The value of 18F-FDG-PET-CT in the management of infective native aortic aneurysms

Abstract

Objective

The objective of this systematic literature review was to explore the value of positron emission tomography combined with low-dose computed tomography (18F-FDG-PET-CT) in the diagnostics of infective native aortic aneurysm (INAA).

Methods

A systematic literature review was performed using the search terms mycotic- and infected aortic aneurysms in Medline and Sciencedirect databases, published between 1 January 2000 and 1 January 2020. Using the PRISMA statement, articles were scrutinized according to a predefined protocol including: timing of 18F-FDG-PET-CT examination, the maximum standardized uptake value (SUVmax), additional findings on examination, and findings on repeated scanning of 18F-FDG-PET-CT.

Results

Four studies were included in the analysis, comprising a total of 11 patients. Two studies were single case reports, and two were small case series, all were graded to be of low quality with high risk of bias. All patients were examined with a preoperative 18F-FDG-PET-CT, and 10 (91%) had increased 18F-FDG uptakes. The median SUVmax value was 6.53, range 4.46–9.23. The mean duration of antibiotic therapy prior to 18F-FDG-PET-CT was not known. Two patients were examined with repeated 18F-FDG-PET-CT examinations after treatment, where a decrease in SUVmax values could be demonstrated after successful treatment.

Conclusion

The literature on 18F-FDF-PET/CT for diagnosing infective native aortic aneurysms is scarce. However, there might be a role for 18F-FDF-PET/CT in the management of the disease, in particular for patients with clinical suspicion of INAA without convincing findings on CT. SUVmax values ranging from 4.5 to 6.5 could be guiding and suggestive of metabolic activity in agreement of INAA. However, further conclusions on its usefulness, robustness and specific SUVmax values are premature, and a definitive cut-off value is probably not attainable.

Keywords

Infective native aortic aneurysm 18F-FDG-PET-CT positron emission tomography PET-CT mycotic aneurysm

Introduction

Infective native aortic aneurysm (INAA), also known as mycotic aortic aneurysm, is caused by an infection in the aortic wall, which degrades its integrity, forming an aneurysm with high risk of rupture.^1,2 There is no pathognomonic symptom or radiologic sign of INAA; instead, the diagnosis is based on a combination of clinical picture, laboratory tests and radiological findings on computed tomography (CT).^1,3 The European Society for Vascular Surgery (ESVS) guidelines on management of abdominal aortic aneurysms report that the following findings on CT are suggestive for INAA: saccular aneurysm, multi-lobular aneurysm, eccentric aneurysm, peri-aortic gas, soft tissue mass, rapid expansion (days) and/or rupture, atypical location (e.g. para-visceral) or multiple aneurysms in different aortic locations.^3–7 18F-labeled fluoro-2-deoxyglucose tracer with positron emission tomography combined with computed tomography (18F-FDG-PET/CT) is not mentioned in these guidelines.

18F-FDG-PET/CT imaging demonstrates uptake of radioactive-labeled glucose in cells or tissue with enhanced glucose metabolism, as in inflammatory cells or microorganisms, referring to inflammation or infection.⁸ This diagnostic method is combined with CT for anatomical correlation.⁹ The main objective interpretation criterion for infection is the calculated maximum standardized uptake value (SUVmax), but diagnostic values for INAA remain unknown.^8,10,11

The recently published guidelines from the ESVS on the management of graft and endograft infections (VGEI) state that 18F-FDG-PET/CT has an established role in the assessment of suspected VGEI. The guidelines recommend CT as first-line diagnostic modality, but in situations of clinical suspicion of vascular graft/endograft infection without convincing findings on CT, the use of 18F-FDG-PET/CT is recommended as an additional imaging modality to improve diagnostic accuracy.¹⁰

Thus, there might be a potential value and role of 18F-FDG-PET-CT in the management of INAAs, however yet undefined. The objective of this study was to explore the value of 18F-FDG-PET-CT in the diagnostic work-up for patients with INAA, through a systematic scrutiny of the literature.

