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Doppler Ultrasound in Gynecology
The two largest studies addressing endometrial
changes in an asymptomatic population (Kurjak et al.
1994, Schulman et al. 1994) showed that ultrasound
examination could be expected to detect
Three endometrial carcinomas,Five endometrial hyperplasias,Five polyps per 1000 patients.
Could these results be improved by the addition of color Doppler ultrasound? More specifically, can the relatively high rate of false positive results when look­ing only at endometrial thickness be improved? Possibly detection can be improved by instilling fluid into the uterine cavity (saline infusion sonography), such as the sonohysterography of Cullinan et al. (1995). In this procedure the instillation of fluid into the uterine cavity markedly improves the quality of the
3
image in B-mode as well as in Doppler ultrasound.
Bourne et al. reported in 1990 and 1991 that re­sistance in the uterine vascular supply was considera­bly lower than in control groups when an endometrial neoplasm was present. In all carcinomas of the en­dometrium the PI in the uterine a. was below 1.8. The
Fig. 20.27 B-mode image of an endometrial carcinoma, con­firmed by histology.
authors attributed the difference to angiogenesis in the endometrium and the adjoining myometrium.
Hata and his collaborators (1991) examined 10 patients with endometrial carcinoma. They found an elevated blood flow in the region of the tumor itself with a PI of 0.535 (0.158). In the course of the same study blood flows in a total of 291 benign and 17 malig­nant uterine tumors were compared: The RI was 0.58 (0.12) in uterine myomas and 0.34 (앧 0.03) in en- dometrial carcinoma. The authors concluded that below a cutoff level for the RI of 0.4 an equivocal lesion should be considered to be malignant, while those be­tween 0.4 and 0.5 were considered to be suspicious.
Bourne and his collaborators (1992) examined uterine blood flow in 227 postmenopausal patients— 72 patients with uterine bleeding and 155 who were asymptomatic. In this study patients with endometrial carcinoma had an average endometrial thickness of
20.2 mm, while in asymptomatic patients the en­dometrium was atrophied, and the average thickness was 1.35 mm. In endometrial carcinoma the PI was relatively low at 1.0, while in atrophic endometrium it was 3.8.
In a color Doppler ultrasound analysis of en­dometrial blood flow published in 1995, Sheth and his co-workers found no difference between malignant and benign tumors.
Will color Doppler examination, then, play a role in the future when a decision is made regarding how to proceed with the investigation? Granberg and Bourne (1997) answered the question in the negative, pointing out that when endometrial thickening is found it must be followed by histological examination of the en­dometrium, regardless of the Doppler ultrasound find­ings. This opinion may be countered by the finding that the common endometrial changes found during tamoxifen treatment, i.e., endometrial thickening and sclerosis in Fleischer’s subendometrial zone 1 (cf. above), can mimic endometrial hyperplasia. In such cases the B-mode image may resemble endometrial
194
a b
Fig. 20.28a, b Endometrial carcinomas in color Doppler.
Endometrial Diagnosis
thickening that actually does not exist in this form. Curettage only yields tiny particles of an essentially atrophic endometrium. In 1995 Exacoustos et al. de­scribed four possible sonographic changes in the en­dometrial pattern of patients taking tamoxifen (20−
30 mg q.d.):
Echogenic endometrium with good boundaries,
subendometrial halo, and homogeneous struc-
tured;
Echogenic endometrium with good boundaries,
containing small echo-free cysts;
Echogenic endometrium with nonhomogeneous
structure, small cystic parts, and blurring of the
boundary between the endometrium and the sub­endometrial layer;
Echogenic endometrium with nonhomogeneous ar-
chitecture, blurred boundaries, and partly inter­rupted halo, i.e., increased density or sclerosis in the subendometrial layer.
In our own study of 20 patients, so far unpublished, we found that in an endometrium which was found to be 10 mm thick by transvaginal sonography (corre­sponding to Exacoustos’s fourth pattern), there was no corresponding finding by hysteroscopy or histology. On the contrary, the uterine cavity contained only atrophic endometrium, and this was confirmed by his­tological examination of targeted tissue areas. It seems likely that in such a patient population ultrasound con­trol would find the appearance of endometrial hyper­plasia immediately after curettage, since the increased subendometrial density that mimics endometrial hy­perplasia continues to be present. In such cases the in­troduction of color Doppler might be successful in dis­criminating between suspicious findings: By our cri­teria renewed operative intervention would only be in­dicated if abnormal vessels supervene.
