Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging for Monitoring the Immune Response of Immunogenic Chemotherapy

Junjiao Hu; Xin Yu; Peidi Yin; Bin Du; Xiangran Cai

doi:10.3389/fonc.2022.796936

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging for Monitoring the Immune Response of Immunogenic Chemotherapy

Front Oncol. 2022 May 13:12:796936. doi: 10.3389/fonc.2022.796936. eCollection 2022.

Authors

Junjiao Hu^{1

2}, Xin Yu¹, Peidi Yin³, Bin Du⁴, Xiangran Cai¹

Affiliations

¹ Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China.
² Medical Imaging Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
³ Department of Pathology, First Affiliated Hospital of Jinan University, Guangzhou, China.
⁴ Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

Objective: To evaluate the predictive value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the quantitative assessment of conventional chemotherapy-activated immune responses in mouse tumor models and clinics.

Methods: A total of 19 subcutaneous tumor-bearing mice were randomly divided into treated and control groups. Both groups had orderly IVIM DWI examinations before and on days 6 and 12 after the administration of cyclophosphamide (CPA) or saline. Pathologic examinations were performed, including HE staining and immunohistochemistry (IHC). The expressions of immune-related genes in the tumor were measured by qPCR. In addition, six patients with breast cancer requiring neoadjuvant chemotherapy (NACT) also underwent functional MRI examinations and IHC to determine potential antitumor immune response.

Results: At the end of the study, the CPA treatment group showed the lowest tumor volume compared to the control group. For pathological examinations, the CPA treatment group showed a lower percentage of CD31 staining (P < 0.01) and Ki-67 staining (P<0.01), and a higher percentage of TUNEL staining (P < 0.01). The tumoral pseudodiffusion coefficient (D*) value showed a positive correlation with the CD31-positive staining rate (r = 0.729, P < 0.0001). The diffusion related parameters (D) value was positively correlated with TUNEL (r = 0.858, P < 0.0001) and negatively correlated with Ki-67 (r = -0.904, P < 0.0001). Moreover, a strong induction of the expression of the immune responses in the CPA treatment group was observed on day 12. D values showed a positive correlation with the Ifnb1-, CD8a-, Mx1-, Cxcl10- (r = 0.868, 0.864, 0.874, and 0.885, respectively, P < 0.0001 for all). Additionally, the functional MRI parameters and IHC results in patients with breast cancer after NACT also showed a close correlation between D value and CD8a (r = 0.631, P = 0.028).

Conclusions: The treatment response induced by immunogenic chemotherapy could be effectively evaluated using IVIM-DWI. The D values could be potential, sensitive imaging marker for identifying the antitumor immune response initiated by immunogenic chemotherapy.

Keywords: diffusion-weighted imaging; immune response prediction; intravoxel incoherent motion; magnetic resonance imaging; metronomic chemotherapy.