Evaluation of fetal brain development in growth restriction subtypes using brain MRI volume measurement

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Fei. Xie, Chun. Yan. Zhong, Wei Tang, Song Peng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7093866/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background This retrospective study aims to explore the value of brain MRI volume measurements in evaluating fetal brain development in fetal growth restriction (FGR) fetuses, by comparing different FGR subtypes with appropriate gestational age (AGA) fetuses. Methods A total of 158 fetal brain MRI with suspected abnormal development, identified through ultrasound screening at this hospital between 2021 and 2025 were analyzed. Ninety-eight cases were FGR fetuses (43 early-onset subtype and 55 late-onset subtype), and 60 were AGA fetuses. Three-dimensional reconstruction and image segmentation were performed on fetus intracranial tissues, brain parenchyma, cerebellum and brainstem. Changes in brain volume at different gestational weeks were analysed to assess the development of fetal brain anatomical structures. Results In both groups, the Pearson correlation coefficients for brain parenchyma, brain stem, and cerebellum volume with head circumference and gestational age were greater than 0.8, indicating a strong correlation. The difference in brain parenchyma, brain stem, and cerebellum volume between early-onset FGR fetuses and AGA fetuses was statistically significant. The difference in brain parenchyma volume between late-onset FGR fetuses and AGA fetuses was statistically significant, while there was no statistically significant difference in brain stem volume between FGR and AGA fetuses at 34 weeks or later, nor in cerebellum volume at 36 weeks or later. Discussion Fetal brain MRI at gestation serve as a valuable supplement to ultrasound screening. This technique helps assess brain development in fetuses with various FGR subtypes, offering further reference for prenatal diagnosticians in evaluating fetal brain development. Further studies are needed to dynamically monitor and assess the prognosis of brain MRI volumes in fetuses with early-onset FGR. Magnetic resonance imaging Fetal growth restriction Fetal brain volume Image segmentation Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Fetal growth restriction (FGR), characterized by low body weight due to pathological factors that impair fetal growth potential, affects as high as 5–10% of pregnancies and approximately 30 million fetuses worldwide each year [ 1 ] . Studies have found that FGR is most commonly caused by placental insufficiency, resulting in significant perinatal morbidity and mortality [ 2 ] . Despite a universal consensus on its definition has not been reached, there is global agreement on its classification into early-onset and late-onset subtypes according to the timing of occurrence [ 3 ] . Early-onset FGR refers to delayed fetal growth that occurs earlier than 32 weeks of gestation, while late-onset subtype occurs after this gestational week. This classification is based on studies identifying 32 weeks of gestation as the cutoff for differentiating between early- and late-onset FGR fetuses, as it helps maximize the differences in underlying etiology, Doppler parameters, complications, and pregnancy outcomes [ 4 ] . Early-onset FGR is more prone to placental lesions and generally has a poorer prognosis compared to the late-onset subtype [ 5 ] . Ultrasound screening (US) is the primary method for prenatal evaluation of fetal development, allowing real-time observation of fetal structure, growth parameters and placental condition in. It can also detect deformities, monitor growth and development, offering the advantages of being non-invasive, safe, and repeatable, which benefits both eugenics and clinical decision-making. In recent years, fetal magnetic resonance imaging (MRI) has been widely used in major prenatal diagnostic centres. It is a crucial tool for evaluating fetal brain development and complements the US technique. MRI provides important value in evaluating FGR fetal brain injury or structural defects, calculating brain segmentation volumes, and assessing brain gyrus development [ 6 – 8 ] . Currently, there are few studies on the application of brain segmentation volume calculation to assess FGR fetal brain development, and the findings remain controversial. This study compares the brain segmentation volumes of fetuses with different subtypes of FGR to those of appropriate for gestational age (AGA) fetuses, and evaluates potential differences in fetal brain development, hoping to provide more reliable evidence for the clinical evaluation of FGR fetuses. Materials and method Participants selection This retrospective study included pregnant women who underwent MRI examinations at our hospital due to suspected fetal development abnormalities identified through ultrasound screening (US) between January 2021 and March 2025. Among these, 43 cases were clinically diagnosed with early-onset FGR, and 55 cases with late-onset FGR. The diagnostic criteria were based on the 2020 guidelines from the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) [ 9 ] . Early-onset FGR is defined by any of the following criteria: an estimated fetal weight (EFW) or abdominal circumference below the 3rd percentile for the corresponding gestational age by ultrasound before 32 weeks of pregnancy; loss of end-diastolic umbilical artery blood flow; or EFW or abdominal circumference below the 10th percentile for the corresponding gestational age, combined with a uterine artery or umbilical artery pulsation index above the 95th percentile for the corresponding gestational age. Late-onset FGR is diagnosed after 32 weeks of gestation if any of the following conditions are met: EFW or abdominal circumference is below the 3rd percentile for the corresponding gestational age, or two of the following criteria are satisfied: EFW or abdominal circumference is below the 10th percentile for the corresponding gestational age; EFW or abdominal circumference decreases by more than two quartiles; cerebral placenta rate is below the 5th percentile for the corresponding gestational age, or umbilical artery pulsatile index is above the 95th percentile for the corresponding gestational age. Sixty cases of appropriate for gestational age (AGA) fetuses are included, all of which are single-fetal pregnancies between 26 and 37 weeks of gestation. All pregnant women voluntarily undergo MRI examinations and sign informed consent for regular prenatal care. We retrieved basic information about pregnant women and fetal MRI images from the PACS system. The exclusion criteria include: (1) missing or incomplete clinical history, (2) poor brain image quality in all MRI columns due to motion artifacts or non-standard acquisition of scanning planes in fetal head images, and (3) presence of severe central nervous system complications in addition to FGR. Fetal brain MRI scan The scan was performed using a 1.5T MRI system (Philips) equipped with a phased array coil. Pregnant women are positioned supine and are required to cooperate with breath-holding when necessary. The tracing sequence adopts SSH_TSE sequence, and the acquisition time is 25s; the BTFE_BH sequence, and the acquisition time is about 35s. The fetal skull was scanned in transverse, sagittal, and coronal planes with a slice thickness of 4 mm and a slice spacing of -1 mm to obtain T2WI images of the fetal brain in these three planes. Additionally, the T1WI and DWI sequences were scanned in the two vertical planes of the fetal skull. The films are jointly analysed by two radiologists with prenatal diagnostic qualifications; the fetal head circumference is measured at the level of thalamus in the cross-section of the fetal brain (Fig. 1 ). Image segmentation and volume calculation All brain MRI images were independently segmented by two radiologists with prenatal MRI diagnostic credentials using Itk-Snap software. The segmented fetal craniocerebral anatomy includes brain parenchyma, brain stem, and cerebellum, and images of different anatomical structures are annotated using different colours (Fig. 2 ). After segmentation, the software is used to measure and calculate the volume of each anatomical structure of the fetal brain corresponding to the pixel number of different anatomical tissues (unit: mm 3 ). In the study, if the difference between the measurement data of the two surveyors is ≤ 10%, the average value is taken directly; if the gap is > 10%, a third person reviews the data, and the final value is