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Reduction of Organ Motion by Combined Cardiac Gating and Respiratory Gating
Int. J. Radiation Oncology Biol. Phys., Vol. 68, No. 1, pp. 259 –266, 2007 Copyright © 2007 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/07/$–see front matter
doi:10.1016/j.ijrobp.2006.11.057
PHYSICS CONTRIBUTION
REDUCTION OF ORGAN MOTION BY COMBINED CARDIAC GATING AND RESPIRATORY GATING ZHIHENG WANG, PH.D., CHRISTOPHER G. WILLETT, M.D.,
AND
FANG-FANG YIN, PH.D.
Department of Radiation Oncology, Duke University Medical Center, Durham, NC Purpose: To investigate whether the effect of organ motion can be further reduced with the application of a cardiac gating technique, together with respiratory gating. Methods and Materials: Axial and coronal images through the heart and liver were continuously scanned with fast cine magnetic resonance imaging scans at three different gating settings: (1) without respiratory and cardiac gating; (2) with respiratory gating, but without cardiac gating; and (3) with both respiratory and cardiac gating. The effect of motion for either the heart or liver was analyzed with probability maps. Results: With the application of respiratory gating only, the marginal region on the probability map was reduced by 10.0% in the axial slice and 19.8% in the coronal slice for the heart. It was reduced by 5.2% in the axial slice and 20.8% in the coronal slice for the liver. With the application of cardiac gating together with respiratory gating, the marginal region on the probability map was reduced further. The reduction was 8.0% in the axial slice and 13.6% in the coronal slice for the heart and 5.9% in the axial slice and 7.0% in the coronal slice for the liver. Conclusion: The effect of organ motion can be further reduced with the application of cardiac gating together with respiratory gating. The potential application to treatment planning merits further investigation. © 2007 Elsevier Inc. Organ motion, Respiratory gating, Cardiac gating, Treatment margin, Radiotherapy.
INTRODUCTION
8 mm and range of 5–17 mm, under normal respiration. The motion was measured along the superoinferior direction with ultrasonography. Under deep breathing, the mean peak-totrough liver motion was 37 mm (standard deviation, 8; range, 25–57). For the pancreas, Suramo et al. (6) reported a mean motion of 20 mm (range, 10 –30 mm) under normal respiration. Under deep breathing, the mean pancreas motion was 43 mm (range, 20 – 80 mm). Respiratory gating can be used to reduce the effect of intrafraction organ motion (7–22). The range of tumor motion is greatly reduced when the radiation beam is gated at the selected respiratory phase or amplitude. The margins of the radiation field can be reduced accordingly. Despite respiratory gating, residual motion exists during treatment of thoracic malignancies (23–25). In contrast, studies of the effect of cardiac gating on radiotherapy has not been evaluated extensively. At present, it is unclear how much intrafractional organ motion could be further reduced using cardiac gating integrated with respiratory gating. This study compared internal organ motion assayed by respiratory-gated magnetic resonance imaging (MRI) scans, with and without cardiac gating. These
With the development of new technologies in radiation oncology, radiation dose can now be delivered precisely to the target tumor volume while sparing critical normal tissue. However, this advantage may be diminished for tumors located in either the thoracic or abdominal regions because of internal organ motion induced by the respiratory and cardiac cycles and other physiologic events (1–3). Extra margins are typically added to the radiation fields to ensure the proper coverage of the target volume within its full range of motion. This is undesirable because more of the normal and nontarget tissues will be included in the target volume and will receive a high radiation dose. For lung tumors, Ross et al. (4) used an ultrafast computed tomography scanner to study the tumor motion related to the respiratory and cardiac cycles. The motion in the anteroposterior and lateral directions ranged from 5 to 22 mm for tumors in the lower lobe of the lung. For tumors in the hilar region, the lateral motion ranged from 0 to 16 mm. For tumors in the mediastinum region, the lateral motion ranged from 0 to 13 mm. For liver excursion, Davies et al. (5) reported a mean peak-to-trough motion of 10 mm, with a standard deviation of
late Dr. Tom Raidy for performing the magnetic resonance imaging scans and Dr. Mark Oldham for useful discussions. The authors also thank Ms. Jane Hoppenworth for editing the manuscript. Received April 11, 2006, and in revised form Nov 7, 2006. Accepted for publication Nov 9, 2006.
Reprint requests to: Zhiheng Wang, Ph.D., Department of Radiation Oncology, Duke University Medical Center, DUMC 3295, Durham, NC 27710. Tel: (919) 660-2188; Fax: (919) 681-7183; E-mail: [email protected] Conflict of interest: none. Acknowledgments—The authors thank Mr. Kevin Kelly and the 259
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data have clarified how the treatment margin from a defined clinical target volume to planning target volume can be further reduced if cardiac gating is integrated with respiratory gating.
