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1
Department of Radiology, Kaohsiung Veterans General Hospital, 386 Ta-chung 1st
Rd., Kaohsiung, 813, Taiwan.
2
School of Medicine, National Yang-Ming University, 155, Li-Nong St., Sec. 2,
Peitou, Taipei, Taiwan, R.O.C.
3
Division of Respiratory Care, Department of Medicine, Kaohsiung Veterans
General Hospital, Kaohsiung, 813, Taiwan, R.O.C.
4
Present address: Division of Respiratory and Critical Care Medicine, Duke
University Medical Center, Erwin Rd., Durham, NC 27710.
5
Present address: Department of Medicine, Maria Parham Hospital, 566 Ruin Creek
Rd., P. O. Drawer 59, Henderson, NC 27536.
6
Department of Surgery, Division of Thoracic Surgery, Kaohsiung Veterans
General Hospital, Kaohsiung, 813, Taiwan R.O.C.
7
Division of Nuclear Medicine, Kaohsiung Veterans General Hospital, Kaohsiung,
813, Taiwan, R.O.C.
Received July 10, 2001;
accepted after revision September 6, 2001.
M.-T. Wu and H.-B. Pan were supported in part by NSC88-2314-B-075B-007
(National Scientific Council, Taiwan).
Abstract
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SUBJECTS AND METHODS. Forty-four patients with lung cancer undergoing lung resection with preoperative CT and perfusion scintigraphy were enrolled. Quantitative CT used a dual threshold (-500 and -910 H) on standard preoperative CT to semiautomatically extract lung volume without emphysema or tumor and atelectasis, which we defined as "functional lung volume." Prediction was calculated from preoperative FEV1 multiplied by the fractional contribution of functional lung volume of the remaining lung by quantitative CT. Perfusion scintigraphy was the standard method. Predictions were correlated with postoperatively measured FEV1.
RESULTS. Both quantitative CT and perfusion scintigraphy predicted postoperative FEV1 well in patients who underwent pneumonectomy (n = 28, r = 0.88 vs r = 0.86) and in lobectomy (n = 16, r = 0.90 vs r = 0.80) (both, p < 0.001). There was good agreement between the two methods by the Bland-Altman method. In the four patients with low measured postoperative FEV1 (<40% predicted normal), quantitative CT had true-positive prediction in four and perfusion scintigraphy, in only two.
CONCLUSION. Given its simplicity, we proposed that quantitative CT be widely used in predicting postoperative FEV1.
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The functional loss resulting from lung resection varies with the extent of resection, the relative function of the tissue removed compared with that remaining, and the degree of baseline impairment. To predict the functional loss, quantitative radionuclide pulmonary perfusion scintigraphy is the current most widely applied method to evaluate the split lung function [4,5,6]. However, perfusion scintigraphy was often limited to patients with low preoperative FEV1 because of cost [4, 7]. Furthermore, prediction errors may be large in some cases [8], and the accuracy is not improved by the combined use of ventilation scintigraphy [5, 6].
CT of the chest is the primary modality to stage non-small cell lung cancer and to identify those patients with localized disease who are likely to benefit from surgical resection [9]. Quantitative CT measurement of lung attenuation has been successfully used to assess the extent of emphysema and has shown good correlation with pathologic findings and lung function testing [10,11,12]. More recently, quantitative CT has been applied to assess the regional distribution of emphysema and ventilation function before lung volume reduction surgery [13,14,15]. We have developed a novel quantitative CT method, based on standard preoperative CT, to predict FEV1-PO [16]. However, the prediction has not been directly compared with that by the perfusion scintigraphy method. In recent years, the precision and efficiency of quantitative CT have improved substantially. This improvement makes quantitative CT technically simple and practical for routine use. We compared the prediction of FEV1-PO by quantitative CT versus by perfusion scintigraphy in 44 patients with lung cancer and tested our hypothesis that quantitative CT is suitable to be widely used in predicting FEV1-PO in patients with lung cancer.
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Lung Function Testing
Standard spirometry (Pulmonary Function Laboratory 2450; SensorMedics,
Anaheim, CA) was performed according to the normal procedure
[17] within 2 weeks before
surgery. Postoperative spirometry was measured at the end of the 3rd month
(mean, 11.4 weeks) after surgery with the same equipment and technique. The
measurements were normalized as a percentage of predicted normal value (pred)
[18].
Quantitative CT Method
Preoperative CT of the chest was performed using a Somatom Plus 4 or Plus
unit (Siemens, Erlangen, Germany) within 3 weeks before surgery. We used the
following parameters: 24-30 sec of scan time, 110 mA, 120 kVp,
standard-spatial-frequency reconstruction algorithm, and 8-mm collimation with
a pitch of 1.25. Images were reconstructed with 8-mm increment. Before CT,
patients practiced having a constant end of full inspiration. CT was then
performed during breath-holding at the end of full inspiration. IV contrast
medium was administered to delineate the boundaries between tumor and
mediastinal structures.
Semiautomated CT Analysis of "Functional Lung
Volume"
We used the manufacturer-provided program, Pulmo (Siemens)
[19] to semiautomatically
extract the lung parenchyma (Fig.
