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First published online February 28, 2007
British Journal of Radiology (2007) 80, 437-445
© 2007 British Institute of Radiology
doi: 10.1259/bjr/34082277
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Full paper

Value of contrast-enhanced multiphase CT in combined PET/CT protocols for oncological imaging

A C Pfannenberg, MD 1 P Aschoff, MD 1 K Brechtel, MD 1 M Müller, MD 2 M Klein, MD 2 R Bares, MD 2 C D Claussen, MD 1 and S M Eschmann, MD 2

Departments of 1 Diagnostic Radiology and 2 Nuclear Medicine, Eberhard-Karls-University Tuebingen, Hoppe-Seyler- Strasse 3, 72076 Tuebingen, Germany

Correspondence: Anna Christina Pfannenberg, Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany. E-mail: christina.pfannenberg{at}med.uni-tuebingen.de


   Abstract
Top
 Abstract
Introduction
 Methods and materials
 Results
 Discussion
 Conclusion
 References
 
To evaluate the additional value of contrast-enhanced multiphase CT in comparison with low-dose non-contrast CT in combined positron emission tomography (PET)/CT protocols for oncological imaging, we retrospectively analysed 100 patients with different malignant tumours. All patients underwent a PET/CT consisting of a multiphase CT protocol including a low-dose non-enhanced attenuation scan and an arterial and portal–venous contrast-enhanced scan followed by a whole-body PET. PET/CT studies were analysed by different categories to determine the added value of contrast-enhanced CT. The additional value was defined as new information provided by diagnostic CT and not available from the low-dose CT, resulting in change of PET/CT interpretation. The results were validated either by histopathology or by clinical-radiological follow up at ≥6 months. The clinical impact was evaluated with respect to changes in patient management. Diagnostic multiphase CT was of additional value in 52 out of 100 patients with 85 suspected lesions. In 40 out of 100 patients, no additional value could be detected. Eight patients were excluded due to inconclusive diagnosis in both methods including fusion. The analysis showed the greatest benefit of diagnostic CT in the categories localization of pathological fluorodeoxyglucose (FDG) uptake and precise tumour delineation, changing PET/CT interpretation in 42% and 31% of patients, respectively. The benefit of diagnostic CT was influenced by the tumour type demonstrating the highest impact in gastrointestinal, lung and neuroendocrine tumours. Diagnostic CT changed clinical management in 21 patients (21%). Diagnostic multiphase CT as part of the combined PET/CT protocol has the potential to provide considerable additional value in specific clinical conditions with resultant change of management in a substantial proportion of patients.


   Introduction
Top
 Abstract
 Introduction
Methods and materials
 Results
 Discussion
 Conclusion
 References
 
Numerous reports have underlined the incremental value of combined anatomical–functional imaging with positron emission tomography (PET)/CT for staging and re-staging of cancer [1–10]. To maximize the efficiency of PET/CT to be a real "one-stop-shop" oncology examination, a number of questions have first to be answered. One controversial issue refers to the optimal scanning protocol [4, 8, 11–14]. The question is how much CT is needed in order to address specific diagnostic issues. Today, different approaches are adopted for PET/CT scanning, with CT protocol positioned between two possible extremes: (1) CT is only used as a fast transmission source for attenuation correction, performed with very low radiation dose ("low dose CT") and little emphasis on anatomic co-registration. In this approach PET/CT is performed in addition to an independent diagnostic CT examination. (2) CT is used not only for attenuation correction but also for diagnosis and co-registration. CT is performed with standard radiation dose and intravenous and oral contrast ("diagnostic CT") to obtain diagnostic image quality. In this approach, PET/CT replaces a separate staging CT.

It appears in practice that local conditions, specific expertise of users and site preferences dictate the extent of PET/CT acquisition protocols, especially the quality of the CT portion [4, 12, 13]. Recent studies have shown that oral and intravenous contrast agents can be administered at no expense to the combined image quality but modifications and optimization of protocols are necessary to avoid artefacts in the PET images and to ensure appropriate attenuation correction [11, 13–17]. In addition, to prevent severe mismatch of internal organs in co-registration of PET and CT, adapted breathing protocols for CT acquisition have to be implemented. Normal expiration breath-hold and free breathing have been found to be most suitable [18, 20].

