Abstract
PURPOSE: This study aims to assess how T2 heterogeneity biases IMPULSED-derived metrics of tissue microstructure in solid tumors and evaluate the potential of estimating multi-compartmental T2 and microstructural parameters simultaneously. METHODS: This study quantifies the impact of T2 relaxation on IMPULSED-derived microstructural parameters using computer simulations and in vivo multi-TE IMPULSED MRI in five tumor models, including brain, breast, prostate, melanoma, and colon cancer. A comprehensive T(2) + IMPULSED method was developed to fit multi-compartmental T(2) and microstructural parameters simultaneously. A Bayesian model selection approach was carried out voxel-wisely to determine if the T(2) heterogeneity needs to be included in IMPULSED MRI in cancer. RESULTS: Simulations suggest that T2 heterogeneity has a minor effect on the estimation of d in tissues with intermediate or high cell density, but significantly biases the estimation of vin with low cell density. For the in vivo animal experiments, all IMPULSED metrics except vin are statistically independent on TE. For B16 tumors, the IMPULSED-derived vin exhibited a notable increase with longer TEs. For MDA-MB-231 tumors, IMPULSED-derived vin showed a significant increase with increasing TEs. The T2 + IMPULSED-derived T2in of all five tumor models are consistently smaller than T2ex . CONCLUSIONS: The findings from this study highlight two key observations: (i) TE has a negligible impact on IMPULSED-derived cell sizes, and (ii) the TE-dependence of IMPULSED-derived intracellular volume fractions used in T(2) + IMPULSED modeling to estimate T2in and T2ex . These insights contribute to the ongoing development and refinement of non-invasive MRI techniques for measuring cell sizes.