**2. Literature review**

focus was on 3D mammography imaging simulation setup. Five main steps have been carefully checked and successfully produced: (a) the production of X-ray radiation or source after careful and detailed physics check. This includes the interaction between the X-ray photons and the object (the 3D breast phantom) that is used on scan as well as the detector system and its associated electronics modelled. (b) Next is the realistic modelling of anthropomorphic breast phantoms to check if the effectiveness of prediction of the simulation is successfully achieved. A computer simulation model is developed to estimate the radiation dose to the breast that would be incurred using mammography. Mono-energetic normalized glandular dose coefficients, DgN(E), were computed for energies 11–120 keV using breast phantoms of various sizes and compositions.

Breast cancer is one of the most common cancers in Saudi Arabia [1] and, thus, is an important health problem [2]. In the Western world, it is the second most frequent cause of cancer death in women (after lung cancer) [3]. Statistics show that a large number of women in Europe, North America, Australia and many Latin-American countries suffer from this life-threatening disease [4]. Worldwide, in the year 2005, the number of new cases exceeded 1.2 million [3]. Breast cancer is rare in women below the age of 20 years and less common below the age of 30 years, but it is more aggressive and thus has a lower survival rate. The incidence rate, however, rises dramatically over the age of 50 years. This could be due to several risk factors such as family history, genetics, early menstruation, late menopause and other factors that have not yet been identified. Breast cancer can also occur in males and often fatal, but it is extremely rare. The above problems have prompted global governments to put constant efforts to increase patient's recovery level against this disease. Early and accurate detection with mass screening programmes helps improve a woman's chances for successful treatment. It also minimizes pain, suffering and anxiety that surround patients and their families.

The current and the most cost-effective technique used for screening and diagnosis of breast cancer is X-ray mammography. It is the state of the art for earlier detection to improve both prognosis and survival rate [5]. This may be due to its good availability, high sensitivity and relatively low cost/patient. Despite the above efforts, the mortality rate of breast cancer still remains high and in the UK, for example, accounts for ~17% of all female deaths [6, 7]. This is due to some limitations of the current mammographic procedures. As a result, a large number of cases with positive mammography results undergo invasive surgical breast biopsies. Breast biopsy is still widely used and thus is the only fail-safe method to determine whether a lesion is malignant. Of all biopsy cases, only about 25% prove to be malignant. Moreover, a majority of the diagnosed women below the age of 50 have a dense breast tissue.

This is a problem as it obscures lesions and results in false-negative mammography.

In addition, the size, shape and appearance of the female breast are not constant but undergo a number of changes during the lifetime of women. For instance, changes occur during

**Keywords:** mammography, breast cancer detection, 3D imaging

**1. Introduction**

156 New Perspectives in Breast Imaging

Cancer is a disease that starts in a localized organ or tissue and then grows out of control. Breast cancer is an important health problem as in the western world; it is the second most frequent cause of cancer death in women (after lung cancer) [6, 7]. Statistics show that a large number of women in Europe, North America, Australia and many Latin-American countries suffer from this life-threatening disease [8]. Worldwide, in the year 2005, the number of new cases exceeded 1.2 million [7]. Breast cancer is a heterogeneous disease as it has different cell types and different behavioural characteristics and appearances. Understanding the types of breast cancer and their growth pattern is important for imaging purposes. Breast cancer is usually categorized into two main types: invasive (infiltrating) and non-invasive (in situ) cancer. In situ means that the cancer cells are at early stage, i.e. remains localized to ducts (milk passages) or lobule (milk producing glands) with no micro-invasion to the surrounding fatty tissue. Once the basement membrane is penetrated, the cancer cells break into the surrounding tissue and are referred to as invasive breast carcinoma. Breast cancer is rare in women below the age of 20 years and less common below the age of 30 years, but it is more aggressive and thus has a lower survival rate. The incidence rate, however, rises dramatically over the age of 50 years. This is may be due to several risk factors such as family history, genetics, early menstruation, late menopause and other factors that have not yet been identified. Breast cancer can also occur in males and often fatal, but it is extremely rare. The above problems have prompted global governments to put constant efforts to increase patient's recovery level against this disease. Early and accurate detection with mass screening programmes helps improve a woman's chances for successful treatment. It also minimizes pain, suffering and anxiety that surround patients and their families. The current and the most cost-effective technique used for screening and diagnosis of breast cancer is X-ray mammography. It is the state of the art for earlier detection to improve both prognosis and survival rate [9].

