Khadija Benali

Respective Performance of 18F-FDG-PET and Radiolabeled Leukocyte Scintigraphy for the Diagnosis of Prosthetic Valve Endocarditis

Echocardiography plays a key role in the diagnosis of infective endocarditis (IE) but can be inconclusive in patients in whom prosthetic valve endocarditis (PVE) is suspected. The incremental diagnostic value of 18F-FDG PET and radiolabeled leukocyte scintigraphy in IE patients has already been reported. The aim of this study was to compare the respective performance of 18F-FDG PET and leukocyte scintigraphy for the diagnosis of PVE in 39 patients. Methods: 18F-FDG PET and leukocyte scintigraphy were performed on 39 consecutive patients admitted because of clinically suspected PVE and inconclusive echocardiography results. The results of 18F-FDG PET and leukocyte scintigraphy were analyzed separately and retrospectively by experienced physicians masked to the results of the other imaging technique and to patient outcome. The final Duke–Li IE classification was made after a 3-mo follow-up. Results: Of the 39 patients, 14 were classified as having definite IE, 4 as having possible IE, and 21 as not having IE. The average interval between 18F-FDG PET and leukocyte scintigraphy was 7 ± 7 d. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93%, 71%, 68%, 94%, and 80%, respectively, for 18F-FDG PET and 64%, 100%, 100%, 81%, and 86%, respectively, for leukocyte scintigraphy. Discrepancies between the results of 18F-FDG PET and leukocyte scintigraphy occurred in 12 patients (31%). In patients with definite IE, 5 had true-positive 18F-FDG PET results but false-negative leukocyte scintigraphy results. Of these 5 patients, 3 had nonpyogenic microorganism IE (Coxiella or Candida). Of patients for whom endocarditis had been excluded, 6 had true-negative leukocyte scintigraphy results but false-positive 18F-FDG PET results. These 6 patients had been imaged in the first 2 mo after the last cardiac surgery. The last patient with a discrepancy between 18F-FDG PET and leukocyte scintigraphy was classified as having possible endocarditis and had positive 18F-FDG PET results and negative leukocyte scintigraphy results. Conclusion: 18F-FDG PET offers high sensitivity for the detection of active infection in patients with suspected PVE and inconclusive echocardiography results. Leukocyte scintigraphy offers a higher specificity, however, than 18F-FDG PET for diagnosis of IE and should be considered in cases of inconclusive 18F-FDG PET findings or in the first 2 mo after cardiac surgery.

Role of radiolabelled leucocyte scintigraphy in patients with a suspicion of prosthetic valve endocarditis and inconclusive echocardiography

AIMS In patients with a suspicion of prosthetic valve endocarditis (PVE), detection of perivalvular infection can be difficult based only on echocardiography. The aim of this retrospective study was to test the interest of radiolabelled leucocyte scintigraphy (LS) for the detection of perivalvular infection in patients with a suspicion of PVE and inconclusive transoesophageal echocardiography (TEE). METHODS AND RESULTS LS was performed in 42 patients. The results of LS were classified as positive in the cardiac area (intense or mild), or negative. Macroscopical aspects and bacteriology were obtained from patients who underwent cardiac surgery (n = 10). Clinical outcome was collected in patients treated medically (n = 32). Among patients with intense signal with LS who underwent surgery (n = 6), five had an abscess confirmed during intervention and one, post-operatively. Patients with intense accumulation of radiolabelled leucocytes with scintigraphy and treated medically (n = 3) had a poor outcome: death (n = 1); prosthetic valve dehiscence (n = 1); and recurrent endocarditis (n = 1). Among patients with mild activity with LS (n = 5), one patient developed a large prosthetic valve dehiscence during the follow-up. The remaining four patients were treated medically and did not present any recurrent endocarditis after a median follow-up of 14 months. No abscess was detected in patients with negative LS who underwent surgery (n = 4). Among the patients with negative LS treated medically (n = 24), none presented recurrent endocarditis after a mean follow-up of 15 ± 16 months. Patient management was influenced by the results of LS in 12 out of 42 patients (29%). CONCLUSION This study suggests that LS is useful for the identification of perivalvular infection in patients with a suspicion of PVE and inconclusive TEE.

