Published online before print February 7, 2008, 10.1148/radiol.2471070682
(Radiology 2008;247:197-203.)
© RSNA, 2008
Fetal Body Volume at MR Imaging to Quantify Total Fetal Lung Volume: Normal Ranges1
Mieke M. Cannie, MD,
Jacques C. Jani, MD, PhD,
Filip Van Kerkhove, MD,
Joke Meerschaert, MD,
Frederik De Keyzer, MSc,
Liesbeth Lewi, MD,
Jan A. Deprest, MD, PhD, and
Steven Dymarkowski, MD, PhD
1 From the Departments of Radiology (M.M.C., F.V.K., J.M., F.D.K., S.D.) and Obstetrics and Gynaecology (J.C.J., L.L., J.A.D.), University Hospital Gasthuisberg, 3000 Leuven, Belgium. Received April 17, 2007; revision requested June 12; revision received July 18; accepted August 16; final version accepted September 28. J.C.J. supported by a doctoral grant from the European Commission via the Fifth Framework Programme (EuroTwin2Twin, QLG1-CT-2002-01632).
Address correspondence to J.A.D. (e-mail: Jan.Deprest{at}uzleuven.ac.be).
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ABSTRACT
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Purpose: To prospectively determine normal ranges of total fetal lung volume (TFLV) based on fetal body volume (FBV) and to determine whether prediction of TFLV based on such ranges is independent of fetal biometric indexes.
Materials and Methods: The study was approved by the Ethics Committee on Clinical Studies; informed consent was obtained. Magnetic resonance imaging volumetric measurement of fetal lung, liver, and body was performed in 200 fetuses without abnormalities affecting these structures. FBV was assessed with planimetric measurements by using T2-weighted half-Fourier rapid acquisition with relaxation enhancement at 16–40 weeks of gestation. TFLV was correlated to gestational age (GA), liver volume, and FBV. Observed-expected (O/E) ratio for TFLV was calculated by expressing the observed TFLV as a percentage of the expected mean TFLV for GA, liver volume, or FBV. Three groups of fetuses were defined on the basis of biometric percentiles for fetal weight obtained through ultrasonography: fetuses with weight at or below the 5th percentile, those with weight at or above the 95th percentile, and those with weight between these two percentiles (eutrophic). Median O/E ratios, based on GA and FBV, in fetuses with weight below the 5th percentile and in those with weight above the 95th percentile, were compared with median O/E ratio of eutrophic fetuses (Mann-Whitney U test).
Results: TFLV correlated best with FBV, according to the following cubic fit: TFLV = [(2.0 · 10–9) · FBV3] – [(1.19 · 10–5) · FBV2] + (0.0508 · FBV) – 1.79 (r2 = 0.85, P < .001). In 174 eutrophic fetuses, normal median O/E ratio based on GA was 99.1% (range, 31.2%–158.0%), which was higher than that in 11 fetuses with weight at or below the 5th percentile (46.2%; range, 15.7%–87.3%) (P < .01) and lower than that in 15 fetuses with weight at or above the 95th percentile (146.8%; range, 87.2%–204.2%) (P < .01). Normal median O/E ratio, based on FBV, was independent of biometric indexes irrespective of the percentile for fetal weight.
Conclusion: FBV correlated best with TFLV, irrespective of biometric variables.
© RSNA, 2008
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INTRODUCTION
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Accurate prediction of lethal pulmonary hypoplasia is a clinical need, particularly in the second trimester of pregnancy (1–3). At postmortem, the diagnosis of pulmonary hypoplasia is based on the measurement of the lung–body weight ratio (4). Lungs are classified as being hypoplastic when the lung–body weight ratio is 0.015 or less prior to 28 weeks of gestation and 0.012 or less after 28 weeks of gestation (4). In the prenatal period and in an attempt to imitate what is done postnatally as postmortem with the lung–body weight ratio, lung development can be assessed with a variety of medical imaging techniques, which in essence help measure lung size as a proportion to what is expected in a healthy fetus of the same gestational age (GA) or a fetus that has the same biometric variables (5–9). This measurement as a proportion results in the so-called observed-expected (O/E) ratio for total fetal lung volume (TFLV), or relative lung volume (5). This expression of the lung volume of the affected fetus as a percentage rather than as an absolute lung volume allows a better understanding of the severity of the condition of the affected lung not only for parents but also for clinicians (9).
