Prospective assessment of DCE-MRI parameters associated with advanced mandibular osteoradionecrosis after IMRT for head and neck cancer

Purpose: We aim to characterize the quantitative DCE-MRI parameters associated with advanced mandibular osteoradionecrosis (ORN) compared to the contralateral normal mandible. Methods: Patients with the diagnosis of advanced ORN after curative-intent radiation treatment of head and neck cancer were prospectively enrolled after institutional-review board approval and study-specific informed consent. Eligibility criteria included; age>18 years, pathological evidence of head and neck malignancy with history of curative-intent external beam radiotherapy; patients with clinically confirmed high-grade ORN requiring surgical intervention; and no contraindications to MRI. The DCE-MRI acquisition consisted of a variable flip angle T1 mapping sequence and a multi-phase 3D FSPGR sequence. Quantitative maps generated with the Tofts and extended Tofts pharmacokinetic model were used for analysis. Motion correction was applied. Manual segmentation of advanced ORN 3-D volume was done using anatomical sequences (T1, T2, and T1+contrast) to create ORN volumes of interest (ORN-VOIs). Subsequently, normal mandibular VOIs were segmented on the contralateral healthy mandible of similar volume and anatomical location (i.e., mirror image) to create self-control VOIs. Finally, anatomical sequences were co-registered to DCE sequences, and contours were propagated to the respective quantitative parameter maps. Results: Thirty patients were included. Median age at diagnosis was 58 years (range 19-78), and 83% were men. The site of tumor origin was in the oropharynx, oral cavity, salivary glands, and nasopharynx in 13, 9, 6, and 2 patients, respectively. The median time to ORN development after completion of IMRT was 38 months (range 6-184). There were statistically significant higher Ktrans and Ve values in ORN-VOIs compared with controls (0.23 vs. 0.07 min−1, and 0.34 vs. 0.15, p <0.0001 for both) using matched pairs analysis. The average relative increase of Ktrans in ORN-VOIs was 3.2 folds healthy mandibular control VOIs. Moreover, the corresponding rise of Ve in ORN-VOIs was 2.7 folds higher than the controls. Using combined Ktrans and Ve parameters, 27 patients (90%) had at least a 200% increase of either of the studied parameters in the ORN-VOIs compared with their healthy mandible control VOIs. Conclusion: Our results confirm there is a quantitatively significant higher degree of leakiness in the mandibular vasculature as measured using DCE-MRI parameters of areas affected with an advanced grade of ORN versus healthy mandible. We were able to measure significant increases in quantitative metrics compared to values from the non-ORN mandibular bone. Further efforts are ongoing to validate these findings to enable the use of these DCE-MRI parameter thresholds for the early detection of subclinical cases of ORN.