determined as the average value of the two measurements. Statistical analysis Statistical analyses were performed using SPSS software (version 22.0), including student's test, independent t-test, and chi-square test to determine the statistical differences. Pearson correlation analysis was conducted to evaluate the correlation between each anatomical structure of the fetal brain, head circumference and gestational week, with 0.8-1.0 for extremely strong, 0.6–0.8 for strong, 0.4–0.6 for moderate, and 0.2–0.4 for weak correlation. A P value < 0.05 was statistically significant. Results According to the inclusion and exclusion criteria, a total of 158 cases with clear final images and successful segmentation were included in this study, including 98 cases in the normal group (AGA group) and 60 cases in the experimental group (FGR group). The basic information of pregnant women and the fetal head circumference data are shown in Table 1 . Table 1 Basic maternal information and fetal head circumference (mean x ± SD, N/A) FGR group AGA Group Case No. 98 60 Age 29.31 ± 3.96 29.78 ± 4.31 Height 157.70 ± 4.50 157.90 ± 4.53 Weight 60.77 ± 7.23 66.89 ± 9.11 Gestational Week 31.53 ± 3.31 31.57 ± 2.96 Fetal head circumference 271.17 ± 22.64 289.85 ± 23.24 After segmentation of each fetal brain MRI image, the volumes of the brain parenchyma, brain stem, and cerebellum were calculated at different gestational weeks in the FGR and AGA groups (Tables 2 and 3 ). Table 2 The measure brain volumes of various fetal anatomical structures in the FGR group (mean x ± SD, mm 3 ) Subtype Gestational week Number of cases Head circumference Brainstem volume Cerebellum volume Cerebrum volume Early onset 26–27 11 230.8 ± 5.9 1747.1 ± 159.3 3348.5 ± 634.3 87290.5 ± 9185.0 28–29 18 250.1 ± 6.0 1997.8 ± 285.3 4864.5 ± 461.3 112476.7 ± 23443.8 30–31 14 266.1 ± 8.8 2431.1 ± 316.2 6452.6 ± 898.4 139850.0 ± 17085.4 Late onset 32–33 27 278.8 ± 5.1 3588.6 ± 287.1 7192.0 ± 1389.0 160075.2 ± 18675.3 34–35 18 294.0 ± 8.8 4632.6 ± 733.3 10493.5 ± 2017.7 197568.3 ± 16973.9 36–37 10 298.9 ± 10.2 5152.7 ± 686.6 14034.7 ± 1564.9 226422.8 ± 13829.5 Table 3 The measured brain volumes of various fetal anatomical structures in the AGA group (mean x ± SD, mm 3 ) Subtype Gestational week Number of cases Head circumference Brainstem volume Cerebellum volume Cerebrum volume Early onset 26–27 10 257.8 ± 7.7 2661.6 ± 255.2 4636.8 ± 1028.2 113190.0 ± 10292.4 28–29 10 266.5 ± 6.1 2803.1 ± 367.8 5584.0 ± 914.0 131610.0 ± 8762.1 30–31 10 288.2 ± 6.1 2998.8 ± 538.0 8494.2 ± 1166.3 158620.0 ± 10879.3 Late onset 32–33 10 297.1 ± 6.2 4087.4 ± 496.3 10441.8 ± 1057.7 194050.7 ± 18151.0 34–35 10 310.7 ± 9.1 4959.8 ± 540.0 13157.7 ± 2030.5 232869.0 ± 18279.1 36–37 10 318.8 ± 7.97 5538.0 ± 596.4 15490.0 ± 2153.4 258949.8 ± 27165.0 The differences in brain parenchyma, brain stem, and cerebellum volumes between early-onset FGR fetuses and AGA fetuses were statistically significant. Statistical analyses revealed significant differences in brain parenchyma volumes between late-onset FGR fetuses and AGA fetuses, whereas no significant differences were indicated in brain stem volumes between FGR fetuses and AGA fetuses at 34 weeks of gestation or later, nor in cerebellum volumes between FGR fetuses and AGA fetuses at 36 weeks or later (Table 4 ). Table 4 Statistical differences in brain volumes between FGR fetus and AGA fetus ( t -value/ P -value) Subtype Gestational week Head circumference Brainstem volume Cerebellum volume Cerebrum volume Early onset 26–27 9.056/0.000 9.957/0.000 3.493/0.002 6.095/0.000 28–29 6.877/0.000 6.468/0.000 2.787/0.010 2.469/0.020 30–31 6.826/0.000 3.255/0.004 4.851/0.000 3.050/0.006 Late onset 32–33 9.119/0.000 3.817/0.030 6.692/0.000 4.950/0.000 34–35 4.751/0.000 1.233/0.228 3.334/0.003 5.133/0.000 36–37 4.883/0.000 1.340/0.197 1.792/0.101 3.374/0.003 In both the FGR and AGA groups, Pearson correlation analyses indicated a very strong correlation, with coefficients above 0.8, between brain parenchyma, brain stem, and cerebellum volumes, as well as head circumference and gestational week (Table 5 , Figs. 3 & 4 ). Table 5 Correlation between brain volumes and gestational week and head circumference in FGR and AGA fetuses (Pearson correlation coefficients) FGR group AGA Group Volumes Gestational week Head circumference Gestational week Head circumference Brainstem 0.917 0.867 0.909 0.880 Cerebellum 0.888 0.844 0.952 0.942 Cerebrum 0.936 0.910 0.964 0.959 Significance of the volumes of FGR fetuses and AGA fetuses on MRI This study used MRI data of fetal brains to obtain the volumes of fetal brain parenchyma, cerebellum and brain stem for both FGR and AGA fetuses through segmentation software. A comparative analysis and correlation analysis were conducted to determine the relationship with head circumference and gestational week. The differences in the volumes of cerebrum parenchyma, brain stem, and cerebellum between early-onset FGR fetuses and AGA fetuses was statistically significant. The differences in cerebrum parenchymal volumes between late-onset FGR fetuses and AGA fetuses were statistically significant, but there was no statistically significant differences in brain stem volumes at 34 weeks or later nor cerebellum volumes at 36 weeks or later. In both early- and late-onset FGR fetuses, cerebrum parenchyma, brain stem, and cerebellum volumes are strongly correlated with head circumference and gestational age. In a prospective observational study, researchers use 3D-MRI imaging of 35 FGR fetuses at a median gestational age of 30 weeks. Compared with 79 AGA fetuses, cerebrum volumes and cerebellum volumes in the FGR group are significantly smaller than those in the AGA group, and there is no significant difference in the brain stem volumes between the two groups [ 10 ] . A cohort study analyses MRI scan data from 26 FGR fetuses due to diagnosis of placental insufficiency, and measures the volumes of the supratentorial brain, left and right hemispheres, and cerebellum using semi-automatic methods, and the absolute volumes and percentiles of all brain structures in the FGR group are smaller compared to those of 66 fetuses in the control group [ 11 ] . A prospective observational case-control study found that 14 FGR fetuses at 35 weeks of gestation had smaller brain volumes compared to 26 non-FGR fetuses [ 12 ] . Controversially, a study comparing fetal MRI scans between 20 FGR fetuses and 19 AGA fetuses at 20–36 weeks of gestation showed no significant difference in brain volumes [ 13 ] . Another study examined fetal MRI scans from 40 cases of placental-derived FGR and compared them with 78 cases of non-placental lesions, and there was no significant difference in fetal brain volumes between the two groups [ 14 ] . Conversely, there is research reported larger cerebellum volumes in FGR fetuses compared to AGA fetuses at 37 weeks of gestation [ 15 ] . The clinical feasibility of FGR subtypes on MRI scan FGR can be categorized into two subtypes: early onset and late onset. Early-onset FGR refers to fetuses diagnosed before 32 weeks of gestation, while late-onset FGR is diagnosed after 32 weeks. Early-onset FGR is primarily associated with placental insufficiency and tends to have a relatively poor prognosis. In the present study, significant differences were observed in the volumes of the cerebrum parenchyma, brain stem, and cerebellum between early-onset FGR fetuses and AGA fetuses. However, as gestational age progressed, the differences in brain stem volumes between late-onset FGR fetuses and AGA fetuses were not statistically significant at 34 weeks or later, nor were the cerebellum volumes at 36 weeks or later between the two groups. Our findings are consistent with recent studies, indicating that in late-onset FGR fetuses, fetal brain development has always being retarded as gestational age increases, while the development gaps in the brain stem and cerebellum gradually narrow compared to AGA fetuses. In contrast, early-onset FGR fetuses constantly show relatively delayed development in the cerebrum, brain stem and cerebellum throughout gestation. An association has been reported between perinatal outcomes and FGR subtypes, suggesting that late-onset FGR fetuses typically experience milder clinical outcomes due to less severe blood flow abnormalities, while early-onset FGR fetuses tend to develop more severe clinical outcomes that may be linked to significant uterine placental vascular insufficiency, maternal hypertension, or genetic disorders [ 16 – 17 ] . Recently, functional MRI imaging techniques, such as SWI [ 18 ] and T2* [ 19 ] Sequences have