Rupture is an acute and life-threatening complication of abdominal aortic aneurysm (AAA) and its incidence increases in parallel with aortic diameter. Nowadays, surgery is currently indicated for aneurysms with diameter≥5.5 cm. However, even in AAAs of subthreshold diameter (4.0–5.5 cm) the incidence of acute complications remains significant, ranging from 1 to 5% per year. Thus, risk stratification in these patients remains a major issue in vascular medicine and calls for a better capability to explore mechanisms underlying AAA acute complications. This task has been facilitated by studies documenting a relevant role for inflammatory infiltrates able to accelerate the proteolysis of elastin and collagen of aortic wall via the release of matrix metalloproteinases and proinflammatory cytokines. These biological mechanisms recently gained renewed interest due to the capability of positron emission tomography (PET)/CT imaging with fluorodeoxyglucose (FDG) to highlight the insulin-independent glucose uptake of activated lymphocytes and macrophages infiltrating the diseased aortic segment. However, more recent reports, including our own experience, were barely able to spot any visible FDG uptake in AAAs whose diameter size was just below the surgical threshold of 5.5 cm [15, 16In the present studies, we planned to verify the prevalence of visible FDG uptake in aneurysmal walls, adopting a case control approach. Moreover, we tested the hypothesis that with increasing AAA diameter cell density is too low to permit any visible FDG uptake. The first study included 40 males (mean age: 74 years, range: 59-93 years), with asymptomatic infrarenal AAA. The mean diameter of AAA was 4.9 cm (range: 4.8e5.4 cm), detected by computed tomography (CT) scan. Control Subjects: 44 age-matched controls subjects (mean age: 71 years, range: 59-85 years, 24 males, 20 females) who were selected from a population of patients without any clinical evidence of atherosclerotic disease. Patients and controls underwent simultaneous FDG-PET/ CT imaging from the skull base to the femoral neck. For the quantitative analysis, circular CT-based regions of interest (ROIs) were drawn on the AAA, on all the aortic segments, and on the large vessel included in the study (carotid, subclavian, and iliac arteries). FDG uptake was quantified by calculating the mean and maximum standardized uptake values (SUVs) within each ROI and normalizing for the blood-pool SUV to obtain the final target-to-background ratio.The metabolic activity in the aneurysmal aortic segment was even lower with respect to both the adjacent non aneurysmal samples of patient group and the corresponding arterial segments of control subjects (P < 0.001 and P < 0.01, respectively). In the second study (PET)/CT imaging was performed in 12 consecutive candidates for AAA surgical repair and in 12 age- and sex-matched controls. At intervention, aneurysmal walls were cut into three sequential blocks. Block A was frozen to cut three 5-μm slices for incubation with 2–3 MBq of FDG for 5 min. Block C was first incubated with the same tracer solution for the same time and subsequently frozen to cut three 5-μm slices. Autoradiographic images were co-registered with immunohistochemical pictures of cell density, type and DNA synthesis as assessed on block B. No visible uptake in abdominal aorta occurred in any patient or control subject. Immunohistochemistry documented a severe loss of wall structure, with low numbers of cells. Tracer retention directly correlated with overall cell density and with prevalence of cells synthesizing DNA. The metabolic nature of FDG uptake was confirmed by the selective effect of preliminary freezing that decreased tracer content by 90% in regions with high cell density and only by 34% in cold acellular areas.So the loss of tissue structure and the marked decrease in cell density account for the low prevalence of positive findings at FDG PET imaging, at least in asymptomatic patients bearing AAAs whose diameter is close to surgical indication
Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens
