Elemental and phase composition of breast calcifications

Despite the importance of calcifications in early detection of breast cancer, and their proposed association with tumour growth, remarkably little detail is known about their chemical composition, or how this relates to pathology. One reason for this gap is the difficulty of systematically and precisely locating calcifications for analysis, particularly in sections taken from diagnostic archives. Two simple methods were developed which can achieve this in sections cut from wax embedded breast tissue. These are based on micro-CT and x-ray fluoroscopy mapping, and were used to locate calcifications for further study. The elemental composition of calcifications in histological sections was measured using energy-dispersive x-ray spectroscopy in an environmental scanning electron microscope. Variations in Ca:P ratio could in principle be detected non-invasively by dual energy absorptiometry, as demonstrated in a proof of principle experiment. However, the Ca:P ratio was found to lie in a narrow range similar to bone, with no significant difference between benign and malignant. In contrast, a substantial and significant difference in Na:Ca ratio was found between benign and malignant specimens. This has potential for revealing malignant changes in the vicinity of a core needle biopsy. The phase composition and crystallographic parameters within calcifications was measured using synchrotron x-ray diffraction. This is the first time crystallite size and lattice parameters have been measured in breast calcifications, and it was found that these both parallel closely the changes in these parameters with age observed in foetal bone. It was also discovered that these calcifications contain a small proportion of magnesium whitlockite, and that this proportion increases from benign, to carcinoma in-situ, to invasive cancer. When combined with other recent evidence on the effect of magnesium on hydroxyapatite precipitation, this suggests a mechanism explaining observations that carbonate levels within breast calcifications are lower in malignant specimens

Characterization of breast calcification types using dual energy X-ray method

Calcifications are products of mineralization whose presence is usually associated with pathological conditions. The minerals mostly seen in several diseases are calcium oxalate (CaC2O4), calcium carbonate (CaCO3) and hydroxyapatite (HAp). Up to date, there is no in-vivo method that could discriminate between minerals. To this aim, a dual energy X-ray method was developed in the present study. An analytical model was implemented for the determination of the Calcium/Phosphorus mass ratio (mca/mp ). The simulation was carried out using monoenergetic and polyenergetic X-rays and various calcification thicknesses (100 to 1000 um) and types (CaC2O4, CaCO3, HAp). The experimental evaluation of the method was performed using the optimized irradiation conditions obtained from the simulation study. X-ray tubes, combined with energy dispersive and energy integrating (imaging) detectors, were used for the determination of the mca/mp in phantoms of different mineral types and thicknesses. Based on the results of the experimental procedure, statistical significant difference was observed between the different types of minerals when calcification thicknesses were 300 um or higher

Dual Energy Method for Breast Imaging: A Simulation Study

Dual energy methods can suppress the contrast between adipose and glandular tissues in the breast and therefore enhance the visibility of calcifications. In this study, a dual energy method based on analytical modeling was developed for the detection of minimum microcalcification thickness. To this aim, a modified radiographic X-ray unit was considered, in order to overcome the limited kVp range of mammographic units used in previous DE studies, combined with a high resolution CMOS sensor (pixel size of 22.5 m) for improved resolution. Various filter materials were examined based on their K-absorption edge. Hydroxyapatite (HAp) was used to simulate microcalcifications. The contrast to noise ratio (CNR ) of the subtracted images was calculated for both monoenergetic and polyenergetic X-ray beams. The optimum monoenergetic pair was 23/58 keV for the low and high energy, respectively, resulting in a minimum detectable microcalcification thickness of 100 m. In the polyenergetic X-ray study, the optimal spectral combination was 40/70 kVp filtered with 100 m cadmium and 1000 m copper, respectively. In this case, the minimum detectable microcalcification thickness was 150 m. The proposed dual energy method provides improved microcalcification detectability in breast imaging with mean glandular dose values within acceptable levels

Imaging of the Breast

Early detection of breast cancer combined with targeted therapy offers the best outcome for breast cancer patients. This volume deal with a wide range of new technical innovations for improving breast cancer detection, diagnosis and therapy. There is a special focus on improvements in mammographic image quality, image analysis, magnetic resonance imaging of the breast and molecular imaging. A chapter on targeted therapy explores the option of less radical postoperative therapy for women with early, screen-detected breast cancers

Feature analysis methods for intelligent breast imaging parameter optimisation using CMOS active pixel sensors

