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

Abstract Background Hyperpolarized carbon-13 (HP-13C) 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-13C 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 [1-13C]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-13C imaging at routine clinical timepoints overlapped treatment, including radiotherapy (RT), temozolomide (TMZ) chemotherapy, and anti-angiogenic/investigational agents. Apparent rate constants for [1-13C]pyruvate conversion to [1-13C]lactate (kPL) and [13C]bicarbonate (kPB) were simultaneously quantified based on an inputless kinetic model within normal-appearing white matter (NAWM) and anatomic lesions defined from 1H MRI. The inter/intra-subject consistency of kPL-NAWM and kPB-NAWM was measured in terms of the coefficient of variation (CV). Results When excluding scans following anti-angiogenic therapy, patient values of kPL-NAWM and kPB-NAWM were 0.020 s-1 ± 23.8% and 0.0058 s-1 ± 27.7% (mean±CV) across 17 HP-13C MRIs, with intra-patient serial kPL-NAWM/kPB-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 kPL-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 kPL relative to kPL-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 kPB in patients was reduced to unquantifiable values compared to kPB-NAWM. Conclusion Serial measures of HP [1-13C]pyruvate metabolism displayed consistency in the NAWM of healthy volunteers and patients. Both kPL and kPB were globally elevated following bevacizumab treatment, while progressive disease demonstrated elevated kPL in gadolinium-enhancing and non-enhancing lesions. Larger prospective studies with homogeneous patient populations are planned to evaluate metabolic changes following treatment.