JNM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in JNM
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allen-Auerbach, M.
Right arrow Articles by Czernin, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allen-Auerbach, M.
Right arrow Articles by Czernin, J.
Journal of Nuclear Medicine Vol. 47 No. 2 298-301
© 2006 by Society of Nuclear Medicine

Clinical Investigation

Standard PET/CT of the Chest During Shallow Breathing Is Inadequate for Comprehensive Staging of Lung Cancer

Martin Allen-Auerbach, MD1, Kristen Yeom, MD2, John Park, MD, PhD2, Michael Phelps, PhD1 and Johannes Czernin, MD1

1 Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Center, UCLA David Geffen School of Medicine, Los Angeles, California; and 2 Department of Radiological Sciences, UCLA David Geffen School of Medicine, Los Angeles, California

Correspondence: For correspondence or reprints contact: Martin Allen-Auerbach, MD, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Center, UCLA David Geffen School of Medicine, 10833 Le Conte Ave., A-243 CHS, Los Angeles, CA 90095-6942. E-mail: mauerbach{at}mednet.ucla.edu Guest Editor: Dominique Delbeke, MD, PhD.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 References
 
The incidence of malignancy associated with subcentimeter pulmonary nodules (micronodules) in patients with malignant disease has been reported to be as high as 58%. Thus, detection of small lung nodules is important for appropriate staging of lung cancer. Because of respiratory motion, small parenchymal lung lesions can be missed on CT acquired during shallow breathing. Micronodules are usually too small to be characterized reliably with 18F-FDG PET. We aimed to determine the incidence of missed pulmonary micronodules on PET/CT studies acquired during shallow breathing. Methods: The study included 142 consecutive cancer patients (62 male and 80 female; mean age, 54 y) who underwent whole-body PET/CT during shallow breathing and breath-hold CT of the chest during maximal inspiration. CT findings were reviewed independently, and noncalcified nodules missed on the shallow-breathing scan were evaluated for size, location, and metabolic activity. Results: Breath-hold chest CT detected an additional 125 parenchymal lung nodules (mean size, 3.4 ± 1.6 mm; range, 1–9 mm) in 48 (34%) of the 142 patients. In these patients, 3 nodules, on average, were missed during shallow breathing. In 18 patients (13%), micronodules were identified exclusively on breath-hold images. None of the missed nodules demonstrated 18F-FDG uptake. Conclusion: Acquisition of standard PET/CT chest images during shallow breathing is inadequate for comprehensive cancer staging.

Key Words: PET/CT • cancer • lung • staging • breath-hold


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 References
 
The increasing use of PET/CT has led to the development of new imaging protocols to optimize fusion of PET and CT images. With current multidetector-CT technology, anatomic images of the chest or even the whole body can be acquired within seconds to minutes (1,2). Acquisition times for PET images, however, range from 7 min with lutetium oxyorthosilicate crystal–based technology (3,4) to more than 30 min for bismuth germanate crystal–based PET systems (5).

To optimize coregistration, both the CT and the PET portions of the examination are acquired during continuous shallow breathing (6–9). Respiratory motion does not significantly compromise the interpretation of PET images but does result in an unsatisfactory evaluation of the lung parenchyma on CT images. Subcentimeter nodules can be missed, and normal anatomic structures such as blood vessels can have an ambiguous appearance suggesting abnormality where there is none (10–12). The limited sensitivity of PET for subcentimeter lesions further limits the characterization of small pulmonary nodules (13,14).

The incidence of malignancy in subcentimeter pulmonary nodules (micronodules) of patients with known malignancy has been reported to range from 10% to 58% (15–18). Thus, identifying subcentimeter nodules has important implications for the staging and restaging of cancer and for establishing prognosis and initiating the most appropriate treatment.

The aim of the current study was to determine the incidence at which pulmonary micronodules are missed on PET/CT studies acquired during shallow breathing.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 References
 
Patient Population
This study included 142 consecutive patients (62 male and 80 female; mean age, 54 ± 28 y; range, 4–88 y) who underwent PET/CT between April 1 and June 30, 2004, and breath-hold CT of the chest during maximal inspiration. The PET/CT study was indicated for staging and restaging of various types of cancer (Table 1). The study complied with the regulations of the UCLA Institutional Review Board and of the Health Insurance Portability and Accountability Act.


