(A) Comparisons of MRH-NF/MBP results with reference histology and MRI-based markers that are commonly used to characterize axon and myelin in the brain (MTR: magnetization transfer ratio; FA: fractional anisotropy; DR: radial diffusivity) as well as linear prediction of NF and MBP (fitting-NF/MBP) based on five MRI parameter maps (T2, MTR, FA, MD, and MK). (B) Even though MRH-NF/MBP were trained using coronal sections, they were able to generate maps for other orthogonal sections (e.g., horizontal sections shown here) from three-dimensional (3D) MRI, as expected from the local ensemble average property. The results show general agreements with structures in comparable horizontal MTR, FA, and five-parameter linear fitting maps. (C) Receiver operating characteristic (ROC) analyses of MRH-NF and MRH-MBP show enhanced specificity to their target structures defined in the reference data than MTR, FA, DR, and five-parameter linear fittings. Here, DR values from diffusion-weighted images (DWIs) with b-values of 2000 and 5000 s/mm2 are examined separately. (D) The distribution of randomly selected 3 × 3 MRI patches in the network’s 2D feature spaces of MRH-NF and MRH-MBP defined using the t-distributed stochastic neighbor embedding (t-SNE) analyses. (E–F) Enlarged maps of the cortical (E) and hippocampal (F) regions of normal C57BL6 mouse brains comparing the tissue contrasts in MRH-NF/MBP with histology and MRI. In (E), white arrows point to a layer structure in the hippocampus. ROC analyses performed within the cortex and hippocampus show that MRH-NF/MBP have higher specificity than FA, MTR, and DR, but with lower areas under the curve (AUCs) than in C due to distinct tissue properties. (G) Relative contributions of T2-weighted (T2W), MT, diffusion MRI (DWI-L: b = 2000 s/mm2; DWI-H: b = 5000 s/mm2) for the whole brain, white matter, and cortex/hippocampus. *: p < 0.005 (paired t-test, n = 4, from left to right, p = 0.0043/0.000021/0.00072/0.0014 for NF, p = 0.000058/0.000035/0.000002/0.00392 for MBP, respectively). Details on the contributions of each MRI contrast can be found in Figure 3—figure supplement 3.