A novel optical detector concept for dedicated and multi-modality in vivo small animal imaging

Abstract

An optical detector suitable for inclusion in tomographic arrangements for non-contact in vivo bioluminescence and fluorescence imaging applications is proposed. It consists of a microlens array (MLA) intended for field-of-view definition, a large-field complementary metal-oxide-semiconductor (CMOS) chip for light detection, a septum mask for cross-talk suppression, and an exchangeable filter to block excitation light. Prototype detector units with sensitive areas of 2.5 cm x 5 cm each were assembled. The CMOS sensor constitutes a 512 x 1024 photodiode matrix at 48 μm pixel pitch. Refractive MLAs with plano-convex lenses of 480 μm in diameter and pitch were selected resulting in a 55 x 105 lens matrix. The CMOS sensor is aligned on the focal plane of the MLA at 2.15mm distance. To separate individual microlens images an opaque multi-bore septum mask of 2.1mm in thickness and bore diameters of 400 μm at 480 μm pitch, aligned with the lens pattern, is placed between MLA and CMOS. Intrinsic spatial detector resolution and sensitivity was evaluated experimentally as a function of detector-object distance. Due to its small overall dimensions such detectors can be favorably packed for tomographic imaging (optical diffusion tomography, ODT) yielding complete 2 π field-of-view coverage. We also present a design study of a device intended to simultaneously image positron labeled substrates (positron emission tomography, PET) and optical molecular probes in small animals such as mice and rats. It consists of a cylindrical allocation of optical detector units which form an inner detector ring while PET detector blocks are mounted in radial extension, those gaining complementary information in a single, intrinsically coregistered experimental data acquisition study. Finally, in a second design study we propose a method for integrated optical and magnetic resonance imaging (MRI) which yields in vivo functional/molecular information that is intrinsically registered with the anatomy of the image object.