METHODS AND MATERIALS Five healthy volunteers were scanned in an MRI scanner equipped with respiratory and cardiac gating. The scanner used in this study was a GE Signa (General Electric, Milwaukee, WI). A respiratory bellow was used for the respiratory gating signal (26 – 30). The bellow was wrapped around the torso of the subject. The signals from the respiratory bellow were fed into the MRI scanner to trigger the scanning pulse sequences. The electrocardiogram (ECG) signals of the subject were also fed into the scanner (30 – 33). The MRI pulse sequences can be triggered with signals from the respiratory bellows or the ECG, or a combination of both. The respiratory gating window was set to a 25% phase centered at the lowest point of expiration. For the scans with both cardiac and respiratory gating, the data acquisition was activated only when the ECG waveform was at the flat region of the diastolic phase and the respiratory signal was simultaneously within the gating window. Each subject was placed on the MRI couch in the supine position and scanned with MRI body coils. A localization scan was performed first with a repetition time (TR) of 54 ms, echo time (TE) of 1.7 ms, and a field of view (FOV) of 48 cm. Axial slices were then prescribed for the heart and liver. The scans were performed with three different gating settings: (1) without either respiratory or cardiac gating, (2) with respiratory gating but without cardiac gating, and (3) with both respiratory and cardiac gating. The scans with neither respiratory nor cardiac gating were performed with the single-shot fast-spin echo (SSFSE) pulse sequence. The scanning parameter settings were a TR of 748 ms, TE of 29 ms, slice thickness of 5 mm, phase encoding of 128, readout of 256, and FOV of 34 cm. The scan was continuously repeated 20 times with a frame rate of 80 frames per minute. The scans with respiratory gating, but without cardiac gating, were performed with the SSFSE pulse sequence, also. The scanning parameter settings were a TR of 3,231 ms, TE of 29 ms, slice thickness of 5 mm, phase encoding of 128, readout of 256, and FOV of 34 cm. The scan was continuously repeated 20 times with a frame rate of 19 frames/min. The scans with both respiratory and cardiac gating were performed with a fast spoiled gradient echo pulse sequence. The scanning parameter settings were a TR of 5.1 ms, TE of 1.8 ms, slice thickness of 5 mm, phase encoding of 128, readout of 256, and FOV of 34 cm. The scan was continuously repeated 20 times with a frame rate of 60 frames/min. The scans were repeated for a coronal slice through the heart and liver with the same setting as the axial slices. The FOV for the coronal slices was 48 ⫻ 48 cm. All the images were saved in the Digital Imaging and Communications in Medicine (DICOM) format and transferred to a computer for analysis. The DICOM images were read into MATLAB (Math Works, Natick, MA). The image set with 20 continuous scans was written into a movie file to visually observe the motions. The different images were obtained by subtracting the image with the first image. For each subject, the contours of the heart and liver were drawn on the corresponding axial and coronal slices for each image of the set of 20 continuous scans. A probability map was reconstructed separately for each heart and liver slice to show the probability of the organ appearing at a
Fig. 1. Axial slice of heart acquired with single-shot fast-spin echo (SSFSE) sequence (a) and contours of heart for all 20 repeated scans with three different gating settings: (b) without any gating; (c) with respiratory gating only; and (d) with both respiratory and cardiac gating.
certain location on the map. A probability of 100% means that the organ appears at this location all the time. A probability of 0% means that the organ never appears at this location. The area of probability between 0% and 100% is the marginal region in which the organ regularly moves in and out. If a radiation field is designed to cover all the pixels with a probability ⬎0% in the probability map, the organ will be irradiated during any phase of the motion cycles. If a radiation field is designed to tolerate a 5% error, the field can be shrunk to cover the area with a probability ⬎5% on the probability map. To construct the probability map, the area within the contour of each organ was assigned a pixel value of 1, and the area outside the contour was assigned a pixel value of 0. The pixel values were then summed for all the images within the continuous scan set and renormalized to the maximum of 100%. Probability maps were calculated for each gating setting. The ratio of the marginal area to the average area of the organ contours was calculated and compared to show the effect of gating on organ motion. The margins along the anteroposterior, superoinferior, and left–right direction were also compared among the three different gating settings.
RESULTS An axial slice of the heart is shown in Fig. 1a. It was acquired with the SSFSE sequence and a TR of 748 ms and TE of 29 ms without any gating applied. The scan was repeated continuously 20 times. The contours of the heart for all 20 repeated scans without any gating were overlaid together (Fig. 1b). Figure 1c shows the contours of the heart on the same axial slice acquired with respiratory gating but
Combined cardiac and respiratory gating
Fig. 2. Coronal slice of heart acquired with single-shot fast-spin echo (SSFSE) sequence (a) and contours of heart for all 20 repeated scans with three different gating settings: (b) without any gating; (c) with respiratory gating only; and (d) with both respiratory and cardiac gating.
without cardiac gating. Figure 1d shows the contours of the heart acquired with both respiratory and cardiac gating. Figure 2a shows the coronal slice of the heart acquired with the SSFSE sequence. Figure 2b shows the contours of the heart for all 20 repeated scans without any gating. Figure 2c shows the contours of the heart on the same coronal slice acquired with respiratory gating but without cardiac gating, and Fig. 2d shows the contours of the heart acquired with both respiratory and cardiac gating. The probability maps of the heart were calculated and are shown in Fig. 3, with Fig. 3a– c for the axial slice and Fig. 3d–f for the coronal slice. Figure 3a,d was reconstructed from the scans without any gating. Figure 3b,e was reconstructed from the scans with respiratory gating, but without cardiac gating. Figure 3c,f was reconstructed from the scans with both respiratory and cardiac gating. Figure 4 shows the marginal regions of the probability maps at which the probability was ⬎5% and ⬍95% for the heart (Fig. 4a– c shows the axial slice and Fig. 4d–f the coronal slice). Figure 4a,d was reconstructed from the scans without any gating. Figure 4b,e was reconstructed from the scans with respiratory gating, but without cardiac gating. Figure 4c,f was reconstructed from the scans with both respiratory and cardiac gating. The percentage of the area of the marginal region normalized to the area of the contour is 44.5% for the axial scans without any gating (Fig. 4a). It reduced to 25.5% for the axial scans with respiratory gating but without cardiac gating (Fig. 4b). It decreased further to 17.3% for the axial scans with both respiratory and cardiac
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gating (Fig. 4c). For the coronal slice shown in Fig. 4d–f, the percentage of the area of the marginal region was 37.3% for the scans without any gating (Fig. 4d). This percentage decreased to 30.7% for the scans with respiratory gating but without cardiac gating (Fig. 4e) and decreased further to 16.6% for the scans with both respiratory and cardiac gating (Fig. 4f). The mean and standard deviation of the percentages of the marginal region for all 5 subjects in this study are listed in Table 1. In the axial slice for the heart, the mean percentage of the marginal region in the probability maps decreased from 32.9% without any gating to 22.9% with respiratory gating but without cardiac gating. An average 10% reduction of the marginal region was achieved with respiratory gating only. For the coronal slice of the heart, the mean percentage of marginal region in the probability maps decreased from 56.9% without any gating to 37.1% with respiratory gating but without cardiac gating. An average 19.8% reduction of the marginal region was achieved with respiratory gating only. With both respiratory and cardiac gating, the mean percentage of marginal region in the probability maps of the heart in the axial slice decreased further to 14.9%. An average additional 8.0% reduction of the marginal region was achieved with the added cardiac gating. For the coronal slice of the heart, the mean percentage of marginal region in the probability maps decreased further to 23.5% with both respiratory and cardiac gating. An average additional 13.6% reduction of the marginal region was achieved with the added cardiac gating. Table 2 lists the margins along the anteroposterior, superoinferior, and left–right directions for the heart with three different gating settings. An axial slice of the liver of 1 volunteer is shown in Fig. 5a. It was acquired with the SSFSE sequence and a TR of 748 ms and TE of 29 ms without any gating applied. The scan was repeated continuously for 20 times. The contours of the liver for all 20 repeated scans without any gating were
Fig. 3. Probability maps of heart with (a– c) for axial slice and (d–f) for coronal slice. (a,d) Reconstructed from scans without any gating. (b,e) Reconstructed from scans with respiratory gating but without cardiac gating. (c,f) Reconstructed from scans with both respiratory and cardiac gating.
