18F-FDG PET-CT for Early Detection of Vascular Graft Infection: Mid-term Results

ABSTRACT: Infection of prosthetic vascular grafts is a rare but severe complication in reconstructive vascular surgery. It carries a potential vital risk of bacteremia and sepsis. In spite of improved surgical techniques and use of systemic antibiotics, the prevalence of infection of prosthetic vascular grafts is 1%-6% and is associated with high morbidity and mortality. The early diagnosis of this complication can significantly reduce morbidity and mortality.

VASCULAR DISEASE MANAGEMENT 2012:9(7):E113-E120

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Infection of prosthetic vascular grafts is a rare but severe complication in reconstructive vascular surgery.¹ It carries a potential vital risk of bacteremia and sepsis. Despite improved surgical techniques and use of systemic antibiotics, the prevalence of infection with prosthetic vascular grafts is 1%-6%² and is associated with high morbidity and mortality.³ The early diagnosis of this complication can significantly reduce morbidity and mortality.

When diagnosing graft infections, imaging methods such as ultrasonography, computed tomography, and magnetic resonance imaging are widely available.^4,5 However, morphological imaging techniques lack the capacity to differentiate between active infection and reparative tissue reactions.⁶

Positron emission tomography (PET) using radioactive fluorine-positron emission tomography-fluoro-D-deoxyglucose (18F-FDG-PET) is a widely used and well-established clinical tool for oncology. It provides added diagnostic accuracy in orthopedics for diagnosing suspected chronic osteomyelitis as well as the detection and localization of infectious diseases.^14,15 The added value of hybrid imaging combining PET with CT modalities has been recognized and evaluated for tumor staging of the lung,¹⁶ stomach,¹⁷ intestine,¹⁸ thymus,²⁹ head, and neck.¹⁹ 18F-FDG is a radiotracer of increased intracellular glucose metabolism. It therefore shows higher activity (uptake) in malignant tissue, as well as in infectious and inflammatory processes.

Material and Methods

The protocol of this retrospective study has been submitted to the Ethical Commission of the University Hospital of Geneva (Geneva, Switzerland).

Patients

The study population consisted of 17 consecutive patients with suspected vascular graft infection between June 2006 and July 2010 (15 males; 44-90 years). The time elapsed from the primary surgery was between 4 weeks and 7 years. During the first intervention, patients received different vascular grafts. Of the total number of patients included in the study, 5 underwent surgical repair of the abdominal aorta, 3 underwent procedures for chronic or acute dissected abdominal aorta, and 2 subjects were surgically treated for ruptured aneurysm of the abdominal aorta. One patient required replacement of the ascending thoracic aorta whereas the remaining 11 patients were surgically treated for chronic peripheral artery diseases of the lower extremities (Table 1). Nine out of the 17 patients received Dacron prostheses: 4 in the abdominal aorta, 1 in the ascending aorta, and 4 in the lower extremities. Two patients had xenografts in the abdominal aorta; 2 were treated with homografts in the lower extremities; and 4 with polytetrafluoroethylene (PTFE) prosthetic grafts. The decision for the prosthesis was made according to the surgical indication.

All 17 patients underwent complete staging examinations (physical, blood and wound cultures, diagnostic CT of the abdomen and lower extremities). In cases manifesting fluid collection (liquid vs hematoma vs abscess) around the prosthesis as revealed by CT, whole-body 18F-FDG PET-CT was performed.

In all patients, graft infections were suspected on the basis of symptoms (local pain, macroscopically detected local inflammatory signs), pathological changes around the wound, and fever. The laboratory parameters included white blood cells (WBCs), C-reactive protein (CRP), and blood cultures (Table 2).

Blood analyses showed increased infection parameters such as WBCs >10 g/L in 10 patients and CRP >50 mg/L in 15 patients. Four patients showed positive blood cultures. Blood cultures were done only in patients with temperatures >38°C at the time of hospital admission without the benefit of antibiotic treatment. Accordingly, this was manifested in 5 cases.

The time interval after implantation of the first graft was between 4 weeks and 7 years until the first sign warranted suspicion of infection and re-hospitalization. There is usually ≥4 weeks postoperative delay for PET imaging to avoid false-positive imaging results due to postoperative inflammation.

18F-FDG PET-CT

Imaging
All patients underwent the same standard imaging protocol for PET-CT. Briefly, patients had to fast for 6 H before intravenous injection of 7.5 MBq/kg of 18F-FDG. After ≈45-60 min, patients were positioned supine on the scanner table with their arms above their head. Acquisition time for each bed position was dependent upon weight: 1 min/position in patients with weights >50 kg but <75 kg and 4 min/position in patients with weights >75 kg but <100 kg. Patients underwent whole body examinations through multiple bed positions from the base of the skull to the mid-thigh, extending to the lower extremities in patients with peripheral grafts. PET-CT imaging studies were acquired on a hybrid PET-CT system (Biograph Sensation 16, Siemens/CTI) with an axial PET field of view of 16.2 cm and a helical multidetector CT scanner. PET-CT acquisition was done clinically down to the toes in the case of the lower extremity. CT imaging was performed during shallow breathing.

