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Abstract

There are both benefits and risks associated withmost medical procedures. Medical imaging,especially imaging that exposes patients to ionizingradiation, is no exception. The goal of medicalimaging is to provide the most useful medical infor-mation, at the lowest risk commensurate with pro-viding that information. Mammography exposesthe breast, one of the tissues most sensitive toionizing radiation. Therefore, it is important todetermine what level of image quality is requiredto permit appropriate medical decision making andconsequently how much radiation is required.In this Report the technical aspects of mammogra-

phy are reviewed in detail and the principles of mam-mographic image quality are discussed withemphasis on the connection between image qualityand absorbed dose to the breast tissue. The newlyemerging modality, digital mammography, is alsoconsidered in some detail. While the importanceof quality control (QC) for mammography is

emphasized, there are several excellent publicationson this topic so it is not covered extensively. Instead,what is provided is an outline of the aspects ofimaging performance that should be tested uponinstallation of the equipment (acceptance testing)and periodically during its use (routine QC). As well,in the Appendices, some of the major QC programsin various countries or regions are described alongwith examples of test tools used in those programs.This Report is intended for healthcare policy

decision makers, radiologists, referring physicians,medical physicists, and medical imaging radiogra-phers (technologists). Mammography is widelyused in many countries, with the potential of alarge benefit in reducing mortality from breastcancer and facilitating the management of thisdisease. The principles discussed in this Reportshould be helpful to the reader in helping toprovide this benefit while reducing radiation-related risks to acceptable levels.

Journal of the ICRU Vol 9 No 2 (2009) Report 82 10.1093/jicru/ndp032Oxford University Press

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1. Introduction

Mammography plays an important role in thedetection and diagnosis of breast cancer as well asin localization for biopsy and therapy. Earlier detec-tion has contributed to reduction of mortality frombreast cancer. To realize the benefits of mammogra-phy it must be carried out on high-quality equip-ment that is properly maintained and calibrated.The examinations must be performed by well-trained radiographers and interpreted by skilledradiologists with specialized experience inmammography.The physics of image formation has been studied

extensively, and the principles of achieving highquality are well understood. Modern mammogra-phy is accomplished using a fairly complex systemof technology in which the x-ray source size, thex-ray spectrum produced, the beam geometry,breast compression, image receptor (the deviceused to absorb x rays transmitted by the breast andacquire the image), image processing and viewingcomponents have all been chosen to maximize thepossibility of detecting small breast cancers.While mammography is the most widely used

imaging modality for the breast, other imaging toolssuch as ultrasound and breast magnetic resonanceimaging (MRI) provide complementary informationto facilitate accurate diagnosis by discovering somecancers not visible on mammography, by revealingthe true extent of disease or by ruling out false posi-tive findings on mammography. New techniquessuch as digital mammography, tomosynthesis andcomputer-aided detection and diagnosis can furtherincrease the accuracy of mammography.The benefits of any medical imaging procedure

must be balanced against any risks imposed by theprocedure. In the case of mammography, the mainbenefits are: reasonable reassurance that breastcancer is not present (in the case of a negativeexamination result) or earlier detection of breast

cancer and the possibility of reduced mortality ormorbidity associated with treating less-advanceddisease in the case of a positive test. The risksinclude false reassurance that cancer is not present(a false-negative examination), and unnecessaryconcern that cancer might be present when in factit is not (false-positive examination). Becausemammography delivers a dose of ionizing radiationto the breast, the risk of radiation-induced breastcancer must also be considered.Maintaining the mammography system in its

optimum condition requires implementation andregular performance of a quality assuranceprogram in which technical quality control testingis conducted at regular intervals. Performance pro-blems discovered through these tests should beattended to through prompt action to restore theequipment to proper operating specifications in atimely manner.No medical examination has experienced as

much controversy as x-ray mammography (ACS,2003; Ernster and Kerlikowske, 1999; Feig, 2002;Kopans, 2003; US Preventive Services Task Force,2002). This is especially true with respect to its usefor screening asymptomatic women (Berrington deGonzalez and Reeves, 2005; Miller, 2001; 2003;Tabar et al., 2003). Concerns have been expressedboth in relation to its efficacy and the potential riskassociated with the absorbed doses received.However, the value of mammography has now beendemonstrated in several studies. Nevertheless, it isimportant that it is carried out in an optimizedmanner, i.e., that the image quality be optimum forthe task of detection and diagnosis of breast cancerand that the dose received be as low as is possible,consistent with achieving the required level ofimage quality. This Report considers these issuesas well as those pertaining to the quantification ofimage quality in mammography.

Journal of the ICRU Vol 9 No 2 (2009) Report 82 doi:10.1093/jicru/ndp017Oxford University Press



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2. Mammography in Clinical Practice

Mammography is an x-ray imaging procedure forexamining the breast. It is used primarily for thedetection and diagnosis of breast cancer, but alsofor the guidance of needle biopsies and pre-surgicallocalization of suspicious areas.

2.1 Breast Cancer

Internationally, breast cancer has been thecancer of highest incidence and mortality inwomen. More than 1 million were diagnosed withbreast cancer internationally in 2002 with morethan 477,000 deaths (Parkin et al., 2005; WHO,2004). The cause or causes of breast cancer are notcompletely understood; however, it has beendemonstrated that mortality is substantiallyreduced if disease is detected at an early stage(Duffy et al., 2006; Smart et al., 1995; Tabar et al.,1993; 2003).

Although the probability of developing breastcancer increases with a womans age (seeTable 2.1), the age distribution of the female popu-lation causes the percentage of the total breastcancer incidence to vary only slightly with agebetween the ages 45 and 64 (see Table 2.2).

Mammography is an effective method for detect-ing early-stage breast cancer. It is used both forinvestigating symptomatic patients (diagnosticmammography) and for screening of asymptomaticwomen in selected age groups. In screening, it isthe only imaging method that has so far beendemonstrated to contribute to reduction of mor-tality due to breast cancer (Duffy et al., 2006).

2.2 Anatomy and Physiology of the Breast

The mammogram must accurately represent theanatomy of the breast, illustrated in Figure 2.1.The breast is a compound exocrine-modified sweatgland that rests on the pectoralis muscle of theanterior chest wall. It can extend from the mid-axillary line laterally to the sternum medially andfrom the second to the sixth costal cartilage. Thebasic structure of the breast is the lobe that drains

by the lactiferous duct opening onto the nipple.Within each lobe there are multiple lobules. Theterminal ductal lobular unit is the site of origin ofmost breast disease and is normally only about3 mm to 5 mm in size. It consists of the extralobu-lar terminal duct and the lobule. The latter is com-prised of the intralobular terminal duct and theacini. The arterial supply is primarily from thelateral thoracic and intercostal arteries withbranches from the internal mammary artery. Thelymphatic system is the route of spread of breastcancer to other parts of the body. The lymphaticvessels drain primarily to the axillary, interpec-toral, supraclavicular, and internal mammarynodes. However, there is also free communicationto the opposite breast and into the abdomen.

The breast is vestigial in children and men anddevelops at puberty in women due to stimulationby estrogen and progesterone from the ovaries.However, other hormones such as growth andthyroid hormones, the adrenal corticosteroids, andinsulin are also required. The fluctuation inhormone levels during the normal menstrual cycleresults in the cyclical proliferation then atrophy ofthe hormone-sensitive tissues in the breast. Thismight have an effect on the development of patho-logical conditions. At menopause, the loss of estro-gen and progesterone usually results in a decreasein the amounts of epithelial and connective tissue,which is observable in the mammogram. However,the common use of hormone-replacement therapy,other endogenous hormones and drugs might actu-ally result in an increase in the parenchymal andstromal tissues at menopause.

2.3 Pathology of the Breast

The most significant disease of the breast iscancer. For most women a breast problem can beclassified as being due to cancer or not due tocancer, with the actual cause of the latter beingless important. Breast cancer is the commonestcancer and the second commonest cause of cancerdeath in women in western countries. In thesecountries, the incidence continues to increase




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slightly, while the mortality rate has declinedslightly since 1985 and more so since 1990. Morerecently, a reduction in breast cancer incidence forthe year 2003 was reported (Ravdin et al., 2007). Itis speculated that this might be due to reduced useof hormone-replacement therapy. Breast cancer inmen does occur but accounts for less than 1 % ofbreast cancers.

Most breast cancers are carcinomas that arise inthe epithelium of the terminal ductal lobular unit.Invasive carcinomas are divided into ductal (90 %)and lobular (10 %). In situ carcinomas are thosethat have not extended beyond the basement mem-brane of the duct or acinus. Other cancers areuncommon, but, of these, lymphomas and metas-tases are most likely to be seen.

2.4 Radiological Signs of Breast Cancer

The routine radiographic examination consists ofthe mediolateral oblique and craniocaudal views asillustrated in Figure 2.2. The primary radiographicsigns of malignancy are calcifications, masses,asymmetrical or new densities, and architecturaldistortion. Secondary changes can occur in thenipple, skin, and lymph nodes. Correlation with theclinical history and physical findings is necessary.

