Quantitative susceptibility mapping and R1 measurement: Determination of the myelin volume fraction in the aging ex vivo rat corpus callosum

In studies of the white matter (WM) in aging brains, both quantitative susceptibility mapping (QSM) and direct R1 measurement offer potentially useful ex vivo MRI tools that allow volumetric characterization of myelin content changes. Despite the technical importance of such MRI methods in numerous age‐related diseases, the supposed linear relationship between the estimates of either the QSM or R1 method and age‐affected myelin contents has not been validated. In this study, the absolute myelin volume fraction (MVF) was determined by transmission electron microscopy (TEM) as a gold standard measure for comparison with the values obtained by the aforementioned MR methods. To theoretically evaluate and understand the MR signal characteristics, QSM simulations were performed using the finite perturber method (FPM). Specifically, the simulation geometry modeling was based on TEM‐derived structures aligned orthogonally to the main magnetic field, the construct of which was used to estimate the magnetic field shift (ΔB) changes arising from the conjectured myelin structures. Experimentally, ex vivo corpus callosum (CC) samples from rat brains obtained at 6 weeks (n = 3), 4 months (n = 3), and 20 months (n = 3) after birth were used to establish the relationship between changes quantified by either QSM or R1 with the absolute MVF by TEM. From the ex vivo brain samples, the scatterplot of mean MVF versus R1 was fitted to a linear equation, where R1mean = 0.7948 × MVFmean + 0.8118 (Pearson's correlation coefficient r = 0.9138; p