Search PubMed⌕ Search

Biomedical subjects

Martin J Yaffe

Publications and source records attributed to Martin J Yaffe.

29 records · Page 2Linked to original sources
PubMed2004

Experimental manipulation of radiographic density in mouse mammary gland.

INTRODUCTION: Extensive mammographic density in women is associated with increased risk for breast cancer. Mouse models provide a powerful approach to the study of human diseases, but there is currently no model that is suited to the study of mammographic density. METHODS: We performed individual manipulations of the stromal, epithelial and matrix components of the mouse mammary gland and examined the alterations using in vivo and ex vivo radiology, whole mount staining and histology. RESULTS: Areas of density were generated that resembled densities in mammographic images of the human breast, and the nature of the imposed changes was confirmed at the cellular level. Furthermore, two genetic models, one deficient in epithelial structure (Pten conditional tissue specific knockout) and one with hyperplastic epithelium and mammary tumors (MMTV-PyMT), were used to examine radiographic density. CONCLUSION: Our data show the feasibility of altering and imaging mouse mammary gland radiographic density by experimental and genetic means, providing the first step toward modelling the biological processes that are responsible for mammographic density in the mouse.

Animals↗
PubMed2004

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.

Breast↗
PubMed2004

A polymorphic locus in the promoter region of the IGFBP3 gene is related to mammographic breast density.

BACKGROUND: Mammographic breast density is a significant risk factor for breast cancer. Women with dense tissue accounting for more than 60-75% of the area of the breast have a 4- to 6-fold increase in their risk of breast cancer, compared to women with little or no breast density. A high circulating level of insulin-like growth factor-I (IGF-I) and low IGF binding protein 3 (IGFBP-3) level have been associated with increased breast density in premenopausal women. Genetic polymorphisms in the IGF1 and IGFBP3 genes may influence breast and serum levels of these growth factors. The aims of this study were to determine whether polymorphic variations in the IGF1 and IGFBP3 genes are associated with breast density, and serum IGF-I and IGFBP-3 levels, and whether serum IGF-I and IGFBP-3 levels are associated with mammographic density. METHODS: A total of 441 white women, recruited from Women's College Hospital (Toronto, Ontario), enrolled in this study. Each woman completed a questionnaire, detailing information on age, menstrual history, hormone use, diet, and medical and mammography history. Blood samples were taken for DNA extraction to genotype the subjects for polymorphic variants in the two candidate genes, and for measurement of circulating levels of IGF-I and IGFBP-3. Mammographic films were retrieved from Women's College Hospital and digitized using a laser film scanner. The digitized images were assessed for breast density using a computer-assisted method. RESULTS: There was a positive association between serum IGFBP-3 levels and the number of A alleles at a previously described polymorphic locus in the promoter region of the IGFBP3 gene among premenopausal women (P = 0.01). There was also a positive trend in the mean percentage of breast density by the number of A alleles of the IGFBP3 gene among premenopausal women (P = 0.0005). Women with two A alleles had a 5-fold increase in the odds of having a percentage of breast density greater or equal to 28%, compared with women with no A allele (P = 0.002). However, there was no association between serum IGF-I and IGFBP-3 levels and breast density among premenopausal women (P > 0.05). CONCLUSIONS: This is the first study to report a strong relationship between a polymorphic gene locus (IGFBP3) and mammographic breast density. However, we could not confirm an association between serum IGF-I levels and breast density among premenopausal women, as demonstrated in previous studies.

Adult↗
PubMed2003

Contrast-enhanced digital mammography: initial clinical experience.

PURPOSE: To investigate the potential of using intravenous contrast material with full-field digital mammography to facilitate the detection and characterization of lesions in the breast. MATERIALS AND METHODS: Twenty-two women scheduled for biopsy because they were suspected of having abnormalities at breast imaging underwent imaging with contrast material-enhanced digital mammography. Six sequential images of the affected breast were obtained, with a contrast agent injected intravenously between the time the first and second images were obtained. Image processing included registration and logarithmic subtraction. Lesions were evaluated for the presence, morphology, and kinetics of enhancement. Lesion type, size, and pathologic findings were correlated with the findings at contrast-enhanced digital mammography. RESULTS: At contrast-enhanced digital mammography, enhancement was observed in eight of 10 patients with biopsy-proved cancers. In one case of ductal carcinoma in situ and one case of invasive ductal carcinoma, enhancement was not observed. No enhancement was seen in seven of 12 cases in which lesions were suspected of being malignant at initial imaging but were benign. Morphology generally correlated with the pathologic diagnosis. The kinetics of lesion enhancement showed similarity to that seen with gadolinium-enhanced magnetic resonance imaging but was not consistent. CONCLUSION: The results of this preliminary study suggest that contrast-enhanced digital mammography potentially may be useful in identification of lesions in the mammographically dense breast. Further investigation of contrast-enhanced digital mammography as a diagnostic tool for breast cancer is warranted.

