse reactions have been described.4,39 The overall rate of adverse reactions to radiopharmaceuticals is reported to be between 1 to 2 per 100,000 doses.39 CTPA for PE requires an iodine-based contrast agent.The frequency of severe, life-threatening reactions with contrast are rare (0.001% to 0.01%).40 Moderate reactions resembling an allergic response are also very unusual and range in frequency from 0.004% to 0.7%.40 Radiation-related Risks  Among the modalities to detect pulmonary embolism, both V/Q scanning and CTPA expose the patient to ionizing radiation. In general, CTPA confers larger doses of radiation than V/Q scanning. Effective Doses of Radiation41,42 Procedure Average Dose Range (mSv) V/Q scan 0.21 to 2.4 CTPA 4.2 to 19.9 CTPA = computed tomography pulmonary angiography; mSv = millisievert; V/Q = ventilation-perfusion scintigraphy In general, V/Q scanning is minimally safer than CT.
9	Relative availability of personnel with expertise and experience required for the test	As of 2006, there were 2,034 diagnostic radiologists, 221 nuclear medicine physicians, 12,255 radiological technologists, 1,781 nuclear medicine technologists, and 2,900 sonographers available across Canada. Yukon, Northwest Territories, and Nunavut do not have the available personnel to perform and interpret tests to detect PE. Other jurisdictions (e.g., Prince Edward Island) may offer limited nuclear medicine services. Depending upon the centre, and assuming the necessary equipment is available, it is estimated that more than 95% of procedures could likely be performed in a timely manner using CTPA.
10	Accessibility of alternative tests (equipment and wait times)	For V/Q scans, nuclear medicine facilities with gamma cameras (including SPECT) are required. As of January 1, 2007, there was an average of 18.4 nuclear medicine cameras per million people, with none available in the Yukon, Northwest Territories, or Nunavut.43 A report from the CIHI states that, as of January 1, 2007, CT scanners were available at a rate of 12.8 per million people in Canada; however, there were none available in Nunavut.43 For CT scanners, the average weekly use ranged from 40 hours in Prince Edward Island to 69 hours in Ontario, with a national average of 60 hours.43 In 2010, the average wait time for a CT scan in Canada is 4.2 weeks.44 Depending upon the centre and assuming the necessary expertise is available, it is estimated that more than 95% of procedures could be performed in a timely manner using CTPA.
11	Relative cost of the test	According to our estimates, the cost of V/Q scanning is $295.23 ($370.93 for SPECT). CTPA is a minimally less costly alternative. Relative costs Test Total costs ($) Cost of test relative to 99mTc-based test ($) V/Q Scan 370.93 Reference CTPA 266.41 –104.52

CIHI = Canadian Institute for Health Information; CT = computed tomography; CTPA = computed tomography pulmonary angiography; MIIMAC = Medical Isotopes and Imaging Modalities Advisory Committee; PE = pulmonary embolism; SPECT = single-photon emission computed tomography; V/Q = ventilation-perfusion scintigraphy.

Criterion 1: Size of affected population (link to definition)

PE is the third most common acute cardiovascular emergency after myocardial infarction and stroke,⁴⁵ and is estimated to be responsible for 5% to 10% of all deaths in United States hospitals.⁴⁶

The accurate size of population affected by PE is difficult to obtain because most pulmonary emboli are detected on autopsy. About 80% of patients with an identified PE at autopsy are unsuspected or undiagnosed before death.¹⁵ The prevalence of PE in patients who are clinically suspected is only 30%.²¹ Approximately 600,000 patients each year are diagnosed with PE in the United States.^31,32 The corresponding figures for Canada are unavailable. PE was reported to be the cause of death in more than 545 Canadians in 2007.⁴⁷

PE and DVT are different manifestations of a single condition named venous thromboembolism (VTE).⁴⁸ The annual incidence of VTE is approximately one in 1,000 persons.³² Among patients with DVT, 32% have a clinically silent (asymptomatic) PE diagnosed by lung scan, pulmonary angiography, or CT scan.^14,15 Therefore, routine screening for PE in patients with DVT has been suggested.¹⁵ In 79% of patients with PE, DVT can be found in lower limbs if sensitive diagnostic methods are used.⁴⁹

The results of the National Hospital Discharge Survey showed that the incidence of PE in hospitalized patients was 0.40% (95% CI, 0.39% to 0.40%) and did not change over the period of 1979 to 1999.⁵⁰ The incidence rates were similar in women and men, and amongst Whites and Blacks.⁵⁰ DeMonaco et al. reviewed PE hospital discharge data from the Pennsylvania Health Care Cost Containment Council to estimate PE incidence rates from 1997 to 2001. Based on the results of this study, the incidence of PE increased from 47 per 100,000 patients to 63 per 100,000 patients during the five-year period (mean increase of 0.004% per year).⁵¹ This mean annual increase in risk was significantly higher in women than men (0.013%), in African-American race than Whites (0.031%), and in patients who were more than 70 years old (0.0007%; P < 0.0001 for all). However, there was a significant decrease in the severity of illness scores. The authors discussed that the increasing incidence of PE could be due to increasing early diagnosis of PE after introduction of spiral CT in the state of Pennsylvania.⁵¹

Return to Summary Table.

Criterion 2: Timeliness and urgency of test results in planning patient management (link to definition)

Undiagnosed or untreated PE can be fatal or result in disabling morbidity from pulmonary hypertension or recurrent PE in survivors.³⁴ A timely and adequate treatment with anticoagulants/central venous filter can reduce mortality and morbidity.⁴ Conversely, incorrect diagnosis of the condition unnecessarily exposes patients to the risk of anticoagulant therapy, which can result in adverse effects and bleeding complications (about 3%).⁵² Therefore, patients suspected of having PE should be promptly evaluated using appropriate diagnostic tests and receive anticoagulant therapy if the diagnosis is confirmed.³²

According to the Saskatchewan hospital guidelines, V/Q lung scan or CT scan should be performed within the first 24 hours in patients with suspected acute PE (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011).

Return to Summary Table.

Criterion 3: Impact of not performing a diagnostic imaging test on mortality related to the underlying condition (link to definition)

Untreated PE can be rapidly fatal, and some survivors of undiagnosed PE can suffer disabling morbidity from pulmonary hypertension.^31,34

The mortality rate of undiagnosed and untreated PE is 30%. However, a timely diagnosis and adequate anticoagulation therapy can reduce the mortality rate to 2% to 8%.^4,33

Return to Summary Table.

Criterion 4: Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition (link to definition)

Undiagnosed and untreated PE may lead to disabling morbidity from pulmonary hypertension and right ventricular failure,^4,34 and predispose patients to recurrent VTE.³⁶ Pulmonary hypertension occurs in 4% to 5% of patients following PE,³⁵ with a probability of 31% in the first year following PE and 38% in successive years.³⁵

Undiagnosed and untreated PE may also lead to potentially fatal early recurrences.⁴ The likelihood of PE recurrence is 2.5% for the first year following PE and 0.5% for successive years.³⁷

Return to Summary Table.

