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‡ Baolei Guo and Can Chen contributed equally to this work and are joint first authors.
Affiliations
Department of Vascular Surgery, Zhongshan Hospital, Institute of Vascular Surgery, Fudan University, Shanghai, ChinaNational Clinical Research Center for Interventional Medicine, Shanghai, China
Department of Vascular Surgery, Zhongshan Hospital, Institute of Vascular Surgery, Fudan University, Shanghai, ChinaNational Clinical Research Center for Interventional Medicine, Shanghai, China
Department of Vascular Surgery, Zhongshan Hospital, Institute of Vascular Surgery, Fudan University, Shanghai, ChinaNational Clinical Research Center for Interventional Medicine, Shanghai, China
Previous studies on the relationship between positron emission tomography (PET) images and abdominal aortic aneurysm (AAA) progression have shown contradictory results, and the objective of this study was to systematically review the role of PET in predicting AAA prognosis.
Data Sources
PubMed, Embase, and Web of Science were searched for studies evaluating the correlation between PET imaging results and AAA growth, repair, or rupture.
Review Methods
Two authors independently performed the study search, data extraction, and quality assessment following a standard method.
Results
Of the 11 studies included in this review, nine used 18F-fluorodeoxyglucose (18F-FDG) PET and computed tomography (CT) imaging, whereas the remaining two used 18F-sodium fluoride (18F-NaF) PET/CT and 18F-FDG PET/magnetic resonance imaging (MRI). Findings from the 18F-FDG PET/CT studies were contradictory. Six studies found no significant association or correlation, and two studies found a significant negative correlation between 18F-FDG uptake and AAA expansion. Additionally, one study found that the 18F-FDG uptake was statistically positively related to the expansion rate in a specific AAA subgroup whose AAAs expanded significantly. Two studies suggested that increased 18F-FDG uptake was significantly associated with AAA repair, while the other studies either found no association between 18F-FDG uptake and AAA rupture or repair or failed to report the occurrence of clinical events. One PET/CT study that used 18F-NaF as a tracer showed that an increased tracer uptake was significantly associated with AAA growth and clinical events. Finally, the 18F-FDG PET/MRI study indicated that 18F-FDG uptake was not significantly correlated with AAA expansion.
Conclusion
A definitive role for 18F-FDG PET imaging for AAA prognosis awaits further investigation, and new PET tracers such as 18F-NaF have the potential to be a promising method for predicting AAA clinical outcomes.
This systematic review summarises the prognostic value of positron emission tomography (PET) with different tracers, including 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF), in abdominal aortic aneurysms (AAA). As current findings on this topic are inconsistent, it is difficult to provide guidance for clinical decision making. Further study should be carried out on how useful PET imaging data are as clinical markers of aneurysm growth and rupture. In addition, more tracers with high sensitivity and specificity are needed, while tracers such as the 18F-NaF uptake may be a promising predictor for the clinical outcomes of AAA patients.
Introduction
Although the prevalence of abdominal aortic aneurysms (AAAs) in subjects over 60 years of age has decreased to 1.2% to 3.3% over the last few decades,
The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial.
AAAs expand progressively with variable rate, and rupture is the most feared complication, with an incidence of approximately 1% – 5% per year in patients with AAA.
Editor’s Choice – European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
Editor’s Choice – European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
The UK Small Aneurysm Trial Participants Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms.
Editor’s Choice – European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial.
Novel molecular and cellular imaging techniques that evaluate the inflammatory progress of AAAs have been developed to predict prognosis and provide predictive markers of clinical progression.
However, none have been used in practice due to a lack of substantial evidence on their effectiveness. Positron emission tomography (PET), an imaging modality targeting molecular elements of the inflammatory process, including focally increased glucose metabolism and arterial wall microcalcification by means of 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF), respectively,
As there is no consensus on the relationship between the PET tracer uptake and AAA expansion or clinical outcomes, a systematic review was conducted to determine the role of PET in predicting the prognosis of AAA.
Materials and Methods
Protocol registration
This study was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA)
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.
It has been registered on PROSPERO under the registration number CRD42020200055.
