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Assessment of Fetal Lung Growth in Utero with Echo-planar MR Imaging

¹ Department of Obstetrics and Gynaecology (K.R.D., P.N.B., I.R.J.)
² Magnetic Resonance Centre, Department of Physics (P.A.G., R.J.M.), City Hospital, Hucknall Rd, Nottingham, England, NG5 1PB.

	Abstract

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To measure changes in normal fetal lung volume with increasing gestation by using echo-planar magnetic resonance (MR) imaging.

MATERIALS AND METHODS: Fifty-six singleton fetuses were examined longitudinally with respect to lung volume by using echo-planar MR imaging between 19 weeks gestation and term.

RESULTS: Lung volume increased exponentially with gestation from 8 to 125 mL. Volume was related to gestation by using the equation, volume = 0.8375e^0.1249g (R² = 0.77), where g = gestation. Lung volume had a direct relationship to fetal volume with increasing gestation (R² = 0.75). There was no significant relationship between amniotic fluid volume and lung volume (R² = 0.11).

CONCLUSION: Variation in lung volumes can be assessed by using echo-planar MR imaging, regardless of variations in amniotic fluid volume. These measurements are less than those obtained from postmortem and neonatal studies but are similar to those obtained by using three-dimensional ultrasonography. Lung volume estimations obtained by using echo-planar imaging may have important clinical and research applications when noninvasive assessment of lung volume is required.

Index terms: Fetus, growth and development, 856.128 • Fetus, MR, 60.121416, 60.12146, 856.92 • Fetus, respiratory system, 856.92 • Magnetic resonance (MR), echo planar, 60.12146

	Introduction

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Accurate assessment of fetal lung volume has a number of potentially important clinical applications, particularly with regard to pulmonary hypoplasia. Antenatal measurement of the amount of lung tissue could be assessed prospectively when obstetric intervention is anticipated, but concerns regarding lung development exist.

Echo-planar magnetic resonance (MR) imaging has been used to assess lung volume changes in the fetus in a small cross-sectional study of abnormal pregnancies (1) and in infants with respiratory problems (2). The advantage of this technique is that images are acquired in milliseconds, and, thereby, the problems of subject motion that lead to distortion of conventional MR images are overcome (3). MR imaging is considered safe in the second and third trimesters. The results of follow-up examinations in infants in whom imaging was performed in utero have shown no ill effects as a result of imaging (4). More recently, attempts have been made to quantify fetal lung volume in normal pregnancy by using three-dimensional ultrasonography (US) (5,6). This technique has a reported error of 0.4%–1.0% (7,8) but, to our knowledge, has yet to be validated in pregnancies associated with abnormal amniotic fluid volume, which has been shown in the past to affect the accuracy of US measurements (9).

The purposes of this study were to measure lung volume serially by using echo-planar MR imaging, establish the pattern of lung volume variation in normal pregnancy, and relate these changes to overall fetal volume and amniotic fluid volume.

	MATERIALS AND METHODS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
This was an observational study of 56 women (mean maternal age, 28 years) with singleton fetuses who were examined two to five times each between 19 weeks gestation and term. The volunteers were recruited during 2 years. The Table summarizes the characteristics of these volunteers. All of the women in the study had uncomplicated pregnancies, with no medical complications in the antenatal period, and they subsequently were delivered of healthy babies. The birth weight of the neonates was in the normal range (above the fifth percentile) corrected for maternal height, maternal weight, parity, ethnic origin, and sex of the neonate. Exclusion criteria were multiple fetuses, medical antenatal complications such as hypertension and preeclampsia, and poor obstetric outcome, including admission of the baby to the neonatal intensive care unit in the postnatal period.

The volunteers were enrolled between 19 weeks gestation and term and were recruited when they presented for fetal anomaly imaging. Posters advertising the study were in the US department, and the volunteers were given a telephone number to call if they were interested in participation. Approval to perform imaging in the volunteers was obtained from the local hospital ethical committee, and written informed consent was obtained from the volunteers before the initial imaging session. No remuneration was paid to the volunteers, and the results were not available to the clinicians involved in the antenatal care of the volunteers.

