Breast tissue characterisation using low angle X-ray scattering

Breast Tissue Characterisation

Using Low Angle X-ray Scattering

Ghirmay Kidane

UCL

University College London

Submitted for

The Degree of Doctor of Philosophy

University of London

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A BSTR A C T

X

T h is thesis presents the application o f a L o w -a n g le x-ray scattering system based on an en e rg y dispersive technique to the characterisation o f breast tissues. L o w angle scatter of

x -rays at diagnostic energies is p re d o m in a n tly coherent. T his c o h e re n c e gives rise to

interference effects resulting in x-ray diffraction patterns that are characteristic o f the

scattering m aterial. T h e shapes o f scattering distributions for low a tom ic n u m b e r m edia

such as breast tissues ex hibit one or m o re intense pea ks c lo se to the transm ission

direction. T h e position and the shapes o f the peaks d ep e n d up o n the interatom ic and

in te rm o le c u la r c o n figurations o f the soft tissues.

T h e m e a su re m e n ts o f the scattering properties o f breast tissues, so m e anim al tissues, and

tissue substitute m aterials have been ca rried out using an en e rg y dispersive x-ray

diffraction system o v er the m o m e n tu m tran sfer range o f 0.70 to 3.50 nm'V O ne hundred

an d tw enty one sam ples o f ex c ise d fem ale breast tissues, eight anim al tissues, and test

o bjects such as perspex, polyethylene and w a te r have been used. R esults from the

diffraction system have been c o m p a re d with those from histological analysis for all h u m a n tissues. It has been found that tissue types can be ch a ra c te rise d on the basis o f

sh ap e o f the scatter spectrum and on its relative intensity. T h e shape s are significantly different betw een tissue types in the range from 1.0 p er nm to 1.8 per nm*'. This

su g g ested that differences in the distribution o f coh e ren tly sca tte red ph o to n s in breast tissues w o u ld allow better d isc rim inating signals in breast im a g in g if particular values o f

m o m e n tu m transfer are m onitored.

A n ew tech n iq u e is desc rib ed which p ro d u c es im ages b ase d on selective m o m e n tu m

transfer region. T h e system uses a m a m m o g ra p h ie x-ray tube to ac q u ire diffraction data at

scatter angle o f ~9^. Im ages are re co n stru cted from the diffraction data, which represent

the co h e ren t-sc atter intensity in the m o m e n tu m transfer space a ro u n d 1.1 nm '. At this

m o m e n tu m transfer value the co h e ren t-sc atter intensity ratio o f d is e a s e d tissue to healthy

tissue w as m inim ised. T his system perm its the x-ray diffraction properties o f small

inclusions e m b e d d e d in large tissue sizes to be m e a su re d in -vitro . In this study im ages

o b tain ed by transm ission m eth o d s and by co herent scattering te c h n iq u e have been

re co rd e d for several inclusions in blocks of h u m a n breast tissues a n d anim al tissues. S m a lle r inclusions that are less distin g u ish ab le with tran sm issio n im ages have been

Contents

1. B

r e a s t

a n a t o m y

,

p a t h o l o g y

a n d

IMAGING TECHNIQUES... 15

1.0 INTRO D U CTIO N ... 15

1.1 THE B R E A ST ...16

1.1.1 Breasta n a t o m y...16

1.2 MOLECULAR COMPOSITION OF HUMAN CELLS...18

1.2.1 Distinctionbetweenhealthyand Cancerc e l l s...19

1.3 CLASSIFICATION OF BREAST TISSU E... 20

1.3.1 Connectivetissue... 20

1.3.1.1 Fibrous Tissue ... 21

1.3.1.2 Adipose T issu e ... 22

1.3.1.3 Blood ...22

1.4 CANCEROUS TISSUE... 23

1.4.1 Epidem iology...23

1.4.2 Pathologyof Cancerous Tissu e...23

1.4.2.1 In-situ carcinoma ... 24

1.4.2.2 Infiltrating carcinoma ... 25

1.4.3 Benignt issu e...26

1.5 TECHNIQUES OF BREAST IM A G IN G ...27

1.5.0 Introduction... 27

1.5.1 X-RAY MAMMOGRAPHY...28

1.5.2 X-RAY IMAGING SYSTEM CONSTRAINTS...31

1.5.3 Reductionofx-rayscatter...32

1.5.4 Imagereceptors... 33

1.5.4.1 Film-screen systems ...33

1.5.4.2 Digital radiography ...34

1.5.5 Radiation DOSE...35

1.6 OTHER TECHNIQUES OF BREAST IM A G IN G... 36

1.6.1 Ultra sonography... 37

1.6.1.1 B-mode scanning ... 37

1.6.1.2 Doppler sonography ...38

1.6.2 MR Breast Im a g in g... 38

1.6.3 Positron Emission Tomography (PET)... 39

1.6.4 Single Photon Im a g in g... 39

1.6.5 Co n c lu sio n s... 40

1.7 NECESSITY TO IMPROVE IMAGE C O N TR A ST... 40

1.8 X-RAY SCA TTER ...41

1.8.1 Coherentx-ray scatter... 42

2. LOW ANGLE X-RAY SCATTERING... 47

2.1 BASICS OF PHOTON-MATTER IN TERA CTIO N ...47

2.1.1 Attenuation...47

2.2.2 X-RAY SCATTERING... 49

2.2.2.1 Coherent scatter ...50

2.2.2.2 Bragg diffraction ...51

2.2.2.3 Atomic form factor ... 52

2.2.2.4 Condensed material ... 53

2.2.2.5 Incoherent scatter ...55

2.3 ENERGY DISPERSIVE X-RAY D IFFR A C TIO N ... 56

2.3.1 Rangeofscatterangles... 56

2.4 LOW ANGLE X-RAY SCATTERING SY S T E M ... 57

2.4.1 Descriptionofexperimentalset-u p... 57

2.4.2 Photoncollection...60

2.4.3 System Alignm ent... 61

2.4.3.1 Slit Response ... 62

2.4.3.2. Scatter angle selection ...64

2.4.3.3 Angular distribution of coherent scatter from soft tissue ...66

2.4.3.4 Consistency of the scatter angle ...67

2.5 GEOMETRICAL CONSIDERATION OF THE COLLIMATION SYSTEM ... 68

2.5.1 Optimumdimensionofcollimationa perture...68

2.5.2 Spreadoftheprimaryb e a m... 69

2.6 STABILITY OF X-RAY O U TPU T... 70

2.7 SCATTER MEASUREMENTS OF AMORPHOUS M ATERIALS...73

2.8 DETERMINATION OF THE MOLECULAR DIFFERENTIAL C RO SS-SEC TIO N ...75

2.8.1 Diffractometer CORRECTION PROCEDURE...76

2.8.1.1 The shape of the incident spectrum ... 76

2.8.1.2 Effect of Attenuation ... 80

2.8.1.3 Multiple scatter ... 82

2.8.1.4 Background subtraction ... 84

2.9 L in e a r DIFFERENTIAL SCATTERING COEFFICIENT {y[ster~^cnf^i)...85

2.10 QUANTITATIVE ANALYSIS OF AMORPHOUS M ATERIALS...88

2.10.1 Peakpositionsoftwocomponentsoftt issu e s...89

2.11 MOMENTUM RESO LU TIO N ...90

2.11.1 Angular Bl u r r in g...90

2.11.2 Energyresolution...91

2.12 SPECTRAL SELECTIVE MOMENTUM TRANSFER IM AGING... 92

c?