Search strategy and selection
PubMed, Embase, and Web of Science were searched for articles published up to 26 October 2020. The search strategies consisted of medical subject headings and text words for abdominal aortic aneurysm, PET, computed tomography (CT), and magnetic resonance imaging (MRI). The detailed search strategies are listed in Appendix S1. Additionally, the references of all selected studies were checked to improve the documented detection rate.
Studies that enrolled adult patients with AAAs and analysed PET in conjunction with CT or MRI imaging to evaluate the molecular characteristics of AAA were included. Studies with insufficient data on the relationship between PET imaging findings and AAA expansion, rupture, or repair; studies that included patients with mycotic aneurysms, prior AAA repair, concomitant connective tissue disease, or vasculitis; and case reports, case series, and reviews were excluded. Two investigators (BL.G and C.C.) independently selected the eligible literature, and any conflicts were resolved by a third investigator (DQ.G or WG.F).
Data extraction
Data from eligible studies were independently abstracted by two researchers (BL.G. and C.C.) using a pre-designed data extraction template, and any disagreements were resolved by discussion or assistance provided by DQ.G. or WG.F. The data extraction template included three parts: (1) study characteristics including author(s), year of publication, study design, inclusion and exclusion criteria, sample size; (2) patient characteristics including age, sex, follow up time, PET imaging techniques, method of measuring tracer uptake, and AAA clinical outcome; (3) PET imaging results, patient clinical outcomes, and the relationship between them.
was applied independently by BL.G. and C.C. to assess the risk of bias in the included studies. The tool consists of six domains including study participation, study attrition, prognostic factor measurement, outcome measurement, study confounding and statistical analysis, and risk of bias can be rated as high, moderate, or low. Studies with ≥5 low risk domains and ≥2 high risk domains were judged as having an overall low and high risk of bias, respectively, and the remaining studies were assessed as having an overall moderate risk of bias.
Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies.
The initial search resulted in 361 articles after duplicates were removed, of which 47 were selected for full text review. Ultimately, a total of 11 articles were retained and included in this review.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
The study selection process is presented as a PRISMA flow diagram in Figure 1.
Figure 1Preferred reporting items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram for literature screening for studies on positron emission tomography (PET) images and abdominal aortic aneurysm (AAA) growth, repair or rupture.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
did not clarify its design. Sample sizes ranged from 14 to 151 participants, giving a total sample size of 508 individuals. The proportion of male participants was 91% and the mean or median age ranged from 68 to 78 years. Nine
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
stated that all patients were within the normal range. The applied injection to scan time interval between the 18F-FDG injection and PET image acquisition varied from 60 to 180 minutes among the studies included in this review (five studies
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
used both maximum standard uptake values (SUVmax) and maximum tissue to background ratios (TBRmax) as indices of accumulation and metabolic activity of PET tracers in the aortic wall, and five studies selected SUVmax,
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
did not specify which measurement was used. SUVmax, which is calculated as decay corrected tissue radioactivity divided by body weight and injected dose, is a common and validated measure of tissue radiotracer uptake. rSUV is calculated by dividing the aortic SUVmax by liver SUVmax, while TBRmax is calculated by dividing the aortic SUVmax by the blood pool SUV. SUVmax, rSUV, and TBRmax are all dimensionless units, and a higher value suggests higher metabolic activity. All but one study
came from European countries. Characteristics of the included studies, the AAA patients evaluated, and the imaging techniques used are summarised in Table 1, Table 2, Table 3 and Supplementary Table S1.
Table 1The characteristics of 11 studies on positron emission tomography (PET) images and abdominal aortic aneurysm (AAA) growth, repair or rupture
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
SUVmax = maximum standardised uptake value; TBRmax = maximum target to background ratio; SUVRL = SUV to liver; SUVRV = SUV to venous background; rSUV = aortic SUVmax/liver SUVmax; MDS = most diseased segment; 18F-FDG =18F-fluorodeoxyglucose; NR = not reported; SUVmean = mean standardised uptake value; TBRmean = mean target to background ratio.
∗ Presented as mean ± standard deviation or median (interquartile).
