Metabolic alterations: a biomarker for radiation-induced normal brain injury-an MR spectroscopy study

Abstract

Purpose: To assess if interval changes in metabolic status in normal cerebral tissue after radiation therapy (RT) can be detected by 2D CSI (chemical shift imaging) proton spectroscopy.

Materials and methods: Eleven patients with primary brain tumors undergoing cranial radiation therapy (RT) were included. 2D-CSI MRS was performed before, during, and after the course of RT with the following parameters: TE/TR 144/1500 ms, field of view (FOV) 24, thickness 10 mm, matrix 16 x 16. The metabolic ratios choline/creatine (Cho/Cr), N-acetylaspartate (NAA)/Cr, and NAA/Cho in normal brain tissue were calculated.

Results: NAA/Cr and Cho/Cr were significantly decreased at week 3 during RT and at 1 month and 6 months after RT compared to values prior to RT (P < 0.01). The NAA/Cr ratio decreased by -0.19 +/- 0.05 (mean +/- standard error [SE]) at week 3 of RT, -0.14 +/- 0.06 at the last week of RT, -0.14 +/- 0.05 at 1 month after RT, and -0.30 +/- 0.08 at 6 months after RT compared to the pre-RT value of 1.43 +/- 0.04. The Cho/Cr ratio decreased by -0.27 +/- 0.05 at week 3 of RT, -0.11 +/- 0.05 at the last week of RT, -0.26 +/- 0.05 at 1 month after RT and -0.25 +/- 0.07 at 6 months after RT from the pre-RT value of 1.29 +/- 0.03. Changes in Cho/Cr were correlated with the interaction of the radiation dose and dose-volume at week 3 of RT, during the last week of RT (P < 0.005), and at 1 month after RT (P = 0.017).

Conclusion: The results of this study suggest that MRS can detect early metabolic changes in normal irradiated brain tissue.

Figure 1a-e

Axial post Gd-DTPA T1-weighted images before RT (a) and 6 months after the completion of RT (b). The radiation iso-dose contours are overlaid on post Gd-DTPA T1-weighted images (left). The large white boxes represent the VOIs for MRS acquisition, and small white boxes depict the individual VOIs for spectral analysis. The three representative spectra prior to RT (c), at 3 weeks of RT (d) and 6 months after RT (e) were from the corresponding bright white boxes in top panels. Color contours denote isodose lines of radiation.

Figure 2

Differences of ratios of NAA/Cr (square), Cho/Cr (triangle) and NAA/Cho (diamond) at week 3 and week 6 during RT, and 1 month and 6 months after the completion of RT compared to the values prior to RT. Significant interval changes were observed in NAA/Cr and Cho/Cr during and after RT and in NAA/Cho at 1 month after RT. Error bar: standard error of the mean.

Figure 3

The relationships between the product of the local doses received at the time and the brain volume receiving high doses (>40Gy) and the ratios of Cho/Cr at week 3 (a) and week 6 (b) during RT and 1 month after the completion of RT (c), suggesting the interaction effect of the dose and the dose-volume on the metabolite.