Methods

A systematic literature search was performed according to the PRISMA statement in Medline and Sciencedirect databases to identify all publications on mycotic aortic aneurysms in the English language between 1 January 2000 and 1 January 2020.¹² Search terms included mycotic aortic aneurysm and infected aortic aneurysm. The term infective native aortic aneurysm was introduced in March 2020;¹ hence, it was not used in the literature search. Reference lists were also scrutinized to identify additional papers.

The methodological quality of papers was individually assessed using Methodological Index for Non-Randomized Studies (MINORS) score.¹³ The MINORS-score is a sum of separate item scores (from zero to two) with a global maximum of 24 for comparative studies and 16 for non-comparative studies, and each article is given a grade according to the final score; Low <12; medium 12–15, and high = 16. Quality assessment was not used as exclusion criteria.

Data were extracted for each paper according to a predefined protocol regarding: full clinical picture (including symptoms, laboratory tests, concurrent infection), medical history, bacteriology, other radiology findings and intra-operative findings in order to confirm the diagnosis. Furthermore, specifically, the following data were noted: aortic location of aneurysms, culture results, level of C-reactive protein (CRP), timing of 18 F-FDG-PET/CT, SUVmax value on 18 F-FDG-PET/CT, and additional findings on timing of 18 F-FDG-PET/CT, repeated scanning of 18 F-FDG-PET/CT and findings.

The following definition was used for INAA; INAA is an aortic aneurysm, which is caused by microbial infection of the aortic wall. The infection causes degradation of the vessel wall, resulting in formation of a localized aneurysm. The microbial infection is predominantly bacterial, but may also be fungal, or possibly viral in patients with advanced HIV infection. An aorta with extensive atherosclerosis, or a preexisting aneurysm, is susceptible to such infection. The common definition of degenerative aortic aneurysm based on diameter is not applicable to these aneurysms because the morphology is predominantly saccular, multilobular or amorphous. Hence, other infective states involving the aorta such as aortic graft infections and secondary aorto-enteric/bronchial fistulas are not part of this disease entity.^1,3 Studies that did not have a diagnostic work-up in line with the aforementioned were excluded, as were studies that did not provide specified SUVmax-values.

A vascular graft or endograft infection was defined according to the MAGIC criteria.^6,14 Postoperative infection-related complications (IRCs) were defined as postoperative development of persistent or recurrent sepsis, vascular graft or endograft infection, recurrent infective aortic aneurysm or development of aorto-enteric/bronchial fistula.¹

The primary data search was performed by one author (DH) in collaboration with university librarians, and the results were double-checked by the other authors (IH, PGdS, KS). Data extraction was performed by (DH, KS). The quality assessment of the included articles was performed independently by two authors (PGdS, IH), and these results were in turn scrutinized by two authors (DH, KS). In case of disagreement between investigators, this was resolved by discussion until consensus was achieved (all authors).

Statistical analysis

Data were analyzed using a statistical software package (SPSS 22, IBM Corporation, Armonk, NY, USA). Data were assessed for normality with histograms. Continuous data were expressed as median (range), or mean (standard deviation, SD) and categorical variables as proportions (%).

Further statistical analyses were not performed due to the limited findings of the literature search, and meta-analyses were not possible.

Results

Study and patient characteristics

Four studies were identified containing a total of 11 patients, see Figure 1 and Table 1.^15–18 Two studies were case reports containing one patient each, and two were retrospective case series, see Table 1. All studies graded low in methodological quality with high risk of bias, see Table 1.

Figure 1.

PRISMA flow diagram.

Table 1.

List of included papers with respective grade of quality.

Study	Country	Study design	Time period	No of patients	Follow-up (median in months)	Aim of study	MINORS-Score
Choi et al.¹⁵	Korea	Case report	2007	1	12	Report results of experience	8
Murakami et al.¹⁶	Japan	S-c. Retro.	2007–2012	5	32	Report results of experience	9
Tsang et al.¹⁷	China	S-c. Retro.	2012–2016	4	18	Report results of experience	9
Ribeiro et al.¹⁸	UK	Case report	2018	1	1.5	Report results of experience	6

No: number; MINORS: Methodological Index for Non-randomized Studies; Retro: retrospective study; S-c: single center.