This thesis explores the concept of real time imaging parameter optimisation in digital mammography using statistical information extracted from the breast during a scan. Transmission and Energy dispersive x-ray diffraction (EDXRD) imaging were the two very different imaging modalities investigated. An attempt to determine if either could be used in a real time imaging system enabling differentiation between healthy and suspicious tissue regions was made. This would consequently enable local regions (potentially cancerous regions) within the breast to be imaged using optimised imaging parameters. The performance of possible statistical feature functions that could be used as information extraction tools were investigated using low exposure breast tissue images. The images were divided into eight regions of interest, seven regions corresponding to suspicious tissue regions marked by a radiologist, where the final region was obtained from a location in the breast consisting solely of healthy tissue. Results obtained from this investigation showed that a minimum of 82% of the suspicious tissue regions were highlighted in all images, whilst the total exposure incident on the sample was reduced in all instances. Three out of the seven (42%) intelligent images resulted in an increased contrast to noise ratio (CNR) compared to the conventionally produced transmission images. Three intelligent images were of similar diagnostic quality to their conventional counter parts whilst one was considerably lower. EDXRD measurements were made on breast tissue samples containing potentially cancerous tissue regions. As the technique is known to be able to distinguish between breast tissue types, diffraction signals were used to produce images corresponding to three suspicious tissue regions consequently enabling pixel intensities within the images to be analysed. A minimum of approximately 70% of the suspicious tissue regions were highlighted in each image, with at least 50% of each image remaining unsuspicious, hence was imaged with a reduced incident exposure

Mammography

In this volume, the topics are constructed from a variety of contents: the bases of mammography systems, optimization of screening mammography with reference to evidence-based research, new technologies of image acquisition and its surrounding systems, and case reports with reference to up-to-date multimodality images of breast cancer. Mammography has been lagged in the transition to digital imaging systems because of the necessity of high resolution for diagnosis. However, in the past ten years, technical improvement has resolved the difficulties and boosted new diagnostic systems. We hope that the reader will learn the essentials of mammography and will be forward-looking for the new technologies. We want to express our sincere gratitude and appreciation?to all the co-authors who have contributed their work to this volume

System parameters and performance specifications for the application of Diffraction Enhanced Imaging and Multiple Image Radiography to breast imaging

The Diffraction Enhanced Imaging (DEI) method is a novel x-ray imaging technique that dramatically extends the capability of conventional x-ray imaging. X-ray imaging has traditionally been dependent on x-ray absorption to generate contrast, and is the physical mechanism of contrast in planar x-ray imaging and computed tomography. DEI utilizes the Bragg peak of perfect crystal diffraction to convert angular changes into intensity changes, providing a large change in intensity for a small change in angle. The use of a silicon analyzer crystal in the path of the x-ray beam generates two additional forms of image contrast, refraction and extinction. Objects that have very little absorption contrast may have considerable refraction and extinction contrast, this improving visualization and extending the utility of x-ray imaging. An area of medicine where this technique could have a dramatic impact is in breast imaging, where the key diagnostic structures often have low absorption contrast, especially in the early stages of disease. In order to develop a DEI clinical prototype imaging system, a systematic assessment of the engineering parameters for the breast imaging application must be determined. This body of work investigates the primary imaging parameters of DEI (x-ray beam energy, crystal reflections, angular sampling) and demonstrates how the unique properties of DEI can be capitalized upon to address the engineering limitations of flux, dramatically reducing the dose required for imaging. The results from this analysis are used to describe a plausible design for a non-synchrotron based DEI breast imaging system

Development of in vivo Raman spectroscopy for the diagnosis of breast cancer and intra-operative margin assessment

Thesis (Ph. D.)--Harvard University--MIT Division of Health Sciences and Technology, 2005.Includes bibliographical references.Breast cancer is the most commonly diagnosed cancer among women in the United States. It is the most common cause of death in women ages 45-55. Optical techniques can potentially play a diagnostic role in several aspects of breast cancer evaluation and treatment. This thesis outlines progress on the use of Raman spectroscopy to diagnose breast cancer. Laboratory studies on fresh-frozen tissues are used to demonstrate that the detailed information provided by Raman spectroscopy yields accurate breast disease diagnosis. A Raman spectroscopic-based diagnostic algorithm was developed which classifies samples into four categories according to specific pathological diagnoses: normal, fibrocystic change, fibroadenoma, and infiltrating carcinoma. Cancerous lesions were separated from non- cancerous tissues with a sensitivity of 94% and a specificity of 95%. Further, use of a spectral model based on the morphological structures that comprise breast tissue allows increased understanding of the relationship between a Raman spectrum and tissue disease state. Based on the excellent results of our laboratory work, two clinical studies were undertaken. These studies translate Raman spectroscopy from a laboratory technique into a clinically useful tool. The first study tests the diagnostic algorithm in a prospective manner on freshly excised tissue. Preliminary results are promising. The second study is the first demonstration of in vivo data acquisition of Raman spectra of breast tissue. The culmination of this research is the demonstration of accurate intra-operative margin status assessment during partial mastectomy surgeries.(cont.) Application of our previously developed diagnostic algorithm resulted in perfect sensitivity and specificity in this small in vivo data set. These preliminary findings indicate that Raman spectroscopy has the potential to lessen the need for re-excision surgeries resulting from positive margins and thereby reduce the recurrence rate of breast cancer following partial mastectomy surgeries. The experiments and theory presented throughout this thesis demonstrate that Raman spectroscopy is a viable clinical tool that can be used to accurately diagnosis breast cancer and breast disease.by Abigail Susan Haka.Ph.D