Mammography is a low-energy (25–32 keV) X-ray examination of the soft tissues of the breast. It uses the variation in density between normal mammary features and abnormal tissue structures (lesion) to produce the image. The current widely used technique is based on screen-film technology. It is considered the gold standard in breast imaging as it is fast and available and has a lower cost than the scintimammography. It has two main applications: as a screening method in asymptomatic patients and as a diagnostic method in symptomatic populations. The former application is extremely important, and its introduction has significantly reduced the mortality rate of breast cancer in many countries [10, 11]. The American Cancer Society (ACS), the Department of Health and Human Services (HHS), the American Medical Association (AMA) and the American College of Radiology (ACR) recommend screening mammography every year for women, beginning at age 40. This is because the screening services accurately detect micro-calcifications and non-palpable soft tissue masses which until now have been beyond other imaging methods thanks to the high spatial resolution (50100 μm). Research has shown that annual mammograms lead to early detection of breast cancers, when they are most curable and breast-conservation therapies are available. The National Cancer Institute (NCI) adds that women who have had breast cancer and those who are at increased risk due to a genetic history of breast cancer should seek expert medical advice about whether they should begin screening before age 40 and about the frequency of screening. A recent review [12] estimated that screening leads to a reduction in breast cancer mortality of 15 and to 30% overdiagnosis and overtreatment. This means that for every 2000 women invited for screening throughout 10 years, one will have her life prolonged. In addition, 10 healthy women, who would not have been diagnosed if there had not been screening, will be diagnosed as breast cancer patients and will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress for many months because of false-positive findings. Normally, screening is achieved

by exposing the breast to X-rays after being gently compressed between two plates and then taking two views for each breast. A craniocaudal (imaging from above to below) and lateral views are generally taken. A lead grid is used to reduce scattering photons that reach the film. Diagnostic mammography is used for assessing the size of the lesion, for pre-surgical localization of suspicious areas of breast and in the guidance of needle biopsies.

cases exceeded 1.2 million [7]. Breast cancer is a heterogeneous disease as it has different cell types and different behavioural characteristics and appearances. Understanding the types of breast cancer and their growth pattern is important for imaging purposes. Breast cancer is usually categorized into two main types: invasive (infiltrating) and non-invasive (in situ) cancer. In situ means that the cancer cells are at early stage, i.e. remains localized to ducts (milk passages) or lobule (milk producing glands) with no micro-invasion to the surrounding fatty tissue. Once the basement membrane is penetrated, the cancer cells break into the surrounding tissue and are referred to as invasive breast carcinoma. Breast cancer is rare in women below the age of 20 years and less common below the age of 30 years, but it is more aggressive and thus has a lower survival rate. The incidence rate, however, rises dramatically over the age of 50 years. This is may be due to several risk factors such as family history, genetics, early menstruation, late menopause and other factors that have not yet been identified. Breast cancer can also occur in males and often fatal, but it is extremely rare. The above problems have prompted global governments to put constant efforts to increase patient's recovery level against this disease. Early and accurate detection with mass screening programmes helps improve a woman's chances for successful treatment. It also minimizes pain, suffering and anxiety that surround patients and their families. The current and the most cost-effective technique used for screening and diagnosis of breast cancer is X-ray mammography. It is the state of the art for earlier detection to improve both prognosis and survival rate [9].