The American College of Radiology has estab-lished a standardized system and terminology forreporting mammographic findings. The BreastImaging Reporting and Data System (BI-RADS)

Figure 2.1. Anatomy of the breast. (a) A schematic lateral view ofthe breast. (b) A mediolateral oblique projection mammogram inwhich a number of anatomic structures are identified: (A)pectoralis muscle, (B) nipple, (C) adipose tissue, (D) glandulartissue, (E) blood vessel, (F) lymph node, (G) Coopers ligaments, (H)latissimus dorsi muscle. From NCRP Report 149 (NCRP, 2004).

Table 2.1. Probability of a woman developing breast cancer atdifferent ages

Age group Probability of developing breast cancer (%)

,40 0.484049 1.435059 2.56069 3.5.70 3.88Total 12.28

Data from DevCan (2005) and Horner et al. (2009).

Table 2.2. Age distribution of female breast cancer incidence

Age group Relative incidence of breast cancer (%)

,45 104554 235564 28.65 39Total 100

Data from Horner et al. (2009).

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(ACR, 2003) provides nomenclature for describingradiological signs of malignancy and benigndisease.

2.4.1 Calcifications

Calcifications are evaluated according to theirdistribution (location and number) and morphology(size, shape, and density). Calcifications that arebilateral, symmetrical, or diffuse in distribution aremore likely benign as in fibrocystic changes. Thosethat are unilateral, linear, segmental, or clusteredare of greater concern. Benign calcifications tend tobe smooth, round, sharp, lucent-centered, dense, orcoarse such as in fibroadenomata. Those of inter-mediate concern are more amorphous, indistinct, orcoarse-heterogeneous. Malignant calcifications tendto be fine-pleomorphic, irregular, linear, andbranching. Calcifications of ductal carcinomain situ can be quite characteristic. However, thereis overlap between benign and malignant appear-ances that can often be clarified only by furtherradiographic images, usually coned compressionmagnification views or biopsy. Percutaneous stereo-tactic guided core or vacuum-assisted biopsy isindicated in some cases. As these calcifications canbe only a few hundred micrometers in diameter, itis extremely important to have excellent imagequality that allows their identification andcharacterization.

2.4.2 Masses

Masses are assessed according to their location,size, number, and relative density, but more

importantly on their shape and margin. There is aconsiderable variability, but generally a solitarydominant lesion is of more concern than multiplesmall similar masses. Masses are evaluated asbeing high, equal, or low density compared to anequal volume of fibroglandular tissue. Masses con-taining radiolucent fat are very likely to be benign,such as an intramammary lymph node or a hamar-toma. Masses that are relatively dense for theirsize compared to normal breast tissue raise moresuspicion. The BI-RADS descriptors for shapes asbeing round, oval, lobular, and irregular reflect, inthat order, increasing suspicion. Similarly, the levelof concern ascribed to margins of masses increasesin the following order: circumscribed, obscured,microlobulated, indistinct, to spiculated. Typicallybenign common masses might be cysts or fibroade-nomata. To be able to appreciate these featuresrequires images that have been produced withoptimum exposures, contrast, and resolution.Additional mammographic coned views and anultrasound examination can be used for furtherassessment.

2.4.3 Asymmetry

The asymmetry refers to the difference in volumeor relative density of breast tissue or prominentducts. The need is to determine if the finding isdue to normal breast tissue or an obscured massusing the same tools as for masses. To find newasymmetries requires comparison with the oppositebreast and with any previous examinations thatcan be obtained.

Figure 2.2. Illustrative mammograms. (a) Craniocaudal view. ( b) Mediolateral oblique view.

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2.4.4 Architectural Distortion

Architectural distortion is seen as straight linesradiating from a central area and retraction orbulging of a contour. Architectural distortion isoften subtle and difficult to perceive without high-quality images. Its causes can be benign or malig-nant, and careful correlation with the history andphysical findings must be done. Surgical scars cancause a very suspicious appearance. Againadditional mammographic views and ultrasoundevaluation might be necessary.

2.4.5 Other Signs

Intramammary and axillary lymph nodes arenoted for abnormalities in size, shape, and theabsence of the normally fatty hilum. Skin thicken-ing or retraction and nipple retraction are alsosigns of concern.

2.5 Indications for Mammography

2.5.1 Symptomatic Women: Diagnosis

Mammography is used to investigate breastsymptoms as well as the findings detected onscreening mammograms or clinical examination.This would include women in the followingsituations:

Possible abnormality on screening mammograms. Women over 40 years of age with breast implants. Palpable mass. Ultrasound is the imaging

modality of choice for a mass in the womanunder 30 years of age, pregnant, or lactating.

Unilateral nipple discharge from a single orificethat is serous or bloody.

Skin changes, such as dimpling or rash. Nipple inversion, deviation, or rash. Axillary lymphadenopathy. Metastatic adenocarcinoma of an unknown

primary source. Severe persistent focal pain or tenderness unre-

lated to the menstrual cycle. Previous treatment for breast cancer.

2.5.2 Asymptomatic Women: Screening

Screening mammography is done to detectunsuspected breast cancer in asymptomaticwomen. In those women with an average risk ofbreast cancer, annual or biennial mammographicscreening is performed in some jurisdictions forwomen 40 years of age or older. For example thescreening programs in 8 of 10 Canadian provincesaccept women at age 40 (PHAC, 2006). Similarly,

the Australian program accepts women from age 40(Barratt et al., 1997). Screening has been shownto be beneficial for those up to the age of about74 years.

American recommendations for screening womenat very high risk due to genetic mutations or sig-nificant family histories of breast or ovarian cancerhave recently been published (Saslow et al., 2007).There is now strong evidence (Kriege et al., 2004;Kuhl et al., 2005; MARIBS, 2005; Warner et al.,2004) that contrast-enhanced breast magnetic-resonance imaging (MRI) is a more accuratemethod for screening these women and is rec-ommended in addition to mammography. However,if mammography is used for this purpose, the com-monly accepted ad hoc recommendations are tobegin mammographic screening at approximately10 years prior to the age of diagnosis of breastcancer in the first-degree relative.

2.6 Role of Ultrasound

In ultrasound breast imaging, a piezoelectrictransducer is used to create a series of short pulsesof focused sound (mechanical waves) in the fre-quency range 7.5 MHz to 15 MHz. By coupling thetransducer to the breast with a gel, the pulses pro-pagate into the breast, and part of their energy isreflected from tissue interfaces encountered alongtheir path, so that a single pulse will provide mul-tiple reflected pulses. These pulses travel backtowards the transducer, which is switched intoreceiving mode to convert the returning energyinto a radio-frequency electrical signal. The totaltime between emission from the transducer anddetection of the energy is proportional to theround-trip distance between the transducer and aparticular tissue structure, and inversely pro-portional to the speed of sound in the tissue. Fromthe timing of the returning pulses and theirstrength, an image can be formed containing infor-mation on the morphology and mechanical proper-ties (e.g., stiffness) of the tissue.

Advantages of ultrasound imaging are that it isnot adversely affected by radiographically densetissue, it does not require the use of ionizing radi-ation, and it is relatively inexpensive. Furthermore,the images are inherently tomographic, and so arefree from the problems of superposition thatcan limit the effectiveness of mammography.Compression of the breast is not necessary. On theother hand, one of the limitations of ultrasound isthat it is highly operator dependent. This makes itless reproducible. Therefore, a physician shouldeither conduct the examination or be close at hand to


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supervise it. Ultrasound is also less effective thanmammography in demonstrating microcalcifications.

Indications:

As the first imaging modality to evaluate apalpable mass in women ,30 y, lactating, orpregnant.

As an ancillary modality to investigate a clini-cal or mammographic finding, to assess extent of malignant disease including

the axilla, to distinguish between cystic and solid lesions, to look for unknown primary adenocarcinoma, to evaluate serous or bloody nipple discharge, to assess implant integrity.

To guide fine-needle aspiration of cystic and solidlesions.

To guide large-core needle biopsy and pre-operative wire localization.

Although ultrasound can sometimes detect smallinvasive carcinoma not evident on mammography,its use for routine screening has not been scientifi-cally validated at this time. Research into its use toscreen women at high risk for developing breastcancer and with mammographically dense breastscontinues.

Ultrasound guidance is the method of choice forcore-needle biopsy of ultrasound-visible lesionseven if they are seen on other modalities. It is pri-marily used to obtain tissue for pathological diag-nosis of a mass, including the mammographicallyoccult mass that might be associated withcalcifications.

2.7 Role of MRI

Magnetic-resonance imaging (MRI) can be highlyeffective in detecting breast cancer. In breast MRIthe patient lies prone within the bore of a powerfulelectromagnet. This is often of the superconductingtype with a field strength of 1.5 or 3 Tesla. Thiscauses the magnetic spins of the protons, primarilyin water, in the body to align with the strong mag-netic field. A series of magnetic-field gradients andradio-frequency (RF) pulses (referred to as a pulsesequence) is then used to stimulate the protonsand reorient their magnetic spins. As the excitedproton spins relax to realign with the main field,they emit RF electromagnetic energy. The strengthof the signal and the relaxation times of theprotons reveal information about their environ-ment, which varies according to tissue type and isoften different between healthy and malignanttissues. Clever design of the pulse sequence andswitching of gradient fields provides variation of

resonant frequency or phase of the RF signal withposition in the patient. Through Fourier transformanalysis, the positional dependence of the origin ofsignals can be deduced and an image can bereconstructed.

