“…This naturally comes at the cost of an additional, inevitable trade-off between bias and variance of the estimates. Such a trade-off could be optimized using adaptive regularization criteria such as those discussed, for instance, for 2 relaxometry (Canales-Rodríguez, Pizzolato, Piredda, Hilbert, Kunz, Pot, Yu, Salvador, Pomarol-Clotet, Kober et al, 2021a;Canales-Rodríguez, Pizzolato, Yu, Piredda, Hilbert, Radua, Kober and Thiran, 2021b). Moreover, in the future, the integration of necessary constraints (Haije, Özarslan and Feragen, 2020) while fitting the signal could ensure that the optimization of Eq.…”