Optimization is an important component in linear and nonlinear medical image registration. While common non-derivative approaches such as Powell's method are accurate and efficient, they cannot easily be adapted for parallel hardware. In this paper, new optimization strategies are proposed for parallel, shared-memory (SM) architectures. The Dividing Rectangles (DIRECT) global method is combined with the local Generalized Pattern Search (GPS) and
Multidirectional Search (MDS) and to improve efficiency on multiprocessor systems. These methods require no derivatives, and can be used with all similarity metrics. In a multiresolution framework, DIRECT is performed with relaxed convergence criteria, followed by local refinement with MDS or GPS. In 3D-3D MRI rigid registration of simulated MS lesion volumes to normal brains with
varying noise levels, DIRECT/MDS had the highest success rate, followed by DIRECT/GPS. DIRECT/GPS was the most efficient (5-10 seconds with 8 CPUs, and 10-20 seconds with 4 CPUs). DIRECT followed by MDS or GPS greatly increased efficiency while maintaining accuracy. Powell's method generally required more than 30 seconds (1 CPU) with a low success rate (0.3 or lower). This work indicates that parallel optimization on shared memory systems can markedly improve registration speed and accuracy, particularly for large initial misorientations.