Cancers and other abnormalities can stimulate thegrowth of new, poorly formed blood vessels (tumorneoangiogenesis). In breast MRI, leakage and poolingof an intravenously injected paramagnetic contrastagent (gadolinium DTPA) from these vessels in thevicinity of a tumor affect the magnetic properties ofprotons in tissue water nearby, and these changes areimaged. MRI has been demonstrated to be very sensi-tive in the detection of breast cancer. It is particularlyuseful in high-risk women, for example those whocarry genetic mutations that place them at ten-foldelevated risk of breast cancer compared to the generalpublic. It is considerably more sensitive than eitherultrasound or mammography in these women, and,when combined with one or both of these modalitiesin a screening regimen, it provides almost 100 % sen-sitivity in detecting breast cancer (Kuhl et al., 2005;Kriege et al., 2004; Leach et al., 2005; Lehman et al.,2005; Saslow et al., 2007; Warner et al., 2004).Currently, however, its specificity is low compared tomammography, resulting in a higher than desiredfalse-positive yield in screening.

Indications:

Screening of women at very high risk for breastcancer because of genetic mutations.

To look for an unknown primary adenocarcinoma. To determine extent of malignancy primary or

residual. To monitor response to neoadjuvant chemotherapy. To differentiate recurrent malignancy from a scar. To address problems in mammographically dense

breasts. To assess implant integrity.

2.8 Clinical Qualitative Evaluation of theMammographic Process

Professional and government organizations haveset standards for the practice of mammography.In several countries (the USA, UK, Australia,New Zealand, Canada, Japan, Latin Americancountries), peer review of clinical image quality isperformed as part of an accreditation process (CAR,1998; 2008; Hendrick, 1999; McLelland et al., 1991;Moore et al., 2005; Morimoto et al., 2004; Terada,2002; Workman et al., 2006). Images are assessedby the radiologist or a quality-control radiographerfor positioning, compression, exposure, contrast,sharpness, noise, artifacts, and examination identi-fication according to the criteria discussed below.

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Positioning. The objective is to maximize theamount of breast tissue examined. The mediolat-eral oblique view must show adequate visualizationof posterior tissues, no sagging at the inframam-mary fold, and the pectoral muscle should bewithin 2 cm of the nipple line. The craniocaudalview should show no excess exaggeration mediallyor laterally. No portion of the breast should beexcluded from the mammogram, and there shouldbe no skin folds or other body parts projected overthe breast.

Compression. Compression is adequate if there isgood separation of parenchymal densities withuniform exposure levels and no patient motion.

Exposure. A proper exposure provides adequatepenetration of dense and fatty parts of the breasts,but does not generally over-expose or under-exposethe image receptor for any region of the breasts. Itmust be possible to identify microcalcifications withinor superimposed on dense fibroglandular tissue.

Contrast. There should be adequate contrastbetween the fatty and fibroglandular parts of thebreast over as much of the breast as possible.

Sharpness. Image should have sufficient sharp-ness (spatial resolution) to provide good delineationof linear structures, feature margins, and microcal-cifications. High spatial resolution is necessary toboth identify and characterize lesions.

Noise. The image should not contain excessivefluctuation in signal (either random or caused bydiagnostically irrelevant structures) that could limitvisualization of fine detail needed for diagnosis.

Artifacts. Images are evaluated for the presenceof artifacts related to screens, grids, handling, pro-cessing, and foreign substances. These couldobscure significant findings.

Examination identification. The images shouldbe properly identified with the patients name, aunique identifier such as birth date or facilityregistration number, facility, date, mammographicview and axillary side, cassette, and technologistwho performed the examination.

2.9 Reporting

The need to clearly communicate the radiologistsinterpretation to the referring physician hasresulted in the development of standardized

terminology by the American College of Radiology.The BI-RADS covers the areas of mammography,ultrasound, and MRI (ACR, 2003).

There are recommendations for mammographicdescriptors of masses, calcifications, and architec-tural distortion, with special cases and associatedfindings. The location of lesions should be identifiedby clockface, quadrant, and depth with some specialterms. There are also recommendations for thestructure of a report. This report should include theindication for the examination, a reference to breastcomposition, a description of any significant finding,comparison with prior examination (if necessary),and an overall impression. The use of final assess-ment categories indicates to the clinician the level ofconcern for malignancy and provides managementrecommendations.

2.10 The Mammographic Examination

As described in Section 2.4, breast cancer isdetected on the basis of four types of signs on themammogram:

the characteristic morphology of a tumor mass, certain presentations of mineral deposits called

microcalcifications, architectural distortion of normal tissue patterns

caused by the disease, and asymmetry between images of the left and right

breast.

Detection of these features depends critically onthe quality of the mammogram. It is necessary tohave adequate contrast, latitude (dynamic range),and spatial resolution in the image to see details ofthe skin, nipple, subcutaneous and retromammaryfat, fibroglandular tissue, supportive connectivetissue, and pectoralis muscle. In order to be able todiscuss factors affecting the quality of mammogra-phy, a brief review of the principles of mammo-graphic imaging is presented in the next section.

There are several excellent textbooks on the clini-cal aspects of mammography, and breast ultra-sound and MRI (e.g., Bassett et al., 2005; Morrisand Liberman, 2005; Stavros et al., 2005; Tabaret al., 2004).


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3. Production of the Mammogram

The mammogram is formed when x rays from aquasi-point source irradiate the breast, and thetransmitted x rays are recorded by an image recep-tor. Because of the spreading of the x rays from thesource, structures are magnified as they are pro-jected onto the image receptor. The signal is aresult of differential attenuation of x rays alongpaths through the structures of the breast.The essential technical requirements of high-

quality mammography are:

to include as much of the breast tissue as poss-ible on the mammographic image,

to provide adequate contrast in the image of allparts of the breast to allow detection of the differ-ences in x-ray attenuation between normalbreast tissue and cancer,

to obtain sufficient spatial resolution to allowvisualization of the fine detail associated withthe signs of breast cancer,

to control the level of random fluctuation (noise)in the image, thereby facilitating the reliabledetection of cancer, and

to maintain the absorbed dose to the breast atthe lowest level consistent with achieving theabove.

The essential features of image formation are sum-marized in Figure 3.1. Figure 3.1a depicts a simpli-fied schematic model of the breast inmammography (Fahrig et al., 1992), andFigure 3.1b illustrates a one-dimensional profile ofx-ray transmission through the breast, based onthis model. A region of reduced transmission corre-sponding to a structure of interest such as a tumor,a calcification, or normal fibroglandular tissue isshown. The imaging system must have sufficientspatial resolution to delineate the edges of finestructures in the breast. Typically, it is desirable toresolve a structural detail as small as 50 mm.Variation in x-ray attenuation due to differences intissue composition and mass density gives rise tocontrast. The detectibility of structures providingsubtle contrast is impaired, however, by randomfluctuations in the profile, referred to as mottle ornoise. The imaging system must have adequate

dynamic range to demonstrate subtle differences intissue composition and density, both near the edgeof the breast where there is very little attenuation(high signal), and in the center of the breast wherethe mean signal might be reduced to as low as 1 %of its value in the absence of attenuation1. Becausethe breast is sensitive to ionizing radiation, which,at least for high doses, is known to cause breastcancer, it is desirable to use the lowest absorbeddose compatible with the required diagnostic imagequality.

3.1 Physics of Image Formation

In the model of Figure 3.1a, a breast composed ofa mixture of adipose tissue and fibroglandulartissue is considered. For the simplified case ofmonoenergetic x rays of energy E, with a linearattenuation coefficient of the tissue, m(E), and inwhich, for the moment, the detection of scattered xrays is neglected, the number of x-ray photonsrecorded in an area of fixed size in the image back-ground is proportional to

NbE N0EhE emEt; 3:1

and the number recorded in the shadow of thelesion or other structure of interest is

NlesionE N0EhE emEtTm0ET: 3:2

In Eqs. (3.1) and (3.2), N0(E) is the number of xrays that would be incident on that area of thedetector in the absence of tissue in the beam, m(E)and m0(E) are the linear attenuation coefficients ofthe breast tissue and the lesion, respectively, t isthe thickness of the breast, and T is the thicknessof the lesion. The factor h(E) is the x-ray quantum-detection efficiency of the detector, given by:

hE 1 emdEtd ; 3:31Such as in a 7 cm thick compressed breast composed of 60 %fibroglandular tissue [m(20 keV) 0.80 cm21] and 40 % adiposetissue [m(20 keV) 0.46 cm21]. Attenuation coefficients frommeasurements of Johns and Yaffe (1987).




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where md(E) is the linear attenuation coefficient ofthe active (i.e., signal-producing) x-ray absorbinglayer in the detector and td is its thickness.The difference in x-ray transmission gives rise to

radiation contrast, which can be defined as

Cns DN= N 2 NbNlesion= Nb Nlesion ;3:4

where DN Nb 2 Nlesion, N (Nb Nlesion) / 2, andCns ignores effects of scattered radiation.

