Evaluation of Temozolomide Treatment for Glioblastoma Using Amide Proton Transfer Imaging and Diffusion MRI

Simple Summary Glioblastoma (GBM), the most frequent and malignant histological type of glioma, is associated with a very high mortality rate. MRI is a useful method for the evaluation of tumor growth. However, there are few studies that have quantitatively evaluated the changes in disease state after TMZ treatment against GBM, and it is not fully understood how the effects of treatment are reflected in the quantitative values measured on MRI. We used the C6 glioma rat model to evaluate the tumor changes due to chemotherapy at different doses of TMZ in terms of quantitative values measured by neurite orientation dispersion and density imaging (NODDI) and amide proton transfer (APT) imaging using 7T-MRI. These methods can evaluate the microstructural changes caused by TMZ-induced tumor growth inhibition. This study aimed to evaluate tumor changes due to chemotherapy with temozolomide (TMZ) in terms of quantitative values measured by APT imaging and NODDI. We performed TMZ treatment (administered orally by gavage to the TMZ-40 mg and TMZ-60 mg groups) on 7-week-old male Wistar rats with rat glioma C6 implanted in the right brain. T2WI, APT imaging, diffusion tensor imaging (DTI), and NODDI were performed on days 7 and 14 after implantation using 7T-MRI, and the calculated quantitative values were statistically compared. Then, HE staining was performed on brain tissue at day 7 and day 14 for each group to compare the results with the MR images. TMZ treatment inhibited tumor growth and necrotic area formation. The necrotic areas observed upon hematoxylin and eosin (HE) staining were consistent with the MTR low-signal areas observed upon APT imaging. The intracellular volume fraction (ICVF) map of the NODDI could best show the microstructure of the tumor, and its value could significantly highlight the difference in treatment effects at different TMZ doses. APT imaging and NODDI can be used to detect the microstructural changes caused by TMZ-induced tumor growth inhibition. The ICVF may be useful as a parameter for determining the effect of TMZ.

Automated summary

This study evaluated the effects of chemotherapy with temozolomide (TMZ) on glioblastoma (GBM) tumors using APT imaging and NODDI. The results showed that TMZ treatment inhibited tumor growth and necrotic area formation. The ICVF map of NODDI was able to best show the tumor's microstructure and highlighted the differences in treatment effects at different TMZ doses.