A prospective multi-centre study of the value of FDG-PET as part of a structured diagnostic protocol in patients with fever of unknown origin

Purpose Since ¹⁸F-fluorodeoxyglucose (FDG) accumulates in neoplastic cells and in activated inflammatory cells, positron emission tomography (PET) with FDG could be valuable in diagnosing patients with fever of unknown origin (FUO). The aim of this study was to validate the use of FDG-PET as part of a structured diagnostic protocol in the general patient population with FUO. Methods From December 2003 to July 2005, 70 patients with FUO were recruited from one university hospital (n=38) and five community hospitals (n=32). A structured diagnostic protocol including FDG-PET was used. A dedicated, full-ring PET scanner was used for data acquisition. FDG-PET scans were interpreted by two staff members of the department of nuclear medicine without further clinical information. The final clinical diagnosis was used for comparison with the FDG-PET results. Results Of all scans, 33% were clinically helpful. The contribution of FDG-PET to the final diagnosis did not differ significantly between patients diagnosed in the university hospital and patients diagnosed in the community hospitals. FDG-PET contributed significantly more often to the final diagnosis in patients with continuous fever than in patients with periodic fever. FDG-PET was not helpful in any of the patients with normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Conclusion FDG-PET is a valuable imaging technique as part of a diagnostic protocol in the general patient population with FUO and a raised ESR or CRP.     

Value of FDG PET in patients with fever of unknown origin.

Fever of unknown origin (FUO) is a diagnostic challenge, because the cause of such fever may be manifold. Studies on the use of positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG), for the diagnosis of inflammation in patients with osteomyelitis or HIV have been promising and suggest its use in patients with FUO. In this study, we used FDG PET in 16 patients with FUO in whom conventional diagnostics had not been conclusive. In 12 patients, (75%) non-physiological accumulations of FDG were found which led to the final diagnosis in 11 patients (69%). FDG PET was negative in four patients (25%). Two of these patients had rheumatic fever, while in the other two patients the origin of fever could not be detected within 3 months after PET by any other laboratory or imaging means. These findings point to the high sensitivity of FDG whole-body PET for the detection of morphologically assessable foci as an origin of FUO. Moreover, they suggest a high negative predictive value of FDG PET in the setting of FUO, since in no patient with a negative FDG PET could a morphological origin of the fever be determined. In conclusion, FDG whole-body PET appears to be a promising diagnostic tool in patients with FUO, in whom conventional diagnostics had been unsuccessful.     

^18FDG—PET诊断不明原因发热

目的 :探讨18FDG PET对不明原因发热 (FUO)的诊断价值和显像特点。材料和方法 :静脉注射18FDG后 ,对常规影像学及实验室检查未发现异常的 2 6例FUO患者进行PET显像。结果 :2 0例发现至少一处非生理性的FDG聚集 ,其中8例最后证实为肿瘤 ,12例为感染或其他良性疾病 ;6例PET显像阴性 ,2例确诊为风湿 ,2例自行好转 ,1例未能确诊 ,1例肾癌为假阴性。结论 :在其他各种检查方法均难以解释FUO的原因时 ,FDG PET可以提供较可靠的诊断信息。     

F-18 FDG-PET/CT in evaluation of patients with fever of unknown origin

Objectives

This study was carried out to evaluate the diagnostic utility of FDG-PET/CT in patients with fever of unknown origin (FUO).

Methods

Medical records of 103 patients who underwent FDG-PET/CT and anatomic imaging as a part of FUO workup were analyzed. Final diagnosis of the cause of FUO was reached based on serologic assays, cultures, biopsy, surgery or 6 months of clinical follow-up.

Results

The definite cause of fever was established in 69/103 patients. Abnormal FDG uptake was found in 63/103 patients and contributed to the final diagnosis (TP) in 62 patients (98.48 %). Of the remaining 40 patients with negative PET/CT, the final definite cause of fever (FN) could be determined only in seven patients (17.5 %). PET/CT had a sensitivity, specificity, positive predictive value and negative predictive value of 90, 97, 98.4 and 82.5 % compared to 43.5, 67.6, 73.2 and 37.1 %, respectively, for anatomic imaging. FDG-PET/CT had a higher accuracy (92.2 vs. 51.5 %; p = 0.003) compared to anatomic imaging for suggesting a cause of FUO.

