Pediatric neuroradiologist and pediatric neurologist using preterm brain atlas.During 3^rd trimester of brain development, dramatic structural changes take place and underlie the brain circuit formation at birth. Preterm births have increased significantly [1]. The large brain morphological differences of the preterm brain at 33 or 36 postmenstrual week (PMW) to that at 40PMW makes it necessary to establish age-specific atlases for preterm brains. In this study, with diffusion MRI (dMRI) data acquisition of 82 preterm and term normal neonates, we aimed to establish a digital atlas including comprehensive labeling of all major gray and white matter structures for preterm brains at 33 and 36 PMW. We demonstrated these atlases and showed the morphological changes of the major neural structures, specifically ganglionic eminence (GE) and uncinate fasciculus (unc), from 33PMW to 40PMW with JHU-neonate-SS atlas [2] as the reference.Subjects and data acquisition: 82 preterm and term normal neonates (age range 31 to 42 PMW) were recruited and divided into three groups 33, 36 and 39 PMW according to their ages at scan time. Diffusion weighted image (DWI) was acquired from 3T clinical scanner (Philips, Best, The Netherland) using a single-shot EPI sequence (SENSE factor = 2.5) without sedation. The dMRI imaging parameters were: TE=78ms, TR=6850ms, in-plane field of view= 168x168mm², in-plane imaging resolution=1.5x1.5mm², slice thickness=1.6mm, slice number=60, 30 independent diffusion encoding directions, b-value = 1000 sec/mm², repetition=2. Single-subject templates at 33, 36 and 39 PMW: Single-subject brain templates at 33, 36 and 39 PMW were established using Diffeomap (mristudio.org), following the same steps elaborated in the literature [2]. Computation of Jacobian determinants: Test data of 15 subjects with 5 at 33PMW, 5 at 36PMW and 5 at 39PMW were registered to the established single-subject templates using large deformation diffeomorphic metric mapping (LDDMM) registration [3]. Logarithms of the averaged whole brain Jacobian determinant were computed with LDDMM transformation matrices. Establishment of the DTI atlas at 33 and 36 PMW: The annotation and labeling of all major gray matter structures were conducted with contrasts from mean diffusivity (MD) maps and averaged DWI images using guidance of available atlases [2,4,5]. All major white matter tracts were manually delineated with contrasts from orientation-encoded DTI color maps and the anatomical information from tractography. Manual delineation was conducted on axial images with ROIEditor (mristudio.org), followed by adjustment in coronal and sagittal images. Identification of major structural differences based on atlases of 33PMW and 36PMW as well as the published term brain neonatal atlas: The morphological differences among major structures were examined by visual inspection from an experienced neuroanatomist, based on the established atlases of 33PMW and 36PMW in this study and term brain neonatal atlas (JHU-neonate-SS) [2]. Jacobian determinants: Jacobian determinants, shown in Fig 1, demonstrate that dramatic brain morphological changes from 33 to 39 PMW. Smallest Jacobian determinants at the diagonal entries in Fig 1 were found with age of the test data subject same as that of the single-subject template. Larger absolute Jacobian determinants were found with bigger age difference between age of the test data subject and that of the single-subject template. Gray and white matter DTI atlas at 33 and 36 PMW: The comprehensive labels of single-subject template at 33 and 36 PMW are shown in Fig 2 (Cau: caudate nucleus; STG: superior temporal gyrus; EC: entorhinal cortex; Amyg: amygdala) on the underlying high resolution MD maps and orientation-encoded DTI color maps, respectively. The atlases cover as many as 22 brainstem and cerebellar structures, 39 cerebral white matter structures, 12 deep gray matter structures and 52 cerebral cortical structures. Dramatic structural changes from 33PMW to 40PMW: Dramatic morphological changes were found in most gray and white matter structures. As shown in Fig 2a-2c, the size decreases of GE from 33PMW to 36PMW and its final disappearance at around 40PMW are most striking. Dramatic size increase of unc is also highlighted in Fig 2d-2f.The results of the Jacobian determinant showed it is critical to establish a brain atlas on every gestational week. Moreover, the dramatic morphological changes of GE and unc shown in Fig 2 suggest that major neural structures still undergo rapid growth from 33PMW to 40PMW. The established age-specific comprehensive gray and white matter atlases of 33PMW and 36PMW brains may be used for not only understanding this highly ordered development processes but also serving as clinical anatomical references to detect neural abnormalities.