Three compartment model approach to acquiring kinetic information of reactive contrast agent for MRI

Abstract

Contrast-enhanced MRI (CE-MRI) is one of the most promising functional magnetic resonance imaging techniques to acquire enhanced anatomical structure and/or information regarding hemodynamics and metabolism. Some established CE-MRI techniques include magnetic resonance angiography, dynamic contrast enhanced (DCE) MRI, and dynamic susceptibility contrast (DSC) MRI. In all of these techniques, contrast agent is required to be inert and have low retention in the body, while the sequence itself has to be fast enough to observe the first pass of the tracer bolus. Emerging research trend in theragnostic agent has opened up the possibility of cancer-treating drug to exhibit property of contrast enhancement as well. In this study, we explore the possibility of this theragnostic agent as contrast agent for T1-weighted dynamic MRI scan. Further, we proposed a three-compartment model to derive the contrast agent’s kinetic properties. The contrast agent movement was monitored through signal enhancement curve, while the contrast agent concentration were calculated to confirm the injection and circulation. The proposed model predicted contrast agent concentration in tumor area reliably with correlation of 0.6. The proposed model has demonstrated its ability to model the circulation of contrast agent in A549 tumor-bearing mice which can be used to characterize tumor metabolism activity and/or drug uptake patterns. This is the first time a therapeutic agent circulation is modeled from MRI signal using a three compartment model, which is able to explain kinetics of contrast agent that is reactive and have a high retention in vivo.