View this table:
[in this window]
[in a new window]
  		TABLE 1 Indications for PET/CT in the 142 Patients

 
Image Acquisition
PET/CT was performed using the Reveal RT scanner (CPS Innovations). This system combines a dual-slice-detector CT scanner (Somatom Emotion; Siemens Medical Systems) with an ECAT ACCEL PET scanner (Siemens/CPS Innovations).

While resting on a reclining chair, the patients received a 7.8 MBq/kg dose of 18F-FDG intravenously and drank 900 mL of barium sulfate. The imaging sequence began 60 min after tracer injection, after the patients had been placed on the scanner table in the arms-up position. We first obtained an initial scout scan to define the imaging field, followed by a low-dose (130 kVp, 35 mAs, 4-mm slice collimation, and pitch of 2) maximum-inspiration breath-hold CT scan of the chest. Immediately afterward, whole-body CT with intravenous contrast material was performed using the following parameters: 130 kVp, 120 mAs, 1-s tube rotation, 4-mm slice collimation, and bed speed of 8 mm/s (i.e., pitch of 2). This scan was followed by the PET emission scan, using a weight-based protocol as recently described (3,4). Scanning encompassed 6–8 bed positions (depending on patient height) from the mid thigh to the base of the skull.

Image Reconstruction
CT images were reconstructed using conventional filtered backprojection, at 3.4-mm axial intervals to match the slice separation of the PET data. PET images were reconstructed using iterative algorithms (ordered-subsets expectation maximization: 2 iterations and 8 subsets) to a final image resolution of 8.8 mm in full width at half maximum. Attenuation was corrected by mapping the CT Hounsfield units to the linear attenuation coefficients as previously described (19,20).

The low-dose breath-hold CT scan of the chest was reconstructed using conventional filtered backprojection at 5-mm axial intervals.

Image Analysis
The 142 patients were identified retrospectively. The 2 sets of CT studies (shallow breathing and breath hold) were analyzed prospectively and by consensus by 2 radiologists and 1 nuclear medicine specialist who were unaware of the patient's history and other imaging findings. The viewing station of a picture archiving and communication system was used for review of the CT images. Syngo software (Siemens) was used for review of the fused images. CT scans were presented to the readers in a random and unpaired sequence. All noncalcified nodules missed on the shallow-breathing scan were evaluated for size (largest diameter) and location. 18F-FDG uptake was assessed visually and was defined as positive if greater than the level of the surrounding lung tissue.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 References
 
A total of 160 noncalcified lung nodules smaller than 1 cm were detected on CT scans acquired during shallow breathing.

Breath-hold CT detected 125 additional noncalcified lung nodules smaller than 1 cm in 48 (34%) of 142 patients. In 18 of these 48 patients (i.e., 13% of the study population of 142 patients), 38 small lung nodules were detected only on the breath-hold CT scan, with an average of 2 nodules missed on the images acquired during shallow breathing. Eighty-seven additional nodules (an average of 3 nodules missed on the images acquired during shallow breathing) were detected in 30 of these 48 patients in addition to nodules seen in the shallow-breathing images.

The size of the missed nodules ranged from 1 to 9 mm (Figs. 1–3 GoGo) and averaged 3.4 ± 1.6 mm. The left lower lobe of the lung was the most frequent location at which nodules were missed (Table 2). None of the missed nodules demonstrated 18F-FDG uptake.


Figure 1
View larger version (8K):
[in this window]
[in a new window]
  		FIGURE 1.  Size distribution of nodules missed on shallow-breathing CT.

 

Figure 2
View larger version (80K):
[in this window]
[in a new window]
  		FIGURE 2.  A 7-mm nodule (arrow) seen on maximum-inspiration CT (A) and missed on shallow-breathing CT (B) in left lower lobe of lung in patient with lung cancer.

 

Figure 3
View larger version (62K):
[in this window]
[in a new window]
  		FIGURE 3.  A 4-mm nodule (arrow) seen on maximum-inspiration CT (A) and missed on shallow-breathing CT (B) in left lower lobe of lung in patient with pancreatic cancer.

