Keywords Diagnostic accuracy - perfusion lung scan - Prospective Investigative Study of Acute
Pulmonary Embolism Diagnosis criteria - pulmonary thromboembolism
Introduction
The application of lung perfusion scan for the detection of acute pulmonary thromboembolism
(APTE) has been overwhelmed in our clinical practice for years by pulmonary computed
tomography (CT) angiography corresponding with its reportedly high accuracy. Five
years ago, when the lung perfusion scans were reported according to the probability-based
criteria of Modified Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED),[1 ] we had seldom lung perfusion scan requests peaking to 1 or 2 per week. The lack
of radioaerosol or Technegas ventilation scans hindered further the use of nuclear
medicine scintigraphy for the detection of APTE in Iran where the ventilation scan
with81 Kr is available in few centers once a week. The results of PIOPED I and II
studies highlighted the flaws of perfusion scan for the diagnosis of APTE.[2 ],[3 ] On the other hand, the high sensitivity for CT angiography leads to a significant
clinical burden mainly secondary to the diagnosis of subsegmental pulmonary artery
thromboembolism.[4 ] The benefit of the treatment of these subsegmental PTEs is not well documented.
Furthermore, the high radiation to the breast of the youngsters and the complications
of the radiocontrast substrates were considered as significant drawbacks.[5 ] Meanwhile, the widespread use of single-photon emission computed tomography (SPECT)
imaging in different scintigraphy protocols was employed for pulmonary perfusion scans
in certain studies.[6 ],[7 ] The use of SPECT imaging for pulmonary perfusion scan is still not a guideline-supported
advice, but in our practice, we found its superior application over usual planar imaging.[8 ] We discussed the reasons for the low referral with the local pulmonologists. Seemingly,
high rates of intermediate and low probability for PTE reports were the main obstacle.
In line with other investigators, including the practice in the Montefiore Medical
Center, we changed our reporting system from probability-based PIOPED criteria into
definite reporting based on the Prospective Investigative Study of Acute Pulmonary
Embolism Diagnosis (PISAPED) criteria.[9 ] Furthermore, SPECT imaging was used in abnormal scans with suspicious wedge-shaped
perfusion defects. The performance of the scan was seemingly convincing and there
was an increase in the clinical requests for pulmonary perfusion scan. After 5 years
of clinical practice, the ratio of requests for CT angiography and perfusion scans
dramatically changed and at the time of this publication CT angiography and lung perfusion
scan have an equal share of the requests for the evaluation of APTE (i.e., about 600
requests per year). In the current study, we assess the results of the lung perfusion
scans that were reported using PISAPED criteria done 3 years ago to document the diagnostic
accuracy of the method.
Methods
The study population consists of 147 consecutive patients of a single pulmonologist
(MA) hospitalized from March 2014 who had been sent for lung perfusion scan to the
department of nuclear medicine of our teaching university hospital. The pulmonologist
was piloting the already implemented protocol in the hospital to substitute PISAPED
for PIOPED criteria. Patients were injected with 1–3 mCi 99m Tc-MAA (Pars Isotope, Tehran, Iran) containing 250,000–750,000 particles. The injection
and imaging were done in a supine position and imaging was done by either ADAC Forte
(ADAC Laboratories, Milpitas, CA, USA) or AnyScan (Mediso, Budapest, Hungary) dual-head
gamma cameras. The abnormal planar images with suspicious or indeterminate perfusion
defects underwent SPECT imaging. The matrix size of 128 × 128, projection time of
12 s, and 60 stops were employed. The report was done by two nuclear physicians (MA
and SF). They accessed the medical files, clinical risk factors, and chest CT or chest
X-ray of the patients. The scan was reported as one of the following three categories:
(1) normal or negative for APTE, (2) positive for or in favor of APTE, and (3) suggesting
certain further procedures including ventilation scan or chest CT or stating that
the scan is nondiagnostic. Any single moderate- or large-size wedge-shaped peripheral
perfusion defect larger than the findings of chest X-ray or CT scan was considered
an evidence of APTE irrespective of the location or multiplicity of the defects. The
clinical data of the patients were collected. The presence of S1Q3T3, ST-T changes
in precordial leads and right bundle branch block were considered as electrocardiograph
findings in favor of PTE.[10 ] The presence of right ventricular (RV) enlargement and highly pulmonary pressure
were considered signs in favor of PTE in echocardiography.[11 ] Wells' score was also calculated; the scores ≥4 were considered highly probable
for PTE.[12 ] Inherited and acquired risk factors for PTE were also collected, and the number
of risk factors was calculated.[13 ],[14 ] Patients were followed up, and the final diagnosis about the presence or absence
of APTE was made retrospectively by the pulmonologist; she had access to all data
including clinical probability, results of the laboratory data, and imaging including
scan and CT angiography and the follow-up of the patients. The exact process she employed
for the final diagnosis is rather undefinable; however, it can be underscored that
improvement of the patients with anticoagulation in the line of positive imaging on
one hand and recurrence hence confirmation of the PTE in the follow-up period on the
other hand were the main decision anchors and lead points. Furthermore, many of patients
who had discordant results of pulmonary perfusion scan with the clinical probability
for APTE had CT angiography imaging. When the CT angiography was positive, the scan
was considered false negative. In our hospital, this approach is now included in the
protocol for the assessment of suspected patients for APTE.[15 ] Patients without either recurrence during the follow-up or anticoagulation were
considered negative for APTE.
