Intrauterine ultrasonography with a high-frequency probe: Preliminary report

Instruments & Methods

INTRAUTERINE ULTRASONOGRAPHY WITH A HIGH-FREQUENCY PROBE: PRELIMINARY REPORT

Akihiko Kikuchi, MD, Takashi Okai, MD, PhD, Koichi Kobayashi, MD, Masato Sakai, MD, Eiji Ryo, MD, and Yuji Taketani, MD, PhD Intrauterine ultrasonography was performed using miniature probes and high-frequency ultrasound to examine the possible clinical applications of this technique to gynecology. There were 44 women in the study population (age 19-76; ten with a normal uterus, nine fibromyoma, 15 endometrial cancer, ten cervical cancer). The probe was easily introduced into the endometrial cavity in 36 subjects (81.8%). No notable complications were encountered. In subjects with a normal uterus, the endometrium in the secretory phase showed a clearly demarcated hyperechoic area, and higher resolution was obtained than with transvaginal scanning. In patients with fibromyomas, myoma nodules were not clearly visualized because of the attenuation of ultrasound. Myometrial invasion of endometrial cancer was estimated correctly in ten of the 11 patients in which the lesion was visualized. In the subjects with cervical cancer, intracervical scanning was completed in only five cases, and an endocervical lesion was identified in three cases. Intrauterine ultrasonography with a high-frequency miniature

From the Division of Gynecology, Saitama Cancer Center, Saitama; and the Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.

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probe may be a useful tool, especially in the preoperative evaluation of endometrial cancer and possibly in infertility practice. However, this modality does not appear to be satisfactory for cervical lesions. ( O b s t e t Gyneco11995;85.a~57 61)

Transvaginal ultrasonography is widely used in gynecology because it provides clearer images of the uterus than does a transabdominal approach. However, there is still some difficulty in the evaluation of endometrium in infertility patients I and in the preoperative assessment of uterine malignant tumors. 2 The combination of high-frequency ultrasound and a probe that can be introduced into the uterine cavity may provide more detailed information in these areas. There have been a few reports on intrauterine ultrasonography,3-s but the probes used in these studies had two major problems: 1) The probes were not small enough to be introduced through the cervix without cervical dilation or anesthesia; and 2) the ultrasound frequency was relatively low (eg, 7.5 MHz), so the images obtained were not high resolution. Because low frequencies were used, this technique offered little advantage over traditional transvaginal ultrasound. Over the past few years, the use of high-frequency intraluminal ultrasound and miniature probes has emerged as an imaging modality for vascular diseases. 6 Ragavendra et al 7 reported the use of a commercially available, catheter-based ultrasound transducer (12.5 MHz) introduced through the cervix and into the endometrial cavity of seven women undergoing voluntary termination of first-trimester pregnancies. They concluded that anatomic structures (eg, the neural tube) in the developing human embryo could be imaged successfully. However, the safety of this method in obstetric use has not yet been determined. We applied this procedure to gynecologic diseases to determine the possible clinical applications of intrauterine ultrasonography with a high-frequency miniature probe.

Method We performed intrauterine radial-scan ultrasonography using a miniature probe (2 mm in diameter) with high-frequency (15-20 MHz) ultrasound (SSD-550; Aloka, Tokyo, Japan). The probe, threaded in a disposable sheath with sterile water inside, was inserted into the uterine cavity. Figure 1 shows the tip of the probe and the sheath tube. For intrauterine radial scanning, the patient was placed in the lithotomy position. The vagina was cleaned with an antiseptic, then the probe was inserted

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Transducer assembly

Transducer

Sheath tube Figure 1. A 1 × l-ram transducer is at the tip of the probe; sterile water is in the sheath tube.

into the uterine cavity up to the fundus. While the probe was withdrawn gradually, we obtained cross-sectional images of the whole uterus. Ten patients without uterine diseases (eg, ovarian cysts) and nine with uterine fibromyomas underwent transvaginal and intrauterine ultrasonography at Tokyo University Hospital between May 25, 1992, and June 1, 1992. Fifteen patients with endometrial cancer and ten with cervical cancer underwent preoperative intrauterine ultrasonography at Tokyo University Hospital or Saitama Cancer Center between April 20, 1992, and February 17, 1994. These 44 women, ages 19-76, formed

Figure 2. Endometrium in the mid-secretory phase (15 MHz). The endometrium showsa clearlydemarcated hyperechoicarea. The probe is embedded in the thick anterior endometrium. Calibration, 1 mm.