To date, the only available normal ranges of TFLV are typically calculated on the basis of GA and would exclude multiple pregnancies or fetuses under the 5th and above the 95th percentile for weight as determined by using ultrasonography (US) (6,7).
Several biometric markers that can be obtained through the same magnetic resonance (MR) imaging examination, such as fetal body volume (FBV) or liver volume, have been proposed as an alternative to calculate relative lung volume in fetuses with normally developed lungs and those affected with pulmonary hypoplasia (5,8,9). It was recently demonstrated that, in healthy fetuses, TFLV correlated better with FBV than with GA (9). The advantage of these biometric markers is that they may be applied irrespective of the actual fetal growth, expressed as a percentile for weight, or they may be applied if the pregnancy is multiple, but normal ranges of TFLV that are based on FBV are not yet available (9). Thus, the purpose of our study was to prospectively determine normal ranges of TFLV that are based on FBV and to determine whether prediction of TFLV that is based on such ranges is independent of fetal biometric indexes.
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MATERIALS AND METHODS
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Study Participants and Design
The study was approved by the Ethics Committee on Clinical Studies of University Hospital Gasthuisberg, Leuven, Belgium; informed consent was obtained. This was a single-institution, cross-sectional, prospective study. All consecutive patients who were referred between January 2005 and October 2006, who underwent a fetal MR examination as clinically indicated, and who matched the study criteria were asked to participate in the study. In all fetuses, US examination was performed within 1 week or less before the MR examination, and biometric percentiles for weight derived from singleton normal ranges were provided (10). In all patients, GA was dated on the basis of the first-trimester US scan, which is routinely offered in Belgium. Fetuses were included irrespective of their biometric percentiles for weight or whether they were from singleton or multiple pregnancies. Twin fetuses that were included were typically referred for laser therapy for severe twin-to-twin transfusion syndrome (TTTS) with stage I–III and nonhydropic stage IV according to Quintero et al (11), with selective intrauterine growth retardation, or with a discordant fetal structural anomaly.
Fetuses suspected of having anomalies involving the fetal thorax (potentially affecting lung volume) or any other structural abnormalities (potentially affecting body volume or liver size) were excluded. Also excluded were fetuses from diabetic patients and those with MR images degraded by fetal motion artifacts despite fetal sedation. During the fetal MR examination, care was taken by the attending radiologist to ensure that the entire fetus was imaged so that all biometric variables could be obtained.
The 200 fetuses that were included were imaged between 16 and 40 weeks GA with no structural fetal anomalies (singleton fetus with extrafetal anomalies [n = 23]; normal twin fetus from a twin pair with a discordant anomaly [n = 13]; both fetuses from a twin pregnancy affected by selective intrauterine growth retardation [n = 6]; and fetuses from pregnancies complicated by TTTS stage I [n = 10], stage II [n = 14], stage III [n = 14], or nonhydropic stage IV [n = 3]), seroconversion for cytomegalovirus or toxoplasmosis (n = 53), isolated mild hydrocephaly (n = 12) or other central nervous system abnormalities (n = 35), unilateral renal anomalies (n = 8), gastrointestinal anomalies (n = 4), complications following procedures for fetal heart anomalies (n = 2), facial dysmorphism (n = 2), and a fetal ovarian cyst (n = 1). Postnatal clinical follow-up data (183 of 191) or postmortem reports (eight of 191) were available in 95.5% (191 of 200) of fetuses, which were included in the TFLV range, and normal lung development was confirmed in all 191 fetuses.
MR Imaging
MR imaging was performed with a clinical 1.5-T whole-body unit (Magnetom Sonata; Siemens Medical Systems, Erlangen, Germany) with gradient-switching capabilities of 25 mT/m in 300 µsec. A maternal sedative, flunitrazepam (Rohypnol; Roche, Basel, Switzerland), 0.5 mg, was orally administered 30 minutes prior to MR imaging to reduce fetal movements and related motion artifacts. Patients were positioned in a left lateral position to prevent supine hypotension syndrome (aortocaval compression), with a combined six-channel phased-array body coil and a two-channel spine coil positioned over the lower pelvic area.
