P2-09-12: High Resolution Diffusion MRI Characterizes Tumor Stromal Boundaries.

Abstract

Background: Studies of 3D cell cultures have shown that mammary epithelial cell growth and morphogenesis is regulated by extracellular matrix (ECM) stiffness, linking ECM stiffening to malignant transformation. Tumors are consistently stiffer than normal adjacent tissue, and matrix stiffening is caused by ECM cross-linking and increased deposition of collagen. Some evidence suggests that collagen orientation at tumor boundaries can promote tumor metastasis. Measuring the stiffness of the tumor boundaries and adjacent stromal tissue may give additional information 1) about tumor microenvironment and 2) to guide treatment. Diffusion-weighted imaging (DWI) MRI measures the mobility of water in tissue and may be sensitive to this phenomenon. Material and Methods: MRI data was collected on patients with locally advance breast cancer enrolled in an IRB-approved study at UCSF and signed informed consent. In addition to a standard dynamic contrast enhanced (DCE) MRI, a high-resolution diffusion-weighted image (HR DWI) was acquired with an echo planar imaging sequence and the following parameters: TR/TE=4000/64.8 ms, b=0,600, FOV=70×140mm, matrix=28×64, and voxel size=0.55×0.55×4.0mm. Apparent diffusion coefficient (ADC) maps were created. HR DWI images were segmented into tumor and non-enhancing, surrounding stromal tissue. A proximity mapping method was used to measure ADC values at the inner edge of tumor and at increasing distances from the tumor boundary on HR DWI. The mean was calculated for the voxels in 1 mm increments, starting at 5 mm into the tumor (−5 mm) and ending at 2.5 cm away from the tumor (25 mm). Results: The average of the changes per 1 mm shell was largest for the transition of the tumor boundary (Table 1). In Table 1, the −5 to 0 mm, 0 to 5 mm, and 5 to 25 mm columns represent inside the tumor, tumor boundary, and outside the tumor, respectively. In general, ADC values were consistently lower inside the tumor than outside. The greatest changes per 1 mm shell was seen in the transition from inside to outside tumor, although the values varied among tumor types. Each of the three cases analyzed had different patterns of ADC values. Discussion: These preliminary studies show that water mobility measurements change at the tumor boundary, with different patterns observed among individual patients. We are further investigating the influence of density and tumor margin morphology on these ADC measurements. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-12.