3. L

i n e a r

d i f f e r e n t i a l

s c a t t e r i n

<?

COEFFICIENTS OF BREAST TISSUE... 95

3.1 INTRODUCTION... 95

3.2 BREAST TISSUE SAM PLES... 96

3.2.1 TISSUE CLASSIFICATION...96

3.2.2 Ti s s u e s t o r a g e... 99

3 . 2 .3 Ti s s u e h a n d l i n g a n d p r o c e s s i n g... lO I 3.2.4 Ef f e c to f f r e e z i n g a n d s t o r a g e...102

3.2.5 Hi s t o l o g i c a la n a l y s i s p r o c e d u r e... 103

3.3 SCATTER SIGNATURE M EASUREM ENT... 104

3.3.1 Pr o c e d u r e...104

3.3.1.1 Systematic parameters... 104

3.3.1.2 Rotation of sample...106

3.4 TISSUE CHARACTERISATION...107

3 .4 .1 De t e r m i n a t i o n o f M M -f o r m f a c t o r s...1 0 7 3.4.2 Ca l c u l a t i o n o ft h e s c a l i n g f a c t o r... 108

3 . 4 .3 Co m p a r i s o n o f m o l e c u l a rl i n e a rd i f f e r e n t i a l s c a t t e r i n g COEFFICIENT ( / ) FOR VARIOUS BREAST TISSUE CLASSIHCATION... I l l 3.4.3.1 Adipose Tissue...114

3.4.3.2 Fibroglandular and average breast tissue ... 114

3.4.3.3Carcinoma ... 115

3.4.3.4 Fibroadenoma ...115

3.4.3.5 Benign tissue ...116

3.4.4 Mo l e c u l a r Fo r m Fa c t o r... IIS 3.4.5 Pe a k h e i g h t a n a l y s i s o fs c a t t e r s i g n a t u r e s...122

3.5 EFFECTS OF INCLUSIONS...126

3.6 TISSUE SIM ULATION...127

3.6.1 Re c o n s t r u c t i o n o f s i g n a t u r e sf o r m u l t i-c o m p o n e n t t i s s u e... 128

3.6.2 Di s t i n c t i o nb e t w e e n c a r c i n o m a a n d n o r m a l t i s s u e... 131

3.7 ASSESSMENT OF FAT CONTENT OF BREA ST...132

3.7.1 C a l i b r a t i o n CURVE... 133

3.7.1.1 Preparation of the sample for calibration curve... 134

4. A

p p l i c a t i o n

o f

c o h e r e n t

s c a t t e r

IN TISSUE IMAGING... 141

4.0 INTRODUCTION...141

4.1 THE DESIGN AND CONSTRUCTION OF A SPECTRAL SELECTIVE MOMENTUM TRANSFER IMAGING (SSMTl) SY S T E M ... 142

4.1.1 Selectionofmomentumtransferspace... 143

4.1.2 Matching Momentum Transferfeaturestothe MAMMOGRAPHIC X -R A Y SPECTRA...144

4.2 THE SSMTI IMAGING DEV ICE...147

4.2 1 SSMTl EXPERIMENTAL SET-UP... 147

4.2.2 System Alignm ent... 149

4.3 COMPONENTS OF THE SYSTEM ... 152

4.3.1 Detectors... 152

4.3.2 Collimators... 153

4.3.2.1 Scattering volume...155

4.3.3 Scanning...158

4.4 MOMENTUM RESOLUTION OF SSMTl SYSTEM ...158

4.4.1 Angular Blurring... 159

4.4.2 Energyresolution... 160

4.5. X-RAY OUT PUT FLUCTUATION... 161

4.6 DETECTOR INSTABILITY...162

4.7 BACKGROUND SUBTRACTION... 163

4.8 SIMULATION OF SCATTER SIGNATURES... 164

4.9 ENERGY-ANGLE DIAGRAM ...166

4.10 IN-VITRO IM AGING...168

4.10.1 Constructionofblocksoftissuesforim aging...168

4.11 DIFFRACTION AND TRANSMISSION IM A G ES...172

4.12 SIGNAL-TO-NOISE RA TIO ... 176

4.13 D O SE... 178

4.14 EFFECT OF ATTENUATION...179

4.15 SENSITIVITY OF SCATTERING VOLUM E... 181

5. C o n c l u s i o n a n d f u r t h e r w o r k ...i84

5.1 L A B O R A T O R Y B A S E D D IF F R A C T IO N M E A S U R E M E N T S ... 184

5. 1. 1 Sa m p l e p r e p a r a t i o n...184

5.1.2 Sc a t t e r m e a s u r e m e n t s... 184

5.1.3 P e a k HEIGHT...187

5.2 A P P L IC A T IO N O F L A B O R A T O R Y B A S E D D IF F R A C T IO N ... M E A S U R E M E N T S ...187

5 .2 .1 Sp e c t r a l Se l e c t iv e m o m e n t u m t r a n s e e r i m a g i n g... 187

5.3 C L IN IC A L A P P L IC A T IO N O F T H E S SM T I - F U T U R E W O R K ... 189

5.3.1 Re a s o n s fo rc o n s id e r in g S SM TI int h ec l in ic a lc o n t e x t... 189

5.3.1 FUTURE W O R K... 191

5 .3 .L I S o u rc e ... 191

5 .3 .1.2 C o llim atio n ...191

5.3.1.3 D e te cto rs... 192

5.3.2 Pr o p o s a l s f o r an e w SSM TI s y s t e m...193

A P P E N D I X ... ^ .. ? . . ' . .'.7%Zr... 19 4 ^ 1 Ti s s u e s a n d c e l l s ...19 4 E R R O R ! B O 0 K M A R K N O T D E F I N E D . 2. X-RAY SCATTERING AND BRAGG'S LA W... 197

3. Sc a t t e r in g v o l u m eo ft h eS S M T I ... 203

REFERENCE... 207

A

FIGURES

Figure 1.1

Diagram illustrating anatomy of breast

17

Figure 1.2

Cut surface of a biopsy specimen containing an infiltrating

carcinoma 24

Figure 1.3

Cut surface of a biopsy specimen containing a typical

fibroadenoma 26

Figure 1.4

X-ray diffraction patterns from a crystalline and amorphous

material

43

Figure 2.1

The interaction cross section for water.

