2553 - Radiation Therapy Effects on Spectroscopic MRI Metabolites in Recurrent Glioblastoma

Purpose/Objective(s): Spectroscopic MRI–derived choline (Cho)/N-acetyl aspartate (NAA) ratios are often used for RT planning, with Cho/NAA > 2 frequently interpreted as positive for high-risk glioblastoma. We hypothesized that radiation therapy (RT) of primary glioma induces dose-dependent alterations in metabolite ratios that can confound spectroscopic MRI (sMRI) measurements used for recurrent glioblastoma (rGBM) RT planning. Regions receiving higher radiation doses may demonstrate elevated Cho/NAA ratios from reduced NAA levels as a function of focal radiation injury.

Materials/Methods: Eighteen patients with rGBM, who all previously had maximal safe resection, concurrent radiation to 60 Gy in 30 fractions, and chemotherapy underwent 3 T whole-brain sMRI at the time of recurrence. The sMRI was acquired using a spatial-spectral echo-planar readout with spin-echo excitation, yielding a working voxel size of 4.4 × 4.4 × 5.6 mm, with approximately 5200 spectra analyzed per patient. sMRI scans were aligned to the planning CT and radiation dose map from the primary treatment via MIM software. The original PTV was excluded to reduce confounding from active tumor. Metabolite levels for Cho, NAA, and creatine (Cr) were quantified and normalized to contralateral normal-appearing white matter. DICOM images were exported into Python for analysis, where the corresponding sMRI metabolite maps and radiation doses were overlaid and plotted using scatter plots.

Results: Combining normal appearing brain metabolite data from all patients, linear regression demonstrated a weak trend towards increasing Cho/NAA with prior radiation dose (.0027/Gy, r2=0.0058, p<0.001). This is primarily explained by a trend of decreasing NAA with prior radiation dose (-.19%/Gy, r2=0.012, p<0.001). Since NAA is a marker of healthy brain, decreases reflect local brain injury from prior high dose RT. There was little effect of prior radiation dose on Cho (.051%/Gy, r2=0.00046, p<0.001). A small effect of prior radiation on Cr was also observed (-0.10%/Gy, r2=0.0036, p<0.001). Per patient univariate analyses were not significant for metabolites compared to time to recurrence, age, and primary PTV size.

Conclusion: This data demonstrates a weak dose dependent effect of RT on sMRI metabolites. Cho/NAA>2x is typically used as a marker of high-risk glioblastoma. But in the rGBM setting, corrected value maps could be considered. For example, Cho/NAA>2x is positive for 0 Gy prior dose, but Cho/NAA>1.838x (2x – [.0027/Gy * 60Gy]) is positive for 60 Gy prior dose.