Positron emission tomography and computed tomography angiography for the diagnosis of giant cell arteritis: A real-life prospective study.

AbstractThe use of 18F-fluoro-deoxyglucose positron emission tomography scan (FDG-PET) and computed tomography angiography (CTA) to improve accuracy of diagnosis of giant cell arteritis (GCA) is a very important clinical need. We aimed to compare the diagnostic performance of FDG-PET and CTA in patients with GCA.FDG-PET and CTA were acquired in all consecutive patients suspected for GCA. Results of FDG-PET and CTA were compared with the final diagnosis based on clinical judgment, temporal artery biopsy (TAB) findings, and ACR criteria. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for each method.Twenty-four patients suspected for GCA were included. Fifteen (62.5%) were ultimately diagnosed as having GCA. Among them, all fulfilled ACR criteria and 6 had biopsy-proven GCA. Strong FDG uptake in large vessels was found in 10 patients who all had GCA. Mean maximal standard uptake values (SUVmax) per patient measured at all the arterial territories were of 3.7 (range: 2.8–4.7). FDG uptake was negative in 14 patients including 9 and 5 patients without and with GCA, respectively. Mural thickening suggestive of aortitis or branch vessel arteritis was observed on CTA in 11 patients with and 2 patients without GCA. No mural thickening was observed in 11 patients including 7 patients without and 4 patients with GCA. Overall, sensitivity was 66.7% and 73.3%, specificity was 100% and 84.6%, NPV was 64.3% and 64.6%, and PPV was 100% and 84.6% of FDG-PET and CTA, respectively.Both FDG-PET and CTA have a strong diagnostic yield for the diagnosis of GCA. FDG-PET appeared to have a higher PPV as compared to CTA and may be the preferred noninvasive technique to explore patients with suspected GCA.

Detection of 18fluoride sodium accumulation by positron emission tomography in calcified stenotic aortic valves.

Aortic valve stenosis progression rate is highly variable among patients and to date remains unpredictable. Evaluation of osteoblastic activity inside aortic valves may help identify patients with fast aortic stenosis progression rates and worse prognoses. Fluoride-18 sodium (FNa) is a clinically approved positron emission tomographic (PET) radiotracer with high and rapid bone uptake. The aim of this study was to test whether FNa accumulates in degenerative aortic valves and can be detected with PET imaging. Five patients with severe aortic stenosis and 10 patients free of aortic valvular calcium on computed tomography underwent PET imaging 40 minutes after the injection of 4 MBq/kg of FNa for oncologic or rheumatologic purposes. Maximal standard uptake values (SUVs) were measured retrospectively in aortic valves using PET imaging. Tissue-to-background ratios were calculated for each patient by dividing the maximal SUV measured in aortic valves by the mean SUV of blood. In patients with severe aortic stenosis, an intense accumulation of FNa was detected in aortic valve region on PET imaging, whereas only low activity was found in patients free of valvular calcification (median maximal SUV 2.6 g/ml/kg [interquartile range (IQR) 2.3 to 3.6] vs 2.0 g/ml/kg [IQR 1.7 to 2.2] and median tissue-to-background ratio 2.2 [IQR 2.0 to 2.7] vs 1.5 [IQR 1.5 to 1.7], respectively, p = 0.008 for both). Intraobserver variability for maximal SUV and tissue-to-background ratio in aortic valves was measured at 0.99 and interobserver variability at 0.98 and 0.97, respectively. In conclusion, in this pilot study, FNa accumulated in patients with severe aortic stenosis and could be quantified on PET imaging with good reproducibility. FNa PET imaging represents a promising imaging modality to evaluate osteoblastic activity inside calcified aortic valves.