48

Figure 2.2

The comparison of the independent free atom, free molecule

and the diffraction data of water 54

Figure 2.3

Experimental set-up of the energy dispersive difractometer,

photographic image and schematic representation. 58

Figure 2.4

The collimation system, photographic image and schematic

Representation

59

Figure 2.5

The focal spot images through the pinhole at two different

distances to test system alignment

61

Figure 2.6

The schematic illustration of the collimation movement to

align the collimation system

62

Figure 2.7

The performance of the slit across the primary beam and

angular position 63

Figure 2.8

The low angle x-ray scatter signatures of adipose tissue at

different scatter angle. 65

Figure 2.9

The angular distribution of the coherent scatter of adipose

and fibrous tissue

66

Figure 2.10

Comparison between the theoretical and the experimental

diffraction curves of CaCOs

67

Figure 2.11

Schematic illustration of the spread of the primary beam

69

Figure 2.12

The x-ray out put using ionisation chamber at different

Figure

2.13 Integrated peak counts of polyethylene diffraction curve at

different measurement time

72

Figure 2.14

The low angle x-ray scatter signatures of tissue substitute

and animal tissues measured using the diffractometer 74

Figure 2.15

The typical spectra of an incident photon and scattered signatures

of adipose and carcinoma tissues 77

Figure 2.16

The schematic set up of the system used to obtain the incident

spectrum

78

Figure 2.17

The measured scattered spectra from the industrial x-ray tube

79

Figure 2.18

The spectral correction factor for different energy values

80

Figure 2.19

The relative scatter contribution to the scattering of photons

incident on water slab 83

Figure

2.20 The typical measured background from the EDXRD 85

Figure

2.21 The measured and theoretical linear differential scattering coefficient of adipose tissue (a) after normalisation applied

and (b) compared with the results of others 87

Figure

2.22 Scatter signature of tissues in their pure form and in mixed form 89

Figure

2.23 The schematic diagram of a slit height effect on the

EDXRD technique 91

Figure 2.24

The momentum spread for(a) polyenergetic x-ray spectra and

(b) different object detector distance

92

Figure 2.25

The typical scatter signatures of two different materials plotted

on the same momentum transfer axis.

93

Figure 3.1

Distribution of the samples used in the investigation of breast

tissue characterisation with the age of the patients.

97

Figure 3.2

Healthy and diseased breast divisions.

98

Figure 3.3

Scatter signature of Infiltrating ductal carcinoma and ductal

carcinoma in situ 99

Figure 3.4

Scatter signature of a fresh and dry tissue samples stored

at room temperature 100

Figure 3.5

Demonstration that the tissue storage process had no on

Figure 3.6

The histological procedure of the technique used to analyse

the tissues.

103

Figure 3.7

Normal breast and carcinoma seen under a low-power

scanning lens. 104

Figure 3.8

Typical scatter signatures taken for adipose tissue, fibroglandular

tissue, carcinoma and benign tissue. 105

Figure 3.9

The signature of normal breast tissue produced when the sample

was irradiated at different positions.

106

Figure 3.10

Comparison of the linear differential scattering coefficient

between the measured and calculated for breast tissue and

tissue substitute materials 110

Figure 3.11

Measured linear differential scattering coefficient of different

types of breast tissues

113

Figure 3.12

Molecular form factor measured for (a) Perspex and healthy

breast tissues and (b) compared with Peplow and Verghese (1998)

121

Figure 3.13

The measured signature of filled, under filled breast tissue samples

124

Figure 3.14

The correlation between the peak height and the histological

estimation of the concentration for adipose tissue and

fibroglandular tissue

125

Figure 3.15.

Demonstration of the effect of the inclusion of another

tissue type within the scattering volume

127

Figure 3.16

Demonstration of the reconstructed and measured linear

differential scattering coefficient of healthy breast tissue

130

Figure 3.17

Comparison of the scatter signatures for the calculated

‘pure’ carcinoma sample with that of both normal

breast tissue and a fibroglandular tissue.

132

Figure 3.18

Diffraction signatures of fat lump lean meat and a sample

made from a mixture of 40% fat and 60% lamb lean meat 139

Figure

3.19 The fat tissue calibration curve 135

Figure

3.20 Comparison between the EDXRD analysis and pathologically

assessed contents of fat in the healthy breast samples

136

Figure 4.1

The peak position difference linear differential scattering

Figure 4.3

The experimental set-up of (a) schematic illustration and

(b) photographic images of the “SSMTI” system

149

Figure 4.4

Geometry of the alignment for a standard mammography and

the SSMTI system

150

Figure 4.5

Images of the focal spot through circular aperture collimators

151

Figure 4.6

Vertical and horizontal profile plots through the image

of figure 4.5.

152

Figure 4.7

The schematic representation of the collimation system

154

Figure 4.8

The schematic representation of the scattering volume

155

Figure 4.9

The coherent scatter signature of healthy breast tissue at

the scatter angle of -9.3^ and molybdenum spectrum

and different collimation dimension

157

Figure 4.10

Geometrical representation of angular blurring from finite

dimensions of the annular collimation.

159

Figure 4.11

The x-ray output for several exposure times measured using

the ion chamber

161

Figure 4.12

Demonstration of detector instability for repeated

measurements on a block of lard.

162

Figure 4.13

The typical measured background from the SSMTI system

163

Figure 4.14

Scatter signatures of healthy and cancerous tissues measured

using the tungsten target x-ray tube.

164

Figure 4.15

The computed and measured scatter signatures of healthy and

Diseased breast tissues from Mo incident spectra at the scatter

angle of 9.3*^

165

Figure 4.16

A 2-D surface plot and 3-D curve of the contrast of the healthy

and cancerous breast tissues at different scatter angle and energy

167

Figure 4.17

The profile through the Energy-Angle diagram of figure 4.13.

168

Figure 4.18

Schematic representation and x-ray film images of meat for

the fat and mixed tissue matrices respectively

170

Figure 4.19

The diagram of the cancerous tissue inclusions in healthy

breast tissue.

171

Figure 4.20

The scatter and transmission images of meat inclusions in

animal fat matrix.

172

Figure 4.22

The scatter and transmission images of the lamb lean meat

inclusions in the mixed tissue matrix

173

Figure 4.23

The profile through the scatter and transmission images of

figure 4.23.

174

Figure 4.24

Scatter and transmission images of the cancerous tissue

inclusions in breast tissue.

175

Figure 4.25

Profiles through the images of figure 4.25

176

Figure 4.26

The total linear attenuation coefficient of different breast tissues

179

Figure 4.27

SNR of an image of a lamb lean meat inclusion in lard when

the primary beam is attenuated by different thickness of

tissue substitute material.

180

Figure 4.28

Schematic representation and a 2D scatter images of the

meat inclusion (wedge shaped) in the fat matrix

181

Figure 4.29

The profile through the image of figure 4.28

182

Figure 5.1

The concentration of fat level in breast tissue.

