Time-dependent diffusion MRI in determining mismatch repair status of endometrial cancer

Abstract Objectives Mismatch repair (MMR) proteins are important in determining therapeutic strategy in endometrial cancer (EC). We investigated the role of microstructural parameters derived from time-dependent diffusion magnetic resonance imaging (td-dMRI) in differentiating MMR status of EC. Materials and methods This prospective single-center study enrolled patients with suspected EC who underwent preoperative td-dMRI. Tumors were classified as MMR-deficient (dMMR) and MMR-proficient (pMMR) by immunohistochemistry. The microstructural parameters, including intracellular volume fraction ( $${v}_{{in}}$$ v i n ), cell diameter ( $$d$$ d ), cellularity ( $${{\rm{\rho }}}$$ ρ ), extracellular diffusivity ( $${D}_{{ex}}$$ D e x ), and water exchange rate constant ( $${k}_{{in}}$$ k i n ), were derived by fitting td-dMRI data with three methods (IMPULSED, JOINT, and EXCHANGE), together with the apparent diffusion coefficient (ADC). Differences in these microstructural parameters between dMMR and pMMR EC were compared. The diagnostic performances were evaluated by the areas under the receiver operating characteristic curve (AUC). Results Eighty-two patients (17 dMMR, 61.8 ± 10.1 years and 65 pMMR, 58.6 ± 11.8 years) were recruited. dMMR EC exhibited higher $${v}_{{in}}$$ v i n , $${{\rm{\rho }}}$$ ρ and lower $${D}_{{ex}}$$ D e x , ADC values than pMMR EC ( p ≤ 0.003). IMPULSED and JOINT demonstrated higher AUCs than conventional ADC ( p = 0.025 and 0.046, respectively). The combined selected microstructural parameters ( $${v}_{{\mathrm{in}}}$$ v in and $${D}_{{ex}}$$ D e x ) derived from JOINT achieved an AUC of 0.903; JOINT demonstrated superior parametric stability and marginally better calibration than IMPULSED. Conclusion In this exploratory study, td-dMRI discriminated between dMMR and pMMR ECs, providing information on the intricate microscopic organizational structures in tumors. The microstructural parameters may serve as a promising method to improve the diagnostic efficacy of diffusion-weighted MRI in differentiating MMR status of EC. Key Points Question There remains an unmet need for noninvasive, preoperative tools to assess DNA MMR status in EC. <ja