Patrick Veit-Haibach, MD

Primary malignant musculoskeletal tumors are an inhomogeneous group of lesions originating from mesenchymal tissues. Soft-tissue sarcomas can derive from fatty tissue (liposarcoma), muscles (leiomyosarcoma, rhabdomyosarcoma), connective tissue (fibrosarcoma), blood vessels (angiosarcoma), and neurogenic tissue (malignant peripheral nerve sheath tumor, malignant schwannoma). Bone sarcomas arise from either bony tissue (osteosarcoma) or cartilage (chondrosarcoma).



Sarcomas are relatively rare compared with colon cancers, bronchial tumors, or malignant breast lesions. The incidence of sarcoma is about one or two new cases per 100,000 individuals per year. Osteosarcomas and the Ewing's sarcoma family, which includes peripheral neuroectodermal tumors, are important childhood cancers. Adults most often present with osteosarcoma and chondrosarcoma.



The majority of musculoskeletal tumors arise in the extremities, with the lower limbs affected more frequently than the upper limbs. Men and boys are affected more often than women and girls. Younger patients generally have better outcomes, and new surgical limb salvage procedures are now delivering excellent functional results. 



Prompt diagnosis of these tumors is crucial, as prognosis and therapeutic options are much more promising at the early stages of malignancy. Diagnosis is often delayed, however, owing to a lack of specific clinical symptoms and misinterpretation of radiological findings. Several lesions may be detected incidentally on imaging studies. Typical symptoms include pain, palpable mass, and pathological fractures.



Staging is performed according to systems set out by the Musculoskeletal Tumor Society System and the American Joint Committee on Cancer.

 Criteria used for staging include tumor extent

(T-stage), presence of lymph node metastases 

(N-stage), presence of distant metastases (M-stage), and histological grading (G). Approximately 15% to 20% of patients with osteosarcoma present with pulmonary metastases at initial staging. Metastases can occasionally occur in the bone, lymph nodes, brain, or soft tissue as well.



Imaging plays a major role in the diagnostic workup, treatment, and post-therapy evaluation of patients with musculoskeletal tumors. Classification of the lesion as malignant or benign, biopsy guidance, local staging, treatment response, and follow-up are all based mainly on imaging.



Several imaging modalities have been used for the diagnosis of musculoskeletal tumors. Plain-film radiography and ultrasound are generally used first, because of their availability and low cost. X-rays will typically be requested for suspect bone lesions and ultrasound for soft-tissue lesions. If these modalities show normal or indeterminate findings, but the patient has persisting symptoms, then additional imaging studies will often be required.



Sarcoma staging was performed with CT prior to the growth of clinical MRI. CT now has a more limited role, though it remains useful when assessing cortical involvement or cortically based lesions such as osteoid osteoma, periosteal reaction, matrix mineralization, and lesions in flat bones.



MRI is now considered the reference standard for local staging of musculoskeletal tumors, due to the modality's superior anatomic resolution and its delineation of bony structures, soft tissue, vessels, and nerves. MRI can determine the intra- and extracompartmental extent of the tumor and its relationship to critical neurovascular structures. The modality is also highly sensitive to bone marrow lesions.



Three-phase bone scintigraphy may also be used to evaluate bone tumors. The rise of MRI and PET, however, means that the importance of the conventional bone scan is decreasing. Coregistered PET/CT studies have gained widespread acceptance over the past few years for general oncology applications,

 but experience in patients with musculoskeletal tumors remains limited at present.

There is no gold standard MRI protocol for imaging sarcomas. Most examinations are performed on 1.5T or 3T systems. The most commonly used sequences are T1- and T2-weighted (fast/ultrafast) spin-echo imaging, T1-weighted imaging with fat saturation, short-tau inversion recovery, and gadolinium-enhanced T1-weighted MRI. The acquisition of sagittal, axial, and coronal orientations will depend on the type and site of the tumor and physicians' preferences. Most protocols include at least one sequence covering the entire affected bone/limb with a large field-of-view for identification of skip lesions.



Commercially available MRI systems already exhibit superior image quality in terms of signal-to-noise and contrast-to-noise ratios. New sequences are constantly being evaluated. Research into new MRI techniques, such as diffusion-weighted imaging, MR elastography, and MR spectroscopy, is currently being assessed. These techniques are really in their infancy, however, in terms of clinical use.



MRI has several possible roles in the evaluation of malignant musculoskeletal tumors. The tumor's blood supply can be imaged using contrast-enhanced dynamic (perfusion) MRI. Gadolinium-enhanced MRI can also assist in the differentiation of benign and malignant lesions in certain cases, such as cystic myxoid sarcomas. Another possible indication is differentiation of high- and low-flow hemangiomas. This distinction is used to decide whether the patient should undergo embolization or surgery. Dynamic contrast-enhanced MRI can also be used to differentiate slowly enhancing lesions; for example, hematoma and hemorrhagic sarcoma, as well as cystic and aneurysmatic lesions.

MRI is an important tool for biopsy guidance, ensuring that the needle is directed into the vascularized, viable part of the tumor. This approach should avoid unrepresentative or misleading histologies. It may be best to perform MRI prior to biopsy, given that hematoma and edema caused by intervention can complicate diagnoses.

 The overlap in enhancement patterns between malignant and benign lesions, however, means that MRI cannot replace biopsy altogether for unclear musculoskeletal lesions.



Early studies showed that MRI was unable to distinguish benign musculoskeletal masses from malignant lesions in many cases. An accuracy of 55% was reported, with the presence of malignant lesions overestimated 

 Other investigators have examined this same question separately for soft-tissue masses and bone tumors. MRI has been reported to have a sensitivity of 66% and a specificity of 58% when differentiating benign soft-tissue masses from malignant tumors. These results suggest that MRI has limited clinical value for definitive diagnoses. A slightly different picture can be found when considering malignant bone tumors"here, sensitivity rises to 86% and specificity to 67%.

Some researchers now suggest that MRI should be used to estimate the tumor's biological activity rather than its status as benign or malignant. This could be achieved using contrast-enhanced or perfusion MRI to evaluate typical enhancement patterns in relation to their time-activity curve.

Presurgical monitoring during neoadjuvant chemotherapy is another possible indication for MRI. This could help define the optimal time point for surgery. Dynamic contrast-enhanced and diffusion-weighted MRI promise to distinguish between therapy-induced changes and viable persistent tumor.

 Metabolic imaging with PET/CT or PET/MRI may, however, be a better tool for assessing treatment response. Although whole-body MRI is becoming more widespread, it is time-consuming and could lead to contrast protocols being compromised.



Histopathologic classification is a vital step in the management of sarcomas. Tumor grade will have a significant impact on prognosis. Sarcomas can be extremely heterogeneous, and biopsies should be directed toward the most aggressive part of the lesion. PET/CT can identify the most metabolically active tumor part (Figure 1).



Fluorine-18 FDG uptake, measured semiquantitatively as the maximum standardized uptake value, has been shown to correlate with histopathologic grading in sarcomas.

