Quantitative MRI of Gd-DOTA Accumulation in the Mouse Brain After Intraperitoneal Administration: Validation by Mass Spectrometry.

Abstract

In mice, intraperitoneal (ip) contrast agent (CA) administration is convenient for mapping microvascular parameters over a long-time window. However, continuous quantitative MRI of CA accumulation in brain over hours is still missing. To validate a quantitative time-resolved MRI technique for mapping the CA kinetics in brain upon ip administration. Prospective, animal model. 25 C57Bl/6JRj mice underwent MRI. 7-T, gradient echo sequence. Gd-DOTA concentration was monitored by MRI (25 s/repetition) over 135 minutes with (N = 15) and without (N = 10) ip mannitol challenge (5 g/kg). After the final repetition, the brains were sampled to quantify gadolinium by mass spectrometry (MS). Upon manual brain segmentation, the average gadolinium concentration was compared with the MS quantification in transcardially perfused (N = 20) and unperfused (N = 5) mice. Precontrast T1 -maps were acquired in 8 of 25 mice. One-tailed Spearman and Pearson correlation between gadolinium quantification by MRI and by MS, D'Agostino-Pearson test for normal distribution, Bland-Altman analysis to evaluate the agreement between MRI and MS. Significance was set at P-value <0.05. MRI showed that ip administered CA reached the blood compartment (>5 mM) within 10 minutes and accumulated continuously for 2 hours in cerebrospinal fluid (>1 mM) and in brain tissue. The MRI-derived concentration maps showed interindividual differences in CA accumulation (from 0.47 to 0.81 mM at 2 hours) with a consistent distribution resembling the pathways of the glymphatic system. The average in-vivo brain concentration 2 hours post-CA administration correlated significantly (r = 0.8206) with the brain gadolinium quantification by MS for N = 21 paired observations available. The presented experimental and imaging protocol may be convenient for monitoring the spatiotemporal pattern of CA uptake and clearance in the mouse brain over 2 hours. The quantification of the CA from the MRI signal in brain is corroborated by MS. N/A TECHNICAL EFFICACY: Stage 1.