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Diagnostic Sonography of Blood Flow in Breast Tumors
3
ground noise, since they are the result of the addition
of frequency shifts, and not, as in a conventional Doppler, their mean. For this reason power Doppler can be
used at higher amplification, enabling a more sensitive
and continuous display of the vessels. Sensitivity is increased fortyfold. This procedure makes it possible to
detect flow velocities of 0.4 mm/s (Sohn et al. 1996).
Because angio color is extremely sensitive to low
blood flows in vessels formed by angiogenesis, artifacts formed by patient respiration, pulse, or movements are very frequent. Another drawback of the procedure is also due to its very high sensitivity: some of
the blood vessels detected by power Doppler with extraordinarily low blood flows cannot be quantified by
conventional PW Doppler. Quantification is not
possible in angio mode alone. Work in progress is attempting to relate the number of color pixels in a ROI
to the total sample volume, using computerized systems, but this model does not provide absolute figures.
Fig. 22.5 Color Doppler sonographic display of a breast tumor
without administration of contrast medium.
Introduction of Ultrasound Contrast Media
In many cases the color signals and the quality of the
Doppler flow curves obtained by the usual instrumentation are not adequate for reaching a satisfactory conclusion for the staging of a breast tumor. The introduction of ultrasound contrast media to amplify the echo
signal can improve the evaluation of the degree of
vascularization.
For this procedure 2.5 g of granular galactose are
shaken with 7.5mL H
tion to form a fluid with a concentration of 300 mg/mL.
The microbubbles formed at the surface of the
granules by the agitation are stabilized by adding 1 mg
of palmitic acid, which keeps them in the hepatic and
pulmonary circulations. About 20−25 seconds after the
bolus of contrast medium is injected intravenously
into the peripheral circulation, the intensity of the
Doppler signal increases by 10−20dB (Schlief 1991).
The microbubbles increase the echogenicity of the
blood by forming a boundary with increased acoustic
impedance on their surface.
Side effects due to the contrast medium are rare.
They include transient sensations of pain, heat, or cold
at the injection site (Schlief 1993, Madjar 1997/8).
Hereditary galactosemia is an absolute contraindication to the use of ultrasound contrast medium. Studies
published in the literature to date report a subjective
impression of improved display, primarily of small
tumor vessels (
al. 1993, Madjar et al. 1993).
Considered from a fundamental point of view the
use of sonographic contrast media, by displaying the
dynamics of the circulation in a tumor, can serve as a
diagnostic aid for staging. In this way it resembles
magnetic resonance imaging (MRI), and such studies
are being undertaken. However, a drawback to be considered is that administering a contrast medium represents an additional diagnostic step for both patient and
examiner, and that this can be quite time-consuming.
Finally, more evidence is required to confirm that this
procedure truly provides additional information that
broadens the diagnostic base for staging and so justifies the additional effort in clinical practice.
Figs.
O shortly before the examina-
2
22.5, 22.6) (Cosgrove 1992, Duda et
204
컅 Fig. 22.6 Color Doppler sonographic display of a breast tumor
with administration of contrast medium. Especially the small
tumor vessels can be identified more easily.
Color-Coded Doppler Ultrasound in the Differential Diagnosis of Breast Tumors
Color-Coded Doppler Ultrasound in the Differential Diagnosis of Breast Tumors
The first studies addressing the differential diagnosis
of breast tumors by color-coded Doppler ultrasound
described a purely qualitative display of blood vessels
around the primary lesion. When blood vessels were
then demonstrated in a sonographically equivocal
tumor, the tumor was likely to be malignant, while it
was considered to be benign in the absence of such
vessels (Britton and Coulden 1990).
In contrast to this finding, Adler et al. (1990) could
not demonstrate any blood vessels in 18% of patients
with breast cancer, while they detected bloods vessels
in 97% of all patients they examined who had no suspicious lesions. These results indicate that a purely qualitative description of blood flow is not sufficient for
differential diagnosis.