The MR protocol for this study consisted only of T2-weighted images. Parameters of the T2-weighted images consisted of repetition time msec/echo time msec, 1000/88; 38 adjacent sections with a 4-mm section thickness; intersection gap, 0 mm; field of view, 380 x 380 mm; matrix, 173 x 256; partial Fourier factor, 5/8; resulting pixel resolution, 1.8 x 1.5 x 4.0 mm3; and bandwidth, 475 Hz/pixel.
T2-weighted MR imaging was performed by using a single-shot half-Fourier rapid acquisition with relaxation enhancement sequence in orthogonal transverse, coronal, and sagittal planes according to the fetal orientation. No breath hold was requested of the patient. The radiologist (M.M.C., with 3 years of experience with fetal MR at the start of the study) adjusted the field of view, the number of sections, and image orientation for each fetus as required for optimal acquisition of images and measurements. Sequences in which images were degraded by fetal motion were repeated with the same parameters. The mean examination time was 20 minutes ± 4 (standard deviation) per patient.
MR Planimetry
Planimetric measurements of lung and liver volumes were all performed by one author (M.M.C.). For total FBV planimetric measurements, one of four possible operators (M.M.C., with 3 years of experience, or J.C.J., F.V.K., or J.M., with 1 year of experience each at the start of the study) performed the measurements. Lung and liver volumes were calculated on the T2-weighted half-Fourier rapid acquisition with relaxation enhancement MR images in the transverse plane (12) by using the sequences that allowed complete imaging of either the lungs or the liver without motion artifacts.
As to the plane wherein delineations were performed to obtain FBV, we used any of the transverse, coronal, or sagittal planes that provided the best images, as demonstrated in an earlier study (13).
The corresponding areas of lung, liver, and total fetal body were determined on each section by using free-form regions of interest on a picture archiving and communication system (Impax; Agfa-Gevaert, Mortsel, Belgium). The measured areas were added and multiplied by the section thickness to determine the entire volume of the right and left lungs (allowing calculation of TFLV), liver volume, and total FBV (Fig 1).

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Figure 1a: (a, b) T2-weighted single-shot half-Fourier rapid acquisition with relaxation enhancement MR images (1000/88) of monochorionic diamniotic twin pregnancy at 19 weeks 5 days of gestation. Fetus 1 (left) has selective intrauterine growth restriction and fetus 2 (right) is eutrophic. (a) Sagittal view shows delineation of FBVs of both fetuses with freehand regions of interest. (b) Transverse view shows delineation of fetal lungs. O/E ratio that was based on GA was 36.9% for fetus 1 and 113.8% for fetus 2, whereas corresponding O/E ratio that was based on FBV was 58.0% for fetus 1 and 94.3% for fetus 2. Arrows show intertwined membrane.
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Figure 1b: (a, b) T2-weighted single-shot half-Fourier rapid acquisition with relaxation enhancement MR images (1000/88) of monochorionic diamniotic twin pregnancy at 19 weeks 5 days of gestation. Fetus 1 (left) has selective intrauterine growth restriction and fetus 2 (right) is eutrophic. (a) Sagittal view shows delineation of FBVs of both fetuses with freehand regions of interest. (b) Transverse view shows delineation of fetal lungs. O/E ratio that was based on GA was 36.9% for fetus 1 and 113.8% for fetus 2, whereas corresponding O/E ratio that was based on FBV was 58.0% for fetus 1 and 94.3% for fetus 2. Arrows show intertwined membrane.
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On the MR images, lung volume, liver volume, and total FBV could be measured in all fetuses. The time required to measure the parameters ranged between 5 and 10 minutes for the lungs and liver and was up to 30 minutes for the total FBV, depending on fetal size and sectional plane used for delineation.
Statistical Analysis
Linear regression analysis and analysis with polynomial equations of the second and third orders were respectively performed to fit separate curves to the medians and to determine the significance of association between TFLV and GA, liver volume, and FBV separately. Each regression curve used a least-squares approximation of the curve to the points. The best quality fit of our data for the TFLV with GA, liver volume, and FBV, especially at the extremes of the curves, was obtained by using cubic regression equations (14–16).