Essential Considerations for Clinical Practice
The results of color Doppler ultrasound for en­dometrial diagnosis are not yet solid to the point where they could be used materially to determine treatment decisions in clinical practice. Endometrial thickness of less than 5 mm speaks against the ex­istence of an endometrial carcinoma with a high degree of probability. If the thickness of the en­dometrium 8 mm, display of vessels in general and high diastolic flow with a RI 0.4 is highly suspicious of a malignancy.
In conclusion,I would like to quote an apt commen­tary by S. Granville, which I consider rather punctilious but to the point:
“Transvaginal sonography, including color Doppler sonography, offers a very sensitive glimpse into the pathological changes of the female pelvis. It is evident that the limits of the procedure often lie in the ex­aminer rather than in the procedure or the instrumen­tation. Hence delicate inquiries should be undertaken only by experienced examiners. Ultrasound is learnt neither by acquiring numerous certificates in endless courses, nor by reading overview articles like the pre­sent one. Experience can only be gained by insonating thousands of patients, by comparing one’s own find­ings with those of the facility, and by results confirmed in surgery. It is only from such experience that a ‘feel­ing’ can be developed for what conclusions a pro­cedure can and cannot support.”
This is the sense in which I would like to urge those of my colleagues who are active in using ultrasound to add color Doppler ultrasound to many of their inquir­ies.
Advanced Topics
195
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196
21 Diagnosis of the Uterine Tube
by Transvaginal Sonography
One in five couples in the United States is infertile; there are about 60−80 million such couples worldwide. Infertility is defined as the inability of a couple to con­ceive after one year of unprotected intercourse. Etio­logic factors affect the woman in about 45 % of cases, the man in 40 %, while 15% remain undiagnosed. A dis­tinction is made between primary infertility, if the couple has never conceived, and secondary infertility, if there has been a prior pregnancy (Runnebaum and Rabe 1994).
Investigation of the oviduct plays a cardinal role in the diagnostic workup of infertility. Besides hormonal and cervical factors, as well as factors relating to the man, the patency and functionality of the fallopian tube is the organic prerequisite for a successful meet­ing of the ovum and spermatozoon. In 30−40 % of cases the uterine tube is the factor responsible for female in­fertility. In secondary infertility the involvement of the oviduct rises to 60 %. The reasons for this might be genital infections, such as an asymptomatic salpingitis, or tubal endometriosis (Runnebaum and Rabe 1994).

Application of Ultrasound in Diagnosis of the Uterine Tube

The uterus and ovaries can be displayed by B-mode im­aging without difficulty. Unless they are altered by pathology the uterine tubes are not accessible to this diagnostic procedure. For their investigation a fluid must be instilled through the cervix into the uterine cavity and thence into the lumens of the oviducts to make them echogenic for display by B-mode imaging (Rimbach et al. 1995).
Sonographic diagnosis of the fallopian tube by trans­cervical instillation of contrast medium has in the past few years become an ambulatory alternative to fluoro­scopic hysterosalpingography and chromolaparoscopy.
The use of ultrasound for tubal diagnosis allows the af­fected patients to avoid the stresses of iodine-contain­ing contrast media, radiographs, or anesthesia and surgery. Since the procedure does not use major re­sources either in terms of personnel or instrumenta­tion, it can easily be integrated into routine clinical practice (Degenhardt 1995).
Display of the Tube by Contrast Sonography
This procedure uses an opalescent solution made up of microparticles of galactose and an aqueous galactose solution. The solution is made up just before the pro­cedure by vigorously shaking D-galactose granules
with a 20 % aqueous D-galactose solution for 5 seconds.
The shaking induces air microbubbles to settle on the surface of the galactose microparticles and initiates changes in the way sound is displayed sonographically.