Criterion 5: Relative impact on health disparities (link to definition)

Health disparity might be present if disadvantaged social groups systematically experience poorer health or more health risks than do more advantaged social groups.⁵³ Disadvantaged groups can be defined based on gender, age, ethnicity, geography, disability, sexual orientation, socioeconomic status, and special health care needs. Our targeted search found disparity concerns in the following disadvantaged groups:

Residents of rural and remote areas
Much of the medical imaging equipment and expertise required for the diagnosis of PE are unavailable or inaccessible to residents of rural areas (refer to Criterion 10 — Accessibility of alternative tests — for more information).Therefore, timely diagnosis of PE is less likely in rural or remote facilities.⁵⁴ Given the emergent nature of PE, the unavailability of appropriate diagnostic tests may lead to missed diagnosis or unnecessary anticoagulation.⁵⁴

Ethnic and racial groups
In the United States, the incidence of VTE has been shown to be 30% to 50% higher in African-Americans than in Whites.^55-58 American Indians, Alaskan Natives, and Asians have been reported to have a significantly lower rate of PE as compared to Blacks and Whites.^55,56 African- Americans have also been shown to have a 30% higher chance of mortality within 30 days following the diagnosis of PE.⁵⁹ Although factors such as genetics or other comorbid conditions (e.g., obesity and diabetes) can directly or indirectly impact the incidence of PE, the above-mentioned differences in incidence and mortality rates can be attributable to disparities in diagnosis and care.⁶⁰

Women and children
V/Q scanning and spiral CT involve exposure to ionizing radiation. This can be a concern in testing pediatric patients, as the risk of radiation-induced cancer is shown to be two to three times greater in children and adolescents than in adults.³⁹ The risk of pulmonary embolism increases during pregnancy.³⁹ At the same time, there is concern regarding fetal exposure to radiation with either V/Q scanning or CTPA.³⁹ V/Q SPECT is generally recommended as first line in this special population.³⁹

CTPA delivers relatively high doses of radiation to the breast and lung tissues. This can pose a greater risk of radiation-induced breast cancer to young women who have breast tissue with a higher cellular turnover rate. The estimated radiation dose from CTPA (10 to 70 millisievert [mSv]) is much greater than V/Q scan (less than 1.5 mSv).³⁹ Based on the most recent Biologic Effects of Ionizing Radiation report (BEIR VII),⁶¹ the lifetime attributable risk of breast cancer from a breast dose of 20 milligrays (mGy) delivered by CTPA is approximately 1/1,200 for a woman aged 20, 1/2,000 for a woman aged 30, and 1/3,500 for a woman aged 40.³⁹ A V/Q scan is therefore preferred over CTPA in young women with suspected PE.⁶²

Return to Summary Table.

Criterion 6: Relative acceptability of the test to patients (link to definition)

V/Q scanning
Patients may have concerns about radiation exposure and the intravenous injection of a radiopharmaceutical agent.

CT
Patients undergoing CT scan may have concerns about radiation exposure and may also feel claustrophobic while in the scanner. This is less of a problem with new CT scanners (MIIMAC expert opinion). Patients may be required to hold their breath for a substantial period of time, which is seen as "uncomfortable" and "difficult."⁶³

V/Q scanning versus CT
In a prospective study published in 2005, Katsouda et al.³⁸ evaluated patient satisfaction with spiral CT versus V/Q scanning in 63 patients who were clinically suspected of having PE. All patients underwent sequential testing with V/Q scanning and contrast-enhanced spiral CT. The primary outcome of the study was diagnostic accuracy, and patient satisfaction was measured as a secondary outcome. The proportion of the patients who rated their satisfaction as "good" or "very good" was 85.7% for spiral CT, as compared with 14.3% for V/Q scanning. The authors described the V/Q scans as being obtained using standard techniques; however, these techniques and the radiopharmaceutical used were not described in the study publication.

Return to Summary Table.

Criterion 7: Relative diagnostic accuracy of the test (link to definition)

Guidelines
Our search of the grey literature identified three guidelines on the prevention, diagnosis, and treatment of PE.^2,30 Their recommendations, as they pertain to imaging and the detection of PE, are described, as follows:

An eleventh edition of the Institute for Clinical Systems Improvement (ICSI) guidelines for venous thromboembolism diagnosis and treatment was published in March 2011.⁶⁴ These guidelines recommend CTPA as the first line study of choice, unless a contraindication exists.⁶⁴ In cases where a contraindication exists, V/Q scan is recommended instead.⁶⁴

The 2010 Scottish Intercollegiate Guidelines Network (SIGN) guidelines for the prevention and management of venous thromboembolism also recognize CTPA as the gold standard for detecting acute pulmonary embolus.⁶⁵ Again, in cases where CTPA is contraindicated, the authors recommend isotope lung scintigraphy (V/Q scan).⁶⁵

The European Association of Nuclear Medicine (EANM) guidelines for V/Q scan,^2,30 published in 2009, express a preference for V/Q SPECT over planar V/Q. They further recommend technegas as the radioaerosol of choice for ventilation scintigraphy in patients with chronic obstructive pulmonary disease.^2,30

Systematic reviews and meta-analyses
Six systematic reviews and meta-analyses identified in the literature search reported on the relative diagnostic accuracy of V/Q scanning and CTPA in the diagnosis of PE.^20-25 Two reviews^22,23 were excluded because they did not report summary estimates of diagnostic accuracy (i.e., sensitivity, specificity), and two^21,25 were excluded because they included older technologies and therefore their estimates of diagnostic performance were deemed out-of-date. The two included analyses^20,24 were published in 2005. Different techniques (i.e., V/Q SPECT and V/Q planar) and products (i.e., ^133mXe, ^81mKr, ^99mTc-DTPA, ^99mTc-labelled technegas, ^99mTc-MAA) may have been lumped together in some of the analyses.

Hayashino et al.(2005)²⁰ conducted a meta-analysis comparing helical (spiral CT) or V/Q scanning in the diagnosis of PE with pulmonary angiography as the gold standard. The authors searched the English language articles in MEDLINE from 1990 to 2003 for helical CT and from 1985 to 2003 for V/Q scan. Helical CT articles were searched from 1990 onwards, as the earlier CT equipment was different. Twelve articles were included in the review: Two of the studies compared helical CT and V/Q scanning to angiography, seven compared CT alone to angiography, and three compared V/Q alone to angiography. The ventilation studies included in the review used ¹³³Xe, ^99mTc-pyrophosphate (PYP), or ^99mTc-DTPA, as the radioisotope and perfusion studies used ^99mTc-MAA.²⁰ To calculate the sensitivity and specificity of the tests, three thresholds were specified based on the prospective investigation of the pulmonary embolism diagnosis (Prospective Investigation of Pulmonary Embolism Diagnosis or PIOPED) criteria (high, intermediate, low, near normal, or normal pre-test probabilities of PE).⁶⁶ A random effects model was used to pool the data from the studies (Appendix 3). A summary receiver operating characteristic (ROC) analysis that summarizes the sensitivity and specificity of different tests into a single ROC curve was used for the indirect comparison of CTPA versus V/Q scan. Based on the results of the meta-analysis and ROC analysis, the authors concluded that helical CT and V/Q scanning had similar discriminatory power when the high probability threshold was used. They also suggested that helical CT could be superior to V/Q scanning, in terms of discriminatory power, when normal or near normal threshold was used.

