Quantitative Ultrasound Texture Analysis to Assess Developmental Differences in Twin and Singleton Fetal Lungs 1,2 1 2 2 2 2 Sleiman R. Ghorayeb , PhD, Christina Karras , BS, Insaf Kouba , MD, Matthew Blitz , MD, Nathan Keller , MD, Luis A. Bracero , MD 1School of Engineering and Applied Sciences, Ultrasound Research Laboratory, Hofstra University; 2Division of Maternal-Fetal Medicine, North Shore University Hospital
OVERVIEW Lung immaturity remains the most common cause of morbidity and mortality in preterm and early-term neonates. To date, no study has examined the relationship between fetal lung heterogeneity indices in twin and singleton fetuses. Although gestational age is the best predictor of lung maturity, respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN) and Bronchopulmonary Dysplasia (BPD) are not restricted to preterm (<34 weeks of gestation) births. Late preterm (34 0/7–36 6/7 weeks of gestation) and early term (37 0/7–38 6/7 weeks of gestation) infants have significantly higher rates of these complications than infants born at or beyond 39 weeks of gestation. Thus, identification of fetuses at risk for respiratory morbidity after birth due to lung prematurity or hypoplasia remains very important in the practice of obstetrics. The decision to proceed with or delay delivery is often dependent on the ability to properly assess fetal lung maturity and the presence or absence of lung hypoplasia.
METHODS – IMAGE ACQUISITION AND ANALYSIS
RESULTS
STATISTICAL ANALYSIS
We performed a cohort study (between January and June 2023) which included women with singleton and twin gestations who had routine pregnancy ultrasound examinations at ≥ 24 weeks gestational age, for a variety of indications.
During the study period fetal lung images were analyzed for 240 twin and 388 singleton fetuses respectively. In total, 388 singleton images and 474 twin images were analyzed. The largest number of fetal lung images for singletons (51 images) were obtained at 35 weeks of gestation, while the largest number of fetal lung images for twins (64 images) were obtained at 34 weeks of gestation.
HI was calculated for each fetal lung image. For both twin and singleton fetuses HI averages and standard deviations were generated for each gestational week from 24 weeks onward. Two sample t-tests were used to compare the mean HI at each gestational week for twin and singleton fetuses. Differences in mean HI between the higher and lower HI twin fetuses were also calculated at each gestational week to determine the change in HI between twin fetuses. A p-value < 0.05 denoted statistical significance in this study.
All images were obtained from GE Voluson E8 and E10 ultrasound systems for uniformity. The ultrasound machines were all equipped with convex array transducers with a frequency range from 3 to 7.5 MHz. All examinations were performed by experienced sonographers and reviewed by maternal fetal medicine physicians.
Average fetal lung HI for twin and singleton fetuses at each gestational week from 24 through 38 weeks of gestation is shown. . A statistically significant increase in mean HI was observed in singleton compared to twin fetuses from 35 through 38 weeks of gestation.
Representative ultrasound images of the fetal lung was achieved using a transverse view of the fetal thorax at the level of the fourchamber view. These were then examined using a proprietary program to determine the HI of each ultrasound image, with investigators blinded to the status of each lung. Exclusion criteria included poor image quality.
In singleton fetuses there was an increase in HI from a minimum of 1.278 at 24 weeks to 2.381 at 38 weeks (∆ +1.103). In twin fetuses the HI decreased from 1.483 at 24 weeks to 1.32 at 38 weeks (∆ -0.163) with a peak of 1.484 at 35 weeks of gestation. The average fetal lung HI for the higher and lower HI twins at each gestational week as well as the average ∆ twin HI throughout gestation are graphically shown.
AIM OF THE STUDY Quantitative ultrasound texture analysis of fetal lung has been proposed as a promising noninvasive method to predict the differences in fetal lung maturity, fetal lung hypoplasia, and neonatal respiratory morbidity between singleton and twin fetuses. Additional information then can be extracted from these images by applying quantitative processing methods that characterize the tissue. Our aim is to differentiate preterm (<37 weeks of gestation) from term (≥37 weeks of gestation) singleton fetal lungs and twin fetal lungs by quantitative texture analysis of ultrasound images. To quantify the extent of heterogeneity associated with lung maturity, we employed a unique, noninvasive technique to determine the Heterogeneity Index (HI) in twin fetal lung ultrasound images, and then compared HI in ultrasound of immature lungs with mature lungs of singleton pregnancies to twin pregnancies.
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HETEROGENEITY INDEX 1. The Floyd-Steinberg dithering algorithm was employed to transform the pixels of an ultrasound image into a binary map. 2. To obtain the HI value, for each dithered image, a region of interest (ROI) is selected. 3. The ROI is divided into a number of sub-ROIs which contain 100 pixels in each. 4. For each of the sub-ROIs, the number of white pixels are counted and then stored as percentages. 5. The average of the five highest and five lowest percentages are used to obtain HI value for the image. 6. Repeat this process on two different ROI’s on the most prominent lung in the image, then average to obtain the most accurate results. 7. An average of the five highest and five lowest peaks were used to obtain a HI value for the image.
The curves generated for the average higher HI twin and the average lower HI twin have very similar shapes throughout gestation. Both the higher and lower HI twin fetuses show relative peaks in HI at 35 weeks of gestation. The average ∆ twin HI increased gradually throughout gestation reaching a maximum at 38 weeks gestational age.
Weeks of Gestation
Singleton HI Average + SD
Twin HI Average + SD
p-value
24
1.278 + 0.076
1.483 + 0.264
0.044
25
1.446 + 0.226
1.512 + 0.403
0.60
26
1.412 + 0.128
1.417 + 0.213
0.93
27
1.423 + 0.172
1.454 + 0.404
0.80
28
1.372 + 0.212
1.441 + 0.237
0.30
29
1.491 + 0.200
1.348 + 0.184
0.018
30
1.515 + 0.277
1.386 + 0.190
0.068
31
1.387 + 0.138
1.417 + 0.267
0.63
32
1.509 + 0.252
1.413 + 0.181
0.071
33
1.512 + 0.251
1.418 + 0.225
0.12
34
1.474 + 0.266
1.437 + 0.226
0.54
35
1.621 + 0.248
1.484 + 0.268
0.007
36
1.690 + 0.362
1.478 + 0.305
0.003
37
2.262 + 0.465
1.388 + 0.189
<0.001
38
2.381 + 0.516
1.320 + 0.024
0.006
CONCLUSIONS A significant divergence in mean HI between singleton and twin fetuses from 35 through 38 weeks of gestation was found. While fetal lung HI in singleton fetuses may be useful in the prediction of preterm from term fetal lungs, the same may not be true in twin fetuses. It is important to recognize that most twin pregnancies are not carried to term and deliver at a mean age of 35.0 weeks of gestation. A peak in mean fetal lung HI in singleton fetuses has been previously shown to occur around 39 weeks of gestation. The National Center for Health Statistics – Division of Vital Statistics estimated that from 2016 to 2019 the mean gestational age for birth in singletons was 38.5 weeks while in twins it was 35.0 weeks. These mean gestational ages of birth correlate very closely to the timing of HI peaks found in this study for twin (35 weeks) and singleton (38 weeks) fetuses. Noninvasive determination of fetal lung maturity will likely continue to become an increasingly important concept in prenatal care as the percentage of spontaneous and medically indicated late preterm and early term births continues to rise in the United States.