Transvaginal Doppler examination of uteri with myomas

J Clin Ultrasound 24:135-140, MarchlApril 1996 0 1996 by John Wiley & Sons, Inc. CCC 0091-2751/96/030135-06

Transvaginal Doppler Examination of Uteri with Myomas

Povilas Sladkevicius, MD, PhD,* Lil Valentin, MD, PhD,? and Karel MarsB1, MD, PhDt

Abstract: The uterine arteries and arteries in the wall and core of myomas were examined with transvaginal color and spectral Doppler ultrasound in 28 premenopausal and 17 postmenopausal women with uterine myomas. Eighteen premenopausal women and 100 postmenopausal women without myomas served as the controls for uterine artery Doppler measurements. The respective median time-averaged maximum velocity and pulsatility index (PI) values for the left uterine artery were 36.1 c d s anci 1.36 in premenopausal women with myomas vs. 17.6 c d s and 2.58 in controls; p = 0.0001. The corresponding values in postmenopausal women were 13.9 cm/s and 1.93 vs. 11.0 cm/s and 2.33; p < 0.05. PI values < 1.0 were recorded from 92% (24/26) of the myomas in premenopausal women and from 69% (11/16) of those in postmenopausal women. We conclude that uterine myomas substantially affect blood flow velocity in the uterine arteries, and that PI values < 1.0 are common in uterine myomas and do not indicate malignancy. 0 1996 John Wiley & Sons, Inc. Indexing Words: Doppler ultrasonography . Myoma . Uterine arteries . Color Doppler

Palpable pelvic tumors can be characterized by ultrasonography. Some tumors, eg, ovarian en- dometriotic cysts and benign ovarian teratomas, have such a typical appearance in gray-scale ultrasound examinations that a histological diagnosis may be suggested on the basis of ultrasound tumor Benign uterine leiomyomas, too, are usually easily recognized with gray- scale ultrasonography, but may sometimes be dif- ficult to differentiate from solid ovarian tumors. Doppler ultrasound is a new diagnostic modality that has been used to characterize pelvic tumors, transvaginal color and spectral Doppler examinations having been suggested to enable discrimi- nation between benign and malignant adnexal

The aim of this study was to use Dopp- ler velocimetry to describe blood flow velocities in the uterine arteries of uteri with myomas, to com- pare them with those of normal uteri, and to char-

From the *Department of Obstetrics and Gynecology, Vilnius University, Vilnius, Lithuania; and t Department of Obstet- rics and Gynecology, Malmo University Hospital, Malmo, Sweden. For reprints contact Dr. Lil Valentin, Department of Obstetrics and Gynecology, Malmo University Hospital, S-20502 Malmo, Sweden.

VOL. 24, NO. 3, MARCH/APRIL 1996

acterize the blood circulation of benign uterine leiomyomas.

SUBJECTS AND METHODS

The study was approved by the Ethics Committee of the Medical Faculty, Lund University, Sweden. All participants gave their informed consent after the nature of the procedures had been fully explained.

The group studied comprised 28 premenopausal women who were to undergo laparotomy because of myomas causing symptoms, and 17 asymptomatic postmenopausal volunteers with myomas incidentally detected in transvaginal ultrasound examinations (see below). A histological diagnosis of benign uterine leiomyoma was made in all premenopausal women. In the 17 postmenopausal volunteers, the myoma diagnosis was es- tablished based on the ultrasound image. Eigh- teen hea l thy premenopausal volunteers examined on the seventh day after follicular rupture (the day of follicular rupture being deter- mined from daily transvaginal ultrasound examinations of the dominant ovary), and 100

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SLADKEVICIUS ET AL.

asymptomatic healthy postmenopausal volunteers without sonographically detectable myomas constituted the respective control groups for the uterine artery Doppler measurements. All the 135 volunteers took part in research projects, the purpose of which was to establish normal refer- ence data for transvaginal color and spectral Doppler ultrasound examinations. The age of the women and time elapsed since the menopause are presented in Table 1. None of the women used any form of hormonal medication.

All of the 28 women who underwent laparotomy were examined within 8 days preceding the operation (14 of them being examined before cycle day 14) using both transabdominal and transvaginal gray-scale sonography . The transabdominal examinations were necessary to adequately measure uterine size in the women with a large uterus. Gray-scale ultrasound examinations of the other women and all Doppler examinations were carried out transvaginally. Transvaginal examinations were performed with the women in the lithotomy position.

