Multiscale 3D bioimaging: from cell, tissue to whole organism

While electron microscopes and AFMs are capable of high resolution imaging to molecular levels, there is an ongoing problem in integrating these results into the larger scale structure and functions of tissue and organs within a complex organism. Imaging biological samples with optical microscopy is predominantly done with histology and immunohistochemistry, which can take up to a several weeks to prepare, are artifact prone and only available as individual 2D images. At the nano resolution scale, the higher resolution electron microscopy and AFM are used, but again these require destructive sample preparation and data are in 2D. To bridge this gap, we describe a rapid non invasive hierarchical bioimaging technique using a novel lab based x-ray computed tomography to characterize complex biological organism in multiscale- from whole organ (mesoscale) to calcified and soft tissue (microscale), to subcellular structures, nanomaterials and cellular-scaffold interaction (nanoscale). While MicroCT (micro x-ray computed tomography) is gaining in popularity for non invasive bones and tissue imaging, contrast and resolution are still vastly inadequate compared to histology. In this study we will present multiscale results from a novel microCT and nanoCT (nano x-ray tomography system). The novel MicroCT can image large specimen and tissue sample at histology resolution of submicron voxel resolution, often without contrast agents, while the nanoCT using x-ray optics similar to those used in synchrotron radiation facilities, has 20nm voxel resolution, suitable for studying cellular, subcellular morphology and nanomaterials. Multiscale examples involving both calcified and soft tissue will be illustrated, which include imaging a rat tibia to the individual channels of osteocyte canaliculli and lacunae and an unstained whole murine lung to its alveoli. The role of the novel CT will also be discussed as a possible means for rapid virtual histology using a biopsy of a human regenerated bone sample done without contrast agents and that of other soft tissues with contrast agents. Comparison between histology, SEM and MRI will be given.