Results
Patients (male: 68, 46.6%) aged 55.9 ± 17.2 were followed up for 6.2 ± 5.3 months
(1–48 months). The follow-up was not completed in six patients. Of all, 21 (14.3%)
patients were diagnosed to have PTE. The clinical characteristics and findings of
patients with respect to their final diagnosis are presented in [Table 1 ]. The scans were positive, negative, and indeterminate in 17 (11.6%), 126 (85.7%),
and 4 (2.7%) patients, respectively. The accuracy of the test for the diagnosis of
PTE was 87.9%. The diagnostic performance of the perfusion scan is presented in [Table 2 ]. The frequency of highly probable cases for PTE according to the Wells' criteria
correlated with the final diagnosis [85.7% vs. 35.3% in patients positive and negative
for PTE, respectively; [Table 1 ]. The results of echocardiography, as we defined a predictor for PTE, were inversely
correlated with the occurrence of PTE [25% in patients positive vs. 45.6% in patients
negative for PTE; [Table 1 ]. Four patients out of nine with false-negative results were highly probable for
APTE: three of them had multiple lung metastases and a patient had a previous history
of PTE. Among other patients with false-negative results, a patient had sleep apnea
with acute respiratory distress; a patient had a history of lichen planus with acute
dyspnea; and a female patient was receiving oral contraceptive pills with dyspnea.
A report was technically wrong in which a positive scan with indicative findings had
erroneously been reported negative for APTE.
Discussion
Table 1 Health characteristics, Wells´ score, echography, and electrocardiogram findings
of patients with and without pulmonary thromboembolism
Table 2 Diagnostic performance of the perfusion scan
The diagnostic accuracy of lung perfusion scan based on the PISAPED reporting system,
without the use of ventilation scan, in the setting of our inpatient suspected PTE
cases was about 88%. False-negative results are concerning, and about half of the
false-negative reports occurred in patients clinically probable for PTE. We employed
PISAPED criteria without ventilation scan which has been superior over the old PIOPED
and modified PIOPED criteria.[16 ] The evidences, opposing the essential theory to detect PTE based on the mismatch
perfusion and ventilation, indicate degrees of matched perfusion and ventilation defects
occur in PTE patients during the course of disease.[17 ]
The radiation dose from the lung perfusion scan with the injection of 1–3 mCi 99m Tc-MAA is below 2 mSv, which is far below the radiation from the chest CT and chest
angiographies (personal communication, unpublished data). Many dose reduction protocols
for CT angiography are not actually employed in practice. Furthermore, the radiation
to the chest and breast of young female patients and its cancer-added risk are concerning.
Addition of SPECT imaging does not add into the injected dose, and by obviation of
the need for ventilation scan would keep the radiation optimally low. The dose employed
in pregnant women is even reduced with a lower number of used particles with preserving
the quality of the scan to be diagnostic.[18 ] Hence, future studies may focus on the dose reduction in general population assessing
the quality of the scan and its diagnostic accuracy.
In the setting of inpatients who have a high prevalence of diabetes and history of
frequent use of radiologic contrast agents, lung perfusion scan provides with the
advantage that imposes no further burden on the renal system. The lung perfusion scan
is quite affordable comparable to the fee for CT angiography in our practice. Disadvantages
are among the unavailability during the night hours and the failure to diagnose conditions
other than PTE. Albeit, in our setting, most of the patients have had a chest CT which
could be used for both evaluation of other pathologies and for comparison with SPECT
images.
The subsegmental PTE cannot be detected in the lung perfusion scan using the PISAPED
criteria. In PISAPED criteria, at least one moderate-to-large size perfusion defect
should be detected which comprises more than 25% of any segment.[19 ] Subsegmental occlusions which would result in defects less extended than this cutoff
could not be evaluated. This might be a source of the error and the reason for false-negative
results. Nevertheless, the clinical importance of subsegmental PTEs is controversial.[20 ] Three of false-negative patients were cancer patients. We may consider this fact
in the way that perfusion defects and lung metastases were undifferentiable for the
nuclear physician reviewing SPECT and chest CT images. The prevalence of chronic obstructive
pulmonary disease (COPD) in inpatient subjects suspected of APTE is high. Nevertheless,
just one of false-negative results occurred in an asthmatic patient, whereas many
chest X-ray and CT images were abnormal. We do not believe that abnormal chest findings
in COPD patients obviate the use of perfusion scan for the diagnosis of PTE.
The clinical probabilities and the Wells' criteria score correlated very strongly
with the final diagnosis. The absence of such correlation for the echocardiographic
findings could possibly be rooted in the wrong selection we did among the echocardiographic
findings for PTE. RV dysfunction and RV shape (i.e., D sign) are possibly more important
than the presence of RV dilation and pulmonary hypertension.[21 ] Because the clinical risk factors were reviewed interpreting the scan, pretest clinical
probability could introduce bias in interpretation of images. However, if the objective
is to evaluate the overall scan value, one may add clinical/laboratory data into the
test.
Conclusion
The accuracy of perfusion-only lung scan was reasonably high using PISAPED criteria
in our practice. Considering the cost, low radiation burden, and absence of nephrotoxicity,
the lung perfusion scan could be used effectively in inpatient settings.
