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Obstetric Imaging |
1 From Depts of Obstetrics and Gynecology (S.T., M.T., Y.H., T.M., K. Ueno, K. Uehara, O.N., K. Miyakoshi, K. Minegishi, H.I., Y.Y.), Diagnostic Radiology (H.S.), and Pediatrics (K.I.), School of Medicine, Keio University, Tokyo, Japan. Received Mar 6, 2003; revision requested May 23; final revision received Nov 17; accepted Jan 5, 2004. Address correspondence to K. Miyakoshi, Div of Reproductive Sciences, Oregon National Primate Research Center, 505 NW 185th Ave, Beaverton, OR 97006 (e-mail: miyakosh@ohsu.edu).
| ABSTRACT |
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MATERIALS AND METHODS: MR imaging lung volumetry and US biometry were performed in 90 fetuses at 2539 weeks gestation. In the control group of 73 fetuses, normal lung development was confirmed at neonatal follow-up and the normative ratio of MR imagingmeasured FLV to US-estimated FBW (FLV/FBW) was determined. The high-risk group included 17 fetuses at risk for PH. The FLV/FBW was compared between the control and high-risk groups and with US parameters for predicting the development of PH in the high-risk group. Measurements 2 or more standard deviations below the mean control group measurement were considered abnormal. Comparisons of the FLV/FBW between groups were made by using the Student t test. The association between development of PH and measurement of each parameter was analyzed by using the Fisher exact probability test.
RESULTS: In the control group, the FLV/FBW decreased with gestational age during the third trimester and had a normal distribution (mean ratio, 0.028 mL/g; range, 0.0150.444 mL/g). The mean FLV/FBW for the nine fetuses with PH (0.012 mL/g ± 0.008) was significantly lower (P < .001) than that for the control group (0.028 mL/g ± 0.007). Fetuses with abnormal FLV/FBW values were at significantly greater risk (P < .05) for PH development. Abnormal FLV/FBW values had higher diagnostic accuracy than abnormal US parameters. Sensitivity of the FLV/FBW was 89% (eight of nine fetuses); specificity, 88% (seven of eight fetuses); positive predictive value, 89% (eight of nine fetuses); negative predictive value, 88% (seven of eight fetuses); and accuracy, 88% (15 of 17 fetuses).
CONCLUSION: The FLV/FBW reflects the adequacy of intrauterine lung growth and can help predict PH.
© RSNA, 2004
Index terms: Fetus, growth and development Fetus, MR, 60.121411, 60.121412, 60.121416 Fetus, respiratory system Fetus, US, 60.12981, 60.12989 Lung, congenital malformation, 60.14
| INTRODUCTION |
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Various parameters measured at ultrasonography (US) have been proposed for use in predicting pulmonary hypoplasia. Some authors (3,4) have found that the lung area, the ratio of lung area to thoracic area, and the ratio of thoracic circumference to abdominal circumference are useful for evaluating possible pulmonary hypoplasia. However, unfavorable imaging conditions, including oligohydramnios and maternal obesity, can compromise spatial resolution at US.
Owing to advances in magnetic resonance (MR) imaging techniques, fast MR imaging modalities have been widely used to evaluate fetal abnormalities. Several authors (57) have demonstrated the use of fetal lung volume (FLV) measurement at fast MR imaging for prenatal assessment of pulmonary hypoplasia. In previous studies of MR imaging lung volumetry, the relative lung volume, defined as a percentage of the expected lung volume, was used to estimate fetal lung growth (8,9). However, expected lung volumes based on gestational age are not applicable to growth-restricted or macrosomic fetuses.
