An accurate diagnosis of acute pulmonary embolism (PE) is essential and remains a challenge for clinicians and imaging experts. PE is a severe and potentially fatal disease with a high incidence of two per 1000 persons per year in the Western countries [1–4].
Ventilation/perfusion (V/Q) scintigraphy using two-dimensional planar imaging is currently the standard nuclear medicine method applied in patients suspected of PE. We have recently shown that V/Q single photon emission computed tomography (SPECT) combined with a low-dose CT scan has a high diagnostic accuracy and is superior in sensitivity and specificity than pulmonary multidetector computer tomography (MDCT) angiography . This, together with previous data, may indicate that V/Q SPECT probably has a superior diagnostic performance compared with planar imaging [6–9].
The objective of this study was to compare the diagnostic performance of planar V/Q scintigraphy with that of V/Q SPECT on a head-to-head basis in patients suspected of PE using a composite gold standard including pulmonary MDCT angiography, V/Q SPECT in combination with low-dose CT, clinical history and follow-up data, D-dimer, ECG, transthoracic echocardiography, and ultrasound of the lower extremity veins.
Study design, selection criteria, and patients
This was a prospective study carried out in consecutive patients with suspected acute PE at Frederiksberg Hospital from June 2006 to February 2008. All patients were referred to the Department of Clinical Physiology and Nuclear Medicine, Frederiksberg Hospital, Denmark, for a V/Q SPECT suspected of PE. The regional ethics committee approved the study (H-KF-308395) and written informed consent was obtained from all patients. The study protocol was compliant with guidelines in the Helsinki Declaration on human experimentation. Patients were eligible if there was a suspicion of PE, defined as an acute onset of new or worsening shortness of breath or chest pain without any obvious cause and with a positive D-dimer test (>0.5 mg/l) or a Wells score of more than 2 .
Out of 72 patients who met our inclusion criteria, 31 (15 men) were excluded from the study on account of allergy to iodine contrast agents (N=1), impaired renal function (P-creatinine>0.120 mmol/l/l; N=21), a decision not to participate in the study (N=4), lack of cooperation (N=2), absence of peripheral venous access (N=2), or technical issues (N=1).
One patient was ineligible to participate because of low clinical suspicion caused by a Wells score of less than 2 and a negative D-dimer.
The remaining 41 patients all consented to diagnostic testing, including pulmonary MDCT angiography, V/Q SPECT, blood pressure measurement, and blood samples. All patients were followed up for at least 6 months after the scans with telephone interview and review of hospital charts.
The pulmonary MDCT angiography and V/Q SPECT were all performed using an integrated two-headed γ-camera and an MDCT (16 slice) scanner (Philips Precedence, Philips Healthcare, Eindhoven, The Netherlands).
Computed tomography acquisition parameters and reconstruction
The CT protocol consisted of two successive acquisitions with the patients scanned in the supine position. The first acquisition consisted of a low-dose CT scan (kVp: 140, mAs/slice: 20, collimator: 16×1.5 mm, rotation time: 0.5 s, pitch: 0.813) and was obtained during tidal breathing.
The second MDCT acquisition consisted of a pulmonary MDCT angiography in suspended, deep inspiration. Pulmonary MDCT angiography was carried out in cranial–caudal direction at 120 kV and 230 mAs with 16×0.75 mm collimation, pitch 0.94, rotation time 0.5 s, and acquisition in a 512×512 matrix. The pulmonary MDCT images were obtained with administration of 80 ml contrast (Optiray, Tyco/Health care, Mallinckrodt, USA) at 4.3 ml/s into a cubital vein followed by a saline chaser bolus of 42 ml injected with a flow rate of 4.3 ml/s.
To ensure optimal opacification of the lung arteries, the scan was performed using bolus tracking, entering a circular region of interest in the trunk of the pulmonary artery. The threshold for triggering was preset at 100 HU.
The pulmonary MDCT angiography was reconstructed with a contiguous slice thickness of 0.8 mm and transferred to a dedicated workstation where they were reviewed (Extended Brilliance Workspace, Philips Medical Systems, Eindhoven, The Netherlands).
All scans were evaluated by C.V.J. and P.V.R. with eight and 15 years of experience, respectively, in reviewing pulmonary MDCT angiography.