189

Figure 5.2

Schematic representation of the system that could be used to

detected the relatively low intense scatter photons

192

Figure 5.3

Schematic illustration of SSMTI for clinical application

193

Figure A l.l

M olecular arrangements of proteins

195

Figure A2.1

Diagrammatic illustration of the coherent scattering of

x-rays by a single electron 199

Figure

A2.2 Diffraction of x-rays by a crystal. AA and BB wave fronts 201

Figure

A3.1 The schematic illustration of the scattering volume 203

Figure

A3.2 (a) the scattering volume and (b) an extrapolated representation

TABLES

Table 1.1

The relative amount molecular composition in cells

18

Table 1.2

Breast tissue components and their function

21

Table 1.3

The classification of healthy and diseased breast tissues

27

Table 1.4

The characteristics of different breast imaging techniques

28

Table 1.5

The quality criteria for x-ray mammography

30

Table 1.6

System dose of different image receptors

34

Table 2.1

The range of scatter angles for n-fatty acids and water

57

Table 3.1

Chemical and physical properties of the scattering samples

109

Table 3.2

M olecular linear differential scattering coefficient for

different breast tissues

117

Table 3.3

The average relative error in the absolute molecular

linear differential scattering coefficients

118

Table 3.4

M olecular form factors of breast tissue. Average

breast tissue represents 50% fat and 50% fibroglandular

119

Table 3.5

The average relative error in the calculated molecular

form factors of the breast tissues 122

Table

3.6 List of 121 breast tissue samples classified histologically

and related to the measured peak positions and peak heights

123

Table 3.7

The scatter and attenuation relationship between lamb lean

meat and fibrous tissue and breast fat and animal fat

134

Table 4.1

The contrast between the linear differential scattering coefficient

of healthy tissues and cancerous tissue at

x

values of

1.1

nm'^ and

1.6 nm'^

147

Table 4.2

The calculated scattering volumes for different primary

and scattering beam apertures

156

Table 4.3

The angular uncertainty for a range of collimation lengths

160

Table 4.4

The measured contrast and SNR for different size inclusion

Acknowledgement

I would like to thank my supervisor Professors R D Speller and Dr. G J Royle for their

support and invaluable guidance throughout the project.

My big thanks go to Dr. Dmitra Daramabara for her helpful advice and support. I am also

grateful to Professor A. Hanby for his help in providing me with breast tissue samples and

for his guidance in the pathological analysis of the tissues and to Dr Angelo Taibi for his

useful discussion. Many thanks to Giulia Scannavini, Antonio Soares and all other

colleagues in the radiation physics group.

I am extremely grateful to thank my cousin Mr. Tekeste Sebhatu for his support

throughout this PhD work. Special thanks must also be given to Hadas Andemeskel for

her constant encouragement. I must also acknowledge my gratitude to my cousin

Yohannes Tseggay.

-

1

-Breast anatomy, pathology and

imaging techniques

1.0 Introduction

Breast cancer is a m ajor problem for women in the western world. It also occurs in

men, but the incidence is about one hundredth that of women. Incidence rates have

been increasing in many countries and it was anticipated that nearly one million cases

might be diagnosed in the world in the year 2000 (Day and Miller, 1988). Amongst the

women the risk of breast cancer rises rapidly from about the age of 30 to the age of 50,

thereafter, in low-incidence countries (e.g. Japan) there is no increasing risk with

increasing age. However in high incidence countries (e.g. USA and Western Europe)

there is moderate rise in incidence with increasing age for the rest of the life span.

Efforts to improve the current diagnostic techniques are underway. The most common

diagnostic technique, after clinical examination, is x-ray mammography. Within the

screening techniques, mammography is neither 100% sensitive nor 100% specific for

the early detection of malignant tumours; some false negative and false positive

diagnosis occurs leading to missed cancers and inappropriate biopsies. Thus, a new

method for increasing the diagnostic information content of mammographie images is

sought. One method would be to use the scattering properties of the different types of

breast tissue to enhance the visibility of the disease. X-rays are always scattered during

mammographie examinations. These scattered x-rays degrade the image quality of

transmission images, and thus, several efforts have been made to remove scattered

photons from reaching the detector (e.g. introduction of grids or slits between the

patient and the image receptor). This thesis considers the use of scattered photon

information to improve sensitivity and specificity of mammography.

This chapter describes the general overview of the thesis including the survey of

literature in the field of low angle x-ray scattering. Classification of healthy and non-

healthy breast tissues, anatomy of the breast and the current techniques of breast

imaging have been reviewed. Advantages, disadvantages and problems associated with

x-ray mammography are treated in more detail. The use of coherently scattered photons

to characterise breast tissue has also been included.

1.1 The breast

1.1.1 Breast anatomy

The fully developed female breast is a well-differentiated apocrine sweat gland that

originates in the ectoderm and secrejf milk during lactation. Each breast of a female

extends from the sternum to the mid-axillary line, and lies anterior to the pectorial

muscles. A thin outer dermal layer covers a subdermal layer of adipose tissue that

varies in thickness from several mm to one cm. Cooper’s ligaments are scalloped

interlobular and intralobular strings of fibrous connective tissue extending from the

pectorial fascia to the skin to support the glandular tissue. Cooper’s ligaments also

support the ducts, blood vessels, lymph channels, and varying quantities of adipose

Lactiferoiis diict

AmpiiUa

Areob

Adipose tissue

Pectoralis major

? ^ Glandular tissue

^ ITormective tissue, stram a

Nipple v/ith opening o f lactiferous duct

Figure 1.1 Diagram illustrating anatomy o f breast

Each breast is c o m p o s e d o f 15 to 20 lobes o f g la n d u la r tissue. T h e lobes are p a d d e d and

sepa rated from each oth er by fibrous c o n n e c tiv e tissue and fat. T h e in terlobular co n n e ctiv e tissue fo rm s su sp en so ry ligam ents, w h ic h attach the breast to the und erly in g

m uscle fascia an d to the overly in g deiTnis. As s u g g e ste d by their nam e, the su sp en so ry

ligam ents pro v id e natural support for the breasts, like a built-in brassiere. W ith in the

lobes there are sm a lle r units called lobules. T h e d ucts from the various lobules unite,

fo rm in g a single lactiferous (m ilk ca rrying) d uct for each lobe, in o ther w ords, the

secretory cells are a ira n g e d in little grape like clusters called g lan d u lar alveoli. T h e

main ducts c o n v e rg e to w ard s the nipple, like the sp o k e s o f a wheel. T h u s, there are 15

to 20 tiny o p e n in g s on the surface o f ea ch nipple. T h e lobules, to g e th e r with its

term inal duct are called the term inal duct lo b u lar unit (T D L U ).

