Quantitative assessment of tumor responses after radiation therapy in a DLD-1 colon cancer mouse model using serial dynamic contrast-enhanced magnetic resonance imaging

Abstract

Purpose: The purpose of this study was to investigate the predictability of pretreatment values including Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) derived parameters (K(trans), K(ep) and V(e)), early changes in parameters (K(trans), tumor volume), and heterogeneity (standard deviation of K(trans)) for radiation therapy responses via a human colorectal cancer xenograft model.

Materials and methods: A human colorectal cancer xenograft model with DLD-1 cancer cells was produced in the right hind limbs of five mice. Tumors were irradiated with 3 fractions of 3 Gy each for 3 weeks. Baseline and follow up DCE-MRI were performed. Quantitative parameters (K(trans), K(ep) and V(e)) were calculated based on the Tofts model. Early changes in K(trans), standard deviation (SD) of K(trans), and tumor volume were also calculated. Tumor responses were evaluated based on histology. With a cut-off value of 0.4 for necrotic factor, a comparison between good and poor responses was conducted.

Results: The good response group (mice #1 and 2) exhibited higher pretreatment K(trans) than the poor response group (mice #3, 4, and 5). The good response group tended to show lower pretreatment K(ep), higher pretreatment V(e), and larger baseline tumor volume than the poor response group. All the mice in the good response group demonstrated marked reductions in K(trans) and SD value after the first radiation. All tumors showed increased volume after the first radiation therapy.

Conclusion: The good response after radiation therapy group in the DLD-1 colon cancer xenograft nude mouse model exhibited a higher pretreatment K(trans) and showed an early reduction in K(trans), demonstrating a more homogenous distribution.

Fig. 1

An exceptional case, mouse #3, was assigned to the poor response group although it showed a large area of necrosis (NF=0.49). (A) Serial DCE-MRI with color mapping shows the change in K^trans. Pretreatment K^trans showed a relatively low value (0.11). K^trans increased after the first radiation therapy (K₁R=1.51). Red color represents the higher value of K^trans and blue color represents the lower value. An outgrowing tumor was identified after the first radiation therapy (arrow). (B) H&E staining of the newly grown tumor, which separated from the main mass, showed rare necrosis. The original magnification is ×2. The red line indicates the tumor border and the blue line indicates the area of necrosis. NF, necrotic fraction; H&E, hematoxylin and eosin.

Fig. 2

Comparison of quantitative parameters between the good and the poor response groups upon baseline imaging. (A) K^trans, (B) K_ep, (C) V_e, (D) pretreatment tumor volume.

Fig. 3

Comparison of K^trans between the good and the poor response groups after the 1st radiation therapy. (A) Early changes in K^trans and (B) early changes in standard deviation for K^trans (SD). The y-axis represents the ratio of the value after the 1st radiation therapy to the pretreatment value. The horizontal solid line at the ratio of 1 represents no change within the interval.

Fig. 4

A representative case of good response in mouse #2. (A) Serial DCE-MRI with color mapping shows higher pretreatment K^trans (0.29) and marked reduction in K^trans after the first radiation therapy (K₁R=0.47). (B) H&E staining of the corresponding section in mouse #2. The original magnification is ×2. Necrosis is identified in the center of the tumor. The red line indicates the tumor border and the blue line indicates the area of necrosis. The necrosis factor was 0.46. Histogram shows the heterogeneous distribution of K^trans at baseline with an SD of 0.09 (C) and the homogenous distribution of K^trans with an SD of 0.05 after the first radiation therapy (D). DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging; SD, standard deviation; H&E, hematoxylin and eosin.