Conclusions

PET/CT showed high sensitivity and specificity in suggesting a definite diagnosis in the evaluation of FUO.     

Applications of fluorodeoxyglucose positron emission tomography in the diagnosis of infection

The purpose of this study was to assess the accuracy of fluorodeoxyglucose positron emission tomography (FDG PET) in diagnosing infection in a large population of patients and in a variety of clinical circumstances where the performance of conventional imaging modalities has been questioned. We retrospectively analysed 167 FDG PET scans obtained to evaluate 175 anatomical sites for the presence of infection. The major indications for the scans were (1) complicated orthopaedic hardware (n=97), (2) chronic osteomyelitis (n=56), and (3) other (n=14: six fever of unknown origin, three vascular grafts, and five soft tissue). We assessed the overall diagnostic accuracy of FDG PET for each of these indications. In addition, we further analysed this modality's effectiveness by grouping the scans into specific clinical situations. A final diagnosis was made on the basis of surgical pathology and clinical follow-up for a minimum of 6 months. The overall accuracy of FDG PET in evaluating orthopaedic hardware was 96.2% for hip prosthesis, 81% for knee prosthesis, and 100% in 15 patients with other orthopaedic devices. Among the patients in our sample suspected of having chronic osteomyelitis, the accuracy was 91.2%. FDG PET was inaccurate in three cases of fever of unknown origin and accurate in all vascular graft and soft tissue infections. In 49 patients with a clinically apparent soft-tissue infection, FDG PET was able to detect or exclude underlying osteomyelitis with an accuracy of 92.3%. Among the 23 patients who had recent orthopaedic procedures, FDG PET imaging was accurate in 87% of cases. It is concluded that FDG PET is a highly effective imaging modality in the assessment of patients with suspected infection.     

Nuclear medicine diagnosis of patients with fever of unknown origin (FUO)

Fever of unknown origin (FUO) in immunocompetent and non neutropenic patients is defined as recurrent fever of 38.3 degrees C or greater, lasting 2-3 weeks or longer, and undiagnosed after 1 week of appropriate evaluation. The underlying diseases of FUO are numerous and infection accounts for only 20-40% of them. The majority of FUO-patients have autoimmunity and collagen vascular disease and neoplasm, which are responsible for about 50-60% of all cases. In this respect FOU in its classical definition is clearly separated from postoperative and neutropenic fever where inflammation and infection are more common. Although methods that use in-vitro or in-vivo labeled white blood cells (WBCs) have a high diagnostic accuracy in the detection and exclusion of granulocytic pathology, they are only of limited value in FUO-patients in establishing the final diagnosis due to the low prevalence of purulent processes in this collective. WBCs are more suited in evaluation of the focus in occult sepsis. Ga-67 citrate is the only commercially available gamma emitter which images acute, chronic, granulomatous and autoimmune inflammation and also various malignant diseases. Therefore Ga-67 citrate is currently considered to be the tracer of choice in the diagnostic work-up of FUO. The number of Ga-67-scans contributing to the final diagnosis was found to be higher outside Germany than it has been reported for labeled WBCs. F-18-2'-deoxy-2-fluoro-D-glucose (FDG) has been used extensively for tumor imaging with PET. Inflammatory processes accumulate the tracer by similar mechanisms. First results of FDG imaging demonstrated, that FDG may be superior to other nuclear medicine imaging modalities which may be explained by the preferable tracer kinetics of the small F-18-FDG molecule and by a better spatial resolution of coincidence imaging in comparison to a conventional gamma camera.     