been increasingly applied to evaluate the hemodynamics and cerebral oxygen levels in FGR fetuses, allowing for non-invasive evaluation of fetal brain tissue oxygenation, microbleeding and venous blood flow distribution. These methods provide new imaging biomarkers for monitoring cerebral blood perfusion and hypoxia-induced injury in FGR fetuses. There are some limitations in this study, such as a small sample size and the absence of a standardized reference value range. Future studies should focus on the FGR fetal MRI scan protocol, expanding the clinical validation cohort, and combining multimodal imaging with long-term neurodevelopmental follow-up, to clarify the clinical value of these functional imaging parameters in the early diagnosis and prognosis evaluation of FGR fetuses. Strengths and promising prospects Currently, there are relatively few studies on the precise segmentation of FGR brain tissues, primarily due to the special challenges associated with fetal MRI imaging. Traditional MRI scans often face significant challenges in obtaining high-resolution, motion-free images due to the fetus’s autonomous movements and the influence of maternal respiratory movements, further complicating subsequent segmentation and analysis of brain tissues. Additionally, either manual or semi-automatic segmentation of fetal brain tissues are time-consuming, making it difficult to implement such methods in clinical practice [ 20 – 21 ] . Despite these challenges, advancements in medical imaging technology offer promising prospects for the future of fetal MRI brain tissue segmentation research. First, the use of high-field strength MRI scanners and rapid imaging sequences can significantly enhance image resolution and reduce motion artifacts, thereby providing high-quality raw data for subsequent segmentation. Second, the optimization of deep learning and AI-assisted segmentation algorithms is expected to enable automatic segmentation of fetal brain tissues, greatly reducing the time of manual intervention and improving the accuracy and repeatability of segmentation. Finally, the establishment of a multicenter, large-sample database and the development of a standardized segmentation protocol will further facilitate the clinical application of this technology in the early diagnosis, prognosis evaluation, and intervention strategy development for FGR. Limitations and future perspectives This research has the following limitations. Firstly, as a retrospective study, the assessment of MRI brain volumes of FGR fetuses is limited to specific gestational weeks and does not include dynamic observations, so the brain development of early-onset FGR fetuses cannot be accurately evaluated beyond 32 weeks. We are planning to conduct relevant research in the future. Secondly, we used 2D-MRI data to evaluate fetal brain volumes, with data collected from 1.5T MRI equipment. Since measurements were manually taken using software, the accuracy was not as accurate as directly collecting 3D data, a limitation that could be addressed with a 3D-MRI scanner. Lastly, our study only analyzed the volumes of cerebrum parenchyma, brain stem and cerebellum in FGR subtypes, without evaluating finer brain structures. This is because fetuses at early gestational ages are hard to distinguish between structures such as cerebral lobes, basal ganglia and thalamus. Taken together, the findings of this study demonstrate a strong correlation between fetal brain volumes and gestational weeks. Fetal brain MRI during pregnancy is a valuable complement to ultrasound screening. This study provides brain volume data of different FGR subtypes between 26 and 37 weeks of gestation, proving that fetal brain MRI can be a useful tool for evaluating fetal brain development in FGR fetuses. Abbreviations FGR Fetal growth restriction AGA Aappropriate gestational age US Ultrasound screening MRI Magnetic resonance imaging EFW Estimated fetal weight Declarations Acknowledgements The authors sincerely thank all radiologists who participated in this study for their valuable contributions. Authors’ contributions CF X and S P investigated and wrote the manuscript. CF X, S P and CY Z conducted statistical analyses and designed this study. CF X, W T and CY Z participated in data collection, acquisition, analyses and interpretation and assisted in completing the draft. All contributors reviewed the manuscript and agreed to publish it. Funding The Chongqing young and middle-aged medical high-end talent project (YXGD202472) supported this study. Data availability The data used or tested in this study can be obtained from the corresponding authors upon request. Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki developed by the World Medical Association in 2000. The Clinical Research Ethics Committee of Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University) has approved this study (No: 2025057). After the benefits of the study were explained, the participants agreed to take part. Participants were informed that they had right to withdraw from the study at any time. Confidentiality is ensured by excluding questions that contain identifying information and by storing completed questionnaires and results in secure areas. 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Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 10 Dec, 2025 Reviews received at journal 27 Nov, 2025 Reviewers agreed at journal 21 Nov, 2025 Reviews received at journal 18 Nov, 2025 Reviewers agreed at journal 04 Sep, 2025 Reviewers invited by journal 27 Jul, 2025 Editor invited by journal 14 Jul, 2025 Editor assigned by journal 12 Jul, 2025 Submission checks completed at journal 12 Jul, 2025 First submitted to journal 10 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7093866","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":492697295,"identity":"4107d87f-38df-4f5e-94c6-97ec2a4eb97e","order_by":0,"name":"Chuan. Fei. Xie","email":"","orcid":"","institution":"Chongqing Health Center for Women and Children","correspondingAuthor":false,"prefix":"","firstName":"Chuan.","middleName":"Fei.","lastName":"Xie","suffix":""},{"id":492697296,"identity":"28936020-d472-4cad-b027-c4e664e31f90","order_by":1,"name":"Chun. Yan. Zhong","email":"","orcid":"","institution":"Chongqing Health Center for Women and Children","correspondingAuthor":false,"prefix":"","firstName":"Chun.","middleName":"Yan.","lastName":"Zhong","suffix":""},{"id":492697297,"identity":"3d5cdd18-083f-46e4-9ac1-891cd7677db9","order_by":2,"name":"Wei Tang","email":"","orcid":"","institution":"Chongqing Health Center for Women and Children","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Tang","suffix":""},{"id":492697298,"identity":"4c8cfd5e-b735-43f0-8cd3-48fcc84ea536","order_by":3,"name":"Song Peng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtUlEQVRIiWNgGAWjYLACxn//6/tJ1MPGzDizgWQtGw4Qq9icvffwyx88bMzGx5M3MPyo2EZYi2XPuTRrHgkeNrMzzwoYe87cJqzF4EaOmTGDgQSP2Y0cA2bGNmK03H9jZvgjwUDCeAbRWm7wGD/gOZBgYCBBrBbLnhwzZt6GAwkSQL8cJMov5uxnjD/+BGrhb0/e+OBHBTEOA0aKBISZYHCAsHqIFuYPMC1E6RgFo2AUjIKRBwCcYTtjLPaSoAAAAABJRU5ErkJggg==","orcid":"","institution":"Chongqing Health Center for Women and Children","correspondingAuthor":true,"prefix":"","firstName":"Song","middleName":"","lastName":"Peng","suffix":""}],"badges":[],"createdAt":"2025-07-10 14:08:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7093866/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7093866/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88034937,"identity":"ced34233-cf87-49c0-9dba-4c603dc78678","added_by":"auto","created_at":"2025-07-31 16:10:27","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":661779,"visible":true,"origin":"","legend":"\u003cp\u003eFetal MRI head circumference measurement standard level.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7093866/v1/8df74eeb38c056b81ba6b457.jpeg"},{"id":88035802,"identity":"892653fb-ee51-462a-95b5-85cefede4ea1","added_by":"auto","created_at":"2025-07-31 16:18:27","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":942159,"visible":true,"origin":"","legend":"\u003cp\u003eFigure A-C is 27 weeks fetal MRI, Figure D-F is 30 weeks fetal MRI, Figure G-I is 33 weeks fetal MRI, Figure J-L is 36 weeks fetal MRI ; the brainstem is marked blue, the cerebellum is marked green, and the brain is marked red, and a VR image is generated.