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- •Color Doppler Sonography in Gynecology and Obstetrics
- •Preface
- •Contributors
- •Contents
- •Physical and Technical Principles
- •Principles of Ultrasound Instrumentation
- •Analysis of B-Mode Information and Artifacts
- •Duplex and Color Doppler Sonography
- •Physical Principles of Motion Detection
- •Technical Principles and Equipment Settings
- •1 Physical and Technical Principles of Color Doppler Sonography
- •Historical Development
- •B-Mode Sonography
- •Physical Principles of Echo Production
- •Analysis of Doppler Information and Artifacts
- •New Technical Processes and Approaches
- •New Developments in Transducer Technology
- •New Techniques of Signal Acquisition and Processing
- •2 Safety Aspects of Doppler and Color Doppler Sonography
- •Mechanisms of Tissue Effects
- •Heating
- •Cavitation
- •Risk Assessment of Various Ultrasound Techniques
- •Duplex Sonography
- •Color Doppler
- •Power Doppler
- •Color Velocity Imaging (CVI)
- •Transvaginal Scanning
- •Ultrasound Contrast Agents
- •Exposure of Gas-Containing Tissues
- •Measures to Limit Risk
- •Recommendations
- •General Recommendations
- •Pulsed Doppler
- •Appendix: Statements on the Biological Safety of Diagnostic Ultrasound Fields
- •EFSUMB Statement on the Clinical Safety of Diagnostic Ultrasound
- •WFUMB Statement on Thermal Effects in Clinical Applications
- •3 Uterine Blood Flow in Fertile and Infertile Women
- •Uterine Blood Supply
- •Changes in Uterine Blood Flow during the Menstrual Cycle
- •Blood Flow Parameters in the Uterine Arteries
- •Uterine Blood Flow in InfertileWomen
- •Uterine Blood Flow and Fertilization Rate
- •Uterine Blood Flow in the Normal Cycle and during Ovarian Stimulation with Confirmed Ovulation
- •Endometrial Imaging
- •Conclusions
- •4 Uterine Causes of Infertility
- •Ultrasound Detection of Uterine Abnormalities
- •Congenital Anomalies
- •Endometrial Polyps
- •Submucous Leiomyomas
- •Adenomyosis
- •Endometritis
- •Asherman Syndrome
- •Ultrasound Detection of Endometrial Causes of Infertility
- •Effect of Endometrial Thickness and Morphology on Fertility
- •Effect of Age on Endometrial Function
- •Endometrial Peristalsis
- •Cervical Factor
- •Decline of Fertility in the Perimenopausal Period
- •Uterine Receptivity
- •Oocyte Quality
- •Ovarian Function
- •Effects of Estradiol and Progesterone on Vascular Resistance
- •Sympathetic Innervation of the Uterus
- •Estrogen Effect
- •Progesterone Effect
- •Effect of Age on Ovarian and Uterine Perfusion
- •Authors’ Study
- •Interpretation of the Results
- •Functional Evaluation of the Endometrium
- •Authors’ Studies
- •Patients and Methods
- •Examination Procedures
- •Results
- •Discussion of the Role of Doppler Examinations
- •Summary
- •Applications of Doppler Sonography in Reproductive Medicine
- •Assessment of Tubal Patency
- •Patients and Method
- •Examination Technique
- •Results
- •Discussion of the Value of the Test Procedures
- •Summary
- •8 Abnormalities of Corpus luteum Function
- •Morphology and Biochemistry of the Corpus luteum
- •Conventional Methods in the Diagnosis and Treatment of Luteal Phase Defect
- •Possible Causes of Luteal Phase Defect
- •Diagnosis of Luteal Phase Defect
- •Treatment of Luteal Phase Defect
- •Ultrasound and Doppler Sonography in the Detection of Luteal Phase Defect
- •LUF Syndrome
- •Blood Flow in the Corpus luteum during Early Pregnancy
- •Fallopian Tube Catheterization
- •Aspiration of Ovarian Cysts
- •Drainage of Cul-de-Sac Abscesses
- •Selective Reduction of Multiple Pregnancies
- •Techniques of Ultrasound Tubal Imaging
- •Hysterosonosalpingography
- •9 Interventional Ultrasound in Reproductive Medicine
- •Follicular Aspiration in Assisted Reproduction
- •Transabdominal Follicular Aspiration
- •Transurethral Follicular Aspiration
- •Transvaginal Follicular Aspiration
- •Embryo Transfer
- •Obstetric Ultrasound
- •Overview
- •Monitoring Folliculogenesis
- •Development of the Corpus luteum
- •Changes in Endometrial Blood Flow
- •Luteal Blood Flow in Normal and Abnormal Pregnancies
- •Trophoblastic Invasion and Development of the Placenta
- •Implantation
- •Development of the Intervillous Circulation
- •Classic Theory
- •Objections and Alternative Theories
- •Color Doppler Studies
- •Vascularization of the Yolk Sac and Vitelline Duct
- •Changes in Uterine Perfusion after Placentation
- •Uterine Arteries and Spiral Arteries
- •Embryonic and Fetal Circulation
- •Fetal Vessels
- •Summary
- •12 Color Doppler Sonography in Ectopic Pregnancy
- •Importance of Transvaginal Sonography and Serum hCG
- •Transvaginal Color Doppler Sonography
- •Diagnostic Efficiency
- •Author’s Studies
- •Assessment of the Method
- •Summary
- •Conditions of Intrauterine Life
- •Physical Principles
- •Anatomical and Physiological Principles
- •Adaptive Processes during Pregnancy
- •Technique of Transvaginal Pulsed Doppler Flowmetry
- •Authors’ Studies
- •Uterine Perfusion in a Normal Pregnancy
- •Uterine Perfusion in an Abnormal Pregnancy
- •Discussion
- •Uterine Perfusion in a Normal Pregnancy
- •Uterine Perfusion in an Abnormal Pregnancy
- •Uterine Perfusion on Medication or after Uterine Manipulation
- •Summary
- •Doppler Flowmetry of Maternal Vessels as a Screening Test?
- •Applications of Color Doppler Sonography during Pregnancy
- •Technique of Transvaginal Doppler Sonography
- •Normal Development of Uterine Artery Doppler Spectra
- •Normal Values in Early Pregnancy
- •Early Doppler Examination of Uteroplacental Blood Flow in Abnormal Pregnancy
- •Patients
- •Results
- •Discussion
- •Summary
- •Establishing Normal Curves
- •Methodology
- •Defining the Normal Population
- •Plotting Quantile Curves
- •Results
- •Discussion
- •16 Venous Doppler Sonography
- •Historical Development
- •Physiology
- •Umbilical Vein
- •Ductus venosus
- •Inferior Vena Cava
- •Hepatic Veins
- •Clinical Applications
- •Intrauterine Growth Retardation Due to Chronic Placental Insufficiency
- •Growth Discordance in Multiple Pregnancy
- •Hydrops fetalis
- •Conclusion
- •Other Diseases
- •Specific Obstetric Problems
- •Importance of Nuchal Cord
- •Color Doppler Study on the Diagnosis of Nuchal Cord
- •Examination Technique
- •Results
- •Importance of Nuchal Cord Diagnosis in the Biophysical (ABCD) Profile
- •Role of Doppler Sonography in NC
- •Summary
- •18 Chronic Placental Insufficiency
- •Definitions
- •Definition and Incidence of Chronic Placental Insufficiency
- •Intrauterine Growth Retardation
- •Diagnosis of Chronic Placental Insufficiency
- •Diagnostic Systems
- •Indications for Doppler Sonography
- •Clinical Management of Chronic Placental Insufficiency Suspected from Doppler Findings
- •Antenatal Fetal Heart Rate Monitoring
- •Pathological Changes in Organ Systems
- •Biophysical Profile
- •Summary
- •Identifying Cases with IUGR
- •Obstetric Management
- •Surveillance of Compromised Fetuses
- •Absent End-Diastolic Flow (AEDF) and Reverse Flow
- •Absent End-Diastolic Flow in the Umbilical Artery and/or Fetal Aorta
- •Reverse Flow in the Umbilical Artery and/or Fetal Aorta
- •Clinical Results of AEDF or Reverse Flow in the Umbilical Artery and/or Fetal Aorta
- •Significance of Severely Abnormal Doppler Findings
- •Summary
- •20 Fetal Doppler Findings in Late Pregnancy
- •Physiological Findings in Late Pregnancy
- •Aorta: Quantitative Analysis
- •Aorta: Qualitative Analysis
- •Cerebral Arteries
- •Renal Arteries
- •Femoral Arteries
- •Changes in Findings at Term and in Postterm Pregnancies
- •Term Effect
- •Circulatory Balance
- •Summary
- •Pathophysiology and Technical Problems
- •Changes in Uterine ArteryWaveforms during Labor
- •Our Results
- •Discussion of Uterine Doppler Changes during Labor
- •IntrapartumWaveform Changes in Umbilical and Intrafetal Vessels
- •Umbilical Cord Doppler during Labor
- •Effect of Intrapartum FHR Decelerations on Quantitative Parameters of Umbilical Blood Flow
- •Direct Effect of Intrapartum Fetal Hypoxia or Hypoxemia on Blood Flow Patterns in the Umbilical Arteries and Vein
- •Summary
- •22 Color Doppler Ultrasound in Fetal Echocardiography
- •Congenital Heart Disease—Incidence and Risk Factors
- •General Introductory Remarks on Color Doppler Sonography of the Fetal Heart
- •Special Features of Fetal Echocardiography
- •Ultrasound Examination of the Fetal Heart
- •Normal Findings
- •Management of Suspected Congenital Heart Disease
- •23 Use of Color Doppler in Echocardiography
- •Importance of Color Doppler Echocardiography in Prenatal Diagnosis
- •Examination of the Normal Heart
- •Equipment Settings
- •Examination Technique
- •Cardiac Valve Regurgitation
- •Functional Physiological Tricuspid Regurgitation
- •Pathological Tricuspid Regurgitation
- •Tricuspid and Mitral Valve Regurgitation
- •Semiquantification of AV Valve Regurgitation
- •Anomalies of Visceroatrial Blood Flow
- •Anomalies of Atrioventricular Blood Flow
- •Anomalies of Ventriculoarterial Blood Flow
- •Anomalies of Blood Flow through the Cardiac Septa
- •Color Doppler Sonography in Fetal Arrhythmias
- •Summary
- •Structure of the Human Placenta
- •Weight and Dimensions
- •Early Development of the Human Placenta
- •Structure of the Villous Tree
- •Microstructure of the Terminal Villus
- •Maturation of the Placenta
- •Vascular Architecture of the Villous Tree
- •Regulation of Villous Blood Flow
- •Concept of the Placentone
- •Morphology and Physiological Transformation of the Maternal Basal-Plate Vessels
- •Placental Insufficiency
- •Definition and Etiology of Placental Insufficiency
- •Placental Compensatory Mechanisms
- •Classification of Placental Insufficiency by its Progression
- •Morphological Counterparts of Latent or Overt Placental Insufficiency
- •Clinical Aspects of Placental Insufficiency
- •Pathophysiological Aspects of Placental Insufficiency
- •Pathomorphological Aspects of Placental Insufficiency
- •Validation of Doppler Findings by Placental Histology
- •Resistance Index of the Umbilical Arteries
- •End-Diastolic Blood Flow Velocities in the Umbilical Arteries
- •Clinical and Diagnostic Value of Doppler Sonography of the Umbilical Arteries
- •Gynecological Ultrasound
- •Classification of Uterine Anomalies
- •Diagnosis and Complications of Septate Uterus
- •Ultrasound in the Diagnosis and Treatment of Septate Uterus—Authors’ Results
- •Patients and Methods
- •Results
- •New Thoughts on Old Problems
- •Changes in the Normal Endometrium during the Menstrual Cycle
- •Changes in Endometrial Blood Flow during the Menstrual Cycle
- •Submucous Leiomyomas
- •Endometrial Polyps
- •Endometrial Hyperplasia
- •Adenomyosis
- •Endometritis
- •Incomplete Abortion
- •Decidua
- •Examination Technique, Anatomy, and Physiology
- •Leiomyomas (Fibroids)
- •Vascularization of Leiomyomas
- •Management of Uterine Leiomyomas and the Importance of Color Doppler Sonography
- •Medical Treatment with GnRH Agonists
- •Surgical Treatment
- •Vascular Diseases in the Lesser Pelvis (Varicose Veins or Arteriovenous Malformations)
- •Incidence of Endometrial Carcinoma
- •Diagnostic Investigation of Suspicious Endometrial Findings
- •Color Doppler Sonography
- •Examination of the Uterine Artery
- •Experience at the Department of Obstetrics and Gynecology, Homburg University Hospital, Saar
- •Patients and Methods
- •Visualization and Morphology of the Vessels
- •Resistance Indices of Endometrial Vessels
- •Effect of Menopausal Status and Hormone Use
- •Effect of Histopathological Parameters, with Reference to Prognostic Factors
- •Subendometrial and Myometrial Vessels
- •Summary
- •30 Malignant Uterine Tumors
- •Endometrial Carcinoma
- •Incidence
- •Risk Factors
- •Target Group for Screening
- •Screening: Dream or Reality?
- •Authors’ Experience
- •Review of the Literature
- •Uterine Sarcoma
- •Authors’ Experience
- •Cervical Carcinoma
- •Conclusion
- •Treatment of Cervical Carcinoma
- •Assessing Treatment Response with Pulsed Color Doppler Sonography
- •Authors’ Studies
- •Discussion
- •Summary
- •Appearance of Normal Ovaries by B-Mode and Color Doppler Ultrasound
- •Specific Adnexal Masses
- •Cystic and Cystic-Solid Ovarian Masses
- •Solid Ovarian Masses
- •Conclusions
- •33 Malignant Adnexal Tumors
- •Color Doppler Sonography of Adnexal Malignancies
- •Review of the Literature
- •Neoangiogenesis
- •Detecting Blood Vessels and Defining their Location
- •Vascular Patterns
- •Pulsed Doppler Waveforms
- •Vascular Impedance
- •Blood Flow Velocities
- •Stages of Malignant Tumors
- •False-Positive Results
- •Conclusions
- •Contribution of Transvaginal Color Doppler Sonography
- •Three-Dimensional Imaging
- •Three-Dimensional Imaging of Vascular Patterns
- •Display Modes for Three-Dimensional Vascular Images
- •Ultrasound Technology in Tumor Diagnosis
- •Problems in the Interpretation of 3D Power Doppler Data
- •Current Methods for Evaluating Vascular Geometry and Function
- •Technique for Evaluating Vascular Geometry
- •Example of 3D Power-Mode Imaging of Benign and Malignant Gynecological Tumors
- •Advances in Tumor Therapy
- •Summary
- •Future Outlook
- •35 Ovarian Cancer Screening
- •Incidence and Five-Year Survival Rates of Ovarian Cancer
- •Requirements of a Screening Program
- •Definition
- •Screening Methods
- •Screening Parameters
- •Possible Screening Tests
- •Bimanual Pelvic Examination
- •Cul-de-sacWashings and Radiological Studies
- •Tumor Marker
- •Ultrasound
- •Who Should be Screened?