To gain some insight into the primary factorsresponsible for radiation contrast, we assume thatthe x-ray beam is monoenergetic and continue toignore the detection of scattered radiation. Undersuch conditions, the radiation contrast would be

Cns 1 eDmt

1 eDmt ; 3:5

i.e., contrast, in this simplified situation, woulddepend only on the thickness of the lesion and Dm,the difference between the linear x-ray attenuationcoefficient of the lesion and that of the backgroundmaterial.Shown in Figure 3.2 are x-ray attenuation coeffi-

cients as functions of x-ray energy, determinedfrom measurements on samples of three types ofmaterials found in the breast: adipose tissue,normal fibroglandular breast tissue, and infiltrat-ing ductal carcinoma (one type of breast tumor)(Johns and Yaffe, 1987). Both the attenuation coef-ficients themselves and their difference (m0 2 m),decrease with increasing E. As shown inFigure 3.3, which is based on Eq. (3.5), Cns falls asx-ray energy increases. Note that the radiationcontrast of a small calcification in the breast issimilar to that for a tumor, because of the greaterdifference in attenuation coefficient betweencalcium and breast tissue. This is due to therelatively higher atomic number of the calcium,which increases the cross section for photoelectricabsorption. As energy increases, the importance ofthe photoelectric effect diminishes, and the con-trast of the microcalcification falls below that of thetumor.For a given image recording system (image recep-

tor), a proper exposure requires a specific value of

Figure 3.2. Linear x-ray attenuation coefficients of tissueswithin the breast, plotted versus x-ray energy. Tumor tissue isinfiltrating ductal carcinoma. Data are from Johns and Yaffe(1987). Solid line: infiltrating ductal carcinoma; dashed line;fibroglandular tissue; dotted line: adipose tissue.

Figure 3.3. Calculated radiation contrast for a 5 mm thicktumor, and for a 0.2 mm thick microcalcification. Dashed line:5 mm tumor; continuous line: 0.2 mm calcification.

Figure 3.1. (a) Simple model of the breast. The bulk of thebreast tissue is assumed to consist of a uniformly distributedmixture of specified proportions of fibroglandular tissue andadipose tissue, by mass. (b) One-dimensional profile of x-raytransmission through this breast model.


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x-ray energy fluence transmitted by the breast andincident on the receptor, i.e., a specific value of Nbinto a given area. The breast entrance air kerma,Ka,e (see Section 6.1.2), required to produce animage is, therefore, proportional to

Ka;e /NbemEt: 3:6

Because m decreases with energy, the requiredexposure for constant signal, Nb, at the imagereceptor will increase if E is reduced to improveimage contrast. A measure of the risk ofradiation-induced breast cancer better thanentrance air kerma is the mean glandular dose(MGD), DG (ICRU, 1998; 2005; NAS/NRC, 2006).DG is calculated as

DG Ka;ecG;Ka;e ; 3:7

where cG,Ka,e is a conversion factor, described inICRU Report 74, Appendix E (ICRU, 2005),obtained experimentally or by Monte Carloradiation-transport calculations, which convertsentrance air kerma to MGD in a simulated breastof specified composition and thickness (Wu et al.,1991). The conversion factor increases with E, sothat the MGD does not fall as quickly with energyas does entrance air kerma. The trade-off betweenimage contrast and absorbed dose necessitatesimportant compromises in establishing mammo-graphic operating conditions. Dosimetry in mam-mography is discussed further in Section 6.

3.2 Equipment for Mammography

3.2.1 The X-Ray Unit

The components of the imaging system will bedescribed briefly here, while their design will berelated to the imaging performance requirementsof mammography in later sections.The mammography unit consists of an x-ray tube

and an image receptor mounted on opposite sidesof a mechanical assembly or gantry. Because thebreast must be imaged from different aspects andto accommodate patients of different height, theheight of the assembly can be adjusted, and it canbe rotated about a horizontal axis as shown inFigure 3.4.Most general radiography equipment is designed

such that the image field is centered below thex-ray source. In mammography, the systems geo-metry is arranged as in Figure 3.5a, in which a ver-tical line from the x-ray source grazes the chestwall of the patient and intersects orthogonally withthe edge of the image receptor closest to thepatient. If the x-ray beam were centered over thebreast as shown in Figure 3.5b, some of the tissuenear the chest wall would be projected inside of thepatient where it could not be recorded.X rays for mammographic imaging are produced

in a specially designed tube. Electrons emitted by aheated cathode assembly are accelerated in an elec-tric field and focused to strike a positively chargedanode. The area on the anode upon which the xrays impinge is referred to as the target or focalspot, and it is made of a material such as molyb-denum, rhodium, or tungsten, the choice of whichdepends on the desired x-ray spectrum. The spec-trum consists of both bremsstrahlung radiation andcharacteristic x rays specific to the target material.

Figure 3.4. Schematic diagram of a mammography system.

Figure 3.5. Basic beam geometry for mammography. (a) Correctalignment. (b) Incorrect alignment, illustrating a tissue cutoffthat would occur if a centered beam were used.

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Both the continuous spectrum of bremsstrahlungphotons and the monoenergetic characteristic x raysare usually referred to in this case as x rays. Inmodern mammography systems, a high-frequency(20 kHz) voltage waveform is used to excite x-rayproduction (Barnes, 1991). This waveform providesan almost constant potential to the tube.2 Typically,potentials ranging from about 20 kV to 40 kV,chosen according to the thickness and compositionof the breast, are applied to the tube for clinicalimaging.Because of the relatively low energy of electrons

used in mammography, the efficiency of x-ray pro-duction is very low, and most of the kinetic energyof impinging electrons is dissipated in the anode asheat. To accommodate this heat while allowing theeffective focal spot size used in image formation tobe small, the target is formed on the surface of arotating anode disk, and the anode is tilted withrespect to the incident electrons (see Figure 3.6) sothat the heat is spread over a greater area.Depending on their angle of emission, x raysformed in the target material must, therefore, tra-verse different path lengths through the target intraveling from their point of production to theimage plane. Referring to Figure 3.6, it is seen thatthis causes there to be greater attenuation of x raystraveling toward the nipple side of the

mammogram than toward the chest wall side. Theresultant variation in x-ray fluence along thenipplechest wall axis is referred to as the heeleffect.Radiation leaving the x-ray tube passes through

a tube port, generally composed of beryllium, ametallic spectrum-shaping filter, a beam-definingaperture, and a plastic plate, that compresses thebreast. The compression plate should be reasonablyrigid and compress the breast to a uniform thick-ness, although some manufacturers have employedtilting paddles to improve positioning.Those photons transmitted through the breast

and the breast-support platform are incident on ananti-scatter grid and then pass through thehousing of the image receptor, finally being inci-dent on the image receptor, where they interactand deposit most of their energy locally.Mammography systems are designed to minimizethe distance between the breast and the imagereceptor to keep the magnification factor low andavoid increasing the geometric unsharpness.

3.2.2 Automatic Exposure Control

It is difficult for the technologist to estimate theattenuation of the breast by inspection, and, there-fore all mammography units should be equippedwith automatic exposure control (AEC). The AECsensor is located behind the image receptor so thatit does not cast a shadow on the image. The sensordetects the small fraction of the x-ray fluence thatis transmitted through both the breast and thereceptor and provides a signal used to discontinuethe exposure when a certain preset amount of radi-ation has been received by the image receptor. Thelocation of the sensor must be adjustable so that itcan be placed behind the appropriate region of thebreast in order to obtain proper image signal inthat region. For film mammography, AEC devicesmust be calibrated so that constant image opticaldensity (OD) is obtained, independent of variationsin breast attenuation caused by spatial variationsin tissue composition and thickness, kilovoltagesetting, or field size. A different approach isrequired for digital systems for which the imagebrightness and contrast are readily adjustableusing the computer display. Here, the exposurelevel is set to achieve a desired imagesignal-to-noise ratio. This will be discussed furtherin Section 5.The signal from the sensor of the AEC is influ-

enced by point-to-point inhomogeneity in attenu-ation of the breast tissue. Therefore, the size of thesensor and the position at which the sensor isplaced under the breast can have a large effect on

Figure 3.6. Schematic of the anode of a rotating-anode x-raytube, illustrating the angled surface on which the targetmaterial is deposited and the reference axis used forspecification of focal-spot size by manufacturers.

2For this reason, in the remainder of this Report, excitationvoltages will be referred to simply in terms of kV rather thanpeak kV.


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the exposure used to acquire the mammogram. Inaddition, with modern equipment, AEC is compu-ter controlled so that relatively sophisticated cor-rections can be made during the exposure fornonlinear characteristics of the film (Haus andJaskulski, 1997).

3.2.3 Magnification Mammography

In order to increase the visibility of structureswithin the breast, geometric magnification with orwithout localized compression is often used.Magnification mammography is performed byincreasing the distance from the breast to theimage receptor. This is accomplished by mountinga radiolucent spacer on the image receptor housingand positioning the breast on the surface of thisspacer. The main purpose of magnification in thisapplication is to render the projection of theanatomy larger with respect to the limited spatialresolution and noise properties of the screen-filmsystem and, in particular, to reduce the effect ofnoise on visualization of fine detail (Doi and Imhof,1977; Sickles et al., 1977). Magnification increasesthe effect of geometric unsharpness (Haus, 1977),and to avoid excessive reduction of spatial resol-ution (see Section 5.3.2.1) a smaller focal spot isnecessary. Typically a nominal spot size of0.1 mm is used for this purpose compared to thenominal 0.3 mm focal spot normally used forcontact mammography. Note that due to manufac-turers convention for defining the nominal focalspot size, the actual size of the focal spot is gener-ally markedly larger than the nominal size(Barnes, 1991). This is discussed further in Section5.3.2.1.

