The Therapeutic Response of Gastrointestinal Stromal Tumors to Imatinib Treatment Assessed by Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging with Histopathological Correlation.

Feng Pan,Yi Wang,Nan Hong,Chunfang Zhang,Weizhen Wu,Jin Cheng,He Wang,Jie Den,Gayle E Woloschak

doi:10.1371/journal.pone.0167720

Feng Pan, Yi Wang + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0167720

Copy DOI

Journal: PloS one	Publication Date: Dec 2, 2016
Citations: 9	License type: CC BY 4.0

Affiliation: Peking University People's Hospital, Peking University

Abstract

PurposeTo exploit the intravoxel incoherent motion (IVIM) diffusion-weighted (DW) MRI when evaluating the therapeutic response of gastrointestinal stromal tumors (GIST) to Imatinib in a mouse model.Materials and MethodsMice with xenografts bearing cells from the GIST-T1 cell line were randomly divided into a treated group receiving Imatinib and a control group. DWMRI scans with 14 b-values (0–1500 s/mm2) were performed before and after treatment (days 1, 3 and 7). IVIM related parameters perfusion fractions (fp) and perfusion-related diffusion coefficients (D*) and the conventional apparent diffusion coefficients (ADC) were calculated by fitting the DWMRI signal decay. The mean changes from baseline to each post-treatment time point for each measurement (ΔADC, Δfp and ΔD*) were calculated. The differences of mean changes between the two groups were tested for statistical significance. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans.ResultsIncreases in ADC of the treated group were higher than those of the control group after treatment, whereas statistical significances were not observed. Compared to the control group, D* in the treated group decreased significantly (ΔD*treated = -41%, -49%, and -49% with P = 0.0001, 0.0001 and 0.0001), and fp increased significantly (Δfptreated = 79%, 82% and 110%, with P = 0.001, 0.0001 and P = 0.0007) on days 1, 3 and 7 after treatment. Histopathological analyses demonstrated different tumor tissue characteristics between the treated and control groups.ConclusionIVIM measurements may serve as more sensitive imaging biomarkers than ADC when assessing GIST response to Imatinib as early as one day after treatment.

Highlights

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal cancer of the gastrointestinal tract
Compared to the control group, D* in the treated group decreased significantly (ΔD*treated = -41%, -49%, and -49% with P = 0.0001, 0.0001 and 0.0001), and fp increased significantly (Δfptreated = 79%, 82% and 110%, with P = 0.001, 0.0001 and P = 0.0007) on days 1, 3 and 7 after treatment
intravoxel incoherent motion (IVIM) measurements may serve as more sensitive imaging biomarkers than apparent diffusion coefficients (ADC) when assessing GIST response to Imatinib as early as one day after treatment

Summary

Introduction

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal cancer of the gastrointestinal tract. They originate from the proliferation of interstitial cells of Cajal[1]. The cells in GIST express a growth factor receptor with tyrosine kinase activity termed c-kit. This receptor, the product of the proto-oncogene c-kit, can be detected by immunohistochemical staining for CD117[1]. In order to optimize individual patient care and to avoid ineffective treatment and unnecessary toxicity, several noninvasive imaging modalities have been used to evaluate GIST response to Imatinib[6,7,8]

Objectives

Methods

Results

Conclusion