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7093866/v1/6cddff4d0470d12f62818643.jpeg"},{"id":88035799,"identity":"72a63813-a80c-4819-8490-e452a14aaa7e","added_by":"auto","created_at":"2025-07-31 16:18:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":133930,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot of FGR fetal brain volumes including cerebrum, cerebellum and brainstem (mm\u003csup\u003e3\u003c/sup\u003e, weeks)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7093866/v1/47ed04d6e9a3fd6a44f3fac2.png"},{"id":88037154,"identity":"3ae3bf85-e6f9-41d0-8d68-416cf3751245","added_by":"auto","created_at":"2025-07-31 16:26:27","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":95908,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot of AGA fetal brain volumes including cerebrum, cerebellum and brainstem (mm\u003csup\u003e3\u003c/sup\u003e, weeks)\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7093866/v1/29bbdfe07d6caec9ed97d0ca.png"},{"id":88037810,"identity":"6f08f3f7-0c8f-4a64-8c6c-177384eda89c","added_by":"auto","created_at":"2025-07-31 16:34:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2567563,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7093866/v1/1dc0ac52-07a3-42e5-ab30-633a815e3b4c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of fetal brain development in growth restriction subtypes using brain MRI volume measurement","fulltext":[{"header":"Background","content":"\u003cp\u003eFetal growth restriction (FGR), characterized by low body weight due to pathological factors that impair fetal growth potential, affects as high as 5\u0026ndash;10% of pregnancies and approximately 30\u0026nbsp;million fetuses worldwide each year\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Studies have found that FGR is most commonly caused by placental insufficiency, resulting in significant perinatal morbidity and mortality\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Despite a universal consensus on its definition has not been reached, there is global agreement on its classification into early-onset and late-onset subtypes according to the timing of occurrence\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eEarly-onset FGR refers to delayed fetal growth that occurs earlier than 32 weeks of gestation, while late-onset subtype occurs after this gestational week. This classification is based on studies identifying 32 weeks of gestation as the cutoff for differentiating between early- and late-onset FGR fetuses, as it helps maximize the differences in underlying etiology, Doppler parameters, complications, and pregnancy outcomes\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Early-onset FGR is more prone to placental lesions and generally has a poorer prognosis compared to the late-onset subtype\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eUltrasound screening (US) is the primary method for prenatal evaluation of fetal development, allowing real-time observation of fetal structure, growth parameters and placental condition in. It can also detect deformities, monitor growth and development, offering the advantages of being non-invasive, safe, and repeatable, which benefits both eugenics and clinical decision-making. In recent years, fetal magnetic resonance imaging (MRI) has been widely used in major prenatal diagnostic centres. It is a crucial tool for evaluating fetal brain development and complements the US technique. MRI provides important value in evaluating FGR fetal brain injury or structural defects, calculating brain segmentation volumes, and assessing brain gyrus development\u003csup\u003e[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eCurrently, there are few studies on the application of brain segmentation volume calculation to assess FGR fetal brain development, and the findings remain controversial. This study compares the brain segmentation volumes of fetuses with different subtypes of FGR to those of appropriate for gestational age (AGA) fetuses, and evaluates potential differences in fetal brain development, hoping to provide more reliable evidence for the clinical evaluation of FGR fetuses.\u003c/p\u003e"},{"header":"Materials and method","content":"\u003cp\u003e\u003cb\u003eParticipants selection\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis retrospective study included pregnant women who underwent MRI examinations at our hospital due to suspected fetal development abnormalities identified through ultrasound screening (US) between January 2021 and March 2025. Among these, 43 cases were clinically diagnosed with early-onset FGR, and 55 cases with late-onset FGR. The diagnostic criteria were based on the 2020 guidelines from the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Early-onset FGR is defined by any of the following criteria: an estimated fetal weight (EFW) or abdominal circumference below the 3rd percentile for the corresponding gestational age by ultrasound before 32 weeks of pregnancy; loss of end-diastolic umbilical artery blood flow; or EFW or abdominal circumference below the 10th percentile for the corresponding gestational age, combined with a uterine artery or umbilical artery pulsation index above the 95th percentile for the corresponding gestational age. Late-onset FGR is diagnosed after 32 weeks of gestation if any of the following conditions are met: EFW or abdominal circumference is below the 3rd percentile for the corresponding gestational age, or two of the following criteria are satisfied: EFW or abdominal circumference is below the 10th percentile for the corresponding gestational age; EFW or abdominal circumference decreases by more than two quartiles; cerebral placenta rate is below the 5th percentile for the corresponding gestational age, or umbilical artery pulsatile index is above the 95th percentile for the corresponding gestational age. Sixty cases of appropriate for gestational age (AGA) fetuses are included, all of which are single-fetal pregnancies between 26 and 37 weeks of gestation.\u003c/p\u003e\u003cp\u003eAll pregnant women voluntarily undergo MRI examinations and sign informed consent for regular prenatal care. We retrieved basic information about pregnant women and fetal MRI images from the PACS system. The exclusion criteria include: (1) missing or incomplete clinical history, (2) poor brain image quality in all MRI columns due to motion artifacts or non-standard acquisition of scanning planes in fetal head images, and (3) presence of severe central nervous system complications in addition to FGR.\u003c/p\u003e\u003cp\u003e\u003cb\u003eFetal brain MRI scan\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe scan was performed using a 1.5T MRI system (Philips) equipped with a phased array coil. Pregnant women are positioned supine and are required to cooperate with breath-holding when necessary. The tracing sequence adopts SSH_TSE sequence, and the acquisition time is 25s; the BTFE_BH sequence, and the acquisition time is about 35s. The fetal skull was scanned in transverse, sagittal, and coronal planes with a slice thickness of 4 mm and a slice spacing of -1 mm to obtain T2WI images of the fetal brain in these three planes. Additionally, the T1WI and DWI sequences were scanned in the two vertical planes of the fetal skull. The films are jointly analysed by two radiologists with prenatal diagnostic qualifications; the fetal head circumference is measured at the level of thalamus in the cross-section of the fetal brain (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eImage segmentation and volume calculation\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll brain MRI images were independently segmented by two radiologists with prenatal MRI diagnostic credentials using Itk-Snap software. The segmented fetal craniocerebral anatomy includes brain parenchyma, brain stem, and cerebellum, and images of different anatomical structures are annotated using different colours (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After segmentation, the software is used to measure and calculate the volume of each anatomical structure of the fetal brain corresponding to the pixel number of different anatomical tissues (unit: mm\u003csup\u003e3\u003c/sup\u003e). In the study, if the difference between the measurement data of the two surveyors is \u0026le;\u0026thinsp;10%, the average value is taken directly; if the gap is \u0026gt;\u0026thinsp;10%, a third person reviews the data, and the final value is determined as the average value of the two measurements.