The early alteration of brainstem and cerebellum, and their relationship with cerebral cortex: an in vivo fetal magnetic resonance imaging assessment

Introduction

The fetal brain undergoes complex and dynamic development processes during gestation. Fetal brain development lasts from the fourth week of gestation until birth (1). The cerebral cortex, brainstem, and cerebellum are the primary components of brain development. Due to their unique location, complex anatomical structure, and important physiological functions, the differentiation process of the brainstem and cerebellum has been the focus of recent research in the fields of neurogenetics, developmental biology, and fetal neuroimaging (2-4). The brainstem and cerebellum play crucial roles in human activities. The brainstem is the vital center, controlling physiological activities such as respiration, heartbeat, blood pressure, digestion, and vasoconstriction (5). The midbrain is the reflex center for hearing and vision, and the pons plays a role in regulating sleep. The cerebellum is an essential structure for regulating movement, coordinating movements, and maintaining body balance. Additionally, the cerebellum plays a crucial role in learning, adaptation, and emotional cognition. The brainstem and cerebellum synergistically contribute to higher motor control, balance regulation, and language development later in development. The brainstem and cerebellum develop earlier, starting 4–6 weeks after conception, which increases their susceptibility to influencing factors during intrauterine development (6,7). Abnormal development of the brainstem and cerebellum can lead to malformations such as pontocerebellar hypoplasia, Joubert syndrome and related disorders, cobblestone malformation complex, rhombencephalosynapsis, brainstem disconnection, Dandy-Walker malformation, and cerebellar vermian dysgenesis (8-10). The brainstem, cerebellum, and cerebral cortex are interconnected, forming neural circuits that support behavioral and cognitive functions (11). The development of the cerebral cortex is closely related to the development of the brainstem and cerebellum. Therefore, normal and healthy development of the fetal brainstem and cerebellum is essential for postnatal growth. Customizing brainstem and cerebellar growth trajectory charts helps to accurately identify infants at risk of adverse perinatal outcomes. Accurate assessment of the morphology and size of the fetal brainstem and cerebellum before delivery is particularly important for guiding clinical interventions and optimizing pregnancy outcomes (12).

Ultrasound is the most commonly used and convenient imaging method for prenatal examinations globally, but its limitations include that ultrasound images of the brainstem and cerebellum can be compromised due to the position of the fetal head in the maternal pelvis and the anatomy of the posterior cranial fossa. With the development of rapid imaging technology, fetal magnetic resonance imaging (MRI) has become a critical prenatal imaging tool for the prevention and control of birth defects. Compared with ultrasound, MRI has multi-directional scanning, rich soft tissue contrast, non-invasiveness, and safety. Intrauterine MRI has become an ideal choice for detailed measurement of the brainstem and cerebellum throughout pregnancy (13). Although the clarity of fetal brain MRI is affected by fetal movement and maternal body shape, the rapid development of advanced acquisition and post-processing technologies has made three-dimensional (3D) visualization of the fetal brain possible. Studies suggest that 3D MRI provides comparable fetal brain biometry to conventional MRI, with improved measurement confidence using a single reconstructed volume (14).

Many previous studies have measured two-dimensional (2D) biometric parameters in the brainstem and cerebellum during mid to late pregnancy to observe their changes with gestational age (GA). However, 2D parameters are limited to measurements at a specific level and cannot fully reflect the overall development of the brainstem and cerebellum (14). Some studies have already drawn maps of various brain structures (15,16). However, existing brain atlases, primarily derived from non-Chinese populations, are not suitable as references for assessing fetal brain development in China due to racial differences in brain morphology (17,18). This study aimed to address this gap by establishing population-specific volumetric growth trajectories for the Chinese fetal brainstem and cerebellum using 3D MRI. Currently, due to the technical challenges in obtaining high-quality 3D images, studies quantitatively measuring fetal brainstem and cerebellum volumes remain scarce. To overcome the limitations of conventional 2D measurements, this study leverages advanced 3D MRI reconstruction techniques, thereby providing a comprehensive assessment of brain structure volumetric growth within a Chinese cohort.