 This approach has certain limitations, however, due to overlap of FDG uptake in benign and malignant soft-tissue and bone sarcomas.

 Although FDG uptake of sarcomas is typically higher than that of benign lesions, some nonmalignant tumors can be avidly FDG-active, leading to misinterpretations. Examples include fibrous dysplasia, chondroblastoma, and inflammatory lesions such as Brodie abscess.

MRI is clearly superior to PET alone for viewing the anatomic details of tumor extent. Adding CT to PET helps overcome this weakness, particularly with reference to the bony anatomy. PET/CT studies can also reveal periosteal reactions, cortical destruction, calcifications, and other important details. The staging accuracy of PET/CT has been shown to be significantly higher than PET alone in bone and soft-tissue sarcoma.

PET/CT is increasingly being used to monitor treatment response in a variety of cancers, including lymphoma, gastrointestinal stromal tumors, and lung cancer. Evaluation of therapy response is important for sarcomas as well. The percentage of tumor necrosis found in histology after chemotherapy has been shown to be a powerful predictor of outcome in sarcoma patients.

 Although MRI is often used for this indication, it is limited in its ability to differentiate between viable and nonviable tumor parts. FDG uptake offers a much better reflection of the number of viable tumor cells (Figure 2).

Another important advantage of a combined PET/CT protocol is the possibility of obtaining high-resolution CT images of the lung. Lung metastases occur in a significant number of sarcoma patients. Their detection may alter the prognosis significantly. Small lung metastases may not be seen on FDG-PET because of their small size and respiratory motion. This is especially true for metastases in the basal parts of the lungs. PET/CT protocols in sarcoma patients should consequently include a diagnostic lung CT examination.

Integrated whole-body PET/MR scanners are not yet available commercially, and their clinical value remains subject to speculation. PET/

MR studies are currently derived from software-based fusion of PET and MR images obtained on separate scanners.

 We have found this process to be difficult and time-consuming. Identical patient positioning is crucial to obtain a perfect match, but variance in scanner geometries and examination protocols make this tricky to achieve in practice. More studies are needed to evaluate the possible value of integrated PET/MR scanners in sarcoma patients. These investigations should be based on prospective coregistration of images, not retrospective fusion.



Adequate modality selection is crucial for the successful diagnosis and treatment of malignant musculoskeletal tumors. MRI is the most important "second-step" imaging tool if x-ray or ultrasound findings are suspicious 

biopsy. CT and bone scintigraphy may be helpful in selected cases.



The role of PET/CT in malignant musculoskeletal tumors is not yet clearly defined. This modality can certainly provide important information for biopsy guidance, tumor staging, and therapy response.



Coregistered PET/MR may be able to combine the benefits of MR with those of PET/CT, though this needs further evaluation. Integrated PET/MR systems promise to reduce the time required for scanning and image fusion and thus reduce patients' radiation burden. No imaging modality can yet replace the need for biopsy in ambiguous cases. 



1. Greene FL, Page DL, Fleming ID, et al. AJCC Cancer staging manual, 6th ed. New York: Springer-Verlag, 2002.



2. Antoch G, Saoudi N, Kuehl H, et al. Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT) for tumor staging in solid tumors: comparison with CT and PET. J Clin Oncol 2004;22(21):4357-4368.



3. Tateishi U, Yamaguchi U, Seki K, et al. Bone and soft-tissue sarcoma: preoperative staging with fluorine 18 fluorodeoxyglucose PET/CT and conventional imaging. Radiology 2007;245(3):839-847.



4. Verstraete KL, Van der Woude HJ, Hogendoorn PC, et al. Dynamic contrast-enhanced MR imaging of musculoskeletal tumors: basic principles and clinical applications. J Magn Reson Imaging 1996;6(2):311-321.



5. Verstraete KL, Lang P. Bone and soft tissue tumors: the role of contrast agents for MR imaging. Eur J Radiol 2000;34(3):229-246.



6. Ma LD, Frassica FJ, Scott WW, Jr., et al. Differentiation of benign and malignant musculoskeletal tumors: potential pitfalls with MR imaging. Radiographics 1995;15(2):349-366.



7. Barile A, Regis G, Masi R, et al. Musculoskeletal tumours: preliminary experience with perfusion MRI. Radiol Med (Torino) 2007;112(4):550-561.



8. Dyke JP, Panicek DM, Healey JH, et al. Osteogenic and Ewing sarcomas: estimation of necrotic fraction during induction chemotherapy with dynamic contrast-enhanced MR imaging. Radiology 2003;228(1):271-278.



9. Lang P, Wendland MF, Saeed M, et al. Osteogenic sarcoma: noninvasive in vivo assessment of tumor necrosis with diffusion-weighted MR imaging. Radiology 1998;206(1): 227-235.



10. Folpe AL, Lyles RH, Sprouse JT, et al. (F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma. Clin Cancer Res 2000;6(4):1279-1287.



Articles

Primary malignant musculoskeletal tumors are an inhomogeneous group of lesions originating from mesenchymal tissues. Soft-tissue sarcomas can derive from fatty tissue (liposarcoma), muscles (leiomyosarcoma, rhabdomyosarcoma), connective tissue (fibrosarcoma), blood vessels (angiosarcoma), and neurogenic tissue (malignant peripheral nerve sheath tumor, malignant schwannoma).

Imaging helps in diagnosis of musculoskeletal masses

Primary malignant musculoskeletal tumors are an inhomogeneous group of lesions originating from mesenchymal tissues.

Soft-tissue sarcomas can derive from fatty tissue (liposarcoma), muscles (leiomyosarcoma, rhabdomyosarcoma), connective tissue (fibrosarcoma), blood vessels (angiosarcoma), and neurogenic tissue (malignant peripheral nerve sheath tumor, malignant schwannoma). Bone sarcomas arise from either bony tissue (osteosarcoma) or cartilage (chondrosarcoma).

Sarcomas are relatively rare compared with colon cancers, bronchial tumors, or malignant breast lesions. The incidence of sarcoma is about one or two new cases per 100,000 individuals per year. Osteosarcomas and the Ewing's sarcoma family, which includes peripheral neuroectodermal tumors, are important childhood cancers. Adults most often present with osteosarcoma and chondrosarcoma.

The majority of musculoskeletal tumors arise in the extremities, with the lower limbs affected more frequently than the upper limbs. Men and boys are affected more often than women and girls. Younger patients generally have better outcomes, and new surgical limb salvage procedures are now delivering excellent functional results.

Prompt diagnosis of these tumors is crucial, as prognosis and therapeutic options are much more promising at the early stages of malignancy. Diagnosis is often delayed, however, owing to a lack of specific clinical symptoms and misinterpretation of radiological findings. Several lesions may be detected incidentally on imaging studies. Typical symptoms include pain, palpable mass, and pathological fractures.