These changes include simple backscatter effects and
an increase in contrast, caused by the oscillations in­duced by ultrasound in the air microbubbles.
One property essential for the clinical application of the contrast medium is stability under pressure while it is being introduced and during ultrasound examina­tion. This property is not changed materially by the mi­crobubbles in the suspension (Degenhardt 1995).
Undesirable side effects occurring during use in more than 1000 patients were mainly related to va­sovagal reactions, such as vertigo, nausea, sweating, and transient mild pain. During the examinations there have been no known allergic reactions to date (Degenhardt 1995). The only contraindication to the use of the substance is hereditary galactosemia (inci­dence 1:30 000).
Contrast-enhanced sonographic examination of the uterine tubes can be undertaken if a genital infection such as colpitis, endometritis, or salpingitis can be ex­cluded and the serum white cell count is 10000/µL. Lactic acid suppositories may be inserted to prepare the vagina, but they are not essential, since the vagina will be disinfected with povidone-iodone or some sim­ilar preparation immediately before the tube is dis­played by contrast ultrasound examination.
In order not to endanger a possible early pregnancy, sonographic display of the oviducts should be per­formed in the first half of the menstrual cycle, i. e., be­tween the sixth and tenth day of the cycle. At that time the cervix is of course slightly dilated, so that instru­mental dilatation is as a rule not necessary (Degen­hardt 1995, Deichert et al. 1988).
Advanced Topics
197
Diagnosis of the Uterine Tube by Transvaginal Sonography
For the placement of the balloon catheter a self-re­taining speculum helps to visualize the external os of the cervix. The catheter can usually be introduced into the cervical canal with a forceps without grasping the cervix. The balloon is inflated in the uterine cavity with 3−4 mL room air or normal saline solution and the catheter fixed above the internal os by light traction. As a rule the fixation of the catheter is not painful. At the same time an assistant can prepare the suspension, draw it into a syringe, and attach this to the catheter (Degenhardt 1995).
The vaginal probe used for this procedure should reach frequencies of 5−10 MHz to achieve a high reso­lution. After the patient has been prepped the vaginal ultrasonic probe can be introduced into the vagina next to the narrow-lumen transcervical catheter. Firstly, the uterus is displayed in longitudinal view. The
3
contrast medium first reaches the uterine cavity and there can serve to highlight any malformations. As a rule 2−5 mL of the contrast medium are sufficient to outline the cavity. The cross section of the uterine fun­dus is then imaged and, to begin with, careful intermit­tent release of the contrast medium will display the in­tramural section of the fallopian tube, followed by the isthmus and the ampulla (Degenhardt 1995, Rimbach et al. 1995). The sequence of this examination is re­peated on the contralateral side. As a rule less than
10mL of the contrast medium is required for this ex-
amination, so that the 15 mL of contrast medium generally available from the suspension provides an adequate reserve.
If the tubes are occluded bilaterally, the procedure can be uncomfortable or painful. The patient should be warned about this possibility. In such cases pressure builds in the cavity, so that there appears to be re­sistance to the application of contrast medium. If the tubal occlusion is confirmed sonographically, the con­trast medium should be reaspirated, in order to avoid any undesirable side effect (Degenhardt 1995).
In B-mode sonography the contrast medium pro­vides precise information about the structure and cali­ber of the lumens of the uterine tubes and their patency within a few minutes. If a tube is patent, the
contrast medium escapes from the ampullary segment of the tube into the abdominal cavity and can be de­monstrated in the space of Douglas. The galactose so­lution is absorbed from the abdominal cavity within 24 hours. If the fallopian tube is obstructed proximally, the only portions displayed are the uterine cavity and intramural segment of the pathologically altered tube. In the presence of a sactosalpinx the contrast medium collects in the distal portion of the uterine tube, but no discharge from the tube can be displayed. The findings should be documented by still or video imaging.
Supplementation by Doppler
If escape of the contrast medium cannot be displayed by B-mode imaging, color Doppler can be used to supplement the procedure. The flow of contrast me­dium at the transition from the infundibulum to the abdominal cavity can be confirmed positively by color display (Degenhardt 1995, Rimbach et al. 1995). For uncomplicated examinations display by color Doppler does not shorten the duration of the examination (Dei­chert et al. 1988).