3.2.4 Screen-Film Mammographic Image Receptor

When first introduced, mammography wascarried out using direct-exposure radiographic filmin order to obtain the high spatial resolutionrequired (Egan, 1970). Since the mid-1970s, high-resolution fluorescent screens have been used toconvert the x-ray pattern formed by the breast intoa visible-light image. These screens are used inconjunction with radiographic film, most frequentlycoated on just one side with photographic emulsion.The configuration for a single screen and single-emulsion film is shown in Figure 3.7. With thisarrangement, the x rays pass through the cover ofa light-tight cassette and the film to impinge uponthe screen. Alternatively, the receptor can be adigital detector as discussed in Section 4.2.

3.2.4.1 Screen-Film. The most common imagereceptor used in mammography has been thescreen-film combination. While the light emissionof the screen is linearly related to the amount ofabsorbed energy from the x-ray beam, the film hasa highly nonlinear characteristic. This is generallydescribed by the characteristic curve of the film,also known as the HurterDriffield (H&D) curve(see Figure 3.8), which is a plot of the OD of theprocessed film versus the logarithm (base 10) of thelight exposure to the film under specified proces-sing conditions. In some cases, the H&D curvecombines the response of the screen and filmtogether, in which case the abscissa of the plot is interms of log relative x-ray exposure.

Figure 3.7. Schematic representation of a mammographyscreen-film image receptor. A system employing a singleintensifying screen and a single-emulsion film is shown.

Figure 3.8. Characteristic (H&D) curve of a screen-filmcombination for mammography.

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The H&D curve provides information regardingthe sensitivity of the image receptor as well as thecontrast characteristics of the film. The steeper theslope or gradient of the curve, the greater the con-trast (optical-density diffference) that will be dis-played to the viewer. Latitude refers to the range ofx-ray exposures (corresponding to paths throughthe breast experiencing different attenuationfactors) that can be accommodated by the filmwhile providing an acceptable gradient. Furtherdiscussion on gradient and latitude will be providedin Section 5.3.1.5.

3.2.4.2 Film Processing. Mammography film isprocessed in an automatic processor similar to thatused for general radiographic films. It is importantthat the development temperature, developmenttime, and rate of replenishment of the developer

chemicals be compatible with the type of film emul-sion used and be designed to maintain good con-trast of the film. These factors affect thecharacteristic response curve of the film in terms ofits sensitivity, gradient, and fog level. Increasedtime and/or temperature of processing normallyprovides increased sensitivity and contrast, but atthe expense of increased fog. In addition, imagenoise levels are increased because fewer x rays areused to produce the image in these cases.Proper replenishment is required in order to

maintain stability of the processing over time.Replenishment replaces the chemicals carriedover from one tank to the next, as well as repla-cing the used and oxidized chemicals. Adequatefixing and washing of the film to remove all chemi-cal residue is required to ensure the archivalquality of the film.


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4. Digital Mammography

There are several technical factors associatedwith screen-film mammography that limit itsability to display the finest or most subtle detailsand to produce images at the most efficient levelof absorbed dose to the patient. In screen-filmmammography, the film must act as an image-acquisition detector as well as a storage anddisplay device. Because of the sigmoidal shape ofthe H&D curve of film (see Figure 3.8), the range ofx-ray exposures over which the film gradient is ade-quately high, i.e., the image latitude or dynamicrange, is limited. If a tumor is located in either arelatively lucent or more opaque region of thebreast, then the contrast displayed to the radiol-ogist can be inadequate because of the limited gra-dient of the film. This is particularly a concern inpatients whose breasts contain large amounts offibroglandular tissue, the so-called dense breast.Another limitation of film mammography is the

effect of structural noise due to the granularity ofthe film emulsion used to record the image and thespatial nonuniformity of sensitivity of the intensify-ing screen. This impairs the detectibility of micro-calcifications and other fine details within thebreast. While quantum noise (see Section 5.2.1) isunavoidable, it should be possible to greatly reducestructural noise by technical improvements.Existing screen-film mammography also suffersbecause of the inefficiency of grids in removingscattered radiation (see Section 5.3.1.4) andbecause of compromises in spatial resolution versusquantum-detection efficiency inherent in thescreen-film image receptor.Many of the limitations of conventional mammo-

graphy can be effectively mitigated with a digitalmammography imaging system, in which imageacquisition, display, and storage are performedindependently, allowing optimization of eachprocess. For example, acquisition is performed withhighly efficient, low-noise x-ray detectors. Becausethe image is stored digitally, it can be displayedwith contrast that is independent of the detectorproperties but rather defined by the needs of theradiologist. Whatever image-processing techniquesare found useful can conveniently be applied,

ranging from simple contrast enhancement to his-togram modification and spatial-frequency filtering(see Section 4.3 and Pisano et al., 2000a; 2000b).After processing, the digital image can be dis-

played using either hard-copy or soft-copymethods. In hard-copy display, the image is printedonto a light-sensitive material such as film, gener-ally by scanning with a fine laser beam. The film isthen viewed on a viewbox. Alternatively, soft-copydisplay is performed on a high-resolution videomonitor.One of the most valuable aspects of digital mam-

mography is that because the data are provided indigital form, it is possible to develop techniquesthat use the data quantitatively in specializedapplications that include image processing, three-dimensional image reconstruction (tomosynthesis),and quantitative image analysis. For example, themammogram can be analyzed using feature identi-fication tools to search for signs of cancer. Thisapproach, called computer-aided diagnosis (CAD),is discussed in Section 4.4.

4.1 Detectors for Digital Mammography

The performance of the digital mammographysystem depends critically on the characteristics ofthe x-ray detector. The detector should have the fol-lowing characteristics:

Efficient absorption of the incident radiationbeam.

Linear response over a wide range of incidentradiation intensity.

Low intrinsic noise. Adequate spatial resolution. Field of view appropriate to accommodate therange of breast sizes encountered clinically (atleast 18 cm 24 cm and preferably 24 cm 30 cm field size).

Adequate sensitivity to avoid excessive patientexposure and to allow acceptable imaging timeand heat loading of the x-ray tube.

Image display will be discussed in Section 5.3.3.




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4.2 Types of Digital Mammography Systems

Five main approaches have been taken in thedevelopment of digital mammography systems.These vary mainly in the detector design and thex-ray acquisition geometry: photostimulable phos-phors (Type 1), active-matrix-readout area detec-tors with either a CsI phosphor layer (Type 2) or anamorphous selenium layer (Type 3) as the x-rayabsorbing medium, signal-integrating slot detectors(Type 4), and quantum-counting slot detectors(Type 5). In the first three, the entire image isacquired simultaneously, while in the last twosystems, only a portion of the image is acquired atone time and the full image is obtained by scanningthe x-ray beam and detector across the breast. Areadetectors offer convenient, fast image acquisitionand can be used with conventional x-ray machines,but can still require a grid. Slot systems are slower,require a scanning x-ray beam, but use relativelysimple detectors and have excellent intrinsic effi-ciency at scatter rejection.Digital mammography found its initial appli-

cation in small area (5 cm 5 cm) systems to facili-tate stereotactic breast biopsy (Karellas et al.,1992). These systems use a lens or a fiberoptictaper to couple a phosphor to a charge-coupleddevice (CCD) whose format is approximatelysquare and typically provide 1 k 1 k images with50 mm pixels. Adjustment of display contrastenhances the localization of the lesion, while theimmediate display of images (no film processing isrequired) greatly accelerates the clinical procedure.Various detector technologies are being used for

full-breast digital mammography. These includescintillators coupled to large-area photodiode arrayson an amorphous silicon substrate, scintillatorscoupled to multiple CCDs, photostimulable phos-phors with scanned-laser readout, and a large-areaamorphous selenium absorber evaporated onto anamorphous silicon substrate containing an array ofdetection electrodes and thin-film transistor (TFT)readout switches. A review of detector technologiesfor digital mammography is given below. Additionaldetail can be found in Yaffe (1999).One advantage of scanning systems is that the

scattered radiation originating in the breast can bevery efficiently rejected from the detector, in thisway improving contrast and signal-to-noise ratio(SNR) without a significant dose penalty. Anotheris that the detector in a scanning system needsonly to measure radiation transmitted throughpart of the breast at any one time, and, therefore,for a given pixel size, fewer detector elements ordels are required than in a full-area system. Thiscan have marked cost advantages.

