Radiation-induced changes of relative cerebral blood volume in normal-appearing white matter of glioma patients following proton therapy

Introduction
Adjuvant radio(chemo)therapy (RT) is a common treatment of primary brain tumor patients. Irradiation with protons reduced radiation exposure to the tumor-surrounding tissue. As the normal tissue is still unavoidably exposed to a certain amount of radiation, the aim of this study was to determine the radiation effect on normal appearing white matter (WM) of glioma patients treated with proton RT based on the changes of the relative cerebral blood volume (rCBV).

Methods
MRI data of 14 glioma patients (grade II-IV) undergoing gross tumor resection followed by proton RT were acquired prior to RT and 3, 6 and 9 months after RT and included T1-weighted images and dynamic susceptibility contrast (DSC) imaging.
Planning CTs, dose maps and CTV contours were registered to the T1w-images using ANTs1 and WM segmentation was done on T1w-images using SPM122. Normal-appearing tissue was censored by excluding the CTV and voxels appearing abnormal on FLAIR imaging.
CBV-maps were calculated voxel wisely as the area under curve determined by integrating the y-variate fit to the time curves of the 4D DSC image. Relative CBV (rCBV) maps were normalized to a reference region of white matter receiving less than 1Gy. Time-dependent alterations ΔrCBV were determined by the percentage difference between follow-up and baseline measurement for the whole brain WM as well as for dose-separated bins of low (1-20Gy), medium (20-40Gy) and high dose regions (>40Gy).

Results and conclusion
The evaluation of whole brain WM as well as of dose-separated regions showed no significant alterations between baseline and follow-up rCBV. A trend toward decreasing perfusion appeared after 9 months after RT in the high-dose range. Previous studies measured a radiation-induced decrease in WM blood volume prominently appearing in the high-dose range3,4,5. A study showing early radiation response of decreasing rCBV followed by a recovery 3 months after RT agrees with our observation of constant rCBV 3-9 months after radiation6. In future studies our focus will be on the evaluation of brain subregions as well as the analysis of GM radiation response.