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Figure 3. Endometrialcancer with no myometrialinvasion (15 MHz). The endometriun-t appears hypoechoic and is clearly discriminated from the surrounding normal myometrium.

the study population. The purpose of the study and possible complications (such as bleeding, perforation, or infection) were explained to these subjects; they all gave informed consent. In cases of uterine malignancies, intrauterine ultrasonograms were compared to postoperative histologic findings.

Experience Of the 44 patients examined, the probe was easily introduced through the cervix into the endometrial cavity in 36 cases (81.8%) without cervical dilation and anesthesia. The probe could not be introduced into the uterine cavity in eight cases (one fibromyoma, two endometrial cancers, one post-conization, and four cervical cancers). We did not experience any notable complications (eg, heavy bleeding, perforation, or infection). In w o m e n with a normal uterus, the endometrium appeared hypoechoic or isoechoic compared with the myometrium in the proliferative phase, and it was not clearly discriminated from the myometrium. In the secretory phase, on the other hand, the endometrium showed a clearly demarcated hyperechoic area, and the probe was embedded in the thick endometrium in some patients (Figure 2). In patients with fibromyomas, m y o m a nodules, including submucosal ones, were not clearly visualized because of the attenuation of ultrasound. In those with endometrial cancer, good visualization of the lesions was achieved in 11 of 13 cases in which the probe could be introduced. In two cases in which the myometrial

Obstetrics & Gynecology

Table 1. Correlation Between Estimation of Myometrial

Invasion by Intrauterine Ultrasonography and Histologic Evaluation Histologic evaluation None

? Ultrasonogram None Mild Deep

Figure 4. Endometrial cancer with mild myometrial invasion at the posterior wall (20 MHz). The lesion appears hyperechoic. Except for the posterior site, the margin of the lesion is smoothly outlined, suggesting no invasion or only superficial invasion. However, mild invasion to the posterior myometrium is seen dearly (arrows).

invasion was limited to the fundal region, no lesions could be identified. We categorized the depth of myometrial invasion as none, mild (cancer invaded less than half of the myometrium), and deep (cancer invaded more than half of the myometrium) (Figures 3-5). In the 11 cases with good visualization, intrauterine sonograms were compared to postoperative histologic findings (Table 1). In ten of the 11, the depth of myometrial

Figure 5. Endometrial cancer with deep myometrial invasion (15 MHz). The cancer is invading the anterior myometrium deeply

(arrows).

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Mild

Deep

3

1 5

2

invasion was accurately diagnosed, but it was underestimated in one. Cervical invasion of endometrial cancer could also be seen (Figure 6). In our ten patients with cervical cancer, the probe passed through the full length of the cervix in only five cases. In the remaining five, the probe could not be introduced far enough to allow intracervical scanning, one because of previous conization and the others because of tumor growth. In three of the five cases in which intracervical scanning was achieved, the tumor area was demonstrated clearly (Figure 7). Of the remaining two cases, one was a microinvasive cancer, and the other was cancer of an ectocervical type, so that no lesions were found in the cervical canal as judged by postoperative histologic examinations.

Comment There have been reports of a miniature ultrasound probe being introduced into the blood v e s s e l s , 6 u r e t h r a , 8 and digestive tract. 9 The ultimate advantage of

Figure 6. Cervical invasion of endometrial cancer (15 MHz). This sonogram shows the image of intracervical scanning. The hyperechoic area is the tumor lesion (arrows).