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were performed using SPSS software (version 22.0), including student's test, independent t-test, and chi-square test to determine the statistical differences. Pearson correlation analysis was conducted to evaluate the correlation between each anatomical structure of the fetal brain, head circumference and gestational week, with 0.8-1.0 for extremely strong, 0.6\u0026ndash;0.8 for strong, 0.4\u0026ndash;0.6 for moderate, and 0.2\u0026ndash;0.4 for weak correlation. A \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAccording to the inclusion and exclusion criteria, a total of 158 cases with clear final images and successful segmentation were included in this study, including 98 cases in the normal group (AGA group) and 60 cases in the experimental group (FGR group). The basic information of pregnant women and the fetal head circumference data are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBasic maternal information and fetal head circumference (mean x\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, N/A)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFGR group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAGA Group\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase No.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29.31\u0026thinsp;\u0026plusmn;\u0026thinsp;3.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.78\u0026thinsp;\u0026plusmn;\u0026thinsp;4.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e157.70\u0026thinsp;\u0026plusmn;\u0026thinsp;4.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e157.90\u0026thinsp;\u0026plusmn;\u0026thinsp;4.53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60.77\u0026thinsp;\u0026plusmn;\u0026thinsp;7.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66.89\u0026thinsp;\u0026plusmn;\u0026thinsp;9.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGestational Week\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.53\u0026thinsp;\u0026plusmn;\u0026thinsp;3.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.57\u0026thinsp;\u0026plusmn;\u0026thinsp;2.96\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFetal head circumference\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e271.17\u0026thinsp;\u0026plusmn;\u0026thinsp;22.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e289.85\u0026thinsp;\u0026plusmn;\u0026thinsp;23.24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAfter segmentation of each fetal brain MRI image, the volumes of the brain parenchyma, brain stem, and cerebellum were calculated at different gestational weeks in the FGR and AGA groups (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThe measure brain volumes of various fetal anatomical structures in the FGR group (mean x\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSubtype\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGestational week\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNumber of cases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHead circumference\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBrainstem volume\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCerebellum volume\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCerebrum volume\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eEarly onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u0026ndash;27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e230.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e1747.1\u0026thinsp;\u0026plusmn;\u0026thinsp;159.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e3348.5\u0026thinsp;\u0026plusmn;\u0026thinsp;634.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e87290.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9185.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28\u0026ndash;29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e250.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e1997.8\u0026thinsp;\u0026plusmn;\u0026thinsp;285.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e4864.5\u0026thinsp;\u0026plusmn;\u0026thinsp;461.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e112476.7\u0026thinsp;\u0026plusmn;\u0026thinsp;23443.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30\u0026ndash;31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e266.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e2431.1\u0026thinsp;\u0026plusmn;\u0026thinsp;316.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e6452.6\u0026thinsp;\u0026plusmn;\u0026thinsp;898.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e139850.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17085.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eLate onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32\u0026ndash;33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e278.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e3588.6\u0026thinsp;\u0026plusmn;\u0026thinsp;287.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e7192.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1389.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e160075.2\u0026thinsp;\u0026plusmn;\u0026thinsp;18675.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34\u0026ndash;35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e294.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e4632.6\u0026thinsp;\u0026plusmn;\u0026thinsp;733.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e10493.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2017.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e197568.3\u0026thinsp;\u0026plusmn;\u0026thinsp;16973.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36\u0026ndash;37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e298.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e5152.7\u0026thinsp;\u0026plusmn;\u0026thinsp;686.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e14034.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1564.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e226422.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13829.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThe measured brain volumes of various fetal anatomical structures in the AGA group (mean x\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSubtype\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGestational week\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNumber of cases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHead circumference\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBrainstem volume\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCerebellum volume\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCerebrum volume\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eEarly onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u0026ndash;27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e257.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e2661.6\u0026thinsp;\u0026plusmn;\u0026thinsp;255.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e4636.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1028.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e113190.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10292.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28\u0026ndash;29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e266.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e2803.1\u0026thinsp;\u0026plusmn;\u0026thinsp;367.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e5584.0\u0026thinsp;\u0026plusmn;\u0026thinsp;914.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e131610.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8762.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30\u0026ndash;31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e288.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e2998.8\u0026thinsp;\u0026plusmn;\u0026thinsp;538.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e8494.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1166.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e158620.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10879.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eLate onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32\u0026ndash;33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e297.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e4087.4\u0026thinsp;\u0026plusmn;\u0026thinsp;496.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e10441.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1057.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e194050.7\u0026thinsp;\u0026plusmn;\u0026thinsp;18151.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34\u0026ndash;35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e310.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e4959.8\u0026thinsp;\u0026plusmn;\u0026thinsp;540.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e13157.