In our institution, offering a close collaboration between nuclear medicine and radiology experts as well as having high-end scanning technology available, we follow the concept to perform both high-quality PET and high-quality CT protocols. This meets the standards of stand-alone CT protocols for oncological imaging in the use of contrast material, detector collimation and beam current [11, 14, 15, 19]. Using state-of-the-art diagnostic CT protocols for PET/CT may require scanning of tumours in more than a single contrast enhancement phase and application of oral contrast agents. With the hardware and software capabilities of the latest lutetium oxyorthosilicate (LSO) PET/CT scanner with integrated 16 row multidetector CT, it is now possible to implement a multiphase diagnostic CT in the combined PET/CT scanning protocol. This protocol offers the unique possibility of comparing standardized contrast-enhanced CT with the non-contrast low-dose scan for attenuation correction in the same patient at the same time, both integrated in the multiphase protocol. Numerous studies have reported increased staging accuracy of PET/CT compared with PET and CT alone [4, 6–10, 21]. Data comparing accuracy of contrast-enhanced PET/CT with non-contrast PET/CT in the same patients are, as yet, not available.

To reduce the radiation burden for the patients, we developed institution-specific guidelines for the CT part of the combined PET/CT protocol depending on the specific clinical question. An ultra low-dose non-contrast scan is performed for the following reasons: recently performed state-of-the-art whole-body CT, therapy monitoring, staging of thyroid cancer before radioiodine therapy, renal insufficiency and contrast allergy. On the basis of these guidelines, about 30–40% of our PET/CT patients undergo a non-enhanced PET/CT study only with an ultra low-dose (30 mAs) CT scan. Indications for performing a multiphase standard dose (160 mAs) contrast-enhanced CT study as part of the PET/CT protocol are (1) patients referred for the first ("one-stop-shop") whole-body staging examination in our institution without recent state-of-the-art whole-body CT, (2) equivocal results of previous examinations, especially unclear liver lesions, (3) patients with neuroendocrine tumours and other malignancies with suspected hypervascular liver lesions and (d) suspicion of hepatocellular or cholangiocellular carcinoma. In the remaining patients a single-phasic portal–venous contrast-enhanced CT is performed. In radiation therapy planning different approaches exist. For staging purposes, the patients undergo a standard dose contrast-enhanced CT. For dose calculation, an additional non-contrast low-dose scan (80–100 mAs) is usually required.

The objective of our study was to evaluate the impact of contrast-enhanced multiphase CT on the PET/CT interpretation and the clinical management by comparing fused datasets of non-enhanced and contrast-enhanced PET/CT in patients with different malignancies.


   Methods and materials
Top
 Abstract
 Introduction
 Methods and materials
Results
 Discussion
 Conclusion
 References
 
Patient population
Between October 2004 and January 2005 a total of 217 consecutive oncological patients were examined by PET/CT at our institution. In 63 patients the PET/CT protocol consisted of a low-dose non-contrast CT and PET because of recently performed diagnostic whole-body CT, planned radioiodine therapy or renal insufficiency. In 54 patients a single-phase contrast-enhanced CT and in 100 patients a multiphase contrast protocol was performed. Only the 100 patients with the multiphase PET/CT study were included in the retrospective evaluation. This group included 29 women and 71 men with a mean age of 60.7 years; range 24–90 years. 13 patients presented with bronchial carcinoma (BC), six with lymphoma, 15 with gastrointestinal tumours (12 colorectal cancers, one gastric cancer, one pancreatic cancer, one gall bladder carcinoma), eight with germ cell cancer (GCT), six with head and neck tumours (H/N), 15 with prostate cancer (PC), 13 with neuroendocrine tumours (NET), nine with melanoma, five with breast cancer, three with cervical cancer and seven with cancer of unknown primary (CUP). The PET/CT studies were performed according to our institutional guidelines, with all patients giving their written informed consent. The indications for performing a multiphase CT protocol in these patients were equivalent to our stand-alone CT protocols in oncological imaging: new patients without available state-of-the-art whole-body staging examination (this applied to six lymphoma, five gastrointestinal tumours, eight germ cell tumours, 15 prostate cancers, seven CUP, five breast cancers, three cervical cancers and four melanomas), equivocal or insufficient results of previous examinations, especially according to precise assessment of tumour extent before local therapy (13 bronchial carcinomas, 10 gastrointestinal tumours, six head and neck tumours, five melanomas) and tumours with hypervascular liver lesions (13 neuroendocrine tumours).