Based on this finding, increased attention was
devoted to quantitative analysis of Doppler flow curves
derived from tumor vessels (Dock 1993, Konishi 1992).
A further attempt to differentiate benign from malignant findings in the female mammary gland was based
on the detection of a difference in the RIs of the breasts
on the healthy and affected sides (Sohn et al. 1992b,
1993). Current opinions differ considerably regarding
the conclusions that can be drawn from measurements
of perfusion (Jellins 1988, Madjar et al. 1989, 1991a,
1991b, Sohn et al. 1992b, 1993).
The following markers can be examined and
assessed:
왘 Number of vessels in the tumor and its immediate
surroundings,
왘 Calculated Doppler parameters (quotient, RI, PI),
왘 Shape and characteristics of the Doppler flow curve,
왘 Comparison of perfusion in the healthy and affected
breasts in the same patient,
왘 Size and number of individual color pixels or color
surfaces in a tumor.
The differential diagnosis of breast tumors using the
number of blood vessels detected seems problematic.
As noted above, CW Doppler requires a systematic and
time-consuming examination of the whole breast, and
the results depend very much on the examiner’s experience. With color-coded ultrasound the vessels are
detected by using the number of color pixels and surfaces displayed. Often the course of a tumor vessel cannot be determined with confidence, because only
single pixels or small color surfaces are displayed.
Therefore, if the loops of a single vessel appear several
times in one ultrasonic cut, the possibility that it will
be counted several times in the total number of vessels
cannot be excluded with confidence.
The most reproducible constants are the conventional Doppler parameters. Hence in recent years
quantitativeanalysis of blood flow in tumor vessels has
increasingly been using calculated Doppler parameters
(Blohmer and Guski 1995, Dock 1993, Konishi 1992,
Madjar et al. 1991a, Sohn et al. 1992a, 1993). However,
the velocities calculated from the Doppler flow curve
depend on the angle of the incident sound waves (Sohn
et al. 1993). In routine clinical practice it is difficult,
especially for very small tumor vessels, to assure an
optimal angle. The profile of the Doppler curve can of
course be defined objectively to some extent by the RI
and the PI, both almost independent of the angle.
Therefore, the RI is most often used in daily clinical
practice. The vascular resistance is then expressed as a
number between 0 and 1 or as a percentage. The
lowest measured RI values of a tumor and its immediate surrounding tissue are always used for evaluation.
The differences between the vascular supply of
benign and malignant tumors are found in the capillary bed. As noted before, tumor vessels formed by angiogenesis have no muscular layer. Moreover, the total
vascular diameter increases as the number of new
capillaries increases, reducing the resistance.
Variousworking groups havesuggested a cutoff level
in the RI of 쏝0.7 or 70% to distinguish between benign
and malignant tumors. By this measure Doppler ultrasound of the breast has a sensitivity of 84 % and specificity is 80 %. The positive predictive value is given as
71% and the negative predictive value as 90% (PetersEngl et. al. 1995).
However, determining an absolute value for a cutoff
level for blood flow does not appear promising, given
just the physiological changes in the glandular tissue of
the breast and the very varied histological changes in
breast tumors that may show varying degrees of differentiation and often very different patterns of vascularization. Moreover,blood flow depends on the size of the
lesion. In the evaluation of conventional Doppler findings, a drawback we have previously described several
times is that, because of their slow flow rates, it is difficult or impossible to detect the small vessels formed
by neovascularization (Sohn and Meyberg 1995).
The characteristics and shape of the Doppler curve
provide important criteria for the evaluation of tumor
perfusion. Mostly, when the changes in the breast are
benign, systole is relatively high, and by comparison
diastole is low. Systole can clearly be distinguished
from diastole. Whether the resistance is high or low
can be concluded from the shape of the curve. An early
diastolic notch in the Doppler flow curve suggests high
vascular resistance. This characteristic blood flow
curve defines vessels with a flexible muscular layer,
such as run through normal glandular tissue and
benign lesions (Fig. 22.7).
