A Randomized Double-Blind Placebo-Controlled Trial of the Effect of Vitamin D3 Supplementation on Breast Density in Premenopausal Women.

Background: This double-blind, placebo-controlled parallel group trial assessed whether oral supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 over one year reduces percent mammographic breast density in premenopausal women.Methods: The trial was conducted between October 2012 and June 2015, among premenopausal female volunteers from Quebec City (Quebec, Canada). Women were randomized with ratio 1:1:1:1 to one of four study arms (1,000, 2,000, or 3,000 IU/day vitamin D3 or placebo). The primary outcome was mean change in percent mammographic breast density. Participants and research team were blinded to study arm assignment.Results: Participants (n = 405) were randomized to receive 1,000 (n = 101), 2,000 (n = 104), or 3,000 IU/day (n = 101) vitamin D3, or a placebo (n = 99). The primary analysis included 391 participants (96, 99, 100, and 96, respectively). After the one-year intervention, mean ± SE change in percent breast density in the arms 1,000 IU/day (-5.5% ± 0.5%) and 2,000 IU/day (-5.9% ± 0.5%) vitamin D3 was similar to that in the placebo arm (-5.7% ± 0.5%) (P values = 1.0). In the 3,000 IU/day vitamin D3 arm, percent breast density also declined but slightly less (-3.8% ± 0.5%) compared with placebo arm (P = 0.03). Adherence to intervention was excellent (92.8%), and reporting of health problems was comparable among study arms (P ≥ 0.95). All participants had normal serum calcium.Conclusions: In premenopausal women, one-year supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 resulted in a reduction of percent breast density no greater than that seen with the placebo.Impact: At doses of 1,000-3,000 IU/day, vitamin D supplementation will not reduce breast cancer risk through changes in breast density. Cancer Epidemiol Biomarkers Prev; 26(8); 1233-41. ©2017 AACR.

Measured and calculated K-fluorescence effects on the MTF of an amorphous-selenium based CCD x-ray detector.

PURPOSE: Theoretical reasoning suggests that direct conversion digital x-ray detectors based upon photoconductive amorphous-selenium (a-Se) could attain very high values of the MTF (modulation transfer function) at spatial frequencies well beyond 20 cycles mm(-1). One of the fundamental factors affecting resolution loss, particularly at x-ray energies just above the K-edge of selenium (12.66 keV), is the K-fluorescence reabsorption mechanism, wherein energy can be deposited in the detector at locations laterally displaced from the initial x-ray interaction site. This paper compares measured MTF changes above and below the Se K-edge of a CCD based a-Se x-ray detector with theoretical expectations. METHODS: A prototype 25 µm sampling pitch (Nyquist frequency = 20 cycles mm(-1), 200 µm thick a-Se layer based x-ray detector, utilizing a specialized CCD readout device (200 × 400 area array), was used to make edge images with monochromatic x-rays above and below the K-edge of Se. A vacuum double crystal monochromator, exposed to polychromatic x-rays from a synchrotron, formed the monochromatic x-ray source. The monochromaticity of the x-rays was 99% or better. The presampling MTF was determined using the slanted edge method. The theory modeling the MTF performance of the detector includes the basic x-ray interaction physics in the a-Se layer as well as effects related to the operation of the CCD and charge trapping at a blocking layer present at the CCD/a-Se interface. RESULTS: The MTF performance of the prototype a-Se CCD was reduced from the theoretical value prescribed by the basic Se x-ray interaction physics, principally by the presence of a blocking layer. Nevertheless, the K-fluorescence reduction in the MTF was observed, approximately as predicted by theory. For the CCD prototype detector, at five cycles mm(-1), there was a 14% reduction of the MTF, from a value of 0.7 below the K-edge of Se, to 0.6 just above the K-edge. CONCLUSIONS: The MTF of an a-Se x-ray detector has been measured using monochromatic x-rays above and below the K-edge of selenium. The MTF is poorer above the K-edge by an amount consistent with theoretical expectations.

Functional imaging using diffuse optical spectroscopy of neoadjuvant chemotherapy response in women with locally advanced breast cancer.

PURPOSE: Functional imaging with tomographic near-infrared diffuse optical spectroscopy (DOS) can measure tissue concentration of deoxyhemoglobin (Hb), oxyhemoglobin (HbO2), percent water (%water), and scattering power (SP). In this study, we evaluated tumor DOS parameters and described their relationship to clinical and pathologic outcome in patients undergoing neoadjuvant therapy for locally advanced breast cancer. EXPERIMENTAL DESIGN: Ten patients were enrolled and intended to undergo five scans each. Scans were taken up to 3 days before treatment and at 1, 4, and 8 weeks after neoadjuvant treatment before surgery. Changes in volume of interest weighted tissue Hb, HbO2, %water, and SP corresponding to the tumor were compared with clinical and pathologic response. RESULTS: All patients' tumor volumes of interest were significantly different compared with background tissue for all parameters. Five patients had a good pathologic response. Four patients were considered nonresponders. One patient initially did not respond to chemotherapy but, after a change in chemotherapy, had a good response. In the five patients with a good response, the mean drop in Hb, HbO2, %water, and SP from baseline to the 4-week scan was 67.6% (SD = 20.8), 58.9% (SD = 20.3), 51.2% (SD = 28.3), and 52.6% (SD = 26.4), respectively. In contrast, the four nonresponders had a mean drop of 17.7% (SD = 9.8), 18.0% (SD = 20.8), 15.4% (SD = 11.7), and 12.6% (SD = 10.2) for Hb, HbO2, %water, and SP, respectively. CONCLUSIONS: Responders and nonresponders were significantly different for all functional parameters at the 4-week scan, except for %water, which approached significance. Thus, DOS could be used as an early detector of tumor response.