Roy et al.(2005)²⁴ conducted a systematic review of literature published between 1990 and 2003 in order to assess the likelihood ratios of the diagnostic tests used to detect PE. Overall, 48 studies were included in this review, including two studies of V/Q scan and seven studies of CTPA. The authors were unable to pool the results of the studies evaluating V/Q scanning. The pooled random positive likelihood ratio for CT was 24.1.

Primary studies
Gutte et al. (2010)²⁶ conducted a prospective study comparing V/Q SPECT and planar V/Q lung scanning in diagnosing acute PE. Both of these technologies were performed using ^99mTc-MAA, but the results are included here to assist in the interpretation of other comparisons.²⁶ Among the 36 study participants, V/Q SPECT was found to have a sensitivity of 100% and a specificity of 87%.²⁶ In comparison, planar V/Q scanning was both less sensitive (64%) and less specific (72%).²⁶

In a 2009 publication, the same group of researchers assessed the diagnostic ability of V/Q SPECT compared with multidetector computed tomography in patients with suspected PE.²⁷ Eighty-one patients were included in the analysis.²⁷ Final diagnoses were made using all available information: electrocardiography, sonography, D-dimer levels, clinical data, and follow-up from hospital files and telephone interviews.²⁷ Diagnostic performance was measured for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (Table 2).²⁷ The authors concluded that lung scintigraphy performed as V/Q SPECT, in combination with low-dose CT without contrast enhancement, should be considered as first-line in the work-up of PE, where possible.²⁷

Table 2: Diagnostic Performance of SPECT versus CT²⁷

Modality	Sens. (%)*	Spec. (%)*	PPV (%)*	NPV (%)*	Acc. (%)*	Non-diagnostic Rate (%)*
V/Q SPECT	97 (82-100)	88 (75-95)	82 (65-93)	98 (88-100)	91 (83-93)	5 (1-12)
V/Q SPECT plus low-dose CT	97 (83-99)	100 (93-100)	100 (88-100)	98 (90-100)	99 (93-100)	0 (0-4)
Perfusion SPECT plus low-dose CT	93 (81-98)	51 (43-55)	57 (49-60)	91 (76-98)	68 (58-72)	17 (10-28)
Pulmonary MDCT angiography	68 (49-83)	100 (93-100)	100 (84-100)	83 (71-92)	88 (78-94)	0 (0-4)

Acc. = accuracy; MDCT = multidetector computed tomography; NPV = negative predictive value; PPV = positive predictive value; Sens. = sensitivity; Spec. = specificity; V/Q SPECT = ventilation/perfusion single-photon emission computed tomography.
*Values in parenthesis are 95% confidence intervals.

An Australian study by Miles et al. (2009) also compared SPECT V/Q scintigraphy and CTPA in the diagnosis of PE.²⁸ The sensitivity and specificity of SPECT were calculated against a reference diagnosis based on all available information, made by a panel of respiratory physicians.²⁸ Sensitivity and specificity values for CTPA were not calculated, but concordance between SPECT and CTPA was presented.²⁸ One hundred patients with clinically suspected acute PE were recruited; 99 underwent planar V/Q scanning, 87 underwent SPECT V/Q scanning, and 95 underwent CTPA.²⁸ SPECT was found to have a sensitivity of 83%, a specificity of 98%, and to agree with CTPA diagnosis in 95% of cases.²⁸

A third study investigated the relative diagnostic performance of V/Q scanning, compared with CT, in the diagnosis of PE.²⁹ Eighty-two patients were included in the analysis; 42 underwent CTPA with a 16-detector CT and 40 with a 64-detector CT. Twenty-eight patients underwent V/Q scanning using ^99mTc-MAA for perfusion scanning and ^99mTc-DMSA for ventilation scanning.²⁹ A single-head gamma camera was used for imaging.²⁹ Two patients with non-diagnostic scans were excluded from the analysis.²⁹ The authors found the sensitivities of both CTPA and V/Q scanning to be 91.7%. CTPA outperformed V/Q scanning in specificity (100.0% versus 92.9%).²⁹

Return to Summary Table.

Criterion 8: Relative risks associated with the test (link to definition)

Non–radiation-related risks

V/Q Scan
V/Q test has been reported to be safe to use and few allergic reactions have been described.^4,39 The overall rate of adverse reactions to radiopharmaceuticals is reported to be one to two per 100,000 doses.³⁹ Allergies and adverse reactions to ^99mTc-MAA were reported in the 1970s,^39,67 but there have been no adverse events to modern V/Q scanning techniques reported, as the size and number of radionuclide particles are much smaller now than they were in the 1970s.⁶⁷ V/Q scan is associated with no toxicity to body organs.⁶⁷

CT
Some patients may experience an allergic reaction to the contrast agent (if required), which may worsen with repeated exposure.⁶⁸ In addition, patients may experience mild side effects from the contrast agent such as nausea, vomiting, or hives. A 2009 retrospective review of all intravascular doses of low-osmolar iodinated and gadolinium contrast materials administered at the Mayo Clinic between 2002 and 2006 (456,930 doses) found that 0.15% of patients given CT contrast material experienced side effects, most of which were mild. A serious side effect was experienced by 0.005% of patients.⁶⁹ CT is contraindicated in patients with elevated heart rate, hypercalcemia, and impaired renal function. Contrast is contraindicated in patients with renal failure or end-stage renal disease, as they are at risk of nephrogenic systemic fibrosis. According to the American College of Radiology Manual on Contrast Media,⁴⁰ the frequency of severe, life-threatening reactions with gadolinium are extremely rare (0.001% to 0.01%). Moderate reactions resembling an allergic response (i.e., rash, hives, urticaria) are also very unusual and range in frequency from 0.004% to 0.7%.⁴⁰

Radiation-related risks

Among the modalities to detect pulmonary embolism, both V/Q scanning and CTPA expose the patient to ionizing radiation. Table 3 summarizes the estimated effective dose of radiation in adults, as well as the estimated dose absorbed by mother and fetus during pregnancy for the aforementioned tests. As the table shows, in general CTPA carries larger doses of radiation than V/Q scanning does. However, during the first and second trimesters of pregnancy, V/Q scans are associated with a higher fetal absorbed radiation dose compared with CTPA.

