A robust MRI contrast agent for specific display of the interstitial stream

Abstract

Experimental and clinical studies have reported phenomena of long-range fluid flow in interstitial space. However, its behaviours and functions are yet to be addressed. The imaging of the interstitial stream in vivo can clarify its transportation route and allow further understanding of physiological mechanisms and clinical relevance. Here to illustrate the route of the interstitial stream leading to the kidney, we design and synthesize a magnetic resonance imaging (MRI) contrast agent PAA-g-(DTPA-gadolinium). This MRI agent has a high longitudinal relaxivity for higher MRI contrast and large size to avoid leakage across the interstitial space. Using dynamic contrast enhanced MRI, histochemical staining, and trace element analysis of gadolinium, we track the nano-scale PAA-g-(DTPA-gadolinium) transported in the interstitial stream. The agent can be applied for a wide range of imaging and analysis of tissues and organs, thereby enabling advances in the fields of physiology, pathology, and pharmacology.