Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma

Objectives: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard.

Methods: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SI_lt - SI_pre)/(SI_ea - SI_pre), where SI_pre, SI_ea, and SI_lt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves.

Results: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001).

Conclusion: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC.

Clinical relevance statement: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC.

Key points: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.