Adult↗
PubMed2003

A volumetric method for estimation of breast density on digitized screen-film mammograms.

A method is described for the quantitative volumetric analysis of the mammographic density (VBD) from digitized screen-film mammograms. The method is based on initial calibration of the imaging system with a tissue-equivalent plastic device and the subsequent correction for variations in exposure factors and film processing characteristics through images of an aluminum step wedge placed adjacent to the breast during imaging. From information about the compressed breast thickness and technique factors used for taking the mammogram as well as the information from the calibration device, VBD is calculated. First, optical sensitometry is used to convert images to Log relative exposure. Second, the images are corrected for x-ray field inhomogeneity using a spherical section PMMA phantom image. The effectiveness of using the aluminum step wedge in tracking down the variations in exposure factors and film processing was tested by taking test images of the calibration device, aluminum step wedge and known density phantoms at various exposure conditions and also at different times over one year. Results obtained on known density phantoms show that VBD can be estimated to within 5% accuracy from the actual value. A first order thickness correction is employed to correct for inaccuracy in the compression thickness indicator of the mammography units. Clinical studies are ongoing to evaluate whether VBD can be a better indicator for breast cancer risk.

Absorptiometry, Photon↗
PubMed2002

Heritability of mammographic density, a risk factor for breast cancer.

BACKGROUND: Women with extensive dense breast tissue visible on a mammogram have a risk of breast cancer that is 1.8 to 6.0 times that of women of the same age with little or no density. Menopausal status, weight, and parity account for 20 to 30 percent of the age-adjusted variation in the percentage of dense tissue. METHODS: We undertook two studies of twins to determine the proportion of the residual variation in the percentage of density measured by mammography that can be explained by unmeasured additive genetic factors (heritability). A total of 353 pairs of monozygotic twins and 246 pairs of dizygotic twins were recruited from the Australian Twin Registry, and 218 pairs of monozygotic twins and 134 pairs of dizygotic twins were recruited in Canada and the United States. Information on putative determinants of breast density was obtained by questionnaire. Mammograms were digitized, randomly ordered, and read by a blinded investigator. RESULTS: After adjustment for age and measured covariates, the correlation coefficient for the percentage of dense tissue was 0.61 for monozygotic pairs in Australia, 0.67 for monozygotic pairs in North America, 0.25 for dizygotic pairs in Australia, and 0.27 for dizygotic pairs in North America. According to the classic twin model, heritability (the proportion of variants attributable to additive genetic factors) accounted for 60 percent of the variation in density (95 percent confidence interval, 54 to 66) in Australian twins, 67 percent (95 percent confidence interval, 59 to 75) in North American twins, and 63 percent (95 percent confidence interval, 59 to 67) in all twins studied. CONCLUSIONS: These results show that the population variation in the percentage of dense tissue on mammography at a given age has high heritability. Because mammographic density is associated with an increased risk of breast cancer, finding the genes responsible for this phenotype could be important for understanding the causes of the disease.

Adipose Tissue↗
PubMed2002

A slot-scanned photodiode-array/CCD hybrid detector for digital mammography.

We have developed a novel direct conversion detector for use in a slot-scanning digital mammography system. The slot-scan concept allows for dose efficient scatter rejection and the ability to use small detectors to produce a large-area image. The detector is a hybrid design with a 1.0 mm thick silicon PIN photodiode array (the x-ray absorber) indium-bump bonded to a CCD readout that is operated in time-delay integration (TDI) mode. Because the charge capacity requirement for good image quality exceeds the capabilities of standard CCDs, a novel CCD was developed. This CCD consists of 24 independent sections, each acting as a miniature CCD with eight rows for TDI. The signal from each section is combined off-chip to produce a full signal image. The MTF and DQE for the device was measured at several exposures and compared to a linear systems model of signal and noise propagation. Because of the scanning nature of TDI imaging, both the MTF(f) and DQE(f) are reduced along the direction of the scanning motion. For a 26 kVp spectrum, the DQE(0) was measured to be 0.75+/-0.02 for an exposure of 1.29 x 10(-5) C/kg (50 mR).

