Can Biomarkers and PET Imaging Predict Abdominal Aortic Aneurysm Growth Rate?

Background: Abdominal aortic aneurysm (AAA) is a life-threatening condition due to the risk of aneurysm growth and rupture. Biomarkers linked to AAA pathogenesis are attractive candidates for AAA diagnosis and prognosis. The aim of this study was to assess circulating biomarkers levels relationship with PET imaging positivity and their predictive value in AAA growth rate. Methods: A total of 164 patients with AAA had whole body [18F]FDG PET/CT examination and blood drawn for biomarkers analysis at inclusion. Of these, 121 patients had at least one follow-up imaging assessment for AAA progression. Median (quartiles) imaging follow-up period was 32.8 months (15.2-69.6 months). Results: At baseline, PET was visually positive in 28 (17%) patients. Among PET+ patients, female proportion was higher compared to PET-patients (respectively, n = 6, 21.4% vs. n = 11, 8.1%, p = 0.046). Biomarkers of inflammation (CRP, CCL18), of proteolytic activity (MMP9), of extracellular matrix, and calcification regulation (OPN, OPG) were all significantly increased in PET+ patients (p < 0.05). During follow-up, rapid AAA growth (increase in size ≥ 1 cm per year) was observed in 36 (29.8%) patients and several biomarkers (CRP, MMP9, OPN, and OPG) were increased in those patients compared to patients without rapid growth (p < 0.05). Conclusions: Although PET positivity at baseline was not associated with rapid growth, CRP levels showed a significant association.

Positron Emission Tomography/Computed Tomography Predicts and Detects Complications After Endovascular Repair of Abdominal Aortic Aneurysms.

Purpose: To assess if aortic 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) could play a role in predicting complications after endovascular aneurysm repair (EVAR). Materials and Methods: This study involved 2 cohorts of men with abdominal aortic aneurysm treated by EVAR: those who underwent a PET/CT scan before EVAR (n=17) and those who had a PET/CT during follow-up (n=34). Uptake of FDG was measured as the standardized uptake value (SUV). D-dimer, a marker of fibrinolysis, was measured in blood drawn concomitantly with the PET/CT. Results: A significant uptake of FDG in the aneurysm wall was detected by PET/CT before EVAR in 6 of 17 patients. During the first year after EVAR, type II endoleaks developed in 5 of these FDG+ patients vs 3 of 11 FDG- patients (p=0.04). Two of the FDG+ patients had continued sac growth and required conversion to open repair. A significant association between sac growth rate, SUV, and the presence of endoleak was found in the 34 patients who underwent PET/CT after EVAR. Finally, D-dimer was significantly increased in patients with both endoleak and positive PET/CT in the post-EVAR group. Conclusion: This study suggests that the presence of FDG uptake in the aortic wall might be a useful tool to predict patients at high risk of developing post-EVAR complications.

18F- FDG PET/CT joint assessment of early therapeutic response in rheumatoid arthritis patients treated with rituximab.

BACKGROUND: 18F-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. RESULTS: High 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. CONCLUSIONS: These 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.

Gene expression study in positron emission tomography-positive abdominal aortic aneurysms identifies CCL18 as a potential biomarker for rupture risk.

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 with-out 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.

Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.

BACKGROUND: The relationship between biomechanical properties and biological activities in aortic aneurysms was investigated with finite element simulations and 18F-fluoro-deoxy-glucose (18F-FDG) positron emission tomography. METHODS AND RESULTS: The study included 53 patients (45 men) with aortic aneurysms, 47 infrarenal (abdominal aortic) and 6 thoracic (thoracic aortic), who had ≥1 18F-FDG positron emission tomography/computed tomography. During a 30-month period, more clinical events occurred in patients with increased 18F-FDG uptake on their last examination than in those without (5 of 18 [28%] versus 2 of 35 [6%]; P=0.03). Wall stress and stress/strength index computed by finite element simulations and 18F-FDG uptake were evaluated in a total of 68 examinations. Twenty-five (38%) examinations demonstrated ≥1 aneurysm wall area of increased 18F-FDG uptake. 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, 18F-FDG positron emission tomographic uptake correlated positively with both wall stress and stress/strength index (P<0.05). 18F-FDG uptake was particularly high in subjects with personal history of angina pectoris and familial aneurysm. CONCLUSIONS: Increased 18F-FDG positron emission tomographic uptake in aortic aneurysms is strongly related to aneurysm location, wall stress as derived by finite element simulations, and patient risk factors such as acquired and inherited susceptibilities.

Endoscopic findings in case of incidental colonic uptake in PET-CT how to improve PET-CT specificity?

Unexpected colonic 18FDG focal uptakes (UCFU) in PET CT occur in 1.3-3.3% of cases in retrospective study and are often associated with significant colorectal findings in endoscopy, especially neoplastic lesions. The purpose of our prospective study was to evaluate the significance of UCFU and to assess criteria improving PET CT specificity for advanced adenoma and neoplasia. This study was conducted in a single institution from April 2012 to September 2013. In the 2904 patients who benefit from PET CT, 52 had an UCFU and 43 were referred for colonoscopy. After endoscopy, 8 examinations showed no colonic abnormality (18.6%), 7 showed benign lesion (16.3%), 18 showed advanced adenoma (42.9%) and 10 showed carcinoma (23.3%). There were more false positives results in the proximal colon compared to distal colon. Eighteen patients had UCFU and tomodensitometric abnormalities in the same colonic area. This pathological combination was strongly associated to the diagnosis of malignancy. Comparing standardized uptake values (SUV), we showed statistically significant difference between the adenocarcinoma and advanced adenoma groups and a difference at the margin of statistical significance between adenocarcinoma and benign lesion groups. Any cut off value could be determined. In conclusion, we confirmed that UCFU are often associated to endoscopic findings and neoplastic lesions and justify systematic endoscopic exploration. Considering the fragility of oncologic patients, criteria improving PET CT specificity are needed to select endoscopies which should be performed quickly from those who could be delayed. We showed that associated tomodensitometric abnormality and high focal FDG activity are more predictive of a neoplastic lesion.

18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.

UNLABELLED: 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 (PET+), 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 = 10) and from PET+ patients (n = 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 PET+, 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, PET+ 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.

Multimodality Staging of Lung Cancer.

Computed tomography (CT) is the primary noninvasive imaging modality for staging of non-small cell lung cancer. Magnetic resonance imaging compliments CT in tumor staging in specific situations. [(18)F]Fluorodeoxyglucose positron emission tomography/CT is useful in detecting additional regional nodal and distant metastatic sites of disease, thereby reducing the number of unnecessary surgeries. However, noninvasive imaging modalities lack sufficient accuracy for nodal staging in all cases and, hence, preoperative lymph node sampling with invasive techniques such as mediastinoscopy, thoracoscopy, and fine-needle aspiration cytology guided by endobronchial ultrasound or endoscopic ultrasound is frequently required in selected patients.

Complementary Assessment of Abdominopelvic Disorders with PET/CT and MRI.

This article reviews the current performance and status of PET/CT and MR imaging in four different abdominopelvic malignancies: cervical, pancreatic, and rectal cancers and liver metastases, as well as in Crohn's disease. The authors discuss the complementary aspects of these imaging techniques to evaluate the nature of the lesion, its local extent, and distant spread. These disease conditions represent pertinent clinical models in which PET/MRI may, if and when available, constitute a powerful tool in the management of patients.