Histological brain slices are widely used in neuroscience to study the anatomical organization of neural circuits. Systematic and accurate comparisons of anatomical data from multiple brains, especially from different studies, can benefit tremendously from registering histological slices onto a common reference atlas. Most existing methods rely on an initial reconstruction of the volume before registering it to a reference atlas. Because these slices are prone to distortions during the sectioning process and often sectioned with non-standard angles, reconstruction is challenging and often inaccurate. Here we describe a framework that maps each slice to its corresponding plane in the Allen Mouse Brain Atlas (2015) to build a plane-wise mapping and then perform 2D nonrigid registration to build a pixel-wise mapping. We use the L2 norm of the histogram of oriented gradients of two patches as the similarity metric for both steps, and a Markov random field formulation that incorporates tissue coherency to compute the nonrigid registration. To fix significantly distorted regions that are misshaped or much smaller than the control grids, we train a context-aggregation network to segment and warp them to their corresponding regions with thin plate spline. We have shown that our method generates results comparable to an expert neuroscientist and is significantly better than reconstruction-first approaches.
* Mark Horowitz
* Jing Xiong
* Jing Ren
* Liqun Luo
 Xiong, J., Ren, J., Luo, L., & Horowitz, M. (2018). Mapping mouse brain slice sequence to a reference brain without 3D reconstruction. bioRxiv, 357475.
 Ren, J., Friedmann, D., Xiong, J., Liu, C. D., Ferguson, B. R., Weerakkody, T., … & Weissbourd, B. (2018). Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems. Cell, 175(2), 472-487.