Patient preparation
Patients planned for fluorodeoxyglucose (FDG) studies fasted overnight prior to the intravenous administration of 18F-FDG. The injected dose of 18F-FDG varied between 350 MBq and 450 MBq depending on patient weight: in patients with body mass index (BMI) <25 350–400 MBq were administered, in those with BMI >25 400–450 MBq. The blood glucose was measured before injection of the tracer to ensure blood glucose levels <11.1 mmol l–1. During the uptake phase of 45–60 min, the patients were instructed to rest comfortably. In patients referred for staging of prostate cancer and neuroendocrine tumours the tumour-seeking PET tracers 11C-Choline (800 MBq) and 68Ga-DOTATOC (100 MBq) were administered, respectively. All patients with predominant abdominal studies were asked to drink 1500 ml of mannitol 2% as a negative oral contrast agent prior to scanning in order to distend the bowel. No tranquillizers or muscle relaxants were administered.

PET/CT imaging protocol
In all patients, PET/CT was performed using the Hi-Rez Biograph 16 (Siemens Medical Solutions, Knoxville, TN). This system consists of a high-resolution 3D LSO PET and a state-of-the-art 16 row multislice CT. The PET scanner has an axial field of view (FOV) of 15.5 cm and a slice thickness of 4.25 mm. Emission data were acquired for 6–8 bed positions, typically from the base of the skull to the upper thigh (in patients with melanoma the lower extremities were also included). The PET acquisition time was usually 3 min per FOV; patients with BMI>25 were examined at 4 min per FOV. CT was operated with a peak voltage of 120 kV, a tube current of 30 mAs (ultra low dose) or 160 mAs (standard dose), rotation time 0.5 s, collimation of 0.75/1.5 mm, table feed 12/24 mm, reconstructed slice thickness/increment 5/5 mm and 3/2 mm, respectively. Patients were positioned on the scanning table with their arms raised in order to reduce beam-hardening artefacts, unless head and neck lesions were suspected. The combined examination began with a topogram to define the PET/CT examination range. We performed an ultra low-dose (30 mAs) non-contrast CT scan first for attenuation correction due to the fact that the currently available scanner software does not allow the use of split CT spiral for attenuation correction of PET. After the low-dose scan, a standard multiphase CT protocol was applied including a bolus-triggered arterial-phase thorax and liver scan, a portal–venous abdomen and pelvis scan and, if necessary, a post-contrast liver scan, followed by the PET scan. A total volume of 120 ml of the intravenous contrast agent Ultravist 370 (Schering AG, Germany) with an iodine concentration of 370 mg ml–1 was administered with a flow of 2 ml s–1. To prevent contrast-induced artefacts, we optimized the injection protocol with a 40 ml saline chaser. Depending on the scan range and the emission time as well as the time for reconstruction of the CT images, the whole PET/CT scan was completed within 35–45 min.

During preliminary studies, we tested different scanning and breathing protocols to optimize contrast-enhanced CT studies [20]. According to the results of our tests patients were asked to stop breathing in normal expiration during CT scans for optimal co-registration. However, an additional low-dose CT of the thorax in full inspiration was required in several patients for the detection of small lesions in the lung.

Image reconstruction
Diagnostic CT scans were reconstructed with 3 mm slice thickness in the coronal and 5 mm in the axial plane (reconstruction increment 2 mm and 3 mm, respectively). In addition, several special post-processing reconstructions and window-level settings (lung and bone window, maximum intensity projection (MIP) reconstruction of the lung) were applied. The non-enhanced low-dose CT data were reconstructed with the identical slice thickness of 5 mm (axial) and increment of 5 mm and used for attenuation correction of PET emission images. PET images were reconstructed by using an iterative algorithm (ordered-subset expectation maximization: 2 iterations, 8 subsets). The reconstructed PET, CT and fused images were displayed on the manufacturer's workstation (e-soft, Siemens Medical Solutions) in axial, coronal and sagittal planes using a matrix of 128x128 pixels for the PET and 512x512 pixels for the CT.