Table 3: Estimated of Effective Radiation Dose (mSv) from V/Q Scanning and CTPA³⁹

Patient Group		V/Q Scan			CTPA
		Ventilation 99mTc-DTPA*	Ventilation Technegas†	Perfusion 99mTc-MAA‡	Single slice	4-slice	16-slice	64-slice
Adult		0.21	0.75	2.4	NA	4.2	14.4	19.9
Pregnant women	Breast	0.04	0.13	0.6	NA	NA	10 to 20	NA
	Lung	0.3	2.2	6.7	NA	NA	10	NA
Fetus	Early	0.12	0.008	0.35	NA	NA	0.24 to 0.47	NA
	1st trimester	0.09	0.008	0.48	0.003 to 0.020	NA	0.61 to 0.66	NA
	2nd trimester	0.05	0.010	0.55	0.008 to 0.077	NA	NA	NA
	3rd trimester	0.06	0.012	0.46	0.051 to 0.131	NA	0.06 to 0.23	NA

CTPA = computed tomography pulmonary angiography; DTPA = diethylenetriamine pentaacetic acid; MAA = macroaggregated albumin; mSv = millisievert; NA = not available; ^99mTc = technetium-99m; V/Q = ventilation/perfusion scintigraphy.
*30 megabecquerels (MBq) in adults and 20 MBq in pregnancy.
^†50 MBq in adults and 20 MBq in pregnancy.
^‡200 MBq in adults and 100 MBq in pregnancy.

Return to Summary Table.

Criterion 9: Relative availability of personnel with expertise and experience required for the test (link to definition)

The personnel required for the performance of the imaging tests to detect a PE are presented by imaging modality. A summary of the availability of personnel required for the conduct of methods to detect a PE, by V/Q scan or CT, is provided in Table 4.

V/Q scintigraphy 
In Canada, physicians involved in the performance, supervision, and interpretation of V/Q scans should be nuclear medicine physicians or diagnostic radiologists with training and expertise in nuclear imaging. Physicians should have a Fellowship of Certification in Nuclear Medicine or Diagnostic Radiology with the Royal College of Physicians and Surgeons of Canada and/or the Collège des médecins du Québec. Nuclear medicine technologists are required to conduct V/Q scans. Technologists must be certified by the Canadian Association of Medical Radiation Technologists (CAMRT) or an equivalent licensing body.

All alternative imaging modalities
In Canada, physicians involved in the performance, supervision, and interpretation of diagnostic CT scans should be diagnostic radiologists⁴³ and must have a Fellowship or Certification in Diagnostic Radiology with the Royal College of Physicians and Surgeons of Canada and/or the Collège des médecins du Québec. Foreign-trained radiologists also are qualified if they are certified by a recognized certifying body and hold a valid provincial licence.⁷⁰

Medical radiation technologists (MRTs) must be certified by the Canadian Association of Medical Radiation Technologists (CAMRT) or an equivalent licensing body.

Service engineers are needed for system installation, calibration, and preventive maintenance of the imaging equipment at regularly scheduled intervals. The service engineer's qualification will be ensured by the corporation responsible for service and the manufacturer of the equipment used at the site.

Qualified medical physicists (on-site or contracted part-time) should be available for the installation, testing, and ongoing quality control of CT scanners and nuclear medicine equipment.⁷⁰

CT
For the performance of CT scan, medical radiation technologists who are certified by CAMRT, or an equivalent licensing body recognized by CAMRT, are required. The training of technologists specifically engaged in CT should meet with the applicable and valid national and provincial specialty qualifications.

Table 4: Medical Imaging Professionals in Canada, 2006⁴³

Jurisdiction	Diagnostic Radiology Physician	Nuclear Medicine Physician	Medical Radiation Technologists	Nuclear Medicine Technologists	Medical Physicists
NL	46	3	263	15	NR
NS	71	5	403	71	NR
NB	47	3	387	55	NR
PEI	7	0	57	3	0
QC	522	90	3,342	460	NR
ON	754	69	4,336	693	NR
MB	58	8	501	42	NR
SK	61	4	359	36	NR
AB	227	18	1,229	193	NR
BC	241	21	1,352	212	NR
YT	0	0	0	0	0
NT	0	0	26	1	0
NU	0	0	0	0	0
Total	2,034	221	12,255	1,781	322*

AB = Alberta; BC = British Columbia; MB = Manitoba; ON = Ontario; NB = New Brunswick; NL = Newfoundland and Labrador; NR = not reported by jurisdiction; NS = Nova Scotia; NT= Northwest Territories; NU = Nunavut; PEI= Prince Edward Island; QC = Quebec; YT = Yukon.

* This represents a total for all of the jurisdictions.

Return to Summary Table.

Criterion 10: Accessibility of alternative tests (equipment and wait times) (link to definition)

There are notable variations in the availability of medical imaging technologies across Canada. Table 5 provides an overview of the availability of equipment required to detect pulmonary embolism.

Table 5: Diagnostic Imaging Equipment in Canada, 2007⁴³

	Nuclear Medicine Cameras	CT Scanners	SPECT/CT Scanners
Number of devices	603	419	35
Devices per million people	18.4	12.8	1.6
Average number of hours of operation per week (2006-2007)	40	60	n/a
Provinces and territories with no devices available	YT, NT, NU	NU	NL, PEI, NS, MB, AB, YT, NT, NU

AB = Alberta; CT = computed tomography; MB = Manitoba; NS = Nova Scotia; NT = Northwest Territories; NU = Nunavut; PEI = Prince Edward Island; SPECT/CT = single-photon emission computed tomography/computed tomography; YT = Yukon.

V/Q Scanning
For V/Q scans, nuclear medicine facilities with gamma cameras (including SPECT) are required. As of January 1, 2007, there was an average of 18.4 nuclear medicine cameras per million people, with none available in the Yukon, Northwest Territories, or Nunavut.⁴³

CT
A report from the Canadian Institute for Health Information states that, as of January 1, 2007, CT scanners were available at a rate of 12.8 per million people in Canada; however, there were none available in Nunavut.⁴³ For CT scanners, the average weekly use ranged from 40 hours in PEI to 69 hours in Ontario, with a national average of 60 hours.⁴³

In 2010, the average wait time for a CT scan in Canada was 4.2 weeks.⁴⁴

Return to Summary Table.

Criterion 11: Relative cost of the test (link to definition)

Fee codes from the Ontario Schedule of Benefits were used to estimate the relative costs of V/Q scanning and CTPA. Technical fees are intended to cover costs incurred by the hospital (i.e., radiopharmaceutical costs, medical/surgical supplies, and non-physician salaries). Maintenance fees are not billed to OHIP — estimates here were provided by St. Michael's Hospital in Toronto. Certain procedures (i.e., PET scan, CT scan, MRI scan) are paid for, in part, out of the hospital's global budget; these estimates were provided by The Ottawa Hospital. It is understood that the relative costs of imaging will vary from one institution to the next.

According to our estimates (Table 6), the cost of V/Q scanning is $295.23 ($370.93 for SPECT). CTPA is a minimally less costly alternative.

