Multimodality imaging beyond CLEM: Showcases of combined in-vivo preclinical imaging and ex-vivo microscopy to detect murine mural vascular lesions.

In imaging, penetration depth comes at the expense of lateral resolution, which restricts the scope of 3D in-vivo imaging of small animals at micrometer resolution. Bioimaging will need to expand beyond correlative light and electron microscopy (CLEM) approaches to combine insights about in-vivo dynamics in a physiologically relevant 3D environment with ex-vivo information at micrometer resolution (or beyond) within the spatial, structural and biochemical contexts. Our report demonstrates the immense potential for biomedical discovery and diagnosis made available by bridging preclinical in-vivo imaging with ex-vivo biological microscopy to zoom in from the whole organism to individual structures and by adding localized spectroscopic information to structural and functional information. We showcase the use of two novel imaging pipelines to zoom into mural lesions (occlusions/hyperplasia and micro-calcifications) in murine vasculature in a truly correlative manner, that is using exactly the same animal for all integrated imaging modalities. This correlated multimodality imaging (CMI) approach includes well-established technologies such as Positron Emission Tomography (microPET), Autoradiography, Magnetic Resonance Imaging (microMRI) and Computed Tomography (microCT), and imaging approaches that are more novel in the biomedical setting, such as X-Ray Fluorescence Spectroscopy (microXRF) and High Resolution Episcopic Microscopy (HREM). Although the current pipelines are focused on mural lesions, they would also be beneficial in preclinical and clinical investigations of vascular diseases in general.

Remote RF excitation for small-bore MR imager at 15.2 T.

We report a method for remote excitation of the RF signal for preclinical-equivalent ultra high field Magnetic Resonance Imaging (MRI). A parallel-plate waveguide together with a bio-inspired surface coil were used to perform remote excitation experiments to acquire images with a small-bore MR imager at 15.2 T. The imager bore size limits the RF coil transmitter dimensions, so the Gielis super-formula was used to design an RF coil with small dimensions. Electromagnetic simulations of the principal mode were run to study the waveguide filled with air and loaded with a saline solution-filled tube. Radiation patterns were also computed in a semi-anechoic chamber for the same scenarios as above. A saline solution-filled spherical phantom and a formaldehyde-fixed mouse phantom were used to acquire images. Radiation patterns showed an omnidirectional distribution with no side lobes, and a very smooth behaviour with almost no loss of information in the saline solution-filled tube and without. The theoretical wave impedance was calculated and compared with simulated results showing an excellent correspondence. Spherical phantom image data and simulation results of B1 were contrasted and showed an important correlation. Ex vivo mouse images were of high quality and exhibited clear delineation of anatomical structures. These imaging results are in very good agreement with the simulations. Numerical, theoretical and experimental results validate this approach, using a bio-inspired surface coil with a simple waveguide for preclinical small-bore MRI at ultra high field.