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459

Figure 7. Cervical cancer with deep invasion (15 MHz). This sonogram shows the image of intracervical scanning. The relativelyhyperechoic area is the lesion (arrows).

intraluminal ultrasonography is that the unique position of the probe allows the use of a high-frequency transducer that provides detailed information of organ morphology. In gynecology, a few reports 3-5 have described experience with intrauterine ultrasonography; these studies have used relatively low-frequency probes, mainly in the evaluation of endometrial cancer. To our knowledge, this is the first report of the clinical application of intrauterine ultrasonography with a high-frequency probe in gynecologic diseases. The probe was easily introduced through the cervix into the endometrial cavity in 81.8% of our subjects. This success rate is satisfactory, considering our procedure was performed without any analgesia or cervical dilation. In previous reports, 3-5 the probes used were 7 m m in diameter, and required cervical dilation with Hegar dilators or laminaria tents. Our miniature probe, 2 m m in diameter, could be introduced into the uterine cavity in 81.8% of the subjects without such procedures. In combination with the procedures to dilate the cervical canal, we can expect better results. Of the eight cases in which the probe could not be introduced into the uterine cavity, four involved cervical cancer growing into the cervical canal, and one subject had undergone conization. In both situations, stenosis of the cervical canal was the reason for failure. In the remaining three subjects (one fibromyoma, two endometrial cancers), tumor growth into the endometrial cavity prevented the probe from reaching the fundus. This technique seemed to be inappropriate for these eight cases. With this technique, higher resolution could be achieved than with transvaginal scanning. Especially in

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the secretory phase, fine images of the endometrium were obtained, as shown in Figure 2. Several studies have attempted to correlate endometrial development (thickness and texture) and pregnancy outcome, but the results are conflicting. 1 Because the texture demonstrates structural and functional changes of the endometrium, intrauterine scanning with high-frequency ultrasound m a y provide a better understanding of the endometrial status in infertility patients. It is said that the degree of myometrial invasion is closely related to the prognosis of endometrial cancer. Use of intrauterine scanning allowed accurate estimation of myometrial invasion of endometrial cancer in ten of the 11 cases in which the lesions were detected. Minimal invasion was especially imaged clearly. This was because the transducer and the reflecting structure were close and the image resolution was greatly improved with high-frequency ultrasound. In the case shown in Figure 4, preoperative transvaginal ultrasonography was not performed; however, even if it had been, the minimal invasion would have been difficult to see. We had three cases in which the diagnosis could not be m a d e correctly. In these three cases, the m y o m e trial invasion was deepest around the fundus. The images obtained with this method are cross-sectional, ie, perpendicular to the long axis of the uterus, so that the evaluation of the fundus is theoretically difficult. The results of this modality appear to be extremely poor in cervical cancer cases, given that the technique was unsuccessful in half of the patients and successfully imaged only 30% of the lesions. Nevertheless, intracervical scanning could offer a new perspective for evaluating the depth of interstitial invasion of cervical cancer, especially of endocervical types. In some cases, accurate assessment of the extent of the tumor m a y be clinically desirable, but the probes cannot be introduced. One of the methods for cervical dilation m a y be used in these cases. We do not routinely perform hysteroscopy as a preoperative examination for uterine malignancies. Although hysteroscopy gives detailed information on the endometrium and cervical epithelium, it cannot visualize the depth of cancer invasion. With our procedure, we believe it is possible to diagnose the depth of myometrial and cervical interstitial invasion. The probe used in this study was designed for intravascular use. For gynecologic applications, there is room for further development. This report is preliminary, so comparisons with other diagnostic methods, such as transvaginal ultrasonography, computed tomography, and magnetic resonance imaging, have yet to be performed. However, based on our findings, intrauterine ultrasonography with high-frequency ultrasound would be useful, especially in preoperative

Obstetrics & Gynecology

s t a g i n g of e n d o m e t r i a l cancer a n d p o s s i b l y in infertility practice. F o r cervical lesions, this m o d a l i t y d o e s n o t a p p e a r to be satisfactory at present.

incontinence with intraurethral US: Preliminary results. Radiology 1993;187:141-3. 9. Miller LS, Liu JB, Klenn PJ, et al. Endolurninal ultrasonography of the distal esophagus in systemic sclerosis. Gastroenterology 1993; 105:31-9.