We know that there are anatomical connections between various brain structures. For instance, the brainstem connects to both cerebral hemispheres via the midbrain and to the spinal cord via the medulla oblongata, whereas the cerebellum connects to the brainstem through the cerebellar peduncle. There are functional connections between brain structures. Both the brainstem and cerebellum can receive projections from the cerebral cortex (19,20). Consequently, we hypothesized that the developmental trajectories of the brainstem and cerebellum are related to the cerebral cortex—a relationship underexplored due to limited in vivo imaging tools. Thomason et al. have confirmed that connections between brain regions exist during pregnancy (21). However, there is limited research on the relationship between brainstem and cortical development, as well as between cerebellum and cortical development. Therefore, this observational cross-sectional study aimed to investigate the volumetric growth patterns of fetal brainstem and cerebellum in a Chinese population using 3D MRI reconstruction and to explore their developmental relationships with the cerebral cortex. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-218/rc).

Methods

Experimental design

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of The Second Hospital of Lanzhou University (No. 2021A-601) and informed consent was exempted from all participants as individual consent for this retrospective analysis was waived.

We first collected qualified normal fetal brain MRI scans (conventional sagittal, coronal, axial), and then reconstructed the 3D volume of the fetal brain. We manually delineated the brainstem and cerebellum regions using 3D images, measured their volumes, and described their growth trajectories using a growth model. In addition, volumetric measurements, qualitative morphological assessments of the brainstem and cerebellar vermis were performed in the mid-sagittal plane, and the cerebellar hemispheres were evaluated in the axial plane, to characterize structural changes across GA. The range of GA 20–40 weeks was selected to capture critical developmental stages of the brainstem and cerebellum during mid to late pregnancy, despite potential variability. We also applied automatic segmentation to extract the cerebral cortex and described the relationship between fetal brainstem and cortical development, as well as the relationship between cerebellum and cortical development.

Participants

We acquired MRI scans from 308 pregnant women at GA 20–40 weeks with healthy pregnancies at The Second Hospital of Lanzhou University from January 2016 to February 2023. All pregnant women signed an informed consent form for MRI examination. The image quality was inspected by experienced radiologists (a senior attending physician and a senior professional physician). We excluded 67 cases of moderate to severe widening of the fetal lateral ventricles, 9 cases of widening or cyst of the posterior cranial fossa, 8 cases of absence of the corpus callosum, 2 cases of anencephaly, 7 cases of cerebellar vermis hypoplasia or Dandy-Walker malformation, 10 cases of cerebral hemorrhage, 8 cases of ependymal or subendometrial cysts, 6 cases of intrauterine growth restriction, and 19 cases of irregular baseline and unmeasurable fetal brain MRI scans. Finally, 172 cases of fetal brain MRI scans met the inclusion criteria (Figure 1). The age of pregnant women ranged from 16 to 47 years. The sex of each fetus was unknown.

Figure 1 Participant’s inclusion and exclusion process. MRI, magnetic resonance imaging.

Image acquisition

All MRI scans were obtained using a 3.0 Tesla (T) Signa MRI scanner (Ingenia, Philips Medical System, Amsterdam, the Netherlands) and a 1.5 T Signa MRI scanner (Aera, Siemens Medical System, Erlangen, Germany). Pregnant women were scanned in a supine or left lateral position without the use of any sedatives or magnetic resonance (MR) contrast agents, while breathing freely. We used foam ear plugs and ear shields to reduce the scanner noise. According to the 2015 American College of Radiology/Society for Pediatric Radiology (ACR-SPR) “Fetal MRI” guidelines, all fetuses completed cross-sectional, sagittal, and coronal brain scans, with a focus on T2-weighted imaging (T2WI) sequences. The total scanning time was approximately 10–12 minutes. Two different MRI scanner coils and T2WI sequence parameters are shown in Table 1.