 Criteria used for staging include tumor extent (T-stage), presence of lymph node metastases (N-stage), presence of distant metastases (M-stage), and histological grading (G). Approximately 15% to 20% of patients with osteosarcoma present with pulmonary metastases at initial staging. Metastases can occasionally occur in the bone, lymph nodes, brain, or soft tissue as well.

Imaging plays a major role in the diagnostic workup, treatment, and post-therapy evaluation of patients with musculoskeletal tumors. Classification of the lesion as malignant or benign, biopsy guidance, local staging, treatment response, and follow-up are all based mainly on imaging.

Several imaging modalities have been used for the diagnosis of musculoskeletal tumors. Plain-film radiography and ultrasound are generally used first, because of their availability and low cost. X-rays will typically be requested for suspect bone lesions and ultrasound for soft-tissue lesions. If these modalities show normal or indeterminate findings, but the patient has persisting symptoms, then additional imaging studies will often be required.

Sarcoma staging was performed with CT prior to the growth of clinical MRI. CT now has a more limited role, though it remains useful when assessing cortical involvement or cortically based lesions such as osteoid osteoma, periosteal reaction, matrix mineralization, and lesions in flat bones.

MRI is now considered the reference standard for local staging of musculoskeletal tumors, due to the modality's superior anatomic resolution and its delineation of bony structures, soft tissue, vessels, and nerves. MRI can determine the intra- and extracompartmental extent of the tumor and its relationship to critical neurovascular structures. The modality is also highly sensitive to bone marrow lesions.

There is no gold standard MRI protocol for imaging sarcomas. The majority of examinations are performed on 1.5T or 3T systems. The most commonly used sequences are T1- and T2-weighted (fast/ultrafast) spin-echo imaging, T1-weighted imaging with fat saturation, short-tau inversion recovery, and gadolinium-enhanced T1-weighted MRI. The acquisition of sagittal, axial, and coronal orientations will depend on the type and site of the tumor and physicians' preferences. Most MRI protocols include at least one sequence covering the entire affected bone/limb with a large field-of-view for identification of skip lesions.

Commercially available MRI systems already exhibit superior image quality in terms of signal-to-noise ratio and contrast-to-noise ratio. Further¬more, a large variety of new sequences are constantly being evaluated. Research into new MRI techniques, such as diffusion-weighted imaging, MR elastography, and MR spectroscopy, is currently being assessed. These techniques are really in their infancy, however, in terms of clinical use.

 The overlap in enhancement patterns between malignant and benign lesions, however, means that MRI cannot replace biopsy altogether for unclear musculoskeletal lesions.

Early studies showed that MRI was unable to distinguish benign musculoskeletal masses from malignant lesions in many cases. An accuracy of 55% was reported, with the presence of malignant lesions overestimated  by 39%.

 Other investigators have examined this same question separately for soft-tissue masses and bone tumors. MRI has been reported to have a sensitivity of 66% and a specificity of 58% when differentiating benign soft-tissue masses from malignant tumors. These results suggest that MRI has limited clinical value for definitive diagnoses. A slightly different picture can be found when considering malignant bone tumors-here, the sensitivity rises to 86% and the specificity to 67%.

 Some researchers now suggest that MRI should be used to estimate the tumor's biological activity rather than its status as benign or malignant. This could be achieved using contrast-enhanced or perfusion MRI to evaluate typical enhancement patterns in relation to their time-activity curve.

 Presurgical monitoring during neoadjuvant chemotherapy is another possible indication for MRI. This could help define the optimal time point for surgery. Dynamic contrast-enhanced and diffusion-weighted MRI promise to distinguish between therapy-induced changes and viable persistent tumor.

 Metabolic imaging with PET/ CT or PET/MRI may, however, be a better tool for assessing treatment response. Although whole-body MRI is becoming more widespread, it is time-consuming and could lead to contrast protocols being compromised.

Histopathologic classification is a vital step in the management of sarcomas. Tumor grade will have a significant impact on prognosis. Sarcomas can be extremely heterogeneous, and biopsies should be directed toward the most aggressive part of the lesion. PET/CT can identify the most metabolically active tumor part (Figure 1).

MRI is clearly superior to PET alone for viewing the anatomic details of tumor extent. Adding CT to PET helps overcome this weakness, particularly with reference to the bony anatomy. PET/CT studies can also reveal periosteal reactions, cortical destruction, calcifications, and other important details. The staging accuracy of combined PET/CT has been shown to be significantly higher than PET alone in bone and soft-tissue sarcoma.

Integrated whole-body PET/MR scanners are not yet available commercially, and their clinical value remains subject to speculation. PET/MR studies are currently derived from software-based fusion of PET and MR images obtained on separate scanners.

 We have found this process to be difficult and time-consuming. Identical patient positioning is crucial to obtain a perfect match, but variance in scanner geometries and examination protocols make this tricky to achieve in practice. More studies are needed to evaluate the possible value of integrated PET/MR scanners in sarcoma patients. These investigations should be based on prospective coregistration of images, not retrospective fusion.

Adequate modality selection is crucial for the successful diagnosis and treatment of malignant musculoskeletal tumors. MRI is the most important "second-step" imaging tool if x-ray or ultrasound findings are suspicious for a bone or soft-tissue tumor. MRI can help assess a lesion's malignancy, reveal its extension, and guide the required biopsy. CT and bone scintigraphy may be helpful in selected cases.

The role of PET/CT in malignant musculoskeletal tumors is not yet clearly defined. This modality can certainly provide important information for biopsy guidance, tumor staging, and therapy response.

Coregistered PET/MR images may be able to combine the benefits of MRI with those of PET/CT, though this needs further evaluation. Integrated PET/MRI systems promise to reduce the time required for scanning and image fusion and thus reduce patients' radiation burden. No imaging modality can yet replace the need for biopsy in ambiguous cases.

DR. STROBEL is a dual-board-certified radiologist and nuclear medicine physician, and DR. HANY is a dual-board-certified radiologist and nuclear medicine physician, at the University Hospital Zurich, in Switzerland. Both are consultants in nuclear medicine. DR. VEIT-HAIBACH is a resident in the department of nuclear medicine at the same institution.