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Fig. 4. Marginal regions of probability maps at which probability was ⬎5% and ⬍95% for heart: (a– c) axial slice and (d–f) coronal slice. (a,d) Reconstructed from scans without any gating. (b,e) Reconstructed from scans with respiratory gating but without cardiac gating. (c,f) Reconstructed from scans with both respiratory and cardiac gating.
overlaid together and are shown in Fig. 5b. Figure 5c shows the contours of the liver on the same axial slice acquired with respiratory gating but without cardiac gating, and Fig. 5d shows the contours of the liver acquired with both respiratory and cardiac gating. Figure 6a shows the coronal slice of the liver acquired with the SSFSE sequence. Figure 6b shows the contours of the liver for all 20 repeated scans without any gating. Figure 6c shows the contours of the liver on the same coronal slice acquired with respiratory gating but without cardiac gating, and Fig. 6d shows the contours of the liver acquired with both respiratory and cardiac gating. The probability maps of the liver were calculated and are shown in Fig. 7, with Fig. 7a– c showing the axial slice and Fig. 7d–f showing the coronal slice. Figure 7a,d was reconstructed from the scans without any gating. Figure 7b,e was reconstructed from the scans with respiratory gating but
Table 1. Mean and standard deviation of percentages of marginal region of heart scanned with three different gating settings
No gating (%)
Respiratory gating only (%)
Table 2. Margins along anteroposterior, superoinferior, and left– right directions for heart with three different gating settings No gating (mm)
Respiratory and cardiac gating (%)
Heart slice orientation
Mean
SD
Mean
SD
Mean
SD
Axial Coronal
32.9 56.9
11.7 32.1
22.9 37.1
5.8 11.4
14.9 23.5
2.2 9.2
Abbreviation: SD ⫽ standard deviation.
without cardiac gating. Figure 7c,f was reconstructed from the scans with both respiratory and cardiac gating. Figure 8 shows the marginal regions of the probability maps at which the probability was ⬎5% and ⬍95% for the liver, with Fig. 8a– c showing the axial slice and Fig. 8d–f showing the coronal slice. Figure 8a,d was reconstructed from the scans without any gating. Figure 8b,e was reconstructed from the scans with respiratory gating but without cardiac gating. Figure 8c,f was reconstructed from the scans with both respiratory and cardiac gating. Figure 8a shows the percentage of the area of the marginal region normalized to the area of the contour, which was 36.5% for the axial scans without any gating. This percentage decreased to 25.6% for the axial scans with respiratory gating but without cardiac gating (Fig. 8b). It decreased further to 19.1% for
Respiratory gating only (mm)
Respiratory and cardiac gating (mm)
Margin direction
Mean
SD
Mean
SD
Mean
SD
Anterior Posterior Superior Inferior Left Right
11.1 12.9 11.1 10.1 11.0 14.7
3.3 7.6 6.1 1.3 9.3 11.8
7.1 8.6 7.9 8.4 6.9 10.4
1.3 2.0 2.5 5.0 2.4 7.1
3.7 5.7 5.0 5.7 5.6 4.5
1.2 1.8 3.3 2.1 1.1 2.3
Abbreviation: SD ⫽ standard deviation.
Combined cardiac and respiratory gating
Fig. 5. Axial slice of liver acquired with single-shot fast-spin echo (SSFSE) sequence (a) and contours of heart for all 20 repeated scans with three different gating settings: (b) without any gating; (c) with respiratory gating only; and (d) with both respiratory and cardiac gating.
the axial scans with both respiratory and cardiac gating (Fig. 8c). Figure 8d–f shows the percentage of the area of the marginal region for the coronal slice, which was 50.1% for the scans without any gating (Fig. 8d). This percentage decreased to 27.5% for scans with respiratory gating but without cardiac gating (Fig. 8e) and decreased further to 15.8% for scans with both respiratory and cardiac gating (Fig. 8f). Table 3 lists the mean and standard deviation values of the percentages of the marginal region for all 5 subjects in this study. For the liver in the axial slice, the mean percentage of the marginal region in the probability maps decreased from 30.2% without any gating to 25.0% with respiratory gating but without cardiac gating. An average 5.2% reduction of the marginal region was achieved with respiratory gating only. For the coronal slice of the liver, the mean percentage of the marginal region in the probability maps decreased from 49.4% without any gating to 28.6% with respiratory gating but without cardiac gating. An average 20.8% reduction of the marginal region was achieved with respiratory gating only. With both respiratory and cardiac gating, the mean percentage of marginal region in the probability maps decreased further to 19.1% for the liver in the axial slice. An average additional 5.9% reduction of the marginal region was achieved with the added cardiac gating. For the coronal slice of the liver, the mean percentage of the marginal region in the probability maps decreased further to 21.6% with both respiratory and cardiac gating. An average additional 7.0% reduction of the marginal region was achieved with the added cardiac gating.
