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23 Female Pelvis Antonia Carla Testa, Erika Fruscella, Gabriella ferrandina, Marinella Malaggese, Giovanni Scambia, Caterina Exacoustos, and

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23 Female Pelvis

Antonia Carla Testa, Erika Fruscella, Gabriella ferrandina, Marinella Malaggese, Giovanni Scambia, Caterina Exacoustos, and Emilio Quaia

A. C. Testa, MD; E. Fruscella, MD; G. Ferrandina, MD;

M. Malaggese, MD

Gynecologic Oncology Unit, Catholic University of Sacred Heart, L.go A. Gemelli 8, 00168 Rome, Italy

G. Scambia, MD

Oncology Department, Catholic University of Sacred Heart, Centro di Ricerca e Formazione ad Alta Tecnologia nelle Sci- enze Biomediche, Campobasso, Italy

C. Exacoustos, MD

Department of Surgery, Obstetrics and Gynecology Unit, Uni- versity of Rome “Tor Vergata”, Rome, Italy

E. Quaia, MD

Department of Radiology, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy

23.1

Introduction

Ultrasound (US) is considered the preferred imag- ing procedure in the study of female pelvis because it is widely available, non-invasive and able to provide definitive diagnostic information in many patholo- gies (Derchi et al. 2001). As a first step, the female pelvis has to be examined by transabdominal US to provide global delineation of all organs and to allow a panoramic and complete evaluation of large lesions. Transvaginal US should be employed after transabdominal US and is the best examination technique to evaluate the female pelvis (Derchi et al. 2001). Sonohysterography is an examination technique which provides a better analysis of the endometrial surface through distension of the endo- metrial lumen with 30 ml of sterile saline.

Microbubble-based contrast agents have been used in gynecological and obstetric US (Ordén et al.

1999a,b). The principal application is the assessment of

CONTENTS

23.1 Introduction 323 23.2 Ovarian Tumors 323 23.3 Uterine Fibroids 325

23.4 Evaluation of Fallopian Tube Patency 327 References 328

vascularization of ovarian tumors. Other applications include the assessment of vascularization of uterine fibromas and the assessment of tubal patency.

23.2

Ovarian Tumors

Even though ovarian tumors are less frequent than uterine tumors, these lesions are the principal cause of death from gynecological malignancy (Derchi et al. 2001). Since ovarian tumors determine non-spe- cific symptoms in early stages, they are commonly discovered at advanced stages. Most ovarian tumors are benign, while 15% are malignant and 5% are sec- ondary tumors (Derchi et al. 2001). Epithelial tumors are the most common (70%–75% of all cases), and can be serous, mucinous, and endometrioid (Derchi et al. 2001). Although the final diagnosis of an adnexal mass is based on findings at histologic examination, it is desirable to differentiate preoperatively between benign and malignant tumors to select the time, place, and type of surgery.

US is a well-established imaging modality for the assessment of pelvic masses and a subjective evalu- ation of the gray-scale US image by an expert sonog- rapher can reach an accuracy of more than 90% in discriminating between benign and malignant adnexal masses (Valentin 1997). The absence of solid components and the absence of irregularities in an adnexal mass at US suggest benignity, whereas any irregularity – be it in the outline, the cyst wall or in the echogenicity of a tumor – suggests malig- nancy (Valentin 2004).

Malignant tumors are generally well-vascular-

ized, with flow signals both at the periphery and in

the central regions of the mass, while benign ovar-

ian tumors appear relatively poorly vascularized

(Derchi et al. 2001). Malignant ovarian tumors have

certain specific characteristics, such as neovessels

with irregular course and arteriovenous shunts with

high blood flow velocities. Muscularization of the

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vessel walls is incomplete and results in formation of tumoral lakes, low resistance to flow, and little systolic-diastolic variation in blood flow velocity.

Color Doppler and power Doppler US can be used to detect neovascularization characteristic of malig- nant lesions (Tekay and Jouppila 1992). However, the combination of gray-scale US morphology and Doppler flow imaging information does not seem to yield much improvement in diagnostic accuracy (Stein et al. 1995), even though it may increase the diagnostic confidence to make a correct diagnosis of benignity or malignancy (Valentin 2004).

Recently, a multicenter study (International Ovar- ian Tumor Analysis, IOTA) based on artificial intelli- gence models has been conducted in >1000 patients.