1. Greene FL, Page DL, Fleming ID, et al. AJCC Cancer staging manual, 6th ed. New York: Springer-Verlag, 2002.
 2. Antoch G, Saoudi N, Kuehl H, et al. Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT) for tumor staging in solid tumors: comparison with CT and PET. J Clin Oncol 2004;22(21):4357-4368.
 3. Tateishi U, Yamaguchi U, Seki K, et al. Bone and soft-tissue sarcoma: preoperative staging with fluorine 18 fluorodeoxyglucose PET/CT and conventional imaging. Radiology 2007;245(3):839-847.
 4. Verstraete KL, Van der Woude HJ, Hogendoorn PC, et al. Dynamic contrast-enhanced MR imaging of musculoskeletal tu¬mors: basic principles and clinical applications. J Magn Reson Imaging 1996;6(2):311-321.
 5. Verstraete KL, Lang P. Bone and soft tissue tumors: the role of contrast agents for MR imaging. Eur J Radiol 2000;34(3):229-246.
 6. Ma LD, Frassica FJ, Scott WW, Jr., et al. Differentiation of benign and malignant musculoskeletal tumors: potential pitfalls with MR imaging. Radiographics 1995;15(2):349-366.
 7. Barile A, Regis G, Masi R, et al. Musculoskeletal tumours: preliminary experience with perfusion MRI. Radiol Med (Torino) 2007;112(4):550-561.
 8. Dyke JP, Panicek DM, Healey JH, et al. Osteogenic and Ewing sarcomas: estimation of necrotic fraction during induction chemotherapy with dynamic contrast-enhanced MR imaging. Radiology 2003;228(1):271-278.
 9. Lang P, Wendland MF, Saeed M, et al. Osteogenic sarcoma: noninvasive in vivo assessment of tumor necrosis with diffusion-weighted MR imaging. Radiology 1998;206(1):227-235.
 10. Folpe AL, Lyles RH, Sprouse JT, et al. (F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma. Clin Cancer Res 2000;6(4):1279-1287.
 11. Aoki J, Watanabe H, Shinozaki T, et al. FDG PET of primary benign and malignant bone tumors: standardized uptake value in 52 lesions. Radiology 2001;219(3):774-777.
 12. Aoki J, Watanabe H, Shinozaki T, et al. FDG-PET for preoperative differential diagnosis between benign and malignant soft tissue masses. Skeletal Radiol 2003;32(3):133-138.
 13. Strobel K, Bode B, Lardinois D, Exner U. PET-positive fibrous dysplasia-a potentially misleading incidental finding in a patient with intimal sarcoma of the pulmonary artery. Skeletal Radiol 2007;36(Suppl 1):S24-S28.
 14. Strobel K, Hany TF, Exner GU. PET/CT of a Brodie abscess. Clin Nucl Med 2006;31(4):210.
 15. Raymond AK, Chawla SP, Carrasco CH, et al. Osteosarcoma chemotherapy effect: a prognostic factor. Semin Diagn Pathol 1987;4(3):212-236.
 16. Schulte M, Brecht-Krauss D, Werner M, et al. Evaluation of neoadjuvant therapy response of osteogenic sarcoma using FDG PET. J Nucl Med 1999;40(10):1637-1643.
 17. Shapeero LG, Vanel D. Imaging evaluation of the response of high-grade osteosarcoma and Ewing sarcoma to chemotherapy with emphasis on dynamic contrast-enhanced magnetic resonance imaging. Semin Musculoskelet Radiol 2000;4(1):137-146.
 18. Daldrup-Link HE, Franzius C, Link TM, et al. Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET. AJR 2001;177(1):229-236.
 19. Somer EJ, Benatar NA, O'Doherty MJ, et al. Use of the CT component of PET-CT to improve PET-MR registration: demonstration in soft-tissue sarcoma. Phys Med Biol 2007;52(23):6991-7006.
 20. Somer EJ, Marsden PK, Benatar NA, et al. PET-MR image fusion in soft tissue sarcoma: accuracy, reliability and practicality of interactive point-based and automated mutual information techniques. Europ J Nucl Med Mol Imaging 2003;30(1):54-62.

Imaging aids diagnosis of musculoskeletal masses

Integrated PET/CT scanners entered clinical practice in 2001. Their quasisimultaneous acquisition of complementary anatomic and functional information has revolutionized diagnosis and treatment monitoring for many oncological diseases.

PET/CT has the advantage of acquiring whole-body examinations in a single step. This enables referring oncology physicians to plan therapy according to the imaging and complementary laboratory results. Defining the extent of disease according to existing guidelines is not easy, however. These guidelines are generally based on experiences with stand-alone CT and PET systems and long follow-up studies. Questions then arise: Do we need combined PET/CT response criteria, and for which cancers might these be useful?

CT-based evaluations of therapy use changes to tumor size and/or characteristic contrast enhancement patterns to indicate changes to underlying morphology. Either Response Evaluation Criteria for Solid Tumors (RECIST)1 or World Health Organization criteria for solid tumors can be used to define therapy response. These criteria have also been adapted for other solid tumors, such as pleural mesothelioma.2

RECIST has become the most widely used response tool in routine clinical applications, following evidence that unidimensional and bidimensional criteria show no relevant differences in response evaluation or prognostic impact.3 Contrast-enhancement patterns can also play an important role in monitoring treatment response. Central necrosis of lesions and cystic degeneration are widely accepted parameters, and they were used routinely prior to PET/CT imaging.

PET uses radioisotope tracers to depict metabolic changes indicative of malignancy. Fluorine-18 FDG is used most widely for general oncological tasks. A high proportion of experience in diagnosis and therapy response with PET is based on F-18 FDG. Other PET tracers under investigation include carbon-11 methionine, F-18 tyrosine, and F-18 DOPA.

Measurements of functional information generally include a standardized uptake value (SUVmax). This measurement is regarded as the gold standard. Alternative methods, such as total lesion glycolysis or tumor volume defined by PET measurements, are currently the subject of trials. Therapy monitoring with FDG-PET is generally based on consensus criteria from the European Organisation for Research and Treatment of Cancer (EORTC).4 The criteria have not been revised since their introduction in 1999, though they have been adapted for several tumor entities. Combined PET/CT response criteria are likely needed to assess tumor regression properly.

Combined PET/CT evaluation has already been shown to have a huge impact on the diagnosis of several cancers and is expected to expand to other applications.

Lymphoma. The imaging subcommittee of the International Harmonization Project in lymphoma has produced a new guideline on PET and PET/CT response criteria for Hodgkin's disease and aggressive non-Hodgkin's lymphoma.5 The "basic" EORTC parameters had previously defined progressive metabolic disease, stable metabolic disease, partial metabolic response, and complete metabolic response in terms of percentage differences between actual SUVmax and baseline SUVmax. The new criteria take CT parameters into account as well.

The guidelines state that contrast-enhanced CT may serve as an adequate alternative for therapy assessment. They recommend that either contrast-enhanced CT or PET/CT be used, at least for initial staging. The PET component of PET/CT, however, is still highlighted as the leading response tool. CT parameters are used partly to define the location of lesions and extent of involvement for certain indications, such as hepatic and splenic lesions and lymph nodes.

Some problems related to combined response evaluation are not discussed. Gross disease will shrink and glucose metabolism decrease, causing a reduction in SUV in most patients. Residual morphological tissue (up to 2-cm diameter, short axis) without metabolic activity can be found during therapy or at the end of treatment in some patients, however. This is especially the case for patients starting treatment with large lymph node masses. If PET is taken to be the main response tool, then these residual masses are not considered relevant. An assessment based on CT alone would have classified these patients as partial responders. PET/CT, on the other hand, classifies them as complete metabolic responders (Figure 1).

Data evaluating the clinical significance of these residual nonactive masses are not yet available. Prospective studies are needed to determine if these patients relapse early or tend to have a higher overall relapse rate.