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Fig. 6. Coronal slice of liver acquired with single-shot fast-spin echo (SSFSE) sequence (a) and contours of heart for all 20 repeated scans with three different gating settings: (b) without any gating; (c) with respiratory gating only; and (d) with both respiratory and cardiac gating.
Table 4 lists the margins along the anteroposterior, superoinferior, and left–right directions for the liver with three different gating settings. DISCUSSION Cardiac gating, applied together with respiratory gating, can further reduce the marginal region. However, the stan-
Fig. 7. Probability maps of liver with (a– c) for axial slice and (d–f) for coronal slice. (a,d) Reconstructed from scans without any gating. (b,e) Reconstructed from scans with respiratory gating but without cardiac gating. (c,f) Reconstructed from scans with both respiratory and cardiac gating.
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Fig. 8. Marginal regions of probability maps at which probability was ⬎5% and ⬍95% for liver with (a– c) for axial slice and (d–f) for coronal slice. (a,d) Reconstructed from scans without any gating. (b,e) Reconstructed from scans with respiratory gating but without cardiac gating. (c,f) Reconstructed from scans with both respiratory and cardiac gating.
dard deviations for the reductions of the marginal regions were large. This suggests that the reduction of the marginal region gained by adding cardiac gating might not be significant for some cases, especially for the liver. The scanning parameters for three different gating settings were programmed to have the greatest achievable frame rate for each individual scan. The total scanning time was not the same for the three different gating settings. A global shift, if existed, might be added to the motion that associated with respiratory and cardiac cycling for a longer scanning duration. For this study, the longest scanning time for a gated set of 20 images was about 1.05 min. No global shift was found during the scanning time. Because of the limitations of the technique, the same SSFSE sequence could not be used for combined respiratory and cardiac gating. However, the organ motion was ana-
Table 3. Mean and standard deviation of percentages of marginal region of liver scanned with three different gating settings
No gating (%)
Respiratory gating only (%)
Table 4. Margins along anteroposterior, superoinferior, and left– right directions for liver with three different gating settings No gating (mm)
Respiratory and cardiac gating (%)
Liver slice orientation
Mean
SD
Mean
SD
Mean
SD
Axial Coronal
30.2 49.4
6.0 11.4
25.0 28.6
5.1 4.9
19.1 21.6
5.7 6.7
Abbreviation: SD ⫽ standard deviation.
lyzed independently within each set, which consisted of either all T1- or all T2-weighted images. The organ boundaries can be seen clearly in both types of images. The contours were drawn by the same person. For consistency of contouring, the contours for the three gating settings were drawn within the same period. For a second independent motion check, a movie was reconstructed from the images for each gating setting. The breathing rate variation during the scan is a potential source of error. Each subject was trained before the scan to breathe regularly to minimize the breathing rate variation. The axial and coronal slices are two-dimensional images. The results could be different with three-dimensional volumes. Because of the speed limitation of MRI scans, it is
Respiratory gating only (mm)
Respiratory and cardiac gating (mm)
Margin direction
Mean
SD
Mean
SD
Mean
SD
Anterior Posterior Superior Inferior Left Right
7.2 8.6 10.9 10.9 11.8 6.1
1.2 2.8 3.1 2.0 3.0 2.1
7.1 5.7 8.1 6.2 9.1 5.7
3.5 1.6 3.0 1.6 2.7 1.3
4.0 3.5 4.4 4.5 5.5 4.1
0.5 0.5 2.0 0.9 1.4 1.5
Abbreviation: SD ⫽ standard deviation.
Combined cardiac and respiratory gating
practically impossible to perform continuous volumetric scans with each volumetric scan repeated in seconds. To obtain a three-dimensional volumetric cardiac and respiratory gated scan will take approximately 3–10 min for a single three-dimensional image set, depending on the size of the scanning volume. The motions in the continuous scan can also include components other than respiration and cardiac cycling, such as overall position change, coughing, and so forth. Overall position changes and the occurrence of coughing are unpredictable. They cannot be controlled for using either respiratory gating or cardiac gating, and they were beyond the scope of this study. Although the use of cardiac gating technique could potentially reduce the treatment margin needed for some tumors within the thoracic and abdominal regions, its application to actual treatment delivery needs further investigation. The cardiac cycles consist of the systolic and diastolic phases. The diastolic phase is usually relatively long and flat on the ECG curves. If ECG signals are used for cardiac gating during radiotherapy, the beam could be turned on during the flat diastolic phase so that a large fraction of the beam-on time would be within the cardiac cycle. The frequencies of the cardiac and respiratory cycles are usually very different. Each respiratory cycle contains several cardiac cycles. As a result, the phases of the cardiac and respiratory cycles during which the radiation beam
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could be turned on can be separately set without any interference between the cardiac and respiratory cycles. The respiratory phase should be determined first. Once the respiratory cycle reaches the beam-on phase, the cardiac cycle can then be checked to determine whether the diastolic phase has been reached to activate the treatment beam. Cardiac gating might be more reproducible than respiratory gating because the ECG curve has a long diastolic flat region. If we assume 200 –500 total monitor units are needed to deliver 180 cGy, using 600 monitor units/min, a 25% respiratory gating window, and a 40% cardiac gating window, the total beam-on time would be 3.3– 8.3 min. Although the beam-on time is only a few minutes, the actual treatment time, including preparation and patient setup, could be much longer. CONCLUSION The effect of cardiac motion on the treatment margin was characterized for both the heart and the liver. It was noted that a substantial treatment margin could be reduced for the heart by including cardiac gating. Cardiac gating might also reduce the treatment margin for the liver. In some clinical settings, the application of cardiac gating, together with respiratory gating, might be therapeutically advantageous. Additional investigation is required to establish the practical implementation of cardiac gating for radiation delivery.