Table 6: Cost Estimates Based on the Ontario Schedule of Benefits for Physician Services Under the Health Insurance Act (September 2011)⁷¹

Fee Code	Description	Tech. Fees ($)	Prof. Fees ($)	Total Costs ($)
V/Q scan
J860	Perfusion and ventilation scintigraphy — same day	176.25	62.80	244.45
J866	Application of tomography (SPECT)	44.60	31.10	75.70
Maintenance fees — from global budget		50.78		50.78
TOTAL		271.63	93.90	370.93
CTPA
X407	CT — Thorax — with IV contrast		79.85	79.85
Maintenance fees — from global budget		36.56		36.56
Technical cost — from global budget		150.00		150.00
TOTAL		186.56	79.85	266.41

CT = computed tomography; CTPA = computed tomography pulmonary angiography; IV = intravenous; Prof. = professional; SPECT = single-photon emission computed tomography; Tech. = technical; V/Q = ventilation/perfusion.

Return to Summary Table.

References

1. Thompson BT, Hales CA. Overview of acute pulmonary embolism. 2010 Dec 3 [cited 2011 Jul 6]. In: UpToDate [Internet]. Version 19.1. Waltham (MA): UpToDate; c2005 - . Available from: http://www.uptodate.com Subscription required.
2. Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, Jonson B, 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 [Internet]. 2009 [cited 2011 Sep 30];36(8):1356-70. Available from: http://www.eanm.org/publications/guidelines/gl_pulm_embolism_part1.pdf
3. Miniati M, Prediletto R, Formichi B, Marini C, Di RG, Tonelli L, et al. Accuracy of clinical assessment in the diagnosis of pulmonary embolism. Am J Respir Crit Care Med. 1999 Mar;159(3):864-71.
4. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J [Internet]. 2008 [cited 2011 Oct 4];29(18):2276-315. Available from: http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-APE-FT.pdf
5. Goldhaber SZ, Visani L, De RM. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353(9162):1386-9.
6. Reinartz P, Buell U. Pulmonary embolism from a nuclear medicine perspective. C2I2. 2005;3(1):9-12.
7. Tapson VF. Treatment of acute pulmonary embolism. 2011 Feb 8 [cited 2011 Jul 6]. In: UpToDate [Internet]. Version 19.1. Waltham (MA): UpToDate; c2005 - . Available from: http://www.uptodate.com Subscription required.
8. Kanne JP, Lalani TA. Role of computed tomography and magnetic resonance imaging for deep venous thrombosis and pulmonary embolism. Circulation. 2004 Mar 30;109(12 Suppl 1):I15-I21.
9. Murray JF, Mason RJ. Diagnosis of pulmonary embolism. 5th ed. In: Murray and Nadel's textbook of respiratory medicine. Philadelphia: Elsevier Saunders; 2010.
10. Runyon MS, Webb WB, Jones AE, Kline JA. Comparison of the unstructured clinician estimate of pretest probability for pulmonary embolism to the Canadian score and the Charlotte rule: a prospective observational study. Acad Emerg Med. 2005 Jul;12(7):587-93.
11. Miniati M, Bottai M, Monti S, Salvadori M, Serasini L, Passera M. Simple and accurate prediction of the clinical probability of pulmonary embolism. Am J Respir Crit Care Med. 2008 Aug 1;178(3):290-4.
12. Barghouth G, Yersin B, Boubaker A, Doenz F, Schnyder P, Delaloye AB. Combination of clinical and V/Q scan assessment for the diagnosis of pulmonary embolism: a 2-year outcome prospective study. Eur J Nucl Med. 2000 Sep;27(9):1280-5.
13. Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004 Aug;2(8):1247-55.
14. Moser KM, Fedullo PF, LitteJohn JK, Crawford R. Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis. JAMA. 1994 Jan 19;271(3):223-5.
15. Stein PD, Matta F, Musani MH, Diaczok B. Silent pulmonary embolism in patients with deep venous thrombosis: a systematic review. Am J Med. 2010;123(5):426-31.
16. Pistolesi M, Miniati M. Imaging techniques in treatment algorithms of pulmonary embolism. Eur Respir J Suppl. 2002 Feb;35:28s-39s.
17. Pleszewski B, Chartrand-Lefebvre C, Qanadli SD, Dery R, Perreault P, Oliva VL, et al. Gadolinium-enhanced pulmonary magnetic resonance angiography in the diagnosis of acute pulmonary embolism: a prospective study on 48 patients. Clin Imaging. 2006;30(3):166-72.
18. Kluge A, Luboldt W, Bachmann G. Acute pulmonary embolism to the subsegmental level: diagnostic accuracy of three MRI techniques compared with 16-MDCT. AJR Am J Roentgenol. 2006;187(1):W7-14.
19. Kearon C. Diagnosis of pulmonary embolism. CMAJ. 2003 Jan 21;168(2):183-94.
20. Hayashino Y, Goto M, Noguchi Y, Fukui T. Ventilation-perfusion scanning and helical CT in suspected pulmonary embolism: meta-analysis of diagnostic performance. Radiology. 2005;234(3):740-8.
21. van Beek EJ, Brouwers EM, Song B, Bongaerts AH, Oudkerk M. Lung scintigraphy and helical computed tomography for the diagnosis of pulmonary embolism: a meta-analysis. Clin Appl Thromb Hemost. 2001;7(2):87-92.
22. Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med. 2000 Feb 1;132(3):227-32.
23. Zophel K, Bacher-Stier C, Pinkert J, Kropp J. Ventilation/perfusion lung scintigraphy: what is still needed? A review considering technetium-99m-labeled macro-aggregates of albumin. Ann Nucl Med. 2009;23(1):1-16.
24. Roy PM, Colombet I, Durieux P, Chatellier G, Sors H, Meyer G. Systematic review and meta-analysis of strategies for the diagnosis of suspected pulmonary embolism. BMJ. 2005;331(7511):259.
25. Cueto SM, Cavanaugh SH, Benenson RS, Redclift MS. Computed tomography scan versus ventilation-perfusion lung scan in the detection of pulmonary embolism. J Emerg Med. 2001;21(2):155-64.
26. Gutte H, Mortensen J, Jensen CV, von der RP, Petersen CL, Kristoffersen US, et al. Comparison of V/Q SPECT and planar V/Q lung scintigraphy in diagnosing acute pulmonary embolism. Nucl Med Commun. 2010;31(1):82-6.
27. Gutte H, Mortensen J, Jensen CV, Johnbeck CB, von der RP, Petersen CL, et al. Detection of pulmonary embolism with combined ventilation-perfusion SPECT and low-dose CT: head-to-head comparison with multidetector CT angiography. J Nucl Med [Internet]. 2009 [cited 2011 Mar 10];50(12):1987-92. Available from: http://jnm.snmjournals.org/content/50/12/1987.long
28. Miles S, Rogers KM, Thomas P, Soans B, Attia J, Abel C, et al. A comparison of single-photon emission CT lung scintigraphy and CT pulmonary angiography for the diagnosis of pulmonary embolism. Chest. 2009;136(6):1546-53.
29. Wang F, Fang W, Lv B, Lu JG, Xiong CM, Ni XH, et al. Comparison of lung scintigraphy with multi-slice spiral computed tomography in the diagnosis of pulmonary embolism. Clin Nucl Med. 2009;34(7):424-7.
30. Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, Jonson B. EANM guidelines for ventilation/perfusion scintigraphy : Part 2. Algorithms and clinical considerations for diagnosis of pulmonary emboli with V/P(SPECT) and MDCT. Eur J Nucl Med Mol Imaging. 2009;36(9):1528-38.
31. American College of Emergency Physicians Clinical Policies Committee, Clinical Policies Committee Subcommittee on Suspected Pulmonary Embolism. Clinical policy: critical issues in the evaluation and management of adult patients presenting with suspected pulmonary embolism. Ann Emerg Med. 2003;41(2):257-70.
32. Thompson AB, Bailey KL, Baustian G, Lim W. Pulmonary embolism. In: First CONSULT. Maryland Heights (MO): MD Consult, Elsevier Inc; 2011.
33. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax. 2003 Jun;58(6):470-83.
34. Menzel T, Wagner S, Kramm T, Mohr-Kahaly S, Mayer E, Braeuninger S, et al. Pathophysiology of impaired right and left ventricular function in chronic embolic pulmonary hypertension: changes after pulmonary thromboendarterectomy. Chest. 2000 Oct;118(4):897-903.
35. Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004 May 27;350(22):2257-64.
36. Ambrosetti M, Ageno W, Spanevello A, Salerno M, Pedretti RF. Prevalence and prevention of venous thromboembolism in patients with acute exacerbations of COPD. Thromb Res. 2003;112(4):203-7.
37. Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007 Oct;98(4):756-64.
38. Katsouda E, Mystakidou K, Rapti A, Argentos S, Kelekis NL, Mastorakou R, et al. Evaluation of spiral computed tomography versus ventilation/perfusion scanning in patients clinically suspected of pulmonary embolism. In Vivo. 2005 Sep;19(5):873-8.
39. Schembri GP, Miller AE, Smart R. Radiation dosimetry and safety issues in the investigation of pulmonary embolism. Semin Nucl Med. 2010 Nov;40(6):442-54.
40. ACR Committee on Drugs and Contrast Media. ACR manual on contrast media [Internet]. Version 7. Reston (VA): American College of Radiology; 2010. [cited 2011 Oct 5]. Available from: http://www.acr.org/SecondaryMainMenuCategories/quality_safety/contrast_manual/FullManual.aspx
41. Lee CI, Elmore JG. Radiation-related risks of imaging studies. 2011 [cited 2011 Apr 20]. In: UpToDate [Internet]. Version 19.1. Waltham (MA): UpToDate; c2005 - . Available from: http://www.uptodate.com Subscription required.
42. Kirsch AJ, Grattan-Smith JD, Molitierno JA. The role of magnetic resonance imaging in pediatric urology. Curr Opin Urol. 2006;16(4):283-90.
43. Canadian Institute for Health Information. Medical imaging in Canada 2007 [Internet]. Ottawa: The Institute; 2008. 199 p. [cited 2011 Apr 12]. Available from: http://secure.cihi.ca/cihiweb/products/MIT_2007_e.pdf
44. Barua B, Rovere M, Skinner BJ. Waiting your turn: wait times for health care in Canada [Internet]. 20th ed. Vancouver (BC): Fraser Institute; 2010 Dec. 90 p. [cited 2011 Apr 15]. (Studies in health care policy). Available from: http://www.fraserinstitute.org/uploadedFiles/fraser-ca/Content/research-news/research/publications/waiting-your-turn-2010.pdf
45. Giuntini C, Di RG, Marini C, Melillo E, Palla A. Pulmonary embolism: epidemiology. Chest. 1995 Jan;107(1 Suppl):3S-9S.
46. Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A, et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743-53.
47. Statistics Canada. Table 102-0529 - deaths, by cause. Chapter IX: diseases of the circulatory system (100 to 199), age group and sex, Canada, 2007, CANSIM [Internet]. Ottawa: Statistics Canada; 2002. [cited 2011 Feb 22]. Available from: http://www5.statcan.gc.ca/cansim/pick-choisir?lang=eng&searchTypeByValue=1&id=1020529
48. Moser KM. Venous thromboembolism. Am Rev Respir Dis. 1990 Jan;141(1):235-49.
49. Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008 Mar 6;358(10):1037-52.
50. Stein PD, Beemath A, Olson RE. Trends in the incidence of pulmonary embolism and deep venous thrombosis in hospitalized patients. Am J Cardiol. 2005 Jun 15;95(12):1525-6.
51. DeMonaco NA, Dang Q, Kapoor WN, Ragni MV. Pulmonary embolism incidence is increasing with use of spiral computed tomography. Am J Med. 2008 Jul;121(7):611-7.
52. Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. Chest. 2001 Jan;119(1 Suppl):108S-21S.
53. Braveman P. Health disparities and health equity: concepts and measurement. Annu Rev Public Health. 2006;27:167-94.
54. Bosomworth J. Diagnosing pulmonary embolism in a rural setting. Can J Rural Med [Internet]. 2005 [cited 2011 Feb 28];10(2):100-6. Available from: http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/cjrm/vol-10/issue-2/pdf/pg100.pdf
55. White RH, Zhou H, Murin S, Harvey D. Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996. Thromb Haemost. 2005;93(2):298-305.
56. White RH, Zhou H, Romano PS. Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California. Ann Intern Med. 1998;128(9):737-40.
57. Stein PD, Kayali F, Olson RE, Milford CE. Pulmonary thromboembolism in Asians/Pacific Islanders in the United States: analysis of data from the National Hospital Discharge Survey and the United States Bureau of the Census. Am J Med. 2004;116(7):435-42.
58. Schneider D, Lilienfeld DE, Im W. The epidemiology of pulmonary embolism: racial contrasts in incidence and in-hospital case fatality. J Natl Med Assoc. 2006;98(12):1967-72.
59. Ibrahim SA, Stone RA, Obrosky DS, Sartorius J, Fine MJ, Aujesky D. Racial differences in 30-day mortality for pulmonary embolism. Am J Public Health. 2006;96(12):2161-4.
60. Hooper WC. Venous thromboembolism in African-Americans: a literature-based commentary. Thromb Res. 2010;125(1):12-8.
61. Committee to Assess Health Risks from Exposure to Low Levels of Radiation, National Research Council. Health risks from exposure to low levels of ionizing radiation: BEIR VII Phase 2 [Internet]. Washington DC: National Academies Press; 2006. [cited 2011 Mar 1]. Available from: http://www.nap.edu./books/030909156X/html
62. Parker MS, Hui FK, Camacho MA, Chung JK, Broga DW, Sethi NN. Female breast radiation exposure during CT pulmonary angiography. AJR Am J Roentgenol. 2005 Nov;185(5):1228-33.
63. Svensson MH, Svensson E, Lasson A, Hellstrom M. Patient acceptance of CT colonography and conventional colonoscopy: prospective comparative study in patients with or suspected of having colorectal disease. Radiology [Internet]. 2002 [cited 2011 Jun 13];222(2):337-45. Available from: http://radiology.rsnajnls.org/content/222/2/337.long
64. Institute for Clinical Systems Improvement. Venous thromboembolism diagnosis and treatment [Internet]. 11th ed. Bloomington (MN): ICSI; 2011 Mar. 93 p. [cited 2011 Oct 4]. (Health Care Guidelines). Available from: http://www.icsi.org/venous_thromboembolism/venous_thromboembolism_4.html
65. Scottish Intercollegiate Guidelines Network (SIGN). Prevention and management of venous thromboembolism [Internet]. Edinburgh: SIGN; 2010 Dec. 87 p. [cited 2011 Oct 4]. (SIGN publication no. 122). Available from: http://www.sign.ac.uk/pdf/sign122.pdf
66. Gottschalk A, Sostman HD, Coleman RE, Juni JE, Thrall J, McKusick KA, et al. Ventilation-perfusion scintigraphy in the PIOPED study. Part II. Evaluation of the scintigraphic criteria and interpretations. J Nucl Med. 1993 Jul;34(7):1119-26.
67. Leblanc M, Paul N. V/Q SPECT and computed tomographic pulmonary angiography. Semin Nucl Med. 2010 Nov;40(6):426-41.
68. Siddiqi NH. Contrast medium reactions. 2011 Apr 20 [cited 2011 Oct 5]. In: Medscape reference [Internet]. New York: WebMD; c1994 - . Available from: http://emedicine.medscape.com/article/422855-overview.
69. Hunt CH, Hartman RP, Hesley GK. Frequency and severity of adverse effects of iodinated and gadolinium contrast materials: retrospective review of 456,930 doses. AJR Am J Roentgenol [Internet]. 2009 Oct [cited 2011 Jun 13];193(4):1124-7. Available from: http://www.ajronline.org/cgi/reprint/193/4/1124
70. Royal College of Physicians and Surgeons of Canada. Objectives of training in nuclear medicine [Internet]. Ottawa: The College; 2009. [cited 2011 Jun 13]. Available from: http://rcpsc.medical.org/residency/certification/objectives/nucmed_e.pdf
71. Ontario Ministry of Health and Long-Term Care. Schedule of benefits for physician services under the Health Insurance Act: effective September 1, 2011 [Internet]. Toronto: OMHLTC; 2011. [cited 2011 Oct 5]. Available from: http://www.health.gov.on.ca/english/providers/program/ohip/sob/physserv/physserv_mn.html