Colorectal cancer. Contrast-enhanced abdominal CT is generally performed in patients with colorectal cancer. The presence and extent of liver metastases, or other distant metastases, are of particular interest. The therapeutic strategy is different in rectal cancer. Diagnosis of a T3-stage cancer and any N-stage disease will be followed by neoadjuvant radio/chemotherapy. Pelvic MRI is considered the reference standard in these patients.

PET has already been shown to be more accurate than contrast-enhanced CT in staging colorectal cancer. This is especially true for M-staging, owing to PET's superior detection of distant metastases. PET has additionally shown potential in monitoring treatment response in patients with hepatic metastases.6

PET/CT colonography has shown superior results in TNM-staging compared with CT alone.7 Combining PET and CT criteria could still be useful for the evaluation of rectal cancer after radio/chemotherapy and for the assessment of hepatic metastases. Decreases in metabolic activity and lesion size, according to EORTC and RECIST criteria, correlate in most cases. Histological evaluation of residual masses with normalized FDG uptake, however, reveals viable tumor tissue in the majority of cases (Figure 2).

Data on the relationship among FDG avidity, the size and number of lesions after neo-adjuvant chemotherapy, and patient outcome are not yet available. A combination of CT- and PET-based criteria could consequently help when planning treatment strategies for patients with colorectal cancer.

Breast cancer. CT plays no role in diagnosing primary breast cancer, though it can be used to detect distant bone and soft-tissue metastases. PET has again shown encouraging results in the detection of lymph nodes and distant metastases. PET/CT has performed better than PET alone when diagnosing metastatic and recurrent breast cancer.8

The evaluation of bone metastases during therapy is rather complicated. Osteoblastic metastases may initially be overlooked on PET in certain cases, due to an absence of FDG uptake. These same metastases will be clearly visible on CT.9,10 How should they be evaluated? Analysis of these metabolically inactive masses should seemingly be based on morphological criteria. But RECIST criteria regard bone metastases as nonmeasurable lesions, which makes post-therapy follow-up challenging.

Osteolytic metastases, on the other hand, are detected easily on CT and PET. PET can often detect these metastases earlier than CT; an uptake is visible, but no morphological change can be seen at that time. The metastases' size remains stable after therapy, but they become more sclerotic and lose their metabolic activity. How should they be handled? Some authors claim if a metastasis changes from lytic to blastic and is no longer FDG-avid, then it has been cured. But these metastases may still be viable for several indications.

There is a clear need for combined PET/CT evaluation criteria in patients whose breast cancer has metastasized, particularly if these lesions are in the bone.

Gastrointestinal stromal tumor. Several studies have been published concerning therapy response in gastrointestinal stromal tumors.11,12 Most studies found PET/CT to be more accurate at assessing therapy response than either CT alone or PET alone. PET/CT also provided relevant prognostic information. Patients with an absence of elevated glucose metabolism after initiation of treatment survived for a statistically significantly longer period than did patients with detectable glucose uptake.

The CT part of the PET/CT study was less accurate in terms of evaluating therapy response when RECIST criteria were applied, mainly because liver metastases of gastrointestinal stromal tumors do not shrink much when treated, even in long-term survivors. A significant number of patients will thus not be regarded as responders. Alternative CT-based criteria for assessing the response of gastrointestinal stromal tumors to treatment have been proposed. These advocate that a 10% reduction in tumor size or a 15% decrease in tumor density should be enough to qualify a patient as a partial responder. A figure of 25% was used in previous studies.13

PET-specific criteria and modified morphological parameters may be included in an optimized combined PET/CT response assessment for gastrointestinal stromal tumors. These findings could also lead researchers to explore other tumor entities using disease-adapted response criteria.

Ear, nose, and throat cancers. The primary methods for the detection and characterization of ear, nose, and throat cancers are CT and MRI, based on international guidelines.14 FDG-PET has already shown remarkable results for the detection of tumors and lymph nodes in ENT cancer.15,16 Diagnosis can be impaired by artifacts and inflammatory lesions, however. Detection of pathologically involved cervical lymph nodes on CT is based on typical contrast enhancement patterns as well as size criteria.17 FDG-PET defines tumor response as a decrease in FDG uptake of more than 25%. Any remaining pathological focal glucose metabolism is taken to indicate tumor persistence.

Interpretation of CT is often complex. Lesions may decrease in size, but contrast enhancement may still be present owing to the widening of extracellular space in radiotherapy scar tissue.

Small lesions that have shrunk can easily be overlooked on morphological imaging alone. The use of multislice CT technology, particularly 64-slice CT, means that functional perfusion studies can be integrated into a clinical routine protocol. CT perfusion can be useful in detecting and determining therapy response in several tumor entities.18,19

Evaluations of therapy response on PET/CT are likely to rely more on PET in cases in which the interpretation of CT findings are difficult or PET and CT findings are not concordant. Because most advanced ENT cancers are treated with radio/chemotherapy, the time at which post-therapy FDG-PET/CT is performed is important. We find that four to six weeks after completion of treatment is sufficient.

Mesothelioma. CT-based modified RECIST criteria and PET evaluation with EORTC-based criteria have each been found to be valuable in assessing the response of pleural mesothelioma to treatment.2,20 Data comparing modified RECIST and EORTC criteria in the same patient, and their possible correlation to clinical outcome, are not yet available.

Decreasing FDG uptake during therapy may be taken as a sign of response. Concurrent CT measurements, however, may not change enough to be considered significant (Figure 3).

CT criteria may need some fine-tuning to classify patients' response appropriately, as in the case of gastrointestinal stromal tumors. Reliable definition of combined PET/CT response criteria, through further studies, will help to ensure correct stratification of patients into the appropriate response classes and ensure that therapy can be cost-effective and enhance patients' quality of life.

As more and more PET/CT systems are being installed worldwide, clinical experience of combined modality cancer imaging is growing exponentially. We may expect future studies to examine the role of PET/CT in following up cancers additional to the ones mentioned above.

Novel approaches in quantifying therapy response that go beyond standard RECIST or EORTC criteria are needed, as seen in the cases of lymphoma, gastrointestinal stromal tumors, and mesothelioma. These will have to be evaluated for dual-modality imaging. Visualization tools that can display and analyze baseline and follow-up studies simultaneously, together with new techniques for evaluating response (e.g., CT perfusion) may follow. These may be incorporated in future therapy response protocols too.

DR. VEIT-HAIBACH, DR. STROBEL, and DR. HANY are radiologists and nuclear medicine physicians in the department of medical radiology, division of nuclear medicine, at Zurich University Hospital.

Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92(3):205-216.

Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol 2004;15(2):257-260.

Park JO, Lee SI, Song SY, et al. Measuring response in solid tumors: comparison of RECIST and WHO response criteria. Jpn J Clin Oncol 2003;33(10):533-537.

Young H, Baum R, Cremerius U, et al. Measurement of clinical and subclinical tumor response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Europ J Cancer 1999;35(13):1773-1782.

Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 2007;25(5):571-578.

