Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of 18 F-FDG detected by PET are found in 12% of AAA patients (PET1), who are most often symptomatic and at high rupture risk. Comparing the 18 F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no 18 F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture. Methods: Biopsies of the AAA wall were obtained from patients with no 18 F-FDG uptake (PET0, n 5 10) and from PET1 patients (n 5 8), both at the site positive for uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography. Results: The sites of the aneurysmal wall with a positive 18 F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET1, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET1 patients were characterized by a higher circulating C-reactive protein. Conclusion: Positive 18 F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC in the media and alterations of the expression of genes involved in the remodeling of adventitia and collagen degradation potentially participate in the weakening of the aneurysmal wall preceding rupture.

A neurysms are permanent vascular dilatations that involve the aorta in ≤10% of subjects >65 years of age, with more than half localized in the infrarenal aorta.1,2 Their rupture causes death in ≤90% of cases, 2,3 and according to recent trials, the operative mortality does not exceed 5%. 4 The aneurysm maximal diameter identifies the time point when the risk of rupture exceeds that of repair, hence indicating a preventive intervention in asymptomatic patients. [5][6][7] Research, however, has been driven toward more patient-specific risk assessment because aneurysms above the critical diameter thresholds may never rupture, whereas smaller aneurysms will. 8-10 Clinical Perspective on p 91Rupture occurs when the wall stress exceeds the wall strength. Aortic geometry can be used for finite element simulations (FES) 11,12 providing, among other estimates, wall stress. Before rupture occurs, wall stress is involved in aneurysmal expansion and remodeling; the latter triggers and amplifies numerous biological mechanisms that may result in apposition of an intraluminal thrombus with its own biomechanical 13 and biological characteristics. [14][15][16][17] The biological activity of the aortic wall can be evaluated indirectly through energy consumption using 18 F-fluoro-deoxy-glucose ( 18 F-FDG) as a tracer for positron emission tomographic (PET) imaging. 18 18 F-FDG uptake is not uncommon in aortic aneurysms 19,20 and has been shown to correlate with the amount of inflammatory cells, proteolytic activity, and risk of rupture. [21][22][23] Xu et al 24 previously evidenced associations among biological activity, wall stress estimates, and rupture in 3 patients with aortic aneurysms. The actual relationship between biomechanical parameters and biological activity, however, has never been studied in large series.Our study was designed to assess the relationship and the independent determinants between biomechanical estimates of wall stress and 18 F-FDG uptake in unruptured aortic aneurysms. The mean number of these areas per examination was 1.6 (18 of 11) in thoracic aortic aneurysms versus 0.25 (14 of 57) in abdominal aortic aneurysms, whereas the mean number of increased uptake areas colocalizing with highest wall stress and stress/strength index areas was 0.55 (6 of 11) and 0.02 (1 of 57), respectively. Quantitatively, 18 F-FDG positron emission tomographic uptake correlated positively with both wall stress and stress/strength index (P<0.05). Background-The18 F-FDG uptake was particularly high in subjects with personal history of angina pectoris and familial aneurysm. Conclusions-Increased Methods Study PatientsThis study is part of a larger trial aiming to determine the role of 18 F-FDG PET in aortic aneurysm rupture risk assessment as approved by the institutional review board. 25 It included 53 patients (45 men) with aortic aneurysm who underwent ≥1 whole-body 18 F-FDG PET examination using contrast-enhanced computed tomography (CT) for attenuation correction in a single center within a 5-year period. All pat...

Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in aging populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is observed in the wall of 12% of AAA (A+), with most of them being symptomatic. We previously showed that the metabolically active areas displayed adventitial inflammation, medial degeneration and molecular alterations prefacing wall rupture. The aim of this study was to identify new factors predictive of rupture. Transcriptomic analyses were performed in the media and adventitia layers from three types of samples: AAA without FDG uptake (A0) and with FDG uptake (A+), both at the positive spot (A+ Pos ) and at a paired distant negative site (A+ Neg ) of the same aneurysm. Follow-up studies included reverse-transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA). A large number of genes, including matrix metalloproteinases, collagens and cytokines as well as genes involved in osteochondral development, were differentially expressed in the A+ Pos compared with A+ Neg . Moreover, a series of genes (notably CCL18) was differentially expressed both in the A+ Neg and A+ Pos compared with the A0. A significant increase of CCL18 was also found at the protein level in the aortic wall and in peripheral blood of A+ patients compared with A0. In conclusion, new factors, including CCL18, involved in the progression of AAA and, potentially, in their rupture were identified by a genome-wide analysis of PET-positive and -negative human aortic tissue samples. Further work is needed to study their role in AAA destabilization and weakening.

Background18F–FDG PET/CT has been proposed in the evaluation of the disease activity in rheumatoid arthritis (RA). The goals of this study were to evaluate the reproducibility of the technique, to compare metabolic parameters to clinical, biological and ultrasonographic parameters before and after treatment and to evaluate whether the early metabolic response was related to the outcome. 18F- FDG PET/CT of the hands, wrists and knees was obtained in 15 patients with anti-TNFα refractory RA, at baseline and 16 weeks after treatment with rituximab. The number of PET-positive joints (PET+ joints), the cumulative standard uptake value (cSUV) and the composite index (CI) were defined. The composite clinical index DAS28, CRP serum levels and the number of joints positive at ultrasonography (US+ joints) and the cumulative synovial thickness (CST) were also assessed at baseline and week 24.ResultsHigh interobserver agreement was observed, both at baseline and after treatment. The number of PET+ joints was not correlated with the number of joints tender or swollen. The 3 metabolic parameters were strongly correlated with US, CRP and DAS28 at baseline and with US and CRP (CSUV, CI) at week 16, but no longer with the DAS28 index. The metabolic response based on the change in the visual PET/CT joint analysis predicted the outcome with a high negative predictive value of 91%, with a 91% specificity, and an 86% accuracy.ConclusionsThese preliminary data suggest that 18F- FDG PET/CT is a reproducible and accurate tool for evaluating disease activity in refractory rheumatoid arthritis and its non-response to rituximab. The correlation obtained with US joint assessment gives relevance to objective diseased joints through imaging techniques.