T h e a m o u n t o f adip o se tissue around the lobes o f the glan d u lar tissue d eterm in e s the size o f the breasts an d accounts for th eir soft c onsistency. T h e nipple consists o f

certain other stimuli. In the pinkish areola surrounding the nipple, several rudimentary

milk glands (the areolar glands) may be found. By the time a woman has completed

puberty, her glandular tissue usually has developed to its maximum size. Hormonal

variations related to menstrual cycles, pregnancy, and lactation cause the size of her

glandular tissue to wax and wane. The gradual recession of glandular tissue after

menopause usually makes the breast become moderately flattened, pendulous and less

firm. Although hormonal factors make a w om an’s glandular tissue denser, her genetic

predisposition and the proportion of the total adipose tissue to her total body weight

also influence the ratio of glandular tissue to adipose tissue in her breast. For this

reason it is still normal for some young w om an’s breast to consist primarily of adipose

tissue and some elderly wom an’s breast to consist of exceedingly dense tissue. A

woman’s fibrous tissue extends throughout the entire breast; only a thin layer of

retromamary adipose tissue separates it from the pectorial muscle.

1.2 Molecular composition of human cells

Cells are composed of water, inorganic ions, and organic molecules. W ater is the

dominant mass of the cell, accounting for 70% or more of total cell mass. In most cells,

over 90% of the total mass (excluding water) is represented by very large molecules

called macromolecules. Four major classes o f macromolecules may be identified; such

as: proteins, polysaccharides, lipids and nucleic acids. Of all the macromolecules found

in cells, the proteins are the most chemically and physically diverse. The summary of

these components of cells is given in Appendix I. Table 1.1 shows the relative amount

of cellular composition.

Substance

Percentage of total cell weight (%)

Water 6 5 - 8 5

Protein 1 0 - 2 5

Polysaccharide 1 - 5

Lipid 2 - 1 0

Nucleic acid 0 . 5 - 5

\ 1.2.1 Distinction between healthy and Cancer cells

C an ce r cells ty pically d isplay abn o rm a lities in the m e c h a n ism that re gulate n o rm a l cell

proliferation, differentiation and survival.

A p rim a ry d istinc tion b etw e en c a n c e r cells an d no rm al cells in culture is that norm al

cells d isp lay d e n sity -d e p e n d e n t inhibition o f cell proliferation. N o rm a l cells proliferate

until they reach a finite cell density, w h ich is d e te rm in e d in part by the av a ilability o f

grow th fa cto r a d d e d to the culture m ed iu m . T h e y then cease p roliferating a n d b e c o m e

quiescent. T h e proliferation o f m ost c a n c e r cells how ever, is n ot sensitive to density-

d e p e n d e n t inhibition. M a n y ca n cer cells have re d u c e d re q u irem en ts for ex tra cellu lar

grow th fa cto r b ec a u se o f the lack o f p o ly p e p tid e (w hich controls cell proliferation).

C a n c e r cells are also m ore stringently re g u la ted than norm al cells by cell-cell a n d cell-

matrix interaction. C a n c e r cells are less adh e siv e than norm al cells b e c a u se o f the

reduced ex p re ssio n s o f cell surface ad h e sio n m olecules. C o n seq u en tly , c a n c e r cells are c o m p a ra tiv e ly un re strain ed by interactions with oth er cells and tissue c o m p o n e n ts ,

contrib u tin g to the ability o f m alignant cells to invade and m etastasise. T h e re d u c e d

adhe sive ness o f c a n c e r cells also results in m orp h o lo g ical and c ytoskele ta l alterations.

M any tu m o u r cells are ro u n d e r than norm al with large r nuclei, in part b e c a u se they are

less firm ly attac h ed to e ither the e x tra cellular m atrix o r neig h b o u rin g cells (B o y n to n et al 1982).

M a lignant c e l^ g e n e r a l ly s e c r e ^ p r o te a s e that digests extracellular m atrix c o m p o n e n t,

allow ing c a n c e r cells to invade adjacent n o rm al tissue. E.g. the secretion o f co lla g e n a se

appears to be an im p o rtan t d eterm in a n t o f the ability o f ca rc in o m a s to d igest and

1.3 Classification of breast tissue

The elemental and the molecular compositions of breast tissue are the most important

entities in this research project to study the low angle x-ray scattering properties of the

soft tissues. Therefore, for simplicity in this thesis, female breast is classified into two

broad divisions according to their function and composition. They are the mammary

gland and the connective tissues. The mammary epithelium forms only a minor

component of the total breast tissue mass, but it is the site for most cancerous cells.

Mammary gland and its function has been described in §1.1. The connective tissue and

its components are listed and explained in the next sections.

1.3.1 Connective tissue

Connective tissue is one of the most widespread tissues in the breast, found in or

around the mammary gland of the breast. It exists in different forms e.g. as delicate

tissue-paper webs, tough resilient cords, rigid bones, or fluid. The connective tissues

connect, support, transport, defend and form the supporting framework for the whole

breast and for the mammary gland components (e.g. blood).

The breast connective tissue is composed of three components namely, (a) ground

substance, (b) fibres and (c) cells. The ground substance and fibres make up the extra­

cellular matrix of the connective tissue. The properties of the cells and the composition

and arrangement of the extra-cellular matrix elements vary tremendously, giving rise to

an amazing diversity of connective tissue, each uniquely adopted to perform its specific

function in the breast. For example the matrix can be delicate and fragile to form a soft

'packing' around the mammary gland, or it can form 'ropes' (tendons and ligaments) of

incredible strength.

Ground substance is an amorphous material (living fabric) that fills the space between

the cells and contains the fibres. It is composed of:-(a) Interstitial fluid; (b) Cell

adhesion proteins (serves as glue that allows connective tissue cells to attach

fluid and functions as a molecular ’sieve’ or medium, through which nutrients and other

dissolved substances can diffuse between the blood capillaries and the cells.

The fibres of connective tissue provide support. Three types of fibres are found in

connective tissue matrix such as collagen which provide strength to the matrix, elastic

which allows the tissue to stretch and recoil like a rubber band, and reticular fibres

which form a delicate network that surround small blood vessels and support the soft

tissue of organs.

Major breast component

Tissue type

Location Function

1. Epithelial tissue Glandular Gland Secretion 2. Connective tissue

Fibrous 1. L oose Betw een glands (lobule), superficial fascia 2. D ense Ligaments, Dermis

B lood B lood vessels Transportation, protection A dipose Under skin, padding at Insulation, support and

various points o f breast reserve food

M uscle Smooth N ipple Erection o f nipples

Table 1.2 Breast tissue components and their function

The connective tissues in the breast can be divided into different categories or types

according to the structural characteristics of the intercellular material. The classification

scheme is listed in table 1.2. Fibrous tissues (areolar, adipose, reticular, and dense)

have extra-cellular fibres as their predominant feature. The cells of the various

connective tissues are specialised to produce the extracellular matrix. The cell names

end with suffixes according to the cell function such as blasts (e.g. fibroblast) o i ^ y ^

(e.g. adipocytes).