Findlay M, Young H, Cunningham D, et al. Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil. J Clin Oncol 1996;14(3):700-708.

Veit-Haibach P, Kuehle CA, Beyer T, et al. Diagnostic accuracy of colorectal cancer staging with whole-body PET/CT colonography. JAMA 2006;296(21) 2590-2600.

Fueger BJ, Weber WA, Quon A, et al. Performance of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography and integrated PET/CT in restaged breast cancer patients. Mol Imaging Biol 2005;7(5):369-376.

Nakai T, Okuyama C, Kubota T, et al. Pitfalls of FDG-PET for the diagnosis of osteoblastic bone metastases in patients with breast cancer. Europ J Nucl Med Mol Imaging 2005;32(11):1253-1258.

Fogelman I, Cook G, Israel O, Van der Wall H. Positron emission tomography and bone metastases. Semin Nucl Med 2005;35(2):135-142.

Goerres GW, Stupp R, Barghouth G, et al. The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumors: long-term outcome of treatment with imatinib mesylate. Europ J Nucl Med Mol Imaging 2005;32(2):153-162.

Antoch G, Kanja J, Bauer S, et al. Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med 2004;45(3):357-365.

Choi H, Charnsangavej C, Faria SC, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 2007;25(13):1753-1759.

NCCN. www.nccn.org. In: National Comprehensive Cancer Network.(www.nccn.org/professionals/physician_gls/f_guidelines.asp?button=I+Agree)

Wong WL CE, McGurk M, Hussain K, et al. A prospective study of PET-FDG imaging for the assessment of head and neck squamous cell carcinoma. Clin Otolaryngol Allied Sci 1997;22(3):209-214.

Pauleit D, Zimmermann A, Stoffels G, et al. 18F-FET PET Compared with 18F-FDG PET and CT in patients with head and neck cancer. J Nucl Med 2006;47(2):256-261.

AJCC. AJCC Cancer Staging Manual, 6th ed. Stuttgart, Heidelberg, New York: Springer, 2002: chapters 3-5.

Gandhi D, Chepeha DB, Miller T, et al. Correlation between initial and early follow-up CT perfusion parameters with endoscopic tumor response in patients with advanced squamous cell carcinomas of the oropharynx treated with organ-preservation therapy. AJNR 2006;27(1):101-106.

Goh V, Halligan S, Taylor SA, et al. Differentiation between diverticulitis and colorectal cancer: quantitative CT perfusion measurements versus morphologic criteria-initial experience. Radiology 2007;242(2):456-462.

Ceresoli GL, Chiti A, Zucali PA, et al. Early response evaluation in malignant pleural mesothelioma by positron emission tomography with [18F]fluorodeoxyglucose. J Clin Oncol 2006;24(28):4587-4593.

New criteria refine PET/CT post-treatment follow-up

Combined PET/CT was the first integrated dual-modality solution to reach clinical practice.1 Clinical PET/CT scanners have now been operating for almost a decade. Their quasisimultaneous acquisition of complementary anatomic and functional information has revolutionized oncology diagnosis and therapy assessment.2

PET/CT also makes use of available CT transmission data to correct absorption of emitted annihilation photons during the PET emission scan.3 Such CT-based attenuation correction obviates the need for lengthy transmission scans that previously accounted for 40% of the total PET examination time.

Whole-body oncology examinations with PET/CT, covering a coaxial imaging range of about 100 cm from midear to upper thigh, now take less than 30 minutes. These short scan times are possible on any state-of-the-art PET/CT equipment. So it seems logical to increase patient throughput, assuming that the examination is reimbursable. But as with high-powered cars, driving "fast and furious" is not always-even ever-the best way to arrive at your destination.

Incorporation of two complementary examinations-PET and CT-into one helps overcome the methodological shortcomings of both tomographic imaging modalities. PET/CT scanners can thus be regarded as a technical evolution. PET/CT acquisition protocols are not that different from those for stand-alone PET, which should make the adoption of PET/CT imaging straightforward, at least in nuclear medicine.

In practice, however, operating a PET/CT scanner to the highest diagnostic standards is not that easy (Figure 1), unless you have friends in radiology or make them quickly. Such friendship can help nuclear medicine physicians overcome the methodological hardship of routine PET/CT imaging. Lessons that must be learned about respiratory motion artifacts, for example, were held up as a major reason not to pursue combined imaging in the early days of PET/CT. Practitioners now have the know-how to minimize problems with these artifacts (Figure 2).

Patient positioning also plays a pivotal role in reducing beam-hardening and truncation artifacts from CT. These are particularly apparent when imaging large patients whose arms are inside the field-of-view. PET/CT users have learned that CT-based attenuation correction is also prone to amplification of high-density artifacts from focal accumulation of IV contrast,4 positive oral contrast,5 or metal implants.6

All of these pitfalls can diminish image quality, possibly leading to false diagnostic interpretation and making it hard to sell the power of combined imaging to referring physicians. Several groups that have investigated the challenges of CT-based attenuation correction have proposed modified acquisition schemes. These include breath-hold protocols and the use of extended FOV reconstructions to reduce CT truncation. Their use should improve the accuracy of the attenuation-corrected PET data.7

Nevertheless, a judicious choice of PET/CT referrals and imaging protocols is still required.8 This includes mandatory contrast-enhanced CT in previously undiagnosed patients and in selected patients during follow-up. New protocols for administration of CT contrast have been proposed to optimize enhancement and provide sufficient bowel distention, without excessively increasing photon attenuation.9-10 Metal implants, unfortunately, still give rise to significant artifacts that can be corrected only retrospectively.11

These pitfalls necessitate careful selection, and possible modification, of a standard whole-body PET/CT acquisition protocol. Modifying scan parameters12 and considering external advice related to patient preparation and positioning, as for PET(/CT)-guided radiation therapy planning, may be required. The following are some approaches to disease-specific imaging on PET/CT:

Head and neck imaging. A typical whole-body PET/CT examination involves craniocaudal CT followed by a multibed PET scan in the same direction. Total scan time will be around 30 minutes. It is highly likely that the patient's neck muscles will relax during this period, leading to spatial misalignment of the PET and CT images. Inadequate patient restraint may lead to particularly large misalignment effects that can invalidate the results of image fusion.

Rigid positioning aids, such as vacuum bean bags, can reduce the average head/neck motion in whole-body PET/CT examinations.13 A split protocol should also be adopted for patients in whom a head/neck malignancy is indicated. This comprises a thorax/abdomen scan (arms raised above the head) followed by head/neck scanning of the contiguous imaging range with a slight axial overlap and modified scan parameters such as narrower CT collimation, increased emission scan times, and finer image reconstruction into larger matrices.12 CT contrast volume can be split between the torso and neck scans.

Thoracic imaging. Imaging the thorax of cancer patients is a crucial step in whole-body oncology staging and follow-up. The diagnostic accuracy of PET is known to be inferior to dedicated CT for the detection of small lung lesions. Standard whole-body PET/CT examinations consist of a scout scan followed by a single spiral CT scan, then a multibed emission scan covering the same coaxial range. Reasonable coregistration accuracy, in the absence of respiratory gating options, typically involves acquiring the spiral CT scan during normal expiration or shallow breathing.