- •Age Distribution
- •Family History
- •Conclusion
- •Other Risk Factors
- •Historical Development
- •Blood Flow Detection
- •Number of Tumor Vessels
- •Resistance Index
- •Absolute Velocities
- •Doppler Waveform
- •Comparison of “Mirror Image Areas”
- •Conceptual Misunderstandings in the Interpretation of Doppler Measurements
- •Evolution of Breast Cancer Diagnosis
- •Continuous-Wave Doppler
- •Pulsed Doppler Techniques
- •Color Doppler
- •Equipment Settings
- •Examination Technique
- •Blood Flow Analysis
- •Study Results
- •Discussion
- •Conclusions
- •Flow Resistance in Malignant Breast Tumors
- •Authors’ Studies
- •Patients and Methods
- •Results and Discussion
- •Summary
- •Menopausal Status and Benign–Malignant Tumor Discrimination
- •Authors’ Studies
- •Patients and Methods
- •Results
- •Discussion
- •Summary
- •Applications of Color Doppler Sonography in Breast Cancer
- •Authors’ Studies
- •Methods
- •Results
- •Discussion
- •Conclusion
- •Index

General Aspects of the Ultrasound Investigation of Blood Flow in Breast Tumors
Resistance Index
The blood flow parameters that reflect vascular impedance appear to be the most reproducible. The resistance index (RI) is
most commonly used. Since it ranges from 0 to 1,the RI can also
express vascular impedance as a percentage. Most investiga-
5, 13, 15, 16
tors
characterize a tumor by the lowest RI that can be
recorded in the tumor or its immediate surroundings. Based on
the hypothesis that lower flow resistances can be measured in
malignant tumors due to morphological differences in the
capillary network of malignant and benign lesions, the lowest
measured RI was considered a valid discriminatory parameter
and was used for tumor characterization. However, clinical experience contradicted the validity of this parameter and this
method. Most groups of researchers found a significantly
higher minimum RI in malignant tumors. This did not improve
the discrimination of benign and malignant tumors, however,
and the hypothesis was invalidated. Moreover, the mathematical calculation of minimum RI is subject to irregularities as our
own studies illustrate
18
(Fig. 36.4).
36
Absolute Velocities
Several groups of investigators have worked with absolute
velocities, especially the maximum systolic velocity
Madjar and his group
14
even defined a new blood flow parameter, the flow velocity sum, as a correlate to total blood
flow. When the flow velocities in all the tumor vessels were
added together, the accuracy of benign–malignant discrimination increased to 90%. The use of flow velocities is still problematic, however, due to the angle dependence of the
measured velocities. The nee d to optimize or cor rect for the
beam–vessel angle is time-consuming and is possible only
when the flow can be demonstrated along the vessel axis. This
is extremely difficult in the case of small vessels (Fig. 36.
1,2, 10,13, 15
5).
.
342
a
c
Fig. 36.4 Breast carcinoma with a rich vascular supply.
a Numerous vessels are visible in the color Doppler image.
b
d
b–d The RI is relatively high but shows marked variation within the
tumor (0.67, 0.61, 0.53). Is there a representative RI?

Specific Parameters in the Doppler Examination of Breast Tumors
Fig. 36.5 Blood flow detection along the vessel axis.
a Small vessels (slow blood flow) are often difficult to visualize in
longitudinal section.
Number and Intensity of Color Pixels and Color
Areas
Today the number and intensity of individual color pixels and
color areas can be evaluated with angle-independent Doppler
and non-Doppler methods. The sensitivity of this newer technology is higher than that of conventional color Doppler ultrasound. Disadvantages are a greater susceptibility to errors,
b Blood flow in a peripheral, S-shaped vascular segment. A long-axis
vascular scan can be difficult to acquire. The absolute velocity changes
with the angle correction, which is almost arbitrary. Ideally, blood flow
should be sampled in a straight vascular segment.
problems in comparing findings with different technologies,
and the inability to measure flow velocities. There are study results with conventional Doppler in which increased, high-
velocity blood flow was found in breast carcinomas using a
semiquantitative grading method
6
. One disadvantage of this
method is that the color pixels displayed are strongly dependent on the technology used, the equipment settings, and equipment handling by the examiner, and therefore the method has
not become established in routine clinical use (Fig. 36.
6).
Gynecological Ultrasound
a
Fig. 36.6 Benign–malignant discrimination based on the number of
color pixels and the image area that they occupy has proved to be imprecise. Images a–c illustrate the lack of comparability of different
technologies.
a S-shaped vascular segment defined by color Doppler.
b Power Doppler demonstrates additional vessels.
c Even more intense vascularity is seen in the subtraction view.
b
343
c

General Aspects of the Ultrasound Investigation of Blood Flow in Breast Tumors
36
a
b
Fig. 36.7 The Doppler waveform of malignant tumors does not dis-
a Even waveforms from healthy tissue may exhibit a slow systolic
downstroke and high diastolic flow.