Mean age was 73 years (range 60–85), and gender distribution was male n = 10 (91%) and female n = 1 (9%). Median follow-up time was 12 months (range 10–32). All patients were diagnosed with INAA through a combination of clinical picture, laboratory results including culture results, as well as radiology and 18F-FDG-PET-CT.

18F-FDG-PET-CT

All patients had a preoperative 18F-FDG-PET-CT, although three patients were treated conservatively without surgery. The median SUVmax value was 6.40 (range 4.46–9.23). For details on 18F-FDG-PET-CT findings and SUVmax values, see Table 2.

Table 2.

Results and findings of 18 F-FDG-PET-CT in infective native aortic aneurysms, INAA.

Study and patients	Aortic location of aneurysm	Culture results	Level of CRP (mg/dL)	Finding on CT-scan	Timing of PET-CT	SUVmax	Additional findings	Repeated PET-CT
Choi et al.¹⁵
Patient 1	Infrarenal	Slamonella enteriditis	Elevated	Saccular aneurysm	Prior to antibiotic therapy	6.53	–	Yes, after 1 month showing decrease in F-18 FDG uptake, SUVmax 3.61.
Murakami et al.¹⁶								Findings were in correlation with clinical status as well as normalization of inflammatory. After 1 year there was no FDG uptake.
Patient 2	Abdominal	Negative	2.6	Unclear	Preoperative	9.23	In this case series with comparison
Patient 3	Abdominal	Listeria monocytogenes	7.11	Unclear	Preoperative	7.18	with AAA, it was found that AAA had a SUVmax <2.59 (six patients)	–
Patient 4	Abdominal	Negative	0.03	Unclear	Preoperative	6.23
Patient 5	Abdominal	Salmonella sp.	12.51	Unclear	Preoperative	5.49
Patient 6	Thoracic	Negative	3.66	Unclear	Preoperative	4.46
Tsang et al.¹⁷
Patient 7	Aortic arch	MRSA	2.34	Not performed	Preoperative	6.4	–	Post-TEVAR and antibiotic therapy demonstrated decrease in FDG-uptake with SUVmax values of 2.9
Patient 8	Abdominal	MRSA	17	Not performed	Preoperative	9.2
Patient 9	Aorto-iliac	Salmonella sp.	2.47	No infection	Preoperative	No uptake
Patient 10	Aortic arch	Negative	6.08	Not performed	Preoperative	6.3

Ribeiro et al.¹⁸
Patient 11	Thoracic	Mycobacterium	9.0	Saccular aneurysm	Preoperative	9.0	–	–

AAA: abdominal aortic aneurysm without infection; CRP: C-reactive protein; mg/dL: milligram per litre; CT: computed tomography; PET-CT: ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography combined with CT; MRSA: methicillin-resistant staphylococcus aureus; SUVmax: standardized uptake value; TEVAR: thoracic endovascular aortic repair.

Time of antibiotic therapy prior to the first 18 F-FDG-PET-CT examination was not specified in any of the included studies.

Two patients were examined postoperatively with 18 F-FDG-PET-CT. The first patient demonstrated a SUVmax of 6.53, after one month of antibiotic therapy SUVmax had decreased to 3.61, and after one year, there was no uptake at all. The second patient had a preoperative SUVmax of 6.4 and was then treated with thoracic aortic endovascular repair and antibiotic therapy for four months with a new 18 F-FDG-PET-CT demonstrating decrease in uptake with SUVmax 2.9, and a later scan SUVmax 1.4. After nine months, the patient died because of heart arrest.