The preliminary results of this study demonstrate that the parameter (presence of solid vascularized parts in an adnexal lesion) is highly predictive of malignancy (Timmerman et al. 2004). However, some pelvic masses with solid parts and some mul- tilocular cysts with a high number of locules remain difficult to be classified as benign or malignant.

Microbubble-based contrast agents have been used to enhance Doppler signal in tumoral vessels (Suren et al. 1994; Ordén et al. 1999a,b, 2000).

Recently, dedicated contrast-enhanced US tech- nologies, such as contrast tuned imaging, have been developed to optimize the use of microbubble- based contrast agents and to produce microbubble insonation at low acoustic power for several minutes.

Dedicated contrast specific techniques at low acous- tic power insonation with perfluorocarbon or sulfur hexafluoride microbubbles allow visualization of a dramatically higher number of intralesional vessels in comparison to color Doppler US.

In our preliminary experience in the evaluation of uncertain pelvic masses the application of con- trast tuned imaging with sulfur hexafluoride-filled microbubbles (SonoVue, Bracco, Italy) provided an improvement in the diagnostic confidence of the operator to distinguish benign from malignant adnexal lesions. In particular, the absence of perfu- sion in uncertain pelvic masses, with no detectable vessels in the solid intracystic tissue, improved the

Fig. 23.1a–c. Ovarian cystoadenoma. a Baseline gray-scale US: unilocular- solid ovarian lesion with a cystic (C) and a solid (arrow) component. b Color Doppler US revealing no fl ow signals in the solid component (arrow) of the tumor. c Contrast-enhanced US reveals absence of contrast enhance- ment in the solid component

a b

c

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diagnostic confidence of the operator in making a benignity diagnosis confirmed by histology (Figs. 23.1 and Fig. 23.2), while the presence of per- fusion in uncertain pelvic masses, with detectable vessels in the solid intracystic tissue, could play an important role to confirm the diagnosis of malig- nancy (Fig. 23.3) (Testa et al. 2003b).

An objective digital analysis of kinetics of an air- filled microbubble-based contrast agent in imaging benign and malignant adnexal tumors, with a spe- cial focus on the timing of the transit of the micro- bubble bolus, was shown in a recent study (Ordén et al. 2003). After a quick rise in intensity, the wash- out phase was biphasic, firstly with a fast linear decrease (distribution phase) and, secondly, with a slow linear decrease (elimination phase). Both the baseline and maximum power Doppler intensities, as the rise in intensity compared to time, were sig- nificantly higher in malignant than in benign ovar- ian tumors. The microbubbles arrival time was sig- nificantly shorter in malignant than it was in benign tumors. This could be caused by the high-velocity flow through the arteriovenous shunts that are typi- cally found in malignant neovascularization.

Besides changes in echo-signal intensity, the dura- tion of contrast enhancement and the value of the area under the time-intensity curve appeared to be the best discriminating factors between benign and malignant tumors. Ordén et al. (2003) found that the mean duration of microbubble contrast effect was 190.4 s in malignant tumors, and 103.6 s in benign

tumors. The longer persistence of enhancement in malignant lesions could be explained by microbub- bles pooling of the contrast agent in dilated and blind- ending vessels. The bypass of capillary beds through arteriovenous shunts will reduce the rate of bubble destruction and will result in an higher microbubble concentration in malignant tumors vasculature.

New softwares performing qualitative and quan- titative analysis of the time intensity curves are under evaluation. Qontrast (Contrast Quantifica- tion Tool, AMID and R&D, Bracco, Milan, Italy) software analyzes the time sequences of digitally stored perfusion images and enables objective eval- uation of quantitative perfusion parameters of any portion of an organ during each set of frames. The resulting parametric maps allow the visual assess- ment of perfusion features over the entire selected region (Fig. 23.4). The aim of this representation is to maximize accuracy and reproducibility of results in contrast enhancement analysis and to minimize the inter- and intra-operator variability.