† Prospective cohort study with retrospective growth data
Table 2The characteristics of patients enrolled in the 11 studies on positron emission tomography images and abdominal aortic aneurysm (AAA) progression
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Table 3The characteristics of imaging technique used in the 11 studies on positron emission tomography (PET) images and abdominal aortic aneurysm progression
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
described the relationship between PET/CT imaging results and the occurrence of AAA clinical events including rupture or repair during follow up, and clinical events occurred in all but one study.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Data are presented as mean ± standard deviation, median (range) or median (interquartile range), unless stated otherwise. AAA, abdominal aortic aneurysm; IQR, interquartile range; SUVmax, maximum standardised uptake value; TBRmax, maximum target to background ratio; MDS, most diseased segment; PET (+), positive tracer uptake; PET (−), negative tracer uptake; NR, not report; NA, not applicable; NS, not significant.
∗ Growth rate.
† Spearman rank correlation.
‡ Mann–Whitney test.
§ In case a significant positive correlation was determined on the linear regression of sizes, it was defined as a significant growth of the AAA.
‖ Kaplan–Meier analysis.
¶ Cox regression analysis.
∗∗ Unadjusted linear regression analysis.
†† Adjusted linear regression analysis.
‡‡ Fisher’s exact test.
§§ The definition of significant expansion was not specified in the original study.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
were the first to publish a study concerning the relationship between 18F-FDG uptake and AAA expansion. They recruited 26 non-consecutive AAA patients (mean diameter 63.0 mm) who had undergone CT scans and complementary PET imaging, and PET results of 10 patients revealed an increased 18F-FDG uptake in the aortic wall, which was considered positive. Four of the patients with positive PET images suffered from rapid AAA expansion (>5 mm in 6 months), while two of the 16 negative patients’ AAAs expanded rapidly (p = .16). Only one patient with a positive PET image experienced AAA rupture. The incidence of rupture was similar between subjects in both the positive and negative PET image groups (1/10 vs. 0/16, p = .39). Although a significant difference was seen in the proportion of patients who required urgent surgery between the two groups (5/10 vs. 0/16, p = .018), the authors did not specify the definition of 18F-FDG uptake and if all procedures were performed for ruptured AAAs.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
conducted a pilot study which retrospectively analysed the correlation between increased FDG uptake and AAA growth, comprising 12 asymptomatic and three symptomatic AAA patients. Expanded AAAs were identified in seven patients, of which three were stable (annual expansion rate ≤3 mm), and four were unstable (annual expansion rate >6 mm). The findings revealed no significant correlation between SUVmax and AAA annual expansion rates (Pearson correlation coefficient; p = .15).
also found no significant correlation between FDG uptake (SUVmax) and recent AAA expansion rate (r = .18, p = .60). They prospectively investigated a total of 14 AAA patients who received US scans with subsequent PET/CT within 14 days at intervals of three, six, and 12 months. The AAAs of 10 patients revealed increased FDG uptake (SUVmax > 2.5), and recent annual AAA expansions were observed in seven patients, which were ≤3 mm (three patients), >3 mm and <6 mm (two patients), and >6 mm (two patients).
Based on a large cohort of patients using 18F-FDG PET/CT for oncological evaluation, Lee et al.
analysed the association between FDG uptake and long term growth of aneurysms in patients with a diagnosis of AAA. Eighteen of the 37 patients in their study experienced significant AAA expansion over the follow up period, and the average annual expansion rate was 3.49 ± 2.45 mm. There was no significant difference in 18F-FDG uptake between aneurysms with and without significant expansion (1.55 ± 0.20 vs. 1.57 ± 0.14; p = .56); however, 18F-FDG uptake was positively correlated with AAA expansion rate for the significant growth subgroup (r2 = .260, p = .031). Eleven patients received AAA repair, and patients who underwent intervention had a significantly higher TBRmax value than those who did not (1.76 ± 0.23 vs. 1.54 ± 0.27; p = .023).
50 consecutive patients with small AAAs under surveillance were prospectively enrolled and evaluated at baseline using 18F-FDG PET/CT, of which 40 patients completed a one year follow up. The median annual aneurysm growth was 2.0 mm with a relative growth of 4.4% from baseline. Meanwhile, the median AAA SUVmax and TBRmax was 1.80 and 1.20, respectively. Although the findings revealed a negative correlation between SUVmax and growth during follow up (r = −0.383, p = .015), the correlation between TBRmax and growth rate per year was not significant (r = −.021, p = .889).
