Magnetic resonance imaging of swallowing-related structures in nasopharyngeal carcinoma patients receiving IMRT: Longitudinal dose-response characterization of quantitative signal kinetics

Abstract

Background: We aim to characterize serial (i.e., acute and late) MRI signal intensity (SI) changes in dysphagia-associated structures as a function of radiotherapy (RT) in nasopharyngeal cancer (NPC) patients.

Materials and methods: We retrospectively extracted data on 72 patients with stage III-IV NPC treated with intensity-modulated RT (IMRT). The mean T1- and T2-weighted MRI SIs were recorded for the superior pharyngeal constrictor (SPC) and soft palate (SP) at baseline, early-after IMRT, and last follow up, with normalization to structures receiving <5 Gy.

Results: All structures had a significant increase in T2 SIs early after treatment, irrespective of the mean dose given. At last follow-up, the increase in T2 SI subsided completely for SPC and partially for SP. The T1 SI did not change significantly in early follow-up images of both structures; on late follow-up, patients with mean doses >62.25 Gy had a significant decrease in the corresponding T1 SI for SPC (1.6 ± 0.4 vs. 1.3 ± 0.4, P=0.007) but decreased non-significantly for SP.

Conclusions: Serial MRI acquisitions enable the identification of both early and late radiation-induced changes in swallowing structures after definitive IMRT for NPC. Dose dependent decrease in late T1 SI is associated with higher RT doses to the superior pharyngeal constrictor muscle; while dose independent increase in SI for both structures in early post-RT T2 images is observed and subsides after therapy. Further efforts will seek to elucidate the relationship between dose-dependent muscle SI changes and functional alteration of swallowing muscles.

Keywords: Dose–response; Dysphagia; IMRT; Magnetic resonance imaging; Nasopharyngeal carcinoma; Superior pharyngeal constrictor.

Figure 1

An example patient illustrates the segmentation of the soft palate (anterior) and the superior pharyngeal constrictor (posterior) and co-registration process. 1a) Patient T1-weighted image at baseline, 1b) T2-weighted image at 3 months after RT, 1c) T1-weighted image at 29 months after RT. 1d) The radiation dose grid superimposed on the T1-weighted MR image. 1e) Co-registration of MRI and planning computed tomography (thermal).

Figure 2

A subtraction image between the pre-RT T1-weighted MRI (2a) and the late follow-up T1-weighted MRI (2b) shows the outline of the superior pharyngeal constrictor (2c, red arrow), demonstrating the fibrosis that developed between the 2 time points. Another subtraction image between the pre-RT T2-weighted MRI (2d) and the early follow-up T2-weighted MRI (2e) shows the outline of the superior pharyngeal constrictor (2f, blue arrow head), demonstrating the edema that developed between the 2 time points.

Figure 3

Dichotomous dose-response assessment. 3a: Confirmatory analysis of the RPA-derived dose-threshold; ROC shows split performance for late T1 SI changes in superior pharyngeal constrictors above and below 62.25 Gy as an AUC of 0.707 (P=0.003, with H₀ denoting AUC =0.5). 3b: Bivariate confirmatory analysis shows distributional plots of T1 SI alteration for superior pharyngeal constrictors, stratified by doses above and below 62.25 Gy.

Figure 4

Continuous (non-linear) dose-response characterization of late T1 superior pharyngeal constrictor SI alteration from the baseline. 4a) Confirmatory analysis of the RPA-derived T1 SI change threshold; ROC shows split performance for T1 SI changes of > or <0.57 in the superior pharyngeal constrictors, as a function of D_mean, with an AUC of 0.72 (P=0.013, with H₀ denoting AUC =0.5). 4b) Sigmoidal fit of the observed probability of threshold T1 SI alteration as function of D_mean to superior pharyngeal constrictor muscles (R2=0.93). 4c) Incidence-resampled bootstrap predicted the probability of threshold T1 alteration as a function of dose; 10⁴ independently resampled distributions were individually fit using a maximum likelihood 2P-sigmoidal function, representing the range of possible dose-response normal tissue complication probability curves to best approximate a “true population incidence.”