Magnetic resonance microdynamic imaging reveals distinct tissue microenvironments

Magnetic resonance imaging (MRI) provides a powerful set of tools with which to investigate biological tissues noninvasively and in vivo. Tissues are heterogeneous in nature; an imaging voxel contains an ensemble of different cells and extracellular matrix components. A long-standing challenge has been to infer the content of and interactions among these microscopic tissue components within a macroscopic imaging voxel. Spatially resolved multidimensional relaxation-diffusion correlation (REDCO) spectroscopy holds the potential to deliver such microdynamic information. However, to date, vast data requirements have mostly relegated these type of measurements to nuclear magnetic resonance applications and prevented them from being widely and successfully used in conjunction with imaging. By using a novel data acquisition and processing strategy in this study, spatially resolved REDCO could be performed in reasonable scanning times with excellent prospects for clinical applications. This new MR imaging framework-which we term “magnetic resonance microdynamic imaging (MRMI)”-permits the simultaneous noninvasive and model-free quantification of multiple subcellular, cellular, and interstitial tissue microenvironments within a voxel. MRMI is demonstrated with a fixed spinal cord specimen, enabling the quantification of microscopic tissue components with unprecedented specificity. Tissue components, such as axons, neuronal and glial soma, and myelin were identified on the basis of their multispectral signature within individual imaging voxels. These tissue elements could then be composed into images and be correlated with immunohistochemistry findings. MRMI provides novel image contrasts of tissue components and a new family of microdynamic biomarkers that could lead to new diagnostic imaging approaches to probe biological tissue alterations accompanied by pathological or developmental changes.