 

View this table:
[in this window]
[in a new window]
  		TABLE 2 Distribution of the 125 Nodules Missed on Shallow-Breathing CT

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 References
 
Significance of Micronodules
The prevalence of malignancy in micronodules detected on screening CT of the chest appears to be low, and there has been extensive debate over what constitutes the optimal management of incidentally detected small lung nodules (21–23). However, the incidence of malignancy associated with micronodules in the oncologic population has been reported to range from 10% to 58% (15–18) and probably depends on the underlying malignancy (24,25). In clinical practice, however, the statistical likelihood that a certain cancer will metastasize to the lung will be of only limited value for decisions on an individual patient's management. It is therefore prudent at least to adopt a strategy of close follow-up, even in patients with underlying malignancies that are only rarely associated with lung metastases.

Six of the 18 patients with micronodules that were detected only on the breath-hold studies did have significant metastatic disease elsewhere in the body. Conversely, 12 (66.6%) of the 18 patients had no evidence of other metastatic disease. In these patients, the detection of micronodules would have changed patient management, resulting in close follow-up of the micronodules.

How Much CT?
The results of our study have important implications for diagnosis, treatment, and prognosis. PET/CT is increasingly being proposed for use as a single, comprehensive modality for staging and restaging of cancer. Yet how much CT is needed is still a matter of controversy. Some have proposed that all CT should be done with intravenous contrast material (26), whereas others (27) have questioned the necessity of this approach.

When the lung parenchyma is assessed by CT alone, referring physicians expect the highest diagnostic quality, and breath-hold imaging sequences are considered the state of the art (10–12). Patients referred for PET/CT frequently undergo other imaging studies, including breath-hold CT of the chest. In these patients, an additional breath-hold CT scan of the chest as part of the PET/CT examination would not be necessary. However, the current study demonstrates the importance of breath-hold CT for a comprehensive assessment of cancer patients.

PET and Lesion Size
Because the spatial resolution of current PET scanners is approximately 6–8 mm (28), small lung nodules are not well characterized with 18F-FDG PET. A metaanalysis by Gould et al. found a high number of false-negative PET results for nodules smaller than 1 cm (13). In a more recent study by Nomori et al. looking at the performance of PET in small lung nodules, all malignant nodules smaller than 1 cm gave false-negative PET findings (14). These results were further supported by Crippa et al. (29), who reported a sensitivity of only 23% for detecting tumor-involved lymph nodes 5 mm or smaller in melanoma patients, despite the high glycolytic activity of this type of cancer. Thus, the sensitivity of PET for detecting cancer in small lesions is limited. Adding low-dose breath-hold CT of the chest represents a feasible approach to overcoming the limitations of current PET/CT protocols.

Radiation Dose
Depending on the examination parameters, CT of the chest can result in a radiation dose of up to 27 mSv (30). However, the additional radiation from low-dose CT of the chest amounts to less than 2 mSv (31). This seems a relatively small increment, with negligible additional risks, given that the dose received from whole-body PET/CT is approximately 30 mSv (32). Cancer patients usually undergo multiple radiologic procedures during the course of diagnosis, treatment, and follow-up. Because a single, comprehensive whole-body examination limits the need for additional radiologic examinations, the overall radiation dose received might actually be reduced. This consideration, together with the importance of accurate cancer staging and restaging, justifies the small additional exposure of patients to radiation.

PET/CT has replaced PET at most institutions. Optimal use of this technology requires close interaction between radiologists and nuclear medicine specialists not only in interpreting images but also in selecting image-acquisition protocols. We have demonstrated that low-dose breath-hold CT of the chest adds important diagnostic information.

Study Limitations
Insufficient follow-up data were available. Ideally, follow-up data would have provided information on the fate of the additional nodules detected on breath-hold CT. But the current study was not undertaken to determine the significance of pulmonary micronodules as detected by CT, because such studies have been done previously and have demonstrated that 18%–58% of such nodules represent metastatic disease [15–18]. The slice thickness (5 mm) chosen for low-dose breath-hold CT does not represent the optimum setting for the detection of small pulmonary nodules. However, the settings were chosen as a compromise between image resolution and radiation dose. High-resolution (1 mm) breath-hold CT might have led to the detection of additional nodules.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
References
 