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2030.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e232869.0\u0026thinsp;\u0026plusmn;\u0026thinsp;18279.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36\u0026ndash;37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e318.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e5538.0\u0026thinsp;\u0026plusmn;\u0026thinsp;596.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e15490.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2153.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e258949.8\u0026thinsp;\u0026plusmn;\u0026thinsp;27165.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe differences in brain parenchyma, brain stem, and cerebellum volumes between early-onset FGR fetuses and AGA fetuses were statistically significant. Statistical analyses revealed significant differences in brain parenchyma volumes between late-onset FGR fetuses and AGA fetuses, whereas no significant differences were indicated in brain stem volumes between FGR fetuses and AGA fetuses at 34 weeks of gestation or later, nor in cerebellum volumes between FGR fetuses and AGA fetuses at 36 weeks or later (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eStatistical differences in brain volumes between FGR fetus and AGA fetus (\u003cem\u003et\u003c/em\u003e-value/\u003cem\u003eP\u003c/em\u003e-value)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSubtype\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGestational week\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHead circumference\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBrainstem volume\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCerebellum volume\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCerebrum volume\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eEarly onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u0026ndash;27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9.056/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.957/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.493/0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e6.095/0.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28\u0026ndash;29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6.877/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6.468/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.787/0.010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.469/0.020\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30\u0026ndash;31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6.826/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.255/0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.851/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e3.050/0.006\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eLate onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32\u0026ndash;33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9.119/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.817/0.030\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6.692/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e4.950/0.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34\u0026ndash;35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.751/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.233/0.228\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.334/0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e5.133/0.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36\u0026ndash;37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.883/0.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.340/0.197\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.792/0.101\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e3.374/0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn both the FGR and AGA groups, Pearson correlation analyses indicated a very strong correlation, with coefficients above 0.8, between brain parenchyma, brain stem, and cerebellum volumes, as well as head circumference and gestational week (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u0026amp; \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelation between brain volumes and gestational week and head circumference in FGR and AGA fetuses (Pearson correlation coefficients)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eFGR group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eAGA Group\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVolumes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGestational week\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHead circumference\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGestational week\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eHead circumference\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBrainstem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.917\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.867\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.909\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.880\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebellum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.888\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.844\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.952\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.942\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebrum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.936\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.910\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.964\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.959\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eSignificance of the volumes of FGR fetuses and AGA fetuses on MRI\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study used MRI data of fetal brains to obtain the volumes of fetal brain parenchyma, cerebellum and brain stem for both FGR and AGA fetuses through segmentation software. A comparative analysis and correlation analysis were conducted to determine the relationship with head circumference and gestational week. The differences in the volumes of cerebrum parenchyma, brain stem, and cerebellum between early-onset FGR fetuses and AGA fetuses was statistically significant. The differences in cerebrum parenchymal volumes between late-onset FGR fetuses and AGA fetuses were statistically significant, but there was no statistically significant differences in brain stem volumes at 34 weeks or later nor cerebellum volumes at 36 weeks or later. In both early- and late-onset FGR fetuses, cerebrum parenchyma, brain stem, and cerebellum volumes are strongly correlated with head circumference and gestational age.\u003c/p\u003e\u003cp\u003eIn a prospective observational study, researchers use 3D-MRI imaging of 35 FGR fetuses at a median gestational age of 30 weeks. Compared with 79 AGA fetuses, cerebrum volumes and cerebellum volumes in the FGR group are significantly smaller than those in the AGA group, and there is no significant difference in the brain stem volumes between the two groups\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. A cohort study analyses MRI scan data from 26 FGR fetuses due to diagnosis of placental insufficiency, and measures the volumes of the supratentorial brain, left and right hemispheres, and cerebellum using semi-automatic methods, and the absolute volumes and percentiles of all brain structures in the FGR group are smaller compared to those of 66 fetuses in the control group\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. A prospective observational case-control study found that 14 FGR fetuses at 35 weeks of gestation had smaller brain volumes compared to 26 non-FGR fetuses\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Controversially, a study comparing fetal MRI scans between 20 FGR fetuses and 19 AGA fetuses at 20\u0026ndash;36 weeks of gestation showed no significant difference in brain volumes\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Another study examined fetal MRI scans from 40 cases of placental-derived FGR and compared them with 78 cases of non-placental lesions, and there was no significant difference in fetal brain volumes between the two groups\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Conversely, there is research reported larger cerebellum volumes in FGR fetuses compared to AGA fetuses at 37 weeks of gestation\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eThe clinical feasibility of FGR subtypes on MRI scan\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFGR can be categorized into two subtypes: early onset and late onset. Early-onset FGR refers to fetuses diagnosed before 32 weeks of gestation, while late-onset FGR is diagnosed after 32 weeks. Early-onset FGR is primarily associated with placental insufficiency and tends to have a relatively poor prognosis. In the present study, significant differences were observed in the volumes of the cerebrum parenchyma, brain stem, and cerebellum between early-onset FGR fetuses and AGA fetuses. However, as gestational age progressed, the differences in brain stem volumes between late-onset FGR fetuses and AGA fetuses were not statistically significant at 34 weeks or later, nor were the cerebellum volumes at 36 weeks or later between the two groups.