158 New Perspectives in Breast Imaging

Mammography is a low-energy (25–32 keV) X-ray examination of the soft tissues of the breast. It uses the variation in density between normal mammary features and abnormal tissue structures (lesion) to produce the image. The current widely used technique is based on screen-film technology. It is considered the gold standard in breast imaging as it is fast and available and has a lower cost than the scintimammography. It has two main applications: as a screening method in asymptomatic patients and as a diagnostic method in symptomatic populations. The former application is extremely important, and its introduction has significantly reduced the mortality rate of breast cancer in many countries [10, 11]. The American Cancer Society (ACS), the Department of Health and Human Services (HHS), the American Medical Association (AMA) and the American College of Radiology (ACR) recommend screening mammography every year for women, beginning at age 40. This is because the screening services accurately detect micro-calcifications and non-palpable soft tissue masses which until now have been beyond other imaging methods thanks to the high spatial resolution (50100 μm). Research has shown that annual mammograms lead to early detection of breast cancers, when they are most curable and breast-conservation therapies are available. The National Cancer Institute (NCI) adds that women who have had breast cancer and those who are at increased risk due to a genetic history of breast cancer should seek expert medical advice about whether they should begin screening before age 40 and about the frequency of screening. A recent review [12] estimated that screening leads to a reduction in breast cancer mortality of 15 and to 30% overdiagnosis and overtreatment. This means that for every 2000 women invited for screening throughout 10 years, one will have her life prolonged. In addition, 10 healthy women, who would not have been diagnosed if there had not been screening, will be diagnosed as breast cancer patients and will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress for many months because of false-positive findings. Normally, screening is achieved

The reported sensitivity (the fraction of patients actually having the disease and correctly diagnosed as positive) in lesion detection varies between 69 and 90% [13] depending on the breast density. The specificity (the fraction of patients without the disease, correctly diagnosed as negative) is the major drawbacks of conventional mammography. A variation in specificity between 87 and 97% and a low positive predictive value as low as 15% have also been reported in Ref. [14]. This 'less than perfect' performance may be due to several confounding factors, e.g. poor mammographic technique, observer error, the lesions are non-palpable or at a cellular level and/or the lesions are obscured by the normal breast tissues. In addition, the presence of scars or tissue distortion may hide true small tumours on the mammogram. Moreover, in mammography the ultimate challenge with regard to X-ray image quality and, thus, improving the reliability of screening and early diagnosis, requires better epidemiological understanding of breast tissues, improved diagnostic tools, enhanced quality control, continuous training and efficient management of data and records. Nevertheless, conventional mammography remains the most valuable and cost-effective technique for breast tumour diagnosis.

Over the last two decades, considerable efforts have been carried out to improve the current screen-film mammographic technique. These improvements include image quality, acquisition techniques and interpretation protocol in order to reduce some of the mammographic limitations [15]. Furthermore, a new research effort started 5 years ago focusing on 'digital mammography' (DM) as a possible future direction in breast imaging. Digital mammography, also called full-field digital mammography (FFDM), is a mammography system in which the X-ray film is replaced by solid-state detectors that convert X-rays into electrical signals. These detectors are similar to those found in digital cameras. The electrical signals are used to produce images of the breast that can be seen on a computer screen or printed on special film similar to conventional mammograms. This technique offers many advantages compared to the conventional screen-film-based method [16, 17]. For instance, processing with digital systems increases dynamic range (two to four times the dynamic range of typical film screen) and improved quantum efficiency and storage and display mechanisms. In addition, the use of computer-assisted image interpretation is claimed to be helpful for the physician. This may enhance different features such as computer-aided diagnosis which may further improve the visibility of lesions and improve mammographic sensitivity [18]. Therefore, repeated exposures (which are sometimes needed when using conventional mammography) are not required, and this may reduce the radiation dose. Moreover, it does not need either cassettes or dark rooms or processors and thus allegedly saves space and time in archiving and retrieving DM images. However, DM requires large disk space for saving image data.