Use of pulsed Doppler may also be considered for supplementation. The Doppler signal seen when the intramural segment of the fallopian tube is displayed is characteristic. A narrow sample volume is fixed on the intramural segment of the uterine tube. When the lat­ter is patent, a slowly rising reflex curve can be seen. In cases where the segment is occluded the Doppler sig­nal shows a briefly increased resistance, after which it breaks off abruptly.
This procedure is less suited for the confirmation of an occluded ampullary segment. The Doppler profile only changes when resistance is high due to ampullary occlusion. Initially, the Doppler profile appears unre­markable, since the capacity of the ampulla allows the contrast medium to enter at a normal velocity. An ade­quate amount of contrast medium should be held in reserve before beginning the Doppler examination (Degenhardt 1995).
198

Comparison to Other Procedures

The most effective procedure for establishing tubal morphology and patency continues to be chromola­paroscopy with chromoperturbation. The procedure enables a detailed evaluation of the internal genital or­gans. Nevertheless, it remains impossible to demon­strate the extrusion of blue dye from the fimbriated end in cases of extensive pelvic adhesions. A sono­graphic display using a contrast medium may be of value in these cases.
Hysteroscopic examination allows the uterine cavity to be imaged. Synechiae, submucosal fibroids, and the tubal ostium are accessible for assessment. The course and patency of the oviduct cannot be assessed (Degen­hardt 1995, Rimbach et al. 1995).
The use of conventional hysterosalpingography, which is mediated by radiological contrast media, is limited by the effect of radiographs on the pelvic or­gans. Documentation of the path of the contrast me-
Comparison to Other Procedures
dium requires two to three radiograph films and fluoroscopy of the true pelvis. The radiation received by the ovaries amounts to 1−3.6 cGy (Degenhardt
1995). Scintigraphic examination of tubal motility to assess
functional capacity of the uterine tube (hysterosalpin-
goscintography), as described by Steck et al. (1989), has
not entered routine clinical practice.
We conclude that transvaginal tubal sonography using a contrast medium is a procedure by which tubal patency can be assessed without major complications. Should infertility continue to pose a problem even when patency of the uterine tube has been demon­strated by ultrasound, investigation should be con­tinued by chromolaparoscopy.
Advanced Topics
199
3
200

22 Diagnostic Sonography of Blood Flow in Breast Tumors

Biological Background

In recent years ultrasonographic examination of blood flow has been added to the armamentarium used in the differential diagnosis of breast tumors of uncertain malignancy.
As early as 1907 Goldman first showed that the
growth of a tumor leads to vascular proliferation in the surrounding tissue, and that this phenomenon is a re­sponse of the host to the growth of the tumor. In 1945
Algire and Chalkley discovered that malignant cells can elicit vascular proliferation on a continuous basis and that tumor cells have the property of inducing the
growth of capillary epithelium in vivo. Finally, in 1971, Folkman et al. were able to isolate the factor re­sponsible for angiogenesis in tumors (Folkman et al. 1971, 1987). Currently some authors assert that vascu­lar proliferation in the tissues surrounding a tumor is an essential prerequisite for tumor growth. Beyond that, neovascularization is considered to be a sign of malignancy in a tumor (Delorme 1993, Kaiser et al. 1993, Plate 1993, Possover et al. 1994, Samejima et. al. 1988, Schild and Fendel 1991, Sohn et al. 1992a, Weid­ner et al. 1991). The degree of vascularization in a mammary carcinoma correlates with its invasiveness and its metastasizing potential (Weidner et al. 1991).
Arteriovenous shunts develop and the newly-formed vessels can at times show considerable variation in their caliber, resulting in rather heterogeneous blood flow patterns (Bouck 1994, Horak et al. 1992).
Since the structure of the newly-formed capillaries does not include a muscular layer, their vascular re­sistance is very low, resulting in an extremely low flow rate (Sohn et al. 1992a, 1993, 1994a, b). It is precisely these minimal flow rates that can be brought into focus with the aid of the new color techniques, contributing to preoperative diagnostic staging.