Data interpretation
Any site questioned as possibly malignant on physical examination, CT, PET or other imaging was defined as a suspicious lesion. Primary tumours as well as metastases were included. Image analysis was performed in several steps. In the first step PET and multiphase diagnostic CT images were evaluated independently by two experienced nuclear medicine specialists (SME, MM) and two experienced CT radiologists (CP, PA). On PET images any focal tracer uptake exceeding normal regional tracer accumulation was assessed as "lesion". Subsequently, fused contrast-enhanced PET/CT images were evaluated by the same readers in consensus. In a second interpretation session (4–6 weeks later) the fused images of non-enhanced PET/CT (PET and low-dose CT) were analysed by the combined team of radiologists and nuclear medicine experts and the results were compared with the previous results of fused contrast-enhanced PET/CT (PET and diagnostic CT) to determine the additional value of diagnostic CT on the PET/CT image interpretation. The additional value was defined as new information provided by contrast-enhanced CT and not available by low-dose non-contrast CT, but resulting in modification of the PET/CT image interpretation. The additional value of diagnostic CT was assessed per patient and per lesion on the basis of the following categories: (0) no additional value of diagnostic CT, (1) increased sensitivity of PET/CT in PET negative or only faintly positive lesions, (2) improved localization of pathological FDG uptake, (3) improved tumour delineation, (4) improved differentiation between malignant and physiological FDG uptake, (5) detection of incidental additional findings, not seen in PET or ultra low-dose CT. Category (6) represents equivocal findings despite diagnostic PET/CT. The clinical impact of changes in image interpretation by contrast-enhanced PET/CT was evaluated with respect to changes in patient management. Changes in clinical management included modifications of diagnostic approach by sparing or guiding further procedures (biopsy, endoscopy or others), modifications of therapeutic approach by modification of surgical strategy (planning surgery approach, replacing surgery by another modality), modification of chemotherapy strategy (performing previously unplanned chemotherapy), modification of radiotherapy strategy (optimization of radiation field), optimization of radiofrequency ablation and therapy of clinically significant additional findings. The influence of clinical management by contrast-enhanced multiphase PET/CT was determined in a retrospective analysis by a team of specialists from different fields (oncologists, surgeons, radio-oncologists) together with the PET/CT experts.

Standard of reference
The standard of reference for confirming the presence or absence of malignancy was either histopathology (biopsy or surgery) or clinical-radiological follow up for at least 6 months, based on Response Criteria In Solid Tumours (RECIST). Tumour progression in the follow up CT scan or decrease in lesion size during ongoing systemic therapy were considered positive for the presence of malignancy. Lack of change or decrease in size of a lesion without ongoing systemic therapy over at least a 6 month interval was considered negative for malignancy.


   Results
Top
 Abstract
 Introduction
 Methods and materials
 Results
Discussion
 Conclusion
 References
 
In 40 out of 100 patients with 47 suspected lesions, no additional value of contrast-enhanced CT on PET/CT interpretation could be detected (category 0). In eight patients with nine suspected lesions, neither method could establish a conclusive diagnosis in spite of fusion of diagnostic CT and PET images and further tests were necessary (category 6). In 52 out of 100 (52%) patients, the diagnostic CT was of additional value and resulted in changes of PET/CT interpretation according to category 1–5. The changes of image interpretation referred to 85 suspicious lesions. Presence or absence of malignancy was confirmed by histopathology in 32 lesions and by clinical-radiological follow up over at least 6 months in 53 lesions. Table 1Go presents the different categories of changed image interpretation based on diagnostic CT per patient (n = 52) and per lesion (n = 85). Diagnostic CT yielded the most important benefit in category 2 and 3 with 42% and 31% change of image interpretation, respectively. In 13/52 patients (25%), changes of image interpretation by diagnostic CT referred to more than one category.


