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Contrast-Enhanced, Three-Dimensional Power Doppler Sonography for Differentiation of Adnexal Masses

From the Department of Obstetrics and Gynecology, Medical School University of Zagreb, Sveti Duh Hospital, Zagreb, Croatia.

Address reprint requests to: Asim Kurjak, MD, PhD Department of Obstetrics and Gynecology Medical School University of Zagreb Sveti Duh Hospital, Sveti Duh 64 Zagreb 10000 Croatia E-mail: asim.kurjak{at}public.srce.hr

	Abstract

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Objective: To investigate the potential usefulness of contrast-enhanced, three-dimensional power Doppler sonography in the differentiation of benign and malignant adnexal lesions.

Methods: A total of 45 patients with complex adnexal lesions of uncertain malignancy at transvaginal B mode and/or color Doppler sonography were prospectively evaluated with three-dimensional power Doppler sonography before and after injection of contrast agent. Presence of a penetrating pattern and a mixed penetrating and peripheral pattern suggested adnexal malignancy. All the results were compared with histopathology.

Results: There were 12 cases of ovarian malignancy and 33 benign adnexal lesions. Of the 12 ovarian cancers, seven (58.3%) showed vascular distribution suggestive of malignancy at nonenhanced three-dimensional power Doppler sonography. After injection of contrast agent, a penetrating vascular pattern and/or a mixed penetrating and peripheral pattern were detected in all cases of ovarian malignancy. One cystadenofibroma demonstrated penetrating vessels at initial scan, whereas two benign lesions (fibroma and cystadenofibroma) were misdiagnosed as malignant at contrast-enhanced, three-dimensional power Doppler sonography. The use of a contrast agent with three-dimensional power Doppler sonography showed diagnostic efficiency (95.6%) that was superior to that of nonenhanced three-dimensional power Doppler sonography (86.7%).

Conclusion: Contrast-enhanced, three-dimensional power Doppler sonography provides better visualization of tumor vascularity in complex adnexal masses. If used together with three-dimensional morphologic ultrasound assessment, enhanced three-dimensional power Doppler imaging might precisely discriminate benign from malignant adnexal lesions.

Advances in ultrasonography have led to frequent incidental detection of an early ovarian carcinoma at initial scanning.^1,2 Other ovarian lesions in a differential diagnosis include ovarian endometriomas, pelvic inflammatory disease (PID), and ovarian dermoids. Several attempts have been made to distinguish ovarian malignancy from questionable ovarian lesions on the basis of gray scale ultrasound and/or color Doppler features.^2–5 It has been reported that the presence of intratumoral papillae, solid parts, and thick septa suggests ovarian malignancy. The detectability of these findings varies and their diagnostic value is not established. Thus, the diagnostic ability of gray scale ultrasound is still limited.

Spectral Doppler sonography and color Doppler ultrasound have been used successfully in the evaluation of adnexal tumor vascularity.^4,5 Although previous studies reported that both spectral Doppler and color Doppler ultrasound could provide clinically useful information related to adnexal tumor vascularity, these imaging modalities have inherent limitations, such as lack of sensitivity to slow flow, angle dependency, and aliasing, which occurs when the Doppler shift frequency exceeds one half the pulse repetition frequency.⁶ Furthermore, a nonuniversal selection of Doppler parameters (resistance index [RI] or pulsatility index [PI]); the choice of highest, lowest, or mean impedance values, and the selection of vessels for investigations, together with operator variance and system sensitivity, contribute to the confusion.

Unlike color Doppler ultrasound, which is based on mean frequency shift, power Doppler ultrasound is based on total integrated power of the Doppler spectrum. Concurrently with the development of various sonographic contrast agents, the potential role of power Doppler sonography has increased.^7–9 More recently, technological development enabled the physician to generate three-dimensional vascular images that display tumor morphology and branching pattern of intralesional vessels on-screen interactively.^10–12

The purposes of our study were to evaluate the vascular pattern in questionable adnexal lesions using three-dimensional power Doppler ultrasound with and without echo-enhancing contrast, to determine whether the imaging patterns of identified vessels could be correlated with histopathologic results, and to evaluate whether the information obtained with echo-enhanced, three-dimensional power Doppler ultrasound could improve the diagnostic accuracy in adnexal lesions compared with that with nonenhanced three-dimensional power Doppler ultrasound.

