Correlative dynamic contrast MRI and microscopic assessments of tumor vascularity in RIP-Tag2 transgenic mice
Barbara Sennino1, Hans-Juergen Raatschen, Michael F Wendland
1Department of Cardiovascular Research Institute, Comprehensive Cancer Center, University of California, San Francisco, California, USA.
Abstract:
The purpose of this study was to define the feasibility of dynamic contrast-enhanced magnetic resonance imaging (MRI) to estimate the vascular density and leakiness of spontaneous islet cell tumors in RIP-Tag2 transgenic mice. Dynamic T(1)-weighted spoiled gradient echo (SPGR) imaging at 2.0 T was performed in 17 RIP-Tag2 mice using a prototype blood pool macromolecular contrast medium (MMCM), albumin-(Gd-DTPA)(35). Kinetic analysis of the dynamic enhancement responses based on a two-compartment model was used to estimate fractional plasma volume (fPV) and the coefficient of endothelial permeability (K(PS)) for each tumor. The MRI estimate of fPV was correlated on a tumor-by-tumor basis with corresponding microscopic measurements of vascular density. The fPV assays by MMCM-enhanced imaging ranged from 2.4%-14.1% of tissue volume. Individual tumor fPV values correlated significantly (r = 0.79, P < 0.001) with the corresponding microscopic estimates of vascularity consisting of the combined area densities of lectin-perfused microvessels plus erythrocyte-stained blood lakes. A biotinylated derivative of the albumin-based MMCM confirmed extravasation of the contrast agent from some tumor blood vessels and accumulation in 25% of blood lakes. The K(PS) values ranged from 0 (no detectable leak) to 0.356 mL/min/100 cm(3). Dynamic MMCM-enhanced MRI is feasible in RIP-Tag2 pancreatic tumors, yielding estimates of vascular permeability and microscopically validated measurements of vascular richness.
Insights
Dynamic contrast-enhanced MRI using a macromolecular contrast medium is feasible for assessing pancreatic tumors in RIP-Tag2 mice. This technique accurately estimates tumor vascular density and permeability, correlating well with microscopic findings.
Area of Science:
- Biomedical imaging
- Oncology
- Vascular biology
Background:
- Islet cell tumors in RIP-Tag2 transgenic mice are a model for human neuroendocrine tumors.
- Accurate assessment of tumor vascularity and permeability is crucial for understanding tumor growth and developing therapies.
- Current methods for evaluating tumor microvasculature can be invasive or lack quantitative precision.
Purpose of the Study:
- To determine the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) for quantifying vascular density and endothelial permeability in spontaneous islet cell tumors.
- To validate MRI-derived vascular parameters against established microscopic measurements.
- To assess the utility of a novel albumin-based macromolecular contrast medium (MMCM) in this model.
Main Methods:
- Dynamic T(1)-weighted spoiled gradient echo (SPGR) imaging was performed at 2.0 T in 17 RIP-Tag2 mice.
- A prototype blood pool macromolecular contrast medium (MMCM), albumin-(Gd-DTPA)(35), was administered intravenously.
- Kinetic analysis using a two-compartment model estimated fractional plasma volume (fPV) and the coefficient of endothelial permeability (K(PS)).
- MRI-derived fPV was correlated with microscopic measurements of vascular density (lectin staining and blood lakes).
- A biotinylated MMCM derivative was used to confirm contrast agent extravasation.
Main Results:
- MRI-estimated fPV ranged from 2.4% to 14.1% of tumor volume.
- Tumor fPV values showed a significant positive correlation (r = 0.79, P < 0.001) with microscopic vascular density measurements.
- Extravasation of MMCM was confirmed in 25% of observed blood lakes.
- Estimated K(PS) values for vascular permeability ranged from 0 to 0.356 mL/min/100 cm(3).
Conclusions:
- Dynamic contrast-enhanced MRI with MMCM is a feasible and effective method for evaluating vascular characteristics of pancreatic islet cell tumors in RIP-Tag2 mice.
- This MRI technique provides reliable, quantitative estimates of tumor vascular density and permeability.
- The findings support the use of DCE-MRI as a non-invasive tool for preclinical tumor research and potential therapeutic monitoring.