1A,1B,1C).
Lung parenchyma was first outlined from the mediastinum and chest wall by a
default range of -200 and -1024 H. After applying dual thresholds of -500 and
-910 H, three segments in the lung parenchyma were generated. White area below
-910 H denoted emphysema, black area above -500 H denoted tumor and
atelectasis, and gray area between -500 and -910 H denoted the normal lung
parenchyma. The attenuation histogram of quantitative CT integrated from
multiple slices encompassing both lungs entirely was further segmented between
-500 and -910 H to represent the "functional lung volume"
[16]. Visual inspection of the
functional lung volume maps, as in Figure
1A, could satisfactorily exclude the area of emphysema by the
lower threshold (-910 H), and by the threshold of -500 H, we could exclude the
areas of tumor-related air-space loss, such as tumor itself and
postobstructive atelectasis or areas of non—tumor-related air-space
loss, such as fibrosis and atelectasis due to previous tuberculosis. The
computer calculation took an average of 5 min to complete for a patient.
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Radionuclide Scintigraphy of Lung Perfusion
Standard perfusion scintigraphy was performed after IV injection of 2 mCi
(74 MBq) 99mTc-MAA on a gamma camera (APEX SP-6; Elscint, Israel)
according to the method described by Markos et al.
[5].
Prediction of Postoperative Lung Function
The formulas for prediction of postoperative FEV1 are as
follows:
Quantitative CT—predicted FEV1-PO = preoperative FEV1 x {1 — (regional functional lung volume of the lung or lobes to be removed / total functional lung volume of both lungs)}Perfusion scintigraphy — predicted FEV1-PO = preoperative FEV1 x {1 — (regional radioactivity counts of the lung or lobes to be removed / total radioactivity counts of both lungs)} [5].
The precision of prediction was calculated by percentage error of prediction:
Percentage error = (predicted FEV1-PO — measured FEV1-PO) / measured FEV1-PO x 100%
The calculation of quantitative CT prediction and perfusion scintigraphy prediction were performed by two independent observers who were unaware of the postoperative measurement.
Statistical Analysis
Values were given as mean ± SD, unless specified. Statistical
analysis was performed with SPSS version 9.0 (Statistical Package for the
Social Sciences, Chicago, IL). Simple linear regression and correlation
coefficient were used to evaluate the relationship between quantitative
CT—predicted FEV1-PO and measured FEV1-PO, and the
relationship between perfusion scintigraphy—predicted FEV1-PO
and measured FEV1-PO, and the relationship between quantitative
CT—predicted FEV1-PO and perfusion
scintigraphy—predicted FEV1-PO. Agreement between
quantitative CT—predicted FEV1-PO and perfusion
scintigraphy—predicted FEV1-PO was analyzed with Bland-Altman
method [20] by plotting the
difference between the paired quantitative CT—predicted and perfusion
scintigraphy—predicted FEV1-PO. Limits of agreement were
defined as mean of difference ± 2 SD.
The chi-square test was used to compare the distribution of cases with percentage error greater than ± 15% by quantitative CT versus perfusion scintigraphy.
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Correlation Between Predicted FEV1-PO and Measured
FEV1-PO
The preoperative FEV1 in the pneumonectomy group was 1.81
± 0.46 liters (L) (77.9 ± 16.6% pred) (mean ± SD) and in
the lobectomy group was 2.05 ± 0.46 L (85.8 ± 13.4% pred). The
measured FEV1-PO in the pneumonectomy group was 1.28 ± 0.27
L (51.1 ± 10.3% pred) and was 1.72 ± 0.37 L (72.1 ± 11.1%
pred) in the lobectomy group. The results of prediction by quantitative CT and
perfusion scintigraphy are listed in Table
1. Quantitative CT and perfusion scintigraphy both predicted
postoperative measurement well in pneumonectomy (n = 28, r =
0.88 vs r = 0.86) and in lobectomy (n = 16, r =
0.90 vs r = 0.80) (both, p < 0.001).
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Agreement Between the Two Predictive Methods
The predictions by quantitative CT and perfusion scintigraphy correlated
well (r = 0.84, p < 0.001 in pneumonectomy group and
r = 0.87, p < 0.001 in lobectomy group). Analysis by the
Bland-Altman method [20]
showed good agreement between the two (Fig.
2A,2B).
For the pneumonectomy group, the difference between the two predictions was
-0.13 ± 0.18 L. The limits of agreement (± 2 SD) were -0.49 L
and 0.23 L, respectively. For the lobectomy group, the difference between the
two predictions was -0.06 ± 0.24 L. The limits of agreement were -0.54
L and 0.42 L, respectively.
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Prediction with Percentage Error Greater Than ± 15% of
Measured FEV1-PO
We defined percentage error of prediction greater than ± 15% of
measured FEV1-PO as being clinically meaningful. The distribution
of those patients who had percentage error greater than ± 15% by either
quantitative CT or perfusion scintigraphy was shown in
Table 1. In the pneumonectomy
group, perfusion scintigraphy tended to overestimate FEV1-PO (in
eight of nine patients), and quantitative CT tended to underestimate
FEV1-PO (in four of four patients) with percentage error greater
than ± 15% (Chi square test, p = 0.001).