	Materials and Methods

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The study population included a consecutive series of patients who had complex ovarian lesions during the preceding 12 months. Our study group was limited to patients with complex adnexal lesions of uncertain malignancy at transvaginal B-mode and/or color Doppler sonography. We tested whether penetrating or mixed penetrating and peripheral patterns of vessels were associated with malignancy. Exclusion criteria were as follows: typical benign cysts with absence of internal echoes, a sharply defined smooth wall, no wall enhancement, and increased sonic-through transmission. A total of 45 patients with suspicious masses (33 benign adnexal lesions and 12 ovarian malignancies) were analyzed with three-dimensional power Doppler sonography before and after injection of sonographic contrast agent (Levovist, SHU 508A; Schering AG, Berlin, Germany). The study enrollment period was 1 year. Twenty-seven of the women studied were premenopausal (mean [range] age 34 [19–49] years). Three women were perimenopausal (mean [range] age 49 [47–54] years). The remaining 15 women were postmenopausal (mean [range] age 62 [51–77] years). Two postmenopausal patients had undergone hysterectomy, 12 and 7 years before entering the study.

A valid questionnaire was completed by participants with the help of trained nurses, who confirmed and checked answers. The questionnaire contained detailed inquiries about occupation, parity, personal and family history, breast-feeding, former or present use of oral contraceptives (OCs), ovulation drugs or hormonal replacement therapy (HRT), use of talc in feminine hygiene, smoking, diet, and alcohol use.

Most of the patients in our study group were active or retired lower-level administrative employees and/or small business entrepreneurs (n = 21). Twelve patients were skilled or specialized workers, five were unskilled workers, and four were managers or other high-level administrative employees, whereas three patients were unemployed. Two patients with ovarian carcinoma had one first-degree relative with this cancer. Furthermore, ovarian malignancy was detected in one patient with a personal history of endometrial carcinoma and in one patient with breast cancer. In the group of patients with benign adnexal lesions, there were no data or personal or family history of ovarian, endometrial, breast, or colorectal malignancy. We provide other demographic data in tabular form (Table 1).

Three-dimensional power Doppler studies were performed by a single examiner (SK) with Voluson 530 (Kretz Medison, Zipf, Austria). Volume data acquisition was performed using a 5-MHz transvaginal volume probe. The amount of the volume influences the duration of the scanning procedure (acquisition time approximately 30–60 seconds). Fixed preinstalled instrument settings for pulse repetition frequency (1.0), signal power (2), wall motion filter (61), persistence (rise 0.1, fall 0.3), center frequency (middle), gray/color balance (greater than 192), quality (4), and density (8) of the volume scan were used throughout the examinations. Only power Doppler gain was adjusted to optimize signal quality. Volumetric data were stored on a hard disk to enable full evaluation without loss of information at a later point. During each examination, we defined a cube enclosing the vessels of the adnexal lesion but excluding the iliac vessels or motion artifacts, which are very common as a result of the very sensitive power Doppler.

After performing an initial scan by three-dimensional power Doppler, we injected the enhancing contrast agent. Thereafter, we had to reduce the power Doppler gain because power Doppler noise, such as color blooming artifact, was produced by the effect of the contrast agent. We manipulated the power Doppler gain at the highest level possible that did not produce considerable artifacts, continuously throughout the entire scanning. The resultant power Doppler gains ranged from 70 to 85%. Volumetric data of power Doppler images were stored on the hard disk at 60, 120, 180, 240, 300, 360, 420, and 480 seconds after the initiation of the contrast agent injection.

