Objective
The objective of the study was to characterize total and regional volumetric brain growth in healthy fetuses during the second and third trimesters of pregnancy, using an automated method.
Study Design
We developed and validated an automated method to quantify global and regional in vivo brain volumes using fetal magnetic resonance imaging. We then computed the percentage of growth for each brain structure in a cohort of 64 healthy fetuses (25.4-36.6 weeks’ gestational age).
Results
The cerebellum demonstrated the greatest maturation rate, with a 4-fold increase (384%) in volume between 25.4 and 36.6 weeks, and a relative growth rate of 12.87% per week. Both total brain and cerebral volumes increased by 230% and brain stem volume by 134% over the same gestational age period. Conversely, lateral ventricular volume decreased by 4.18% per week.
Conclusion
The availability and ongoing validation of normative fetal brain growth trajectories will provide important tools for early detection of impaired fetal brain growth upon which to manage high-risk pregnancies.
The in vivo study of fetal brain development has become a major focus in the rapidly evolving field of neuroimaging research. Conventional fetal magnetic resonance imaging (MRI) is an important clinical tool for the qualitative morphological evaluation of the fetal brain. Previously the application of advanced MRI techniques to the fetus was limited by fetal motion, which resulted in low voxel resolution, poor contrast, and motion artifact. In recent years the successful application of advanced MRI acquisition techniques and dedicated postprocessing tools to the fetus has enabled the 3-dimensional (3-D) quantitative evaluation of the developing brain.
Until recently, quantitative MRI studies of brain development during the critical third trimester after conception have been confined largely to ex utero premature infants. For example, 3D-volumetric MRI with tissue segmentation has provided major insights into the rate and progression of brain development during this vulnerable third-trimester period. Total brain volume has been shown to increase linearly at a rate of 22 mL per week. The growth of the immature cerebellum has been shown to be particularly rapid in the third trimester, exceeding cerebral growth and intracranial cavity volume. However, these and other studies have also shown that prematurity-related factors appear to slow down regional and global brain growth.
Quantitative fetal MRI studies describing normal in vivo brain development are needed to better understand the timing and progression of aberrant brain development in the compromised fetus. To date, few studies have applied quantitative MRI techniques to the fetus in vivo. Computation of fetal brain volumes has been based primarily on manually derived measures and on fetuses with suspected or confirmed fetal brain anomalies.
Manual measurements of the brain are difficult and labor intensive. It can take a trained operator several hours to days to manually label a single high-resolution brain MR data set. Manual measurements are also prone to operator-induced bias and are not feasible when dealing with large MRI databases. These limitations impede the widespread use of these powerful techniques.
An automated method for quantifying total brain volume in vivo was recently described in 25 fetuses in which ventriculomegaly was ruled out. More recently Scott et al described an automated method using a spatiotemporal fetal atlas to characterize the different layers of the developing fetal brain (eg, subplate, intermediate zone). Although this report provides important insights into fetal brain development, it primarily focuses on measurements obtained from second-trimester MRI fetuses and does not capture the exuberant and energy-dependent growth that occurs in the third trimester.
The objective of this study was to characterize total and regional volumetric brain growth in a cohort of healthy fetuses studied during the second and third trimester of gestation using an automated template-based method.
Materials and Methods
Study procedures
We prospectively enrolled 68 pregnant women and performed nonsedated fetal MRI studies between 25.4 and 36.6 weeks’ gestational age (GA). Gestational ages were calculated using maternal dates or first-trimester ultrasound measurements, if available. Normal controls were recruited from healthy pregnant volunteers and from pregnancies with a normal fetal echocardiogram performed for a family history of congenital heart disease.
Exclusion criteria included multiple pregnancies, congenital infection, or a maternal contraindication to MRI. We also excluded fetuses with any evidence on antenatal ultrasound of abnormality in the brain or other systems or abnormal karyotype on amniocentesis. Postnatally, newborns underwent a repeat MRI, which was normal in all subjects. The Vineland Adaptive Behavior Scale (VABS) was used to assess functional performance in communication, daily living, socialization, and motor skills in our cohort between 18 and 24 months. Developmental scores on the VABS were age appropriate for all infants.
All fetal MRI studies were performed using a 1.5 Tesla MR scanner (Achiva; Philips Medical System, Best, The Netherlands) and a 5-channel phased array cardiac coil. First, a localizer sequence was performed to determine the location of the fetal head. Then multiplanar single-shot fast spin echo (SSFSE) T2-weighted imaging sequences were obtained using the following parameters: effective echo time 120 milliseconds; repetition time 12500 milliseconds; field of view 330 mm; slice thickness 2 mm with no interslice gap (resolution of 1 × 1 × 2 mm in each acquisition plane), acquisition matrix 256 × 204, and an acquisition time of 18-42 seconds. Axial, coronal, and sagittal views of the fetal brain were acquired.
The study was approved by the Committee on Clinical Investigation and written informed consent was obtained from all participants.
MRI methods
MRI processing
Brain extraction
A universal issue of in vivo fetal brain MRI is the presence of maternal tissue surrounding the fetus. We used an automatic method to extract a mask of the brain from the uterus. First, a region of interest containing the intracranial cavity was automatically defined ( Figure 1, A ) using acquisitions in all 3 planes (ie, coronal, axial, and sagittal that were acquired in succession). The fetal brain limits were defined in the slice direction for each scan. The 3 scans were synthesized into a single volume and the limits of the bounding box were automatically obtained from the slice limits of each of the orthogonal acquisitions, therefore delineating a reduced and contained box around the intracranial cavity. This enabled us to remove the surrounding maternal tissues, which can affect the brain extraction procedure itself. After this first delineation stage, the fetal brain extraction was refined using mincbet, a brain-masking method based on the brain extraction tool. Figure 1, B shows an example of a fetal brain extraction result. The brain extraction step failed in 4 of 68 fetal brain MRI studies. We removed these 4 MRI studies from the study and report the results of the remaining 64 fetuses.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