Detection of Mycotic Aneurysms of Lower Limbs by Whole-Body 18F-FDG-PET

Although they are rare, mycotic aneurysms (MAs) are a potentially severe complication of infective endocarditis (IE) that usually requires a specific therapy. They are most frequently found intracranially, but other locations are possible and are probably underestimated. In addition, as a minor

Characterization of 18F-Fluorodeoxyglucose Uptake Pattern in Noninfected Prosthetic Heart ValvesCLINICAL PERSPECTIVE

Background— 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been recently acknowledged as a diagnostic tool for prosthetic valve endocarditis, but its specificity is limited by uptake on noninfected valves. The objective of this study was to outline the main features of FDG uptake on PET/CT in patients with noninfected prosthetic heart valve (PHV). Methods and Results— Our institution’s PET/CT database was reviewed to identify patients with PHV, excluding those suspected of infection or who had received antibiotic treatment. PET indication, valve location, and type (biological/mechanical) and time from implantation were collected for each patient. Images with and without attenuation correction were considered for interpretation. The pattern of FDG uptake (absent, homogeneous, or heterogeneous) was recorded. Fifty-four PHVs (51 patients) were identified, including 32 biological valves. Indications for PET were oncology (n=26), suspicion of prosthetic valve endocarditis subsequently excluded (n=17), and history of vasculitis (n=11). A periprosthetic FDG uptake was present in 47 (87%) and 30 (56%) PHVs with and without attenuation correction, respectively, and the pattern was homogeneous in all but 4 (7%) and 3 (6%) PHVs, respectively. On quantitative analysis, maximum standardized uptake values was greater in mechanical than in biological valves (4.0 [2.4–8.0] versus 3.3 [2.1–6.1]; P=0.01) and in patients with vasculitis than in those referred for other indications. The uptake intensity did not differ before and 3 months after valve replacement. Conclusions— Noninfected PHVs frequently display homogeneous FDG uptake, which remains steady over time. Caution is, therefore, needed when interpreting FDG PET/CT in suspected prosthetic valve endocarditis, with specific attention to uptake pattern.

Preclinical Validation of 99m Tc-Annexin A5-128 in Experimental Autoimmune Myocarditis and Infective Endocarditis: Comparison with 99m Tc-HYNIC-Annexin A5

Hydrazinonicotinamide-annexin A5 (HYNIC-Anx), a 99m technetium (99mTc)-labeled agent targeting phosphatidylserine, proved to be sensitive for the detection of apoptosis and thrombosis but is no longer available for clinical use. A mutant of human annexin designed for direct 99mTc labeling (referred to as Anx A5-128) showed improved binding affinity to phosphatidylserine and is expected to be used in humans. We compared both radiotracers with regard to pharmacokinetics and diagnostic ability in animal models. Biodistribution studies were performed in normal rats. Radiolabeled Anx A5-128 and HYNIC-Anx were compared in cardiovascular settings involving phosphatidylserine expression: experimental autoimmune myocarditis and infective endocarditis. Initial blood clearance was faster for Anx A5-128 than for HYNIC-Anx, and tissue biodistribution was similar overall for both tracers. The diagnostic sensitivity of Anx A5-128 was excellent and comparable to that of HYNIC-Anx. Anx A5-128 showed biodistribution and diagnostic ability similar to those of the HYNIC-Anx derivative, supporting its translation to clinical use.Hydrazinonicotinamide–annexin A5 (HYNIC-Anx), a 99m technetium (99mTc)-labeled agent targeting phosphatidylserine, proved to be sensitive for the detection of apoptosis and thrombosis but is no longer available for clinical use. A mutant of human annexin designed for direct 99mTc labeling (referred to as Anx A5–128) showed improved binding affinity to phosphatidylserine and is expected to be used in humans. We compared both radiotracers with regard to pharmacokinetics and diagnostic ability in animal models. Biodistribution studies were performed in normal rats. Radiolabeled Anx A5–128 and HYNIC-Anx were compared in cardiovascular settings involving phosphatidylserine expression: experimental autoimmune myocarditis and infective endocarditis. Initial blood clearance was faster for Anx A5–128 than for HYNIC-Anx, and tissue biodistribution was similar overall for both tracers. The diagnostic sensitivity of Anx A5–128 was excellent and comparable to that of HYNIC-Anx. Anx A5–128 showed biodistribution and diagnostic ability similar to those of the HYNIC-Anx derivative, supporting its translation to clinical use.