\u003c/p\u003e\u003cp\u003eOur findings are consistent with recent studies, indicating that in late-onset FGR fetuses, fetal brain development has always being retarded as gestational age increases, while the development gaps in the brain stem and cerebellum gradually narrow compared to AGA fetuses. In contrast, early-onset FGR fetuses constantly show relatively delayed development in the cerebrum, brain stem and cerebellum throughout gestation. An association has been reported between perinatal outcomes and FGR subtypes, suggesting that late-onset FGR fetuses typically experience milder clinical outcomes due to less severe blood flow abnormalities, while early-onset FGR fetuses tend to develop more severe clinical outcomes that may be linked to significant uterine placental vascular insufficiency, maternal hypertension, or genetic disorders\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eRecently, functional MRI imaging techniques, such as SWI\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e and T2*\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e Sequences have been increasingly applied to evaluate the hemodynamics and cerebral oxygen levels in FGR fetuses, allowing for non-invasive evaluation of fetal brain tissue oxygenation, microbleeding and venous blood flow distribution. These methods provide new imaging biomarkers for monitoring cerebral blood perfusion and hypoxia-induced injury in FGR fetuses. There are some limitations in this study, such as a small sample size and the absence of a standardized reference value range. Future studies should focus on the FGR fetal MRI scan protocol, expanding the clinical validation cohort, and combining multimodal imaging with long-term neurodevelopmental follow-up, to clarify the clinical value of these functional imaging parameters in the early diagnosis and prognosis evaluation of FGR fetuses.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStrengths and promising prospects\u003c/b\u003e\u003c/p\u003e\u003cp\u003eCurrently, there are relatively few studies on the precise segmentation of FGR brain tissues, primarily due to the special challenges associated with fetal MRI imaging. Traditional MRI scans often face significant challenges in obtaining high-resolution, motion-free images due to the fetus\u0026rsquo;s autonomous movements and the influence of maternal respiratory movements, further complicating subsequent segmentation and analysis of brain tissues. Additionally, either manual or semi-automatic segmentation of fetal brain tissues are time-consuming, making it difficult to implement such methods in clinical practice\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eDespite these challenges, advancements in medical imaging technology offer promising prospects for the future of fetal MRI brain tissue segmentation research. First, the use of high-field strength MRI scanners and rapid imaging sequences can significantly enhance image resolution and reduce motion artifacts, thereby providing high-quality raw data for subsequent segmentation. Second, the optimization of deep learning and AI-assisted segmentation algorithms is expected to enable automatic segmentation of fetal brain tissues, greatly reducing the time of manual intervention and improving the accuracy and repeatability of segmentation. Finally, the establishment of a multicenter, large-sample database and the development of a standardized segmentation protocol will further facilitate the clinical application of this technology in the early diagnosis, prognosis evaluation, and intervention strategy development for FGR.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations and future perspectives\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis research has the following limitations. Firstly, as a retrospective study, the assessment of MRI brain volumes of FGR fetuses is limited to specific gestational weeks and does not include dynamic observations, so the brain development of early-onset FGR fetuses cannot be accurately evaluated beyond 32 weeks. We are planning to conduct relevant research in the future. Secondly, we used 2D-MRI data to evaluate fetal brain volumes, with data collected from 1.5T MRI equipment. Since measurements were manually taken using software, the accuracy was not as accurate as directly collecting 3D data, a limitation that could be addressed with a 3D-MRI scanner. Lastly, our study only analyzed the volumes of cerebrum parenchyma, brain stem and cerebellum in FGR subtypes, without evaluating finer brain structures. This is because fetuses at early gestational ages are hard to distinguish between structures such as cerebral lobes, basal ganglia and thalamus.\u003c/p\u003e\u003cp\u003eTaken together, the findings of this study demonstrate a strong correlation between fetal brain volumes and gestational weeks. Fetal brain MRI during pregnancy is a valuable complement to ultrasound screening. This study provides brain volume data of different FGR subtypes between 26 and 37 weeks of gestation, proving that fetal brain MRI can be a useful tool for evaluating fetal brain development in FGR fetuses.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eFGR\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFetal growth restriction\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAGA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAappropriate gestational age\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUltrasound screening\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRI\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMagnetic resonance imaging\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEFW\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEstimated fetal weight\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors sincerely thank all radiologists who participated in this study for their valuable contributions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCF X and S P investigated and wrote the manuscript. CF X, S P and CY Z conducted statistical analyses and designed this study. CF X, W T and CY Z participated in data collection, acquisition, analyses and interpretation and assisted in completing the draft. All contributors reviewed the manuscript and agreed to publish it.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Chongqing young and middle-aged medical high-end talent project (YXGD202472) supported this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used or tested in this study can be obtained from the corresponding authors upon request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the \u003cem\u003eDeclaration of Helsinki\u003c/em\u003e developed by the World Medical Association in 2000. \u0026nbsp;The Clinical Research Ethics Committee of Chongqing Health Center for Women and Children (Women and Children\u0026apos;s Hospital of Chongqing Medical University) has approved this study (No: 2025057). After the benefits of the study were explained, the participants agreed to take part. Participants were informed that they had right to withdraw from the study at any time. Confidentiality is ensured by excluding questions that contain identifying information and by storing completed questionnaires and results in secure areas.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eIngrid Dudink,Petra S H\u0026uuml;ppi,St\u0026eacute;phane V Sizonenko, et al. Altered trajectory of neurodevelopment associated with fetal growth restriction[J]. Experimental Neurology. 2022;347: 113885.\u003c/li\u003e\n\u003cli\u003eFleiss Bobbi,Wong Flora,Brownfoot Fiona, et al. Knowledge Gaps and Emerging Research Areas in Intrauterine Growth Restriction-Associated Brain Injury[J]. Frontiers in endocrinology. 2019;10: 188.\u003c/li\u003e\n\u003cli\u003eL C G Molina,L Odibo,S Zientara, et al. Validation of Delphi procedure consensus criteria for defining fetal growth restriction[J]. Ultrasound in Obstetrics \u0026amp; Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology.2020;56(1): 61-6.