Respiration-induced artifacts from earlier PET/CT systems incorporating a single- or dual-row spiral CT scanner, for example, were reduced by following a limited breath-hold protocol.14 This required patients to hold their breath in normal expiration while CT covered the lower thorax and upper abdomen. The use of faster multislice CT systems means that the CT and PET portions can be acquired during shallow breathing. This has been shown to yield satisfactory coregistration accuracy in the region of maximum respiratory mobility-the diaphragm.15

Acquisition of CT data with or without breath-hold instructions during a standard whole-body PET/CT scan still generates blurred CT images that are of inferior radiological quality when compared with dedicated thoracic CT images.16 This problem prompted radiologists at the University of California, Los Angeles to try a new approach, in which they acquired a second ultralow-dose thoracic CT scan in full inspiration.17 The method detected previously unknown micrometastatic lung disease in 13% of patients who had already undergone standard PET/CT. The effective dose from the additional thoracic CT can be limited to 1 mSv if novel dose reduction schemes and efficient CT detector technology are used. This amount adds relatively little to the effective dose of 20 to 24 mSv for a standard diagnostic whole-body PET/CT examination.18

PET/CT colonography. Colorectal cancer constitutes a significant portion of cancer-induced deaths in the industrialized world. Abdominal CT and MRI, and FDG-PET in selected cases, are used together with optical colonoscopy for colorectal cancer staging.19 Clinical experience, however, has shown that nonspecific PET/CT can produce inconclusive findings. Side-by-side viewing of independent CT and PET images may deliver the same diagnostic accuracy but prolong time to diagnosis and treatment.

A PET/CT protocol specific to colorectal cancer has now been suggested.20 Patient preparation includes bowel cleansing and pharmacological relaxation. The acquisition protocol is labeled whole body but actually split into a torso and an abdomen scan. Both are slightly overlapping, and the patient is scanned in supine and prone position for the torso and abdomen, respectively. The colon is distended with lukewarm water prior to the abdominal scan. Contrast-enhanced CT data are acquired for both scans.

We have found that using this protocol can limit overall patient turnaround time to 37 minutes, only slightly longer than for a conventional whole-body PET/CT scan. Initial staging with PET/CT colonography has indicated a high diagnostic accuracy for the combined imaging protocol with respect to TNM staging and its effect on therapy management (Figure 3).

This optimized PET/CT protocol can be recommended in patients with incomplete colonoscopy or those who refuse colonoscopy altogether. PET/CT colonography could become the method of choice for restaging patients with a suspected recurrence at the anastomotic site, given that optical colonoscopy is impaired by its strict endoluminal view. PET/CT colonography will provide referring physicians with an integrated report specific to the local disease that also includes an assessment of metastatic disease. Whole-body PET/CT colonography consequently offers a complete diagnostic workup for colorectal cancer patients prior to decisions on therapy management.

Special imaging protocols. Supine patient positioning is adequate for whole-body imaging in general, but the breast is often compressed when patients are imaged supine, making it difficult to differentiate lesions in the thoracic wall and breast (Figure 4A). Several groups have suggested acquiring an independent PET scan in prone position, with the breast hanging and the arms at the side or raised above the head. Coregistration of functional PET information with breast MRI is complicated, however, by differences in breast shape, based on different patient positioning on the resulting images.

Dedicated PET/CT examinations benefit from the use of additional positioning devices to hold the patient in a particular position and restrict the patient or a specific body region from moving during acquisition. One solution would be to acquire an independent PET scan with patients lying prone, arms at their sides or raised above their head. The coaxial scan could be split into separate scan ranges, as with the head/neck protocol. Alternatively, a dedicated scan range would allow for disease-specific patient positioning (Figure 4B) and scan parameters, though patient turnaround would then be limited by the time required to set up and initiate the independent scan. Further innovation by hardware providers is clearly required to enable timely and efficient modification of PET/CT scan protocols.

Special patient positioning is often necessary when incorporating PET and PET/CT into radiotherapy planning and follow-up. A flat tabletop is mounted on the PET/CT patient pallet, and additional positioning aids such as breast boards or an abdominal cast can then be fixed to this tabletop. PET/CT acquisitions for radiation therapy planning do not usually exceed three or four bed positions.

Gating mechanisms are now being adopted in lung cancer patients to freeze the tumor and surrounding lung.21 The resulting volume-tric anatomic-metabolic information should correspond to the morphology of the patient during gated treatment delivery.

Therapy assessment. PET and CT are both valuable tools for assessing the response of various cancers to therapy. In CT-based evaluations, changes to tumor size or to enhancement patterns are used to indicate any change to underlying morphology.22 PET, on the other hand, uses a radioisotope tracer, usually FDG, to depict metabolic changes.23 Functional information may include a standardized uptake value or total lesion glycolysis.24

The use of PET/CT to monitor therapy response is still not widespread, eight years after the first combined unit was installed in a radiology department. This is due mainly to a lack of finalized consensus guidelines on combined imaging,25 fear of overexposing patients to ionizing radiation from CT, and dearth of prospective studies using patient survival data as the benchmark for therapy response.

More and more PET/CT systems are being installed worldwide, and clinical experience in their use is growing exponentially. We may expect future studies to examine the use of PET/CT in extended follow-up as well as relatively short-term diagnosis and staging of cancer. These studies may mandate novel approaches to quantifying therapy response that go beyond criteria set out by the World Health Organization and the European Organization for Research and Treatment of Cancer.26 Visualization tools that can handle simultaneous display and analysis of baseline and follow-up studies may be performed.27

Clinical adoption and integration of a new imaging technology such as PET/CT is clearly more efficient if imaging experts-nuclear medicine physicians, radiologists, technologists, and physicists-cooperate during the preparation, installation, and operation of the combined system. The ultimate aim is to provide patients with the best diagnosis possible. This process should begin with the adaptation of imaging protocols to suit patients' needs. It should extend to providing referring physicians with a timely single integrated report, detailing anatomic and functional findings together. PET/CT will become a modality of choice only if it is used knowledgeably and reliably by healthcare professionals.

The authors would like to thank Sonja Kinner for preparing parts of the images.

Dr. Beyer is an affiliated research associate in nuclear medicine at the University Hospital Essen in Germany and head of medical operations at Timaq Medical Imaging in Zurich, Switzerland. Dr. Veit-Haibach is a radiologist in the department of diagnostic and interventional radiology and neuroradiology at the University Hospital Essen. Since July 2006, he has worked in the nuclear medicine department at the University Hospital Zurich.

Beyer T, Townsend DW, Brun T, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med 2000;41(8):1369-1379.

Czernin J, Schelbert H. PET/CT imaging: facts, opinions, hopes, and questions. J Nucl Med 2004;45(Suppl 1):1S-3S.