At three-dimensional power Doppler ultrasound, the vascular distribution in adnexal lesions was classified as follows: pattern 0, no signal pattern (which indicated no detectable vessels); pattern 1, peripheral pattern, which indicated blood vessels arose outside the lesion and surrounded the lesion; pattern 2, penetrating pattern, indicating that blood vessels arose outside the lesion and coursed towards the center; and pattern 3, mixed penetrating and peripheral pattern. Three-dimensional power Doppler findings after contrast injection were compared with those before beginning the procedure in terms of sensitivity, specificity, and positive and negative predictive values. Diagnostic efficiency was expressed as the sum of true positives and true negatives divided by the sum of true positives, true negatives, false positives, and false negatives. We tested whether penetrating or mixed penetrating and peripheral patterns of vessels were associated with adnexal malignancy. Schematic presentation of vascular distribution is demonstrated in Figure 1.

View larger version (18K): [in this window] [in a new window]   Figure 1. Vascular distribution in adnexal lesions.

The same surgical team operated on all the cases, and histopathologic diagnosis was considered final. Malignant tumors were classified according to the International Federation of Gynecology and Obstetrics (FIGO) system.¹³ The study protocol was approved by the hospital’s Ethical Committee, and all patients consented to participate in the study.

	Results

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Forty-five patients were referred for three-dimensional power Doppler ultrasound because of indeterminate findings of the complex adnexal mass on transvaginal B-mode and/or color Doppler ultrasound. At laparotomy, 12 women were found to have ovarian cancer, whereas 33 had benign adnexal lesions. Histopathologic examination of the ovarian malignancies revealed eight cases of serous and two cases of mucinous cystadeno-carcinoma, one endometrioid cystadenocarcinoma, and one clear cell carcinoma. Adequate surgical staging was defined according to FIGO guidelines.¹³ There were five stage I cases (three stage Ia, one stage Ib, and one stage Ic), four stage II cases, and two stage III cases, and one patient had stage IV ovarian carcinoma. Table 2 lists histopathologic diagnosis of the adnexal lesions analyzed by enhanced and nonenhanced three-dimensional power Doppler sonography.

The best image quality was obtained in 39 patients 180 seconds after initiation of the contrast injection; after 120 seconds in four patients; and after 240 seconds in two patients.

Of the 12 ovarian cancers, four (33.3%) showed penetrating vessels, three (25.0%) had mixed penetrating and peripheral pattern, and three (25.0%) showed peripheral vessels; in two cases (16.7%), no flow was detectable by nonenhanced three-dimensional power Doppler imaging. The mean (range) diameter of malignant lesions in which penetrating vessels were found at three-dimensional power Doppler ultrasound was 5.2 (2.2–9.5) cm, of lesions with mixed penetrating and peripheral pattern was 5.6 (2.5–9.2) cm, of lesions with peripheral vessels was 5.4 (3–8) cm, and of lesions with no detectable vessels was 9 and 12 cm in diameter. In the group of benign lesions, no detectable flow was found in 12 (36.4%) patients, peripheral vessels were seen in 20 (60.6%), and penetrating vessels were seen in one (3.0%) case. The benign lesion with penetrating vessels was subsequently found to be cystadenofibroma.

By using the presence of penetrating vessels as the diagnostic criterion for malignancy, three-dimensional power Doppler ultrasound demonstrated a diagnostic sensitivity of 58.3% and specificity of 97.0%. The positive and negative predictive values were 87.5% and 86.5%, respectively (Table 3).

With respect to differential diagnosis between malignant and benign ovarian lesions, contrast-enhanced, three-dimensional power Doppler sonography reached diagnostic sensitivity and specificity of 100% and 93.9%, respectively. The positive and negative predictive values of this method were 85.7% and 100%, respectively. Therefore, the diagnostic efficiency was improved with the use of sonographic contrast agent from 86.7% to 95.6% (Table 3).

	Discussion

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In complex adnexal lesions, differentiating benign from malignant lesions can be problematic even though modern ultrasound studies have improved the diagnostic accuracy of these lesions.^2,4,10 In the present study, contrast-enhanced, three-dimensional power Doppler imaging was used for evaluation of adnexal tumor vascularity without considering morphologic findings that suggest malignancy. We found that contrast-enhanced, three-dimensional power Doppler imaging improves visualization of intratumoral vascularity, which may aid in detection of malignant adnexal tumors.