23.3

Uterine Fibroids

Uterine fibroids (fibroleiomyomas) are the most common tumors of the uterus and the most common cause of uterine enlargement. They are benign tumors made of smooth muscle fibers intermixed

Fig. 23.2a,b. Cystic endometriosis in the right ovary. a Baseline US reveals a round lesion with corpuscular content (arrows). b Contrast-enhanced US reveals absence of contrast enhancement in the context of the lesion (arrows) which reveals only a slight peripheral enhancement in the cystic wall. [Images courtesy of Dr. Roberta Padovan, Aloka, Tokyo, Japan]

a b

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Fig. 23.3a–c. Ovarian endometrioid adenocarcinoma. a: Baseline gray-scale US: unilocular-solid ovarian lesion with a cystic (C) and a solid (arrow) component. b Power Doppler US revealing fl ow signals in the solid compo- nent (arrow) of the tumor. c After microbubble injection contrast enhance- ment is revealed in the solid component (arrows) of the tumor

a

b

c

Fig. 23.4. The “QONTRAST” software application to contrast- enhanced US examination of a unilocular ovarian lesion. The resulting parametric map, in which different colors express a different microbubble uptake, allows a visual assessment of perfusion properties over the entire selected region at once

with a variable amount of fibrous connective tissue (Derchi et al. 2001). Fibroids are usually multiple and grow under estrogen influence. They are most commonly located in the intramural myometrium, while submucosal and subserosal fibroids may determine respectively abnormal uterine bleeding or simulate an adnexal mass. At baseline US, uter- ine fibroids appear as well-defined masses with a hypoechoic, or less frequently hyper- or isoechoic, echostructure if compared to myometrium.

Baseline color and power Doppler US are effective

to reveal the vascularization in uterine fibroids. In

our experience (Testa et al. 2003a) the preoperative

Doppler evaluation of uterine fibroids did not pro-

vide predictive information about the proliferative

status of the tumor. A significant correlation was

found between the size of the fibroid and the resistive

index, as well as between the volume of the fibroid

and resistive index. The injection of sulfur hexaflu-

oride-filled microbubbles did not add any further

useful information to baseline US (Fig. 23.5).

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Fig. 23.5a–c. Uterine fi broid. Baseline color Doppler US (a) reveals only some peripheral vessels with arterial fl ow at Dop- pler interrogation. Contrast-enhanced US reveals diffuse con- trast enhancement in the uterine fi broid during arterial phase (b), also with evidence of tumoral vessels, and microbubble washout at late phase (c)

a

b c

23.4

Evaluation of Fallopian Tube Patency

Infertility is a common problem in the developing world, affecting 10%–15% of the couples (Chenia et al. 1997). An important part of any protocol for inves- tigation of the infertile couple is the assessment of fal- lopian tube patency in the woman, as this can influ- ence the future course of treatment. Several authors have suggested saline solution as the first-choice agent to assess the endometrial cavity (Parsons and Lense 1993; Goldstein 1996). X-ray hysterosalpin- gography and laparoscopic dye-test are currently the main procedures for investigating tubal patency.

The recent development of hysterosalpingo con- trast sonography may offer some benefits over these two methods. Hysterosalpingo contrast sonography involves a transvaginal US investigation of the fal- lopian tubes both before and after the injection of a microbubble-based contrast agent into the tubes via the uterine cavity. After initial precontrast trans- vaginal US, the cervix and vagina are cleansed with

sterile sodium chloride solution. A 5-F intrauterine balloon catheter is then introduced transcervically without the use of a tenaculum, unless catheteriza- tion is hindered by marked anteversion, retrover- sion, or flexion of the uterine corpus. The intrauter- ine balloon catheter is employed to avoid reflux of contrast through the cervical os (Campbell et al.

1994; Dietrich et al. 1996; Derchi et al. 2001). The uterine cavity is then analyzed using sterile saline solution and, finally, after Echovist (SHU 454, Scher- ing, Berlin, Germany) or SonoVue (Bracco, Milan, Italy) injection. Microbubbles are slowly injected through the catheter in 1- to 2-ml boluses under US control (Hamilton et al. 1998). Microbubbles firstly fill the isthmic portion of each fallopian tube, while later they fill the whole tube up to the distal por- tion (Fig. 23.6). Both the passage of microbubbles through the tubes and spillage into the peritoneal cavity can be assessed by color Doppler or dedicated contrast specific modes (Derchi et al. 2001).

Hysterosalpingo contrast sonography is considered

a first-line screening method to select infertile women

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Fig. 23.6a–d. Hysterosalpingo contrast-sonography. a,b Transverse section through the uterine fundus following SonoVue injec- tion. The isthmic portion of the left fallopian tube is visualized (arrow). c Normal left fallopian tube which is depicted from the isthmic uterine tract up to the distal tract (arrows), where it spills adjacent to the ovary. d Distal portion of the normal fallopian tube with spill from fi mbrial end (arrow)

a b

c d

in whom more invasive investigations are likely to reveal pathology (Hamilton et al. 1998; Exacoustos et al. 2003). Hysterosalpingography with saline solu- tion is limited in demonstrating fallopian tube patency, especially in the corneal region (Chenia et al. 1997;

Hamilton et al. 1998), while hysterosalpingo contrast sonography provides a complete tubal assessment lim- iting the number of visits that infertile women must undergo (Hamilton et al. 1998).

