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

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 (k_PL) and [¹³C]bicarbonate (k_PB) 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 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-¹³C 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 [1-¹³C]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.