Comparison of spirometry and abdominal height as four-dimensional computed tomography metrics in lung

Comparison of spirometry and abdominal height as four-dimensional computed tomography metrics in lung Wei Lu, Daniel A. Low, a Parag J. Parikh, Michelle M. Nystrom, Issam M. El Naqa, Sasha H. Wahab, Maureen Handoko, David Fooshee, and Jeffrey D. Bradley Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri 63110 Received 22 October 2004; revised 14 February 2005; accepted for publication 26 April 2005; published 23 June 2005 An important consideration in four-dimensional CT scanning is the selection of a breathing metric for sorting the CT data and modeling internal motion. This study compared two noninvasive breathing metrics, spirometry and abdominal height, against internal air content, used as a surrogate for internal motion. Both metrics were shown to be accurate, but the spirometry showed a stronger and more reproducible relationship than the abdominal height in the lung. The abdominal height was known to be affected by sensor placement and patient positioning while the spirometer exhibited signal drift. By combining these two, a normalization of the drift-free metric to tidal volume may be generated and the overall metric precision may be improved. 2005 American Association of Physicists in Medicine. DOI: 10.1118/1.1935776 Key words: breathing motion, spirometry, abdominal height, radiation therapy I. INTRODUCTION Internal respiratory organ motion is the principal reason that intensity modulated radiation therapy IMRT has not been widely accepted for use in lung and upper-abdomen cancer treatment. 1 4 Four-dimensional computed tomography 4D CT is one technique proposed to reduce this uncertainty by retrospectively constructing three-dimensional 3D CT images at various parts of the respiratory cycle. 5 11 Our group has developed a 4D CT technique for free breathing by using a 16-slice CT scanner. 8,12 For both 4D CT 5 12 and gated radiotherapy, 13 18 a metric that monitors breathing motion must be used since time cannot be directly correlated to tumor motion. Various breathing metrics have been proposed, ranging from implanted marker position, 2,5,18 21 abdominal height or chest height, 6,7,9,10,15,18,22,23 spirometry, 8,12,13,16,22 26 abdominal strain gauge, 13 wraparound inductive plethysmography, 22 and temperature sensors. 13 The only commercially available system uses abdominal height Real-Time Position Management, RPM, Varian Medical Systems, Palo Alto, CA, but the relationship between internal motion and abdominal height is sensitive to sensor placement and patient positioning. 15,16,27 A spirometer measures the air flow into the lungs and may provide a useful, verifiable physiologic metric. 12,16 We have found that spirometry is an excellent quantitative metric, but its significant signal drift means that it may not be appropriate as the sole metric for 4D CT or gated radiotherapy. 12,26 This study compared spirometer-measured tidal volume and abdominal height against internal air content, a surrogate for internal motion measurements. 12 The relationship between these two metrics for an entire CT scan session was also examined. II. MATERIALS AND METHODS A. 4D CT with spirometry Brief descriptions of the 4D CT process 8 and internal air content analysis 12,28 are given as follows. Transverse slices 1.5 mm thick were acquired using a 16-slice CT scanner Sensation 16, Siemens Medical Systems, Malvern, PA operated in 12-slice mode. The scanner was operated in ciné mode couch stationary during scanning with 15 scans acquired repeatedly at each couch position for 11 s. Each scan 360 rotation required 0.5 s to acquire followed by a 0.25 s dead time. The data were acquired continuously in space, but there was usually a pause of 4 s between two neighboring couch acquisitions. This process was conducted while the patient underwent synchronized spirometry measurements. The synchronization was provided by a photoresistor connected to the X-Ray On light. 12 Both the spirometry signal and the photoresister signal were measured with approximately 100 samples per second using a customized data acquisition program written in LABVIEW National Instruments, Dallas, TX. 8,28 The spirometry was calibrated to be linear and accurate for tidal volume flow rates greater than 100 ml/s typical breathing flow rates are in excess of 200 ml/s. 28 The slow drift in the spirometry signal was corrected by retrospectively examining the spirometer-measured tidal volume v and the internal air content V for the 15 CT scans. 12 This provided a spirometer-measured tidal volume v for each CT scan. The CT scans were then sorted into variable number of bins usually 10 14 bins, depending on the range of tidal volumes the patient breathed. Each bin was assigned a specific tidal volume and direction of respiration inspiration or expiration. B. Internal air content analysis The internal air content analysis provided a measure of how much air volume was within a CT volume. 29 It was 2351 Med. Phys. 32 7, July 2005 0094-2405/2005/32 7 /2351/7/$22.50 2005 Am. Assoc. Phys. Med. 2351