Evaluation of diagnostic performance of 18F-FDG-PET compared to CT in detecting potential causes of fever of unknown origin in an academic centre

Determining the cause of fever of unknown origin (FUO) often proves challenging to attending physicians and the role of conventional imaging in this setting has been uncertain. In this retrospective study, we examined the role of fluorine-18 fluorodesoxyglucose-positron emission tomography ((18)F-FDG-PET) compared to computed tomography (CT) in diagnosing the potential etiology of FUO. To accomplish this task, we identified patients with FUO who underwent (18)F-FDG-PET for detecting the source of fever. Twenty-four patients (16 males and 8 females, age range = 17-80, mean age = 49.5) were examined with (18)F-FDG-PET of which 18 were also assessed with a diagnostic CT (within 3 weeks, mean interval = 7.5 days). The PET and CT findings were reviewed and the presence of focal (18)F-FDG uptake or gross CT lesions was considered a potential site causing FUO. Of patients who underwent PET alone, ? were reported as positive. Of the 18 who had both PET and diagnostic CT, PET was positive in 18 and CT was positive in only 7 cases. Of positive findings on PET, etiologies included infection (11), non-infectious inflammation (8), lymphoma (3), and other cancers (1). Of positive findings on CT, etiologies included infection (3), lymphoma (1), non-infectious inflammation (2) and other cancers (1). Importantly, we found no cases with positive CT and negative PET findings. In conclusion, accordingly to our findings, (18)F-FDG-PET appears to be of great value in assessing patients with FUO, especially when caused by infection or inflammation. Fluorine-18 FDG-PET is more sensitive than diagnostic CT in detecting and localizing diseased sites, and is the optimal imaging modality to evaluate patients with FUO.     

Potential pitfalls of 18F-FDG PET in a large series of patients treated for malignant lymphoma: prevalence and scan interpretation

OBJECTIVE: To evaluate the prevalence and scan interpretation criteria useful in identifying non-tumoural F-FDG focal uptakes (potential pitfalls) in patients who had been previously treated for a malignant lymphoma studied by positron emission tomography (PET). MATERIALS: Nine hundred and ninety-six consecutive PET scans obtained in 706 patients with malignant lymphoma were reviewed. All patients had been previously treated by first-line chemo-radiotherapy, plus surgery when required, and were then studied by FDG PET to investigate suspected recurrence at doubtful or inconclusive conventional radiological imaging (ultrasound, computed tomography, magnetic resonance imaging). PET was obtained with patients in the fasted condition and after i.v. injection of 370 MBq of F-FDG; imaging was acquired 60-90 min later. In patients with focal FDG uptake the final diagnosis was reached on the basis of histological findings or long-term follow-up. RESULTS: Thirty-one of 134 PET scans (23.1%) showing focal FDG uptake were diagnosed as non-tumoural radiotracer uptake, related to the presence of brown fat in seven cases, thymic hyperplasia in five, muscles contraction in four, lymph node unspecific inflammation in four, mediastinal/pulmonary unspecific inflammation in four, gastritis in two, colitis in two, bacterial abscess in one, lactating breast in one, and herpes zoster in one. Each of the above cited situations has been reported in the literature, generally in the form of sporadic reports, as a potential cause of misinterpretation (false positive) in reading a PET scan with the potential for incorrect patient management. An accurate diagnosis in these patients was important for the following therapeutic decision making. CONCLUSIONS: In the whole series of patients with treated malignant lymphoma, the prevalence of non-tumoural FDG focal uptake during follow-up was relatively low (3.1%); conversely, it was relatively high when considering the sub-group of 'positive' PET only (23.1%). The importance of knowing these situations in order to avoid misinterpretation in reading PET scans needs to be emphasized. In this light, an accurate patient's history and a skilful nuclear medicine physician are very important factors. For the same purpose, it is reasonable to think that the use of hybrid PET/CT tomographs could also play an important role in helping to identify non-tumoural FDG focal uptake.     