In the case of malignant breast tumors the height of
systole is relatively low and that of diastole by com-
Advanced Topics
205
Diagnostic Sonography of Blood Flow in Breast Tumors
3
Fig. 22.7 Characteristic Doppler flow curve of a benign breast
lesion.
parison relatively high. Often it is impossible to distinguish between systole and diastole. The curve declines
from systole continuously to the end of diastole. The
low resistance generated by the formation of vessels
without a muscular layer in malignant changes of the
breast can often be demonstrated by the absence of a
Fig. 22.8).
notch (
However, the fact that very small capillaries without
a muscular layer also occur in normal organs and
benign tissue changes must be taken into account.
Therefore, in the eyes of an experienced examiner, low
resistance is only suggestive. The relative height of systole and diastole can also be unremarkable, and an
early diastolic notch only poorly developed. Moreover,
the evaluation of the shape of the Doppler flow curve
depends solely on the subjective impression of the examiner. The curve cannot be reproduced objectively
and its assessment depends greatly on the examiner’s
experience. The results of one study suggest that a
comparison of the blood flow in the affected and the
normal breast of the same patient can be used for the
differential diagnosis between benign and malignant
lesions (Blohmer et al. 1984). In this study the Doppler
flow parameters in the lesion were compared to those
in an artery in the corresponding quadrant of the contralateral breast. There was a distinct difference between the maximal systolic, end-diastolic, and mean
velocities in the vessels of the malignant and the comparison breast. In the case of the malignant tumor the
velocities in the vessels are typically higher. Attempts
to explain these findings suggest that afferent vessels
Fig. 22.8 Characteristic Doppler flow curve of a malignant
breast lesion.
are usually located in the biologically active periphery
of the tumor. The vessels in the tumor itself grow into
irregular shapes and arrangements. The arteries are
twisted into corkscrews and their caliber manifests
considerable variations. Flow inside such arteries is
turbulent with high flow rates (Kurjack et al. 1992). In
addition, arteriovenous shunts form, in which flow
rates are high (Bouck 1994).
No significant differences in the Doppler flow parameters RI and PI havebeen determined between tumor
vessels and the corresponding vessels in the contralateral breast (Konishi 1992, Madjar et al. 1992). By
using new, very sensitive color techniques it may be
possible in the future to display more clearly the flow
in the terminal vascular bed that characterizes the
tumor more precisely. To date it has only been possible
to use these newer techniques, such as angio mode, for
the analysis of single color pixels or color surfaces.
These are evaluated subjectively according to their intensity, size, and number. Currently computer programs are being developed to quantify blood flow displayed by color Doppler. Here the colored area is compared to the whole B-mode image. Additionally, the intensity of the color surfaces will be taken into account.
In conclusion, we should say that sonographic tumor
staging develops from the sum of a number of separate
pieces of information. When a lesion shows signs of
malignancy on the B-mode image or cannot be clearly
shown to be benign, and if in a color Doppler examination blood flow can be demonstrated, safety demands
that the lesion must be identified histologically.
206
Color-Coded Doppler Ultrasound in the Differential Diagnosis of Breast Tumors
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Index
Note: As Doppler ultrasound is the subject of the book, all entries refer to Doppler ultrasound unless otherwise
indicated. Page numbers followed by “f” and “t” refer to figures and tables respectively.