Kinahan P, Hasegawa B, Beyer T. X-ray based attenuation correction for positron emission tomography/computed tomography scanners. Semin Nucl Med 2003;33(3):166-179.

Antoch G, Freudenberg LS, Egelhof T, et al. Focal tracer uptake: A potential artifact in contrast-enhanced dual-modality PET/CT scans. J Nucl Med 2002;43(10):1339-1342.

Dizendorf E, Hany TF, Buck A, et al. Cause and magnitude of the error induced by oral CT contrast agent in CT-based attenuation correction of PET emission studies. J Nucl Med 2003;44(5):732-738.

Goerres G, Schmid D, Eyrich G. Do hardware artefacts influence the performance of head and neck PET scans in patients with oral cavity squamous cell cancer? Dentomaxillofac Radiol 2003;32(6):365-371.

Beyer T, Bockisch A, Kuhl H, Martinez M-J. Whole-body 18F-FDG PET/CT in the presence of truncation artifacts. J Nucl Med 2006;47(1):91-99.

Bockisch A, Beyer T, Antoch G, et al. Positron emission tomography/computed tomography-imaging protocols, artifacts, and pitfalls. Mol Imaging Biol 2004;6(4):188-199.

Brechtel K, Klein M, Vogel M, et al. Optimized contrast enhanced CT protocols for diagnostic whole-body 18F-FDG PET/CT: single-phase versus multi-phase CT imaging. J Nucl Med 2006 Mar;47(3):470-476.

Antoch G, Kuehl H, Kanja J, et al. Dual-modality PET/CT imaging with a negative oral contrast agent to avoid contrast-induced artefacts: introduction and evaluation. Radiology 2004;230(3):879-885.

Beyer T, Raupach R, Jentzen W, et al. Metal artifacts in combined PET/CT imaging: evaluation and correction. Abstract submitted to EANM 2005 meeting.

Beyer T, Antoch G, Freudenberg LS, et al. Acquisition protocol considerations for combined FDG-PET/CT imaging. J Nucl Med 2004;45(Suppl 1):25S-35S.

Beyer T, Tellmann L, Nickel I, Pietrzyk U. On the use of positioning aids to reduce mis-registration in the head/neck region of whole-body PET/CT studies. J Nucl Med 2005;46(4):596-602.

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. Europ J Nucl Med 2003;30(4):588-596.

Beyer T, Rosenbaum S, Veit P, et al. Respiration artifacts in whole-body 18F-FDG PET/CT studies with combined PET/CT tomographs employing spiral CT technology with 1 to 16 detector rows. Europ J Nucl Med 2005;32:1429-1439.

Kuehl H, Antoch G. How much CT do we need for PET/CT: A radiologist's perspective. Nuklearmedizin 2005;44(Suppl 1):S24-S31.

Allen-Auerbach M, Yeom K, Park J, et al. Standard PET/CT of the chest during shallow breathing is inadequate for comprehensive staging of lung cancer. J Nucl Med 2006;47(2):298-301.

Brix G, Lechel U, Glatting G, et al. Radiation exposure of patients undergoing whole-body dual-modality FDG-PET/CT examinations. J Nucl Med 2005;46(4):608-613.

Filippone A, Ambrosini R, Fuschi M, et al. Preoperative T and N staging of colorectal cancer: accuracy of contrast-enhanced multi-detector row CT colonography-initial experience. Radiology 2004;231(1):83-90.

Veit P, Kuhle C, Beyer T, et al. Whole body positron emission tomography/computed tomography (PET/CT) tumour staging with integrated PET/CT colonography: technical feasibility and first experiences in patients with colorectal cancer. Gut 2006;55(1):68-73.

Nehmeh SA, Erdi YE, Rosenzweig KE, et al. Reduction of respiratory motion artifacts in PET imaging of lung cancer by respiratory correlated dynamic PET: methodology and comparison with respiratory gated PET. J Nucl Med 2003;44(10):1644-1648.

Weber W. Use of PET for monitoring cancer therapy and for predicting outcome. J Nucl Med 2005;46(6):983-995.

Larson SM, Erdi Y, Akhurst T, et al. Tumor treatment response based on visual and quantitative changes in global tumor glycolysis using PET-FDG imaging: The visual response score and the change in total lesion glycolysis. Clin Positron Imaging 1999;2(3):159-171.

Delbeke D, Coleman RE, Guiberteau MJ, et al. Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J Nucl Med 2006;47(5):885-895.

Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92(3):205-216.

Beyer T. Towards truly integrated hardware fusion with PET/CT. Nuklearmedizin 2005;44(Suppl 1):S5-S12.

Combined PET/CT was the first integrated dual-modality solution to reach clinical practice.1 Clinical PET/CT scanners have now been operating for almost a decade. Their quasisimultaneous acquisition of complementary anatomic and functional information has revolutionized oncology diagnosis and therapy assessment.

Oncology tasks require disease-specific PET/CT

Combined PET/CT was the first integrated dual-modality solution to reach clinical practice.

 Clinical PET/CT scanners have now been operating for almost a decade. Their quasisimultaneous acquisition of complementary anatomic and functional information has revolutionized oncology diagnosis and therapy assessment.

PET/CT also makes use of available CT transmission data to correct absorption of emitted annihilation photons during the PET emission scan.

 Such CT-based attenuation correction obviates the need for lengthy transmission scans that previously accounted for 40% of the total PET examination time.

Patient positioning also plays a pivotal role in reducing beam-hardening and truncation artifacts from CT. These are particularly apparent when imaging large patients whose arms are inside the field-of-view. PET/CT users have learned that CT-based attenuation correction is also prone to amplification of high-density artifacts from focal accumulation of IV contrast,

All of these pitfalls can diminish image quality, possibly leading to false diagnostic interpretation and making it hard to sell the power of combined imaging to referring physicians. Several groups that have investigated the challenges of CT-based attenuation correction have proposed modified acquisition schemes. These include breath-hold protocols and the use of extended FOV reconstructions to reduce CT truncation. Their use should improve the accuracy of the attenuation-corrected PET data.

Nevertheless, a judicious choice of PET/CT referrals and imaging protocols is still required.

 This includes mandatory contrast-enhanced CT in previously undiagnosed patients and in selected patients during follow-up. New protocols for administration of CT contrast have been proposed to optimize enhancement and provide sufficient bowel distention, without excessively increasing photon attenuation.

 Metal implants, unfortunately, still give rise to significant artifacts that can be corrected only retrospectively.

These pitfalls necessitate careful selection, and possible modification, of a standard whole-body PET/CT acquisition protocol. Modifying scan parameters

 and considering external advice related to patient preparation and positioning, as for PET(/CT)-guided radiation therapy planning, may be required. The following are some approaches to disease-specific imaging on PET/CT:

Combined PET/CT was the first integrated dual-modality solution to reach clinical practice. Clinical PET/CT scanners have now been operating for almost a decade. Their quasisimultaneous acquisition of complementary anatomic and functional information has revolutionized oncology diagnosis and therapy assessment.