Tumor Microenvironment: Insights from Multiparametric MRI in Pancreatic Ductal Adenocarcinoma

<b>Background/Objectives:</b> The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is characterized by an enriched stroma, hampering the effectiveness of therapy. This co-clinical study aimed to (1) provide insight into early post-treatment changes in the TME using multiparametric magnetic resonance imaging (mpMRI)-derived quantitative imaging biomarkers (QIBs) in a preclinical PDAC model treated with radiotherapy and correlate these QIBs with histology; (2) evaluate the feasibility of obtaining these QIBs in patients with PDAC using clinically approved mpMRI data acquisitions. <b>Methods</b>: Athymic mice (<i>n</i> = 12) at pre- and post-treatment as well as patients with PDAC (n = 11) at pre-treatment underwent mpMRI including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) data acquisition sequences. DW and DCE data were analyzed using monoexponential and extended Tofts models, respectively. DeepLIIF quantified the total percentage (%) of tumor cells in hematoxylin and eosin (H&E)-stained tissues from athymic mice. Spearman correlation and Wilcoxon signed rank tests were performed for statistical analysis. <b>Results</b>: In the preclinical PDAC model, mean pre- and post-treatment ADC and K^trans values differed significantly (<i>p</i> < 0.01), changing by 20.50% and 20.41%, respectively, and the median total tumor cells quantified by DeepLIIF was 24% (range: 15-53%). Post-treatment ADC values and relative change in v_e (rΔv_e) showed a significant negative correlation with total tumor cells (<i>ρ</i> = -0.77, <i>p</i> < 0.014 for ADC and <i>ρ</i> = -0.77, <i>p</i> = 0.009 for rΔv_e). In patients with PDAC, pre-treatment mean ADC and K^trans values were 1.76 × 10^-3 (mm²/s) and 0.24 (min^-1), respectively. <b>Conclusions</b>: QIBs in both preclinical and clinical settings underscore their potential for future co-clinical research to evaluate emerging drug combinations targeting both tumor and stroma.