Abstract
As a non-invasive method for probing in vivo metabolism, hyperpolarized carbon-13 metabolic imaging may enhance the diagnostic assessment of response-to-treatment in patients with glioma. Having demonstrated the feasibility of applying this technique to human glioma (Park et al. 2017), the current study seeks to evaluate the reproducibility of carbon data by measuring serial metabolic changes in white matter. In total, 4 radiologically stable patients (2 male, 2 female) who were treated with radiation and TMZ for heterogeneous diagnoses (GBM, grade III oligo, gliosarcoma, secondary GBM) received either 2 (n=1) or 3 (n=3) serial exams. Following injection of hyperpolarized [1-13C]pyruvate, dynamic echo-planar imaging was acquired with a 3s temporal resolution and 2–8 cm3 spatial resolution. Dynamic data were summed together and the ratio of metabolically-produced lactate relative to pyruvate substrate (lac/pyr) was evaluated in segmented normal-appearing white matter (NAWM, >50% voxel). Median and SD of lac/pyr values in NAWM are reported for serial scans, along with %change per interval: P1-male [0.32 ± 0.14, 0.28 ± 0.11 (-12.5%), 0.33 ± 0.10 (+17.9%)]; P2-male [0.32 ± 0.10, 0.28 ± 0.10 (-12.5%)]; P3-female [0.37 ± 0.09, 0.45 ± 0.14 (+21.6%), 0.59 ± 0.19 (+31.1%)]; and P4-female [0.49 ± 0.14, 0.43 ± 0.12 (-12.2%), 0.44 ± 0.10 (2.3%)]. These results show an average absolute change of 15.7% in lac/pyr within NAWM over the entire population, with considerable overlap of the variance. Patient P3, who was treated with adjuvant agent pembrolizumab, also notably showed a serial increase in lac/pyr. When separating the population according to gender, females demonstrated a higher average lac/pyr value of 0.46, compared to 0.31 in males. In summary, our initial experience with serial hyperpolarized carbon data indicates that the range of lactate-to-pyruvate ratios is relatively consistent across patient scans, but may differ according to gender and adjuvant treatment. Future studies will evaluate changes in the T2 lesion relative to NAWM over the course of treatment.