Longitudinal characterization of early brain growth in-utero has been limited by a number of challenges in fetal imaging, the rapid change in size, shape and volume of the developing brain, and the consequent lack of suitable algorithms for fetal brain image analysis. There is a need for an improved digital brain atlas of the spatiotemporal maturation of the fetal brain extending over the key developmental periods. We have developed an algorithm for construction of an unbiased four-dimensional atlas of the developing fetal brain by integrating symmetric diffeomorphic deformable registration in space with kernel regression in age. We applied this new algorithm to construct a spatiotemporal atlas from MRI of 81 normal fetuses scanned between 19 and 39 weeks of gestation and labeled the structures of the developing brain. We evaluated the use of this atlas and additional individual fetal brain MRI atlases for completely automatic multi-atlas segmentation of fetal brain MRI. The atlas is available online as a reference for anatomy and for registration and segmentation, to aid in connectivity analysis, and for groupwise and longitudinal analysis of early brain growth.

We present a new algorithm, called local MAP STAPLE, to estimate from a set of multi-label segmentations both a reference standard segmentation and spatially varying performance parameters. It is based on a sliding window technique to estimate the segmentation and the segmentation performance parameters for each input segmentation. In order to allow for optimal fusion from the small amount of data in each local region, and to account for the possibility of labels not being observed in a local region of some (or all) input segmentations, we introduce prior probabilities for the local performance parameters through a new Maximum A Posteriori formulation of STAPLE. Further, we propose an expression to compute confidence intervals in the estimated local performance parameters. We carried out several experiments with local MAP STAPLE to characterize its performance and value for local segmentation evaluation. First, with simulated segmentations with known reference standard segmentation and spatially varying performance, we show that local MAP STAPLE performs better than both STAPLE and majority voting. Then we present evaluations with data sets from clinical applications. These experiments demonstrate that spatial adaptivity in segmentation performance is an important property to capture. We compared the local MAP STAPLE segmentations to STAPLE, and to previously published fusion techniques and demonstrate the superiority of local MAP STAPLE over other state-of-the- art algorithms.

The recent development of motion robust super-resolution fetal brain MRI holds out the potential for dramatic new advances in volumetric and morphometric analysis. Volumetric analysis based on volumetric and morphometric biomarkers of the developing fetal brain must include segmentation. Automatic segmentation of fetal brain MRI is challenging, however, due to the highly variable size and shape of the developing brain; possible structural abnormalities; and the relatively poor resolution of fetal MRI scans. To overcome these limitations, we present a novel, constrained, multi-atlas, multi-shape automatic segmentation method that specifically addresses the challenge of segmenting multiple structures with similar intensity values in subjects with strong anatomic variability. Accordingly, we have applied this method to shape segmentation of normal, dilated, or fused lateral ventricles for quantitative analysis of ventriculomegaly (VM), which is a pivotal finding in the earliest stages of fetal brain development, and warrants further investigation. Utilizing these innovative techniques, we introduce novel volumetric and morphometric biomarkers of VM comparing these values to those that are generated by standard methods of VM analysis, i.e., by measuring the ventricular atrial diameter (AD) on manually selected sections of 2D ultrasound or 2D MRI. To this end, we studied 25 normal and abnormal fetuses in the gestation age (GA) range of 19 to 39 weeks (mean=28.26, stdev=6.56). This heterogenous dataset was essentially used to 1) validate our segmentation method for normal and abnormal ventricles; and 2) show that the proposed biomarkers may provide improved detection of VM as compared to the AD measurement.