Currently, the ratio of lung volume to body weight is the most widely used parameter for diagnosing pulmonary hypoplasia (1,2). To the best of our knowledge, however, analyses of the correlation between FLV and the occurrence of pulmonary hypoplasia have been limited. In addition, to our knowledge, no comparative studies have been performed to determine whether US parameters or MR imaging parameters are better predictors of pulmonary hypoplasia. The purposes of our study were to determine the ratio of FLV to fetal body weight (FBW) by using US and MR imaging and to evaluate the use of this ratio for predicting pulmonary hypoplasia in fetuses at high risk.
| MATERIALS AND METHODS |
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The fetuses were assigned to two groups. One group consisted of 73 fetuses at low risk of developing pulmonary hypoplasia, who served as control subjects so that nomographs of FLV could be created. The characteristics of the pregnancies for the control group, with parameters expressed as mean values ± standard deviations, were as follows: maternal age, 29.9 years ± 5.0; gestational age at birth, 37.1 weeks ± 2.0; and birth weight, 2624 g ± 538. The control group included 26 fetuses with cerebral and neural tube abnormalities, 29 fetuses with intraabdominal and abdominal wall abnormalities, four fetuses with cardiac abnormalities, and 14 fetuses without abnormalities. These fetuses had no clinical manifestations of pulmonary hypoplasia, such as a bell-shaped thorax or the requirement for high ventilatory pressures, during postnatal follow-up.
The other group consisted of 17 fetuses who were at risk of developing pulmonary hypoplasia. These fetuses were considered the high-risk group and included nine fetuses with thoracoabdominal anomalies, four fetuses with renal anomalies associated with oligohydramnios, and four fetuses with musculoskeletal dysplasia. The clinical features of neonates with pulmonary hypoplasia are characterized by the immediate onset of severe respiratory insufficiency leading to neonatal death, with small lung capacity and the requirement of high ventilatory pressures in the absence of obstruction or atelectasis (1,2). A pathologic (ie, postmortem) diagnosis of pulmonary hypoplasia was made when the ratio of lung weight to body weight was less than 0.012 (10). In the high-risk group, nine neonates received a diagnosis of pulmonary hypoplasia on the basis of clinical or pathologic findings.
MR Imaging Examination and Image Interpretation
All fetuses were examined at MR imaging with a 1.5-T unit (Signa; GE Medical Systems, Milwaukee, Wis) and a torso-array coil. After a scout acquisition was performed with a fast spoiled gradient-echo sequence, a series of fetal MR images in the transverse, sagittal, and coronal planes were obtained for the depiction of abnormalities. To avoid misregistration caused by fetal movement, each new acquisition was performed according to the images obtained in the immediately preceding acquisition. MR imaging parameters were
/98 (repetition time msec/effective echo time msec), a 31.2-kHz bandwidth, and a total imaging time of 1825 seconds to acquire 15 contiguous sections. This acquisition time allowed maternal breath holding. The supervising radiologist (H.S.), who had a special interest in fetal MR imaging, optimized the field of view. After acquisition of the series of images depicting the abnormalities, transverse images were obtained through the chest of the fetus. The section thickness and intersection gap were 4 and 0 mm, respectively.
In this study, a series of MR images obtained in eight patients were degraded by fetal movement, so imaging was repeated. The cross-sectional area of the lung was measured on each image section by manually tracing the outline of the lung edge (Fig 1a). The masses and herniated viscera were excluded from MR lung volumetry in cases of congenital cystic adenomatoid malformation of lung, bronchopulmonary sequestration, and congenital diaphragmatic hernia (Fig 1b). The area was then multiplied by the thickness of the section, and the individual volumes were summed for each lung. It took 1520 minutes to perform MR image segmentation. The MR imagingmeasured FLV was determined by combining the volumes of both lungs. To normalize the lung volume to the FBW, the ratio of the FLV measured at MR imaging to the estimated FBW measured at US (FLV/FBW) was obtained.
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In addition, in the high-risk group, the bone thoracic circumference, thoracic area, heart area, and lung area were determined by using a cross-section of the fetal chest at the four-chamber-view level, with the heart in ventricular diastole. The abdominal circumference was measured in the transverse plane at the level of the junction of the umbilical vein and the portal sinus. To assess the clinical usefulness of US in predicting the development of pulmonary hypoplasia, three parameters were measured: the thoracic circumferencetoabdominal circumference ratio, the (thoracic area heart area)tothoracic area ratio, and the lung area.