Echo-planar MR imaging was performed on two to five occasions. Most volunteers (34) underwent four imaging examinations. Seven women underwent either two or five echo-planar imaging examinations, and eight underwent five examinations. On each occasion, images were obtained with the Nottingham 0.5-T purpose-built echo-planar MR imaging unit by using the multisection, modulus-blipped echo-planar sequence, which has been shown to be particularly useful. The methods used were as described in our pilot study (1). Thirteen contiguous sections were obtained with single-shot echo-planar MR imaging (effective echo time [TE], 30 msec; matrix, 128 x 128) in a total of 2.5 seconds, but the 10-mm section thickness used in the previous study was reduced to 7 mm to improve accuracy.

Each image was acquired in 130 milliseconds after a single excitation of the spin system. The inplane resolution was 3.5 x 2.5 mm (Fig 1). To image the entire fetus, we obtained the initial multisection images at the fundus of the uterus. By moving the bed on which the woman lay in 9.1-cm steps and repeating multisection imaging at each step, transaxial images were obtained until the fetus was no longer seen. The number of sets of 13 images ranged from three to five, depending on the size of the fetus. Therefore, the overall imaging time was expected to vary between 7.5 and 12.5 seconds. The radio frequency, gradient, and static magnetic field used were within the safety guidelines of the British National Radiological Protection Board (10).

View larger version (175K): [in this window] [in a new window]   Figure 1. Transaxial single-shot echo-planar MR image (effective TE, 30 msec; matrix, 128 x 128) of a cross section through the uterus at 37 weeks gestation shows the placenta (P) posteriorly, the high-signal-intensity amniotic fluid (A), and the fetal thorax (T), with both lungs (L) highlighted.

Statistical analysis to define a normal reference range was not used because of the small sample size and the potential error in longitudinal data related to the variable number of images obtained in each fetus; these images were not considered to be independent of one another. Growth trends between different subjects and in the overall group were not assessed. The results of statistical analyses were displayed graphically, and a line of best fit was constructed. An R² value indicative of the percentage of variation in the dependent variable (as measured by the sum of squares) was also calculated.

	RESULTS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
All echo-planar images of the fetal lungs and fetal volume were acquired in less than 10 seconds. Measurements of fetal lung volume varied with gestation, as illustrated in Figures 2 and 3. The exponential fit was the most significant (volume = 0.8375e^0.1249g [R² = 0.77], where g = gestation.). Sixteen (29%) of 56 serial measurements indicated a decrease in lung volume as term approached. The exponential fit was slightly better when these data were omitted (R² = 0.80). The logarithmic fit and linear fit were similar but inferior to the exponential fit (R² = 0.72). There was a direct correlation (R² = 0.75) between total fetal volume and fetal lung volume, but this relationship appeared to be less constant at higher fetal volumes (Fig 4). The median lung volume was 3.17% of the total fetal volume, with an interquartile range of 2.38%–3.79% (minimum 1.09%, maximum 6.10%). There was no relationship between lung volume and amniotic fluid volume (R² = 0.11).

View larger version (62K): [in this window] [in a new window]   Figure 2. Longitudinal variation in fetal lung volume measurements. Lung volume varies exponentially (line of best fit added) with gestation, but up to a third of individual fetuses have reduced lung volume between 28 weeks gestation and term.

View larger version (111K): [in this window] [in a new window]   Figure 3a. Transaxial single-shot echo-planar MR images (effective TE, 30 msec; matrix, 128 x 128) show increased lung volume in the same region of the fetal thorax at different gestational ages: (a) 22 weeks gestation, (b) 26 weeks gestation, (c) 29 weeks gestation, (d) 36 weeks gestation. L = left and right fetal lungs.

View larger version (114K): [in this window] [in a new window]   Figure 3b. Transaxial single-shot echo-planar MR images (effective TE, 30 msec; matrix, 128 x 128) show increased lung volume in the same region of the fetal thorax at different gestational ages: (a) 22 weeks gestation, (b) 26 weeks gestation, (c) 29 weeks gestation, (d) 36 weeks gestation. L = left and right fetal lungs.

