In recent years, new nonlinear partial differential equation (PDE) based approaches have become popular for solving image processing problems. Although the outcome of these methods is often very promising, their actual realization is in general computationally intensive. Therefore, accurate and efficient schemes are needed. The aim of this paper is twofold. First, we will show that the three dimensional alignment problem of a histological data set of the human brain may be phrased in terms of a nonlinear PDE. Second, we will devise a fast direct solution technique for the associated structured large systems of linear equations. In addition, the potential of the derived method is demonstrated on real-life data.