Predicting Postoperative FEV1 Less Than 40% Predicted
Given that FEV1-PO below 40% normal pred is a general indicator
of higher risk of postoperative morbidity and mortality rates
[3,
5], we specifically reviewed
this subgroup. We had four patients with measured FEV1-PO less than
40% pred. According to quantitative CT prediction, there were six patients
with quantitative CT—predicted FEV1-PO less than 40% pred.
Among them, four had true-positive findings, two had false-positive findings,
and none had false-negative findings of FEV1-PO less than 40% pred.
According to perfusion scintigraphy prediction, there were four patients with
perfusion scintigraphy—predicted FEV1-PO less than 40% pred.
Among them, two had true-positive findings and two had false-positive
findings. Therefore, there were two false-negative findings of
FEV1-PO less than 40% pred by perfusion scintigraphy
prediction.
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We attributed the discrepancies between the predictions by the two methods to be the result of regional ventilation—perfusion mismatch that might be remarkable in some patients with hilar tumor [9, 22]. Retrospectively reviewing the CT findings of our patients, we found that basically there were three types of hilar invasion by the tumor. First, the tumor may block the pulmonary arteries and the bronchi completely and result in total atelectasis and perfusion deficit in the affected lobes or lung. In this scenario, both perfusion scintigraphy and quantitative CT methods predicted FEV1-PO well. Second, the tumor may block the pulmonary artery but not invade the bronchus; therefore, the affected lung and lobes were not atelectatic but were of a large disproportionate perfusion defect [22], as in the example in Figure 3. Perfusion scintigraphy predicted no functional loss by resection of the lung and, therefore, may overestimate the FEV1-PO, as in many cases in Table 1 with percentage error greater than 15%. The perfusion deficit may also cause decrease of lung function and lung attenuation; however, the decrease was not below -910 H and did not affect the calculation of functional lung volume. Last, the tumor may block the artery completely and cause endobronchial stenosis severely but not completely. In this scenario, the affected lobe was not atelectatic; instead, it may have ventilation impairment due to air trapping by the severe endobronchial stenosis [23], as in the example in Figure 4. As a result, only minimal loss of lung function was encountered after surgical resection. However, we found that quantitative CT was less sensitive to detect the lung and lobes with air trapping, given its attenuation was not below our lower threshold (-910 H). Quantitative CT may consequently underestimate FEV1-PO, as in the cases with underestimation more than -15% in Table 1. On the basis of the preceding CT analysis, we found that quantitative CT was not sensitive in detecting the lung function impairment in the lung with decreased attenuation but not as low as that in emphysema. Interpretation should be cautious in patients with severe incomplete endobronchial stenosis.
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Despite the fact that quantitative CT and perfusion scintigraphy both performed well in predicting FEV1-PO, we suggest that quantitative CT be widely used for the following reasons: CT has been a routine procedure in preoperative evaluation of lung cancer. Quantitative CT has been increasingly available from the mainstream of CT scanner manufacturers [21]. Quantitative CT, therefore, does not require a separate procedure. It may have an advantage of time saving and cost reduction overall in the process of preoperative evaluation. It also avoids further radiation exposure. Quantitative CT is simple and can be performed easily by a trained technician using a standard protocol. It is a practical procedure that is now semiautomated and takes approximately 5 min to complete [21]. Quantitative CT also has a more superior and more objective definition of lobar anatomy than perfusion scintigraphy; the latter requires additional multiple oblique projection to evaluate the patients with lobectomy [5]. Last, quantitative CT appears to be good for predicting patients with FEV1-PO less than 40% pred and thus may lead the patients to further evaluation of cardiopulmonary reserve. All these factors tend to make quantitative CT an effective method for assessing split lung function preoperatively in clinical practice. For patients with quantitative CT—predicted FEV1-PO close to or below 40% pred, we suggest that further studies such as perfusion scintigraphy and exercise lung function test should be performed [3].
The limitation of our study was that we had only four of 44 patients with measured FEV1-PO less than 40% pred. However, this number was similar to the series of Markos et al. [5] in which six of 53 patients had FEV1-PO less than 40% pred. More patients with marginal lung function reserve will help to determine the respective sensitivity and specificity of these two methods in predicting FEV1-PO less than 40% pred. Further study should be conducted to evaluate the role of quantitative CT versus perfusion scintigraphy in a comprehensive algorithm of preoperative evaluation to predict and prevent postoperative complications [4, 7].
In summary, we showed that quantitative CT was accurate and was in good agreement with perfusion scintigraphy in predicting FEV1-PO in patients with lung cancer. Given the simplicity and effectiveness of quantitative CT, we proposed that it should be widely used in evaluating lung functional reserve. Perfusion scintigraphy and exercise lung function tests should be used for further evaluation for patients with quantitative CT—predicted FEV1-PO in the range of 40% pred or lower.
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