Calibrated breast density methods for full field digital mammography: a system for serial quality control and inter-system generalization.

PURPOSE: The authors are developing a system for calibrated breast density measurements using full field digital mammography (FFDM). Breast tissue equivalent (BTE) phantom images are used to establish baseline (BL) calibration curves at time zero. For a given FFDM unit, the full BL dataset is comprised of approximately 160 phantom images, acquired prior to calibrating prospective patient mammograms. BL curves are monitored serially to ensure they produce accurate calibration and require updating when calibration accuracy degrades beyond an acceptable tolerance, rather than acquiring full BL datasets repeatedly. BL updating is a special case of generalizing calibration datasets across FFDM units, referred to as cross-calibration. Serial monitoring, BL updating, and cross-calibration techniques were developed and evaluated. METHODS: BL curves were established for three Hologic Selenia FFDM units at time zero. In addition, one set of serial phantom images, comprised of equal proportions of adipose and fibroglandular BTE materials (50/50 compositions) of a fixed height, was acquired biweekly and monitored with the cumulative sum (Cusum) technique. These 50/50 composition images were used to update the BL curves when the calibration accuracy degraded beyond a preset tolerance of ±4 standardized units. A second set of serial images, comprised of a wide-range of BTE compositions, was acquired biweekly to evaluate serial monitoring, BL updating, and cross-calibration techniques. RESULTS: Calibration accuracy can degrade serially and is a function of acquisition technique and phantom height. The authors demonstrated that all heights could be monitored simultaneously while acquiring images of a 50/50 phantom with a fixed height for each acquisition technique biweekly, translating into approximately 16 image acquisitions biweekly per FFDM unit. The same serial images are sufficient for serial monitoring, BL updating, and cross-calibration. Serial calibration accuracy was maintained within ±4 standardized unit variation from the ideal when applying BL updating. BL updating is a special case of cross-calibration; the BL dataset of unit 1 can be converted to the BL dataset for another similar unit (i.e., unit 2) at any given time point using the 16 serial monitoring 50/50 phantom images of unit 2 (or vice versa) acquired near this time point while maintaining the ±4 standardized unit tolerance. CONCLUSIONS: A methodology for monitoring and maintaining serial calibration accuracy for breast density measurements was evaluated. Calibration datasets for a given unit can be translated forward in time with minimal phantom imaging effort. Similarly, cross-calibration is a method for generalizing calibration datasets across similar units without additional phantom imaging. This methodology will require further evaluation with mammograms for complete validation.

Benzo[a]pyrene, but not 2,3,7,8-TCDD, induces G2/M cell cycle arrest, p21CIP1 and p53 phosphorylation in human choriocarcinoma JEG-3 cells: a distinct signaling pathway.

Maternal cigarette smoking is known to disrupt placental growth and function. The polyaromatic hydrocarbon benzo[a]pyrene (BaP) is a major toxicant in cigarette smoke that has been shown to alter placental cell function. This study compared the effects of the benzo[a]pyrene (BaP) with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototype ligand for the aryl hydrocarbon (Ah) receptor, on proliferation and cell cycle progression in the human trophoblastic JEG-3 cell line. BaP, but not TCDD, significantly inhibited proliferation in a dose-dependent manner characterized by G2/M cell cycle phase arrest. No evidence of apoptosis was detected following BaP or TCDD exposure. Immunocytochemistry and Western blot analysis showed that BaP induced expression of nuclear p21CIP1 protein, the major inhibitor of cyclin-dependent kinases. In contrast, CDK1 expression, the main G2 cyclin-dependent kinase, was significantly reduced by 50% with a shift in localization from the nucleus to cytoplasm. Although BaP had no effect on total cellular p53 levels, phosphorylation of p53 at serine 15 (p53 ser-15phos) was markedly increased. The presence of Wortmannin, an inhibitor of PI-3 kinases, decreased BaP-induced p53 ser-15phos, as did the presence of the antioxidant vitamin E. In addition, vitamin E suppressed BaP-induced G2/M arrest without altering the level of induced CYP1A1 protein. Thus, the anti-proliferative effect of BaP involves activation of a p53-dependent pathway involving cell cycle arrest at G2/M, providing evidence of oxidative stress and activation of a DNA damage response pathway in JEG-3 cells.