Correlation between left and right lung volumes was performed by using linear regression analysis. Subsequently, the O/E ratio was calculated by expressing the observed TFLV as a percentage of the expected mean TFLV for GA, liver volume, or FBV.
Fetuses were classified in three groups on the basis of their biometric percentile for weight measured at US: fetuses with weight at or below the 5th percentile, fetuses with weight at or above the 95th percentile, and fetuses with weight between these two percentiles (eutrophic fetuses). Measurement of biometric percentiles for weight by using US were based on the Haddlock equation by taking into account the head circumference, the abdominal circumference, and the femur length (10). On the basis of GA, the median O/E ratios in both the group of fetuses with weight at or below the 5th percentile and the group of fetuses with weight at or above the 95th percentile were compared with the median O/E ratio of the eutrophic fetuses by using the Mann-Whitney U test. The same comparison was performed for the median O/E ratios on the basis of the FBV.
Regression analysis was performed for FBV in terms of GA. Subsequently, in each fetus the observed FBV was expressed as a percentage of the appropriate expected mean for GA. The O/E ratio that was based on FBV was finally correlated with the biometric percentiles for weight at US by using linear regression analysis.
Data were expressed as the median and range. The data were analyzed by using a statistical software package (SPSS 14.0; SPSS, Chicago, Ill) and spreadsheet software (Excel for Windows 2000; Microsoft, Redmond, Wash). A P value of less than .05 was considered significant.
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RESULTS
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Regression Curves of TFLV with GA, Liver Volume, and FBV
The median TFLV was 41.7 mL and ranged from 1.0 mL at an FBV of 47 mL to 132.0 mL at an FBV of 3563.6 mL. TFLV showed a strong correlation with FBV and increased according to the following cubic fit: TFLV = [(2.0 · 10–9) · FBV3] – [(1.19 · 10–5) · FBV2] + (0.0508 · FBV) – 1.79 (r2 = 0.85, P < .001). TFLV correlated also with fetal liver volume and GA; however, the strength of the correlation was best with FBV (Table, Fig 2). There was a strong linear correlation between left and right lung volumes throughout the entire range of FBVs. The right lung volume was calculated as follows: (1.26 · LLV) + 0.90 (r2 = 0.94), where LLV is the left lung volume. The right lung volume accounted for 56.8% of the TFLV.

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Figure 2: Plot of TFLV with FBV in fetuses with normal lungs shows strong correlation between these two parameters, with mean (solid line) and 95% confidence intervals for prediction (dashed lines).
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O/E Ratio in Eutrophic Fetuses, Fetuses with Weight at or below 5th Percentile, and Fetuses with Weight at or above 95th Percentile
There were 174 eutrophic fetuses, 11 fetuses with weight at or below the 5th percentile, and 15 fetuses with weight at or above the 95th percentile. The median O/E ratio in eutrophic fetuses, on the basis of GA, was 99.1% (range, 31.2%–158.0%) and was larger than the corresponding O/E ratio of 46.2% (range, 15.7%–87.3%) for fetuses with weight at or below the 5th percentile (P < .01) and smaller than the O/E ratio of 146.8% (range, 87.2%–204.2%) for fetuses with weight at or above the 95th percentile (P < .01) (Fig 3). In eutrophic fetuses, the median O/E ratio that was based on FBV was 99.1% (range, 45.9%–177.3%) and was not significantly different from the corresponding O/E ratio of 97.9% (range, 52.5%–175.4%) for fetuses with weight at or below the 5th percentile (P = .52) nor from the O/E ratio of 112.2% (range, 68.2%–157.8%) for fetuses with weight at or above the 95th percentile (P = .09) (Fig 3). Similarly, the median O/E ratio that was based on FBV for eutrophic fetuses was not significantly different from the O/E ratio that was based on GA (P = .89).