344
Fig. 36.7b Compare the waveforms in a with spectra sampled from
a carcinoma with a high RI.

Conceptual Misunderstandings in the Interpretation of Doppler Measurements
Fig. 36.7c Early diastolic notch in a parenchymal vessel in the axillary
tail of the left breast.
Doppler Waveform
Typical features cannot be found in the Doppler waveforms
sampled from malignant tumors (Fig. 36.
7a, b). An early dias-
tolic notch in the Doppler waveform, which signifies high
vascular impedance in obstetric ultrasound, is not a differentiating criterion because it is seen only occasionally and also because it may be found in benign lesions and in normal breast
tissue (Fig. 36.
7c, d).
Comparison of “Mirror Image Areas”
Various groups of authors
of asymmetry between the tumor and the contralateral
healthy breast. Several groups found a statistically significant
2, 13, 15, 19
have noted the significance
Fig. 36.7d Diastolic notch recorded in close proximity to a fibroadenoma.
difference between the tumor area and the healthy parenchymal breast tissue. Madjar et al.
counts and maximum velocity, Blohmer
ity, and Sohn
15
in the resistance index. Our group19found a
13
found differences in vessel
2
in maximum veloc-
statistically signif icant elevation of RI in premenopausal
women with a malignant tumor compared with the healthy
glandular tissue in the contralateral breast. On the whole, parameters that reflect vascular impedance, particularly the RI,
have the best reproducibility. As a result, this parameter has
become a focus of international research.
It is our opinion that menopausal status and hormone re-
placement are important as fundamental factors, regardless of
which parameter is studied. But even when these factors are
considered, we feel that the comparative approach to breast
cancer diagnosis is not sufficiently reliable in individual cases
due to the large scatter of the results.
Gynecological Ultrasound
Conceptual Misunderstandings in the Interpretation of Doppler Measurements
Problem areas. The sonographic imaging of blood flow in
breast tumors is still a controversial issue. Despite years of testing, this method is still experimental in nature and has not become established in routine clinical use. Despite rapid technological advances in this area, it has not been possible to establish criteria or define blood flow parameters that would improve the discrimination between benign and malignant lesions. Basic problems lie in the unscientific interpretation of
relationships between the histopathology and vascular physiology of tumors, the anatomical localization of detected flow
signals, and the validity of blood flow characterization by ultrasound measurements.
Unproven claims. Conceptual misunderstandings based on an
unscientific interpretation of presumed relationships have
colored the debate in recent years. It was often claimed, erroneously, that blood flow could be sampled from the capillary
network formed by tumor angiogenesis, yielding characteristic
waveforms and impedance values that could be used to eval-
uate the histomorphology of the angiogenic capillaries of
benign and malignant lesions.
In another unproven claim that was accepted more or less
as fact, malignant tumors were defined as a flow system in
which the resistance to flow was lower than in benign tumors.
The results of studies conducted by our group have cast serious
doubt on both of these claims
16, 17, 19
.
Various authors have speculated whether the resistance indices determined by Doppler sonography or the density of
blood vessels in the color Doppler image might correlate with
the vascular density determined by microscopy. So far there is
no scientific proof that the capillaries formed by tumor angio-
genesis can be detected with ultrasound. It is generally acknowledged that color Doppler imaging can demonstrate
larger-caliber portions of the vascular network that feed and
drain the tumor and can occasionally detect intratumoral vessels as well. Color Doppler is capable only of assessing the
blood flow conditions that are associated with tumor neoan-
giogenesis.
345

General Aspects of the Ultrasound Investigation of Blood Flow in Breast Tumors
346
Neoangiogenic potential and color Doppler signals. Lagalla and
his colleagues
11
proved that color Doppler blood flow signals
do not originate from the vascular network produced by tumor
angiogenesis. These authors correlated the detection or nondetection of color Doppler signals in 22 breast carcinomas with
the angiogenic potential of the lesion evaluated in histological
sections using a scoring system (MAGS = microscopic angiogenesis grading system) base d on the number of blood vessels
in the histological section, hyperplasia, and the mitosis rate of
endothelial cells. Since the histological discoveries of Weidner
20
et al.
, who proved that the density of tumor angiogenesis in
49 breast carcinomas correlated with a poorer prognosis and
an increased rate of distant metastases, it was reasonable to expect that neoangiogenic potential would correlate with the
presence and intensity of detectable flow signals. However, the
highest neoangiogenic potential (score ⬎ 30) was observed in
the four tumors that had no detectable color Doppler signals.
Meanwhile, a score ⬍ 30 was found in 17 of 18 cases with positive color Doppler flow detection. Microscopically, signal detection was found to correlate with vessels larger than 1 mm in
diameter! This led the authors to conclude that color Doppler
flow detection depends on the caliber of the tumor-feeding
vessels and that the absence of flow signals is not a reliable
36
criterion for excluding a malignant tumor.