A
Abdomen (fetal), 160f
wall malformations, 114−115
Abdominal diameter (AD)
antiphospholipid-antibody syn-
drome, 172f
IUGR assessment, 92−93, 92f
A blood flow, 163, 163f
A/B ratio, 26−27, 39
aorta (fetal), 38f
cerebral artery (middle), 38 f, 100f
percentiles, 37f
umbilical artery, 100f
Absent or reversed end-diastolic flow
(ARED), preeclampsia, 106
Absorption, 6
Acardius, 122 f, 126
Acetylsalicylic acid (ASA), 47
preeclampsia, 105
Acidosis, 152
clinical significance of Doppler ul-
trasound, 141
Doppler ultrasound, vs. cardiotoco-
gram, 139−140, 139t
labor, 148
Acoustic output, 21
Acoustic power, 21
Acranius, 126
Adnexal tumor, 85, 89f
Air, resistance to sound waves, 13
Alias phenomenon, 18, 18f, 19f
Allergic reactions, contrast medium,
197
Amniocentesis, 61
Amniotic fluid, 61
anhydramnios, 119, 119f, 120f
hydramnios-oligohydramnios, 127−
128
pregnancy, late stages, 143
reduction, 56
Amniotic fluid index (AFI), 178
A-mode (amplitude mode), 7, 7f
Amplitude-coded flow display, 19−20
Anastomatoses, portal vein, 159
Anemia
fetal, 61, 129−131, 130t
hemodynamic consequences,
129 t
indications, 129t
intraperitoneal transfusion, 130−
131
monitoring treatment, 130
noninvasive procedures, 129−131
maternal, 58
Aneurysm(s)
differential diagnosis, 111
intra-abdominal, 115
Anhydramnios, 119, 119f, 120f
Annular phased array transducer, 13
Antibody titer, 129
Antihypertensives, uteroplacental
hemodynamics, 63−64
Antiphospholipid-antibody syn-
drome, 172−176, 173−176f
anatomical measurements, 172f
aorta, 175f
deep vein thrombosis (DVT), 172
ductus venosus, 176f
inferior vena cava, 176f
middle cerebral artery, 173f, 175f
placental-cerebral ratio, 173f
pulsatility index, 174f, 175f
resistance index, 172
time average maximum velocity
(TAMX), 174f, 175f
umbilical artery, 174f
uterine arteries, 173f, 174f
Aorta (fetal)
A/B ratio, 38f
antiphospholipid-antibody syn-
drome, 175f
arrhythmia, 60 f
bifurcation, 120f
blood flow, 59−60, 59 f
classification, 32
end-diastolic block, 48−49
evaluation criteria, 59
late pregnancy, 143−144t, 144f,
144 t
physiological changes, 60
qualitative analysis, 144, 144 t
quantitative analysis, 143, 144t
reference values, 59−60, 60 t
waveform, notches, 57
blood redistribution, (brain-spar-
ing), 107−108
correct display, 69 f
diagnostic significance of ultra-
sound, 152
Doppler angle, 70f
endarteritis obliterans, 168f
fetal anemia, 130, 130f
fetal growth restriction, 167f, 177f
feto-fetal transfusion syndrome
acceptor, 180f
donor, 179f
index quotient, 37, 38 f
multiple pregnancies, 124
Potter syndrome, 169f
pulsatility index (PI), 38 f
renal arteries, absence, 120 f
resistance index (RI), 38 f, 49, 59t
near term, 148
second/third trimesters, 48−49, 49 f
advantages, 49
bifurcation, 49f, 50 f
diastolic reverse flow, 50f
mean values and standard devia-
tion, 50f
resistance index (RI), 49
reverse flow in inferior vena
cava, 50 f
term effect, 146, 146f, 148
ultrasound errors, 74−75f
Doppler angle, 70f
Aorta (ovarian), 41
Aortic arch, 44 f, 49 f, 176f
Aortic isthmus, 146, 147f
Arcuate artery, ectopic pregnancy,
87−88
Arterial pressure, fetal anemia, 131
Arteries see individual arteries
Arteriovenous shunts, 57−58
Artifacts, 13−15
distal acoustic shadowing, 13, 13f
dorsal sound amplification, 13, 13f
geometrical distortion, 15
margin shadow, 14, 14f
repetition artifact, 14−15, 14f
side lobe, 14, 14f
slice thickness artifact, 14, 14f
Ascites, 118f
Asphyxia (fetal), 139, 148
cesarean section, 141
clinical significance of Doppler ul-
trasound, 141
Index
213