Increased anatomical detail by in vitro MR microscopy with a modified Golgi impregnation method

Golgi impregnation is unique in its ability to display the dendritic trees and axons of large numbers of individual neurons by histology. Here we apply magnetic resonance microscopy to visualize the neuroanatomy of animal models by combining histologic fixation chemistry with paramagnetic contrast agents. Although there is some differential uptake of the standard small-molecular-weight contrast agents by different tissue types, detailed discrimination of tissue architecture in MR images does not approach that of standard histology. Our modified Golgi impregnation method significantly increases anatomic detail in magnetic resonance microscopy images. Fixed mouse brains were treated with a solution containing a paramagnetic contrast agent (gadoteridol) and potassium dichromate. Results demonstrate a specific contrast enhancement likely due to diamagnetic hexavalent chromium undergoing tissue specific reduction to paramagnetic trivalent chromium. This new method dramatically improves neuroanatomical contrast compared to conventional fixation, displaying detail approximating that of histologic specimens at low (4x) magnification.