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  		Table 1. Classification of additional value of contrast-enhanced CT on image interpretation of PET/CT by different categories

 
Increasing sensitivity of PET/CT by diagnostic CT in PET negative or only faintly positive lesions (category 1) is presented in detail in Table 2Go. In nine of 52 patients (17%) with nine suspected lesions, the correct diagnosis could only be established by performing a contrast-enhanced CT as part of the combined PET/CT protocol. This is especially true for PET examinations using other tracers than FDG such as 68Ga-DOTATOC or 11C-Choline with less anatomical background (patients 4,5,7).


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  		Table 2. Additional value of diagnostic CT in PET negative or only faintly positive lesions(category 1)

 
Improvements of localization of pathological FDG uptake (category 2) by diagnostic CT were found in 22 patients with 33 lesions: in 7 patients (four PC, two melanoma, one breast cancer) with 11 lymph nodes ≤10 mm, especially in the pelvis; in three patients (two CRC, one NET) with five liver metastases prior to surgery or radiofrequency ablation; in five patients with NET and seven lesions in the pancreatic and mesenteric region as well as in the skeletal system; in six patients (three CRC, two melanoma, one pancreatic cancer) with nine primary or metastatic lesions in the bowel (Figure 1Go), peritoneum and pancreas; and in one patient (suspicion of recurrent BC) with one hilar mass.


Figure 1
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  		Figure 1. 60-year-old female patient with melanoma. (a) Axial PET and (b) fused image showing a focal fluorodeoxyglucose (FDG) uptake in the right lower abdomen, corresponding to the right ascending colon. (c) The axial low-dose CT scan shows some streaking of the pericolic fat in this region but no mass. (d) In the diagnostic CT with intravenous and oral contrast a vascularized tumour lesion could be clearly delineated (arrow) consistent with a bowel metastasis of melanoma (confirmed by histology).

 
Improvements of tumour delineation (category 3) by diagnostic CT were found in 16 patients with 18 lesions prior to surgery, radiofrequency ablation or radiotherapy, including five patients with five central lung cancers, five patients with four head and neck tumours and one CUP, three patients with three gastric and colorectal tumours (Figure 1Go) and one patient with PC, one patient with gall bladder carcinoma and three liver metastases, and one patient with one mediastinal germ cell tumour.

Diagnostic CT was of additional benefit in differentiating tumour from non-malignant FDG uptake (category 4) in nine patients with 15 lesions: differentiation between malignant lesions and inflammatory or post-chemotherapy changes of the bowel in three patients with five suspected sites, differentiation between residual tumour and abscess after gastric surgery in one patient (Figure 2Go), differentiation between tumour and tuberculous infection lesions of the lung in one patient and differentiating a benign from a malignant adrenal lesion in one patient. In another three patients with seven suspicious sites, diagnostic CT helped to differentiate tumour from physiological FDG uptake: splenosis vs metastases in one NET patient, bladder uptake vs rectal tumour recurrence in one patient and embolised gastric varices vs metastases in one patient.


Figure 2
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  		Figure 2. 71-year-old female patient, s/p recent gastric surgery (signet cell carcinoma), interrupted due to bleeding, referral for evaluation of residual disease. (a) Axial PET and (c) fused image demonstrate a hypermetabolic focus centrally in the middle abdomen consistent with residual tumour or a necrotic mesenteric lymph node (white arrow). (d) Contrast-enhanced CT reveals that this focus corresponds to a post-operative abscess with the typical CT pattern. (b) The non-contrast scan cannot establish the correct diagnosis. (h) Diagnostic CT could also detect the enhancing primary gastric tumour (red arrow) which (e,g) is only faintly visible on PET due to poor FDG uptake in signet cell carcinoma. (f) On the non-contrast scan, the tumour can only be suspected.

 
Relevant additional findings (category 5) were found in nine patients with 10 lesions included five vessel and heart complications in five patients such as aneurysm of the aorta and iliac arteries, significant stenoses and occlusions of femoral arteries and a left atrial thrombus (Figure 3Go), in two patients two complicated renal cysts (Bosniak IIF and III), in one of them an additional pericardial cyst, in one patient a fractured unstable osteolysis of a cervical vertebra and in one patient previously unknown very small pulmonary nodules <8 mm, not seen on the expiration low-dose PET/CT scan. Malignancy of nodules was confirmed by CT follow up demonstrating progress.


