Evaluation of Brain Atrophy after One Year of Whole Brain Irradiation Using Voxel Based Morphometry

Abstract

Whole-brain irradiation has often been used for metastatic brain tumors and in prophylactic irradiation, but there are few reports on the frequency of cognitive decline and brain atrophy. We attempted to adapt an objective method of measuring brain atrophy to patients after whole-brain irradiation, Using Voxel based morphometry (VBM) measured from MRI to determine if brain atrophy has occurred one year after whole brain irradiation. VBM is a method to measure the change in signal intensity when an atrophic brain is transformed into a normal brain by Deformable Image Registration. We use VBM to measure brain atrophy before and one year after irradiation in patients who received whole brain irradiation at our institution. The MRI used for the analysis was a contrast-enhanced T1-weighted image, Sagittal cross-sectional images of 1 mm thickness were obtained from the whole brain using the 3D variable flip angle turbo spin echo sequence, which is clinically used at our hospital for the cancer patient's management. The subjects were 28 patients who had undergone whole-brain irradiation at our hospital and for whom MRIs were available before treatment and after one year. The cases analyzed included patients who received prophylactic Cranial irradiation (PCI) in cases of small cell lung cancer obtained complete remission. Z-scores obtained from the medial temporal lobe were compared before and after whole brain irradiation treatment to quantitatively assess brain atrophy. The Z-score is the normalized difference between the voxel values obtained from the normal group average and the individual case. There were 15 cases of lung cancer, 5 cases of malignant lymphoma, 5 cases of breast cancer, and 3 cases of various types of cancer, with an average age of 65 years. Cases with tumors or brain edema in the vicinity of the hippocampus were excluded. Various irradiation doses were used, but the commonly used radiation doses were 23.4 Gy/13Fr (lymphoma), 25 Gy/10 Fr (PCI), 35 Gy/14 Fr (multiple metastasis). A Paired-samples one sided t-test was performed to Mean z-score of positive values within the medial temporal lobe before and one year after whole brain irradiation. This number reflects the degree of atrophy within the region of interest and is determined as mild atrophy if it is greater than 1.0. The mean Z-score was found to increase at a risk of 0.01 after whole brain irradiation. This means that brain atrophy is progressing after whole brain irradiation. Hippocampal atrophy becomes apparent about a year after whole brain irradiation. It suggests that brain atrophy occurs after radiotherapy. The problem with this study is that the effects of chemotherapy-induced brain atrophy and aging cannot be ruled out.