Image reconstruction

Firstly, we performed a fetal brain segmentation mask based on images from three orientations of the fetal brain, using NiftyMIC pipeline (https://github.com/git-surg/NiftyMIC) (22). Then, we reconstructed a 3D high-resolution fetal brain with an isotropic resolution of 0.8 mm. Subsequently, fetal brain images were extracted based on the brain mask and the high-resolution image. Finally, manual anterior commissure-posterior commissure (AC-PC) correction was performed on the images using SPM in MATLAB (MathWorks, Natick, MA, USA). During the reconstruction process, we excluded images with poor cortical surface quality and gross errors in segmentation, resulting in only 47 qualified 3D brain images (Figure 2).

Figure 2 Image 3D reconstruction. 3D, three-dimensional; T2WI, T2-weighted imaging.

Segmentation of brainstem and cerebellum

The volume of interest (VOI) of the fetal brainstem and cerebellum was manually delineated using ITK-SNAP (https://www.itksnap.org/pmwiki/pmwiki.php) by a senior attending physician and then reviewed by a senior professional physician. The brainstem and cerebellum labeling results of selected cases are displayed in Figure 3.

Figure 3 Image segmentation. (A-D) VOI of the fetal cerebellum. (E-H) VOI of the fetal brainstem. VOI, volume of interest.

Morphological assessment of brainstem and cerebellum

Qualitative morphological assessments of the brainstem and cerebellar vermis were performed in the mid-sagittal plane, and cerebellar hemispheres were evaluated in the axial plane, to characterize structural changes across GA. These evaluations were independently conducted by two senior radiologists, and the consistency of the results was confirmed through visual inspection.

Cerebral cortex segmentation

All 3D reconstructed fetal cerebral cortex segmentation was performed using automatic segmentation technology DrawEM (https://github.com/MIRTK/DrawEM) algorithm (23). Then, fine cortical segmentation was performed on the 3D cerebral cortex of each case (https://github.com/BioMedIA/dhcp-structural-pipeline) (24). Finally, we obtained a total of 286 entire cortical regions of the brain.

Statistical analysis

For each fetus, the volumes of the brainstem and cerebellum were calculated. The relationship between these volumes and GA was analyzed using a nonlinear regression model. Pearson correlation analysis was used to evaluate the relationship between the brainstem volume and cerebral cortical volume, and between cerebellar volume and cerebral cortical volume, across all GAs. The false discovery rate (FDR) correction was applied to adjust for multiple comparisons, with a threshold of P<0.05 indicating statistical significance.

Results

In this study, we acquired MRI from 308 pregnant women at GA 20–40 weeks with healthy pregnancies. The age of the pregnant women was 16–47 years. After excluding fetal abnormal brain and reconstruction screening, we obtained 47 samples between GA 22 weeks and GA 36 weeks. All were Chinese, Han nationality. Table 2 shows the sample size for each gestational week.

Morphological development of brainstem and cerebellum

In addition to volumetric measurements, qualitative morphological changes were observed to provide a comprehensive understanding of brainstem and cerebellar development. Qualitative morphological assessments revealed that, in the mid-sagittal plane (Figure 4), the boundaries of the brainstem (midbrain, pons, and medulla oblongata) and cerebellar vermis were less distinct before GA 28 weeks, with smaller midbrain and medulla oblongata volumes. At GA 28 weeks, the boundaries between these brainstem components became clearly visible. In the third trimester, brainstem volume and morphology changed slowly. For the cerebellar vermis, edges were blurred before GA 28 weeks but became smooth and clearly visible at GA 28 weeks. After GA 28 weeks, sulci appeared, increasing in number with GA.

Figure 4 MRI mid-sagittal position displayed changes of brainstem and cerebellar vermis in normal fetuses at different GA. (A) 24 weeks; (B) 28 weeks; (C) 32 weeks; (D) 36 weeks. GA, gestational age; MRI, magnetic resonance imaging.

The volume changes of the cerebellar hemisphere were observed in the axial plane (Figure 5). In the second trimester, the change in cerebellar volume was slower. There were fewer low signal shadows in the deep white matter of the cerebellum on T2WI. In the third trimester, the volume of the cerebellum changed rapidly. We found an increase in low signal shadows on T2WI in the deep white matter of the cerebellum.