On the other hand, a scanning system requireslonger total exposure time (58 seconds), necessi-tating higher x-ray tube heat loading. Becauseeach part of the breast is exposed for only a veryshort time, scanning does not cause the type ofmotion blurring that is seen in screen-film mammo-graphy. However, if the breast moves during scan-ning, mis-registration artifacts could result.Finally, in a scanning system, the relatively longtime required to complete image acquisitionrestricts the image repetition rate and can be alimitation if dynamic studies are to be carried out.The phosphor-based detectors for digital mam-

mography employ thallium-activated cesium iodide,CsI(Tl), as the x-ray absorber. Cesium iodide can befabricated as pillar or needle-like structures. Theseact like fiber-optic channels, conducting light pro-duced within the phosphor along the length of theneedles, thereby inhibiting lateral spread of thelight. It is this spread in a conventional settledphosphor that is a major contributor to resolutionloss. The fiber-like structure of CsI allows the phos-phor to be made thick enough to achieve highquantum-detection efficiency without significantloss of resolution.In principle, one x-ray photon interacting with

the phosphor can produce several thousand lightquanta. For CsI(Tl), the value is closer to 1600(Sasaki et al., 2006). If the coupling efficiency ofthe optical-collection system is low, however, thenumber of electrons produced in the CCD per inter-acting x-ray can fall to the point at which anadditional noise source, called a secondaryquantum sink, results. The additional noise willlower the SNR, degrading the quality of the image.In any de-magnifying optics (i.e., optics that reducethe size of the image in coupling to the next stageof the imaging system), either lenses or fiber optics,the coupling efficiency falls as the degree ofde-magnification is increased (Maidment and Yaffe,1996; Miller, 1991). In practical terms, this limitsthe de-magnification factor to approximately 2.The five types of digital mammography systems

are described. For convenience, they will bereferred to as Type 1, etc., in later sections.Assessments of the performance of commercialdigital mammography acquisition systems havebeen published by Lazzari et al. (2007), Monninet al. (2007), and Rivetti et al. (2006).

4.2.1 Type 1: Photostimulable-Phosphor System

The detector in this system consists of a plate,containing an x-ray stimulable phosphor material,typically BaFBr (Crawford and Brixner, 1991;Takahashi et al., 1985). The system is similar in


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operation to that of the detectors that have beenused for over 20 years in digital radiography forapplications other than mammography. Absorptionof x rays in the material produce energetic photo-and Compton electrons in the crystal. These losesome of their energy by exciting loosely bound elec-trons in the crystal lattice, some of which becometrapped in the local potential well of the crystal-line phosphor material, where they remain stablefor some time. The number of trapped electrons isproportional to the amount of radiation incident onthe phosphor. After exposure, the phosphor plate isplaced in a reading device where it is scanned witha fine heliumneon laser beam (see Figure 4.1).The red light from the laser discharges the traps,causing the electrons to return to their groundstate with the release of energy by the stimulatedemission of blue light. The blue light can be col-lected from both the top and bottom surfaces of theplate and measured with photo-multiplier tubes.The resulting signal is digitized to form the image.

4.2.2 Type 2: Flat-Plate Cs(I) with PhotodiodeArray

In these systems a CsI(Tl) phosphor layer isdeposited directly onto a large-area matrix of photo-diodes formed on a flat-plate amorphous silicon sub-strate (see Figure 4.2). Each light-sensitive diodeelement is connected by a TFT switch to a series ofcontrol lines and data lines such that the chargeproduced in the diode in response to light emissionfrom the phosphor is read out and can be digitized.There has been considerable research activitydirected toward improvement of the performance ofphosphor-based or indirect conversion flat-paneldetectors (Antonuk et al., 2000; El-Mohri et al.,2007; Rowlands and Yorkston, 2000; Street et al.,2005). The technical performance of several

commercial phosphor-based flat-panel systems hasbeen assessed by Ghetti et al. (2008).

4.2.3 Type 3: Flat-Plate Amorphous Seleniumwith Electrode Array

This system does not employ a phosphor.Instead, x rays are absorbed in a layer of amor-phous selenium, which is deposited on an array ofelectrodes formed on a large-area amorphoussilicon substrate (see Figure 4.3). An electric fieldis imposed across the plate to collect the electronhole pairs produced in x-ray absorption. Thecharges drift to the electrode pads and are collectedthere. During the readout procedure, TFT switcheson each detector element (del) are sequentiallyactivated, one row at a time via control lines, andthe charge is collected along data lines (runningbetween columns of dels) connecting each detectorelement to readout electronics, similar to those in aType 2 system. The design and performance optim-ization of these so-called direct-conversion flat-panel detectors has been discussed by severalinvestigators (Lee, 2006; Polischuk et al., 2001;Rowlands and Yorkston, 2000; Yorker et al., 2002;Zhao et al., 2003).

4.2.4 Type 4: Slot-Scanning CsI IntegratingDetector with CCD Readout

In this system (Tesic and Piccaro, 1996; Tesicet al., 1999), a CsI(Tl) phosphor x-ray absorber iscoupled through a non-tapered fiber-optic plate toseveral CCD arrays. These are joined end-to-end tocreate a slot format (see Figure 4.4). Image acqui-sition is carried out by scanning the detector alongan arc across the chest wall beneath the breast. Thisarc is centered at the focal spot of the x-ray tube,

Figure 4.1. A photostimulable-phosphor type (often called CR)digital mammography system. A double-sided plate readingsystem is shown. Courtesy of Fujifilm Medical Systems.

Figure 4.2. A CsI-phosphor, flat-panel digital mammographysystem.

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and during acquisition the x-ray tube pivots aboutthat position with the x rays collimated into a fanbeam, matching the area of the detector. As thedetector and slot beam move across the breast, thecharge produced in the elements of the CCD isshifted down CCD columns at an equal rate, but inthe opposite direction, so that the signal resultingfrom x rays transmitted through a particular path inthe breast is integrated in the CCD. When eachbolus of signal reaches the last row of the CCD, it isread out and digitized. This technique is called time-delay integration. This system is no longer being pro-duced commercially; however, at the time of writing,there are many units of this type in clinical use.

4.2.5 Type 5: Slot-Scanning Quantum-CountingGaseous or Solid Detector

In the Type 5 systems, the energy of absorbedx rays is converted to charge in a set of manysingle-line detectors based on either depleted crys-talline silicon or a pressurized high-Z gas in anionization chamber. The charge is collected to form

a pulse, which is counted to register the absorptionof an x-ray quantum. Individual linear detectorarrays are arranged adjacently or spaced apart,and the assembly is scanned in a direction orthog-onal to the detector lines to acquire the image (seeFigure 4.5). The physical performance of the silicondetector system has been characterized by Aslundet al. (2007).

4.2.6 Phase-Contrast Digital Mammography

The contrast of mammography and the visibilityof fine structures in the breast are ultimatelydetermined by the difference in x-ray absorptionproperties of different breast tissues. Several inves-tigators have shown that it is possible to achievecomplementary contrast mechanisms in x-raymammography through phase contrast attributedto diffraction and refraction effects at tissue bound-aries (Burattini et al., 1995; Chapman et al., 1996;Ishisaka et al., 2000; Johnston et al., 1996). Theobserved effect is a contrast enhancement at edges.While first demonstrated using monoenergetic xrays generated from synchrotron sources (Arfelliet al., 2000), a more practical implementation hasbeen introduced that allows a conventional x-raytube with a very small focal spot to be used (Hondaand Ohara, 2008; Tanaka et al., 2005). The geo-metrical arrangement of components employs alarge space between the breast and a digital mam-mography detector. This air gap (see Section5.3.1.4) provides good scatter rejection, whichtogether with the edge-contrast effect resultingfrom the phase contrast provides exquisite anatom-ical detail.

4.2.7 Stereotactic Biopsy Devices

Stereoscopic x-ray imaging techniques are cur-rently used for the guidance of needle biopsies

Figure 4.3. A flat-plate amorphous selenium detector system.

Figure 4.4. Slot-scanning CCD-based digital mammographysystem.

Figure 4.5. A slot-scanning system for digital mammographybased on a detector that counts individual x-ray quanta.


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using large-core or vacuum-assisted devices. Theseprocedures can be used to investigate suspiciousmammographic or clinical findings without theneed for surgical excisional biopsies, resulting inreduced patient risk, discomfort, and cost. In thesestereotactic biopsies, the gantry of a mammographymachine is modified to allow angulated views of thebreast (typically 158 from normal incidence) to beachieved. From measurements obtained from theseimages, the three-dimensional location of a suspi-cious lesion is determined, and a needle equippedwith a spring-loaded cutting device can be accu-rately placed in the breast to obtain tissue samples.While this procedure can be performed on anupright mammography unit, there are also dedi-cated systems incorporating specially designedtables to allow the patient to lie prone during theprocedure. The accuracy of sampling the appropri-ate tissue depends critically on the alignment ofthe system components and the quality of theimages produced. A thorough review of stereotacticimaging, including recommended quality-controlprocedures, is given by Hendrick (1999) and byPaquelet (1999).

4.3 Image Processing

Image processing is an integral part of all digitalmammography systems. Processing operations areapplied at several stages in the imaging system.

4.3.1 Flat-Field Correction

The initial operation that takes place is usually aflat-field, uniformity or gain correction. Thespatial non-uniformity in detector sensitivity canbe corrected by imaging a uniformly attenuatingobject and creating a gain map that can be used tocorrect all subsequently acquired images. For flat-panel systems and scanning systems, this trans-formation corrects for non-uniformities in the x-rayfield (e.g., heel effect) as well. In addition, theappearance of bad pixels can be removed from theimages. If a single detector element is defective, itssignal can be replaced by some weighted combi-nation of signals from adjacent dels. This is accep-table if the defective dels are isolated and few innumber, but is of greater concern if signals fromentire patches or lines of the detector are absent orincorrect. Manufacturers specify the number andtype of such defects that are acceptable.For Type 1 systems, the flat-field correction is

currently applied only to the laser readout systemand not to the individual phosphor plates or to thex-ray field. Therefore, artifacts associated withthese sources will remain in the images. Presence

of the uncorrected heel effect in digital images canaffect the results of image-noise measurements inquality-control testing (Alsager et al., 2008).