No objective proof of tumor neovascularity. These results appear to have greater significance that the authors ascribe to
them, for, as our own observations have shown
17, 19
Doppler sonography is incapable of recording blood flow signals from neoangiogenic tumor vessels at the present time. We
must conclude, then, that the biological principles that have
been widely advanced over the years for the color Doppler
assessment of tumor angiogenesis are untrue and should be
discarded. Of course, angiogenesis is essential for the rapid
growth of solid malignant tumors, as Folkman explained in
7
1971
. It is also clear that differences in the prominence of arteriovenous shunts and luminal irregularities (due to the lack of a
smooth-muscle layer) are observed in tumor vessels at the histopathological level. There is no proof, however, that the sonographic evaluation of blood flow can detect these characteristic
histopathological features or the presumed associated
decrease of flow resistance in the capillary bed of breast malignancies. In particular, this type of examination has been unable
to objectify the extremely slow blood flows that are claimed to
characterize the perfusion of malignant tumors.
Comments. These results also mean that the measurements of
resistance indices that have previously been used for benign–
malignant discrimination were not obtained in neoangiogenic
tumor vessels but in larger tumor-feeding vessels. The wall
structure of these vessels does not differ between benign and
malignant lesions, and therefore the blood flow is subject to
different principles.
When we take into account these conceptual misunderstandings, which run like a thread throughout the literature,
we can appreciate whythe flowsmeasured in malignant breast
tumors may show a higher impedance than in benign lesions.
Chapters 38–40 deal with various factors that can fundamentally influence blood flow parameters. First, the usefulness of the minimum RI as a suitable representative parameter
, color
for tumor characterization is investigated. The next chapter explores the effects of menopausal status, hormone replacement
therapy, and age on quantifiable blood flow parameters. The
final chapter examines the usefulness of the RI in the benign–
malignant discrimination and prognostic evaluation of breast
tumors.
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References
20 Weidner NR, Semple JP, Welch WR: Tumour angiogenesis and
metastasis: Correlation in invasive breast carcinoma. New Engl. J. Med.
324 (1991) 1–8
21 Wells PNT, Halliwell M, Skidmore B, Webb AJ Woodcock JP: Tumour
detection by ultrasonic Doppler blood flow signals. Ultrasonics 15
(1977) 231–232
22 White DN, Cledgett PR: Breast carcinoma detection by ultrasonic
Doppler signals. Ultrasound Med. Biol. 4 (1978) 329–335
Gynecological Ultrasound
347

Color Doppler Sonography in the Diagnosis of
348
37
Breast Cancer
H. Madjar
Evolution of Breast Cancer Diagnosis
Improvements in ultrasonography and mammography. Ultra-
sonography of the breast has improved dramatically in recent
years owing to the development of high-resolution ultrasound
systems. Until a few years ago, the investigation of palpable
breast masses and the cystic/solid differentiation of mammographic densities were still considered the only goals of breast
ultrasound. Higher contrast resolution and spatial resolution
led to better soft-tissue discrimination, significantly improving the detection and differential diagnosis of subclinical
disease. Mammography, too, has steadily improved through
37
the development of the grid technique along with modern
film–screen combinations and tube anodes. Meanwhile,
numerous screening studies have documented the value of
early diagnosis in reducing the mortality rates from breast
cancer.
Problems in mammography. Since breast cancer is the most
frequent cancer in women, the reduction of mortality from this
disease has major epidemiological significance. While mammographyis very sensitivein its ability to detect breast tumors,
it cannot provide a definitive diagnosis, and women with abnormal screening results require further testing. In the United
States, approximately 70–90% of women with abnormal
screening results undergo unnecessary breast surgery for
benign conditions. These unnecessary operations are distressful for the patients and can cause scarring that will interfere
with further mammographic follow-ups. Negative biopsies
Fig. 37.1 Typical ultrasound appearance of an invasive ductal breast
carcinoma 16 mm in diameter. The image shows a nonhomogeneous,
hypoechoic mass with irregular, ill-defined margins and a posterior
acoustic shadow.
have economic ramifications as well. Looking at clinical data in
the United States, if we assume that there is a 10% annual positive rate of screening mammograms in a country with 25 million women of screening age and that only 50% of this population will present for screening, we find that approximately 1.25
million women will have suspicious breast findings that warrant further testing. If 50 % of these women are referred for
breast biopsy,the annual costs amount to billions of dollars, assuming a basic cost of $1000 to $5000 per operation. So from
an economic standpoint as well, the specificity of the diagnosis
must be substantially improved.
Problems in ultrasonography. Ultrasound can provide better
soft-tissue discrimination than mammography, but there is a
considerable overlap of diagnostic criteria between benign and
malignant lesions. While carcinomas are typically nonhomogeneous and hypoechoic, with irregular, ill-defined margins
and a posterior acoustic shadow (Fig. 37.
breast changes and especially scars that mimic these findings
and often prompt unnecessary surgery. On the other hand,
benign breast lesions such as fibroadenomas typically appear
as elliptical, uniformly hypoechoic masses with sharp, welldefined margins and good through-transmission of sound. But
there are some fibroadenomas, especially the intracanalicular
and proliferative forms, that are nonhomogeneous and have irregular margins (Fig. 37.
breast cancer that mimic the typical sonographic features of fibroadenoma, such as medullary, mucinous, and solid invasive
ductal carcinomas.