In the study by Murakami et al., the five INAA patients’ findings on 18 F-FDG-PET-CT were compared with six patients with suspected INAA, but who were later diagnosed as degenerative abdominal aortic aneurysms (AAA). The five patients with INAA had a SUVmax > 4.46, and those with AAA <2.59. A correlation between INAA and SUVmax value was observed, INAAs had a mean 6.5 ± 1.8 vs. AAA 1.9 ± 0.5, p < 0.001.¹⁶

Discussion

The current systematic literature review clearly demonstrates the scarcity of literature on 18F-FDG-PET/CT in the management of INAAs. However small, this study identifies potential benefits and a possible role of 18F-FDG-PET/CT when making the diagnosis and evaluating the effectiveness of treatment of INAA.

As successful management of INAAs relies upon making a rapid diagnosis, immediate initiation of antibiotic treatment, and hereafter surgery and long-term antibiotic therapy.³ Diagnostic difficulties might result in delayed or inappropriate management, which could have dire consequences in the individual case. According to the newly published diagnostic criteria by Sörelius et al., cases with two out of three diagnostic criteria are classified as probable INAA if no other differential diagnosis is more likely.¹ For this subgroup of patients, who lack either positive symptoms, positive laboratory findings or typical findings on CT, there is a potential role and value of performing a 18F-FDG-PET/CT. Increased metabolic activity is characteristic for native aortic infection as well as for non-infectious inflammatory aortitis.¹⁹ If bacterial presence cannot be determined, or the findings on CT are atypical for INAA, SUVmax values could be measured to help differentiate between the two. Specific SUVmax cut-off values to make the diagnosis of INAA are lacking; nevertheless, the median 6.40 (range 4.46–9.23) based on the current study could be guiding. Recently published article by Husmann et al. containing 13 patients demonstrates a median SUVmax of 6.6 (interquartile range 4.7–21.8) for INAA patients.²⁰ The article was not included due to publication date outside the frame of the current study but supports the SUVmax value finding of 4.5–6.4 as suggestive for INAA, Husmann et al. state that 18F-FDG-PET/CT demonstrates excellent sensitivity (100%), but specificity was hampered due to false-positive findings, which underscores the importance that the diagnosis of INAA is not made on radiological findings alone. However, the limited access to 18F-FDG-PET/CT might limit the use in the acute setting of INAA. To resolve this issue and to confirm the possible value of 18F-FDG-PET/CT in the management of INAA, a prospective multicentre study would be needed with a standardized examination protocol and survey parameters, preferably according to the European Association of Nuclear Medicine and Society of Nuclear Medicine and Molecular Imaging.^8,9

Repeated scanning after treatment appears beneficial for early detection of postoperative VGEI.^15,17,21 In some cases, there is a reported lack of correlation between inflammatory markers such as CRP and SUVmax.^20,22,23 Postoperative inflammation might result in increased uptake in the perigraft area some months after surgery; therefore, timing of the 18 F-FDG-PET/CT is crucial and interpretation of the SUVmax should be performed with caution. Based on small number of patients, the ESVS suggests a SUVmax > 8 in the perigraft area as the cut-off value for distinguishing infected grafts from non-infected ones.⁶ However, other authors have suggested lower values ranging from 3.8 to 6.3 that correlate favorably with our results.^22,23 Effective antimicrobial therapy can be seen over series of scans as diminished SUVmax values up to no uptake at all.^15,17

As all the included studies in the present systematic review were graded as low in quality with high risk of bias, containing only 11 patients, the results should be interpreted with uttermost care. Owing to the rarity and heterogeneity of the disease, INAAs are extremely difficult and demanding to study. Until large, prospective multicentre studies, or preferably an randomized controlled trial (RCT) can provide data for robust statistics to support recommendations on its management, scrutinizing the existing literature and performing research will remain a fundamental way forward in mapping out the optimal management for this disease.^1,2,4,24 The current study indicates that the number of patients needed for recruitment for an RCT would not be impossible, even though the disease is rare.

Conclusion

The literature on 18F-FDF-PET/CT for diagnosing INAAs is scarce; however, there might be a role for it in the diagnosis and management of the disease. Patients with clinical suspicion of INAA without convincing findings on CT may benefit from the 18F-FDF-PET/CT as a diagnostic tool and in monitoring the effectiveness of treatment. Further conclusions on its usefulness and robustness are premature.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Karl Sörelius

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