Abstract: Medical image fusion plays an important role in the clinical diagnosis of several critical neurological diseases by merging complementary information available in multimodal images. In this paper, a novel CT-MR neurological image fusion framework is proposed using an optimized biologically inspired feedforward neural model in two-scale hybrid ℓ1 − ℓ0 decomposition domain using gray wolf optimization to preserve the structural as well as texture information present in source CT and MR images. Initially, the source images are subjected to two-scale ℓ1 − ℓ0 decomposition with optimized parameters, giving a scale-1 detail layer, a scale-2 detail layer and a scale-2 base layer. Two detail layers at scale-1 and 2 are fused using an optimized biologically inspired neural model and weighted average scheme based on local energy and modified spatial frequency to maximize the preservation of edges and local textures, respectively, while the scale-2 base layer gets fused using choose max rule to preserve the background information. To optimize the hyper-parameters of hybrid ℓ1 − ℓ0 decomposition and biologically inspired neural model, a fitness function is evaluated based on spatial frequency and edge index of the resultant fused image obtained by adding all the fused components. The fusion performance is analyzed by conducting extensive experiments on different CT-MR neurological images. Experimental results indicate that the proposed method provides better-fused images and outperforms the other state-of-the-art fusion methods in both visual and quantitative assessments.