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Figure 3a: (a, b) Box plots of O/E ratio in 174 eutrophic fetuses, 11 fetuses at or below 5th percentile, and 15 fetuses at or above 95th percentile with normal lungs. (a) Plot based on GA. (b) Plot based on FBV. Solid line within each box corresponds to median. Upper and lower bars of boxes correspond to first and third quartiles, respectively. Two vertical lines (whiskers) outside box extend to smallest and largest observations within 1.5 times interquartile range of quartiles (interquartile range extends from third quartile to first quartile). Median O/E ratio that was based on FBV was similar among three predefined groups, but it was different for O/E ratio that was based on GA.
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Figure 3b: (a, b) Box plots of O/E ratio in 174 eutrophic fetuses, 11 fetuses at or below 5th percentile, and 15 fetuses at or above 95th percentile with normal lungs. (a) Plot based on GA. (b) Plot based on FBV. Solid line within each box corresponds to median. Upper and lower bars of boxes correspond to first and third quartiles, respectively. Two vertical lines (whiskers) outside box extend to smallest and largest observations within 1.5 times interquartile range of quartiles (interquartile range extends from third quartile to first quartile). Median O/E ratio that was based on FBV was similar among three predefined groups, but it was different for O/E ratio that was based on GA.
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Correlation between Biometric Percentiles for Weight at US and O/E Ratio That Was Based on FBV at MR Imaging
FBV correlated with GA and increased according to the following cubic fit: FBV = (–0.38 · GA3) + (34.66 · GA2) – (875.85 · GA) + 6921.20 (r2 = 0.91, P < .001). Biometric percentiles for weight as determined at US within 7 days prior to MR imaging examination correlated with the O/E ratio that was based on FBV, which was calculated as follows: (0.66 · WUS) + 64.73, where WUS is the percentile for weight determined at US (r2 = 0.58, P < .001) (Fig 4).
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DISCUSSION
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We confirmed in a large series of cases that FBV, as determined by using fetal MR imaging, correlated better to TFLV than liver volume or GA as per first-trimester US measurements. Our study provides normal ranges of TFLV with FBV over a wide GA range from 16 to 40 weeks gestation. We also showed that proportional TFLV is independent of fetal biometric measurements as determined by using US.
In routine clinical practice, fetuses suspected of having pulmonary hypoplasia have the same, if not a higher, risk for being small or large for GA and may be part of a multiple pregnancy. However, normal ranges are based on singleton pregnancies and on fetuses that are typically within the 5th to 95th growth percentiles. So far, normal ranges for TFLV throughout pregnancy in multiple pregnancies are not yet available. Therefore, it would seem inappropriate to use normal ranges derived from eutrophic singleton pregnancies.
The results of a longitudinal study in which differences of the fetal growth among singleton and multiple pregnancies were evaluated indicated that the predicted estimated fetal weight for twin and triplet pregnancies is between that of eutrophic singletons and singleton fetuses with weight below the 10th percentile (17). According to the birth data from live-born triplet infants in another study (18), from 26 to 35 weeks, the average triplet newborn has a weight corresponding to approximately the 30th percentile level compared with singletons; after 35 weeks, triplet birth weights decrease progressively below those of singletons, reaching the 10th percentile at 38 weeks. On the basis of these data and our findings, one would expect that measurement of the O/E ratio in a fetus derived from a multiple pregnancy and suspected of having pulmonary hypoplasia would be erroneously smaller when calculations are based on GA rather than on FBV.
The use of biometric variables, such as FBV or liver volume, obtained during the same MR examination is made with the assumption that measurements are performed on an organ not affected by the studied disease. In contrast, when FBV is affected (eg, in the case of massive hydrops), normative values that are based on FBV cannot be used. In such a case, it is preferable to use normative curves that are based on the liver volume if it is not affected. Another example is a fetus from a poorly equilibrated diabetic patient with possible increased FBV caused by a redistribution of fat but with unaltered lung size.
In our study, fetal growth assessment was based on biometric indexes determined by using US rather than MR imaging. It has been shown earlier that FBV can be more accurately determined by using MR imaging than US for assessment of fetal weight at term (19). However, in our study, US fetal biometric measurements correlated well with O/E ratio that was based on FBV measurement by using MR imaging.
