Using in vivo diffusion -weighted MRI to quantify treatment response in murine tumors
Diffusion-weighted magnetic resonance imaging (DW-MRI) produces images that represent the amount of water diffusion, or Brownian motion, within the sample tissue. Here, DW-MRI was used to determine whether there are measurable changes in the diffusion properties of a tumor after the tumor is treated with radiation. MCa-29 mammary carcinoma was grown in the hind legs of C3Hk/fam mice. When the tumors had grown to a diameter of approximately 8mm, the tumors were treated with 20Gy of 137CS gamma-rays (mean energy = 662 keV) and then scanned using a DW-MRI sequence. After this initial scan, half of the mice were sacrificed, and the tumors were excised and stained with hematoxylin and eosin (H&E) for histological analysis. The remaining animals were rescanned three days later before being sacrificed for histological analysis. Diffusion data were collected on a 4.7T Bruker Biospin scanner (Billerica, MA). The data were analyzed using a two-compartment model, representing tumor tissue as a slow-diffusing compartment, often associated with intracellular space, and a fast-diffusing compartment, often associated with extracellular space. The analysis yielded the following diffusion parameters: the rate of diffusion in the slow-diffusing compartment (D1), the rate of diffusion in the fast-diffusing compartment (D2) and the volume fraction occupied by the slowdiffusing compartment, or cellular space (CVF). Between the first and second imaging sessions, the mean value of D 1 increased 96% (p=0.03) and the mean D2 increased 62% (p=0.30). The DW-MRI-based CVF remained approximately unchanged (CVF=0.40+/-0.04 versus CVF=0.43+/-0.08, p=0.88). This change did not correlate with the histology-based CVF measurements which, during the same time period, decreased significantly from 0.76+/-0.03 to 0.56+/-0.01 (p<0.001). Although there was disagreement between the CVF measurements made by DW-MRI and histology, some notable trends were apparent. The rates of diffusion in both tissue compartments increased after radiation treatment. A quantitative analysis indicated that after treatment, the tumor became more homogeneous. Although quantitative DW-MRI CVF measurements did not correlate with those made from histology, DW-MRI may provide useful information about how tissue structure is changing after a successful radiation treatment, perhaps before changes are seen in gross tumor size.
Marsh, Rebecca Milman, "Using in vivo diffusion -weighted MRI to quantify treatment response in murine tumors" (2007). Texas Medical Center Dissertations (via ProQuest). AAI3264640.