Intravenous contrast medium was not routinely applied. CT imaging was carried out at 120 kV, 140 mA, and 0.5s per rotation. The CT image was used for attenuated correction of emission data and for image co-registration, which was followed by the PET emission study. After scatter correction, PET images were reconstructed using an iterative algorithm (ordered subset maximization expectation: 2 iterations, 8 subsets). The spatial resolution of the PET images were 5.9 mm transaxially and 5.5 mm axially, respectively, at 1 cm off the center of the gantry. Standard publication NU 2 (NEMA Standard, 2001) showed this specification according to the methodology of the standards and guideline publications of the National Electrical Manufacturers Association (NEMA).

Image analyses
A multidisciplinary team (vascular surgeon, specialist infection physician, nuclear medicine physician, and radiologist) interpreted the PET-CT images using standard clinical interpretations. All areas with increased FDG uptake were interpreted visually on PET, CT, and co-registered PET/CT scans. PET/CT data were displayed with FDG uptake as color overlay on the CT images. In addition, the mean and maximum standardized uptake values (SUV) were measured in each area with visually detectable increased uptake. The maximum standardized uptake value (SUVmax) was defined as the maximum concentration of 18F-FDG divided by the injected dose, corrected for the body weight of the patient, (ie, SUV max = maximum activity concentration/injected dose/body weight).

Accurate PET/CT localization of 18F-FDG uptake in surrounding tissues and vascular graft was registered. Increased 18F-FDG uptake in the area of the vascular graft with intensity higher than the surrounding tissues was considered to be an infectious event.

Cases without increased 18F-FDG uptake or showing only linear uptake of low or moderate intensity around the vascular graft area were defined to be negative for an infectious process. In all cases, the final diagnosis for vascular graft or soft-tissue infections was confirmed by histopathological and microbiological findings obtained during redo-surgery.

Results

CT imaging results from 17 patients with suspected graft infection showed collections (liquid, hematoma) around the prosthesis. Thus, all patients underwent 18F-FDG PET-CT imaging.

In 14 of 17 cases, a positive interpretation for an infected vascular graft was obtained as a result of increased 18F-FDG uptake. The remaining 3 subjects exhibited a negative interpretation for graft infection. In these patients, the mean values of SUV ranged between 2.1 and 10.2, and those of SUVmax between 3.5 and 13.5. In these 3 cases, we discovered an abnormal increase in 18F-FDG uptake outside the graft area but obtained a negative interpretation for vascular graft infection. One of the patients showed abnormal increased uptake in the soft tissue around the abdominal aneurysm sack that we confirmed by drainage but the infection did not involve the aortic xenograft (Figure 1). We diagnosed the patient with an abdominal abscess. The second patient with increased 18F-FDG uptake had an abdominal wound infection (Figure 2). The third patient suffered from abdominal pain and fever due to pneumonia. PET-CT imaging showed no evidence of graft infection.

The 18F-FDG PET-CT confirmed the sites of 18F-FDG uptake in the vascular graft in 14 of 17 patients. Positive graft infection was identified by PET/CT in 14 patients (Figure 3). We performed redo-surgery to replace the infected vascular graft by a new in situ prosthesis (mainly homograft or an extra anatomic bypass graft [synthetic prosthesis]). We found smelly yellow/bloody collection around the prosthesis with infiltration into the environment.

Microbiological and histological (pathological) confirmations of infection of the vascular graft were obtained in 12 of 14 cases, with two false-positive results (Table 2). 

All patients were put on antibiotic therapy before and after the second procedure. One patient required abdominal wound debridement for a deep wound infection. The 18F-FDG PET-CT presented in the study showed a sensitivity of 100%, specificity of 71.4%, positive predictive value of 85%, and negative predictive value of 100% for the detection of vascular graft infection.

Discussion

Vascular graft infection is a serious complication of vascular surgery that can result in high morbidity and mortality.^20,21

Malone et al (1975) described the susceptibility of vascular grafts to bacterial infection in dogs with prosthetic graft replacement of the infrarenal abdominal aorta. A single intravenous infusion of Staphylococcus aureus was given postoperatively. The liability and sensitivity of the prosthetic graft to infection by bacteremic inoculation was 100% up to 1 month after graft implantation, and all grafts were infected.²²

Early accurate diagnosis can change the course of the treatment and outcome. FDG-PET is a new, promising method for detecting infections, especially if the signs and symptoms of infections are not very clear. The combination of symptoms and adequate imaging procedure is indispensable for making the appropriate diagnosis and treatment plan. Traditionally, CT was the method of choice for the diagnosis of graft infection; persistent opacity and perigraft soft-tissue indicated graft infection. The sensitivity of CT can reach >90%, but the specificity is impaired by the presence of extragraft collections.³⁰