Although our study population included only 45 cases, the use of a contrast agent in three-dimensional power Doppler ultrasound appears to improve sensitivity for differentiating benign from malignant adnexal lesions by allowing better detection of malignant tumor perfusion than is obtained by imaging without contrast. However, our results have a fundamental bias because the differential diagnosis between benign and malignant ovarian lesions was based only on the presence or absence of enhancement within the lesion. Although an optimized protocol for contrast-enhanced, three-dimensional power Doppler ultrasound has not been established yet, the selection of an optimal infusion rate and concentration of sonographic contrast agent must be very important in obtaining reliable results. Slower injection rates (approximately 0.2 mL/second) and use of sonographic contrast agent with a 300 mg/dL concentration can reduce the emergence of "blooming artifacts" in early stages of the investigation.⁷ It is expected that these artifacts and high sensitivity to motion may be reduced by optimization of the instrument’s settings.¹⁴ In the clinical setting, the enhancement provided by the contrast agents and resultant color blooming could be compensated for by reducing the scanner’s color flow sensitivity soon after injection and gradually increasing the sensitivity as the effect of contrast diminishes over time.

We found that contrast-enhanced, three-dimensional power Doppler sonography provided better visualization of tumor vascularity in suspicious adnexal lesions than that obtained with non–contrast-enhanced, three-dimensional power Doppler sonography, and this led to a more exact differential diagnosis. In the present study, contrast-enhanced, three-dimensional power Doppler ultrasound showed 100% negative predictive value for malignant ovarian lesions and 85.7% positive predictive value, which was similar to non–contrast-enhanced power Doppler ultrasound. Furthermore, our results show that the pattern of irregularly branching penetrating vessels in suspicious adnexal lesions demonstrated on three-dimensional power Doppler ultrasound with or without contrast enhancement is an important feature that should be considered with other sonographic criteria to predict the likelihood of malignancy.

In deep-lying and necrotic adnexal lesions confirmed by histopathology, non– contrast-enhanced, three-dimensional power Doppler sonography did not demonstrate intratumoral vessels as a result of low velocity flow. In two cases of ovarian malignancy measuring 9 and 12 cm, initial scan by three-dimensional power Doppler did not reveal intratumoral vascularity. Contrast medium administration increased the strength of the returning signal, generating a clear image of central stellate feeding vessels from which a diagnosis can be made (Figure 2). Therefore, the combination of echo-enhancing contrast with three-dimensional power Doppler technique brought us a step closer to angiographic images.

View larger version (124K): [in this window] [in a new window]   Figure 2. Enhanced three-dimensional power Doppler scan of the complex adnexal mass. Penetrating vascular pattern suggests adnexal malignancy which was confirmed by histopathology.

Contrast-enhanced, three-dimensional power Doppler ultrasound was especially useful in patients with ovarian dermoids (n = 9), chronic PID (n = 9), and organizing hematoma with hemorrhagic cyst (n = 1). In these cases, contrast-enhanced, three-dimensional power Doppler ultrasound examination did not reveal signs of vascularity within the solid parts, but visualized peripheral vessels, which was mandatory to avoid false-positive results for malignancy (Figure 3). In seven patients with cystadenoma and five endometriomas, only discrete peripheral vascularization was detected, whereas two lesions (chronic PID and hemorrhagic cyst) remained avascularized. However, in two patients with benign lesions (one fibroma and one cystadenofibroma), contrast-enhanced, three-dimensional power Doppler sonography demonstrated penetrating vessels within the solid component, which led to misdiagnosis of ovarian malignancy. Because the treatment of benign lesions with suspicious morphology consists of surgical resection, these false-positive results did not affect the patients’ management protocols.

View larger version (116K): [in this window] [in a new window]   Figure 3. The same patient as in Figure 2 after injection of the echo-enhancing contrast medium. The solid component is free of color, which indicates absence of vascularity. The peripheral vessels become more prominent and suggest the benign nature of the lesion, which was confirmed by histopathology.