The differentiation between cystic and solid masses can
also be difficult to accomplish with ultrasound if the contents
of the mass are cellular or inspissated (Fig. 37.
changes are another problem. With severe, proliferative forms
of fibrocystic change, disseminated microcalcifications are
frequently seen on mammograms. At ultrasound, these breasts
often show significant fibrosis with strong sound attenuation
(Fig. 37.
making it extremely difficult to rule out cancer or localize a lesion that has been targeted for biopsy (Figs. 37.
diffuse changes pose a major problem, especially in high-risk
patients with a strong family history. Also, the sensitivity of
mammography is often compromised by the radiographically
dense breast parenchyma that exists in younger women. These
problems underscore the need for improvements in preoperative breast diagnosis.
4). Sonograms are difficult to interpret in these cases,
2). Also, there are numerous types of
1), there are fibrocystic
3). Diffuse breast
5,37.6). Such

Fig. 37.2 Intracanalicular fibroadenoma. This benign tumor has
atypical sonographic features, appearing as a nonhomogeneous mass
with irregular margins.
Evolution of Breast Cancer Diagnosis
Assessment of tumor vascularity. Numerous histopathological
and molecular biological studies have shown that the development of a malignant tumor from the in-situ stage requires
neoangiogenesis
neoangiogenesis very likely correlates with the metastatic
potential and prognosis of the malignant tumor
have been applied in various diagnostic procedures such as angiography, thermography,and dynamic MRI. Such studies have
also shown that the blood flow in malignant tumors is increased in comparison with healthy breast tissue.
Thermography. Thermography can measure temperature
differences in the skin caused by local changes in blood flow
and metabolism. Deep breast lesions often do not produce
measurable changes, however, and many physiological conditions can cause changes in heat distribution. As a result, thermography has proved to be a relatively nonspecific test.
2, 12
. It has also been shown that the degree of
13
. These facts
Fig. 37.3 Inspissated cyst containing hemosiderin. FNA biopsy
showed no evidence of proliferative changes. The mass cannot be
positively distinguished from a solid tumor by its B-mode appearance.
Gynecological Ultrasound
Fig. 37.4 Severe fibrotic changes with diffuse sound absorption. Both
the sonograms and mammograms of this patient were very difficult to
read.
Fig. 37.5 Diffusely infiltrating ductal carcinoma. The tumor margins
are difficult to identify.
Fig. 37.6 Diffusely infiltrating lobular carcinoma. Diffuse growth is
particularly common with this type of carcinoma, often delaying the
diagnosis.
349

Color Doppler Sonography in the Diagnosis of Breast Cancer
350
Angiography and MRI. Angiography is too invasive for routine
evaluations. Dynamic MRI with contrast administration has
demonstrated its reliability, but it is a technologically complex
study. Another problem is its limited temporal and spatial resolution, resulting in the frequent detection of blood flow
changes that have no clinical, mammographic, or sonographic
correlates and often are not referable to specific soft-tissue
Continuous-Wave Doppler
Applications. Continuous-wave (CW) Doppler has been used
for many years in neurology and angiology for the diagnosis of
vascular stenosis and venous insufficiency. CW Doppler has
not been used in abdominal or gynecological examinations because it does not simultaneously display the anatomical region
of interest, making it extremely difficult to diagnose deeply situated tumors. CW Doppler has been widely used in pregnant
patients for acoustically locating the uterine arteries and recording pregnancy-associated flow changes. This can be done
with little difficulty, since the anatomical course of these vessels is known and can easily be located.
37
Breast tumors. CW Doppler has been used for approximately
20 years in the analysis of tissue and tumor blood flow in the
breast. This is possible because the mammary gland is a superficial organ that is easily accessible to blind interrogation with
CW Doppler. In particular, it is an easy matter to trace around a
palpable breast mass with a hand-held Doppler probe and record vascular signals
are distinguished from benign lesions by their increased blood
flow. As a result, an asymmetry of vascularity is noted when
the two sides are compared. The initial studies by Wells et al.
were based on the purely acoustic evaluation of an amplified,
high-frequency flow signal and did not yet permit a frequency
spectrum analysis. Since the broad CW Doppler beam often interrogated multiple tumor vessels at one time, the flow signals
were turbulent and rough, and a relatively loud signal was
audible even during diastole. Several years passed before
frequency spectrum analysis was performed. When detailed
comparisons were made between the spectra sampled from
malignant and benign lesions, a relatively high diastolic flow
component was found even in normal parenchymal vessels of
the breast. In contrast to peripheral vascular regions such as
the radial artery or other resistance vessels, the systolic
waveform is broad and rounded, and generally an early diastolic notch is not seen because practically no muscular vascular
resistance occurs in this region (Fig. 37.
signals are compared with those from malignant tumors, the
latter are generally found to have higher systolic and diastolic
flow, although the relationship between systole and diastole is
usually unchanged
Cyclic blood flow variations. High-frequency CW Doppler has
also been used for various other indications. The broad Doppler
beam is relatively favorable for evaluating diffuse parenchymal
blood flow. Serial studies of physiological variations in blood
flow during the normal menstrual cycle have shown that the
cyclic flow variations are relatively small for any given in-
3, 5, 11,14
6
.