2352 Lu et al.: Comparison of spirometry and abdominal height 2352 FIG. 1. Measuring abdominal height. a Video acquisition system consisting of a digital camera pointed at the distance scale moving with the abdomen. b A sample frame taken from a video shows the template position determined by the template matching algorithm. The fiber optic cable appears bright in this sample frame indicating that the CT radiation is on. determined by the Hounsfield values in segmented aircontaining tissues lungs, trachea, bronchi. 12,28 In a previous study, we showed that the internal air content correlated with tissue motion with a residual of less than 1 mm for 12 patients and provided quantitative evaluations for the 4D CT process. 12 In this study, the internal air content was used as a surrogate for internal motion and the basis for metric comparison. C. Abdominal surface height measurement During the 4D CT procedure, an abdominal surface height measurement h was simultaneously acquired through digital video recording of a lightweight block placed on the patient s abdomen Fig. 1 a. The block was positioned between the umbilicus and the xiphoid process, based on the position of greatest tidal excursion as determined by a physician present at the simulation. We took care to tape the block tightly and straight up so that the motion was mostly in the anterior-posterior direction with negligible rotation effect. A distance scale was attached to the block surface facing the camera DCR-TRV 240, Sony, Tokyo, Japan for measurement calibration. A dark dot was marked at the center of the distance scale. It provided a template for automatically tracking of the block position on the digital movie frames Fig. 1 b. The video was synchronized to the CT scanner acquisition by a fiber optic cable connected to the same X-Ray On light as used for spirometry synchronization. Figure 1 b shows that the end of the fiber optic cable appears bright in the sample frame when the CT radiation is on. The video was downloaded from the camera and cropped to reduce the video file size with commercial video processing software PREMIERE V6.5, Adobe Systems Incorporated, San Jose, CA. The video had a sampling rate of 30 frames/s. The position of the block within each frame was automatically tracked using a two-dimensional template matching algorithm 30 implemented in MATLAB The Mathworks, Inc., Natick, MA. The template matching algorithm determines the position of a template in a target frame by finding the maximum normalized correlation between the template and the target. A rectangular region around the center dark dot in the first frame was manually selected as the template. The size of the template was approximately 2 by 2 mm. The template position determined by the algorithm was superimposed on each frame of the video Fig. 1 b. This generated a new video which was retrospectively viewed and from which the uncertainty of the template tracking was estimated for every patient to be less than 0.3 mm in both the lateral and anteroposterior directions. The anteroposterior position of the template provided the abdominal height measurement, which was calibrated from pixels into distance in millimeters using the imaged distance scale. This inexpensive in-house system provided similar surface height measurements to those provided by the RPM system with the advantage that it provided synchronization signals with the CT scanner. D. Comparison of spirometry and abdominal height as 4D CT metrics The spirometer-measured tidal volume and the abdominal height were compared against internal air content V as 4D CT metrics at each couch position 11 s. A patient-specific time offset t was assumed to exist between diaphragm motion causing abdominal motion, internal lung motion, and airflow at the mouth. The value of t between each metric and V was determined by maximizing a cross-correlation function CCF between each metric and V. The CCF evaluates the degree to which two functions are correlated and allows for the identification and estimation of t in two related signals. 12,18,31 33 On the other hand, a specific fractional error in V would correspond to the same fractional error in internal motion estimation, the fitting residual V root mean squared error of a first-order fit between each metric and V was used as a measure of the metric precision. Three 4D CT lung cancer patients and two 4D CT abdomen study patients had both spirometry and abdominal height data and were used in this study. Only couch positions that intercepted the lungs were used in this comparison. E. Comparison of spirometry and abdominal height for entire scan session The abdominal height measurement h was considered drift-free 22,26 and its relationship with the spirometermeasured tidal volume v was examined for the entire CT session 300 600 s. This was done by dividing the CT session into 11 s segments based on the amount of time re-

2353 Lu et al.: Comparison of spirometry and abdominal height 2353 quired to acquire 15 CT scans from a single couch position and correlating h to v in every segment. When examining the relationship of these two metrics in each segment, t between h and v and a baseline drift in tidal volume were observed. We adopted an approach to simultaneously determine t and spirometry drift by maximizing the correlation between h and v for each segment: 1 t was determined by shifting v in time to maximize its correlation with h; 2 a linear spirometer drift correction was applied to v and the slope of the drift was adjusted to again maximize the correlation between v and h. The mean ratio of drift-corrected tidal volume change to the abdominal height change dv/dh, and the mean time offset t h-v were tabulated. III. RESULTS A. Comparison of spirometry and abdominal height as 4D CT metrics Figure 2 a shows the spirometer-measured tidal volume, abdominal height, and internal air content at the times corresponding to the 15 successive CT scans for one couch position. Figure 2 b shows the continuous tidal volume and abdominal height for the same couch position 11 s as shown in Fig. 2 a. The abdominal height changed by about 10 mm for the three breaths shown, while the tidal volume changed by about 500 ml. Because of unintended abdomen motion caused by involuntary abdomen muscle motion and cardiac motion, the abdominal trace has more small vibrations than the tidal volume trace. Similar vibrations were noticeable in surface displacement traces abdominal or chest measured by others. 