 

Appendix 1: Multi-Criteria Decision Analysis Definitions

Domain 1: Criteria Related to the Underlying Health Condition
Criterion	Definition
1. Size of the affected population	The estimated size of the patient population that is affected by the underlying health condition and which may potentially undergo the test. The ideal measure is point prevalence, or information on how rare or common the health condition is.
2. Timeliness and urgency of test results in planning patient management	The timeliness and urgency of obtaining the test results in terms of their impact on the management of the condition and the effective use of health care resources.
3. Impact of not performing a diagnostic imaging test on mortality related to the underlying condition	Impact of not performing the test, in whatever way, on the expected mortality of the underlying condition. Measures could include survival curves showing survival over time, and/or survival at specific time intervals with and without the test.
4. Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition	Impact of not performing the test, in whatever way, on the expected morbidity or on the quality of life reduction of the underlying condition. Measures of impact may include natural morbidity outcome measures such as events or disease severity, or might be expressed using generic or disease-specific quality of life rating scales with and without the test.
Domain 2: Criteria Comparing 99mTc with an Alternative, or Comparing between Clinical Uses
Criterion	Definition
5. Relative impact on health disparities	Health disparities are defined as situations where there is a disproportionate burden (e.g., incidence, prevalence, morbidity, or mortality) amongst particular population groups (e.g., gender, age, ethnicity, geography, disability, sexual orientation, socioeconomic status, and special health care needs). Impact on health disparities is assessed by estimating the proportion of current clients of the 99mTc-based test that are in population groups with disproportionate burdens. (Explanatory note: The implication of this definition is that, everything else being the same, it is preferable to prioritize those clinical uses that have the greatest proportion of clients in groups with disproportionate burdens.)
6. Relative acceptability of the test to patients	Acceptability of the 99mTc-based test from the patient's perspective compared with alternatives. Patient acceptability considerations include discomfort associated with the administration of the test, out-of-pocket expenses or travel costs, factors that may cause great inconvenience to patients, as well as other burdens. This criterion does not include risks of adverse events but is about everything related to the experience of undergoing the test.
7. Relative diagnostic accuracy of the test	Ability of the test to correctly diagnose the patients who have the condition (sensitivity) and patients who do not have the condition (specificity) compared with alternatives.
8. Relative risks associated with the test	Risks associated with the test (e.g., radiation exposure, side effects, adverse events) compared with alternatives. Risks could include immediate safety concerns from a specific test or long-term cumulative safety concerns from repeat testing or exposure.
9. Relative availability of personnel with expertise and experience required for the test	Availability of personnel with the appropriate expertise and experience required to proficiently conduct the test and/or interpret the test findings compared with alternatives.
10. Accessibility of alternatives (equipment and wait times)	Availability (supply) of equipment and wait times for alternative tests within the geographic area. Includes consideration of the capacity of the system to accommodate increased demand for the alternatives. Excludes any limitation on accessibility related to human resources considerations.
11. Relative cost of the test	Operating cost of test (e.g., consumables, heath care professional reimbursement) compared with alternatives.

^99mTc = technetium-99m.

Appendix 2: Literature Search Strategy

OVERVIEW
Interface:		Ovid
Databases:		Ovid MEDLINE In-Process & Other Non-Indexed Citations and Ovid MEDLINE <1948 to January 28, 2011>
Date of Search:		January 31, 2011
Alerts:		Monthly search updates began January 31, 2011 and ran until October 2011.
Study Types:		Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies, and diagnostic accuracy studies.
Limits:		No date limit for systematic reviews; publication years 2006 – January 2011 for primary studies English language Human limit for primary studies
SYNTAX GUIDE
/	At the end of a phrase, searches the phrase as a subject heading
MeSH	Medical subject heading
.fs	Floating subheading
exp	Explode a subject heading
*	Before a word, indicates that the marked subject heading is a primary topic; or, after a word, a truncation symbol (wildcard) to retrieve plurals or varying endings
?	Truncation symbol for one or no characters only
ADJ	Requires words are adjacent to each other (in any order)
ADJ#	Adjacency within # number of words (in any order)
.ti	Title
.ab	Abstract
.hw	Heading word: usually includes subject headings and controlled vocabulary
.tw	Text word: searches title, abstract, captions, and full text
.mp	Keyword search: includes title, abstract, name of substance word, subject heading word and other text fields
.pt	Publication type
.nm	Name of substance word: used to search portions of chemical names and includes words from the CAS Registry/EC Number/Name (RN) fields
.jw	Journal words: searches words from journal names
/du	Diagnostic use
/ri	Radionuclide imaging