. Studies showed that malignancies
7). When these flow
changes. Also, there has been growing evidence in recent years
that physiological blood flow variations can greatly affect the
results of MRI. Motion artifacts are another problem that can
lead to equivocal or false-positive findings. It would be
desirable, then, to have a method for measuring tumor blood
flow and simultaneously imaging the associated tissue structures with high temporal and spatial resolution.
dividual, ranging from 50 Hz to a maximum of 200 Hz. But
when different individuals are compared, the mean frequency
shifts of parenchymal blood flow in the breast show differences as large as 500 Hz. Interestingly, blood flow is lowest
during the first half of the menstrual cycle and increases
markedly from ovulation to menstruation
7
. A pronounced increase equal to several times the baseline level is observed
during the initial weeks of pregnancy.
Benign breast diseases. As the severity of benign breast lesions
increases, we find an associated increase in blood flow compared with normal breast tissue. Since benign breast diseases
are often accompanied by severe symptoms, they are treated
with numerous medications, some of which can have serious
side-effects. In the past, the only way to monitor treatment response in most patients was by noting improvement in their
complaints over time. Doppler sonography, on the other hand,
allows us to measure therapeutic response in cases where
treatment has caused a reduction in blood flow. Since it is reasonable to assume that the increased blood flow in proliferative forms of fibrocystic change is caused by an increase in me-
14
tabolism, we may conclude that a reduction in blood flow
correlates with a regression of proliferative changes
9
.
Chemotherapy for breast cancer. Another problem involves
the neoadjuvant chemotherapyof extensive breast cancers and
the chemotherapy of recurrent tumors. In the past, there has
been no effective method of evaluating therapeutic response in
the living patient. The only parameter that can be used for this
purpose is tumor size, which is monitored by clinical examination or various imaging procedures. This is an extremely crude
method, however, compared with the complicated processes
that take place within the tumor. Still, as in benign conditions,
the assessment of blood flow reflects the proliferation of the
tumor tissue. It has been shown that the measurement of
blood flow with Doppler ultrasound provides a sensitive parameter for assessing tumor response to chemotherapy
4
.
Advantages and disadvantages. The advantage of CW Doppler
is that the signal is not pulsed and high frequencies in the range
of 8–10MHz can be used. Both of these factors contribute to
the high sensitivity of CW Doppler, which can detect even
small blood flows
6
. One disadvantage of CW Doppler is that,
without simultaneous tissue imaging, nonpalpable lesions are
difficult to diagnose.
In the past, the combination of CW Doppler and ultrasound
imaging required a complex setup in which a CW Doppler
probe was incorporated into the central rotary axis of the im-

Color Doppler
ab
c d
Fig. 37.7 CW Doppler spectra.
a Brachial artery.
b Radial artery.
aging transducers in a water-bath scanner3. While this increased the sensitivity of the CW Doppler,water-bath scanning
did not become an established method because of its relatively
c Artery in normal breast parenchyma.
d Artery in a carcinoma.
Pulsed Doppler Techniques
Vascular imaging. In principle, duplex scanning fulfills the
desire for a method that can assess the vascularity of nonpalpable tumors. The lesion is visualized in the B-mode image, the
sample volume is positioned in the vessel of interest, and flow
spectra are recorded. However, duplex scanning was designed
for use in anatomical regions with grossly visible vessels.
Tumor diagnosis. The vascularity that is associated with a
tumor is not completely accessible to diagnostic imaging. It
would be necessary to explore the full extent of the tissue
volume using a one-dimensional, pulsed, range-limited
sample volume, making the examination far too costly and
time-consuming. Another problem is that the sensitivity of
poor spatial resolution compared with modern, high-resolution real-time scanners.
Doppler equipment is determined chiefly by the transmission
frequency, as mentione d above. In most cases the Doppler
frequency is well below the frequency of the imaging system.
With a 5 MHz imaging transducer, for example, the Doppler
frequency is generally in the range of 2–3 MHz. Usually this
means that the sensitivity is too low to detect the microvessels
in a tumor. We tested this by comparing CW Doppler and duplex scanning in a large series of patients. We found that duplex scanning was extremely difficult to use for this application, for methodological reasons, and that the sensitivity was
too low for this type of examination, at least when a 3 MHz
Doppler frequency was used
6
.
Gynecological Ultrasound
Color Doppler
Tumor vascularity. Since the late 1980s, color Doppler instru-
ments have been available that provide a color-encoded flow
image superimposed over a real-time B-mode image
(Fig. 37.
bined gray-scale and Doppler technique for evaluating nonpal-
8). This combination satisfies the demand for a com-
pable focal breast lesions. As in other techniques, however, the
low sensitivity of many color Doppler systems is a serious limiting factor. In the assessment of tumor vascularity, it is important to consider that the type of equipment used has a major
bearing on the quality of the examination. Several studies have
351
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