In vivo co-registered hybrid-contrast imaging by successive photoacoustic tomography and magnetic resonance imaging

Magnetic resonance imaging (MRI) and photoacoustic tomography (PAT) are two advanced imaging modalities that offer two distinct image contrasts: MRI has a multi-parameter contrast mechanism that provides excellent anatomical soft tissue contrast, whereas PAT is capable of mapping tissue physiological metabolism and exogenous contrast agents with optical specificity. Attempts have been made to integrate these two modalities, but rigid and reliable registration of the images for in vivo imaging is still challenging. In this paper, we present a complete hardware-software solution for the successive acquisition and co-registration of PAT and MRI images in in vivo animal studies. Based on commercial PAT and MRI scanners, our solution includes a 3D-printed dual-modality animal imaging bed, a 3-D spatial image co-registration algorithm with bi-model markers, and a robust modality switching protocol for in vivo imaging studies. Using the proposed solution, we successfully demonstrated co-registered hybrid-contrast PAT-MRI imaging that simultaneously display multi-scale anatomical, functional and molecular characteristics on healthy and cancerous living mice. Week-long longitudinal dual-modality imaging of tumor development reveals information on size, border, vascular pattern, blood oxygenation, and molecular probe metabolism of the tumor micro-environment at the same time. Additionally, by incorporating soft-tissue information in the co-registered MRI image, we further show that PAT image quality could be enhanced by MRI-guided light fluence correction. The proposed methodology holds the promise for a wide range of pre-clinical research applications that benefit from the PAT-MRI dual-modality image contrast.