Data and Statistical Analyses
The ratio of MR imagingmeasured FLV to US-estimated FBW, or FLV/FBW, was assessed throughout gestation in the control group. Regression analysis of the relationship between MR imagingmeasured FLV and either gestational age or US-estimated FBW was performed. In addition, the distribution of the FLV/FBW during pregnancy was examined.
The relationship between MR imagingmeasured FLV and either gestational age or US-estimated FBW was also examined in the high-risk group fetuses. The FLV/FBW values in the control group were compared with those in the high-risk group. In the high-risk group, the difference in FLV/FBW between the fetuses with and those without pulmonary hypoplasia also was analyzed. We then evaluated the effectiveness of the FLV/FBW and of the US parameters, including the thoracic circumferencetoabdominal circumference ratio, the (thoracic area heart area)tothoracic area ratio, and the lung area, in predicting pulmonary hypoplasia in the high-risk group. All FLV/FBW measurements that were 2 or more standard deviations below the mean were considered abnormal. All US parameter measurements that were 2 or more standard deviations below the mean also were considered abnormal, as previously reported (3). We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of each parameter for predicting pulmonary hypoplasia.
Data are presented as means ± standard deviations. The Pearson product moment correlation coefficient (r) was used to assess the strength of associations between MR imagingmeasured FLV and either gestational age or US-estimated FBW. Regression analysis was performed to evaluate the FLV/FBW according to gestational age. A Shapiro-Wilks test was used to evaluate the distribution of FLV/FBW values. Comparisons of FLV/FBW values between the control and high-risk groups were made by using the unpaired Student t test. The association between the development of pulmonary hypoplasia and the measurement of each parameter was analyzed by using the Fisher exact probability test. All calculations were performed by using JMP software (SAS Institute, Cary, NC). P < .05 was considered to indicate statistical significance.
| RESULTS |
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| DISCUSSION |
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Several authors have reported race-based differences in gestational agespecific birth weights. Wang et al (12) found that the gestational agespecific mean birth weights of Japanese babies were lower than those of white American babies. The MR imaging FLVs measured in the present study were smaller than those obtained by using US and MR imaging in other fetal lung volumetry studies. These findings indicate that there may be race-based differences in lung volumes (57).
We observed a correlation between MR imaging FLV and US FBW in the fetuses in the control group; the correlation with US FBW was higher than the correlation with gestational age. Shepard et al (13) similarly observed a strong correlation between the lung weight and the body weight of human fetuses at postmortem analysis. In their study, the FLV/FBW appeared to decrease with gestational age during the third trimester in fetuses in the control group.
Several authors have studied the lung weighttobody weight ratio at autopsy of human fetuses (13,14). Wigglesworth et al (14) found that the lung weighttobody weight ratio in fetuses with normal lung growth decreased during the second half of pregnancy. Duncan et al (6) reported that the median postmortem lung volume was 0.0317 of the fetal volume measured at MR imaging; these data are similar to our current study results.
The use of FLVs in the control group was a potential limitation of our study. The control group was not a strictly healthy population: It included fetuses with structural abnormalities. However, all of the control group fetuses had normal chest findings at US and diagnoses not known to be associated with pulmonary hypoplasia. Indeed, no control group fetuses had pulmonary hypoplasia at birth. These findings suggest that the measurements obtained in the control subjects examined in the present study represent reasonable estimates of normal lung development.
The FLV/FBW measurements in the high-risk group were significantly lower than those in the control group (P < .001). In addition, significantly low FLV/FBW values were observed in the fetuses with pulmonary hypoplasia as compared with the values observed in the fetuses who were at high risk for but did not have this abnormality (P = .019). The present study results indicate that fetuses who are at risk for pulmonary hypoplasia have a small lung volume relative to their body weight.