References

Campbell S, Bourne TH, Tan SL, Collins WP (1994) Hysterosal- pingo contrast sonography (HyCoSy) and its future role within the investigation of infertility in Europe. Ultra- sound Obstet Gynecol 1:245-253

Chenia F, Hofmeyer GJ, Moolla S, Oratis P (1997) Sonographic hydrotubation using agitated saline: a new technique for improving fallopian tube visualization. Br J Radiol 70:833- 836

Derchi L, Serafini G, Gandolfo N et al (2001) Ultrasound in gynecology. Eur Radiol 11:2137-2155

Dietrich M, Suren A, Hinney B (1996) Evaluation of tubal patency by hysterocontrast sonography (HyCoSy, Echo- vist) and its correlation with laparoscopic findings. J Clin Ultrasound 24:523-527

Exacoustos C, Zupi E, Carusotti C et al (2003) Hysterosalpingo- contrast sonography compared with hysterosalpingogra- phy and laparoscopic dye perturbation to evaluate tubal patency. J Am Assoc Gynecol Lapar 10:29-32

Goldstein SR (1996) Saline infusion sonohysterography. Clin Obstet Gynecol 39:248-258

Hamilton JA, Larson AJ, Lower AM et al (1998) Evaluation of the performance of hysterosalpingo contrast sonography in 500 consecutive, unselected, infertile women. Hum Reprod 13:1519-1526

Ordén MR, Gudmundsson S, Kirkinen P (1999a) Intravascular ultrasound contrast agent: an aid in imaging intervillous blood flow? Placenta 20:235-240

Ordén MR, Gudmundsson S, Helin HL, Kirkinen P (1999b) Intravascular contrast agent in the ultrasonography of ectopic pregnancy. Ultrasound Obstet Gynecol 14:348-352 Ordén MR, Gudmundsson S, Kirkinen P (2000) Contrast-

enhanced sonography in the examination of benign and malignant adnexal masses. J Ultrasound Med 19:783-788 Ordén MR, Jurvelin JS, Kirkinen PP (2003) Kinetics of a US

contrast agent in benign and malignant adnexal tumors.

Radiology 226:405-410

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Parsons AK, Lense JJ (1993) Sonohysterography for endome- trial abnormalities: preliminary results. J Clin Ultrasound 21:87-95

Stein SM, Leifer-Narin S, Jhonson MB et al (1995) Differen- tiation of benign and malignant adnexal masses: relative value of gray-scale, color Doppler, and spectral Doppler sonography. AJR Am J Roentgenol 164:381-386

Suren A, Osmers R, Kulenkampff D, Kuhn W (1994) Visu- alization of blood flow in small ovarian tumor vessels by transvaginal color Doppler sonography after echo enhancement with injection of Levovist. Gynecol Obstet Invest 38:210-212

Tekay A., Jouppila P (1992) Validity of pulsatility and resistance indices in classification of adnexal tumors with transvagi- nal color Doppler ultrasound. Ultrasound Obstet Gynecol 2:338-344

Testa AC, Pomini F, Fattorossi A et al (2003a) Doppler velo-

cimetry and cytofluorimetric analysis in uterine myomas.

Gynecol Obstet Invest 56:139-142

Testa AC, Timmerman D, Ferrazzi E, Arduini D (2003b) Pre- liminary experience with Sono Vue. 13th world congress on ultrasound in obstetrics and gynecology (abstract). 31 Aug–4 Sept, Paris, France

Timmerman D, Valentin L, Testa AC et al (2004) Classifying ovarian masses and lessons from IOTA trial. Ultrasound Obstet Gynecol 24:261

Valentin L (1997) Gray scale sonography, subjective evalua- tion of the color Doppler image and measurement of blood flow velocity for distinguish benign and malignant tumors of suspected adnexal origin. Eur J Obstet Gynecol 72:63-72

Valentin L (2004) Use of morphology to characterize and manage common adnexal masses. Best Pract Res Clin Obstet Gynaecol 18:71-89

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