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

Background: Hyperpolarized carbon-13 (HP-C-13)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-C-13 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-C-13]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-C-13 imaging at routine clinical timepoints overlapped treatment, including radiotherapy (RT), temozolomide (TMZ) chemotherapy, and anti-angiogenic/investigational agents. Apparent rate constants for [1-C-13]pyruvate conversion to [1-C-13]lactate (k(PL))( )and [C-13] bicarbonate (k(PB)) were simultaneously quantified based on an inputless kinetic model within normal-appearing white matter (NAWM) and anatomic lesions defined from H-1 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-C-13 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(P)(B) in patients was reduced to unquantifiable values compared to k(PB-NAWM). Conclusion: Serial measures of HP [1-C-13]pyruvate metabolism displayed consistency in the NAWM of healthy volunteers and patients. Both k(PL) and k(P)(B) 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.