Delta Ivim MRI As a Biomarker of Radiation-Induced Parotid Injury for Spatial Radiosensitivity Mapping
Abstract
Purpose
Head-and-neck radiotherapy inadvertently irradiates salivary glands, leading to radiation-induced xerostomia. Diffusion MRI provides sensitivity to radiation-induced microstructural tissue changes. We hypothesize that changes in intravoxel incoherent motion (IVIM) parameters can map spatial inhomogeneity of parotid gland radiosensitivity.
Methods
Twelve patients were imaged with diffusion weighted MRI (16 b-values) before and after radiotherapy. Bilateral parotids (n=24) were contoured and sub-segmented into 18 equal volumes (3D Slicer, DICOMautomaton). Model parameters (D,D*,f) were estimated using segmented bi-exponential fitting, with D determined via iterative weighted linear least squares on b-values >200 s/mm2 followed by Levenberg-Marquardt optimization for f and D*. Four patients were excluded from D* and f analysis due to MRI sequence differences. For each sub-segment, mean and third quartile (Q3) values were calculated, with delta (Δ) computed as post- minus pre-treatment. Dose-response relationships were quantified using linear mixed-effects models with random patient and subsegment intercepts. Subsegment radiosensitivity was quantified as residual deviation from expected dose-response models and correlated with a previously published regional importance model. Benjamini-Hochberg correction controlled false discovery rates across 12 tests.
Results
Mixed-effects models revealed significant dose-response relationships for 8 of 12 delta parameter-dose combinations, including ΔD* (β = 0.25 mm²/s per Gy, 95% CI [0.13, 0.37], p(BH) < 0.001) and ΔD (β = 2.4 × 10⁻³ mm²/s per Gy, p(BH) < 0.001). Subsegment radiosensitivity correlated with the regional importance model (ρ = 0.50, p = 0.037), though this did not reach significance after correction for multiple comparisons (p(BH) = 0.14).
Conclusion
IVIM parameters D* and D are sensitive biomarkers of radiation-induced parotid changes. Unlike conventional ADC, D* and D separates perfusion from diffusion, potentially enabling detection of radiation-induced vascular damage and cellular injury. Correlation between IVIM-derived radiosensitivity and the regional importance model provides complementary evidence for spatially heterogeneous dose-response within parotid gland, though larger cohorts are needed.