Figure 5 MRI axis displayed of changes cerebellar hemisphere in normal fetuses at different GA. (A) 24 weeks; (B) 28 weeks; (C) 32 weeks; (D) 36 weeks. GA, gestational age; MRI, magnetic resonance imaging.

GA-related change in the volume of brainstem and cerebellum

This study provided the first volumetric growth curves for the brainstem and cerebellum in Chinese fetuses, identifying a distinct turning point at GA 30 weeks. All evaluated structures had significant volume growth with increasing GA. Pearson correlation analysis showed that the volume of brainstem was positively correlated with GA (r=0.75, P<0.0001), and the volume of cerebellum was correlated with GA (r=0.87, P<0.0001). The changes in brainstem and cerebellar volume with GA during the period of 22–36 weeks of pregnancy were shown using scatter plots and fitted curves (Figure 6). We observed that the volume change curves of the brainstem and cerebellum generally showed an upward trend, and the slope of the curves changed at GA 30 weeks. In other words, GA 30 weeks marked a critical turning point in the growth and development of the brainstem and cerebellum. The brainstem grew rapidly before GA 30 weeks and slowly after GA 30 weeks. The cerebellum exhibited slow growth before GA 30 weeks and an accelerated growth after GA 30 weeks. Overall, we found that the volume of the brainstem and cerebellum increased non-linearly with GA.

Figure 6 The volumetric growth curves of fetal brainstem and cerebellum with GA. (A) Changes in brainstem volume during GA 22–36 weeks. (B) Changes in cerebellar volume during GA 22–36 weeks. GA, gestational age.

The relationship between brainstem and cortex, cerebellum and cortex

There was a connection between the growth of the brainstem and cerebellum and the development of the cerebral cortex. Figure 7 shows these areas with P<0.05 after FDR correction, and illustrates the strength of these relationships. We observed that the brainstem and cerebellum were closely related to the dorsomedial aspect of the posterior frontal lobe, parietal lobe, and occipital cortex. Moreover, their relationship with the right hemisphere was more significant than that with the left hemisphere.

Figure 7 These areas shown are the areas with P<0.05 after FDR correction. (A) The relationship between brainstem and cortex. (B) The relationship between cerebellum and cortex. FDR, false discovery rate; L, left; R, right.

Discussion

This study provides novel insights into the volumetric development of the fetal brainstem and cerebellum in Chinese fetuses, using 3D MRI reconstruction to establish population-specific growth trajectories and their relationships with the cerebral cortex. Obtaining normal fetal brain MRI scans is challenging, as most scans at our institution are performed due to ultrasound abnormalities, limiting sample sizes for certain GA.

Our results showed that the development of brainstem and cerebellum have different time axes and characteristics. The brainstem grows rapidly before GA 30 weeks and changes slowly during the third trimester, whereas the cerebellar volume increases slowly before GA 30 weeks and changes rapidly in the third trimester. In general, we observed that the volume of the brainstem and cerebellum increases non-linearly with GA. GA 30 weeks is a turning point in brainstem and cerebellum volume change. Although prior studies have reported volumetric correlations with GA, this study presents the first establishment of 3D MRI-based growth trajectories for the brainstem and cerebellum in a Chinese fetal cohort. These findings contribute to the development of reference standards for Chinese fetuses, aiding in the early detection of neurodevelopmental abnormalities.

There is a connection between the growth of the brainstem and cerebellum and the development of the cerebral cortex. We observed that the brainstem and cerebellum are closely related to the dorsomedial cerebral cortex, encompassing posterior frontal, parietal, and occipital regions. This suggests that these regions form coordinated neural circuits during fetal development. Notably, their relationship with the right hemisphere is more significant than with the left hemisphere.