Equipment Design↗
PubMed2002

Direct conversion detectors: the effect of incomplete charge collection on detective quantum efficiency.

Direct conversion detectors offer the potential for very high resolution and high quantum efficiency for x-ray imaging, however, variations in signal can arise due to incomplete charge collection. A charge transport model was developed to describe the signal and noise resulting from incomplete charge collection. This signal to noise ratio (SNR) reduction was incorporated into the cascaded systems model for a simple x-ray detector. A new excess noise factor, A(c) (termed the collection noise factor) is introduced to describe the reduction in detective quantum efficiency (DQE). The DQE is proportional to the product of the quantum efficiency and the collection noise factor. If the trapping cross sections for electrons and holes are very different, and if the detector is biased improperly, the collection noise factor can drop to as low as 50%. In addition, the signal loss due to incomplete charge collection will reduce the DQE in the presence of added noise. Because of this, the DQE generally does not continue to improve with greater detector thickness. The collection noise factor and DQE are predicted for CdZnTe, PbI2, and Se. The optimization of detector thickness should be based not only on quantum efficiency but also on the charge collection statistics, which are influenced by bias field and polarity.

Algorithms↗
PubMed2002

Development of contrast digital mammography.

Development of breast tumors is often accompanied by angiogenesis--the formation of new blood vessels. It is possible to image the effects of this process by tracking the uptake and washout of contrast agents in the vicinity of a lesion. In this article, a method for carrying out contrast subtraction mammography on a full-field digital mammography unit is described. Spectral measurements and modeling were performed to optimize the choice of x-ray target, kilovoltage and x-ray beam filtration for contrast digital mammography (CDM) on an available digital mammography system. Phantom studies were carried out to determine the sensitivity of CDM to iodine. Detection of iodine area densities of 0.3 mg/cm2 is possible for a circular object with a radius of 1.3 mm, which allows detection of uptake levels in the breast typically seen with cancer and some benign breast conditions. It was found that with a molybdenum anode x-ray tube, copper filtration could be used to effectively shape the x-ray spectrum to maximize the proportion of x rays with energies above the k edge of iodine. Simple logarithmic subtraction was found to be adequate in suppressing background signals dependent on the x-ray beam intensity and background thickness of the breast. The total x-ray dose from the procedure ranges between 1 and 3 mGy, similar to that from a conventional single view film mammogram. A clinical pilot study is currently being carried out to evaluate this technique.

Algorithms↗
PubMed2002

A CdZnTe slot-scanned detector for digital mammography.

A new high-resolution detector has been developed for use in a slot-scanned digital mammography system. The detector is a hybrid device that consists of a CCD operating in time-delay integration mode that is bonded to a 150-microm-thick CdZnTe photoconductor array. The CCD was designed with a detector element pitch of 50 microm. Two devices were evaluated with differing crystalline quality. Incomplete charge collection was a source of reduction in DQE. This occurs in both devices due to characteristically low mobility-lifetime products for CdZnTe, with the greatest losses demonstrated by the multicrystalline sample. The mobility-lifetime products for the multicrystalline device were found to be 2.4 x 10(-4) and 4.0 x 10(-7) cm2/V for electrons and holes, respectively. The device constructed with higher quality single crystal CdZnTe demonstrated mobility-lifetime products of 1.0 x 10(-4) and 4.4 x 10(-6) cm2/V for electrons and holes. The MTF and DQE for the device were measured at several exposures and results were compared to predictions from a linear systems model of signal and noise propagation. The MTF at a spatial frequency of 10 mm(-1) exceeded 0.18 and 0.56 along the scan and slot directions, respectively. Scanning motion and CCD design limited the resolution along the scan direction. For an x-ray beam from a tungsten target tube with 40 microm molybdenum filtration operated at 26 kV, the single crystal device demonstrated a DQE(0) of 0.70 +/- 0.02 at 7.1 x 10(-6) C/kg (27 mR) exposure to the detector, despite its relatively poor charge collection efficiency.

Cadmium↗