Quantitative functional MRI in a clinical orthotopic model of pancreatic cancer in immunocompetent lewis rats

Objective: To demonstrate feasibility of performing quantitative MRI measurements in an immuno-competent rat model of pancreatic cancer by comparing in vivo anatomic and quantitative imaging measurements to tumor dissemination observations and histologic assays at necropsy. Meterials and methods: Rat ductal pancreatic adenocarcinoma DSL-6A/C1 cell line and Lewis rats were used for these studies. 10⁸ DSL-6A/C1 cells were injected subcutaneously into the right flank of donor rats. Donor tumors reaching 10 mm were excised, and 1 mm³ tumor fragments were implanted within recipient rat pancreas during mini-laparotomy. T1-weighted, T2-weighted, diffusion-weighted, and dynamic contrast-enhanced (DCE) MRI were performed using a Bruker 7.0T ClinScan. After MRI, all animals underwent autopsy. Primary tumor size was measured, and dissemination score was used to assess local invasion and distant metastasis. Primary tumor and all sites of metastases were harvested and fixed for H&E, Masson’s trichrome, and rat anti-CD34 staining. Trichrome slides were scanned and digitized for measurement of fibrotic tissue areas. Anti-CD34 slides were used for microvessel density (MVD) measurements. Results: Primary tumors, local invasion, and distant metastases were confirmed for all rats. No significant differences were found between in vivo MRI measurements (48.7 ± 5.3 mm) and ex vivo caliper measurements (43.6 ± 3.6 mm) of primary tumor sizes (p >.05). Spleen, liver, diaphragm, peritoneum, and abdominal wall metastases were observed on MRI but smaller lung, mediastinum, omen, and mesentery metastases were only observed at necropsy. Contrast uptake observed during DCE measurements was significantly greater in both primary and metastatic tumor tissues compared to skeletal muscle and normal liver tissues. Both primary and metastatic tumors were hyper-intense in T2-weighted images and hypo-intense in T1-weighted images, but no differences were found between quantitative T2 measurements in primary tumors and that in metastases. Similarly, quantitative ADC measurements were similar for both primary tumor and liver metastases (1.13 ± 0.3 × 10^-3 and 1.24 ± 0.4 × 10^-3 mm²/s, respectively). Histologic fibrosis and MVD measurements were similar in primary tumors and metastases. Conclusions: Anatomic and quantitative functional MRI measurements are feasible in orthotropic DSL rat model and will permit non-invasive monitoring of tumor responses during longitudinal studies intended to develop new interventional therapies for primary and metastatic disease.