Despite several advantages, DM does not yet replace screen-film mammography in many centres. However, with continuous technical improvements of the digital system, it is gradually taking over the conventional systems. Both conventional and DM systems suffer from substantial technical and clinical limitations. For instance, these systems are unreliable in imaging patients with dense parenchyma tissue especially in the younger female population due to more glandular tissue. Breast implants can also impede accurate mammogram readings because both silicone and saline implants are not transparent on X-rays. Thus, it blocks a clear view of the tissues behind them. This is true especially if the implant has been placed in front of, rather than beneath, the chest muscles. This issue requires an experienced technologists and radiologists to carefully compress the breasts to improve the view without rupturing the implant. All the above limitations and problems of imaging need to be dealt with to enhance detection efficiency and overcome the drawback. One of the methods that recently employed is the computer-aided detection (CAD) systems. Such systems use a digitized mammographic image that can be obtained from either a conventional film mammogram or a digitally acquired mammogram. The computer software then searches for abnormal areas of density, mass or calcification that may indicate the presence of cancer. The CAD system highlights these areas on the images, alerting the radiologist to the need for further analysis. Despite that mammographic findings are non-specific (cannot always differentiate benign from malignant disease) and often underestimate the size of the detected lesion, X-ray–based imaging is also not useful for breast diagnosis following surgery or radiotherapy as the patient's breasts in these cases have architectural distortion. Mammography is not recommended for women with breast implants and is also not useful following hormonal replacement therapy due to the increase of breast density. It is worth mentioning that X-ray mammography is not always useful for non-palpable tumours. Another group of women close carrying a mutation in BRCA1 (human gene called breast cancer 1, early onset) or BRCA2 (breast cancer 2) genes—are at high genetic risk of cancer, some even having opted for preventative bilateral mastectomy. It is preferred not to repeat scan this group due to X-ray dose, and thus, a more sensitive diagnostic test would be advisable.

Moreover, the size, shape and appearance of the female breast are not constant but undergo a number of changes during the lifetime of women. For instance, changes occur with pregnancy, breast feeding and during the menstrual cycle. In addition, the age of the subject not only influences the shape but also parenchymal density of the breast. That is why young women tend to have dense breasts (more fibro-glandular tissue), creating a rounded appearance. On the other hand, postmenopausal women have breasts containing a large amount of fat. This makes the X-ray mammogram far more effective in older women as the fat content is more radio-translucent (appears darker) than glandular tissue (appears underexposed) in younger women [19]. The above discussion suggests that both the shape and parenchymal density of the breast imposes particular constraints on the choice of imaging modality. The imaging technique should be powerful for initial detection and subsequent follow-up of the diseases. At present, no single technique can be used for all cases of breast cancer detection without showing certain clinical or technical limitations. This implies necessity to address the specific needs that can help for breast tumour imaging to overcome these limitations. For instance, breast compression is often needed as it holds the breast still and enhances the spatial resolution. It also evens out the breast thickness and reduces scatter in X-ray or gamma-ray imaging [20], thus increasing image sharpness. Moreover, it spreads out the tissue so that small abnormalities will not be obscured by the overlying breast tissue. Since the breast is an external organ and extends to the chest wall, it requires appropriate views to be taken. For instance, in X-ray mammography a lateral (from the side) view of the breast allows separation of the chest wall from lesions deep within the breast. On the other hand, in single photon-ray emission imaging, one needs to separate the breast from the heart by employing an appropriate prone (face down) position. However, it has been claimed that with prone imaging view, there is a possibility of missing a small low-intensity medial lesion because of attenuation. This implies that another image is needed but with the camera positioned in the lateral view. In addition, shielding the camera from the background cardiac flux is very useful in tumour detection in terms of contrast and resolution [21, 22].

Having discussed the golden diagnostic technique for breast tumour imaging, the following section will describe the complementary imaging techniques of the breast. The image reconstruction techniques will be then discussed. Section 3 will be closed by presenting some preliminary results and a description of the design details.
