Chantal P. Bleeker-Rovers

Clinical value of FDG PET in patients with fever of unknown origin and patients suspected of focal infection or inflammation

Fever of unknown origin (FUO) and suspected focal infection or inflammation are challenging medical problems. The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients with FUO and patients with suspected focal infection or inflammation. All FDG PET scans ordered because of FUO or suspected focal infection or inflammation in the last 4 years were reviewed. These results were compared with the final diagnosis. Thirty-five FDG PET scans were performed in 35 patients with FUO. A final diagnosis was established in 19 patients (54%). Of the total number of scans, 37% were clinically helpful. The positive predictive value of FDG PET in these patients was 87% and the negative predictive value was 95%. Fifty-five FDG PET scans were performed in 48 patients with suspected focal infection or inflammation. A final diagnosis was established in 38 patients (82%). Of the total number of scans, 65% were clinically helpful. The positive predictive value of FDG PET in these 55 episodes of suspected infection or inflammation was 95% and the negative predictive value was 100%. It is concluded that FDG PET appears to be a valuable imaging technique in the evaluation of FUO and suspected focal infection or inflammation. Furthermore, FDG PET could become a useful tool for evaluating the effect of treatment of infectious and inflammatory processes that cannot reliably be visualised by conventional techniques. However, to assess the additional diagnostic value of this technique, prospective studies of FDG PET as part of a structured diagnostic protocol are warranted.

Imaging of inflammation by PET, conventional scintigraphy, and other imaging techniques.

Nuclear medicine imaging procedures play an important role in the assessment of inflammatory diseases. With the advent of 3-dimensional anatomic imaging, there has been a tendency to replace traditional planar scintigraphy by CT or MRI. Furthermore, scintigraphic techniques may have to be combined with other imaging modalities to achieve high sensitivity and specificity, and some may require time-consuming labeling procedures. On the other hand, new developments such as combined SPECT/CT increase the diagnostic power of scintigraphy. Also, the advent of PET had a considerable impact on the use of nuclear medicine imaging techniques. In this review, we aim to provide nuclear medicine specialists and clinicians with the relevant information on rational and efficient use of nuclear medicine imaging techniques in the assessment of patients with osteomyelitis, infected vascular prostheses, metastatic infectious disease, rheumatoid arthritis, vasculitis, inflammatory bowel disease, sarcoidosis, and fever of unknown origin.Nuclear medicine imaging procedures play an important role in the assessment of inflammatory diseases. With the advent of 3-dimensional anatomic imaging, there has been a tendency to replace traditional planar scintigraphy by CT or MRI. Furthermore, scintigraphic techniques may have to be combined with other imaging modalities to achieve high sensitivity and specificity, and some may require time-consuming labeling procedures. On the other hand, new developments such as combined SPECT/CT increase the diagnostic power of scintigraphy. Also, the advent of PET had a considerable impact on the use of nuclear medicine imaging techniques. In this review, we aim to provide nuclear medicine specialists and clinicians with the relevant information on rational and efficient use of nuclear medicine imaging techniques in the assessment of patients with osteomyelitis, infected vascular prostheses, metastatic infectious disease, rheumatoid arthritis, vasculitis, inflammatory bowel disease, sarcoidosis, and fever of unknown origin.

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.

PurposeSince 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.MethodsFrom 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.ResultsOf 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).ConclusionFDG-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.

PET and SPECT in Osteomyelitis and Prosthetic Bone and Joint Infections: A Systematic Review

