Characterization of serial hyperpolarized (13)C metabolic imaging in patients with glioma

BACKGROUND: Hyperpolarized carbon-13 (HP-(13)C) MRI is a non-invasive imaging technique for probing brain metabolism, which may improve clinical cancer surveillance. This work aimed to characterize the consistency of serial HP-(13)C imaging in patients undergoing treatment for brain tumors and determine whether there is evidence of aberrant metabolism in the tumor lesion compared to normal-appearing tissue. METHODS: Serial dynamic HP [1-(13)C]pyruvate MRI was performed on 3 healthy volunteers (6 total examinations) and 5 patients (21 total examinations) with diffuse infiltrating glioma during their course of treatment, using a frequency-selective echo-planar imaging (EPI) sequence. HP-(13)C imaging at routine clinical timepoints overlapped treatment, including radiotherapy (RT), temozolomide (TMZ) chemotherapy, and anti-angiogenic/investigational agents. Apparent rate constants for [1-(13)C]pyruvate conversion to [1-(13)C]lactate (k(PL)) and [(13)C]bicarbonate (k(PB)) were simultaneously quantified based on an inputless kinetic model within normal-appearing white matter (NAWM) and anatomic lesions defined from (1)H MRI. The inter/intra-subject consistency of k(PL-NAWM) and k(PB-NAWM) was measured in terms of the coefficient of variation (CV). RESULTS: When excluding scans following anti-angiogenic therapy, patient values of k(PL-NAWM) and k(PB-NAWM) were 0.020 s(−1) ± 23.8% and 0.0058 s(−1) ± 27.7% (mean ± CV) across 17 HP-(13)C MRIs, with intra-patient serial k(PL-NAWM)/k(PB-NAWM) CVs ranging 6.8–16.6%/10.6–40.7%. In 4/5 patients, these values (0.018 s(−1) ± 13.4% and 0.0058 s(−1) ± 24.4%; n = 13) were more similar to those from healthy volunteers (0.018 s(−1) ± 5.0% and 0.0043 s(−1) ± 12.6%; n = 6) (mean ± CV). The anti-angiogenic agent bevacizumab was associated with global elevations in apparent rate constants, with maximum k(PL-NAWM) in 2 patients reaching 0.047 ± 0.001 and 0.047 ± 0.003 s(−1) (±model error). In 3 patients with progressive disease, anatomic lesions showed elevated k(PL) relative to k(PL-NAWM) of 0.024 ± 0.001 s(−1) (±model error) in the absence of gadolinium enhancement, and 0.032 ± 0.008, 0.040 ± 0.003 and 0.041 ± 0.009 s(−1) with gadolinium enhancement. The lesion k(PB) in patients was reduced to unquantifiable values compared to k(PB-NAWM). CONCLUSION: Serial measures of HP [1-(13)C]pyruvate metabolism displayed consistency in the NAWM of healthy volunteers and patients. Both k(PL) and k(PB) were globally elevated following bevacizumab treatment, while progressive disease demonstrated elevated k(PL) in gadolinium-enhancing and non-enhancing lesions. Larger prospective studies with homogeneous patient populations are planned to evaluate metabolic changes following treatment.