Evaluation of Effects of TGF-β1 Inhibition on Gastric Cancer in Nude Mice by Diffusion Kurtosis Imaging and In-Line X-ray Phase Contrast Imaging With Sequential Histology

J Magn Reson Imaging. 2019 Jun;49(6):1553-1564. doi: 10.1002/jmri.26523. Epub 2018 Oct 6.

Abstract

Background: Accurate and complete response evaluation after treatment is important to implement individualized therapy for gastric cancer.

Purpose: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and in-line X-ray phase contrast imaging (ILXPCI) in the assessment of the therapeutic efficacy by transforming growth factor beta 1 (TGF-β1) inhibition.

Study type: Prospective animal study.

Animal model: Thirty nude mice subcutaneous xenotransplantation tumor model of gastric cancer for DKI and 10 peritoneal metastasis nude mice model for ILXPCI.

Field strength/sequence: Examinations before and serially at 7, 14, 21, and 28 days after TGF-β1 inhibition treatment were performed at 3T MRI including T2 -weighted imaging (T2 WI) and DKI with five b values of 0, 500, 1000, 1500, 2000 s/mm2 ; ILXPCI examinations were performed at 14 days after treatment.

Assessment: DKI parameters (apparent diffusion coefficient [ADC], diffusivity [D] and kurtosis [K]) were calculated by two experienced radiologists after postprocessing.

Statistical tests: For the differences in all the parameters between the baseline and each timepoint for both the treated and the control mice, the Mann-Whitney test was used. The Spearman correlation test was used to evaluate correlations among the DKI parameters and corresponding pathologic necrosis fraction (NF).

Results: ADC, D, and K values were significantly different between the two groups after treatment (P < 0.05). Serial measurements in the treated group showed that the ADC, D, and K values were significantly different at 7, 14, 21, and 28 days compared with baseline (P < 0.05). There were significant correlations between DKI parameters and NF (ADC, r = 0.865, P < 0.001; D, r = 0.802, P < 0.001; K, r = -0.944, P < 0.001). The ILXPCI results in the treated group showed a stronger absorption area than the control group.

Data conclusion: DKI may be used to evaluate the complete course therapeutic effects of gastric cancer induced by TGF-β1 inhibition, and the ILXPCI technique will improve the tumor microstructure resolution.

Level of evidence: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:1553-1564.

Keywords: DKI; ILXPCI; TGF-β1 inhibition; gastric cancer; therapeutic evaluation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / pharmacology*
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Peritoneal Neoplasms / diagnostic imaging
  • Stomach Neoplasms / diagnostic imaging*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Transforming Growth Factor beta1 / antagonists & inhibitors*
  • X-Rays

Substances

  • Contrast Media
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1