Pathologic parameters used to diagnose pulmonary hypoplasia include the lung weighttobody weight ratio, the radial alveolar count, and the amount of lung DNA relative to body weight (1,2). The radial alveolar count is the number of alveolar septa demarcated by a line starting at the center of a respiratory bronchiole and ending at the angles to the right of the nearest connective tissue septum. A radial alveolar count of less than 4.1 (ie, 75% of the mean normal count) has been shown to be one of the criteria used to diagnose pulmonary hypoplasia (1,2). Of these diagnostic parameters, the lung weighttobody weight ratio is the simplest and most widely used. Pulmonary hypoplasia is characterized by a substantial reduction in lung volume in the clinical setting. We hypothesized that the FLV/FBW might be useful for predicting pulmonary hypoplasia at birth.
We found that fetuses with abnormal FLV/FBW values had a significantly (P < .05) increased risk of developing pulmonary hypoplasia compared with fetuses with normal values. In our study, an FLV/FBW that was 2 or more standard deviations below the control mean value was considered abnormal. We observed a normal distribution of FLV/FBW values in the fetuses in the control group, in support of this definition. In previous studies (8,9) of fetal volumetry at MR imaging, in cases of congenital diaphragmatic hernia, the relative lung volume ratiodefined as the FLV relative to the expected valuecould be used to predict pulmonary hypoplasia and postnatal outcome. Mahieu-Caputo et al (8) found that neonatal death occurred in all fetuses with a relative lung volume ratio of less than 0.35. Paek et al (9) concluded that a relative lung volume ratio of less than 0.4 was suggestive of a poor postnatal outcome. However, the use of the FLV/FBW to predict pulmonary hypoplasia was not investigated in these studies.
Our study results suggest that an abnormally low FLV/FBW is a useful predictor of pulmonary hypoplasia. Given the limited number of cases in our study, further investigations should be performed to assess the clinical applicability of the FLV/FBW for the prediction of pulmonary hypoplasia.
The FLV/FBW had better diagnostic accuracy in the prediction of pulmonary hypoplasia in the fetuses who were at high risk than did the US parameters that we studied. Various US parameters have been proposed for use in assessing fetal lung development (3,4). Yoshimura et al (3) found that the thoracic circumferencetoabdominal circumference ratio and the lung area were useful for evaluating pulmonary hypoplasia. Vintzileos et al (4) reported that of the predictive indexes that they evaluated, the (thoracic area heart area)tothoracic area ratio had the most value for predicting pulmonary hypoplasia. However, two-dimensional US parameters are not necessarily representative of total lung volume.
Three-dimensional US lung volumetry has been investigated for use in assessing lung development, although the use of this examination to predict pulmonary hypoplasia remains to be evaluated (1517). US evaluation of fetal lung growth is limited by poor acoustic differentiation between fetal lung tissue and surrounding structures. Our study results show that the combination of MR imagingmeasured lung volume parameters and US-estimated body weight parametersspecifically, the FLV/FBWwas more useful for predicting pulmonary hypoplasia than any US parameter alone.
| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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Abbreviations: FBW = fetal body weight, FLV = fetal lung volume
Author contributions: Guarantors of integrity of entire study, S.T., Y.Y.; study concepts, M.T., H.S.; study design, S.T., M.T., K. Miyakoshi, H.S.; literature research, S.T., M.T., K. Miyakoshi, H.S.; clinical studies, S.T., Y.H., T.M., K. Ueno, O.N., K. Minegishi, H.I., H.S., K.I.; data acquisition, S.T., Y.H., T.M., K. Uehara, O.N., H.I., H.S.; data analysis/interpretation, S.T., M.T., K. Miyakoshi, H.S.; statistical analysis, S.T., M.T., K. Miyakoshi; manuscript preparation, definition of intellectual content, editing, revision/review, and final version approval, S.T., M.T., K. Miyakoshi, H.S., Y.Y.
| REFERENCES |
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