1.3.1.1 Fibrous Tissue

The fibrous connective tissue of the breast can be broken down into components such

as loose and dense (see table 1.2) according to their function and composition.

Loose connective tissue:- It is loose, common and ordinary. It is loose because it is

tissues in the breast. The matrix of loose (also called areolar) tissue is a soft, viscous

gel mainly because it contains a semifluid or gelatinous ground substance formed

primarily of hyaluronic acid in which all three fibre types are loosely dispersed. The

loose nature of the tissue provides a reservoir of water and salts for surrounding body

tissue.

Dense regular connective tissue:- They have fibres as their predominant element. For

this reason the dense connective tissue is often referred to as dense fibrous connective

tissue. W ith its enormous tensile strength, dense regular connective tissue forms the

ligaments that bind. Some of the connective tissue is irregular. These bundles of

collagen fibres are much thicker and they are interwoven and arranged irregularly,

forming sheets in body areas, where tension is exerted from many different directions.

It is found in the breast skin as the dermis.

1.3.1.2 Adipose Tissue

Adipose tissue is basically a connective tissue, but it differs from other connective

tissues because it contains predominantly fat cells and many fewer fibroblasts,

macrophages, and mast cells. Compared to other connective tissue types, adipose tissue

is very cellular. The adipose cells, which account for about 90% of the tissue mass, are

packed closely together. They form supporting, protective pads around the gland. The

relative amount of fat in the breast increases with age. The molecular structure of fatty

acids are given in Appendix I.

1.3.1.3 Blood

Blood is unique among breast connective tissue because the matrix between the blood

cells is fluid and it is characterised by the lack of fibres in its matrix. This fluid matrix

of blood is called plasma. The red blood cells are unique in their mature form because

they do not contain nuclei. It appear as biconcave discs that have a diameter of 7-8p,m.

Each red blood cell contains about 280 million hemoglobin. The less numerous white

blood cells, active in defence system, are amorphous cells and are capable of oozing

1.4 Cancerous tissue

Epidemiology

t cancer is the most frequent cancer in women in the western world. The

mce rates are continuously increasing in many parts of the world, and in the

trial world the rate is close to about one in 12 women. It is a major cause of death

ddle-aged women of 33 - 55 years (Parkin et al 1988), where there has been an

ase in the mortality rate in the last two decades. Rates of incidence and mortality

breast cancer are about five times higher in North America and northern Europe

in Africa, Asia, and Japan. In Japanese immigrants to the USA the risk of

oping breast cancer is doubled (Stanley et al 1988), suggesting environmental as

as genetic factors in the aetiology of breast cancer. The fat content of the diet may

\ important factor (Armstrong and Doll 1975). Genetic factors are implicated in

t 5% of cases of breast cancer. The risk is increased three-fold if the mother or

■ developed breast cancer before the age of 50 (Bain et al 1980). The risk is

ased further if a relative had bilateral disease or if more than one first degree

ve was affected at an early age (Bain et al 1980). The risk factor of early age at

rche and delayed age of menopause indicates that oestrogen activity is involved in

athogenesis. This is supported by the reduction in incidence of breast cancer at an

age (under 35 years). Nulliparous women and those delaying their first full term

lancy until after the age of thirty also have an increased risk.

I

Pathology of Cancerous Tissue

: of the pathologic lesions arise in TDLU. In these sites malignant transformation is

ated microscopically by the presence of morphological changes within the

idual cells by the way in which these cells are arranged in relationship to each

*. As long as the proliferating malignant cell is present within the confinement of

basement membrane surrounding the ducts, acini, or the covering surface

basement membrane is breached and the malignant cells are seen infiltrating the breast

stroma and tissue spaces, the tumour becomes an invasive carcinoma. The tumour cells

in both the situ and invasive carcinoma may be arranged in a variety o f ways or exhibit

specific features, and these are used in providing the basis for the histological

classification o f breast carcinoma. Malignant epithelial tumours are by far the most

prevalent o f the malignant breast tumours. Figure 1.2 illustrates a biopsy specimen

containing a typical infiltrating carcinoma.

10 mm

I __________ 1

Figure 1.2 Cut surface o f a biopsy specimen containing a typical infiltrating carcinoma. The tumour has an irregular outline and contracts from the surrounding tissue, producing a slightly concave cut surface.

1.4.2.1 In-situ carcinoma

In situ carcinoma is more commonly seen in association with invasive carcinoma. The

in situ carcinoma is divided in to two major components such as ductal and lobular

carcinoma in situ. There are other less common in situ carcinomas such as Paget’s

diseases o f the nipple and \|n tr a c t^ carcinoma. Mixed ductal and lobular carcinoma in

Ductal carcinoma in situ (DCIS):- The gross appearance of the breast tissue involved

varies according to the extent of the disease and its histological type. The tissue may

appear normal, nodular and the ducts involved may be dilated, indurated and contain a

dark grey thick secretion that can easily be expressed out of the ducts. Any part of the

ductal system, from the subareolar lactiferous sinuses down to the terminal duct, deep

within the breast tissue, may be involved, and it is not uncommon for this type of

carcinoma to affect more than one ductal system at the same time.

Lobular carcinoma in situ:- This is another common histological variety of in situ

carcinoma of the breast. The disease usually affects all acini in a lobule or several

lobules. The normal acinous structure is replaced by a solid mass of large

monomorphic cells with faintly stained cytoplasm and rounded nuclei. The affected

acini are enlarged and may be slightly distorted, but they retain their well-defined

contour surrounded by basement membrane. The lobule as a whole becomes markedly

enlarged and may be distorted, but its component acini retain their normal

topographical relationship with a minimal amount of loose fibrous tissue between them.

Pure lobular carcinoma in situ does not produce a palpable mass by itself, but is usually

discovered incidentally amidst or adjacent to a clinically diagnosed benign lesion or as

a result of a mammographie abnormality. M ost patients are premenopausal and in their

fifth decade.

1.4.2.2 Infiltrating carcinoma

This is the most common histological variety of breast carcinoma. The malignant cell

of the invasive carcinoma is arranged in groups of variable sizes and shapes which may

include glandular structures, separated by a variable amount of fibrous tissue. The

invading aggregates of cells usually have jagged, irregular borders rather than the

smooth, rounded contours of DCIS.

Infiltrating labular carcinoma (ILC):- It is the most common histological type of

mammary carcinoma. It was recognised as a distinctive variant of invasive breast

cancer shortly after LCIS was defined as an entity. Unlike its in situ counterpart, ILC

and distant sites. Grossly, ILC may be indistinguishable from its infiltrating ductal

counterpart. Marked stromal fibrosis may be present, causing a discrete mass.

Conversely, ILC may be present with very little stromal response and may be both

grossly and mammographically undetectable.