4.3.2 Resolution Restoration

Blurring in the detector can be partially cor-rected through image processing by deconvolvingthe blurring function of the detector. This pro-cedure can be very effective, but if overdone willalso enhance image noise. It is therefore importantthat the inherent detector resolution is adequateand that the image-noise level is acceptable. Thelatter is accomplished in part through carefuldesign of low-noise detectors and also throughappropriate design and use of automatic exposurecontrol and/or automatic technique control.

4.3.3 Additional Image-Processing Operations

Further image processing is generally carriedout to adapt the image for display and interpret-ation by the radiologist. These image processingoperations differ among manufacturers, but caninclude:

(a) Peripheral compensation to flatten the signallevel at the edge of the breast. This essentiallysuppresses the effect of thickness reductionnear the edge and reduces the dynamic rangeof image signal that the display system mustaccommodate, allowing higher contrast settingsto be used in image display. It is important thatwhen such software is used it does not undulydistort the contour of the breast.

(b) Inversion of the grey scale (black representshigh x-ray transmission) and nonlinear trans-formation (logarithm, square root, etc.) of theimage.

(c) Other image enhancements, for example histo-gram equalization. These are also employed toattempt to optimize contrast throughout thebreast and best utilize the limited dynamicrange of the display system. Image enhance-ment techniques are proprietary to each vendorand in most cases are selectable at the usersdiscretion. The best way to evaluate thesealgorithms is to observe the rendition of keystructures (spiculations, microcalcifications,and margins of benign and malignant lesions)with and without the enhancement activated ina series of sample cases, including images ofboth dense and fatty breasts. It is also impor-tant to know whether the results of imageprocessing are only available locally at theviewing workstation or whether they are pre-served so that the enhanced image can be

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viewed elsewhere. Other considerations relatedto display of digital mammograms are dis-cussed in Section 5.3.3.

4.4 CAD for Mammography

There have been several direct and indirectmeasures of the accuracy of mammography thatindicate that the cancer-miss rate is between 5 %and 35 % (Kavanagh et al., 2000; Lewin et al.,2001; Mushlin et al., 1998; Poplack et al., 2000;Taylor et al., 2005). There are four differentreasons for misses: (i) the cancer is not visible inthe image; (ii) the indications of cancer are verysubtle; (iii) the cancer was visible, but was notreported; and (iv) the image quality was substan-dard due to technical factors related to patient posi-tioning or x-ray exposure. Depending on the study,the first three are approximately equally impor-tant, while the fourth is the cause of missed cancerin less than 10 % of the misses (Bird et al., 1992;Martin et al., 1979; Yankaskas et al., 2001).Further, the positive predictive value (PPV) ofbreast biopsies based on mammography (the prob-ability that cancer is present, given a positiveresult on mammography) can be low, ranging from5 % to 85 % (Elmore et al., 2003). The goal in theUSA for PPV upon biopsy from a screeningprogram is a PPV of between 25 % and 40 %(AHCPR, 1994). In Europe, the goal is a PPV of atleast 34 %, with greater than 50 % desirable(de Wolf and Perry, 1996). Biopsy of benign breastdisease is costly both to the patient, in terms ofemotional and physical trauma, and to society, interms of monetary costs and the use of medicalresources that are often in short supply. CAD isbeing developed for mammography to aid radiol-ogists in detecting cancers. It is thought that CADwill help radiologists reduce errors due to misseddetections and misinterpretations of malignantlesions.There are two main types of CAD schemes being

developed for mammography. The first, which isdirectly applicable to screening mammography, arecomputer-aided detection schemes. The second,which is being developed for diagnostic mammogra-phy, are CAD schemes for classification of lesions.In the detection scheme, the mammogram issearched by the computer algorithm to identifylocations of suspicious regions. These regions arethen flagged for the radiologist to review. In theclassification schemes, an already-detected lesion isscrutinized to determine if the radiologist shouldrecommend a biopsy. A classification scheme ana-lyzes features of the lesion and, in its simplest

form, produces an estimate of the likelihood thatthe lesion is malignant. This information is thenused by the radiologist when interpreting theimage. Note that there are usually other imagingmodalities used by radiologists as adjuncts to diag-nostic mammography, such as ultrasound andmagnetic-resonance imaging (MRI). The radiologistconsiders information from all available imagingstudies and clinical information when making abiopsy recommendation. Further, classificationschemes are being developed for breast ultrasound(Bader et al., 2000; Chang et al., 2000; 2005; Chenet al., 2002; 2004a; Chou et al., 2001; Drukkeret al., 2002; 2003; 2004; Finette et al., 1983; Giger,2004a; Giger et al., 1999; Horsch et al., 2001; 2002;2004; Lefebvre et al., 2000; Sahiner et al., 2004;Sivaramakrishna et al., 2002) and for dynamiccontrast-enhanced breast MRI (Alterson andPlewes, 2003; Chen et al., 2004b; Gilhuijs et al.,1998; Lean et al., 2004; Mountford et al., 2001;Setti et al., 2001; Vergnaghi et al., 2001; Wood,2005).Research into CAD for mammography is very

active. Many studies have been summarized inseveral reviews (Astley and Gilbert, 2004; Doi,2007; Giger et al., 2000; Karssemeijer, 2002;Karssemeijer and Hendriks, 1997; Li et al., 1997;Mata Campos et al., 2000; Nishikawa, 2002; Sajdaet al., 2002; Sampat et al., 2005; Zheng et al.,1995). In addition, a large body of non-peerreviewed research appears in the Society ofPhoto-Optical Instrumentation Engineers (SPIE)Medical Imaging Conference proceedings, the con-ference proceedings of Computers in Radiology andSurgery (CARS), and books from the InternationalWorkshop on Digital Mammography (see, e.g., Doiet al., 1996; Gale et al., 1994; Karssemeijer, 1998;Peitgen et al., 2004; Pisano and Yaffe, 2005; Yaffe,2001).Finally, in addition to these CAD schemes, other

types of CAD techniques are being developed forpurposes such as predicting a womans risk ofdeveloping breast cancer based on mammographicbreast density or mammographic texture of thefibro-glandular tissue (Byng et al., 1996; Booneet al., 1998; Huo et al., 2002a; Li et al., 2004;Pawluczyk et al., 2003; Tahoces, et al., 1995; Weiet al., 2004; Yaffe et al., 1998; Zhou et al., 2001).

4.4.1 Computer-Aided Detection

The goal of CAD is to assist radiologists in detect-ing breast cancer, principally in screening mammo-graphy, although it can be applied to diagnosticmammography as a means to find multifocalcancers (Butler et al., 2004). CAD has the potential


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to be a cost-effective alternative to independentdouble reading by two radiologists, in that the CADalgorithm could be used to simulate the secondradiologist. Double reading has been shown toincrease the cancer detection rate (Anderson et al.,1994; Anttinen et al., 1993; Brown et al., 1996;Ciatto et al., 1995; Duijm et al., 2004; Harvey et al.,2003; Kopans, 2000; Leivo et al., 1999; Taplin et al.,2000; Thurfjell et al., 1994; Warren and Duffy,1995), but it is not widely practiced, especially inNorth America, because of costs and logistics. CADhas the potential to reduce the cancer-miss rate,reduce the variability among radiologists, improvethe consistency of a single radiologist, and makeradiologists more productive. These are importantissues for improving the efficacy of screeningmammography.