The measurement of FBV is a time-consuming enterprise, requiring up to one-half hour in experienced hands. We are not aware of current availability of any semiautomatic method that might shorten this process at this time. Therefore, it would seem more logical to recommend its use only in circumstances when it is truly required (ie, for fetuses with weights above or below the eutrophic percentiles and for multiple pregnancies). This seems warranted, as we did not find any difference between the O/E ratio that was based on GA and the O/E ratio that was based on FBV for eutrophic fetuses.
Our study had some limitations. First, we did not include fetuses from healthy volunteers or fetuses that were, in other words, healthy. We used available data obtained from pregnancies that required fetal MR imaging for other purposes but in which fetal body and lung contour were not at stake. Moreover, nearly one-half of the fetuses were imaged for placental abnormalities and, thus, by definition, were structurally healthy fetuses. As it was stated earlier, plethoric fetuses derived from a TTTS stage IV pregnancy were excluded. However, when the data set becomes available from healthy fetuses, additional work will be necessary.
Second, we included fetuses with oligohydramnios from pregnancies affected by TTTS to give normal ranges of lung development. Nevertheless, it is well known from the literature that only fetuses with early and prolonged oligohydramnios are known to be at risk for pulmonary hypoplasia (20). In fact, all our assessments in fetuses affected with TTTS were performed at early onset of TTTS irrespective of the staging determined by Quintero et al (11). It is also well known from the literature that fetuses derived from a pregnancy with TTTS have not been reported to have developed pulmonary insufficiency at birth (21). Finally, results of clinical and/or postmortem follow-up in more than 95% of the population in our study clearly confirmed that none of the fetuses had pulmonary hypoplasia. Consequently, we thought it appropriate to include the data from the twin pregnancies in the data for the normal range of total FLV.
Third, we did not extend our study to fetuses that were suspected of having pulmonary hypoplasia, with the goal to demonstrate the effect of proportional estimation of lung size on FBV in eutrophic or dystrophic fetuses, as well as in multiple pregnancies. This factor would allow an analysis of covariance for given biometric variables for comparison between affected and healthy fetuses and would reveal differences, if any, between these two populations. Although we suspect no differences will be found, this possibility should be confirmed in future studies.
Finally, we did not test reproducibility of TFLV, liver volume, or FBV measurements. Reproducibility of TFLV and liver volume measurements in trained hands has been shown earlier (9) and was performed in our study by an experienced radiographer. The FBV measurements were performed by one experienced and three less experienced operators, as we have proved earlier that less experienced operators can also accurately measure FBV (9).
In conclusion, we demonstrated that TFLV can be predicted from FBV irrespective of fetal growth and GA. We also provided normal ranges of TFLV on the basis of FBV. In fetuses suspected of having pulmonary hypoplasia, the benefit of FBV measurement in the prediction of postnatal survival remains to be determined.
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ADVANCES IN KNOWLEDGE
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- Fetal body volume (FBV) determined with MR imaging correlates better (r2 = 0.85) to total fetal lung volume (TFLV) than to liver volume measurements (r2 = 0.78) or gestational age (GA) (r2 = 0.77), with P < .001 for all correlations.
- TFLV can be predicted by using FBV measured at MR imaging irrespective of growth pattern or weight of the individual fetus.
- For eutrophic fetuses (5th–95th percentile for weight), GA is reliable for prediction of TFLV; in contrast, for fetuses with weight outside the range of 5th–95th percentile as defined by using biometric measurement at US, FLV is better predicted by using FBV.
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IMPLICATION FOR PATIENT CARE
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- Our study provides normal ranges of FBV and corresponding TFLV, and these ranges can be used for reference lung volumes of fetuses that are suspected of having pulmonary hypoplasia, irrespective of number of fetuses, weight, growth, or GA.
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FOOTNOTES
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Abbreviations: FBV = fetal body volume GA = gestational age O/E ratio = observed-expected ratio TFLV = total fetal lung volume TTTS = twin-to-twin transfusion syndrome
Author contributions: Guarantors of integrity of entire study, M.M.C., J.C.J., J.A.D., S.D.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, M.M.C., J.C.J., F.V.K., J.M., L.L., J.A.D.; clinical studies, M.M.C., J.C.J., F.V.K., J.M., L.L., J.A.D., S.D.; statistical analysis, J.C.J., F.D.K.; and manuscript editing, all authors
Authors stated no financial relationship to disclose.
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