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doi:10.1016/j.ijrobp.2006.11.057
PHYSICS CONTRIBUTION
REDUCTION OF ORGAN MOTION BY COMBINED CARDIAC GATING AND RESPIRATORY GATING ZHIHENG WANG, PH.D., CHRISTOPHER G. WILLETT, M.D.,
AND
FANG-FANG YIN, PH.D.
Department of Radiation Oncology, Duke University Medical Center, Durham, NC Purpose: To investigate whether the effect of organ motion can be further reduced with the application of a cardiac gating technique, together with respiratory gating. Methods and Materials: Axial and coronal images through the heart and liver were continuously scanned with fast cine magnetic resonance imaging scans at three different gating settings: (1) without respiratory and cardiac gating; (2) with respiratory gating, but without cardiac gating; and (3) with both respiratory and cardiac gating. The effect of motion for either the heart or liver was analyzed with probability maps. Results: With the application of respiratory gating only, the marginal region on the probability map was reduced by 10.0% in the axial slice and 19.8% in the coronal slice for the heart. It was reduced by 5.2% in the axial slice and 20.8% in the coronal slice for the liver. With the application of cardiac gating together with respiratory gating, the marginal region on the probability map was reduced further. The reduction was 8.0% in the axial slice and 13.6% in the coronal slice for the heart and 5.9% in the axial slice and 7.0% in the coronal slice for the liver. Conclusion: The effect of organ motion can be further reduced with the application of cardiac gating together with respiratory gating. The potential application to treatment planning merits further investigation. © 2007 Elsevier Inc. Organ motion, Respiratory gating, Cardiac gating, Treatment margin, Radiotherapy.
INTRODUCTION
8 mm and range of 5–17 mm, under normal respiration. The motion was measured along the superoinferior direction with ultrasonography. Under deep breathing, the mean peak-totrough liver motion was 37 mm (standard deviation, 8; range, 25–57). For the pancreas, Suramo et al. (6) reported a mean motion of 20 mm (range, 10 –30 mm) under normal respiration. Under deep breathing, the mean pancreas motion was 43 mm (range, 20 – 80 mm). Respiratory gating can be used to reduce the effect of intrafraction organ motion (7–22). The range of tumor motion is greatly reduced when the radiation beam is gated at the selected respiratory phase or amplitude. The margins of the radiation field can be reduced accordingly. Despite respiratory gating, residual motion exists during treatment of thoracic malignancies (23–25). In contrast, studies of the effect of cardiac gating on radiotherapy has not been evaluated extensively. At present, it is unclear how much intrafractional organ motion could be further reduced using cardiac gating integrated with respiratory gating. This study compared internal organ motion assayed by respiratory-gated magnetic resonance imaging (MRI) scans, with and without cardiac gating. These
With the development of new technologies in radiation oncology, radiation dose can now be delivered precisely to the target tumor volume while sparing critical normal tissue. However, this advantage may be diminished for tumors located in either the thoracic or abdominal regions because of internal organ motion induced by the respiratory and cardiac cycles and other physiologic events (1–3). Extra margins are typically added to the radiation fields to ensure the proper coverage of the target volume within its full range of motion. This is undesirable because more of the normal and nontarget tissues will be included in the target volume and will receive a high radiation dose. For lung tumors, Ross et al. (4) used an ultrafast computed tomography scanner to study the tumor motion related to the respiratory and cardiac cycles. The motion in the anteroposterior and lateral directions ranged from 5 to 22 mm for tumors in the lower lobe of the lung. For tumors in the hilar region, the lateral motion ranged from 0 to 16 mm. For tumors in the mediastinum region, the lateral motion ranged from 0 to 13 mm. For liver excursion, Davies et al. (5) reported a mean peak-to-trough motion of 10 mm, with a standard deviation of
late Dr. Tom Raidy for performing the magnetic resonance imaging scans and Dr. Mark Oldham for useful discussions. The authors also thank Ms. Jane Hoppenworth for editing the manuscript. Received April 11, 2006, and in revised form Nov 7, 2006. Accepted for publication Nov 9, 2006.
Reprint requests to: Zhiheng Wang, Ph.D., Department of Radiation Oncology, Duke University Medical Center, DUMC 3295, Durham, NC 27710. Tel: (919) 660-2188; Fax: (919) 681-7183; E-mail: [email protected] Conflict of interest: none. Acknowledgments—The authors thank Mr. Kevin Kelly and the 259
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data have clarified how the treatment margin from a defined clinical target volume to planning target volume can be further reduced if cardiac gating is integrated with respiratory gating.