View larger version (157K): [in this window] [in a new window]   Figure 3c. Transaxial single-shot echo-planar MR images (effective TE, 30 msec; matrix, 128 x 128) show increased lung volume in the same region of the fetal thorax at different gestational ages: (a) 22 weeks gestation, (b) 26 weeks gestation, (c) 29 weeks gestation, (d) 36 weeks gestation. L = left and right fetal lungs.

View larger version (167K): [in this window] [in a new window]   Figure 3d. Transaxial single-shot echo-planar MR images (effective TE, 30 msec; matrix, 128 x 128) show increased lung volume in the same region of the fetal thorax at different gestational ages: (a) 22 weeks gestation, (b) 26 weeks gestation, (c) 29 weeks gestation, (d) 36 weeks gestation. L = left and right fetal lungs.

View larger version (14K): [in this window] [in a new window]   Figure 4. Changes in fetal lung volume with increasing fetal volume. There is a significant association between the two volumes (R2 = 0.75); however, this relationship becomes less constant as the fetal volume increases.

	DISCUSSION

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
There is little information on fetal lung growth in vivo. In a number of studies, MR imaging has been used in fetal assessment but mainly for fetal abnormality. Small studies (12) of fetal and fetal organ volumes, which are two measurements of lung volume, have been performed by using fast MR imaging. To our knowledge, no other large studies of echo-planar MR imaging in normal pregnancy have been reported. This is the first time echo-planar MR imaging has been performed in a large number (56 pregnancies, 213 measurements) of normal pregnancies, and it follows small studies of abnormal pregnancy (20 measurements) (1) and neonates (nine measurements) (2). The described technique is a quick and convenient method of measuring organ volumes that we have found to be acceptable to the majority of pregnant women, and it is considered to be biologically safe. It offers the advantages over US of not being dependent on adequate amniotic fluid volume or maternal obesity for assessment of lung volume, but it is restrictive because of its limited availability and high cost.

As found in our pilot study of abnormal pregnancy (1), the exponential fit of lung volume was most statistically significant in normal pregnancy, but again, the values were approximately 50% of the reported postmortem lung volumes (13). Fetal volume has been shown by means of echo-planar MR imaging to correlate directly with fetal weight (14). Therefore, if we express the lung volume as milliliters per kilogram, the median (interquartile range) is 31.66 mL/kg (23.85–7.96 mL/kg). In a small (nine-subject) pediatric study (2) of lung volumes estimated by using echo-planar MR imaging, a median of 44 mL/kg (38.75–53.75 mL/kg) was reported. These results show a slightly closer relation, but differences between these values may well be related to the gaseous expansion at birth. The relevance of this finding could easily be investigated in an animal model. Importantly, lung volume estimations performed by using three-dimensional US show similar results and variation, particularly at term (5,6); this finding supports the use of these two techniques for the estimation of lung volume in utero.

In many lung disorders, lung volume abnormalities are associated with oligohydramnios, which may reduce the reliability of the transmission of ultrasound waves but is not a dependent factor in obtaining echo-planar images. Therefore, it is important that intrauterine and extrauterine lung volumes in the same fetuses during normal pregnancies be compared in a future study to confirm this effect. The findings of such studies have potential clinical application in the management of pulmonary hypoplasia.

The finding that lung volume decreases toward term in a substantial number of pregnancies is difficult to explain, but it was also reported with longitudinal three-dimensional US lung volume measurements. Errors in measurement may contribute to this effect and thereby lead to questions regarding the reliability of the technique. Fetal breathing could have an effect on lung volume, but at present, this is impossible to assess at echo-planar imaging. Our initial hypothesis to explain this effect was a proposed reduction in amniotic fluid volume toward term, but we found this not to be the case. Increased crowding within the uterus and chest compression may explain this phenomenon.

The changes in lung volume that we demonstrated with this study could be useful in monitoring the effects of steroids and other new therapies on changes in lung volume, particularly in pregnancies complicated by pulmonary hypoplasia. It remains to be seen whether volumetric estimations offer advantages over the number of two-dimensional US techniques available; however, prenatal MR imaging assessment of the fetus has already been shown to offer benefits over conventional US in the assessment of congenital diaphragmatic hernia (15). Further investigation of the relationship between fetal volume and neonatal lung function must be performed before the described echo-planar MR imaging technique can be applied clinically.