Fever of unknown origin: prospective comparison of diagnostic value of <Superscript>18</Superscript>F-FDG PET and <Superscript>111</Superscript>In-granulocyte scintigraphy

The diagnostic work-up in patients with fever of unknown origin (FUO) is often challenging and frequently includes nuclear medicine procedures. Whereas a role for leucocyte or granulocyte scintigraphy in FUO is generally accepted, a possible role of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in these patients remains to be established. To study this, we compared prospectively, on a head-to-head basis, the diagnostic value of FDG-PET and indium-111 granulocyte scintigraphy in patients with FUO. Nineteen patients with FUO underwent both FDG-PET and ¹¹¹In-granulocyte scintigraphy within 1 week. FDG-PET scans and granulocyte scintigrams were reviewed by different doctors who were blinded to the result of the other investigation. The diagnostic values of FDG-PET and granulocyte scintigraphy were evaluated with regard to identification of a focal infectious/inflammatory or malignant cause of FUO. The sensitivity of granulocyte scintigraphy and FDG-PET were 71% [95% confidence interval (CI): 37–85%] and 50% (CI: 16–84%), respectively. The specificity of granulocyte scintigraphy was 92% (71–100%), which was significantly higher than that of FDG-PET, at 46% (34–62%). Positive and negative predictive values for granulocyte scintigraphy were both 85%. Positive and negative predictive values for FDG-PET were 30% and 67%, respectively. ¹¹¹In-granulocyte scintigraphy has a superior diagnostic performance compared to FDG-PET for detection of a localised infectious/inflammatory or neoplastic cause of FUO. The poorer performance of FDG-PET is in particular attributable to a high percentage of false positive scans, leading to low specificity.     

Fever of unknown origin: prospective comparison of [18F]FDG imaging with a double-head coincidence camera and gallium-67 citrate SPET

Gallium-67 citrate is currently considered as the tracer of first choice in the diagnostic workup of fever of unknown origin (FUO). Fluorine-18 2'-deoxy-2-fluoro-D-glucose (FDG) has been shown to accumulate in malignant tumours but also in inflammatory processes. The aim of this study was to prospectively evaluate FDG imaging with a double-head coincidence camera (DHCC) in patients with FUO in comparison with planar and single-photon emission tomography (SPET) 67Ga citrate scanning. Twenty FUO patients underwent FDG imaging with a DHCC which included transaxial and longitudinal whole-body tomography. In 18 of these subjects, 67Ga citrate whole-body and SPET imaging was performed. The 67Ga citrate and FDG images were interpreted by two investigators, both blinded to the results of other diagnostic modalities. Forty percent (8/20) of the patients had infection, 25% (5/20) had auto-immune diseases, 10% (2/20) had neoplasms and 15% (3/20) had other diseases. Fever remained unexplained in 10% (2/20) of the patients. Of the 20 patients studied, FDG imaging was positive and essentially contributed to the final diagnosis in 11 (55%). The sensitivity of transaxial FDG tomography in detecting the focus of fever was 84% and the specificity, 86%. Positive and negative predictive values were 92% and 75%, respectively. If the analysis was restricted to the 18 patients who were investigated both with 67Ga citrate and FDG, sensitivity was 81% and specificity, 86%. Positive and negative predictive values were 90% and 75%, respectively. The diagnostic accuracy of whole-body FDG tomography (again restricted to the aforementioned 18 patients) was lower (sensitivity, 36%; specificity, 86%; positive and negative predictive values, 80% and 46%, respectively). 67Ga citrate SPET yielded a sensitivity of 67% in detecting the focus of fever and a specificity of 78%. Positive and negative predictive values were 75% and 70%, respectively. A low sensitivity (45%), but combined with a high specificity (100%), was found in planar 67Ga imaging. Positive and negative predictive values were 100% and 54%, respectively. It is concluded that in the context of FUO, transaxial FDG tomography performed with a DHCC is superior to 67Ga citrate SPET. This seems to be the consequence of superior tracer kinetics of FDG compared with those of 67Ga citrate and of a better spatial resolution of a DHCC system compared with SPET imaging. In patients with FUO, FDG imaging with either dedicated PET or DHCC should be considered the procedure of choice.