Figure 3
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  		Figure 3. 46-year-old male patient with lung cancer, re-staging after radiochemotherapy (RCtx) (a–c before and d–f after radiochemotherapy). (a,d) Axial PET scans show decreasing fluorodeoxyglucose uptake after RCtx in the tumour region right lower lobe indicating response to therapy (arrow). (b,e) Although in the non-contrast CT as well as in (c,f) the contrast-enhanced CT the tumour accompanying atelectasis is shown to be disappearing, a progressive mass lesion with infiltration of the left atrium is also visible caused by residual tumour and/or cardiac thrombus, only seen in the contrast-enhanced scan (f, arrow).

 
Comparing the referring diagnoses in the two groups, with and without the additional value of diagnostic CT, it becomes obvious that the impact of diagnostic CT on PET/CT interpretation is influenced by the tumour type (Table 3Go). The benefit of diagnostic CT was high in gastrointestinal, lung and neuroendocrine tumours, moderate in melanoma, prostate cancer and CUP syndrome and low in lymphoma and germ cell tumours.


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  		Table 3. Additional value of diagnostic CT in PET/CT according to type of tumour (patient based)

 
Changes of image interpretation by diagnostic CT influenced therapy management in 21 of 100 (21%) patients. Modifications of diagnostic approach by sparing of further diagnostic tests resulted in two patients and by guiding further procedures such as endoscopy and biopsy in four patients. Modifications of the therapeutic approach by diagnostic CT resulted in a large percentage having improved planning of surgery procedures (seven patients), including laparoscopic lymph node resections. In one patient, the chemotherapy regimen was optimized. Radiotherapy management was changed by diagnostic CT in three patients, mainly due to modifications of the radiation field. In two patients, diagnostic CT was indispensable for planning of radiofrequency ablation. In two patients, detection of clinically significant incidental findings, such as a cardiac thrombus and an unstable vertebral fracture of the cervical spine, changed clinical management.


   Discussion
Top
 Abstract
 Introduction
 Methods and materials
 Results
 Discussion
Conclusion
 References
 
Summarizing the literature, the CT part of the combined PET/CT protocol is commonly applied as a whole-body low-dose scan without intravenous contrast [4–6, 8, 21, 23–25] or as a contrast-enhanced single-phase CT in the portal–venous phase [11, 15, 19]. Data regarding application of multiphase (arterial and portal–venous) CT imaging in combination with PET are not yet available. In a preliminary study, we have shown that high resolution whole-body PET/CT is technically feasible in clinical routine with single- or multiphase contrast enhancement [20].

The aim of our present retrospective study was to assess the added value of contrast-enhanced CT in the combined PET/CT protocol in comparison with non-enhanced low-dose CT in specific clinical situations. The results show an additional value of diagnostic CT in 52% of patients resulting in changes of PET/CT interpretation. The study also indicates that the benefit of diagnostic CT is influenced by the tumour type demonstrating the highest impact in gastrointestinal, lung and neuroendocrine tumours. To obtain a detailed analysis of changes in image interpretation attributed to diagnostic CT, we assessed the modifications of PET/CT interpretation in different categories. The analysis shows the greatest benefit of diagnostic CT in the categories improved localization of pathological FDG uptake and improved local tumour (T) staging. In these subgroups, contrast-enhanced CT changed image interpretation in 42% and 31% of patients, respectively.

Increased accuracy in localizing pathological FDG uptake is a known fundamental benefit of dual modality imaging including non-diagnostic CT protocols [4–6, 8, 21, 22]. However, our results demonstrate an additional value of diagnostic CT in exactly localizing pathological uptake in 39% of suspected sites. This was particularly apparent in patients with gastrointestinal, especially colorectal, tumours with recurrent tumour lesions in the bowel and liver metastases and in patients with neuroendocrine tumours with pancreatic, mesenteric and liver lesions in the 68Ga-DOTATOC PET/CT. The incremental benefit of diagnostic CT in localizing gastrointestinal and peritoneal lesions was due to the improved delineation of the bowel wall by oral and rectal negative contrast agents in combination with standard dose acquisition, contrast administration as well as the application of spasmolytic drugs during diagnostic CT. Regarding patients with neuroendocrine tumours our results underline the fact that highly selective tumour tracers such as 68Ga-DOTATOC which lack anatomical "landmarks" require correlation with high-resolution morphology for correct localization and surgical therapy planning [22]. This relates to a great extent to regions with complex and changing anatomy such as the pelvis and lower abdomen.