OBJECTIVE To review the literature on diagnostic accuracy and clinical value of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging of bone and joint infections. METHODS The PubMed/MEDLINE and Embase (OvidSP) literature databases were systematically searched for publications on SPECT and PET on osteomyelitis and prosthetic bone and joint infections using specific guidelines with MeSH-terms, truncations, and completion using cross-references. RESULTS In 44 original articles (15 for SPECT and 29 for (18)F-fluorodeoxyglucose [FDG]-PET) on osteomyelitis and prosthetic bone and joint infection, 1634 patients were included (580 patients SPECT, 1054 patients FDG-PET). Level of evidence (Oxford criteria) was 2-3b. For SPECT, the highest diagnostic accuracy of 95% for diagnosis of bone and joint infections is achieved with combined (111)In-WBC and (99m)Tc-sulfur colloid. Acceptable diagnostic accuracy was also obtained with (99m)Tc-WBC or (111)In-WBC combined with (99m)Tc-methylene diphosphonate ((99m)Tc-MDP). FDG-PET is useful for diagnosis of osteomyelitis with a sensitivity and specificity generally over 95%. In patients with orthopedic implant infections, sensitivity varies widely from 28% to 91% and specificity from 9% to 97%. This variation in FDG-PET performance in orthopedic implant infections depends largely on the (use of different) criteria to diagnose infection. Determination of the best criteria is still a matter of debate. CONCLUSIONS SPECT/computed tomography (CT) with (111)In-WBC combined with (99m)Tc-MDP or (99m)Tc-sulfur colloid seems to be the best imaging technique for diagnosis of bone and joint infections. FDG-PET is also useful for diagnosis of osteomyelitis with improved spatial resolution over SPECT imaging, allowing more accurate localization. Localization can be further improved by adding CT. Diagnosis of orthopedic implant infections with FDG-PET depends strongly on the localization of the implant and the criteria used to diagnose infection. Confirmation of well defined criteria to diagnose infection on FDG-PET in patients with metallic implants is thus of paramount importance for optimal diagnosis.

Chronic Q fever: review of the literature and a proposal of new diagnostic criteria.

A review was performed to determine clinical aspects and diagnostic tools for chronic Q fever. We present a Dutch guideline based on literature and clinical experience with chronic Q fever patients in The Netherlands so far. In this guideline diagnosis is categorized as proven, possible or probable chronic infection based on serology, PCR, clinical symptoms, risk factors and diagnostic imaging.

Diagnosis of renal and hepatic cyst infections by 18-F-fluorodeoxyglucose positron emission tomography in autosomal dominant polycystic kidney disease.

BACKGROUND Infection of a renal or hepatic cyst is a serious complication of autosomal dominant polycystic kidney disease (ADPKD). Although crucial for successful management, early diagnosis is difficult, largely because of nonspecific symptoms and limitations of conventional imaging techniques. Because of an increased metabolic rate, inflammatory cells take up large amounts of glucose. 18-F-fluorodeoxyglucose (FDG), therefore, represents a promising agent for detection of cyst infections using positron emission tomography (PET). METHODS The authors studied the results of 7 FDG PET scans in 3 ADPKD patients suspected of renal or hepatic cyst infection. Two PET scans were performed in patient A (PET 1 and 2), one PET scan was performed in patient B (PET 3), and 4 PET scans were performed in patient C (PET 4, 5, 6 and 7). RESULTS FDG PET identified the infected cysts in 2 episodes of renal cyst infection (PET 2 and 3), 2 episodes of hepatic cyst infection (PET 6 and 7), and 1 episode of both renal and hepatic cyst infection (PET 1). In patient C, FDG PET was normal after 6 weeks of antibiotic treatment for hepatic cyst infection (PET 4) and again at a time when hepatic cyst infection was suspected, but eventually colchicine intoxication was diagnosed (PET 5). CONCLUSION In these patients, FDG PET proved very helpful in diagnosing and in excluding renal and hepatic cyst infections. It is concluded that FDG PET is a promising new imaging technique enabling early identification of renal and hepatic cyst infections in ADPKD patients.

