BackgroundFluorine-18–sodium fluoride (18F-NaF) uptake is a marker of active vascular calcification associated with high-risk atherosclerotic plaque.ObjectivesIn patients with abdominal aortic aneurysm (AAA), the authors assessed whether 18F-NaF positron emission tomography (PET) and computed tomography (CT) predicts AAA growth and clinical outcomes.MethodsIn prospective case-control (n = 20 per group) and longitudinal cohort (n = 72) studies, patients with AAA (aortic diameter >40 mm) and control subjects (aortic diameter <30 mm) underwent abdominal ultrasound, 18F-NaF PET-CT, CT angiography, and calcium scoring. Clinical endpoints were aneurysm expansion and the composite of AAA repair or rupture.ResultsFluorine-18-NaF uptake was increased in AAA compared with nonaneurysmal regions within the same aorta (p = 0.004) and aortas of control subjects (p = 0.023). Histology and micro-PET-CT demonstrated that 18F-NaF uptake localized to areas of aneurysm disease and active calcification. In 72 patients within the longitudinal cohort study (mean age 73 ± 7 years, 85% men, baseline aneurysm diameter 48.8 ± 7.7 mm), there were 19 aneurysm repairs (26.4%) and 3 ruptures (4.2%) after 510 ± 196 days. Aneurysms in the highest tertile of 18F-NaF uptake expanded 2.5× more rapidly than those in the lowest tertile (3.10 [interquartile range (IQR): 2.34 to 5.92 mm/year] vs. 1.24 [IQR: 0.52 to 2.92 mm/year]; p = 0.008) and were nearly 3× as likely to experience AAA repair or rupture (15.3% vs. 5.6%; log-rank p = 0.043).ConclusionsFluorine-18-NaF PET-CT is a novel and promising approach to the identification of disease activity in patients with AAA and is an additive predictor of aneurysm growth and future clinical events. (Sodium Fluoride Imaging of Abdominal Aortic Aneurysms [SoFIA3]; NCT02229006; Magnetic Resonance Imaging [MRI] for Abdominal Aortic Aneurysms to Predict Rupture or Surgery: The MA3RS Trial; ISRCTN76413758)

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Abdominal aortic aneurysms (AAAs) are an important cause of morbidity and, when ruptured, are associated with >80% mortality. Current management decisions are based on assessment of aneurysm diameter by abdominal ultrasound. However, AAA growth is non-linear and rupture can occur at small diameters or may never occur in those with large AAAs. There is a need to develop better imaging biomarkers that can identify the potential risk of rupture independent of the aneurysm diameter. Key pathobiological processes of AAA progression and rupture include neovascularisation, necrotic inflammation, microcalcification and proteolytic degradation of the extracellular matrix. These processes represent key targets for emerging imaging techniques and may confer an increased risk of expansion or rupture over and above the known patient-related risk factors. Magnetic resonance imaging, using ultrasmall superparamagnetic particles of iron oxide, can identify and track hotspots of macrophage activity. Positron emission tomography, using a variety of targeted tracers, can detect areas of inflammation, angiogenesis, hypoxia and microcalcification. By going beyond the simple monitoring of diameter expansion using ultrasound, these cellular and molecular imaging techniques may have the potential to allow improved prediction of expansion or rupture and to better guide elective surgical intervention.

The level of serum ablumin has been said to be the controlling factor in the accumulation of ascitic fluid in patients with cirrhosis of the liver (1 to 4). Several investigators have reported an increased portal pressure in patients with the disease (5 to 7) and this has been conceded to contribute to the development of ascites. During the past 3 years, we have observed patients with cirrhosis of the liver who have accumulated ascitic fluid in such quantities that repeated paracenteses were required. The plasma levels of albumin and globulin were determined at regular intervals. The patients received, in addition to an adequate diet, an aqueous extract of liver prepared at the Rockefeller Institute for Medical Research. The liver extract, diluted with saline, was administered intravenously. As a result of the combined therapy, the reaccumulation of ascitic fluid was arrested after varying periods of time in the different patients and further paracenteses were unnecessary. We were thus able to compare the plasma levels of albumin and globulin during and after the period of fluid retention. In addition, determinations of plasma proteins were made on a group of patients with severe cirrhosis of the liver in whom ascites had never been present.This report is concerned with these observations. As the results did not indicate that the level of albumin in the plasma was the determining factor in the fluid retention, data are presented to support another theory in explanation of this disturbance. STUDIES ON PATIENTSThe patients selected for this study were those in whom severe liver damage was unquestionably present 1 This research was aided by grants from the Milbank Memorial Foundation and from the Nutrition Foundation.as evidenced by the physical findings and laboratory tests. A history of chronic alcoholism extending over a period of years was given by each patient. During the period of hospitalization, the patients were on the wards of the 3rd (New York University) Medical Division of Bellevue Hospital. When discharged, they were seen regularly in the Meta5olism Clinic of New York University College of Medicine. The diet consisted of 450 grams of carbohydrate, 100 to 120 grams of protein, and 85 grams of fat. Meat was given only once a day and the rest of the protein was derived from milk, eggs, cheese, and gelatine.2 The liver extract8 was given intravenously in doses of 5 to 10 ml. diluted with 40 ml. of N/saline. Two to 3 injections were given weekly. The plasma levels of albumin and globulin were determined by the method of Howe (8). The total proteins were done by the micro Kjeldahl method. Plasma cholesterols were determined by a modification of the Schoenheimer and Sperry method (9)-, and were read in the photoelectric colorimeter (10). Five mgm. of bromsulphalein per kgm. of body weight were injected intravenously for this test and the retention was determined on a sample of plasma withdrawn after one-half hour. The readings were made in a photoelectric colorimeter. The colloid osmotic pressure was calcula...