Departments of Perinatology, Kagawa Medical University, 17501 Ikenobe, Miki, Kagawa 761-0793, Japan
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Abstract |
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Key words: brain vesicle/embryo/growth/intrauterine ultrasonography
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Introduction |
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Flexible catheter-based high-resolution real-time ultrasound transducers have been developed for use in visualization of anatomical structures of the normal human embryo (Ragavendra et al., 1991, 1993
). Fujiwaki et al. (1995) demonstrated that intrauterine sonography could reveal embryonic structures 13 weeks earlier than transvaginal sonography (Fujiwaki et al., 1995
). Moreover, it was possible to obtain finer image quality of very small embryonic structures with intrauterine sonography than with transvaginal sonography (Hata et al., 1997a
). There have been a few reports on embryonic organ measurements by intrauterine sonography in the early first-trimester pregnancy (Hata et al., 1996
, 1997b
). The objective of the current study was to evaluate embryonic brain vesicle growth at early first-trimester gestation with the use of intrauterine sonography with a flexible catheter-based high-resolution real-time miniature transducer.
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Materials and methods |
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Before each procedure, the intrauterine location of the embryo was confirmed by transvaginal sonography. Each patient was prepared and draped in the usual sterile fashion in the dorsolithotomy position. A sterile speculum was inserted into the vagina. The ultrasonic catheter was introduced gently through the cervix and into the endometrial cavity until it could not be advanced any further. Once within the endometrial cavity, the catheter tip was advanced or withdrawn slightly until the embryo was visualized.
The gestational age by menstrual history was compared with that by the crownrump length (CRL) (Iwamoto, 1983; Coulam et al., 1996
; Harkness et al., 1997
). Only those cases with a discrepancy <±3 days were included in the study.
The methods used to obtain embryonic brain measurements have been described in detail elsewhere (Blaas et al., 1994, 1995a
). Essentially, in the sagittal midline section, the length and height of the cavities of the mesencephalon and the diencephalon were obtained (Figure 1
). In a transverse section, the widths of the mesencephalon and diencephalon cavities and the telencephalon were measured (Figure 2
). The length of the telencephalon was measured in a parasagittal section as the longest possible distance from the anterior to the posterior border of the cortex (Figure 3
). The height was measured over the frontal horn, not including the basal ganglia. The planes for the measurement of the length and width of the rhombencephalon cavity are shown in Figure 4
. In the sagittal midline section (Figure 5
), the depth of the rhombencephalic cavity was measured from the pontine flexure to the roof of the fourth ventricle. The dataset contained only one measurement per patient to provide a cross-sectional analysis. After database screening with tests for a normal distribution, a growth curve for the brain vesicle parameter was determined for the cross-sectional data. Dataset regression analysis was carried out, testing the regression of brain vesicle measurements on menstrual age using polynominals of the first through the third degree (Dunn and Clark, 1974
; Rohatgi, 1976
; Bertagnoli et al., 1983
). The different methods were tested and independent variable deletion carried out by analysis of variance applied to the regression, followed by calculation of the step-down method coefficients (Snedecor and Cochran, 1967). The choice of the optimal model was based on the following criteria: largest r2, all coefficients different from 0 and low standard deviation of regression (SDR) (Bertagnoli et al., 1983
). Pathological examination, chromosome analysis and brain vesicle and CRL measurements post abortum could not be done, because the embryos were damaged during the therapeutic abortion.
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Results |
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Two cases (one each at week 6 and 7) were excluded from the study because of the shallow scanning range of high-frequency transducers or inappropriate embryonal position. Nine cases (three at week 6, four at week 7 and two at week 8) were excluded from the study because the discrepancy between the gestational age by menstrual history and that by the CRL was >3 days.
Curvilinear relationships were found between the menstrual age and telencephalon height, diencephalon length, width and height and mesencephalon length respectively (Table I). Linear relationships were found between the menstrual age and telencephalon width, mesencephalon height and rhombencephalon length, width and height respectively (Table I
). Telencephalon length and mesencephalon width were constant throughout menstrual age (Table I
). The normal ranges of embryonic brain vesicle measurements for each day of pregnancy were determined (Tables II, III, IV and V
).
