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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.
References
1 Backe J, Mai R, Rempen A: Farbdopplersonographie bei tastbaren
Mammatumoren im Vergleich zur kontralateralen Brustdrüse. Ul­traschall Klin. Prax. 10 (1995) 1–7
2 Blohmer JU, Bollmann R, Schmalisch A, Chaoui R, Lau HU: Die Differen-
tialdiagnose von Mammatumoren durch den Vergleich der Durch­blutung des Tumors mit der kontralateralen Brust mittels farb­kodierter,gepulster Dopplersonographie. Geburtsh. u. Frauenheilk. 55 (1995) 1–6
3 Britton PD, Coulden RA: The use of Doppler ultrasound in the diagnosis
of breast cancer. Clin. Radiol. 42 (1990) 399–401
4 Burns PN, Halliwell M, Wells PNT, Webb AJ: Ultrasonic Doppler studies
of the breast. Ultrasound Med. Biol. 8 (1982) 127–143
5 Campbell S, Bourne TH, Reynolds K et al.: Role of Colour Doppler in an
ultrasound-based screening programme. In Sharp F, Mason WP, Creas­man W (eds.): Ovarian Cancer 2: Biology, Diagnosis and Management. Chapman and Hall, London 1992, 237 –247
6 Cosgrove DO, Bamber JC, Davey JB, McKinna JA, Sinnett HD: Color
Doppler Signals from Breast Tumours. Radiology 176 (1990) 175–180
7 Folkmann J, Merler E, Abernathy C, Williams G: Isolation of a tumor
factor responsible for angiogenesis. J. Exp. Med. 133 (1971) 275–288
8 Gros ChM, Dale G, Gairand B: Breast echography: criteria of malig-
nancy and results. In Kurjak A (ed.): Recent Advances in Ultrasound Di­agnosis. Excerpta Me dica, Amsterdam 1978, 292–298
9 Halliwell M, Atkinson P, Webb AJ, Wells PNT: Breast tumour detection
by ultrasound blood flow signals. Proc. Amer. Inst. Ultrasound Med. 1 (1978) 96
10 Heilenkötter U, Jagella P: Farbdopplersonographie exstirpationsbed-
ürftiger Mammatumoren. Geburtsh. Frauenheilk. 53 (1993) 247–252
11 Lagalla R, Caruso G, Marasa L, D'Angelo I, Cardinale AE: Capacità angio-
genetica delle neoplasie mammarie e correlazione con le semeiotica color Doppler. Radiol. Med. 88 (1994) 392–395
12 Lypacewicz G, Powalowski T, Lukawska K: Ultrasonic examination of
breast tumours with Doppler method. In Filipczynski L, Zieniuk JK (eds.): Proc. 2nd Congress of the Federation of Acoustical Societies of Europe 1978. Polish Academy of Sciences, Warsaw 1978 Vol. II, 153– 156
13 Madjar H, Sauerbrei W, Münch S, Prömpeler H, Schillinger H:
Methodenanalyse zur Doppleruntersuchung der weiblichen Brust. Ul­traschall in Med. 11 (1990) 196–201
14 Madjar H, Prömpeler H, Wolfahrt R, Bauknecht T, Pfleiderer A: Farb-
dopplerflußdaten von Mammatumoren. Ultraschall in Med. 15 (1994) 69–76
15 Sohn Ch, Grischke EM, Wallwiener D, Kaufmann M, von Fournier D,
Bastert G: Die sonographische Durchblutungsdiagnostik gut- und bös­artiger Brusttumoren. Geburtsh. Frauenheilk. 52 (1992) 397–403
16 Villena-Heinsen C, Ertan AK, Tossounidis I, Holländer M, König J,
Schmidt W: Diagnostische Aussagekraft der Farbdoppler-Sonographie bei Mammatumoren. Geburtsh. Frauenheilk. 55 (1995) 541–547
17 Villena-Heinsen C, Mink D, Ertan AK, Holländer M, Schmidt W: Bewer-
tung der Aussagekraft der Farb- und Spektraldopplersonographie bei Brusttumoren. In Schmidt W (ed.): Jahrbuch der Gynäkologie und Ge­burtshilfe 1995/1996. Biermann, Zülpich 1996, S. 121–136
18 Villena-Heinsen C, König J, von Tongelen B et al.: Validity of the mini-
mal Resistance Index for discrimination between benign and malig­nant Breast Tumours. Eur. J. Ultrasound 7 (1998) 189–193
19 Villena-Heinsen C, Ertan AK, Holländer M, König J, Tossounidis I,
Schmidt W: Diagnostische und prognostische Wertigkeit des Gefäß­widerstandes bei Brusttumoren. Ultraschall in Med. 19 (1998) 10–15
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