The brainstem, comprising the midbrain, pons, and medulla oblongata, is an essential part that controls basic life activities in the early stages of fetal development. The boundary points between the midbrain, pons, and medulla oblongata in the anterior edge of the brainstem are clearly visible in the third trimester. Previous studies on the 2D diameter of fetal brainstem have divided the brainstem into three components for observation. Linear biometric measurement is a fundamental step in clinical practice, which is relatively easy to evaluate in terms of reference standard range (25). Our previously published study on the normal fetal brainstem showed that the growth rate of the pons was faster than that of the midbrain and medulla oblongata during the second and third trimesters (26), consistent with Dovjak et al.’s viewpoint (27). We also found that the height of the pons was always greater than the anterior-posterior diameter of the pons before GA 28 weeks, and after GA 28 weeks, the anterior-posterior diameter of the pons was always greater than the height. In this study, we found that GA 30 weeks is the turning point for changes in brainstem volume. The brainstem volume grows rapidly before GA 30 weeks, and changes slowly during GA 30 weeks until birth. Consequently, we propose that GA 28–30 weeks of pregnancy is a critical period for brainstem development. To our knowledge, there is currently no research focusing on this point. The trend of changes in brainstem volume with GA is consistent with previous literature reports (28), and we all agree that brainstem volume increases non-linearly.

Abnormal brainstem development can cause malformations, such as cerebellar hypoplasia, Joubert syndrome, brainstem disconnection, and so on (29). Additionally, brainstem abnormalities are associated with other systemic diseases. Dovjak et al. (30) found that the brainstem volume of fetuses with congenital heart disease decreases. Therefore, during prenatal examinations, we should first observe whether there are abnormalities in various parts of the brainstem, and then pay attention to the 2D diameter measurement of various parts of the fetal brainstem. In future research and clinical practice, we should focus on changes in the volume of brainstem.

The cerebellum is primarily responsible for coordinating movement and balance. We found that it is difficult to evaluate cerebellar fissures on MRI in early pregnancy. After GA 28 weeks, the number of cerebellar fissures increases with GA, consistent with Triulzi et al. (31), who suggested that the typical hemispherical appearance of the cerebellum can only be detected at around GA 30 weeks. On the MR scans, the anatomical details of the cerebellum of the fetus in the uterus are not clearly displayed before GA 28 weeks. Most of the research on cerebellar anatomy in early pregnancy is derived from fetal specimens fixed in formalin (32).

Most studies on fetal cerebellar have focused on measuring 2D biometric parameters using ultrasound or MRI, which only come from a specific layer and cannot fully reflect the overall development of the cerebellum (33-35). The 3D volumetric approach provides more accurate measurements than 2D radial lines. The earliest study on the relationship between cerebellar MRI volume and GA was published in 2008, which plotted cerebellar volume growth curves based on data from 93 normal fetuses GA 16–40 weeks (36). Although we all agree unanimously that the volume change curve of the cerebellum shows an upward trend and increases nonlinearly with GA, there remain some differences in the graphs. This is because Hatab et al. (36) only used sagittal images of fetal brain MRI, multiplying the area of the cerebellum by the slice thickness to calculate the volume. We used MRI scans of the fetal brain in three directions (sagittal, axial, and coronal) and obtained 3D images of the cerebellum via 3D reconstruction. Another reason may be that our fetal sample size was too small. Guihard-Costa and Larroche (37) proposed that the volume of the cerebellum doubles between the 19th and 35–37 weeks of fetal life. Our results show that the cerebellar volume increases slowly during the GA 22–30 weeks period, and significantly accelerates after GA 30 weeks. This further shows that the turning point of the volume change rate occurs at GA 30 weeks. This highlights that radiologists and ultrasonographers should pay extra attention to changes in the cerebellum during prenatal examinations at GA 30 weeks.

Therefore, accurately measuring cerebellar size and comparing it with assumed normal values is crucial for making accurate prenatal diagnoses, especially in cases of cerebellar hypoplasia and related congenital abnormalities. We know that patients with Down syndrome experience a decrease in cerebellar volume during fetal development (38). However, there is controversy over the changes in cerebellar transverse diameter in this patient population, which is not very useful for clinical guidance (39,40). Olshaker et al. (41) pointed out that fetuses with congenital heart disease have reduced cerebellar volume, whereas transverse cerebellar diameters and vermian areas do not differ between normal fetuses. This is a good reinforcement that cerebellar volume measurement is more accurate than conventional cerebellar biological indicators in observing cerebellar size. Therefore, we need a normal cerebellar volume changes trajectory and a range standard for cerebellar volume with GA to detect abnormalities and evaluate the presence of diseases during prenatal examinations. It may also reveal new windows for future therapeutic intervention strategies to improve neurodevelopmental outcomes.