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Discussion |
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It seems that intrauterine sonography lacks either the manoeuvrability, deep beam penetration or ability to allow perpendicular planes of section to be obtained. The ultrasound measurements of small embryonic structures are associated with an elevated intra-observer variability (Blaas et al., 1994, 1995a
). In this study, all examinations were performed by one examiner (H.T.) with great experience of intrauterine sonography, which reduced intra-observer variability. Consequently, a low coefficient of variation for brain vesicle measurements (<10%) was obtained. Reduced reproducibility of measuring small embryonic structures and/or large biological variation of parameters results in reduced values of r2 (Blaas et al., 1995b
). However, high r2 values for embryonic brain vesicle measurements were obtained in this study.
With respect to the comparison of embryonic brain vesicle measurements between previous transvaginal sonographic studies (Blaas et al., 1994, 1995a
) and our intrauterine sonographic investigation, there are a few subtle differences. In transvaginal sonographic study, the length of telencephalon was gradually increasing between 7 and 9 weeks (Blaas et al., 1994
), whereas this parameter was almost constant over the same period in our study. Surprisingly, the width of diencephalon decreased slowly between 7 and 9 weeks in the transvaginal sonographic study (Blaas et al., 1994
). However, the width of diencephalon moderately increased during the early first trimester of pregnancy in this study. The cause of these discrepancies of embryonic brain vesicle measurements between previous transvaginal sonographic studies and ours is currently unknown. One possible explanation is that finer image quality of very small embryonic brain structures could not be obtained using transvaginal sonography, even if using a 7.5 MHz transvaginal probe, so the problem of image quality in the transvaginal approach may make the measurements of embryonic brain vesicles less reliable during this period.
With respect to the planes and sections used to locate embryonic brain anatomical landmarks in this study, the same methods were employed to obtain embryonic brain measurements as those employed in transvaginal sonography (Blaas et al., 1994, 1995a
). Timor-Tritsch and Monteagudo (1996) proposed standardized transvaginal neurosonographic images of the fetal brain and a new nomenclature that more closely reflects the true anatomical sections (Timor-Tritsch and Monteagudo, 1996
). However, fetal ages of their study group ranged from 1840 weeks of gestation, whereas our embryonic ages varied from 79.9 weeks gestation. Therefore, the new nomenclature proposed by Timor-Tritsch and Monteagudo (1996) may not be suitable for embryonic brain anatomical landmarks.
Blaas et al. (1995c) reported that ultrasound technology used in their study has reached a stage where structures of only a few millimeters can be imaged in vivo in three dimensions with a quality that resembles the plaster figures used in embryonic laboratories (Blaas et al., 1995c). Nevertheless, their three-dimensional sonographic embryonic brain images were not so fine because they used a 7.5 MHz transvaginal probe, highlighting the problem of image quality in the transvaginal approach. If intrauterine sonography with a 20 MHz high-resolution transducer is used for three- dimensional sonographic embryonic brain structures, it will be possible to obtain finer image quality of small embryonic brain cavities.
With respect to limitations associated with intrauterine sonography, it is an invasive diagnostic procedure requiring sterile conditions. Its safety has not been established. Although we and previous authors (Ragavendra et al., 1991, 1993
; Fujiwaki et al., 1995
; Hata et al., 1996
) encountered no immediate complications, the use of intrauterine sonography is not recommended for routine clinical examination in pregnancy at present. Prospective further study is needed to clarify the safety of intrauterine sonography for its clinical use in the early first trimester of pregnancy.
In conclusion, intrauterine sonography provides a novel means for precise measurement of brain vesicles of the embryo. These results suggest that intrauterine sonography may become an important modality in future embryological research and in detection of embryonic brain abnormalities in the early first-trimester pregnancy.
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Acknowledgments |
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Notes |
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References |
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Submitted on November 15, 1999; accepted on March 7, 2000.