The current study demonstrates that maximum-inspiration breath-hold CT should be included with comprehensive whole-body PET/CT of cancer patients if no separate breath-hold chest CT is performed before PET/CT.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 References
 

  1. Klingenbeck-Regn K, Schaller S, Flohr T, et al. Subsecond multi-slice computed tomography: basics and applications. Eur J Radiol. 1999;31:110–124.[Medline]
  2. Rigauts H. A one year experience with the multislice helical CT. JBR-BTR. 1999;82:273–276.
  3. Halpern BS, Dahlbom M, Auerbach MA, et al. Optimizing imaging protocols for overweight and obese patients: a lutetium orthosilicate PET/CT study. J Nucl Med. 2005;46:603–607.[Abstract/Free Full Text]
  4. Halpern BS, Dahlbom M, Quon A, et al. Impact of patient weight and emission scan duration on PET/CT image quality and lesion detectability. J Nucl Med. 2004;45:797–801.[Abstract/Free Full Text]
  5. Beyer T, Kinahan PE, Townsend DW. Optimization of transmission and emission scan duration in 3D whole-body PET. IEEE Trans Nucl Sci. 1997;44:2400–2407.
  6. Bockisch A, Beyer T, Antoch G, et al. Positron emission tomography/computed tomography: imaging protocols, artifacts, and pitfalls. Mol Imaging Biol. 2004;6:188–199.[Medline]
  7. Goerres GW, Burger C, Kamel E, et al. Respiration-induced attenuation artifact at PET/CT: technical considerations. Radiology. 2003;226:906–910.[Abstract/Free Full Text]
  8. Goerres GW, Kamel E, Heidelberg TN, et al. PET-CT image co-registration in the thorax: influence of respiration. Eur J Nucl Med Mol Imaging. 2002;29:351–360.[Medline]
  9. Beyer T, Antoch G, Blodgett T, et al. Dual-modality PET/CT imaging: the effect of respiratory motion on combined image quality in clinical oncology. Eur J Nucl Med Mol Imaging. 2003;30:588–596.[Medline]
  10. Webb W, Mueller N, Naidich D. High-Resolution CT of the Lung. 3rd ed. Philadelphia, PA: Lippincott-Raven; 2000:1–47.
  11. Tarver RD, Conces DJ Jr, Godwin JD. Motion artifacts on CT simulate bronchiectasis. AJR. 1988;151:1117–1119.[Free Full Text]
  12. Mayo JR. High resolution computed tomography: technical aspects. Radiol Clin North Am. 1991;29:1043–1049.[Medline]
  13. Gould MK, Maclean CC, Kuschner WG, et al. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA. 2001;285:914–924.[Abstract/Free Full Text]
  14. Nomori H, Watanabe K, Ohtsuka T, et al. Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images. Lung Cancer. 2004;45:19–27.[Medline]
  15. Keogan MT, Tung KT, Kaplan DK, et al. The significance of pulmonary nodules detected on CT staging for lung cancer. Clin Radiol. 1993;48:94–96.[Medline]
  16. Munden RF, Pugatch RD, Liptay MJ, et al. Small pulmonary lesions detected at CT: clinical importance. Radiology. 1997;202:105–110.[Abstract/Free Full Text]
  17. Chalmers N, Best JJ. The significance of pulmonary nodules detected by CT but not by chest radiography in tumour staging. Clin Radiol. 1991;44:410–412.[Medline]
  18. Benjamin MS, Drucker EA, McLoud TC, et al. Small pulmonary nodules: detection at chest CT and outcome. Radiology. 2003;226:489–493.[Abstract/Free Full Text]
  19. Beyer T, Townsend DW, Brun T, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med. 2000;41:1369–1379.[Abstract/Free Full Text]
  20. Kinahan PE, Townsend DW, Beyer T, et al. Attenuation correction for a combined 3D PET/CT scanner. Med Phys. 1998;25:2046–2053.[Medline]
  21. Jett JR. Limitations of screening for lung cancer with low-dose spiral computed tomography. Clin Cancer Res. 2005;11:4988s–4992s.[Abstract/Free Full Text]
  22. Swensen SJ, Jett JR, Hartman TE, et al. CT screening for lung cancer: five-year prospective experience. Radiology. 2005;235:259–265.[Abstract/Free Full Text]
  23. Swensen SJ, Jett JR, Hartman TE, et al. Lung cancer screening with CT: Mayo Clinic experience. Radiology. 2003;226:756–761.[Abstract/Free Full Text]
  24. Quint LE, Park CH, Lannettoni MD. Solitary pulmonary nodules in patients with extrapulmonary neoplasms. Radiology. 2000;217:257–261.[Abstract/Free Full Text]
  25. Marchevsky A. Metastatic Tumors of the Lung. Vol 44. Florence, KY: Marcel Dekker; 1990:231–247.
  26. Antoch G, Freudenberg L, Beyer T, et al. To enhance or not to enhance? 18F-FDG and CT contrast agents in dual-modality 18F-FDG PET/CT. J Nucl Med. 2004;45(suppl):56S–65S.[Medline]
  27. Schaefer NG, Hany TF, Taverna C, et al. Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging—do we need contrast-enhanced CT? Radiology. 2004;232:823–829.[Abstract/Free Full Text]
  28. Townsend DW. Physical principles and technology of clinical PET imaging. Ann Acad Med Singapore. 2004;33:133–145.[Medline]
  29. Crippa F, Leutner M, Belli F, et al. Which kinds of lymph node metastases can FDG PET detect? A clinical study in melanoma. J Nucl Med. 2000;41:1491–1494.[Abstract/Free Full Text]
  30. Diederich S, Lenzen H. Radiation exposure associated with imaging of the chest: comparison of different radiographic and computed tomography techniques. Cancer. 2000;89(11 suppl):2457–2460.[Medline]
  31. Ravenel JG, Scalzetti EM, Huda W, et al. Radiation exposure and image quality in chest CT examinations. AJR. 2001;177:279–284.[Abstract/Free Full Text]
  32. Wu TH, Huang YH, Lee JJ, et al. Radiation exposure during transmission measurements: comparison between CT- and germanium-based techniques with a current PET scanner. Eur J Nucl Med Mol Imaging. 2004;31:38–43.[Medline]
Received for publication August 4, 2005. Accepted for publication October 31, 2005.