The important value of diagnostic CT in precise tumour delineation applying to 31% of patients in our study was mainly attributed to patients with central lung cancer, head and neck tumour, colorectal recurrent tumours and liver metastases prior to surgery, radiotherapy or radiofrequency ablation. In these cases, planning of the therapeutic approach required to a high degree exact staging of tumour delineation, segmental localization (liver) and defining the extent of infiltration of surrounding structures. The benefit of diagnostic CT in differentiating malignant FDG uptake from non-malignant and physiological uptake in 17% of patients is attributed to the precise characterization of infectious lesions, splenosis, post-operative changes as well as sites of physiological FDG uptake in the bowel and bladder by the typical CT morphology.

The impact of diagnostic CT to increase sensitivity of PET/CT in PET negative or only faintly positive lesions was analysed in greater detail. In this category, we found in 17% of patients a substantial benefit of diagnostic CT in lesion detection and characterization allowing the correct diagnosis only by performing a contrast-enhanced study. This is in accordance with the results of Antoch et al and was especially true for tumour-specific tracers such as 68Ga-DOTATOC or 11C-Choline [11]. In addition to the value of diagnostic CT in lesion localization and characterization diagnostic CT identified relevant additional findings in 17% of patients which influenced clinical management in two out of nine patients. The proper consideration of incidental findings on CT was recently addressed by Schöder et al [24] and Osman et al [25] who found a 3% prevalence of significant incidental CT lesions on non-enhanced PET/CT studies. The higher proportion of additional findings in our study is likely to be due to the diagnostic quality of the CT performed with standard dose and contrast enhancement.

Limitations of our study
The relatively high proportion of changes in PET/CT interpretation by contrast-enhanced CT may be biased by patient selection. First, the patients were selected for diagnostic CT based on institutional guidelines which a anticipated a potential benefit of contrast application in this group; otherwise the patients would have been primarily selected for the "non-contrast group". Second, different tumour types in the patient population with a high proportion of lung, gastrointestinal, prostate and neuroendocrine tumours and the use of non-FDG tracers with less anatomical background in 28% of patients could have influenced the benefit of diagnostic CT. Another limitation is the order in which the PET/CT datasets were evaluated with the contrast-enhanced PET/CT first; this approach may have biased the study results. The assessment of management changes by diagnostic CT was performed retrospectively. An overestimation of the impact on management by this methodology cannot be excluded. The reference standard based on RECIST criteria is limited, lesions that regress on therapy were classified as malignant, but inflammatory lesions could also regress over time.

It is to be noted that in the literature the term "low dose" CT refers to a wide dose range from 30 mAs up to 100–120 mAs which affects CT image quality differently. In our study, the non-enhanced CT scan was always equivalent to a real ultra low-dose scan performed with 35 mAs.


   Conclusion
Top
 Abstract
 Introduction
 Methods and materials
 Results
 Discussion
 Conclusion
References
 
The present study demonstrates that contrast-enhanced multiphase CT as part of the PET/CT examination has the potential to provide considerable additional information when compared with non-contrast PET/CT in specific clinical conditions. The analysis showed the greatest benefit of diagnostic CT in the categories improved localization of pathological FDG uptake and improved local tumour staging. Diagnostic CT as part of a PET/CT protocol influenced clinical management in a substantial number of patients, especially due to better planning of surgical interventions and radiotherapy.


   Acknowledgments
 
We would like to thank our technicians Henriette Heners, Sylvia Storz, Benjamin Gerras, Anke Reckwell and Gabi Boutin for their helpful assistance in the acquisition of the PET/CT data. We gratefully acknowledge the continuing support of our colleagues in the Radiopharmacy Department. We also thank Nasreddin Abolmaali, MD, ZIK OncoRay, Technical University Dresden, Germany for helpful discussions in preparing the manuscript.

Received for publication December 13, 2005. Revision received July 24, 2006. Accepted for publication August 21, 2006.


   References
Top
 Abstract
 Introduction
 Methods and materials
 Results
 Discussion
 Conclusion
 References
 

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