Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Predicting and Monitoring the Response of Anti-Angiogenic Treatment in the Orthotopic Nude Mouse Model of Lung Adenocarcinoma

Background The treatment efficacy of angiogenesis inhibitor could be underestimated at an early stage based on tumor volume changes. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can quantitatively assess tumors at the cellular level, but it is unclear whether it can provide useful information for assessing treatment response of anti-angiogenic treatment for lung adenocarcinoma. Purpose To determine the use of IVIM-DWI for non-invasive monitoring of the early response to anti-angiogenic treatment in the orthotopic transplantation of lung adenocarcinoma model. Study Type Prospective. Population Thirty-seven nude mice were randomized into two groups: treatment group (received bevacizumab + cisplatin, N = 20) and control group (received saline, N = 17). Field Strength/Sequence Single-shot turbo spin-echo (TSE) IVIM-DWI, TSE T2-weighted imaging at 3.0 T. Assessment Tumor volume, IVIM parameters (apparent diffusion coefficient [ADC], diffusivity [D], perfusion fraction [f], and pseudo-diffusion coefficient [D*]) were measured before and 2 hours, 3, 7, 10 and 14 days after treatment. Regions of interest were manually drawn along the inner edge of the tumor by two radiologists with 5 and 10-year experience in magnetic resonance imaging. Pathological examinations (hematoxylin and eosin stain, cluster of differentiation 34) were performed. Statistical Tests Kolmogorov-Smirnov test, repeated-measure two-way analysis of variance test, Mann-Whitney U test, Pearson correlation analysis, receiver operating characteristic curve. P < 0.05 was considered statistically significant. Results The tumor volume of the two groups was significantly different only on day 14 (control group vs. treatment group, 43.15 +/- 18.28 mm(3) vs. 28.41 +/- 1.71 mm(3)). ADC(2h), ADC(10d), D-2h, D-7d, D-10d, and D-14d were significantly higher, while f(10d) and f(14d) were significantly lower in the treatment group compared to those of the control group. Both the oADC(2h) (r = -0.631) and oD(2h) (r = -0.700) showed moderate correlations with the relative tumor volume on day 14. Data Conclusion IVIM has the potential to predict and monitor the early response to anti-angiogenic treatment, earlier than size changes, for lung adenocarcinoma. Level of Evidence 2 Technical Efficacy Stage 4