Ultra-high resolution magnetic resonance microscopy of in situ gadolinium gold nanoparticle-labeled cells in the rat brain

Abstract

Mapping the distribution of cells within a tissue using MR imaging has remained a significant challenge for the field. Cellular MRI can trace cells within tissue, but typically does not achieve the resolution necessary to define a cell's precise anatomical location. To detect cells with ultra-high resolution MRI, a high r₁ relaxivity intracellular contrast agent is required. Localizing this contrast within its biological context also necessitates an isotropic spatial resolution corresponding to the size of a cell's cytoplasm (∼20 μm) to place it within its biological context. We here demonstrate that gadolinium gold nanoparticles (GdAuNP) induce a high T₁-weighted cellular MRI contrast at ultra-high magnetic fields (9.4 T, and 11.7 T) that affords in situ labelled cell detection at very high resolutions (150, 100, 50, and 20 μm). A 20 μm 3D gradient-echo image (400 minutes scan) combined with MR image denoising robustly visualized the distribution of in situ labeled cells in the rat brain. Signal averaging (NA = 5) also consistently afforded the detection of labeled cells. Positive T₁-weighted contrast was confirmed to be caused by GdAuNP using histology. Immunohistochemistry confirmed the presence of GdAuNP almost entirely inside cells, primarily those of the neuronal lineage. Histology verified that the MR images accurately visualized individual cells' distribution within their anatomical context. Cellular resolution MRI of GdAuNP-labeled cells hence affords new avenues to investigate how individual cells contribute to the development, repair, and regeneration of tissues.