Evaluation of scatter effects on image quality for breast tomosynthesis.

Digital breast tomosynthesis uses a limited number (typically 10-20) of low-dose x-ray projections to produce a pseudo-three-dimensional volume tomographic reconstruction of the breast. The purpose of this investigation was to characterize and evaluate the effect of scattered radiation on the image quality for breast tomosynthesis. In a simulation, scatter point spread functions generated by a Monte Carlo simulation method were convolved over the breast projection to estimate the distribution of scatter for each angle of tomosynthesis projection. The results demonstrate that in the absence of scatter reduction techniques, images will be affected by cupping artifacts, and there will be reduced accuracy of attenuation values inferred from the reconstructed images. The effect of x-ray scatter on the contrast, noise, and lesion signal-difference-to-noise ratio (SDNR) in tomosynthesis reconstruction was measured as a function of the tumor size. When a with-scatter reconstruction was compared to one without scatter for a 5 cm compressed breast, the following results were observed. The contrast in the reconstructed central slice image of a tumorlike mass (14 mm in diameter) was reduced by 30%, the voxel value (inferred attenuation coefficient) was reduced by 28%, and the SDNR fell by 60%. The authors have quantified the degree to which scatter degrades the image quality over a wide range of parameters relevant to breast tomosynthesis, including x-ray beam energy, breast thickness, breast diameter, and breast composition. They also demonstrate, though, that even without a scatter rejection device, the contrast and SDNR in the reconstructed tomosynthesis slice are higher than those of conventional mammographic projection images acquired with a grid at an equivalent total exposure.

The dependence of the modulation transfer function on the blocking layer thickness in amorphous selenium x-ray detectors.

Blocking layers are used to reduce leakage current in amorphous selenium detectors. The effect of the thickness of the blocking layer on the presampling modulation transfer function (MTF) and on dark current was experimentally determined in prototype single-line CCD-based amorphous selenium (a-Se) x-ray detectors. The sampling pitch of the detectors evaluated was 25 microm and the blocking layer thicknesses varied from 1 to 51 microm. The blocking layers resided on the signal collection electrodes which, in this configuration, were used to collect electrons. The combined thickness of the blocking layer and a-Se bulk in each detector was approximately 200 microm. As expected, the dark current increased monotonically as the thickness of the blocking layer was decreased. It was found that if the blocking layer thickness was small compared to the sampling pitch, it caused a negligible reduction in MTF. However, the MTF was observed to decrease dramatically at spatial frequencies near the Nyquist frequency as the blocking layer thickness approached or exceeded the electrode sampling pitch. This observed reduction in MTF is shown to be consistent with predictions of an electrostatic model wherein the image charge from the a-Se is trapped at a characteristic depth within the blocking layer, generally near the interface between the blocking layer and the a-Se bulk.

Lag and ghosting in a clinical flat-panel selenium digital mammography system.

We present measurements of lag and ghosting in a FDA-approved digital mammography system that uses a dielectric/selenium based detector structure. Lag is the carryover of signal from a previous image, whereas ghosting is the reduction of sensitivity caused by previous exposure history of the detector. Data from six selenium units were acquired. For the type of selenium detector tested, and under typical clinical usage conditions, the lag was as high as 0.15% of source signal and the ghosting could be as high as 15%. The amount of lag and ghosting varied from unit to unit. Results were compared with data acquired on a phosphor-based full-field digital mammography system. Modifications in the technology of the selenium detectors appear to have resulted in a marked decrease in both lag and ghosting effects in more recent systems.

Detectors for digital mammography.

Interest in digital radiography was stimulated by the enthusiastic acceptance of computed tomography in the early 1970s. It quickly became apparent to the medical community that images with improved information content, whose display characteristics could be manipulated by the viewer, provided many advantages. Subsequently, digital systems for subtraction angiography and later for conventional projection radiography and fluoroscopy were developed. The timing of the introduction of these systems was highly dependent on the readiness of certain key component technologies to meet the requirements of each of these applications. These components are the x-ray detectors, analog to digital converters, computers, data storage systems and high-resolution electronic displays and printers used in image acquisition, storage and display. Mammography represents one of the most demanding radiographic applications, simultaneously requiring excellent contrast sensitivity, high spatial resolution, and wide dynamic range at as low as radiation dose to the breast as is reasonably achievable while meeting the other requirements. For this reason, it is one of the last radiographic procedures to "go digital". Here, some of the considerations related to the detector technology for digital mammography will be discussed and systems currently available will be described.