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
acquired 18F-FDG PET/CT data from 18 AAA patients that had been referred to their department for elective surgery. Of the 18 enrolled patients, a positive and negative 18F-FDG uptake was respectively found in eight and 10 individuals. Superimposed CT and PET images were classified as positive when a focal or segmental 18F-FDG uptake could be observed. The metabolic activity in the AAA expressed as the rSUV (AAA/liver) was significantly higher in the positive uptake patients than in the negative uptake patients. By retrospectively reviewing the follow up growth data, it was found that in the positive and negative 18F-FDG uptake groups, a respective three and one patients experienced significant expansion. The difference between the two groups was not significant (p = .28). It should be noted that the definition of significant expansion is not formally defined.
recruited 39 AAA patients who received 18F-FDG PET and CT angiograms at baseline and nine months later to associate 18F-FDG SUVmax with aneurysm expansion. Nine patients’ AAA expanded significantly (≥2.5 mm) at the follow up time point. Similar to the study of Kotze et al.,
SUVmax at baseline decreased as the aneurysm size increased (1.80 ± 0.45 vs. 2.21 ± 0.52; p = .040) and a trend towards greater change in SUVmax was seen at nine months (10.40 ± 0.85 vs. −0.06 ± 0.57; p = .070) compared with patients whose aneurysms did not grow. Furthermore, it was found that the change in aneurysm size between baseline and nine months was marginally significantly associated with the baseline SUVmax of the aortic wall (p = .049), and the AAA TBRmax of patients with AAA growth was similar to those whose AAAs did not grow.
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
assessed the relationship between 18F-FDG uptake and clinical events (defined as annual AAA expansion of >1 cm, dissection, rupture, or emergency) in 47 patients with unruptured AAAs. Two of 13 with PET positive (≥1 area with >1 cm of 18F-FDG increased signalling) AAAs and two of 34 with PET negative AAAs were observed to experience rapid aneurysm growth after 30 months of follow up (p = .30).
included 151 patients (135 with tumours) from a PET/CT database of consecutive 18F-FDG PET/CT studies conducted in a three year period for routine indications and follow up data on AAA rupture or repair were available for 101 patients. Patients who completed or did not complete follow up were comparable on any baseline characteristic. Over a median 1.5 year follow up period, 20 patients received repair and 79 patients did not, and the AAA SUVmax values were not significantly different between the intervention and non-intervention groups. Two of four patients with ruptured AAAs exhibited a visible increase in 18F-FDG uptake, while 34 patients without rupture had visibly increased tracer uptake (p = .61). However, it should be noted that confounding radiation and chemotherapy related vascular inflammations and alterations in the metabolic milieu may be found among a majority of the patients in the oncology study, with these being related to the underlying malignancy itself.
was designed to investigate whether 18F-NaF PET/CT could predict aneurysm growth and clinical outcomes of those affected with AAA. This prospective cohort study recruited 72 AAA patients who had undergone US, and 18F-NaF PET/CT and CTA scans, and selected AAA growth and the composite of AAA repair or rupture as clinical endpoints. After a mean 510 day follow up period, the median AAA annual growth rate was 2.20 mm, and baseline AAA 18F-NaF uptake was associated with growth independent of the quantification method. When stratified by tertiles, the median AAA annual expansion rate in the highest and lowest tertile of 18F-NaF uptake were 3.10 mm and 1.24 mm, respectively, and the difference was significant (p = .008). 18F-NaF uptake measured by MDS TBRmax (average TBRmax across three axial slices centred on the region of the aneurysm with the highest tracer activity) led to AAA expansion adjusted by known risk factors (p = .042).
