The objective of this study was to examine the predictive value of parameters of 3D ¹H magnetic resonance spectroscopic imaging (MRSI) prior to treatment with radiation/chemotherapy (baseline) and at a postradiation 2-month follow-up (F2mo) in relationship to 6-month progression-free survival (PFS6) and overall survival (OS). Sixty-four patients with newly diagnosed glioblastoma multiforme (GBM) being treated with radiation and concurrent chemotherapy were involved in this study. Evaluated were metabolite indices and metabolite ratios. Logistic linear regression and Cox proportional hazards models were utilized to evaluate PFS6 and OS, respectively. These analyses were adjusted by age and MR scanner field strength (1.5 T or 3 T). Stepwise regression was performed to determine a subset of the most relevant variables. Associated with shorter PFS6 were a decrease in the ratio of N-acetyl aspartate to choline-containing compounds (NAA/Cho) in the region with a Cho-to-NAA index (CNI) >3 at baseline and an increase of the CNI within elevated CNI regions (>2) at F2mo. Patients with higher normalized lipid and lactate at either time point had significantly worse OS. Patients who had larger volumes with abnormal CNI at F2mo had worse PFS6 and OS. Our study found more 3D MRSI parameters that predicted PFS6 and OS for patients with GBM than did anatomic, diffusion, or perfusion imaging, which were previously evaluated in the same population of patients.

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. 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). 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. 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.

Background The purpose of this study was to evaluate the feasibility of using a short echo time, three-dimensional H-1 magnetic resonance spectroscopic imaging (MRSI) sequence at 7 Tesla (T) to assess the metabolic signature of lesions for patients with glioma. Methods Twenty-nine patients with glioma were studied. MRSI data were obtained using CHESS water suppression, spectrally selective adiabatic inversion-recovery pulses and automatically prescribed outer-volume-suppression for lipid suppression, and spin echo slice selection (echo time = 30 ms). An interleaved flyback echo-planar trajectory was applied to shorten the total acquisition time (∼10 min). Relative metabolite ratios were estimated in tumor and in normal-appearing white and gray matter (NAWM, GM). Results Levels of glutamine, myo-inositol, glycine, and glutathione relative to total creatine (tCr) were significantly increased in the T2 lesions for all tumor grades compared with those in the NAWM (P < 0.05), while N-acetyl aspartate to tCr were significantly decreased (P < 0.05). In grade 2 gliomas, level of total choline-containing-compounds to tCr was significantly increased (P = 0.0137), while glutamate to tCr was significantly reduced (P = 0.0012). Conclusion The improved sensitivity of MRSI and the increased number of metabolites that can be evaluated using 7T MR scanners is of interest for evaluating patients with glioma. This study has successfully demonstrated the application of a short-echo spin-echo MRSI sequence to detect characteristic differences in regions of tumor versus normal appearing brain. J. Magn. Reson. Imaging 2015;41:1332–1341.

BACKGROUND AND PURPOSE: Pediatric CNS tumors commonly present challenges for radiographic interpretation on conventional MR imaging. This study sought to investigate the safety and tolerability of hyperpolarized carbon-13 (HP-¹³C) metabolic imaging in pediatric patients with brain tumors. MATERIALS AND METHODS: Pediatric patients 3 to 18 years of age who were previously diagnosed with a brain tumor and could undergo MR imaging without sedation were eligible to enroll in this safety study of HP [1-¹³C]pyruvate. Participants received a one-time injection of HP [1-¹³C]pyruvate and were imaged using dynamic HP-¹³C MR imaging. We assessed 2 dose levels: 0.34 mL/kg and the highest tolerated adult dose of 0.43 mL/kg. Participants were monitored throughout imaging and for 60 minutes postinjection, including pre- and postinjection electrocardiograms and vital sign measurements. RESULTS: Between February 2017 and July 2019, ten participants (9 males; median age, 14 years; range, 10–17 years) were enrolled, of whom 6 completed injection of HP [1-¹³C]pyruvate and dynamic HP-¹³C MR imaging. Four participants failed to undergo HP-¹³C MR imaging due to technical failures related to generating HP [1-¹³C]pyruvate or MR imaging operability. HP [1-¹³C]pyruvate was well-tolerated in all participants who completed the study, with no dose-limiting toxicities or adverse events observed at either 0.34 (n = 3) or 0.43 (n = 3) mL/kg. HP [1-¹³C]pyruvate demonstrated characteristic conversion to [1-¹³C]lactate and [¹³C]bicarbonate in the brain. Due to poor accrual, the study was closed after only 3 participants were enrolled at the highest dose level. CONCLUSIONS: Dynamic HP-¹³C MR imaging was safely performed in 6 pediatric patients with CNS tumors and demonstrated HP [1-¹³C]pyruvate brain metabolism.

Magnetic resonance spectroscopy (MRS) is a powerful tool for noninvasively investigating normal and abnormal metabolism. When used in combination with imaging strategies, multinuclear MRS methods provide detailed biochemical information that can be directly correlated with anatomical features. Hyperpolarized ¹³C MRS is a new technology that reflects real-time metabolic conversion and is likely to be extremely valuable in managing patients with cancer. This article reviews the use of in vivo ³¹P, ¹H, and ¹³C MRS for assessing cancer metabolism in order to provide information for diagnosis, planning treatment, assessing response to therapy, and predicting survival for patients with cancer.