	Footnotes

 
Supported by a grant from the Medical Research Council

Address reprint requests to K.R.D.

Author contributions: Guarantors of integrity of entire study, K.R.D., P.A.G., P.N.B.; study concepts, P.A.G., P.N.B., I.R.J.; study design, P.A.G., P.N.B., I.R.J., K.R.D.; definition of intellectual content, P.A.G., P.N.B., I.R.J., K.R.D.; clinical and experimental studies, K.R.D., R.J.M., P.A.G.; data acquisition, K.R.D., R.J.M., P.A.G.; data analysis, K.R.D., R.J.M.; statistical analysis, K.R.D.; manuscript preparation, K.R.D.; manuscript editing, P.A.G., P.N.B., I.R.J.; manuscript review, P.N.B.

Received March 12, 1998; revision requested May 19, 1998; revision received June 30, 1998; accepted August 21, 1998.

	References

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 

1. Baker PN, Johnson IR, Gowland PA, Freeman A, Adams V, Mansfield P. Estimation of fetal lung volume using echo-planar magnetic resonance imaging. Obstet Gynecol 1994; 83:951-954.[Medline]
2. Chapman B, O'Callaghan C, Coxon R, et al. Estimation of lung volume in infants by echo planar imaging and total body plethysmography. Arch Dis Child 1990; 65:168-170.[Abstract]
3. Johnson IR, Stehling MK, Blamire AM, et al. Study of internal structure of the human fetus in utero by echo planar magnetic resonance imaging. Am J Obstet Gynecol 1990; 163:601-607.[Medline]
4. Baker PN, Johnson IR, Harvey PR, Gowland PA, Mansfield P. A three year follow up of children imaged in utero using echo-planar magnetic resonance. Am J Obstet Gynecol 1994; 170:32-34.[Medline]
5. D'Arcy TJ, Hughes SW, Chiu WSC, et al. Estimation of fetal lung volume using enhanced 3-dimensional ultrasound: a new method and first result. Br J Obstet Gynaecol 1996; 103:1015-1020.[Medline]
6. Lee A, Kratochwil A, Stumpflen I, Deutinger J, Bernaschek G. Fetal lung volume determination by three-dimensional ultrasonography. Am J Obstet Gynecol 1996; 175:588-592.[Medline]
7. King DL, King DL, Jr, Shao MY. Evaluation of in vitro measurement of a three dimensional ultrasound scanner. J Ultrasound Med 1991; 10:77-82.[Abstract]
8. Riccabonna M, Nelson TR, Pretorus DH. Three-dimensional ultrasound: accuracy of distance and volume measurements. Ultrasound Obstet Gynaecol 1996; 7:429-434.[Medline]
9. Campbell S, Wilkin D. Ultrasonic measurement of fetal abdominal circumference in estimation of fetal weight. Br J Obstet Gynaecol 1975; 82:689-697.[Medline]
10. National Radiological Protection Board. Her majesty's stationery office (HMSO) Vol. 2. Didcot, England: Chilton, 1991.
11. Baker PN, Johnson IR, Gowland PA, et al. Measurement of fetal liver, brain and placental volumes with echo-planar magnetic resonance imaging. Br J Obstet Gynaecol 1995; 102:35-39.[Medline]
12. Garden AS, Roberts N. Fetal and fetal organ volume estimations with magnetic resonance imaging. Am J Obstet Gynecol 1996; 175:442-448.[Medline]
13. Langston C, Kida K, Reed M, Thurlbeck WM. Human lung growth in late gestation and in the neonate. Am Rev Respir Dis 1984; 129:607-613.[Medline]
14. Baker PN, Johnson IR, Gowland PA, et al. Fetal weight estimation by echo-planar magnetic resonance imaging. Lancet 1994; 343:644-645.[Medline]
15. Hubbard AM, Adzick NS, Cromblehome TM, Haselgrove JC. Left-sided congenital diaphragmatic hernia: value of prenatal MR imaging in preparation for fetal surgery. Radiology 1997; 203:636-640.[Abstract/Free Full Text]

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