MTE-NODDI: Multi-TE NODDI for disentangling non-T2-weighted signal fractions from compartment-specific T2 relaxation times

Neurite orientation dispersion and density imaging (NODDI) has become a popular diffusion MRI technique for investigating microstructural alternations during brain development, maturation and aging in health and disease. However, the NODDI model of diffusion does not explicitly account for compartment-specific T2 relaxation and its model parameters are usually estimated from data acquired with a single echo time (TE). Thus, the NODDI-derived measures, such as the intra-neurite signal fraction, also known as the neurite density index, could be T2-weighted and TE-dependent. This may confound the interpretation of studies as one cannot disentangle differences in diffusion from those in T2 relaxation. To address this challenge, we propose a multi-TE NODDI (MTE-NODDI) technique, inspired by recent studies exploiting the synergy between diffusion and T2 relaxation. MTE-NODDI could give robust estimates of the non-T2-weighted signal fractions and compartment-specific T2 values, as demonstrated by both simulation and in vivo data experiments. Results showed that the estimated non-T2 weighted intra-neurite fraction and compartment-specific T2 values in white matter were consistent with previous studies. The T2-weighted intra-neurite fractions from the original NODDI were found to be overestimated compared to their non-T2-weighted estimates; the overestimation increases with TE, consistent with the reported intra-neurite T2 being larger than extra-neurite T2. Finally, the inclusion of the free water compartment reduces the estimation error in intra-neurite T2 in the presence of cerebrospinal fluid contamination. With the ability to disentangle non-T2-weighted signal fractions from compartment-specific T2 relaxation, MTE-NODDI could help improve the interpretability of future neuroimaging studies, especially those in brain development, maturation and aging.