Abstract
Extensive desmoplastic stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor progression and to the relative resistance of tumor cells towards (radio) chemotherapy. Thus, therapies that target the stroma are under intense investigation. To allow the stratification of patients who would profit from such therapies, non-invasive methods assessing the stroma content in relation to tumor mass are required. In the current prospective study, we investigated the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI), a radiologic method that measures the random motion of water molecules in tissue, in the assessment of PDAC lesions, and more specifically in the desmoplastic tumor stroma. We made use of a sophisticated DW-MRI approach, the so-called diffusion kurtosis imaging (DKI), which possesses potential advantages over conventional and widely used monoexponential diffusion-weighted imaging analysis (cDWI). We found that the diffusion constant D from DKI is highly negatively correlated with the percentage of tumor stroma, the latter determined by histology. D performed significantly better than the widely used apparent diffusion coefficient (ADC) from cDWI in distinguishing stroma-rich (>50% stroma percentage) from stroma-poor tumors (≤50% stroma percentage). Moreover, we could prove the potential of the diffusion constant D as a clinically useful imaging parameter for the differentiation of PDAC-lesions from non-neoplastic pancreatic parenchyma. Therefore, the diffusion constant D from DKI could represent a valuable non-invasive imaging biomarker for assessment of stroma content in PDAC, which is applicable for the clinical diagnostic of PDAC.
Highlights
Abundant desmoplastic stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC), accounting for up to 90% of the tumor mass [1].The desmoplastic stroma is the result of the excessive deposition of extracellular matrix proteins, proliferation of stroma-producing cells, the most prominent being pancreatic stellate cells, and infiltration of immune cells
Thirty-one patients with final histopathological diagnosis of PDAC underwent diffusion-weighted magnetic resonance imaging (DW-magnetic resonance imaging (MRI)) with seven b-values on the day before surgery with curative intent
Four patients with a final histopathological diagnosis of chronic pancreatitis who underwent the same DW-MRI protocol on the day before partial pancreatic resection were retrospectively analyzed for comparison
Summary
Abundant desmoplastic stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC), accounting for up to 90% of the tumor mass [1].The desmoplastic stroma is the result of the excessive deposition of extracellular matrix proteins, proliferation of stroma-producing cells, the most prominent being pancreatic stellate cells, and infiltration of immune cells. The components of the desmoplastic stroma, such as type I collagen, have been described to enhance proliferation of PDAC cells [5], to increase invasion of tumor cells and to contribute to drug resistance by increasing expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) [6,7]. The tumor-promoting effects of the tumor stroma was not exclusively shown for PDAC, and for other cancers, such as lung or colon cancer [8,9,10]. Beyond these paracrine effects, the fibrotic stroma may act as physical barrier protecting the PDAC cells from the influx of antitumor drugs [4]
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