Of the 22 patients who had ruptured AAAs or underwent AAA repair, 19 had elective repair, and three suffered from rupture. 18F-NaF uptake in subjects with clinical events increased significantly compared with those without clinical events (log2 MDS TBRmax 2.20 ± 0.58 vs. 1.87 ± 0.54; p = .023). The doubling of 18F-NaF uptake as measured by MDS more than doubled the likelihood of AAA rupture or repair (hazard ratio: 2.16; 95% CI 1.03 – 4.50; p = .041), and this risk remained after adjusting for other risk factors (hazard ratio: 2.49; 95% CI 1.07 p = 5.78; p = .034). AAA patients in the highest tertile of 18F-NaF uptake had an increased rate of repair or rupture (11/24 vs. 4/24; p = .043) and a decreased time to clinical events (572 days vs. 709 days; p = .043) when compared with those in the lowest tertile over the follow up period.
conducted a recent study on inflammation assessment by performing 18F-FDG PET/MRI on 15 patients with asymptomatic AAAs. The median baseline AAA diameter was 54 mm and median growth rate over the past year was 3 mm. Thirty-six FDG hotspots defined as focally increased FDG signals were detected in aneurysm walls against an intra-arterial background uptake, and sizes larger than 7 mm were observed in the aneurysm wall of 13 patients. Additionally, the number of FDG hotspots correlated with recent AAA growth (r = .62, p = .010). Late gadolinium enhancement (LGE) in the aneurysm wall was seen in eight of 15 patients, and AAAs with LGE had an increased median growth rate compared with those without (7 mm vs. 2 mm; p = .030). Neither SUVmax (r = −0.198, p = .48) nor TBRmax (r = 0.406, p = .13) in the aneurysmal wall was significantly correlated with recent AAA growth. MRI results showed corresponding focal mural morphological changes in the aneurysm of three of 13 subjects (23%) with focal FDG uptake, and one with positive overlap displayed the fastest annual growth rate of 13 mm.
Risk of bias assessment
Table 5 presents the risk of bias of each study. One study
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
were rated as high, and the main risks were biases related to outcome measurement and study confounding.
Table 5Risk of bias assessment of 11 studies on positron emission tomography images and abdominal aortic aneurysm progression using Quality in Prognostic Studies (QUIPS) tool
Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms.
The present systematic review indicates that relationships between tracer (18F-FDG or 18F-NaF) uptake and clinical AAA prognosis are inconsistent in studies using PET/CT. The findings of the 18F-FDG PET/CT studies were contradictory, and more negative than positive findings were reported on the association between 18F-FDG uptake and AAA expansion, rupture, or repair. Additionally, FDG uptake may be correlated positively with AAA growth rate in a specified subgroup with significant aneurysm expansion. The 18F-NaF PET/CT study showed that tracer uptake is positively associated with AAA expansion and clinical events, and the single study that used 18F-FDG combined with PET/MRI suggested that 18F-FDG uptake is not related to aneurysm expansion.
which aimed to explore the role of 18F-FDG PET scans in AAA subjects did not establish a credible quantitative cut off value for predicting AAA growth due to conflicting evidence in the included studies. Another systematic review
that included six studies relating 18F-FDG PET uptake to AAA progression also obtained contradictory findings, showing that SUVmax either had a negative association or correlation with AAA growth or non-statistically significant associations with AAA expansion. The present review added five additional studies
18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
to the previous review. The additional studies compensated for the insufficient data on the association between 18F-FDG uptake and clinical events including rupture or repair. They also indicate 18F-NaF as a promising PET marker to predict AAA prognosis,
The replacement of separate PET and CT or MRI by hybrid PET/CT or PET/MRI technology integrates molecular data from PET with anatomical details from CT or MRI,
in this review used these fusion techniques. PET/MRI outperforms PET/CT in terms of improved tracer detectability, due to the excellent morphological characteristics of MRI, and a better spatial matching between the PET and MRI and allowed the depiction of disease activity at low radiation dose.
also indicated that FDG hotspots in PET imaging rarely corresponded to MRI findings of inflammatory activity, but patients with LGE and FDG hotspots may experience the worst prognosis, probably because PET and MRI provide information related to glycolysis and phagocytosis, respectively.
The pathological processes of aortic aneurysms involve inflammation, extracellular matrix degradation, microcalcification, hypoxia, and neovascularisation.
Coronary plaque morphology and the anti-inflammatory impact of atorvastatin: a multicenter 18f-fluorodeoxyglucose positron emission tomographic/computed tomographic study.
