Characterization of the Functional and Structural Development of the Human Neonatal Brain From 30 Wks to 45 Wks ga
Characterization of the Functional and Structural Development of the Human Neonatal Brain From 30 Wks to 45 Wks ga
The major goal of this project is to characterize the structural and functional development
 of cortical plate and white matter of the human neonatal brain from the equivalent 30
 gestational weeks to 45 gestational weeks. The project is sponsored by niH R01MH092535.
 Furthermore, it is related to the blue print project of transcriptome atlas (niH RC2MH089921)
 with at least 36 million funding also sponsored by niH.

 Revealing detailed anatomy at different equivalent gestational ages of human neonatal brain
 not only aids in understanding this highly ordered process, but also provides clues to detect
 abnormalities caused by genetic or environmental factors. Cerebral vascular measurements
 offer important information on cerebral metabolism. However, either anatomical or functional
 studies of human brain development during this period are surprisingly scarce. Diffusion
 tensor imaging (DTi), a recently developed technology of magnetic resonance imaging (MRi), is
 capable of noninvasively delineating macroscopic anatomical components with high contrast and
 revealing structures at the microscopic level. Cerebral vascular quantification including
 cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRo2) can also be obtained
 through noninvasive MRi, specifically arterial spin labeling (aSL) and T2-relaxation under
 spin tagging (TRuST) MRi. in this proposed study, the structure and function of neonatal
 brain will be explored using noninvasive MRi technologies. 102 infants will be recruited and
 no sedation will be applied during MRi. The resultant database will provide reference
 standards for diagnostic radiology of premature newborns and reveal the vascular activities
 of these newborn brains. Specifically, three aims will be achieved:

 1. To delineate the anatomical development of complex structure in the cerebral wall and
 white matter tracts of neonatal brains at different equivalent gestational ages.

 2. To quantify the cerebral blood flow and metabolic rate of oxygen of neonatal brain.

 3. To correlate the structural and functional measurements with the gene transcriptome
 results.
102 normal infants with age of 30 gestational weeks to 45 gestational weeks will be recruited
 in partnership with Division of Perinatal-neonatal Medicine which consists of neonatologists
 and pediatricians providing services in Parkland Health and Hospital System (PHHS) and
 Children's Medical Center (CMC) at Dallas. among 102 normal infants, there are 17 subjects at
 each following subgroup, 30-31 gestational weeks, 32-33 gestational weeks, 34-35 gestational
 weeks, 36-38 gestational weeks, 39-42 gestational week and 43-45 gestational weeks. once
 these infants are identified, structural and functional MRi data will be acquired with
 Philips 3T located at Radiology of CMC. The sequence details are as follows: DTi: a
 single-shot echo-planar imaging (ePi) sequence with SenSe parallel imaging scheme
 (SenSitivity encoding, reduction factor [?]2.5) will be used. The imaging matrix will be
 112x112 with a field of view of 168x168mm (nominal resolution of 1.5mm), which will be zero
 filled to 256x256. axial slices of 1.5mm thickness will be acquired parallel to the
 anterior-posterior commissure line (aC-PC). a total of 65 slices will cover the entire
 hemisphere and brainstem without gap. The diffusion weighting will be encoded along 30
 independent orientations and b value will be 1000s/mm2. imaging time for each sequence will
 be 5 minutes and 30 seconds. To increase signal noise ratio (SnR), two repetitions will be
 performed, resulting in DTi imaging time 11 minutes.

 T1/T2-weighted imaging: Co-registered T2 weighted image, using a spin echo sequence, will be
 acquired with the echo time 120ms. Repetition time (TR) will be 4,500ms. The imaging
 resolution will be same as that of DTi. Co-registered FLaiR (Fluid attenuated inversion
 Recovery) T1 weighted image will also be acquired with the same field of view as that in
 diffusion tensor imaging. The T1/T2 weighted imaging time will be 5 minutes.

 Resting state fMRi: Time series of 240 volumes of BoLD (Blood-oxygenation-Level-Dependent)
 images will be acquired with a single-shot gradient-recalled T2* weighted ePi pulse sequence.
 The details of the sequence are as follows: TR [?] 1500 ms; flip angle [?] 90o; slice
 thickness[?]2.5mm; matrix [?] 68 x 68; FoV [?] 168 mm x 168 mm; voxel size[?]2.5x2.5x2.5mm.

 aSL and TRuST: Pseudo-Continuous aSL (PCaSL) sequence combined with a phase-contrast sequence
 will be used to obtain voxel level CBF estimation in units of ml blood per 100 g of tissue
 per min (ml/100g/min). The PCaSL sequence will be: field of view [?] 168x168mm,
 matrix[?]84x84, slice thickness[?]2mm, 50 axial slices acquired with zero gap, voxel
 size[?]2x2x2mm, SenSe factor[?]2.5. The phase contrast MRi will be performed with the slice
 location perpendicular to the four major feeding arteries (left/right internal carotid and
 vertebral arteries) at the level of cervical spine 3 (C3). Baseline venous oxygenation (Yv)
 will be determined in the sagittal sinus using a recently developed
 T2-Relaxation-under-Spin-Tagging (TRuST) MRi technique. The imaging parameters will be: voxel
 size 3.44x3.44x5mm3, four different T2-weightings with Tes of 0ms, 40ms, 80ms and 160ms,
 duration 1 minutes and 12 seconds. The imaging slice will be positioned axially to intersect
 the superior sagittal sinus at the level of approximately 10mm above the sinus congruence.

 Single voxel MRS: Single voxel proton MRS with short Te will be acquired. PReSS (Point
 ReSolved Spectroscopy) will be used.
Inclusion Criteria:

 1. Normal infants of both genders

 2. Any race or ethnicity

 3. Inborn preterm delivered from 30-45 weeks gestation

 4. Medically stable for transport i.e. requiring at most a nasal canula < 2 liters for
 respiratory support.

 Exclusion Criteria:

 1. Infants not delivered from 30-45 weeks gestation

 2. Infants who may have a neurological event at birth

 3. Presence of known or suspected congenital anomalies such as chromosomal anomalies

 4. Major congenital heart disease or congenital infection

 5. Substance abuse and any grade>1 of intraventricular hemorrhage (IVH) by cranial
 ultrasound

 6. Presence of cystic periventricular leukomalacia (PVL) by cranial ultrasound