Pulmonary V/Q SPECT/planar acquisition and reconstruction
The pulmonary SPECT included a perfusion SPECT study and a ventilation SPECT study obtained simultaneously within 13 min (i.e. 36 projections per head of 20 s each over 180°) and performed immediately after the MDCT acquisition with the patient still in the supine position. Both studies were performed simultaneously with low-energy, general-purpose collimators and acquired in a 128×128 matrix.
SPECT datasets were attenuation corrected using the low-dose CT acquisition with iterative reconstruction using the software Autospect+ and Astonish with three iterations and 16 subsets (Philips Medical Systems, Eindhoven, The Netherlands). Then, planar imaging followed the SPECT acquisition. Supine planar images were acquired in posterior, anterior, and four oblique views (right anterior oblique, right posterior oblique, left posterior oblique, and left anterior oblique) with 256×256 matrix, double isotope (120 s). Images were collected with a 20% energy window setting at 140 keV on a single-headed γ-camera (ADAC; Philips Medical Systems) Argus with an LEGP collimator. Perfusion studies were performed after intravenous injection of 150 MBq of 99mTc-macroaggregated albumin (99mTC-MAA) (Mallinckrodt, Hazelwood, Missouri, USA) during two respiratory cycles. Ventilation scintigraphy was conducted during quiet tidal inhalation of 81mKr, which was extracted from a 81Rb–81mKr generator (made at our institution) sized 600 MBq by oxygen flow of 1 l/min.
V/Q SPECT was read blinded to clinical history of the patients on a Jetstream Workstation (Philips Medical Systems) by J.M. (7 years of experience of V/Q SPECT reading). All perfusion and ventilation defects were noted for size and segmental location. PE was diagnosed if one or more perfusion defects (>0.5 segment) with normal ventilation (mismatch) were present (Fig. 1). V/Q SPECT datasets were reviewed first independently and a diagnosis was established. Then the V/Q SPECT was viewed in combination and fused with the pulmonary low-dose CT and a new diagnosis was obtained. We used an automatic 3D imaging registration software tool, where the low-dose CT, V/Q SPECT, and fusion images were displayed in axial, coronal, and sagital planes (Syntegra, Version 2.3.1; Philips Medical Systems).
The planar lung scintigraphy acquisition was viewed on a MEDIC 2000 XP workstation (Gamma-soft; Virum, Denmark) and was reviewed by A.K. (13 years of experience) and C.L.P. (15 years of experience) blinded to clinical history of the patient using the gestalt criteria. The reviewers did not have access to the contemporaneous chest radiograph.
The final diagnosis was made at a consensus side-by-side reading of all lesions detected on the pulmonary MDCT angiography, planar lung scintigraphy, and the V/Q SPECT in combination with low-dose CT using all the available information from ECG, transthoracic echocardiography, Doppler US examinations of the lower extremity veins, D-dimer levels, clinical data, and follow-up from hospital charts or telephone interviews. Finally, PE was ruled out in patients if there was no evidence of PE in the clinical data and follow-up including clinical time course, response to treatment within 6 months, or if they died and PE was an unlikely cause of death.
Descriptive data are shown as means±SD. Means were compared using a two-sample t-test, and a P value of less than 0.05 was considered significant. All statistical analyses were performed using SPSS 15.0 (Chicago, Illinois, USA).
A total of 41 patients were scanned. Patient characteristics are shown in Table 1. At the consensus meeting, five patients were indeterminable regarding the final diagnosis (i.e. no reference available, due to suboptimal technical quality of the datasets). Of the remaining 36 patients, 11 (31%) had PE. Lung scintigraphy planar imaging datasets had a sensitivity of 64% and a specificity of 72% for detection of PE and a positive predictive value and negative predictive value of 50 and 82%, respectively (Tables 2 and 3). V/Q SPECT had a sensitivity of 100% and a specificity of 87% for detection of PE and positive predictive value and negative predictive value of 77 and 100%, respectively (Tables 2 and 3).
On V/Q SPECT, we had three false-positive PE patients. All had moderate mismatched defects, which corresponded to atelectasis, fluid, or fissures on the low-dose CT and pulmonary MDCT angiography.