 

Ovid MEDLINE Strategy
Line #	Search Strategy
1	Technetium/
2	exp Technetium Compounds/
3	exp Organotechnetium Compounds/
4	exp Radiopharmaceuticals/
5	radioisotope*.mp.
6	(technetium* or Tc-99 or Tc99 or Tc-99m or Tc99m or 99mTc or 99m-Tc).tw,nm.
7	Perfusion Imaging/ or Radionuclide Imaging/
8	Pulmonary Embolism/ri
9	Lung/ri
10	Pulmonary Ventilation/
11	(gamma camera imag* or perfusion imaging or radionuclide imaging or radionuclide scan* or lung perfusion or nuclear medicine test* or scintigraph* or scintigram* or scintiphotograph*).tw.
12	(ventilation-perfusion adj5 (imaging or scan* or scintigraph* or SPECT)).mp.
13	("ventilation/perfusion" adj5 (imaging or scan* or scintigraph* or SPECT)).mp.
14	((ventilation and perfusion) adj5 (imaging or scan* or scintigraph* or SPECT)).mp.
15	((VQ or V-Q or "v/q") adj5 (imaging or scan* or scintigraph* or SPECT)).mp.
16	or/1-15
17	Pulmonary Embolism/
18	(pulmonary adj2 (embolism* or embolus or emboli or thromboembolism* or thrombo-embolism*)).tw.
19	or/17-18
20	Meta-Analysis.pt.
21	Meta-Analysis/ or Systematic Review/ or Meta-Analysis as Topic/ or exp Technology Assessment, Biomedical/
22	((systematic* adj3 (review* or overview*)) or (methodologic* adj3 (review* or overview*))).tw.
23	((quantitative adj3 (review* or overview* or synthes*)) or (research adj3 (integrati* or overview*))).tw.
24	((integrative adj3 (review* or overview*)) or (collaborative adj3 (review* or overview*)) or (pool* adj3 analy*)).tw.
25	(data synthes* or data extraction* or data abstraction*).tw.
26	(handsearch* or hand search*).tw.
27	(mantel haenszel or peto or der simonian or dersimonian or fixed effect* or latin square*).tw.
28	(met analy* or metanaly* or health technology assessment* or HTA or HTAs).tw.
29	(meta regression* or metaregression* or mega regression*).tw.
30	(meta-analy* or metaanaly* or systematic review* or biomedical technology assessment* or bio-medical technology assessment*).mp,hw.
31	(medline or Cochrane or pubmed or medlars).tw,hw.
32	(cochrane or health technology assessment or evidence report).jw.
33	or/20-32
34	exp "Sensitivity and Specificity"/
35	False Positive Reactions/
36	False Negative Reactions/
37	du.fs.
38	sensitivit*.tw.
39	(predictive adj4 value*).tw.
40	distinguish*.tw.
41	differentiat*.tw.
42	enhancement.tw.
43	identif*.tw.
44	detect*.tw.
45	diagnos*.tw.
46	accura*.tw.
47	comparison*.tw.
48	Comparative Study.pt.
49	(Validation Studies or Evaluation Studies).pt.
50	Randomized Controlled Trial.pt.
51	Controlled Clinical Trial.pt.
52	(Clinical Trial or Clinical Trial, Phase II or Clinical Trial, Phase III or Clinical Trial, Phase IV).pt.
53	Multicenter Study.pt.
54	(random* or sham or placebo*).ti.
55	((singl* or doubl*) adj (blind* or dumm* or mask*)).ti.
56	((tripl* or trebl*) adj (blind* or dumm* or mask*)).ti.
57	(control* adj3 (study or studies or trial*)).ti.
58	(non-random* or nonrandom* or quasi-random* or quasirandom*).ti.
59	(allocated adj "to").ti.
60	Cohort Studies/
61	Longitudinal Studies/
62	Prospective Studies/
63	Follow-Up Studies/
64	Retrospective Studies/
65	Case-Control Studies/
66	Cross-Sectional Study/
67	(observational adj3 (study or studies or design or analysis or analyses)).ti.
68	cohort.ti.
69	(prospective adj7 (study or studies or design or analysis or analyses or cohort)).ti.
70	((follow up or followup) adj7 (study or studies or design or analysis or analyses)).ti.
71	((longitudinal or longterm or (long adj term)) adj7 (study or studies or design or analysis or analyses or data or cohort)).ti.
72	(retrospective adj7 (study or studies or design or analysis or analyses or cohort or data or review)).ti.
73	((case adj control) or (case adj comparison) or (case adj controlled)).ti.
74	(case-referent adj3 (study or studies or design or analysis or analyses)).ti.
75	(population adj3 (study or studies or analysis or analyses)).ti.
76	(cross adj sectional adj7 (study or studies or design or research or analysis or analyses or survey or findings)).ti.
77	or/34-76
78	Case Reports.pt.
79	77 not 78
80	16 and 19 and 33
81	limit 80 to english language
82	16 and 19 and 79
83	limit 82 to (english language and humans and yr="2006 -Current")

 

OTHER DATABASES
PubMed	Same MeSH, keywords, limits, and study types used as per MEDLINE search, with appropriate syntax used.
Cochrane Library Issue 1, 2011	Same MeSH, keywords, and date limits used as per MEDLINE search, excluding study types and Human restrictions. Syntax adjusted for Cochrane Library databases.

 

GREY LITERATURE SEARCHING
Dates for Search:	March 2011
Keywords:	Included terms for radionuclide imaging and gastrointestinal hemorrhage.
Limits:	No limits

The following sections of our grey literature checklist, "Grey matters: a practical tool for evidence-based medicine" were searched:

• Health Technology Assessment Agencies (selected)
• Clinical Practice Guidelines
• Databases (free)
• Internet Search.

 

Appendix 3: Definitions

Millisievert (mSv): The sievert — named after Rolf Sievert, a Swedish medical physicist — is a unit of dose equivalence. It shows the biological effects of radiation as opposed to the physical aspects, which are characterized by the absorbed dose (see milligray, below). A millisievert is one-thousandth of a sievert.

MilliGray (mGy): The gray — named after Louis Harold Gray, a British physicist — is a unit of absorbed radiation dose of ionizing radiation (e.g., X-rays). It is defined as the absorption of one joule of ionizing radiation by one kilogram of human tissue.

Visual Analog Scale (VAS): A visual analog scale usually consists of a single horizontal line on a page, with verbal and numerical descriptors at each end. Vertical lines and sometimes numbers are added to make scale units. One end point of the line (usually denoted as 10 or 100) is labelled as "the best health state possible," and the opposite end point (denoted as 0) is labelled as "the worst health state possible."