Infiltrating ductal carcinoma:- Infiltrating ductal carcinoma is characterised by the

absence o f features seen in the more specialised forms o f breast carcinoma. The

principal characteristic o f this tumour is the infiltration of the stroma by malignant

epithelial cells that are usually arranged in cords that are two or more cell diameters

wide. The infiltrating cells often form lumina that are reminiscent o f the ductal acinar

pattern o f normal breast tissue.

1.4.3 Benign tissue

The mammary gland is susceptible to physiological changes. These changes may

produce clinical abnormalities. The term benign breast disease encompasses a wide

range o f lesions.

v ' - . '

1 0 m m

t, - ...— , I

Figure 1.3 Cut surface o f a biopsy specimen containing a typical

fibroadenoma. The lesion has a

smooth, rounded outline, a

f Some well-defined entities but others proved to show a mixture of changes affecting

> the TDLU. The changes may be indicative to the risk of subsequent carcinoma. The

benign breast diseases are described by different terms according to the disease type.

The most commonly used terms are Adenosis, Epithelial hyperplasia, Epithelial

metaplasia, cysts and papilloma (Mills et al 1999). Figure 1.3 shows a biopsy specimen

containing a typical fibroadenoma. Fibroadenoma is being the most common benign

mammary tumour of the breast.

In this project, the breast tissues are divided in two major groups such as healthy breast

tissues for those whose cells are growing in a controlled manner and diseased tissues

for those whose cells are grown in an uncontrolled manner. Table 1.3 shows the

classification of these tissue types.

Healthy Breast tissue Diseased Breast tissue

Fibrous tissue Carcinoma Glandular tissue Benign

A dipose tissue Fibrocystic change Fibroadenoma

Table 1.3 The classification of

healthy and diseased breast

tissues

1.5 Techniques of breast imaging

1.5.0 Introduction

The main strategies considered for control of breast cancer are primary prevention,

secondary prevention or screening and improvement in treatment. The female breast is

prone to benign disease, and it is very important to discriminate between benign and

malignant lesions.

Breast imaging plays an increasing role within screening and the diagnosis of

symptomatic women. Imaging methods should have high specificity and sensitivity in

order to identify and control the cancerous area of the breast (Jones 1982). Therefore

detection of a tumour in its early stage is important. Mammography is currently the best

numerous advances in mammography have greatly improved image quality, the

technique does however have shortcomings that limit its sensitivity and specificity.

Multiple areas of improvement have therefore been required not only to film/screen

mammography, but also to search for entirely new techniques in the study of breast

cancers. Table 1.4 shows the summary of the main techniques of breast imaging.

Imaging

technique Resolution Sensitivity Specificity Advantage Disadvantage Mammography Microcalcification

200p.m

Carcinoma > 1cm

90% 50% Screening

N o differentiation between benign & malignant. Difficult to differentiate the presence of malignancy in dense breast

Ultrason graphy Solid mass > 1cm Cyst -2m m (B-mode)

92% Differentiation between solid mass & cyst

N o differentiation between benign & malignant. Unable to detect preinvasive carcinoma MR imaging > 1 cm 90% 30%-90% In conjunction with

conventional mammography imaging to improve specificity

Unable to differentiate between benign and malignant

PET Reliably detected > 1cm -100% 87% Differentiation between malignant & benign

High cost o f PET scanners

Table 1.4 The characteristics o f different breast imaging techniques.

Sensitivity (or true positive fraction) describes the number of correct positive

assessments per number of truly positive cases and specificity (or true negative

fraction) describes the number of correct negative assessments per number of truly

negative cases. They are both inversely related. Higher sensitivity means that fewer

cancers are missed. Higher specificity means that fewer false-positive diagnoses are

made.

1.5.1 X-ray mammography

X-ray mammography is still the most reliable method of detecting breast lesions. It has

proved to be effective in reducing breast cancer mortality in a number of screening

technique. The mammographie criteria for detecting breast disease are essentially of

three kinds such as:

(/) Calcifications, particularly finer particles (microcalcifications)

(ii) Dense tissue nodules and

(Hi) Spécules of fibrous tissue

These structures must be imaged sharply with high contrast and with a low level of

image noise.

There are a number of requirements for good radiographic techniques. Some of the

basic requirements are given below

(1) X-ray mammography is generally performed with a molybdenum target and

molybdenum filter x-ray spectra, with typical filtration thickness of 30p.m (Jones,

1982). The combination of these two gives rise to a spectrum dominated by Mo

characteristic photons (17.4keV and 19.6keV), but Bremsstrahlung photons with

energy higher than the molybdenum k-edge are also contained in the spectrum. The

result of these Bremsstrahlung photons is to produce an intense diffused

background due to Compton interactions with the soft tissue.

(2) One of the objectives of mammography is to achieve the detection of small

microcalcifications. Microcalcifications can be the sole sign of precancerous or of

already infiltrating mammary carcinoma (Paterok et al 1993). Currently

microcalcifications with diameters up to 0.2 mm as the lower limiting size can be

detected (Karila 1987). The imaging of the tissue nodules and fibrous tissue are

also important requirements of mammography but much less is known about

limiting values. Carcinoma up to 1 cm in diameter must be detected.

(3) Breast tissue is very sensitive to the induction of breast cancer by ionising radiation

(4) The exposure should be less than 2 seconds. This requirement is desirable in order

( ? ) to minimise patient pain due to the applicators applied to compress the breast.

Despite all the advantages of x-ray breast imaging, it has failed to detect the difference

between normal and cancerous tissue because of the low differences in absorption

coefficients at the characteristic x-ray energies. Consequently, it is difficult to obtain

radiographs with high contrast. The problem is more pronounced when imaging the

dense breast. Approximately 25% of women have dense breasts (Tabar and Dean

1982). It has shortcomings in terms of sensitivity and specificity. On the one hand 5-

15% of breast cancers are not visualised mammographically (Weinreb and Newstead

1994); on the other hand the overall yield of breast cancers per number of breast

biopsies recommended on the basis of screening mammograms ranges between roughly

10-50% (Weinreb and Newstead 1994, Paterok et al 1993). This demonstrates that the

current x-ray mammography has failed to differentiate between benign and cancerous

lesions.

As it has been mentioned above one of the risks of mammography is the carcinogenic

potential of the ionising radiation. Therefore, each radiological procedure should be

justified and optimised. For radiology the principle of optimisation means that the

radiation dose should be kept as low as compatible with the image quality that is

necessary for diagnosis. Table 1.5 shows the diagnostic requirement for good breast

imaging performance.

Radiographic device Specially dedicated equipment. Anode material: M o Focal spot size < 0.6 mm

Total filtration 0.03 mm M o or 0.5 mm A1 equivalent

Anti-scatter grid Specially designed m oving grid may be necessary Film -screen combination Dedicated high-resolution film -screen combination Focus-film distance > 60 cm

Radiographic voltage 23-35 kV

Automatic exposure control Chamber selected-specially positioned Exposure time < 2 seconds

Breast com pression Should be applied to a level which the patient can tolerate (not exceeding 200N )

The most important characteristics of the radiographic procedure which affect the

resulting image quality are: (1) the focal spot size used together with contact and

magnification technique and, (2) the reduction of scattered radiation and the imaging

geometry of the whole system itself. Image quality is used to indicate the accuracy with

which details can be perceived in a mammogram. Usually image quality is described by

the interaction of contrast, sharpness and noise.