References 1. Khalifa E, Brzyski RG, Oehninger S, Acosta AA, Muasher SJ. Sonographic appearance of the endometrium: The predictive value for the outcome of in-vitro fertilization in stimulated cycles. Hum Reprod 1992;7:681-4. 2. Yamashita Y, Mizutani H, Torashima M, et al. Assessment of myometrial invasion by endometrial carcinoma: Transvaginal sonography vs contrast-enhanced MR imaging. AJR 1993;161:595-9. 3. Obata A, Akamatsu N, Sekiba K. Ultrasound estimation of myometrial invasion of endometrial cancer by intrauterine radial scanning. JCU 1985;13:397-404. 4. Rosenberg P, Hakansson OM. Intrauterine ultrasonography and endometrial caneer. Lancet 1989;i:842-3. 5. Hoetzinger H. Hysterosonography and hysterography in benign and malignant diseases of the uterus: A comparative in vitro study. J Ultrasound Med 1991;10:259-63. 6. Slepian MJ. Application of intraluminal ultrasound imaging to vascular stenting. Int J Card Imaging 1991;6:285-311. 7. Ragavendra N, McMahon JT, Perrella RR. Endoluminal catheterassisted transcervical US of the human embryo. Radiology 1991;181: 779-83. 8. Klein HM, Hermanns RK, Lagunilla J, G~inther RW. Assessment of

Address reprint requests to: Akihiko Kikuchi, M D Division of Gynecology Saitama Cancer Center 818, Oaza-komuro, Ina-machi Kita-adachi-gun Saitama 362 Japan

FIRST-TRIMESTER E N D O C E R V I C A L

ings. Trophoblast cells were identified by microscopy after staining the cultured material with an anti-alpha-hCGantibody bound stain. In ten of 20 cases (50%), trophoblast material was retrieved on irrigation. Of the five additional cases on which culture was attempted, trophoblast was successfully cultured in one, the results were equivocal in two, and culture was unsuccessful in the other two. Trophoblast cells for prenatal diagnosis can be obtained in a significant percentage of cases by first-trimester endocervical irrigation. The advantages of irrigation include technical simplicity, brief duration (less than 3 minutes), and suitability to first-trimester diagnosis. Further testing is necessary to determine the risks. (Obstet Gynecol 1995;85.,461-4)

IRRIGATION: FEASIBILITY OF O B T A I N I N G TROPHOBLAST CELLS FOR P R E N A T A L D I A G N O S I S

R. O. Bahado-Singh, MD, H. Kliman, MD, PhD, T. Yeng Feng, PhD, J. Hobbins, MD, J. A. Copel, MD, and M. J. Mahoney, MD, JD We sought to determine the feasibility of obtaining trophoblast cells for first-trimester prenatal diagnosis using endocervical irrigation. We studied 20 pregnant patients between 7-10.5 weeks" gestation who presented for elective pregnancy termination. Under ultrasound guidance, a specially designed plastic catheter was advanced to the level of the internal cervical os. Gentle flushing and aspiration was performed with 3 mL of normal saline. The material obtained was fixed and stained. A placental pathologist identified trophoblast cells using light microscopy. In another five cases, we attempted to culture the endocervical wash-

From the Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut.

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Received August 22, 1994. Received in revisedform November 7, 1994. Accepted November 9, 1994.

Copyright © 1995 by The American College of Obstetricians and Gynecologists.

There has b e e n a s u r g e in the u s e of p r e n a t a l d i a g n o s i s services o v e r the last decade. This increase is l a r g e l y b e c a u s e of g r o w i n g p a t i e n t a w a r e n e s s of the b u r d e n of genetic disease, the g r e a t e r n u m b e r of d i s o r d e r s t h a t a r e d i a g n o s a b l e p r e n a t a l l y , a n d the n o w w i d e s p r e a d availa b i l i t y of s a m p l i n g t e c h n i q u e s that w e r e f o r m e r l y confined to p i o n e e r i n g u n i v e r s i t y centers. N o n i n v a s i v e m e t h o d s of p r e n a t a l d i a g n o s i s a r e h i g h l y desirable. A d v a n t a g e s of such m e t h o d s i n c l u d e negligible risk of p r e g n a n c y loss o r o t h e r fetal h a r m , easily m a s t e r e d skills for o b t a i n i n g a s p e c i m e n , a n d l o w e r p r o c e d u r a l costs. U s i n g the m e t h o d d e s c r i b e d herein, there is the p o s s i b i l i t y of e a r l y p r e n a t a l d i a g n o -

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