A computer-implemented method for quantifying fat and iron in anatomical tissue includes acquiring a plurality of multi-echo signal datasets representative of the anatomical tissue using a magnetic resonance (MR) pulse sequence. A plurality of multi-echo signal datasets are selected from the plurality of multi-echo signal datasets and used to determine a first water magnitude value and a first fat magnitude value. In response to determining that the multi-echo signal datasets include at least three multi-echo datasets, a first stage analysis is performed. This first stage analysis comprises selecting a first effective transverse relaxation rate value. Next, first algorithm inputs comprising the first water magnitude value, the first fat magnitude value, and the first effective transverse relation rate value are created. Then, a non-linear fitting algorithm is performed based on the first algorithm inputs to calculate a second water magnitude value, a second fat magnitude value, and a second effective transverse relaxation rate value. A first proton density fat fraction value is then determined based on the second water magnitude value and the second fat magnitude value.