The depth and width of the uterus and the length, depth, and width (ie, three orthogonal di- ameters) of the myomas were measured with cal- ipers on the frozen ultrasound image. Measure- ments of the depth of the uterus were taken from a longitudinal sonogram through the thickest part of the uterus and measurements of uterine width from a transverse sonogram through the widest part of the uterus. The size of the uterus (cm) was expressed as the mean of its depth and width. Myoma volume (cm3) was calculated according to the formula: Length (cm) x Depth (cm) x Width (cm) x 0.5.

If more than one myoma was found in the pel- vis, the largest myoma was examined. The uterine arteries and myoma vascularization were vi- sualized with the color Doppler technique, and blood flow velocity waveforms were obtained by placing the Doppler gate over the colored areas and activating the pulsed Doppler function. We obtained arterial Doppler shift spectra from the

wall and core of the myomas. The main stem of both uterine arteries was examined lateral to the cervix at the level of the internal 0s. Because of the tortuosity or smallness of the vessels examined, it was not possible to correct for the in- sonation angle, but the highest achievable Dopp- ler signals were recorded.

The equipment used was an Acuson 128XP ultrasound system with a 5 MHz transvaginal transducer (Acuson Inc., Mountain View, CA). Both in the color and spectral mode, the Doppler ultrasound frequency was 5 MHz. A 125 Hz high- pass filter was used. The color gate, the sample volume, and the color and spectral Doppler gains were adjusted as needed to obtain optimal color Doppler images and Doppler shift spectra. In the ultrasound system used, pulse repetition frequency changes automatically with the depth of the sample volume. The output energy of the Doppler instrument did not exceed 500 mW/cm2 (spatial peak temporal average intensity).

The arterial Doppler shift spectra were analyzed off-line from hard copies, using a digitizer (Hipad TM digitizer, Bausch & Lomb, Houston Instrument Div., Houston, TX.) coupled to a computer (ABC 806, Luxor, Motala, Sweden). Three uniform consecutive heart beats were analyzed and the resulting values averaged. The analysis was based on the envelope of the Doppler shift spectrum. The waveforms were characterized by the time-averaged maximum velocity (TAMXV), and the pulsatility index (PI, ie, peak velocity mi- nus the minimum velocity after the peak, divided by the mean velocity over the cycle').

Statistical calculations were made with the aid of a Macintosh computer, using Statview SE +Graphics'" software (Abacus Concepts, Berkeley, CA, 1988). The Mann-Whitney test was used to determine the statistical significance of differences in continuous data between groups of women. Spearman's rank correlation coeffi- cient was calculated to assess correlations. Two- tailed p-values are given with p < .05 indicating statistical significance.

TABLE 1 Age and Time Elapsed in Years Since the Menopause

Number of Years Age Postmenopause

Number Median (range) Median (range)

Yr Premenopausal women

With myomas 28 45 (30-53) - Without myomas 18 39 (29-45) -

With myomas 17 54 (49-58) 5 (2-10) Postmenopausal women

Without myomas 100 54 (45-62) 5 (1-15)

136 JOURNAL OF CLINICAL ULTRASOUND

UTERI WITH MYOMAS

RESULTS

There were no differences in any Doppler results between women examined before cycle day 14 and those examined on the 14th day of the cycle or thereafter.

Myoma volume and the results of Doppler measurements of TAMXV and PI in myoma arteries are presented in Table 2. Much higher TAMXV values were recorded from the arteries supplying the large myomas of the symptomatic premenopausal women than from those supplying the small myomas of the asymptomatic postmenopausal women. However, PI values did not differ between the groups. In 92% (24126) of the myomas of the premenopausal women and in 69% (11/16) of those of the postmenopausal women, PI values < 1.0 were recorded.

In the postmenopausal women, the TAMXV in the arteries of the myoma wall increased signifi- cantly with increasing myoma volume (r = 0.58, p = 0.021, and there also was a tendency for TAMXV in the arteries of the myoma core to increase with increasing size of the myoma ( r = 0.62, p = 0.07). In the premenopausal women, there was no tendency for TAMXV in myoma arteries to be related to myoma volume. PI values were not related to the size of myomas either in premenopausal or postmenopausal women.

Uterine size and the results of uterine artery Doppler measurements are given in Table 3. Higher TAMXV values and lower PI values were recorded in the uterine arteries of uteri with myomas than in those of normal uteri. This was true both of the premenopausal women with large myomas causing symptoms and of the asymptomatic

postmenopausal women with small myomas incidentally detected at ultrasound examination.