To determine the practical value of this modality, comparative studies of the diagnostic performance of three-dimensional power Doppler ultrasound before and after injection of contrast agents, including evaluation of cost-effectiveness, reproducibility, examination time, and invasiveness, must be performed.

	Footnotes

 
PII S0029-7844(00)00923-6

Received November 22, 1999. Received in revised form February 15, 2000. Accepted February 25, 2000.

	References

Top Abstract Materials and Methods Results Discussion References

 
1. Campbell S, Royston P, Bhan V. Novel screening strategies for early ovarian cancer by transabdominal ultrasonography. Br J Obstet Gynaecol 1990;96:304–11.

2. Kurjak A, Zalud I, Alfirevic Z. Evaluation of adnexal masses with transvaginal color Doppler ultrasound. J Ultrasound Med 1991;10: 295–7.[Abstract]

3. Sassone AM, Timor-Tritch IE, Artner A, Westhoff C, Warren B. Transvaginal sonographic characterization of ovarian disease: Evaluation of a new scoring system to predict ovarian malignancy. Obstet Gynecol 1991;78:70–6.[Abstract/Free Full Text]

4. Kurjak A, Shalan H, Matijevic R, Predanic M, Kupesic S. Stage I ovarian cancer by transvaginal color Doppler sonography: A report of 18 cases. Ultrasound Obstet Gynecol 1993;3:195–8.[Medline]

5. Fleischer AC, Cullinan JA, Peery CV, Jones JW III. Early detection of ovarian carcinoma with transvaginal color Doppler ultrasound. Am J Obstet Gynecol 1996;174:101–6.[Medline]

6. Bourne TH. Should clinical decisions be made about ovarian masses using transvaginal color Doppler? Ultrasound Obstet Gynecol 1994;4:257–60.

7. Albrecht T, Urbank A, Mahler M, Bauer A, Dore CJ, Blomley MJK, et al. Prolongation and optimization of Doppler enhancement with a microbubble ultrasound contrast agent by using continuous infusion: Preliminary experience. Radiology 1998;207:339–47.[Abstract/Free Full Text]

8. Kim AY, Kim SH, Kim YJ, Lee IH. Contrast-enhanced power Doppler sonography for the differentiation of cystic renal lesions: Preliminary study. J Ultrasound Med 1999;18:581–8.[Abstract]

9. Hosten N, Puls R, Lemke AJ, Steger W, Zendel W, Zwicker C, et al. Contrast-enhanced power Doppler sonography: Improved detection of characteristic flow patterns in focal liver lesions. J Clin Ultrasound 1999;27:107–15.[Medline]

10. Kurjak A, Kupesic S, Breyer B, Sparac V, Jukic S. The assessment of ovarian tumor angiogenesis: What does three-dimensional power Doppler add? Ultrasound Obstet Gynecol 1998;12:1–11.[Medline]

11. Suren A, Osmers R, Kuhn W. Three-dimensional color power Angio^TM imaging: A new method to assess intracervical vascularization in benign and pathological conditions. Ultrasound Obstet Gynecol 1998;11:133–7.[Medline]

12. Pairleitner H, Steiner H, Hasenoehrl G, Staudach A. Three-dimensional power Doppler sonography: Imaging and quantifying blood flow and vascularization. Ultrasound Obstet Gynecol 1999; 14:139–43.[Medline]

13. Scully RE. World Health Organization classification and nomenclature of ovarian cancer. Natl Cancer Inst Monogr 1975;42:5.

14. Goldberg BB, Merton AD, Forsberg F, Liu J, Rawool N. Color amplitude imaging: Preliminary results using vascular sonographic contrast agents. J Ultrasound Med 1990;15:127–34.

15. Kurjak A, Kupesic S. Three-dimensional ultrasound and power Doppler in assessment of uterine and ovarian angiogenesis: A prospective study. Croat Med J 1999;40:413–21.[Medline]

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