In CT, changes in soft-tissue density can also be compatible with postoperative fluid, hematoma, regeneration tissue, or infection. Jorgenson et al (1992) concluded that perigraft (para-prosthetic) fluid collections may be a normal phenomenon during the early postoperative period in patients undergoing abdominal aortic aneurysm surgery.²³ The sensitivity of CT is high, but its specificity is dependent upon extragraft infection areas.^5,25 In the 1990s, 67-gallium (Ga) scintigraphy was evaluated for the detection of vascular graft infection. Johnson et al confirmed that the sensitivity between CT (100%) and 67-Ga imaging was not significantly different. Thus, CT was recommended as the initial examination of choice when graft infection is suspected, though 67-Ga scintigraphy can be a complimentary test, adding specificity for a more accurate diagnosis.²⁴ The sensitivity of radiolabelled WBC scintigraphy for detecting infected vascular prostheses has been described, but false-positive results are common in the early postoperative period, and the method can be useful only for long-term follow-up.²⁶ 18F-FDG PET combined with CT is useful for evaluating patients with suspected aortic (abdominal and thoracic) graft infection. Only a few studies showed a high sensitivity and specificity of PET-CT. When focal uptake was set as the positive criterion in 18F-FDG, the specificity and positive value of PET for the diagnosis of graft infection increased significantly to 95%.²⁸ The efficacy of 18F-FDG PET-CT is higher to that of CT in the diagnostic assessment of patients with suspected aortic graft infection.⁶

No absolute cutoff value can be given because the mean and maximum SUV values of the infected regions can vary significantly. Additionally, the suspicion of infection is mainly dependent upon the shape and localization of areas with increased FDG uptake.

Conventional imaging using 111-indium or technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO)-labeled autologous WBCs represent functional imaging methods with distinct specificity.^7-9 The limitations of these methods were imposed by low labeling efficacy and poor imaging quality. More recently, 18F-FDG PET-CT has been used in the context of vascular graft infections^10,11 and presents a highly sensitive, high-resolution imaging technique that combines anatomical with functional information with lower specificity than that of in vitro-labeled WBCs. There have been attempts to develop an infection-specific, positron-emitting tracer with in vitro-labeled 18F-FDG WBCs, but these methods are not yet available for routine clinical use.¹² The goal of the present study was to evaluate the utility of 18F-FDG PET-CT and compare it with conventional CT for suspected infection of abdominal and peripheral vascular grafts.

The sensitivity of 18F-FDG PET-CT investigated in the present study was also very high. The present study revealed an increase in 18F-FDG uptake in 14 of 17 cases. This led to early diagnosis and reoperation, which prevented the risk of sepsis and increased morbidity and mortality. Three patients were considered not to have positive signs of graft infection and underwent medical treatment.

Based on our experience, increased postoperative FDG uptake progressively decreases after surgery and reaches close to normal values ≈4 weeks after surgery. Because the 18F-FDG uptake depends on the metabolic activity of the wound phase and his cells, the extent of uptake is proportional to the number of cells and their proliferative activity in the operative area. At the beginning of the wound healing the number of the activated macrophages and neutrophils is significantly increased in inflammatory tissue, which uses glucose as an energy source for chemotaxis and phagocytosis, and fibroblasts use glucose for proliferation and granulation. At the end of the proliferation phase 3 to 30 days postoperatively the reparative cells are decreasing significantly and also 18F-FDG uptake.³²

When FDG-PET results show positive uptake after this period, infection of vascular prostheses should be considered. False-positive FDG-PET results can be caused by: chronic polyarthritis; venous thrombosis; and sterile inflammation or vasculitis that can result in an abnormal uptake of FDG and appear as positive FDG-PET findings mimicking local infections.²⁷ Wasselius et al³¹ stated that chronic inflammation in synthetic graft material activated by macrophages can provoke increasing 18-FDG uptake. Therefore false-positive results for graft infection (even a long time after surgery) are possible.

In the case of prosthetic vascular graft infection or infection of endoprosthesis, treatment consists of surgical intervention such as replacement of the infected grafts by allo-, auto-, and synthetic grafts for extra anatomic bypass prostheses (depending on availability). At the University Hospital of Geneva, synthetic vascular prostheses (eg, Milicknit, Intervasculaire, Shelhigh, PTFE, Distaflow, Goretex), as well as auto- and homografts are used. The choice of graft materials depends not only on the degree of vascular disease but also on the anatomical localization of the vessels, comorbidity, and general condition of patients.

Conclusion

With greater availability of hybrid PET/CT imaging and its wider application in clinical practice, FDG-PET could be a valuable complement to conventional CT for the detection of postoperative vascular graft infections. Mid-term results of the present study showed a high sensitivity of the combined modalities with the added value of PET for better identification of other sources of infection and inflammation that could be the origin of non-specific symptoms.

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From the ¹Service of Cardiovascular Surgery, University Hospital Geneva, CH-1211, and the ²Service of Nuclear Medicine, University Hospital Geneva, CH-1211, Geneva, Switzerland.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The author reports no conflicts of interest regarding the content herein.
Manuscript received February 27, 2012, provisional acceptance given April 3, 2012, final version accepted April 12, 2012.
Address for correspondence: Saziye Karaca, MD, University Hospital of Geneva, Department of Cardiovascular Surgery, Rue Gabrielle-Perret-Gentil 4 - 1211 Genève 14, Switzerland. Email: saziye.karaca@hcuge.ch