In this study, we investigated prospectively and on a head-to-head basis the diagnostic performances of both V/Q SPECT and planar scintigraphy in consecutive patients suspected of PE. Our major finding was that V/Q SPECT had a high sensitivity and specificity and that it was higher than that of pulmonary planar V/Q scintigraphy.
To the best of our knowledge, this is the first prospective study comparing the diagnostic performance of V/Q SPECT and pulmonary planar V/Q scintigraphy using a composite diagnosis including MDCT and V/Q SPECT in combination with low-dose CT, clinical symptoms, and follow-up data on a head-to-head basis in patients suspected of having PE.
Similar results were found in an experimental study in a porcine model comparing planar imaging with SPECT using 99mTc-MAA albumin and 99mTc-diethylene triamine pentaacetic acid (DTPA) aerosols. They induced artificial emboli labeled with 201TI and showed that SPECT compared with planar imaging had both higher sensitivity (91 vs. 64%) and specificity (87 vs. 79%) . A higher sensitivity (97 vs. 77%) was also shown in a study using Monte–Carlo simulation mimicking PE defects , and an increased sensitivity was also observed in a canine study at the subsegmental level .
The diagnostic performances of V/Q SPECT and planar V/Q scintigraphy have also previously been compared in clinical studies. In a study where planar V/Q scintigraphy images were extracted from V/Q SPECT datasets, sensitivity, specificity, and accuracy of 76/85/81%, respectively, could be achieved compared with 97/91/94% from the original V/Q SPECT images . According to the study mentioned above, SPECT increased the number of detectable defects of the segmental level by 13%, whereas the number of defects of the subsegmental level was increased by 83%. Planar-like images had been generated from the SPECT using either angular summed images [11,12] or reconstructed SPECT data projected through an attenuation map to generate reprojected planar images . However, interpretation of these planar-like images should be made with caution.
However, in our study real planar images were obtained in a separate session. In a previous study, we found that the V/Q SPECT in combination with a low-dose CT had a sensitivity of 97% and a specificity of 100% for the detection of acute PE . In this study, we found a comparably high sensitivity (100%) in V/Q SPECT alone but a specificity that tended to be lower. It seems that the addition of a low-dose CT decreases the incidence of false-positive PE diagnoses and thereby increases the specificity. The addition of a low-dose CT is a valuable tool when determining the origin of the mismatched defect on the V/Q SPECT.
SPECT acquisition has replaced conventional planar imaging in many protocols within nuclear medicine. Given the improvements in sensitivity, specificity, and diagnostic accuracy that have generally accompanied the transition from two-dimensional to three-dimensional imaging, it is surprising that only a limited number of centers routinely use the SPECT technique with V/Q scintigraphy in the work-up of acute PE .
One of the limitations of the two-dimensional planar imaging is that there is a significant overlap of anatomical segments in the lungs predominantly in the bases, where the lung segments are compactly filled. Embolic defects may not be detected if there is a shine through of overlying radioactivity occurring from underlying lung segments with normal perfusion and accordingly, this may reduce the sensitivity and increase the percentage of intermediate scans [14–16]. SPECT avoids this problem making it superior in imaging all segments of the lungs and more accurately defining the size and location of perfusion defects .
Today, two-headed and three-headed gamma cameras are available permitting V/Q SPECT in a short examination time and with no supplementary inconvenience for the patients. The patients sustained the supine position during V/Q SPECT, the immobilization lasted 20 min, and it was well tolerated even by critically ill patients. Only two of 72 patients were ineligible to participate because of discomfort, shortness of breath, or lack of cooperation in the supine position. It should be mentioned that in addition to V/Q SPECT and low-dose CT, we also acquired a diagnostic lung CT and a cardiac CT for research purpose. The patients were in the scanner for approximately 45 min, which is longer than if only V/Q SPECT was performed. In our experience, only 2–3% of patients are not able to cooperate at a V/Q SPECT examination, which is comparable with conventional lung scintigraphy at our departments.
V/Q SPECT has a higher sensitivity and specificity than V/Q scintigraphy planar imaging in the work-up of PE and we recommend V/Q SPECT as a routine procedure for most patients in the diagnosis of acute PE.
The authors are grateful to the technologists and radiographers at the Department of Clinical Physiology and Nuclear Medicine, Frederiksberg Hospital for invaluable assistance.
Conflicts of interest: none declared.
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