\u003c/li\u003e\n\u003cli\u003eSavchev Stefan,Figueras Francesc,Sanz-cortes Magda, et al. Evaluation of an optimal gestational age cut-off for the definition of early- and late-onset fetal growth restriction.[J]. Fetal diagnosis and therapy. 2014; 36(2): 99-105.\u003c/li\u003e\n\u003cli\u003eArsenio Spinillo,Barbara Gardella,Laura Adamo, et al. Pathologic placental lesions in early and late fetal growth restriction[J]. Acta Obstetricia Et Gynecologica Scandinavica.2019;98(12): 1585-94.\u003c/li\u003e\n\u003cli\u003eA Polat,S Barlow,R Ber, et al. Volumetric MRI study of the intrauterine growth restriction fetal brain[J]. European Radiology.2017;27(5): 2110-18.\u003c/li\u003e\n\u003cli\u003eN Andescavage,A duPlessis,M Metzler, et al. In vivo assessment of placental and brain volumes in growth-restricted fetuses with and without fetal Doppler changes using quantitative 3D MRI[J]. Journal of Perinatology : Official Journal of the California Perinatal Association.2017;37(12): 1278-84.\u003c/li\u003e\n\u003cli\u003eLi Kui,Yan Guohui,Zheng Weizeng, et al. Measurement of the Brain Volume/Liver Volume Ratio by Three-Dimensional MRI in Appropriate-for-Gestational Age Fetuses and Those With Fetal Growth Restriction.[J]. Journal of magnetic resonance imaging : JMRI. 2021;54(6): 1796-801.\u003c/li\u003e\n\u003cli\u003eC C Lees,T Stampalija,A Baschat, et al. ISUOG Practice Guidelines: diagnosis and management of small‐for‐gestational‐age fetus and fetal growth restriction[J]. Ultrasound in Obstetrics \u0026amp; Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2020;56(2): 298-312.\u003c/li\u003e\n\u003cli\u003eN Andescavage,A duPlessis,M Metzler, et al. In vivo assessment of placental and brain volumes in growth-restricted fetuses with and without fetal Doppler changes using quantitative 3D MRI[J]. Journal of Perinatology : Official Journal of the California Perinatal Association.2017;37(12): 1278-84.\u003c/li\u003e\n\u003cli\u003ePeretz R,Halevy T,Gafner M, et al. Volumetric Brain MRI Study in Fetuses with Intrauterine Growth Restriction Using a Semiautomated Method.[J]. AJNR. American journal of neuroradiology. 2022; 43(11): 1674-79.\u003c/li\u003e\n\u003cli\u003eMeng Yuan Zhu,Natasha Milligan,Sarah Keating, et al. The hemodynamics of late-onset intrauterine growth restriction by MRI[J]. American Journal of Obstetrics and Gynecology.2016;214(3): 367.e1-367.e17.\u003c/li\u003e\n\u003cli\u003eMellisa S Damodaram,Lisa Story,Elisanda Eixarch, et al. Foetal volumetry using Magnetic Resonance Imaging in intrauterine growth restriction[J]. Early Human Development. 2012; 88: Suppl 1:35-40.\u003c/li\u003e\n\u003cli\u003eD Javor,C Nasel,S Dekan, et al. Placental MRI shows preservation of brain volume in growth-restricted fetuses who suffer substantial reduction of putative functional placenta tissue (PFPT)[J]. European Journal of Radiology.2018;108: 189-93.\u003c/li\u003e\n\u003cli\u003eMagdalena Sanz-Cortes,Gabriela Ega\u0026ntilde;a-Ugrinovic,Rudolf Zupan, et al. Brainstem and cerebellar differences and their association with neurobehavior in term small-for-gestational-age fetuses assessed by fetal MRI[J]. American Journal of Obstetrics and Gynecology.2014;210(5): 452.\u003c/li\u003e\n\u003cli\u003eBujorescu Daniela-Loredana,Raţiu Adrian-Claudiu,Motoc Andrei-Gheorghe-Marius, et al. Placental pathology in early-onset fetal growth restriction: insights into fetal growth restriction mechanisms[J]. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2023; 64(2): 215-24.\u003c/li\u003e\n\u003cli\u003eCecilia Putri Tedyanto,Fransiscus Octavius Hari Prasetyadi,Sianty Dewi, et al. Maternal factors and perinatal outcomes associated with early-onset versus late-onset fetal growth restriction: a meta-analysis[J]. The Journal of Maternal-fetal \u0026amp; Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.2025;38(1): 2505774.\u003c/li\u003e\n\u003cli\u003eBrijesh Kumar Yadav,Edgar Hernandez-Andrade,Uday Krishnamurthy, et al. Dual-Imaging Modality Approach to Evaluate Cerebral Hemodynamics in Growth-Restricted Fetuses: Oxygenation and Perfusion[J]. Fetal Diagnosis and Therapy. 2020; 47(2): 145-55.\u003c/li\u003e\n\u003cli\u003eKirstine Baadsgaard,Ditte N Hansen,David A Peters, et al. T2* weighted fetal MRI and the correlation with placental dysfunction[J]. Placenta. 2023;131: 90-7.\u003c/li\u003e\n\u003cli\u003eVanessa Kyriakopoulou,Deniz Vatansever,Alice Davidson, et al. Normative biometry of the fetal brain using magnetic resonance imaging[J]. Brain Structure \u0026amp; Function. 2017; 222(5): 2295-307.\u003c/li\u003e\n\u003cli\u003ePier Danielle-B,Levine Deborah,Kataoka Miliam-L, et al. Magnetic resonance volumetric assessments of brains in fetuses with ventriculomegaly correlated to outcomes.[J]. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2011;5:595-603.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Magnetic resonance imaging, Fetal growth restriction, Fetal brain volume, Image segmentation","lastPublishedDoi":"10.21203/rs.3.rs-7093866/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7093866/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThis retrospective study aims to explore the value of brain MRI volume measurements in evaluating fetal brain development in fetal growth restriction (FGR) fetuses, by comparing different FGR subtypes with appropriate gestational age (AGA) fetuses.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA total of 158 fetal brain MRI with suspected abnormal development, identified through ultrasound screening at this hospital between 2021 and 2025 were analyzed. Ninety-eight cases were FGR fetuses (43 early-onset subtype and 55 late-onset subtype), and 60 were AGA fetuses. Three-dimensional reconstruction and image segmentation were performed on fetus intracranial tissues, brain parenchyma, cerebellum and brainstem. Changes in brain volume at different gestational weeks were analysed to assess the development of fetal brain anatomical structures.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eIn both groups, the Pearson correlation coefficients for brain parenchyma, brain stem, and cerebellum volume with head circumference and gestational age were greater than 0.8, indicating a strong correlation. The difference in brain parenchyma, brain stem, and cerebellum volume between early-onset FGR fetuses and AGA fetuses was statistically significant. The difference in brain parenchyma volume between late-onset FGR fetuses and AGA fetuses was statistically significant, while there was no statistically significant difference in brain stem volume between FGR and AGA fetuses at 34 weeks or later, nor in cerebellum volume at 36 weeks or later.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e\u003cp\u003eFetal brain MRI at gestation serve as a valuable supplement to ultrasound screening. This technique helps assess brain development in fetuses with various FGR subtypes, offering further reference for prenatal diagnosticians in evaluating fetal brain development. Further studies are needed to dynamically monitor and assess the prognosis of brain MRI volumes in fetuses with early-onset FGR.\u003c/p\u003e","manuscriptTitle":"Evaluation of fetal brain development in growth restriction subtypes using brain MRI volume measurement","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-31 16:10:23","doi":"10.21203/rs.3.rs-7093866/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-10T11:38:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-27T10:47:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"114003924888437795209910852621957285253","date":"2025-11-21T11:18:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-18T20:02:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"43819518660658893224839270023011275326","date":"2025-09-04T15:54:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-27T18:59:31+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-14T18:20:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-12T09:48:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-12T09:48:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2025-07-10T14:07:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5cb0812c-c5f0-4271-9e9e-9e5d463b4cc3","owner":[],"postedDate":"July 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-23T15:08:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-31 16:10:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7093866","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7093866","identity":"rs-7093866","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}