Logan graphical analysis for quantitative evaluation of Calcium channel activity in the pituitary gland using manganese- enhanced MRI (MEMRI)

Introduction: The purpose of this study was to quantitatively evaluate Ca-channel activity in the pituitary gland (Pit) using manganese-enhanced MRI (MEMRI) and Logan graphical analysis (LGA). LGA is an algorithm already widely used with positron emission tomography (PET) for the quantitative analysis of reversible processes such as ligands binding temporarily to neuroreceptors [1]. When adapted to MRI studies where a contrast agent is used as a tracer that enters tissue reversibly, LGA states that there is a certain time t* after tracer administration where a plot of ∫Ct/Ct versus ∫Cp/Ct becomes linear (Ct and Cp are the concentrations of the tracer in tissue and arterial plasma, respectively). As an example, for a two-compartment model, the slope of the linear relationship provides direct information about the inflow and outflow constants of the particular tracer from plasma to tissue. Since manganese ions (Mn2+) can enter excitable cells through Ca2+ channels, Mn2+ ions have been used as a MRI contrast agent for both functional and anatomical studies [2]. However, because the blood brain barrier (BBB) hinders the passage of Mn ions into brain tissue when using manganeseenhanced techniques such as AIM-MEMRI [3], the BBB must be artificially disrupted so that neural activity can be observed. On the other hand, it is well known that Mn2+ ions can enter the central nervous system in circumventricular organs such as the Pit because the BBB is nonexistent or leaky. In this study, the Mn2+ concentrations in the posterior pituitary gland (PPit) were measured with rapidly acquired T1-maps before and after contrast agent injection [4, 5]. The Ca2+-channel activity was varied by administration of excitatory (Glutamate) and inhibitory (Verapamil) agents and the difference in channel activity was evaluated using LGA.