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Biomedical subjects

R Fahrig

Publications and source records attributed to R Fahrig.

At least 37 records · Page 2Linked to original sources

X-ray imaging with amorphous selenium: optimal spectra for digital mammography.

The optimum x-ray spectra for acquisition of digital mammographic images using an amorphous selenium (a-Se) photoconductor are investigated. The recorded images consist of latent charge distributions on the surface of an a-Se plate, which are then read out using two methods, laser discharge, or flat panel recharge. The investigation is based on a model of the breast previously developed for a phosphor-based digital readout system, and has been extended to include the effects specific to the use of photoconductors. The effects of plate thickness, x-ray scatter, readout noise, dose, and the kind of breast tissue on the nature of the optimum spectrum are explored for the two readout methods. The results indicate that use of a kilovoltage setting in the current mammographic range, and a molybdenum target spectrum is appropriate for digital readout of a-Se detectors. This conclusion contrasts with the appreciably higher kilovoltages traditionally used with the xerographic (toner) readout of latent charge images on a-Se.

Biophysical Phenomena↗

Monitoring of induced chromosomal aberrations in S. cerevisiae in agarose gels by pulsed field gel electrophoresis.

Pulsed field gel electrophoresis (PFGE) has been used to detect aberrations of the chromosomal banding pattern referred to as chromosomal aberrations arising after treatment of yeast strain S. cerevisiae MP1 with the three different genotoxic substances 4-nitroquinoline-N-oxide (4-NQO), methotrexate (MTX) and 2-amino-6-mercaptopurine (AMP). Different chromosomal aberrations were detectable directly in the pulsed field gel when growing yeast cells were incubated with a genotoxin for 6 h at 26 degrees C followed by treatment with the genotoxin for another twelve days at 4 degrees C. In the present study, clones of yeast cells were examined. In this way, distinct chromosomal aberrations and not only DNA smear could be detected. Moreover, this method allows selection for yeast strains with specific and rare chromosomal rearrangements.

4-Nitroquinoline-1-oxide↗

X-ray imaging with amorphous selenium: detective quantum efficiency of photoconductive receptors for digital mammography.

Factors affecting the zero spatial frequency detective quantum efficiency of photoconductor-based x-ray detectors operating in the mammographic energy range are modeled for monoenergetic incident x rays. The problem is separated into two sections: the calculation of the x-ray absorption and the Swank factor. X-ray absorption in this energy range, for most practical photoconductors, is dominated by the photoelectric effect. The Swank factor has four components: fluorescence escape, stochastic variations in gain, variations of gain due to incomplete coupling of charge from the photoconductive layer to the detector electrode, and the nonlinear discharge arising from the field-dependent x-ray gain, an effect that is unique to photoconductors. Calculations are performed for selenium, which is currently the most technologically advanced photoconductor available for digital x-ray imaging. For thicknesses of selenium exceeding 50 microns and for energies between 12 and 50 keV, the detective quantum efficiency of this photoconductor is found to exceed that of a conventional Gd2O2S-based mammographic phosphor screen.

Efficiency↗

Optimization of spectral shape in digital mammography: dependence on anode material, breast thickness, and lesion type.

It has been proposed that breast cancer detection can be improved through the use of digital mammography. It is hypothesized that the choice of proper shape of the x-ray spectrum incident upon the breast can yield an improved image signal-to-noise ratio (SNR) for a given dose. To test this hypothesis, an energy transport model incorporating measured breast tissue attenuation coefficients and published exposure-to-dose conversion values was developed to describe the image acquisition process. The choice of applied kilovoltage and filter for Mo and W target x-ray sources has been optimized with respect to SNR and absorbed dose for detectors based on a Gd2O2S scintillating screen under the conditions of perfect coupling of light between the screen and a solid state photodetector. For the W spectra, the optimum filter-kVp combinations could provide 41%, 13%, and 42% improvements in SNR for 2-cm, 6-cm and 8-cm breasts, respectively, over the conventional Mo filtration, for a practical imaging time of 1.0 s. W and Mo spectra produce similar SNR values for a given filter thickness except for the 4-cm breast. Given the limitations of current technology, however, the W spectra produce the optimum SNRs in a shorter imaging time for breast thicknesses greater than and less than 4 cm. The maximum SNR for imaging both infiltrating ductal carcinoma and calcifications is provided by the same filter-kVp combination, allowing optimization based on breast thickness and composition only. The model can now be used to compare and improve upon novel detector designs.

Breast↗

Performance of glass fiber antiscatter devices at mammographic energies.

Using fiber optic manufacturing techniques, it is possible to produce a radiographic grid that discriminates against scattered radiation in two dimensions. Such grids consist of septa composed of glass with a high lead content; the interspace material is air, so that approximately 80% of the grid area is open. In this way, effective high ratio grids can be produced with relatively low Bucky factors. The performance of samples of such grid material is characterized in terms of both scatter rejection and dose efficiency for application in digital mammography in both slot-beam and area-beam geometry. For area beams, five- to tenfold improved scatter rejection relative to conventional grids was observed. In slot configurations, such grids could provide improved SNR/dose performance and more effective utilization of the heat loading capability of the x-ray source.

Fiber Optic Technology↗

A model for optimization of spectral shape in digital mammography.