However, some benign conditions, such as prolifera­tive mastopathies, inflammatory processes, or a lactat­ing breast can lead to increased blood perfusion (Leucht and Madjar 1995, Madjar et al. 1997/98). Due to the rapid technical developments of the last 10 years, different working groups have at times arrived at quite contradictory results (Adler et al. 1990, Bell et al. 1993, Blohmer and Lau 1993, Blohmer et al. 1993a, 1993b, 1994, Britton and Couldon 1990, Burns et al. 1982, Cosgrove 1992, Delorme 1993, Dock 1993, Huber et al. 1993, Konishi 1992, Madjar and Schillinger 1986, Madjar et al. 1989, 1991b, Schild and Fendel 1991, Schild et al. 1993, Sohn et al. 1992b, 1993).
Advanced Topics

Instrumentation

Doppler ultrasound uses the frequency shift in sound
waves emitted from a mobile element to make visible
and measure the motion of erythrocytes in the blood
vessels of a tissue. The degree of frequency shift is re­corded and documented in Hertz, or it is used to calcu­late the flow rate of the erythrocytes in millimeters per second or centimeters per second.
The frequency shift depends on the frequency of the sound waves generated and the velocity of blood flow in the vessels. Because, as noted above, the circulation in a malignant lesion in the female breast is very slow, high Doppler frequencies are required to detect blood flow in a mammary carcinoma (Madjar et al. 1989).
Continuous Wave Doppler
In a continuous wave (CW) Doppler, sound waves are continuously emitted and simultaneously received from the transducer. Using a frequency usually of 10MHz, a transducer with a surface diameter of about 1 cm (pencil probe) is moved systematically over the whole breast. Good skin contact must be maintained throughout the examination. The results of CW Dop­pler recording are reproduced as acoustic noise or a
22.1). It is not
Doppler flow curve on the monitor ( feasible to display the tissue under examination in B­mode image. By the same token vessels cannot be dis­played at a specific depth. Because of the high frequen­cies used with the pencil probe, the sensitivity of this procedure for the display of the breast is very high. Ad-
Fig
201
Diagnostic Sonography of Blood Flow in Breast Tumors
Fig. 22.1 CW Doppler. The results of the measurements are displayed as a Doppler flow curve.
mittedly, because of the small surface area of the probe and the type of signal display, the procedure must be performed absolutely systematically and the examiner must have a great deal of experiencein the detection of nonpalpable tumors in the female breast.
Scientific research, in which the display by CW Dop-
3
pler of the vessels in the breast affected by a tumor was compared with the contralateral side, found a definite increase in the number of vessels on the malignant side. Moreover, in most healthy women the course of the vessels and the blood flow in both breasts were symmetrical. The research also added information on the small circulatory changes in the female breast over the course of the menstrual cycle (Madjar et al. 1998,
1992). Because of the lack of a visual display as a B-mode
image, and because it is very time-consuming, CW Doppler is no longer used in routine diagnostic studies (Madjar et al. 1992, Schild and Fendel 1991, Schild et al.
1993).
from the time interval between sending and receiving sound waves. Hence it becomes possible to display the vessels at specific depths. The findings can also be dis­played simultaneously in B-mode.
The procedure first uses the B-mode image to look for a lesion in the breast. Next the Doppler window, called the “sample volume,” is placed over the region of interest (ROI). As a consequence the blood vessels at precisely this depth of penetration can be displayed with the recorded frequency shift and the correspond­ing Doppler spectrum can be measured (Sohn et al
22.2).
Fig.
1993;
The following parameters are recorded and analyzed by PW Doppler:
Maximal systolic velocity (V I<max sys): AMinimal end-diastolic velocity (VA/B ratio: Q = A/BResistance index (RI): RI = A−B/APulsatility index (PI): PI = A−B/Q
The Doppler spectrum should be recorded at an acute angle, preferably 60°, since otherwise errors could creep into the calculation of velocity. The RI and the PI are largely independent of the angle.