3,34,35 Figure 3 shows the results of linearly fitting each metric to the internal air content for this couch position. The fitting residual was 2.8 ml for tidal volume Fig. 3 a and 4.3 ml for abdominal height Fig. 3 b, suggesting a greater precision of the tidal volume. The slopes of the fitted lines dv/dv and dv/dh represent the ratio of internal air content change to metric change. Figure 4 shows summary plots of these measurements as a function of couch positions for this lung cancer patient couch positions 5 18 are intercepting the lungs. The slopes were normalized to a common range of 0 1 for comparison. The two metrics display the same trend in the slopes Fig. 4 a. This indicates that both metrics have equivalent accuracy in determining changes in internal air content. For most couch positions within the lung, spirometry showed a better precision smaller fitting residual than abdominal height Fig. 4 b. This was true for all five patients. The mean time offset, fitting residual, and correlation between each metric and the internal air content are listed in Table I. We have shown that the mean fitting residuals between v and V v-v for the lung cancer patients corresponded to 3% 8% uncertainties in the overall tidal volumes. 12 For all patients, the spirometer-measured tidal volume had a better mean precision than the abdominal height. The correlation between the tidal volume and internal air content was slightly greater than or equal to that between the abdominal height and internal air content. With regard to FIG. 2. Breathing samples of spirometer-measured tidal volume, abdominal height, and internal air content vs scan index a and vs time b for a couch position in the middle of lung and intercepting the diaphragm. t, for all patients but patient 3, the abdominal height change led the internal air content change. Patient 3 showed a different phase relationship: the internal air content change led the abdominal height change. This was possibly due to the patient s breathing being driven more by the chest than for the other four patients. Further investigation showed that this patient also had the smallest peak-to-peak change in abdominal height 6 mm. The internal air content change led the spirometry change for all patients. The time offset between the spirometry and internal air content was smaller than that between the abdominal height and internal air content for every patient. B. Relationship between spirometry and abdominal height for entire scan session Figure 5 shows the relationship between the abdominal height and tidal volume for an entire scan session 350 s.

2354 Lu et al.: Comparison of spirometry and abdominal height 2354 FIG. 3. Linearly fitting spirometer-measured tidal volume a and abdominal height b to internal air content. Dashed lines represent ± fitting residuals. The values of dv/ dh were relatively unchanged during the session with a mean of 62.61 ml/mm and a standard deviation s.d. of 3.11 ml/mm Fig. 5 a. The residual h-v for a first-order fit between v and h was relatively small with a mean of 19 ml or 3.25% of the overall tidal volume Fig. 5 b. The correlation between h and v r h-v was high throughout the session Fig. 5 c. The time offset t h-v plot shows that the abdominal height change always led the spirometry change with a mean of 0.12 s and a s.d. of 0.02 s Fig. 5 d. These measurements were tabulated for all five patients Table II. The first three lung cancer patients show less variation in dv/dh than the last two abdomen study patients, which might be the result of longer overall scan session times for abdomen study patients 600 s. The time offsets were relatively unchanged for every patient s.d. 0.02 s except for patient 4 s.d. =0.05 s, for whom the time offset increased significantly near the end of the session possibly due to patient relaxation. IV. DISCUSSION AND CONCLUSION The results showed that both metrics were accurate with respect to internal air content. The metric precision varied with the location of interest but spirometry was generally a better metric than the abdominal height for a location within the lung. The mean precision of spirometry within the lung FIG. 4. Summary plots for a lung cancer patient. a Normalized ratios of internal air content to tidal volume dv/dv and to abdominal height dv/dh. b Fitting residuals between tidal volume and internal air content v-v, and between abdominal height and internal air content h-v. was better for all patients, suggesting a stronger and more reproducible relationship of spirometry with internal air content and tissue motion. The time offset between the internal air content and the spirometry was smaller than that between the internal air content and the abdominal height. A recent fluoroscopic study by Hoisak et al. reached the same conclusions for 11 patients with data acquired over extended periods and over multiple days. 23 It has been reported that breathing patterns change when one breathes through a spirometer. 36,37 Gilbert et al. 36 reported that the tidal volume increased by 29±21% for 14 subjects in one study, while Askanazi et al. 37 found increases of 15.5% for 28 subjects. However, when evaluating metrics for 4D CT or gated radiation therapy, it is the relationship between internal motions and the breathing metrics that are the principal consideration. The fact that the tidal volume changes when a spirometer is employed does not necessarily change the relationship between tidal volume and internal motion. This relationship will need verification, but if the use of spirometry significantly affects this relationship, a spirometer can be employed during treatment. Though the internal air content functioned well as a surrogate for tissue motion, and the internal air content change

2355 Lu et al.: Comparison of spirometry and abdominal height 2355 TABLE I. Comparison of tidal volume v and abdominal height h against internal air content V as 4D CT metrics within the lung. Between v and V Between h and V Patient Site Time Fitting Time Fitting offset a residual offset a residual s ml Correlation s ml Correlation 1 Lung 0.02 1.99 0.99 0.07 2.44 0.98 2 Lung 0.03 2.78 0.98 0.07 3.38 0.96 3 Lung 0.03 2.35 0.99 0.15 4.25 0.97 4 Abdomen 0.04 4.42 0.99 0.14 4.65 0.99 5 Abdomen 0.06 1.28 1.00 0.11 2.36 0.99 a A positive time offset indicates that the first variable is leading the second variable. FIG. 5. Relationship between abdominal height h and tidal volume v for the entire scan session. a Ratio of change in v to change in h dv/dh. b Fitting residual between h and v h-v. c Correlation between h and v r h-v. d Time offset between h and v t h-v. can be monitored either locally or globally in the lung, actual tumor motion would be better for evaluating breathing metric in radiotherapy. Reliably tracking tumor motion in 3D is ongoing research. Fluoroscopically tracking implanted markers 2,3,5,18 21 may yield the most reliable 3D tumor position, however, this technique is invasive and has other limitations. 19,21 A recent study showed that tumors in the lung can be tracked with a biplane digital radiography unit, while implanted markers were still needed for tumors in the liver and esophagus. 18 Fluoroscopically tracking the superior-inferior diaphragm motion has been conducted but is limited by the fact that only one-dimensional diaphragm motion was measured. 15,17,34,35 The development of respiration-correlated 4D CT techniques may provide a noninvasive way for tracking and modeling 3D tumor/tissue motion. For the five patients in this study, there was a high correlation between the spirometry and abdominal height 0.98, and their relationship dv/dh and time offset was relatively unchanged for the entire CT session 300 700 s under free breathing. Zhang et al. 26 reported a stable correlation between spirometry and chest wall height for healthy volunteers during normal breathing cycles. Because of the large variation exhibited in breathing patterns, it is important to establish and verify the dv/dh relationship for each scanning session and each treatment session. We have so far assumed that this relationship would change only slightly during each treatment session 10 15 min, in which the patient is kept at a fixed position and undergoes quiet respiration. Our results, acquired during CT simulation, have shown that TABLE II. Relationship between the tidal volume v and abdomen height h for the entire scan session 300 600 s. Values are mean s.d. for all 11 s segments. Patient Site Time offset a s dv/dh ml/mm Fitting residual % Correlation 1 Lung 0.12 0.02 62.61 3.11 3.25 1.04 0.993 0.004 2 Lung 0.06 0.01 61.97 2.19 3.05 0.47 0.994 0.002 3 Lung 0.12 0.02 108.20 6.39 5.92 0.91 0.980 0.004 4 Abdomen 0.11 0.05 66.60 6.53 3.15 1.99 0.996 0.004 5 Abdomen 0.12 0.02 73.91 9.62 5.50 1.74 0.983 0.012 a A positive time offset indicates that the first variable is leading the second variable.

2356 Lu et al.: Comparison of spirometry and abdominal height 2356 this assumption is valid for 6 11 min. If this assumption holds, we hypothesize that it will be possible to acquire both metrics for several breathing cycles and normalize the abdominal height into tidal volume for each patient just before the treatment. 16,25,26 After that, the tidal volume measurement would not be necessary unless removing the spirometer is found to significantly alter the relationship of internal motion and abdomen height. This would be advantageous for patients who did not want to undergo spirometry during the entire process for which the tidal volume was required. Finally, one should be cautious when using any external breathing metrics spirometry and abdominal height to infer internal tumor or tissue motion. 3,23 At the least the following issues need to be addressed. 1 Is there a high correlation between the external metric and internal motion? 2 Is this relationship reproducible during the time of consideration? 3 Is there a mechanism to determine and account for the time offsets between the external metric and internal motion? Nevertheless, external breathing metrics have been demonstrated useful in predicting the tumor motion and thus in reducing the uncertainties caused by respiratory motion for many patients. 6 10,12,13,15,16,18,22 26 A more thorough verification of their relationships with tumor motions by using realtime, direct tumor or indirect implanted marker imaging is under development in our institution. 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