Correlation of Apparent Diffusion Coefficient With Proliferation and Apoptotic Indexes in a Murine Model of Fibrosarcoma: Comparison of Four Methods for MRI Region of Interest Positioning

Abstract

Background: Diffusion-weighted imaging (DWI) has demonstrated great potential in predicting the expression of tumor cell proliferation and apoptosis indexes.

Purpose: To evaluate the impact of four region of interest (ROI) methods on interobserver variability and apparent diffusion coefficient (ADC) values and to examine the correlation of ADC values with Ki-67, Bcl-2, and P53 labeling indexes (LIs) in a murine model of fibrosarcoma.

Study type: Prospective, animal model.

Animal model: A total of 22 female BALB/c mice bearing intramuscular fibrosarcoma xenografts.

Field strength/sequence: A 3.0 T/T1-weighted fast spin-echo (FSE), T2-weighted fast relaxation fast spin-echo, and DWI PROPELLER FSE sequences.

Assessment: Four radiologists measured ADC values using four ROI methods (oval, freehand, small-sample, and whole-volume). Immunohistochemical assessment of Ki-67, Bcl-2, and P53 LIs was performed.

Statistical tests: Interclass correlation coefficient (ICC), one-way analysis of variance followed by LSD-t post hoc analysis, and Pearson correlation test were performed. The statistical threshold was defined as a P-value of <0.05.

Results: All ROI methods for ADC measurements showed excellent interobserver agreement (ICC range, 0.832-0.986). The ADC values demonstrated significant differences among the four ROI methods. The ADC values for oval, freehand, small-sample, and whole-volume ROI methods showed a moderately negative correlation with Ki-67 (r = -0.623; r = -0.629; r = -0.642, and r = -0.431) and Bcl-2 (r = -0.590; r = -0.597; r = -0.659, and r = -0.425) LIs, but no correlation with P53 LI (r = 0.364, P = 0.104; r = 0.350, P = 0.120; r = 0.379, P = 0.091; r = 0.390, P = 0.080).

Data conclusion: The ADC value can be used to evaluate cell proliferation and apoptosis indexes in a murine model of fibrosarcoma, employing the small-sample ROI as a reliable method.

Evidence level: 1 TECHNICAL EFFICACY: Stage 3.

Keywords: apoptosis; apparent diffusion coefficient; fibrosarcoma; proliferation; region of interest.