Multidetector Computed Tomography

The Institutional Animal Care and Use Committee approved this study. Fourteen 3-months old female domestic pigs were randomized in two groups (n=7 each): Control (Lean) pigs were fed standard chow (13% protein, 2% fat, 6% fiber, Purina Animal Nutrition LLC, MN), and obese with a high-fat/high-fructose diet fed ad libitum (5B4L, protein 16.1%, ether extract fat 43.0%, and carbohydrates 40.8%, Purina Test Diet, Richmond, Indiana), for a total of 16 weeks, with free access to water. At 8, 12, and 16 weeks, subcutaneous abdominal adipose tissue biopsies and fasting blood samples were collected under anesthesia and sterile conditions in all pigs. At 16 weeks, the pigs were studied in-vivo with magnetic resonance imaging (MRI, for myocardial oxygenation) followed by multi-detector computed-tomography (MDCT, for cardiac structure, function, and myocardial perfusion) 2 days later. Three days following the completion of in-vivo studies, pigs were euthanized with pentobesearbital-sodium (100mg/kg IV, Sleepaway®, Fort Dodge Laboratories, Fort Dodge, Iowa). Terminal pericardial and subcutaneous abdominal adipose tissue biopsies were collected and tissue studies performed for assessments of fat inflammation and remodeling.

The methodology for acquisition and interpretation of the CAC scans, as well as the reproducibility of the readings, has been reported previously.^{14 (link)} Scanning centers assessed CAC using either an electron-beam CT scanner (Chicago, Los Angeles, and New York) or a multidetector CT system (Baltimore, St Paul, and Winston-Salem). All scanners were cardiac gated. Slice thickness was 3mm using the electron-beam CT scanners and 2.5 mm using the multidetector CT scanners. Each participant was scanned twice for CAC, which was measured during the same examination using the same site-specific scanners. CAC scans were read centrally at the MESA CT Reading Center and were brightness adjusted using a standard phantom to control for any scanner differences.^{15 (link)} In addition to the Agatston score, a volume score was also calculated.^{16 (link)} To qualify as a calcified plaque using CAC scoring, the plaque calcium density, measured in Hounsfield units, must be 130 Hu or higher. The Agatston scoring method for CAC measures each such discrete plaque area in square millimeters. Each discrete plaque area is then multiplied by 1, 2, 3, or 4, depending on the highest density measurement in Hu anywhere in the plaque. Plaques with a maximum density of 130 to 199 Hu are multiplied by 1, those with 200 to 299 Hu by 2, those with 300 to 399 by 3, and those with 400 Hu or greater by 4. These plaque-specific scores are then summed for all slices of the heart to give the Agatston score, which is thus an area score upweighted for increased plaque density. The participants received their Agatston score, were told that the presence of CAC represented hardening of the coronary arteries, and told of their amount of CAC (less than average, average, or greater than average).
The MESA database does not contain the individual area score for each participant. Thus, to calculate the individual area scores, the volume scores in cubic millimeters were divided by the appropriate slice thickness, 2.5 mm or 3 mm, resulting in the area score in square millimeters. The Agatston score was then divided by the area score and the quotient was the average CAC density score for each participant. The formula was: Agatston score/area score = density score. The density score thus ranged from 1 to 4 and reflected the average plaque density for all CT slices from that participant.