METHODS AND MATERIALS Five healthy volunteers were scanned in an MRI scanner equipped with respiratory and cardiac gating. The scanner used in this study was a GE Signa (General Electric, Milwaukee, WI). A respiratory bellow was used for the respiratory gating signal (26 – 30). The bellow was wrapped around the torso of the subject. The signals from the respiratory bellow were fed into the MRI scanner to trigger the scanning pulse sequences. The electrocardiogram (ECG) signals of the subject were also fed into the scanner (30 – 33). The MRI pulse sequences can be triggered with signals from the respiratory bellows or the ECG, or a combination of both. The respiratory gating window was set to a 25% phase centered at the lowest point of expiration. For the scans with both cardiac and respiratory gating, the data acquisition was activated only when the ECG waveform was at the flat region of the diastolic phase and the respiratory signal was simultaneously within the gating window. Each subject was placed on the MRI couch in the supine position and scanned with MRI body coils. A localization scan was performed first with a repetition time (TR) of 54 ms, echo time (TE) of 1.7 ms, and a field of view (FOV) of 48 cm. Axial slices were then prescribed for the heart and liver. The scans were performed with three different gating settings: (1) without either respiratory or cardiac gating, (2) with respiratory gating but without cardiac gating, and (3) with both respiratory and cardiac gating. The scans with neither respiratory nor cardiac gating were performed with the single-shot fast-spin echo (SSFSE) pulse sequence. The scanning parameter settings were a TR of 748 ms, TE of 29 ms, slice thickness of 5 mm, phase encoding of 128, readout of 256, and FOV of 34 cm. The scan was continuously repeated 20 times with a frame rate of 80 frames per minute. The scans with respiratory gating, but without cardiac gating, were performed with the SSFSE pulse sequence, also. The scanning parameter settings were a TR of 3,231 ms, TE of 29 ms, slice thickness of 5 mm, phase encoding of 128, readout of 256, and FOV of 34 cm. The scan was continuously repeated 20 times with a frame rate of 19 frames/min. The scans with both respiratory and cardiac gating were performed with a fast spoiled gradient echo pulse sequence. The scanning parameter settings were a TR of 5.1 ms, TE of 1.8 ms, slice thickness of 5 mm, phase encoding of 128, readout of 256, and FOV of 34 cm. The scan was continuously repeated 20 times with a frame rate of 60 frames/min. The scans were repeated for a coronal slice through the heart and liver with the same setting as the axial slices. The FOV for the coronal slices was 48 ⫻ 48 cm. All the images were saved in the Digital Imaging and Communications in Medicine (DICOM) format and transferred to a computer for analysis. The DICOM images were read into MATLAB (Math Works, Natick, MA). The image set with 20 continuous scans was written into a movie file to visually observe the motions. The different images were obtained by subtracting the image with the first image. For each subject, the contours of the heart and liver were drawn on the corresponding axial and coronal slices for each image of the set of 20 continuous scans. A probability map was reconstructed separately for each heart and liver slice to show the probability of the organ appearing at a
Fig. 1. Axial slice of heart acquired with single-shot fast-spin echo (SSFSE) sequence (a) and contours of heart for all 20 repeated scans with three different gating settings: (b) without any gating; (c) with respiratory gating only; and (d) with both respiratory and cardiac gating.
certain location on the map. A probability of 100% means that the organ appears at this location all the time. A probability of 0% means that the organ never appears at this location. The area of probability between 0% and 100% is the marginal region in which the organ regularly moves in and out. If a radiation field is designed to cover all the pixels with a probability ⬎0% in the probability map, the organ will be irradiated during any phase of the motion cycles. If a radiation field is designed to tolerate a 5% error, the field can be shrunk to cover the area with a probability ⬎5% on the probability map. To construct the probability map, the area within the contour of each organ was assigned a pixel value of 1, and the area outside the contour was assigned a pixel value of 0. The pixel values were then summed for all the images within the continuous scan set and renormalized to the maximum of 100%. Probability maps were calculated for each gating setting. The ratio of the marginal area to the average area of the organ contours was calculated and compared to show the effect of gating on organ motion. The margins along the anteroposterior, superoinferior, and left–right direction were also compared among the three different gating settings.
RESULTS An axial slice of the heart is shown in Fig. 1a. It was acquired with the SSFSE sequence and a TR of 748 ms and TE of 29 ms without any gating applied. The scan was repeated continuously 20 times. The contours of the heart for all 20 repeated scans without any gating were overlaid together (Fig. 1b). Figure 1c shows the contours of the heart on the same axial slice acquired with respiratory gating but
Combined cardiac and respiratory gating
Fig. 2. Coronal slice of heart acquired with single-shot fast-spin echo (SSFSE) sequence (a) and contours of heart for all 20 repeated scans with three different gating settings: (b) without any gating; (c) with respiratory gating only; and (d) with both respiratory and cardiac gating.
without cardiac gating. Figure 1d shows the contours of the heart acquired with both respiratory and cardiac gating. Figure 2a shows the coronal slice of the heart acquired with the SSFSE sequence. Figure 2b shows the contours of the heart for all 20 repeated scans without any gating. Figure 2c shows the contours of the heart on the same coronal slice acquired with respiratory gating but without cardiac gating, and Fig. 2d shows the contours of the heart acquired with both respiratory and cardiac gating. The probability maps of the heart were calculated and are shown in Fig. 3, with Fig. 3a– c for the axial slice and Fig. 3d–f for the coronal slice. Figure 3a,d was reconstructed from the scans without any gating. Figure 3b,e was reconstructed from the scans with respiratory gating, but without cardiac gating. Figure 3c,f was reconstructed from the scans with both respiratory and cardiac gating. Figure 4 shows the marginal regions of the probability maps at which the probability was ⬎5% and ⬍95% for the heart (Fig. 4a– c shows the axial slice and Fig. 4d–f the coronal slice). Figure 4a,d was reconstructed from the scans without any gating. Figure 4b,e was reconstructed from the scans with respiratory gating, but without cardiac gating. Figure 4c,f was reconstructed from the scans with both respiratory and cardiac gating. The percentage of the area of the marginal region normalized to the area of the contour is 44.5% for the axial scans without any gating (Fig. 4a). It reduced to 25.5% for the axial scans with respiratory gating but without cardiac gating (Fig. 4b). It decreased further to 17.3% for the axial scans with both respiratory and cardiac
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gating (Fig. 4c). For the coronal slice shown in Fig. 4d–f, the percentage of the area of the marginal region was 37.3% for the scans without any gating (Fig. 4d). This percentage decreased to 30.7% for the scans with respiratory gating but without cardiac gating (Fig. 4e) and decreased further to 16.6% for the scans with both respiratory and cardiac gating (Fig. 4f). The mean and standard deviation of the percentages of the marginal region for all 5 subjects in this study are listed in Table 1. In the axial slice for the heart, the mean percentage of the marginal region in the probability maps decreased from 32.9% without any gating to 22.9% with respiratory gating but without cardiac gating. An average 10% reduction of the marginal region was achieved with respiratory gating only. For the coronal slice of the heart, the mean percentage of marginal region in the probability maps decreased from 56.9% without any gating to 37.1% with respiratory gating but without cardiac gating. An average 19.8% reduction of the marginal region was achieved with respiratory gating only. With both respiratory and cardiac gating, the mean percentage of marginal region in the probability maps of the heart in the axial slice decreased further to 14.9%. An average additional 8.0% reduction of the marginal region was achieved with the added cardiac gating. For the coronal slice of the heart, the mean percentage of marginal region in the probability maps decreased further to 23.5% with both respiratory and cardiac gating. An average additional 13.6% reduction of the marginal region was achieved with the added cardiac gating. Table 2 lists the margins along the anteroposterior, superoinferior, and left–right directions for the heart with three different gating settings. An axial slice of the liver of 1 volunteer is shown in Fig. 5a. It was acquired with the SSFSE sequence and a TR of 748 ms and TE of 29 ms without any gating applied. The scan was repeated continuously for 20 times. The contours of the liver for all 20 repeated scans without any gating were
Fig. 3. Probability maps of heart with (a– c) for axial slice and (d–f) for coronal slice. (a,d) Reconstructed from scans without any gating. (b,e) Reconstructed from scans with respiratory gating but without cardiac gating. (c,f) Reconstructed from scans with both respiratory and cardiac gating.