In premenopausal women with a normal uterus there was no correlation between uterine size and the results of Doppler measurements. In those with myomas, the TAMXV in the right and left uterine arteries increased (r = 0.55, p = 0.02 and r = 0.42, p = 0.06, respectively) and the PI values in the right uterine artery decreased (r = -0.49, p = 0.03) with increasing uterine size; The PI values in the left uterine artery did not change with uterine size ( r = -0.20; p = 0.38). In postmenopausal women with a normal uterus, the TAMXV in the right and left uterine arteries increased with increasing uterine size (r = 0.29, p = 0.01 and r = 0.29, p = 0.004, respectively), whereas the PI values did not change signifi- cantly. No significant correlation was found between uterine size and the results of uterine artery Doppler measurements in postmenopausal women with uterine myomas.

Typical color Doppler images and Doppler spectra obtained from a uterine myoma are shown in Figure 1.

DISCUSSION

Uterine artery blood flow velocities change during the normal menstrual cycle, the highest TAMXV values and the lowest PI values being recorded in the luteal phase.' In order not to over- estimate any difference in Doppler results between premenopausal women with vs. without myomas, we chose as control values uterine artery TAMXV and PI values obtained in the luteal phase.

TABLE 2 Myoma Volume, Time-Averaged Maximum Velocity (TAMXV), and

Pulsatility Index (PI) in the Arteries of the Wall and Core of Myomas

Premenopausal Postmenopausal Women Women p-Va I u e

(23; 4501 (2; 261 Myoma volume (cm3) 124 In = 281 7 [n = 171 0.0001

Arteries in myoma wall TAMXV (cmls) 26.4 In = 261 11.4[n = 161 0.0001

PI 0.81 0.82 0.34 (1 1.3; 36.9) (5.3; 20.0)

(0.52; 1.14) (0.64; 1.13)

Arteries in rnyoma core TAMXV (cm/s) 14.6 In = 221 7.6 In = 101 0.01

(6.3; 29.3) (3.5; 15.1)

(0.37; 1.09) (0.53; 1.18) PI 0.67 0.66 0.68

Medians are presented with 10th and 90th percentiles in parentheses. Numbers of measurements are given in square brackets. The Mann-Whitney test was used to determine the statistical significance of differ-

ences.

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SLADKEVICIUS ET AL.

TABLE 3 Uterine Size, Time-Averaged Maximum Velocity (TAMXV), and Pulsatility Index (PI) in the Uterine Arteries

Premenopausal Women Postmenopausal Women

With myomas Without myomas With myomas Without myomas (n = 28*) (n = 18) p-Va I ue (n = 17) (n = 100) p-Value

Uterine size (cm) 8.8

Right uterine artery (4.7; 11.9)

TAMXV (cm/s) 39.5

PI 1.48 (23.9; 66.2)

(1.04; 2.10) Left uterine artery

TAMXV (cm/s) 36.1

PI 1.36 (16.1; 72.3)

(0.87; 2.28)

4.8 (4.0; 5.3)

17.4 (12.4; 24.3)

2.50 (1.76; 3.18)

17.6 (12.6; 25.0)

2.58 (1.95; 3.67)

0.0001 3.8 (3.2; 5.9)

0.0001 18.1

0.0001 1.93 (7.3; 29.7)

(1.51; 2.67)

3.5 0.03 (2.8; 4.2)

10.5 0.006

2.23 0.09 (4.7; 20.0)

(1.48; 3.40)

0.0001 13.9

0.0001 1.93 (5.7; 25.6)

(1.25; 2.97)

11.0 0.03

2.33 0.02 (5.9; 19.1)

(1.52; 3.76) ~

Medians are presented with 10th and 90th percentiles in parentheses. *22 measurements of uterine size, 23 measurements from the right uterine artery and 25 from the left. The Mann-Whitney test was used to determine the statistical significance of differences.

We have no unequivocal histologic evidence that the solid uterine tumors of the postmenopausal women were indeed myomas, because small asymptomatic myomas are not an indica- tion for surgery. However, all masses in postmenopausal women judged to be myomas manifested an ultrasound morphology typical of myomas. The masses remained unchanged in size and appearance at follow-up after 10-12 months, and none of the women developed gynecologic symptoms during the follow-up period. Thus, it seems unlikely that any of the presumed myomas was a uterine malignancy. On the other hand, it cannot be excluded that adenomyomas may have been mistaken for myomas, as myomas and adenomyomas may be confused at sonography.’

The present findings indicate that uterine myomas, irrespective of whether they are small and asymptomatic (as in the postmenopausal women of this study) or large and symptomatic (as in the premenopausal women of the study), considerably affect uterine artery blood flow velocity. Higher TAMXV values and lower PI values were recorded in the uterine arteries of uteri with myomas than in those of normal uteri. Weiner and colleagues” and Kurjak and co-workers,ll also found that myomas affect the results of uterine artery Doppler measurements, lower RI and PI

and higher blood flow velocity” being recorded in the uterine arteries of women with myomas compared with those with a normal uterus.