4.4.1.1 Methodology. Most CAD schemes aredesigned using the paradigm shown in Figure 4.6.A digital mammogram is used as input to a CADscheme. This can come from a full-field digitalmammography system or it can come from dataacquired by digitizing a screen-film mammogram.The first step is to preprocess the image to segmentthe breast area from the non-breast area (Bicket al., 1995; Ibrahim et al., 1997; Lou et al., 2000;Mendez et al., 1996; Yin et al., 1994) and to useimage processing to emphasize lesions or certainfeatures of lesions. For example, a bandpass filtercan be used to make microcalcifications more pro-minent (Chan et al., 1987a) or specialized non-linear filters can be used to highlight spiculesassociated with malignant masses (Kegelmeyeret al., 1994; Kobatake et al., 1999; Zwiggelaaret al., 1999). Because lesions range in size, multi-scale approaches are often used (Li et al., 1997;Mata Campos et al., 2000; Sajda et al., 2002; Zhenget al., 1995).After the image has been pre-processed, potential

lesions are identified. The simplest means ofaccomplishing this is to apply grey-level threshold-ing, as both microcalcifications and masses appearbrighter than their surrounding background.Unfortunately, because the contrast of lesions indense breast tissue can be low, simple thresholdingwill either produce many false detections or misssubtle lesions. Various approaches have been usedto improve discrimination of lesions. These includeapplying grey-level thresholding to small regions inthe image (Chan et al., 1990) or creating an imagewhose pixels represent the gradients about eachpixel in the original image and applying athreshold on this gradient image (Kupinski, 2000).Once potential lesions have been identified, they

are segmented from the image using different

techniques. For example, in region growing, aninitial seed pixel or area of the image is chosenand adjacent pixels are tested for a feature con-sidered to identify those pixels as having similarproperties. If the test result is positive, those pixelsare added to the seed region and the process con-tinues on the ever-expanding periphery of the regionuntil the test provides a negative result. Regiongrowing can be effective for segmenting microcalcifi-cations from the mammogram (Veldkamp andKarssemeijer, 1998). Because the borders of massesare often ill-defined or partially obscured by normaltissues of the breast, gradient-based methods arefrequently more effective in these situations thangrey-level-based methods (Kupinski, 2000).To reduce the number of false detections, fea-

tures of the segmented detections are extractedfrom the image. Most features fall into one of thethree categories: intensity based, morphologybased, and texture based. These features can beextracted from the grey-scale image or from theimage after it has undergone a mathematical trans-formation (Wei et al., 1997).There are many different features that can be

used, and an optimal set has not yet been deter-mined. If a large set of features is extracted fromthe images, then a subset of the features arechosen for further analysis. The subset can bedetermined from a stepwise analysis (Chan et al.,1995b) or using a genetic algorithm (Anastasioet al., 1998a; 1998b; Floyd et al., 1996; Kupinskiet al., 1996; Sahiner et al., 1996; 1998; Zheng et al.,1999).

Figure 4.6. Concept of a computer-aided detection (CAD)system.

Digital Mammography

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Once the final feature set has been chosen, thefeatures are merged by a statistical classifier todifferentiate actual lesions from false detections.Many different types of classifiers can be used,such as support-vector machines (Vapnik, 1998),artificial neural networks (Hecht-Nielsen, 1990;Wu et al., 1993), k-nearest neighbor (Duda et al.,2000; Veldkamp et al., 2000), and decision trees(Breiman et al., 1984; Kegelmeyer et al., 1994).Most classifiers have comparable performances,although at least one study has found support-vector machines to be superior to artificial neuralnetworks (Wei et al., 2005a; 2005b).CAD algorithms are trained using a set of

mammograms for which truth (i.e., the presenceor absence of a cancer) is known through biopsyresults or subsequent patient follow-up. Truth dataare also required to evaluate the performance of aCAD algorithm.Care must be taken in training and evaluating

the classifier to avoid biases and to reduce the var-iance in the measured performance. To avoid apositive bias, cases used to train the classifier arenot used to test the classifier. Increasing thenumber of testing cases can improve the perform-ance of the classifier (Zheng et al., 1997) andreduce the variance in the measured performance(Chan et al., 1999b). However, for a finite numberof available cases, this reduces the number of train-ing cases available, which reduces both accuracyand robustness of the classifier. Several studieshave been published addressing this issue (Chanet al., 1999b; Fukunaga and Hayes, 1989; Li andDoi, 2006a; 2006b; 2007), and also the issue of biasif the same cases are used to develop the CADscheme (e.g., selecting features) and to train it(Kupinski and Giger, 1999; Sahiner et al., 2000).Many investigators adopt a bootstrap method todeal with these issues (Chen et al., 2002; Efron andTibshirani, 1997; Yousef et al., 2005; 2006).By applying a threshold to the output of the clas-

sifier, pairs of true-positive fraction and averagenumber of false detections per image can be deter-mined. By plotting these pairs, a free-responsereceiver operating characteristic curve can be gen-erated (Chakraborty, 2000). For a more generaldiscussion of receiver operating characteristic(ROC) analysis, see the beginning of Section 5 andICRU Report 79, ROC Analysis in Medical Imaging(ICRU, 2008). In general, as the true-positivefraction increases, the false-detection rate alsoincreases. How to balance this trade-off so as tomaximize the benefits of CAD to the radiologistis unknown. Studies using simulated CAD perform-ance levels indicate that false-positive rates of 0.5per image or fewer provide more assistance to

radiologists than CAD schemes with higher sensi-tivity and false-positive rates.The results of the CAD algorithm are conveyed

to the radiologist by means of an image annotatedto show the computer detections. Forscreen-film-based CAD systems, a low-resolutionversion of the image is either printed on paper orshown on a monitor. The location of computer-detected masses and clustered calcifications areshown using different symbols for the differentlesions. For digital mammography systems, theCAD output can be annotated directly onto theradiologists display workstation.An alternative method for CAD is to train a clas-

sifier using small regions of the images that eitherdo or do not contain a lesion (El-Naqa et al., 2002;Kalman et al., 1997; Wu et al., 1992). Then animage can be analyzed by extracting small regionsfrom the image that are centered on every pixel inthe image. In this way, the full image is analyzedby the classifier, with the output of the classifierindicating the likelihood that the input region con-tains a lesion. This is most practical for calcifica-tions because they are small and the resultinginput regions can be small. The larger the inputregion, the more difficult it is for the classifier tolearn the appearance of a lesion with high accu-racy. Another drawback of this approach is that theclassifier needs to reach a very high performancelevel to avoid having a high false-detection rate.For a 100 mm pixel image with a breast that is100 cm2 in area, only 1 in 5000 pixels will containa portion of a calcification, assuming 14 calcifica-tions of size 0.4 mm. A specificity of 99 % will giverise to 50 false detections. To reduce the number offalse detections, feature analysis as describedabove can be implemented. Alternatively, thesemethods can be applied to the detections initiallyfound by another CAD scheme (Chan et al., 1995a;Sajda et al., 1996; Zhang et al., 1994).More recent research in CAD considers the combi-

nation of information from multiple images, eitherfrom a different view from the same exam, or fromthe same view from a previous exam. This approachmore closely mimics how a radiologist reads a case,and it can improve the performance of a CAD scheme(Hadjiiski et al., 2004; Huo et al., 2001; Paqueraultet al., 2002; Sun et al., 2004; Yin et al., 1991).One successful approach to developing CAD

techniques is to use knowledge of image acquisitionto model the appearance of the image or objects inthe image. For example, information about theresolution properties of the screen-film system,scattering properties of the breast, and the attenu-ation properties of lesions and breast tissue areused to predict how calcifications should appear in


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the image (Highnam and Brady, 2000; Jiang et al.,1992). This can be used to reduce the rate of falsedetections, because, in general, calcifications arecompact. If the estimated thickness of a detectedstructure (potential calcification) is either muchgreater or much smaller than the diameter of thesignal, it is likely to be a false detection due toeither image artifact (if much greater) or imagenoise (if much smaller).

4.4.1.2 Performance: Laboratory. There are atleast three different types of laboratory testing ofCAD algorithms. The first and simplest is tomeasure the performance of the CAD scheme on aset of cases. The second is to test the CAD schemeon a set of cases that includes cancers that weremissed on mammography. The third is to performan observer study in which radiologists read caseswith and without the computer aid. The ultimatetest of CAD is through clinical evaluation, which isdescribed in the next section. It should be notedthat comparison of different CAD systems issubject to biases due to the cases used to evaluatethe scheme (Nishikawa et al., 1994) and thescoring criteria used to evaluate whether theactual lesion was detected (Kallergi et al., 1999).In general, CAD schemes for microcalcifications

have higher performance than CAD schemes formasses. This reflects the difficulty of differ-entiating actual masses from false detections.Microcalcifications are quite distinct in a mammo-gram because there are few causes for a cluster ofsmall bright objects in a mammogram other thanmicrocalcifications. On the other hand, overlappingtissue can often mimic malignant masses. Further,because masses have lower contrast than microcalci-fications, the borders of masses often blend into thenormal background of the breast. Commercial CADsystems have up to 98 % sensitivity with fewer than0.3 false detections per image for the detection ofmicrocalcifications, but only 85 % sensitivity with0.5 false detections per image for the detection ofbreast masses. Further, mass detection schemeshave difficulty in detecting architectural distortions(Baker et al., 2003). While the sensitivity of thesesystems is comparable to that of radiologists, thefalse-detection rate is high. Assuming radiologistshave a callback rate of 5 % to 10 %, their false-detection rate per image (four images per examin-ation) is between 0.0125 to 0.025, more than anorder of magnitude lower than the combined false-detection rates for masses and microcalcification forCAD. Zheng et al. (2001; 2004a; 2004b) have shownthat the effectiveness of a CAD scheme, in terms ofincreasing radiologists performance, increases asthe false-detection rate decreases.

For film mammography, it has also been shownthat CAD schemes do not always give the sameresult if the same film is digitized and analyzedmultiple times (Malich et al., 2000; Nishikawaet al., 1996; Taylor et al., 2003; Zheng et al., 2003).Because of mechanical variability and noise associ-ated with the digitizer, each time a film is digitizedthe resulting image, while appearing to be thesame, is slightly different. These small differencescan produce small differences in the featuresextracted from the image. As a result, potentiallesions and actual lesions that are near the bound-ary between false and true lesions can cross thatboundary. Therefore, differences in detections canbe obtained upon repeated digitization and analy-sis. This is generally a problem for subtle lesionsand false detections. Detection of non-subtlecancers is usually reproducible. The lack

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