18F-FDG PET/CT for Detection of Metastatic Infection in Gram-Positive Bacteremia

The timely detection of metastatic infectious foci in gram-positive bacteremia is crucial, because these foci often require prolonged antibiotic treatment or drainage. The diagnosis of metastatic infectious foci is difficult because localizing symptoms are often absent. We investigated whether 18F-FDG PET/CT was able to detect such foci and whether detection influenced clinical outcome. Methods: One hundred fifteen nonneutropenic patients with gram-positive bacteremia were prospectively included. Patients with positive blood cultures growing Staphylococcus aureus, Streptococcus species, or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. 18F-FDG PET/CT was performed within 2 wk after the first positive blood culture. Abnormal 18F-FDG uptake had to be confirmed by radiologic, microbiologic, or pathologic studies. Results were compared with a matched historical control group of 230 patients in whom no 18F-FDG PET/CT was performed. Results: Significantly more patients were diagnosed with metastatic foci in the study group (67.8% vs. 35.7%). Of the imaging investigations performed, 18F-FDG PET/CT was the first to delineate infectious foci in 35 patients (30%). In the remaining 70%, either symptoms on physical examination or other imaging techniques first revealed infectious foci. The sensitivity, specificity, negative predictive value, and positive predictive value of 18F-FDG PET/CT were 100%, 87%, 100%, and 89%, respectively. Relapse rates decreased from 7.4% to 2.6% among study patients (P = 0.09) and from 8.9% to 1.4% in patients with S. aureus (P = 0.04). Overall mortality after 6 mo decreased from 32.2% to 19.1% in the 18F-FDG PET/CT group (P = 0.014). Conclusion: In the diagnostic work-up of high-risk patients with gram-positive bacteremia, 18F-FDG PET/CT is a valuable technique that results in lower mortality rates. In patients with S. aureus bacteremia, relapse rates decreased significantly after the addition of 18F-FDG PET/CT.

Fever of Unknown Origin

Fever of unknown origin (FUO) often is defined as a fever greater than 38.3 degrees C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory tests. In general, infection accounts for approximately one-fourth of cases of FUO, followed by neoplasm and noninfectious inflammatory diseases. No diagnosis is reached in up to 50% of cases. Scintigraphic methods, such as (67)Ga-citrate, labeled leukocytes, and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET), are often used in the diagnosis of FUO. In FUO, FDG-PET appears to be of great advantage because malignancy, inflammation, and infection can be detected. FDG-PET does not seem to contribute to a final diagnosis in patients with normal erythrocyte sedimentation rate and C-reactive protein. Image fusion combining PET and computed tomography facilitates anatomical localization of increased FDG uptake and better guiding for further diagnostic tests to achieve a final diagnosis. In conclusion, the body of evidence on the utility of FDG-PET in patients with FUO is growing and FDG-PET will probably become the preferred diagnostic procedure, especially when a definite diagnosis cannot easily be achieved. Because of favorable characteristics of FDG-PET, conventional scintigraphic techniques may be replaced by FDG-PET in institutions in which PET is available.

Chronic Q Fever in the Netherlands 5 Years after the Start of the Q Fever Epidemic: Results from the Dutch Chronic Q Fever Database

ABSTRACT Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age (P = 0.004 and 0.010), proven chronic Q fever (P = 0.020 and 0.002), vascular chronic Q fever (P = 0.024 and 0.005), acute presentation with chronic Q fever (P = 0.002 and P < 0.001), and surgical treatment of chronic Q fever (P = 0.025 and P < 0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively.

Cost-Effectiveness of Routine 18F-FDG PET/CT in High-Risk Patients with Gram-Positive Bacteremia

Gram-positive bacteremia has a high morbidity and mortality rate of approximately 30%. Delayed diagnosis of clinically silent metastatic infectious foci is an important indicator for a complicated outcome. 18F-FDG PET/CT allows detection of focal infection, resulting in lower relapse rates and mortality. Here, we present a cost-effectiveness analysis associated with introduction of 18F-FDG PET/CT for patients with gram-positive bacteremia. Methods: A cost-effectiveness analysis in a prospective 18F-FDG PET/CT group (n = 115) and matched control group (n = 230) was performed alongside a clinical study, the results of which were previously published. Mortality at 6 mo was considered the final effect outcome and was used in the denominator of the incremental cost-effectiveness ratio. Results: Mortality in the 18F-FDG PET/CT group was 19%, compared with 32% in the control group (P < 0.01). Incremental costs of 18F-FDG PET/CT were