Image Fusion for Improving the Spatial Resolution of LA-ICP-MS Imaging.

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging has been employed to determine elemental distributions in biological tissues and has proven to be valuable for studying nanomaterials used in drug delivery systems. However, in LA-ICP-MS imaging, there are often trade-offs between achieving higher spatial resolution, maintaining sensitivity, and minimizing acquisition time. Using a larger laser spot size retains sensitivity and allows for faster image acquisition, but the resulting poorer resolution is often insufficient for characterizing the distributions of nanomaterials in functional units of organs, such as the kidney, liver, and spleen. In this work, we describe an approach to enhance the spatial resolution of LA-ICP-MS imaging using image fusion through the computational integration of LA-ICP-MS and optical microscopy images. This approach maintains the highly precise and sensitive elemental distributions inherent to LA-ICP-MS while leveraging the high spatial resolution of optical microscopy to obtain more detailed suborgan maps for both biological metals and nanomaterials. Our approaches enable the construction of LA-ICP-MS images with 5 μm resolution without changes to hardware, operational time, or sensitivity. The resulting enhanced resolution yields new insights into nanomaterial excretion through the liver and the role of the immune system in recognizing gold nanoparticles in the spleen. This fusion approach promises to serve as a valuable tool for advancing nanomaterial-based drug delivery systems.