Joint estimation of compartment-specific T₂ relaxation and tumor microstructure using multi-TE IMPULSED MRI

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.

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 T₂ + IMPULSED method was developed to fit multi-compartmental T₂ and microstructural parameters simultaneously. A Bayesian model selection approach was carried out voxel-wisely to determine if the T₂ heterogeneity needs to be included in IMPULSED MRI in cancer.

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 $v_{\text{in}}$ with low cell density. For the in vivo animal experiments, all IMPULSED metrics except $v_{\text{in}}$ are statistically independent on TE. For B16 tumors, the IMPULSED-derived $v_{\text{in}}$ exhibited a notable increase with longer TEs. For MDA-MB-231 tumors, IMPULSED-derived $v_{\text{in}}$ showed a significant increase with increasing TEs. The T2 + IMPULSED-derived $T_2^{\text{in}}$ of all five tumor models are consistently smaller than $T_2^{\mathrm{ex}}$ .

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 T₂ + IMPULSED modeling to estimate $T_2^{\text{in}}$ and $T_2^{\mathrm{ex}}$ . These insights contribute to the ongoing development and refinement of non-invasive MRI techniques for measuring cell sizes.