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Fig. 4. Marginal regions of probability maps at which probability was ⬎5% and ⬍95% for heart: (a– c) axial slice and (d–f) coronal slice. (a,d) Reconstructed from scans without any gating. (b,e) Reconstructed from scans with respiratory gating but without cardiac gating. (c,f) Reconstructed from scans with both respiratory and cardiac gating.
overlaid together and are shown in Fig. 5b. Figure 5c shows the contours of the liver on the same axial slice acquired with respiratory gating but without cardiac gating, and Fig. 5d shows the contours of the liver acquired with both respiratory and cardiac gating. Figure 6a shows the coronal slice of the liver acquired with the SSFSE sequence. Figure 6b shows the contours of the liver for all 20 repeated scans without any gating. Figure 6c shows the contours of the liver on the same coronal slice acquired with respiratory gating but without cardiac gating, and Fig. 6d shows the contours of the liver acquired with both respiratory and cardiac gating. The probability maps of the liver were calculated and are shown in Fig. 7, with Fig. 7a– c showing the axial slice and Fig. 7d–f showing the coronal slice. Figure 7a,d was reconstructed from the scans without any gating. Figure 7b,e was reconstructed from the scans with respiratory gating but
Table 1. Mean and standard deviation of percentages of marginal region of heart scanned with three different gating settings
No gating (%)
Respiratory gating only (%)
Table 2. Margins along anteroposterior, superoinferior, and left– right directions for heart with three different gating settings No gating (mm)
Respiratory and cardiac gating (%)
Heart slice orientation
Mean
SD
Mean
SD
Mean
SD
Axial Coronal
32.9 56.9
11.7 32.1
22.9 37.1
5.8 11.4
14.9 23.5
2.2 9.2
Abbreviation: SD ⫽ standard deviation.
without cardiac gating. Figure 7c,f was reconstructed from the scans with both respiratory and cardiac gating. Figure 8 shows the marginal regions of the probability maps at which the probability was ⬎5% and ⬍95% for the liver, with Fig. 8a– c showing the axial slice and Fig. 8d–f showing the coronal slice. Figure 8a,d was reconstructed from the scans without any gating. Figure 8b,e was reconstructed from the scans with respiratory gating but without cardiac gating. Figure 8c,f was reconstructed from the scans with both respiratory and cardiac gating. Figure 8a shows the percentage of the area of the marginal region normalized to the area of the contour, which was 36.5% for the axial scans without any gating. This percentage decreased to 25.6% for the axial scans with respiratory gating but without cardiac gating (Fig. 8b). It decreased further to 19.1% for
Respiratory gating only (mm)
Respiratory and cardiac gating (mm)
Margin direction
Mean
SD
Mean
SD
Mean
SD
Anterior Posterior Superior Inferior Left Right
11.1 12.9 11.1 10.1 11.0 14.7
3.3 7.6 6.1 1.3 9.3 11.8
7.1 8.6 7.9 8.4 6.9 10.4
1.3 2.0 2.5 5.0 2.4 7.1
3.7 5.7 5.0 5.7 5.6 4.5
1.2 1.8 3.3 2.1 1.1 2.3
Abbreviation: SD ⫽ standard deviation.
Combined cardiac and respiratory gating
Fig. 5. Axial slice of liver acquired with single-shot fast-spin echo (SSFSE) sequence (a) and contours of heart for all 20 repeated scans with three different gating settings: (b) without any gating; (c) with respiratory gating only; and (d) with both respiratory and cardiac gating.
the axial scans with both respiratory and cardiac gating (Fig. 8c). Figure 8d–f shows the percentage of the area of the marginal region for the coronal slice, which was 50.1% for the scans without any gating (Fig. 8d). This percentage decreased to 27.5% for scans with respiratory gating but without cardiac gating (Fig. 8e) and decreased further to 15.8% for scans with both respiratory and cardiac gating (Fig. 8f). Table 3 lists the mean and standard deviation values of the percentages of the marginal region for all 5 subjects in this study. For the liver in the axial slice, the mean percentage of the marginal region in the probability maps decreased from 30.2% without any gating to 25.0% with respiratory gating but without cardiac gating. An average 5.2% reduction of the marginal region was achieved with respiratory gating only. For the coronal slice of the liver, the mean percentage of the marginal region in the probability maps decreased from 49.4% without any gating to 28.6% with respiratory gating but without cardiac gating. An average 20.8% reduction of the marginal region was achieved with respiratory gating only. With both respiratory and cardiac gating, the mean percentage of marginal region in the probability maps decreased further to 19.1% for the liver in the axial slice. An average additional 5.9% reduction of the marginal region was achieved with the added cardiac gating. For the coronal slice of the liver, the mean percentage of the marginal region in the probability maps decreased further to 21.6% with both respiratory and cardiac gating. An average additional 7.0% reduction of the marginal region was achieved with the added cardiac gating.
