Objecive Single-photon emission computed tomography (SPECT) of dopamine transporters with techne- tium-99-labeled tropane derivative Tc-99m-TRODAT-1 has recently been suggested to offer valuable information in assessing the functionality of dopaminergic systems. To facilitate the non-invasive examination of the dopamine concentration in vivo, registering magnetic resonance imaging (MRI) and SPECT image is important. This article proposes a new similarity measure for MRI/SPECT registration. Methods The proposed similarity measure combines anatomic features that are characterized by specific binding of nuclear medicine and the distribution of image intensity that are characterized by the normalized mutual information (NMI). A preprocess, a novel two-cluster SPECT normalization algorithm, is also proposed. Results Compared with the conventional NMI-based registration algorithm, the proposed registration frame-work reduces the target of registration error from >7 mm to approximately 4 mm. The error of the specific-to-nonspecific Tc-99m-TRODAT-1 binding ratio (BR), a quantitative measure of TRODAT receptor binding, is also reduced from 0.45 to 0.08 in the healthy subjects and from 0.28 to 0.12 in Parkinson's disease patients. Conclusions A suitable color map, such as "rainbow," for image display enables the two-cluster SPECT normalization algorithm to provide clinically meaningful visual contrast. In addition, registering MRI/SPECT based on the proposed similarity measure improves the accuracy compared with the conventional NMI-based algorithm.