Related articles in JNM:

This Month in JNM

JNM 2006 47: 7a-8a. [Full Text]  



This article has been cited by other articles:


Home page
 JNMHome page
T. Kawano, E. Ohtake, and T. Inoue
Deep-Inspiration Breath-Hold PET/CT of Lung Cancer: Maximum Standardized Uptake Value Analysis of 108 Patients
J. Nucl. Med., August 1, 2008; 49(8): 1223 - 1231.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
M. R. Benz, V. Evilevitch, M. S. Allen-Auerbach, F. C. Eilber, M. E. Phelps, J. Czernin, and W. A. Weber
Treatment Monitoring by 18F-FDG PET/CT in Patients with Sarcomas: Interobserver Variability of Quantitative Parameters in Treatment-Induced Changes in Histopathologically Responding and Nonresponding Tumors
J. Nucl. Med., July 1, 2008; 49(7): 1038 - 1046.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
D. W. Townsend
Dual-Modality Imaging: Combining Anatomy and Function
J. Nucl. Med., June 1, 2008; 49(6): 938 - 955.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
W. V. Vogel, J. A. van Dalen, B. Wiering, H. Huisman, F. H.M. Corstens, T. J.M. Ruers, and W. J.G. Oyen
Evaluation of Image Registration in PET/CT of the Liver and Recommendations for Optimized Imaging
J. Nucl. Med., June 1, 2007; 48(6): 910 - 919.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
S. A. Nehmeh, Y. E. Erdi, G. S.P. Meirelles, O. Squire, S. M. Larson, J. L. Humm, and H. Schoder
Deep-Inspiration Breath-Hold PET/CT of the Thorax
J. Nucl. Med., January 1, 2007; 48(1): 22 - 26.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
K. Brechtel and T. Beyer
Reply: Adequate Evaluation of Image Registration in Hybrid PET/CT.
J. Nucl. Med., September 1, 2006; 47(9): 1557 - 1558.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in JNM
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allen-Auerbach, M.
Right arrow Articles by Czernin, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allen-Auerbach, M.
Right arrow Articles by Czernin, J.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY THE JOURNAL OF NUCLEAR MEDICINE