Evaluation of pancreatic tumor development in KPC mice using multi-parametric MRI

Abstract

BackgroundPancreatic ductal adenocarcinoma (PDA) is a fatal disease with very poor prognosis. Development of sensitive and noninvasive methods to monitor tumor progression in PDA is a critical and unmet need. Magnetic resonance imaging (MRI) can noninvasively provide information regarding underlying pathophysiological processes such as necrosis, inflammatory changes and fibrotic tissue deposition.MethodsA genetically engineered KPC mouse model that recapitulates human PDA was used to characterize disease progression. MR measures of T1 and T2 relaxation times, magnetization transfer ratio (MTR), diffusion and chemical exchange saturation transfer were compared in two separate phases i.e. slow and rapid growth phase of tumor. Fibrotic tissue accumulation was assessed histologically using Masson’s trichrome staining. Pearson correlation coefficient (r) was computed to assess the relationship between the fibrotic tissue accumulation and different MR parameters.ResultsThere was a negative correlation between amide proton transfer signal intensity and tumor volume (r = − 0.63, p = 0.003) in the slow growth phase of the tumor development. In the terminal stage of rapid growth phase of the tumor development MTR was strongly correlated with tumor volume (r = 0.62, p = 0.008). Finally, MTR was significantly correlated with % fibrosis (r = 0.87; p < 0.01), followed by moderate correlation between tumor volume (r = 0.42); T1 (r = − 0.61), T2 (r = − 0.61) and accumulation of fibrotic tissue.ConclusionsHere we demonstrated, using multi-parametric MRI (mp-MRI), that MRI parameters changed with tumor progression in a mouse model of PDA. Use of mp-MRI may have the potential to monitor the dynamic changes of tumor microenvironment with increase in tumor size in the transgenic KPC mouse model of pancreatic tumor.Electronic supplementary materialThe online version of this article (10.1186/s40644-018-0172-6) contains supplementary material, which is available to authorized users.

Identification of variable stages in murine pancreatic tumors by a multiparametric approach employing hyperpolarized 13C MRSI, 1H diffusivity and 1H T1 MRI

“…17,22,23 Careful reading of the literature, however, reveals somewhat contradictory observations between different studies focusing on different contrasts; it has therefore been suggested that multiparametric explorations may be the best way to complement MRCP to target this type of tumor early. 17,24,25 While the aforementioned contrast sources seek correlations with morphological features, another relevant source of contrast may arise from metabolic markers. Although much has been done to elucidate the unique metabolic pathways underlying PDAC from a biological perspective, 26 few molecular imaging approaches have been derived from these and translated into a clinical setting.…”

“…Magnetization transfer (MT) has also been correlated with fibrosis, and has been shown in some cases as a good potential source of contrast 17,22,23 . Careful reading of the literature, however, reveals somewhat contradictory observations between different studies focusing on different contrasts; it has therefore been suggested that multiparametric explorations may be the best way to complement MRCP to target this type of tumor early 17,24,25 …”

A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

“…Thus, glucoCEST at 3 T is not yet practicable in body regions and physical movements and the effects of and made the originally small glucoCEST signal difficult to detect. Nasopharyngeal [ 102 ] and pancreatic cancers [ 106 , 107 , 108 , 109 , 110 ] were studied in animal models. CEST was used to detect tumor [ 108 , 109 , 110 ] and characterize the tumor tissue dynamically during therapy [ 102 , 106 , 107 ].…”

Non-Invasive Monitoring of Stromal Biophysics with Targeted Depletion of Hyaluronan in Pancreatic Ductal Adenocarcinoma

“…Whole tumor volumes were reconstructed from T1W tumor anatomy scans using the Amira software platform (Visualization Sciences Group, Burlington, MA, USA). Details of the MRI protocols employed are presented in Table 1 (see also [21,25]). We employed a water saturation shift referencing (WASSR) modification to CEST imaging as described by others for pre-clinical applications at high Tesla magnet strength [26,27,28].…”