Magnetization transfer explains most of the $T_1$ variability in the MRI literature

Purpose: To identify the predominant source of the $T_1$ variability described in the literature, which ranges from 0.6 - 1.1 s for brain white matter at 3 T. Methods: 25 $T_1$-mapping methods from the literature were simulated with a mono-exponential and magnetization-transfer (MT) models, each followed by mono-exponential fitting. A single set of model parameters was assumed for the simulation of all methods, and these parameters were estimated by fitting the simulation-based to the corresponding literature $T_1$ values of white matter at 3 T. Results: Mono-exponential simulations suggest good inter-method reproducibility and fail to explain the highly variable $T_1$ estimates in the literature. In contrast, MT simulations suggest that a mono-exponential fit results in a variable $T_1$ and explain up to 62% of the literature's variability. Conclusion: The results suggest that a mono-exponential model does not adequately describe longitudinal relaxation in biological tissue. Therefore, $T_1$ in biological tissue should be considered only a semi-quantitative metric that is inherently contingent upon the imaging methodology; and comparisons between different $T_1$-mapping methods and the use of simplistic spin systems - such as doped-water phantoms - for validation should be viewed with caution.