Coronary plaque morphology and the anti-inflammatory impact of atorvastatin: a multicenter 18f-fluorodeoxyglucose positron emission tomographic/computed tomographic study.
inflammation of the aortic wall theoretically can be evaluated by the level of 18F-FDG uptake. However, the binding of 18F-FDG is poorly specific for it can accumulate in all cells that metabolise glucose.
18F-FDG arterial signal is influenced by local hypoxia and uptake by other resident cell types, thus, the active disease may not be reliably detected in diseases that show mild inflammation, such as when there is atherosclerosis or aneurysm formation.
18F-NaF is a promising radiotracer that binds to the hydroxyapatite crystals deposited during microcalcification, and is considered to be able to detect early microcalcification for the identification of necrotic material within the vascular beds that drives further inflammation.
that focused on the predicted value of 18F-NaF PET/CT in future AAA progression, and the findings suggested 18F-NaF uptake has a positive association with AAA expansion or clinical events. One systematic review
on the relationship between carotid plaque PET imaging and cerebral ischaemic disease showed that recent cerebral ischaemia events may be related to an increase in both carotid 18F-FDG and 18F-NaF uptake on PET imaging. Another systematic review
revealed that 18F-FDG PET visualised various inflammatory stages of carotid atherosclerosis evolution and its complications, whereas 18F-NaF PET appeared to reflect more long term outcomes through the demonstration of artery wall microcalcification. In patients receiving dual tracer PET scans, it was found that 18F-NaF PET uptake is likely to be a more sensitive predictor of the evolution of vascular diseases,
The dissimilar findings between the 18F-NaF PET/CT study and 18F-FDG PET/CT studies may be caused by the use of differing tracer types. More specific PET tracers have been shown to be effective in AAA animal models and have been investigated in other cardiovascular diseases.
Target identification for the diagnosis and intervention of vulnerable atherosclerotic plaques beyond (18)F-fluorodeoxyglucose positron emission tomography imaging: promising tracers on the horizon.
These tracers included those that track inflammation, such as 68Ga-DOTA-TATE, 64Cu-DOTA-ECL1i, 68Ga-pentixafor, and 18F nanoparticles; those that track neo-angiogenesis, such as 18F-fluciclatide and 68Ga-NOTA-RGD; and those that target hypoxia, such as 18F-fluoromisonidazole and 18F-HX4. There is hope for the future that these novel PET tracers can be translated into clinical practice.
Alternatively, there is speculation that contradictory features of inflammation might have led to the varying results. Two polarised subtypes of macrophages (M1 and M2) play different roles in inflammation: M1 is generally pro-inflammatory and induces the destruction of tissues, whereas M2 induces the repair and recovery of tissues. Both M1 and M2 macrophages could lead to an increased uptake of tracers in inflammatory tissues. Increased 18F-FDG uptake in aneurysms may suggest the activation of M1 or M2 macrophages, resulting in different outcomes.
In addition, AAA growth is a dynamic process with a specific period of growth and stability and repeating inflammatory damage and repair processes, and is likely to cause cyclic changes in tracer uptake. Although findings from Morel et al.
support the fact that cyclic changes in metabolic activity in AAAs occur during expansion phases, most of the studies in this review only analysed a single time point. Instead of one single measure, metabolic activity may vary with time and changes in SUVmax or TBRmax, which may be a better predictor of AAA progression. When evaluating aortic tracer uptake, comparisons of SUVmax or TBRmax alone between two groups may yield non-significant results, as metabolic activity may remain in the lower range even with increased tracer uptake. An additional point of note is that the multiple inflammatory pathways that are implicated in AAA pathogenesis may account for the contradictory results. Targeting single pathways or cell types might not be effective; something that is supported by the evidence that using only a limited number of drugs with anti-inflammatory properties cannot limit AAA growth.
The 18F-FDG PET imaging protocols used to assess inflammation in atherosclerosis were variable and uncertain. This raises an important question about the source of this poor reproducibility. It is recommended that patients preparing to undergo a PET scan should maintain a pre-scan blood glucose level below 126 mg/dL (7 mmol/L),
Assessment of atherosclerosis in large vessel walls: a comprehensive review of FDG-PET/CT image acquisition protocols and methods for uptake quantification.
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