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Fig. 6. Coronal slice of liver acquired with single-shot fast-spin echo (SSFSE) sequence (a) and contours of heart for all 20 repeated scans with three different gating settings: (b) without any gating; (c) with respiratory gating only; and (d) with both respiratory and cardiac gating.
Table 4 lists the margins along the anteroposterior, superoinferior, and left–right directions for the liver with three different gating settings. DISCUSSION Cardiac gating, applied together with respiratory gating, can further reduce the marginal region. However, the stan-
Fig. 7. Probability maps of liver with (a– c) for axial slice and (d–f) for coronal slice. (a,d) Reconstructed from scans without any gating. (b,e) Reconstructed from scans with respiratory gating but without cardiac gating. (c,f) Reconstructed from scans with both respiratory and cardiac gating.
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Fig. 8. Marginal regions of probability maps at which probability was ⬎5% and ⬍95% for liver with (a– c) for axial slice and (d–f) for coronal slice. (a,d) Reconstructed from scans without any gating. (b,e) Reconstructed from scans with respiratory gating but without cardiac gating. (c,f) Reconstructed from scans with both respiratory and cardiac gating.
dard deviations for the reductions of the marginal regions were large. This suggests that the reduction of the marginal region gained by adding cardiac gating might not be significant for some cases, especially for the liver. The scanning parameters for three different gating settings were programmed to have the greatest achievable frame rate for each individual scan. The total scanning time was not the same for the three different gating settings. A global shift, if existed, might be added to the motion that associated with respiratory and cardiac cycling for a longer scanning duration. For this study, the longest scanning time for a gated set of 20 images was about 1.05 min. No global shift was found during the scanning time. Because of the limitations of the technique, the same SSFSE sequence could not be used for combined respiratory and cardiac gating. However, the organ motion was ana-
Table 3. Mean and standard deviation of percentages of marginal region of liver scanned with three different gating settings
No gating (%)
Respiratory gating only (%)
Table 4. Margins along anteroposterior, superoinferior, and left– right directions for liver with three different gating settings No gating (mm)
Respiratory and cardiac gating (%)
Liver slice orientation
Mean
SD
Mean
SD
Mean
SD
Axial Coronal
30.2 49.4
6.0 11.4
25.0 28.6
5.1 4.9
19.1 21.6
5.7 6.7
Abbreviation: SD ⫽ standard deviation.
lyzed independently within each set, which consisted of either all T1- or all T2-weighted images. The organ boundaries can be seen clearly in both types of images. The contours were drawn by the same person. For consistency of contouring, the contours for the three gating settings were drawn within the same period. For a second independent motion check, a movie was reconstructed from the images for each gating setting. The breathing rate variation during the scan is a potential source of error. Each subject was trained before the scan to breathe regularly to minimize the breathing rate variation. The axial and coronal slices are two-dimensional images. The results could be different with three-dimensional volumes. Because of the speed limitation of MRI scans, it is
Respiratory gating only (mm)
Respiratory and cardiac gating (mm)
Margin direction
Mean
SD
Mean
SD
Mean
SD
Anterior Posterior Superior Inferior Left Right
7.2 8.6 10.9 10.9 11.8 6.1
1.2 2.8 3.1 2.0 3.0 2.1
7.1 5.7 8.1 6.2 9.1 5.7
3.5 1.6 3.0 1.6 2.7 1.3
4.0 3.5 4.4 4.5 5.5 4.1
0.5 0.5 2.0 0.9 1.4 1.5
Abbreviation: SD ⫽ standard deviation.
Combined cardiac and respiratory gating
practically impossible to perform continuous volumetric scans with each volumetric scan repeated in seconds. To obtain a three-dimensional volumetric cardiac and respiratory gated scan will take approximately 3–10 min for a single three-dimensional image set, depending on the size of the scanning volume. The motions in the continuous scan can also include components other than respiration and cardiac cycling, such as overall position change, coughing, and so forth. Overall position changes and the occurrence of coughing are unpredictable. They cannot be controlled for using either respiratory gating or cardiac gating, and they were beyond the scope of this study. Although the use of cardiac gating technique could potentially reduce the treatment margin needed for some tumors within the thoracic and abdominal regions, its application to actual treatment delivery needs further investigation. The cardiac cycles consist of the systolic and diastolic phases. The diastolic phase is usually relatively long and flat on the ECG curves. If ECG signals are used for cardiac gating during radiotherapy, the beam could be turned on during the flat diastolic phase so that a large fraction of the beam-on time would be within the cardiac cycle. The frequencies of the cardiac and respiratory cycles are usually very different. Each respiratory cycle contains several cardiac cycles. As a result, the phases of the cardiac and respiratory cycles during which the radiation beam
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could be turned on can be separately set without any interference between the cardiac and respiratory cycles. The respiratory phase should be determined first. Once the respiratory cycle reaches the beam-on phase, the cardiac cycle can then be checked to determine whether the diastolic phase has been reached to activate the treatment beam. Cardiac gating might be more reproducible than respiratory gating because the ECG curve has a long diastolic flat region. If we assume 200 –500 total monitor units are needed to deliver 180 cGy, using 600 monitor units/min, a 25% respiratory gating window, and a 40% cardiac gating window, the total beam-on time would be 3.3– 8.3 min. Although the beam-on time is only a few minutes, the actual treatment time, including preparation and patient setup, could be much longer. CONCLUSION The effect of cardiac motion on the treatment margin was characterized for both the heart and the liver. It was noted that a substantial treatment margin could be reduced for the heart by including cardiac gating. Cardiac gating might also reduce the treatment margin for the liver. In some clinical settings, the application of cardiac gating, together with respiratory gating, might be therapeutically advantageous. Additional investigation is required to establish the practical implementation of cardiac gating for radiation delivery.
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