The cerebral cortex, brainstem, and cerebellum are primary components of the development of the nervous system and are crucial for maintaining basic life activities (42). They are not only interrelated in terms of anatomical structure, but also have a correlation in functional development. Research has shown that the brainstem provides necessary neural information processing pathways for the cerebral cortex, and a well-developed cerebellum positively impacts the functional development of the cerebral cortex (43). In this study, there was a correlation between the growth of brainstem volume and the dorsomedial cerebral cortex, particularly in the posterior frontal, parietal, and occipital lobes. The cerebellar volume also has a high correlation with the aforementioned regions. This may be because the corticospinal tract mainly distributes from bottom to top to the parietal and occipital lobes, and rarely to the frontal lobe. Trevarrow et al. (44) indicated that the volumes of the brainstem and cerebellum are significantly reduced in patients with cerebral palsy (CP). Liu et al. (45) pointed out that the cortical thickness of the occipital, temporal, and insular lobes increases in patients with CP. This further indicates a significant correlation between the volume changes of the fetal brainstem and cerebellum and the thickness of the cerebral cortex. It is necessary to explore the relationship between volume of the brainstem and cerebellum and cortical thickness during fetal development, which can enable early detection of certain diseases, providing a basis for clinical intervention and treatment.

In addition, we found that the volume of the brainstem and cerebellum is more closely related to the right cerebral hemisphere. Andescavage et al. (46) and Achiron et al. (47) found that there is a significant asymmetry in the structure of the fetal brain, and our viewpoint is highly consistent with this. Therefore, prenatal brain asymmetry may be more common than previously thought, extending beyond structural dimensions to include asymmetric connectivity. The development of the brainstem, cerebellum, and cerebral cortex is highly coordinated and closely related. Understanding these developmental relationships between the cerebral cortex, brainstem, and cerebellum is not only helpful for basic neuroscience research, but also of great significance for early diagnosis and intervention in clinical medicine, especially in fetal and neonatal periods. Advanced technology, especially 3D MRI, can provide critical information for these explorations.

Limitations

There were limitations to this study. Firstly, the fetal brain MRI scans were only from one institution, and the reconstructed sample size was very small. These factors may influence the generalizability of the results. In the future, we hope to collect data from multiple centers, optimize 3D reconstruction methods, increase sample size, and develop reference standards that can represent the brain development of Chinese fetuses. Secondly, we did not measure the volume difference between the two cerebellar hemispheres. Thirdly, the wide range of GA (20–40 weeks) may have introduced variability in the volumetric measurements due to differences in developmental stages. Future studies with narrower GA ranges or larger sample sizes per GA could reduce this variability and enhance the precision of growth trajectories. Additionally, although gender differences in brain morphology and function have been documented (48), this study did not account for sex due to unknown sex data. If possible in the future, detailed grouping will be conducted.

Conclusions

Fetal brainstem and cerebellar development is a rapid, complex, and dynamic process. The 3D volume of the fetal brainstem and cerebellum is closely related to GA, and changes at GA 30 weeks. Establishing a normal fetal brainstem and cerebellar volume growth trajectory can help to identify abnormal growth, development, and malformations. Therefore, early intervention measures and/or support can be provided. Understanding the relationship between the development of the cerebral cortex, brainstem, and cerebellum enables better insight into their synchronous development, facilitating earlier detection of abnormalities and interventions to improve neurodevelopmental outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-218/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-218/dss

Funding: This work was supported by Gansu Province Natural Science Foundation (No. 22JR5RA997), and Gansu Province Clinical Research Center for Functional and Molecular Imaging (No. 21JR7RA438).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-218/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of The Second Hospital of Lanzhou University (No. 2021A-601) and informed consent was exempted from all participants as individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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