It is often difficult in the B-mode image to display the small vessels of a breast tumor formed by angio­genesis. Hence the detection of blood vessels involves a “blind” search of the sample volume, just as with CW Doppler.
min
dias): B
Color-Coded PW Doppler
202
Pulsed Wave Doppler
In pulsed wave (PW) Doppler, sound waves of one frequency are sent and received alternately at defined time intervals. Selected tissue depths can be calculated
Fig. 22.2 PW Doppler. The sample volume is placed into the B­mode image in such a way that the Doppler spectrum of the blood vessels of interest is displayed.
A large proportion of the diagnostic studies of blood flow in obstetrics and gynecology is currently per­formed by color-coded PW Doppler ultrasound. This procedure is especially applicable to sonography of the breast, because it is able to detect blood vessels of which the lumen is below the power of resolution of the B-mode image.
In the color-coded PW Doppler the received Doppler signals are color-coded, i.e., blood flow velocities are transformed on the monitor into various colors and degrees of brightness. In these procedures the direc­tion of flow is meaningless. Depending on the manu­facturer of the instrument, the procedure is based on an analysis of phase shift, runtime, or frequency shift.
In the course of the measuring procedure, a wall fil­ter or high pass filter (HPF) filters out the oscillations of the vascular wall. However, slow flow components of the perfusing circulation are also filtered out. For this reason the wall filter in ultrasound examination of the breast must be high, so that precisely these slow com­ponents of flow velocities can be detected. The PW Doppler can record and measure a Doppler flow curve if the sample volume is placed in the vessel that is dis­played in color.
Because of the very slow blood flows that need to be detected in mammary sonography, instrumental set­tings are very sensitive. Hence the development of ar­tifacts is considerable, not only due to the patient’s res­piration and heart beat, but also her spontaneous movements.
In the procedure the malignant lesion in the patient’s breast is first displayed in the B-mode image. Next the Doppler window of the color-coded Doppler ultrasound is placed over the B-mode image. The sample volume is set low. The detected blood vessels
22.3). Now the sample
are now displayed in color (
volume can be targeted at an acute angle to the vessel that is to be examined. The monitor displays a Doppler flow curve, which can be analyzed. Should measure­ments be unsuccessful at an angle 쏝60°, it is possible to resort to angle correction. In this correction the ac­tual angle is used in calculating the velocity.
The following technical aspects of instrumentation should be addressed when color-coded Doppler ultra­sound is to be used:
Color-coded pulsed wave Doppler technology,Doppler frequencies 5 MHz,Synchronous display of B-mode image and Doppler
flow curve,
Variable size of the sample volume,Variable Doppler angle (it should be adaptable to
the course of the vessel),
Angle correction available,Low measuring range (1 cm/s),Limited expression of flash artifacts (movements in
the surrounding tissue cause color artifacts),
The capability of displaying the Doppler flow curve
at a height at which quantitative measurements can be performed,
Analysis of the usual Doppler parameters by the
system’s software,
Easily handled, lightweight probe.
Fig.
Diagnostic Sonography of Blood Flow in Breast Tumors
Fig. 22.3 In color-coded Doppler ultrasound the detected blood vessels are displayed in color.
Advanced Topics
Angio Color, Angio Mode, Power Doppler
The angio color technique is a procedure that, like con-
ventional color Doppler ultrasound, displays blood flows as a color image superimposed on the B-mode image in real time. In contrast to the traditional color Doppler, angio mode analyzes the amplitude of the echo and consequently provides information concern­ing the number or density of the erythrocytes reflect­ing the ultrasonic beam.
As in the various procedures described above, the examination begins with a B-mode display of the sus­pected primary lesion in the female breast. Next, the color Doppler window is made to coincide with the changes previously outlined by ultrasound. Even very small blood vessels with low flows can be detected
Fig. 22.4 Breast tumor in angio mode. Even very small blood vessels with low flows can be displayed by this procedure.
Fig.
using this method ( the PW Doppler can now be placed over such a vessel, the Doppler flow curve can be recorded, and calcula­tions derived from it.
This system has distinct advantages. Because it uses amplitude, it is independent of the angle between blood flow and the incident ultrasonic beam. Moreover, the amplitude signals include less back-
22.4). The sample volume of
203