X-ray mammography is the most sensitive imaging modality available for the detection of breast cancer. The highest performance can only be achieved, however, if the complete imaging system is optimized. The development of digital mammography offers an opportunity to obtain improved sensitivity in mammography. In such systems, the decoupling of the recording and display processes allows each component of the imaging system to be optimized separately. In this paper we describe a method for optimizing the recording process for digital mammographic techniques. Our method uses an energy transport model of the propagation of signal and noise through the imaging system. The computations make use of experimentally determined data wherever possible so that the number of assumptions in the model can be minimized. The model predicts the signal-to-noise ratio for a constant dose to the breast, and therefore allows comparison and optimization both for different x-ray spectra and for different imaging tasks. The major energy-dependent components of the model have been verified, and good agreement is demonstrated between predictions by the model of both contrast and SNR and experimentally measured values. Calculations for a particular imaging task, detection of a 200-microns cubic calcification in a 6-cm, 50% adipose-50% glandular breast, illustrate application of the model for optimization of spectral shape.

Breast Neoplasms↗

Genetic effects of dioxins in the spot test with mice.

More than any other environmental chemicals, dioxins have been in the limelight of public interest for about 10 years. In addition to carcinogenicity, genetic risk is a cause for concern. Mutagenicity tests performed so far do not give a clear picture. The mutagenic potential of dioxins has to be considered weak or absent. Therefore, it seemed profitable to investigate comutagenicity and co-recombinogenicity of dioxins more thoroughly. The only useful method for investigating comutagenicity and co-recombinogenicity of dioxins in vivo is the spot test with mice. In this test system, a number of cocarcinogens and tumor promoters have shown comutagenic or co-recombinogenic effects. In the present study, tetrachlorodibenzo-p-dioxin (TCDD) and two environmental dioxin mixtures [pentachlorodibenzodioxin (PCDD) 1 and 2] were tested for genetic activity. Given alone, no mutagenic or recombinogenic effects could be observed. In combination with the carcinogenic mutagen ethyl nitrosourea (ENU) at concentrations of 128 micrograms/kg for PCCD 2, 314 micrograms/kg for PCDD 1, and 3 micrograms/kg for TCDD, a doubling of the genetic effectiveness of ENU was observed. The genetic risk can roughly be considered as 1:0.02 for TCDD:PCDD 2 and 1:0.01 for TCDD:PCDD 1. While PCDD 1 and 2 seem to enhance the mutagenic as well as the recombinogenic potential of ENU, TCDD showed mainly co-recombinogenic and antimutagenic activity. This characteristic indicates that TCDD is mainly a tumor promoter.

Animals↗

Adaptive resistance of Saccharomyces cerevisiae to chronic treatment with mutagens being due to a dominant mutation.

The exposure of mammalian cells or tumors for weeks or months to low non-lethal doses of cytostatic drugs may induce multi-drug resistance, which can be enhanced by a variety of DNA-damaging agents. In yeast multi-drug resistance to a variety of drugs has been observed. DNA-damaging agents have not yet been tested. As the appearance of resistance is the result of long-term exposure, we decided to extend the application of test substances to a period of up to 400 days. In such long-term experiments S. cerevisiae MP1 adapted to treatment with low doses of mutagens. Consistent results were obtained for both alkylating and non-alkylating mutagenic substances. Furthermore, the adaptive resistance to the alkylating agent also adapted cells to the non-alkylating agent, which implies that there may be a single pathway for mutagens with different modes of action. Random spore analysis of adapted yeast cells and the back-cross to the parental wild type indicates that a single dominant mutation is responsible for the adaptive resistance.

4-Nitroquinoline-1-oxide↗

Effects of bile acids on the mutagenicity and recombinogenicity of triethylene melamine in yeast strains MP1 and D61.M.

When Saccharomyces cerevisia MP1 was treated with bile acids alone or in combination with triethylene melamine (TEM), cholic acid was found to be comutagenic and antirecombinogenic while lithocholic acid had the opposite effect. Other bile acids enhanced the mutagenic and recombinogenic effects of TEM. Chenodeoxycholic acid, deoxycholic acid and ursodeoxycholic acid had stronger comutagenic than corecombinogenic effects; hyodeoxycholic acid did not show this difference. Ox gall and a mixture of bile acids antagonized the genotoxic effect of TEM, and it therefore seems plausible that in normal composition bile acids neutralize each other, i.e., the comutagenic (corecombinogenic) effect of one substance is antagonized by the antimutagenic (antirecombinogenic) effect of another one. However, when the composition is altered, bile acids may become harmful. Experiments with yeast strain D61.M were performed in order to test for aneuploidy caused by bile acids; no effects were observed.

Aneuploidy↗

Enhancement of carcinogen-induced mutations or recombinations by 12-O-tetradecanoyl-phorbol-13-acetate in the mammalian spot test.

The mammalian spot test is suitable for detecting gene mutations and reciprocal recombinations. When given alone 12-O-tetradecanoyl-phorbol-13-acetate (TPA) did not have any statistically significant effect upon these genetic alterations. In combination with ethylnitrosourea (ENU) however TPA enhanced the effect of the mutagen/carcinogen. The effective dose range of TPA + ENU was very small, i.e., between 2 X 0.2 and 2 X 0.33 mg/kg, but the effect was very strong as shown by the steep slope of the dose-effect curve. The results agree with the hypothesis that the mode of action of cocarcinogens and tumor promoters is a genetic one and that recombination plays an important role in this process.

Animals↗