There may well be a relationship between TAMXV and organ perfusion; in cerebral vessels TAMXV has been shown to correlate very closely with total brain f10w.12-14 The correlation between PI and volume flow is weaker or ab-

138

sent.12-14 The higher TAMXV values and lower PI values recorded in the uterine arteries of women with myomas in the present study probably reflect increased perfusion of the uteri with myomas. This may be an effect of increased uterine size and not necessarily an effect of the myomas per se. Indeed, we found the TAMXV in the uterine arteries to increase with increasing uterine size both in women with myomas and in those without.

In postmenopausal women, there was a significant positive correlation between myoma volume and the TAMXV in the arteries of the wall of the myomas. If vessels in the myoma wall are consid- ered to be “feeder” vessels of the myoma, and if TAMXV is assumed to reflect p e r f ~ s i o n , ’ ~ - ~ ~ then it is to be expected that the TAMXV in wall vessels should increase with increasing myoma volume, larger myomas presumably needing more blood than small ones. However, no relationship was found between myoma size and TAMXV in wall vessels in the relatively large myomas of premenopausal women. This is perhaps to be explained by large myomas having many feeder vessels. 15716 Nonetheless, in the present study, much higher blood flow velocities were recorded in the arteries of the relatively large myomas of the premenopausal women than in the smaller myomas of the postmenopausal women. This difference may have been due to the difference in menstrual status but is perhaps more likely to be explained by the difference in myoma size.

In many studies, PI values <1.0 in a pelvic mass have been taken to indicate malignancy.5,17-22 However, in the present study, PI values <1.0 were recorded from the majority of

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UTERI WITH MYOMAS

FIGURE 1. Typical color Doppler image (A) and Doppler spectrum (B) obtained from a myoma. Note the well-defined straight vessel following the outline of the myoma.

myomas both in premenopausal (93%) and in postmenopausal (69%) women. Kurjak and co- w o r k e r ~ , ~ ~ also reported the arteries of many myomas to manifest low blood flow impedance, and in the experience of Bournez4 “uterine fibroids . . . are characterized by low impedance but high velocity blood flow.” Obviously, PI values d . 0 are common in uterine myomas and do not indicate malignancy.

Although we did not systematically evaluate the vessel tree of the myomas in this study using the color Doppler technique, it is our impression that the color Doppler image of many myomas was typical, a well-defined straight vessel often being seen to follow the outline of the tumor (Fig- ure 1). This finding probably corresponds to the vessel pattern of myomas described by Fern- ~ t r o m . ’ ~ His angiographic studies of myomas

VOL. 24, NO. 3, MARCH/APRIL 1996

showed that blood vessels in the capsule of a uterine myoma were usually arched and manifested partial or complete loss of tortuosity. According to F e r n ~ t r o m , ~ ~ the vessels in the myoma core fol- lowed either a straight or an irregularly tortuous course and anastomosed with one another.

In conclusion, the results of this study indicate that myomas substantially affect the results of Doppler measurements in the uterine arteries. This effect of myomas on uterine blood circulation should be borne in mind both in clinical practice-eg, if Doppler measurements are used to help in differentiating between benign and malignant endometri- urnz6- and in scientific investigations in which Doppler velocimetry is used to study uterine circulation. Finally, PI values <1.0 are frequently recorded in the arteries of uterine myomas and do not necessarily indicate malignancy.

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SLADKEVICIUS ET AL.

ACKNOWLEDGMENTS 12. Hansen NB, Stonestreet BS, Rosenkrantz TS, et al: Validity of Doppler measurements of anterior cerebral artery blood flow velocity: correlation with brain blood flow in piglets. Pediatrics 72:526-531,1983.

13. Greisen G, Johansen K, Ellison PH, et al: Cerebral blood flow in the newborn infant comDarison of

This study was supported by the Malmo General Hospital Cancer Foundation, Funds administered by the M a h o Health Care Administration, Pro- cordia, the Faculty of Medicine of Lund Univer- sity, the Crafoord Foundation, the Anna-Lisa och Sven-Erik Lundgren Foundation for Medical Re- search, The Swedish Society of Medicine, and The Swedish Medical Research Council grant number B96-17X-11605-01A.

Doppler ultrasound and 133xenon clearance. J Pe- diatr 104:411-418, 1984.

14. Rosenberg AA, Norayaman v , Jones MD: Compar- ison of anterior cerebral artery blood flow velocity and cerebral blood flow during hypoxia. Pediatr

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Transvaginal Doppler examination of uteri with myomas