A number of publications, since the introduction of the molybdenum anode and

molybdenum filter, have shown that radiation quality and dose must be matched to the

thickness (under compression) and tissue composition of the breast (Dance and Day

1981, Jennings et al 1993). The conventional anode-filter system adaptations of

radiation quality to object thickness are very limited. The relative energy distribution of

the x-ray spectrum changes only insignificantly with an increase in tube voltage from

25 kV to 30 kV. Therefore the advantage of using a molybdenum anode starts to be lost

for breast thickness above 3 cm because higher kVp has to be used to achieve sufficient

penetration. It is clearly shown in the signal to noise relationship with breast thickness

and energy (Dance and Day, 1981) that Mo imaging is inappropriate for very large

breasts, where it would be preferable to use a slightly higher energy spectrum.

However, with a tungsten anode in combination with molybdenum and rhodium filters,

the energy distribution of the spectrum at higher kV is clearly shifted towards higher

energies in comparison with the spectrum at lower kV and has proved to be better for

the imaging of thicker breasts (Sabel et al 1986).

X

^ 1.5.2(^ray imaging system constraints

The finite size of the focal spot of an x-ray tube leads to geometric unsharpness. Muntz

et al (1985) used multiparameter techniques for the optimisation of the geometrical

configuration. The optimisation is subject to constraints imposed by technology, such

as power limits for the tube focal spot. The size of the focal spot affects the image

sharpness of a structure because it is located at a distance from the film. Therefore, the

focal spot size should be as small as possible for better image sharpness. However, the

avoid exposure times of several seconds, there must be a compromise. Typical values

of the focal spot width and length are in the range of 0.4 - 0.6 mm and 0.6 - 0.85 mm

respectively. The use of a magnification technique along with the standard grid

technique is restricted to the clarification of suspected microcalcifications and the finest

tissue structures (Kratzat 1988). Microcalcifications with diameters in the order of 200

pm are successfully displayed, which appears to be necessary from a clinical point of

view.

1.5.3 Reduction of x-ray scatter

X-ray scatter is one of the main problems of conventional x-ray mammography. Grids

or air gaps are introduced in order to reduce or, if possible, to remove the amounts of

scatter reaching the detector. The techniques used commonly for reducing the scatter

contribution and improving image quality are discussed in the following sections.

Scattered radiation grids.- Image contrast is degraded by scattered radiation arriving at

the image receptor. The contrast reduction varies with breast size and tissue

composition (Dance and Day 1984, Dance et al 1992), and is relatively insensitive to

radiation quality. The employment of anti scatter grids to reduce the amount of scatter

is well established and usually the grid moves during the exposure, but occasionally a

stationary grid arranged either inside or outside the cassette may be found.

A ir gap and slit technique:- Other methods of reducing scatter are air gap and scanning

slit techniques. The air gap technique is applied together with the magnification

technique. Muntz et al (1976) assumed an effective scatter point source to describe the

behaviour of the scatter/primary ratio as a function o f the air gap. In mammography the

same source-image distance is used for both the grid and magnification techniques. The

better solution would be to move the image receptor away from the patient, but this is

hard to achieve because of the limited loading capacity o f the small focal spot (Barnes

For the slit technique the beam is collimated close to the tube and the image receptor to

form a fan beam, which is guided over the breast. By pivoting the x-ray tube, the angle

between the anode disc and the imaging receptor is constant during the scanning

motion, thereby avoiding variations in x-ray fluence due to the heel effect (the pivot

point is the focal spot). Barnes et al (1993) found when quantifying the performance of

scanning slit mammography that a 25 - 45% improvement in contrast over that possible

with conventional grids for 5 to 8 cm thick breasts can be achieved. Decisive for the

efficacy of the slit system is the slit width. On the other hand the tube load increases as

the slit width decreases. A slit width of 7.5 mm close to the film -screen system results

in an image quality comparable with that of conventional grid mammograms at half the

patient exposure. To reduce the tube load Barnes et al (1993) proposed a multiple-slit

assembly. Such a system, they claim, can virtually eliminate scatter in mammography

with little or no loss of the primary x-rays emerging from the breast.

1.5.4 Image receptors

Image receptors form an image by the absorption of energy from the x-ray beam but a

variety of techniques are used to convert the resulting energy distribution into

something that can be visualised by eye. Image receptors in clinical mammography

include film-screen systems and digital sensors.

1.5.4.1 Film-screen systems

In routine mammography film-screen combinations are used almost exclusively as

image receptors. The application of industrial type (non-screen) x-ray film is either no

longer recommended or explicitly forbidden in different countries because of the high

radiation exposure. Often the sensitivity of the image receptor is characterised by the

so-called ‘system dose’ which is usually defined as the air kerma at the location of the

image receptor needed to obtain the receptor-specific exposure. In some countries, for

film-screen combinations there was a wide spread of system doses during the eighties

The typical system dose of a modem film screen system is about 1 - 3% of that of the

non-screen film. Average glandular dose is directly proportional to the system dose.

The reciprocal value of the system dose in turn is proportional to the speed of the image

receptor. Speed and system doses depend considerably upon the film processing, which

also influences contrast, resolution and noise (Haus 1992). Typical values for the

system dose of different image receptors are given in table 1.6.

Image receptor

System dose

For In /X jy

Industrial x-ray film Optical density (including base and fog) o f 2.0

3000

X erox 125 Optimum edge enhancement 1500-3000 Film screen system

During eighties

Optical density (including base and fog) o f 1.5

40-900

Film screen system Since 1990

Optical density (including base and fog) o f 1.5

4 0 -100

Table 1.6 Typical values fo r the system dose o f différent image

receptors. (Taken fro m Sabel et al 1989)

1.5.4.2 D igital radiography

Film screen is still the gold standard for the detection and diagnosis of breast cancer,

but it has certain limitations, which could possibly be overcome if mammograms were

recorded in a digital form. The most important limitation is the narrow dynamic range

(1:25), which must be balanced against the need of wide latitude (1:100) (Yaffe 1992).

The slope of the characteristic curve of the radiographic film determines the contrast

properties and the attenuation difference between a lesion and the surrounding tissue,

which can be seen in the image. Masses and microcalcifications in very dense breasts,

which are important indicators of cancer, are, therefore, hardly visualised by film-

screen combinations. On the contrary, in digital mammography with the help of

windowing the detectability of subtle details is limited only by noise. Digital

mammography, thus, has the potential for improving the display of poorly contrasting

details. Yaffe (1992) discussed various concepts for a digital mammography system: