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.

The purpose of this study was to implement a new lactate-edited 3D 1H magnetic resonance spectroscopic imaging (MRSI) sequence at 3 T and demonstrate the feasibility of using this sequence for measuring lactate in patients with gliomas. A 3D PRESS MRSI sequence incorporating shortened, high bandwidth 180° pulses, new dual BASING lactate-editing pulses, high bandwidth very selective suppression (VSS) pulses and a flyback echo-planar readout was implemented at 3 T. Over-prescription factor of PRESS voxels was optimized using phantom to minimize chemical shift artifacts. The lactate-edited flyback sequence was compared with lactate-edited MRSI using conventional elliptical k-space sampling in a phantom and volunteers, and then applied to patients with gliomas. The results demonstrated the feasibility of detecting lactate within a short scan time of 9.5 min in both phantoms and patients. Over-prescription of voxels gave less chemical shift artifacts allowing detection of lactate on the majority of the selected volume. The normalized SNR of brain metabolites using the flyback encoding were comparable to the SNR of brain metabolites using conventional phase encoding MRSI. The specialized lactate-edited 3D MRSI sequence was able to detect lactate in brain tumor patients at 3 T. The implementation of this technique means that brain lactate can be evaluated in a routine clinical setting to study its potential as a marker for prognosis and response to therapy.

The use of in vivo 13C nuclear magnetic resonance spectroscopy in probing metabolic pathways to study normal metabolism and characterize disease physiology has been limited by its low sensitivity. However, recent technological advances have enabled greater than 50,000-fold enhancement of liquid-state polarization of metabolically active 13C substrates, allowing for rapid assessment of 13C metabolism in vivo. The present study applied hyperpolarized 13C magnetic resonance spectroscopy to the investigation of liver metabolism, demonstrating for the first time the feasibility of applying this technology to detect differences in liver metabolic states. [1-13C]pyruvate was hyperpolarized with a dynamic nuclear polarization instrument and injected into normal and fasted rats. The uptake of pyruvate and its conversion to the metabolic products lactate and alanine were observed with slice-localized dynamic magnetic resonance spectroscopy and 3D magnetic resonance spectroscopic imaging (3D-MRSI). Significant differences in lactate to alanine ratio (P < 0.01) between normal and fasted rat liver slice dynamic spectra were observed. 3D-MRSI localized to the fasted livers demonstrated significantly decreased 13C-alanine levels (P < 0.01) compared to normal. This study presents the initial demonstration of characterizing metabolic state differences in the liver with hyperpolarized 13C spectroscopy and shows the ability to detect physiological perturbations in alanine aminotransferase activity, which is an encouraging result for future liver disease investigations with hyperpolarized magnetic resonance technology.

Purpose

The purpose of this study was to investigate the feasibility of in vivo ¹³ C->¹ H hyperpolarization transfer, which has significant potential advantages for detecting the distribution and metabolism of hyperpolarized ¹³ C probes in a clinical MRI scanner.

Methods

A standalone pulsed ¹³ C RF transmit channel was developed for operation in conjunction with the standard ¹ H channel of a clinical 3T MRI scanner. Pulse sequences for ¹³ C power calibration and polarization transfer were programmed on the external hardware and integrated with a customized water-suppressed ¹ H MRS acquisition running in parallel on the scanner. The newly developed RF system was tested in both phantom and in vivo polarization transfer experiments in ¹ J_CH -coupled systems: phantom experiments in thermally polarized and hyperpolarized [2-¹³ C]glycerol, and ¹ H detection of [2-¹³ C]lactate generated from hyperpolarized [2-¹³ C]pyruvate in rat liver in vivo.

Results

Operation of the custom pulsed ¹³ C RF channel resulted in effective ¹³ C->¹ H hyperpolarization transfer, as confirmed by the characteristic antiphase appearance of ¹ H-detected, ¹ J_CH -coupled doublets. In conjunction with a pulse sequence providing 190-fold water suppression in vivo, ¹ H detection of hyperpolarized [2-¹³ C]lactate generated in vivo was achieved in a rat liver slice.

Conclusion

The results show clear feasibility for effective ¹³ C->¹ H hyperpolarization transfer in a clinical MRI scanner with customized heteronuclear RF system.

Purpose

Although ¹ H spin coupling is generally avoided in probes for hyperpolarized (HP) ¹³ C MRI, enzymatic transformations of biological interest can introduce large ¹³ C-¹ H couplings in vivo. The purpose of this study was to develop and investigate the application of ¹ H decoupling for enhancing the sensitivity for detection of affected HP ¹³ C metabolic products.

Methods

A standalone ¹ H decoupler system and custom concentric ¹³ C/¹ H paddle coil setup were integrated with a clinical 3T MRI scanner for in vivo ¹³ C MR studies using HP [2-¹³ C]dihydroxyacetone, a novel sensor of hepatic energy status. Major ¹³ C-¹ H coupling J_CH  = ∼150 Hz) is introduced after adenosine triphosphate-dependent enzymatic transformation of HP [2-¹³ C]dihydroxyacetone to [2-¹³ C]glycerol-3-phosphate in vivo. Application of WALTZ-16 ¹ H decoupling for elimination of large ¹³ C-¹ H couplings was first tested in thermally polarized glycerol phantoms and then for in vivo HP MR studies in three rats, scanned both with and without decoupling.

Results

As configured, ¹ H-decoupled ¹³ C MR of thermally polarized glycerol and the HP metabolic product [2-¹³ C]glycerol-3-phosphate was achieved at forward power of approximately 15 W. High-quality 3-s dynamic in vivo HP ¹³ C MR scans were acquired with decoupling duty cycle of 5%. Application of ¹ H decoupling resulted in sensitivity enhancement of 1.7-fold for detection of metabolic conversion of [2-¹³ C]dihydroxyacetone to HP [2-¹³ C]glycerol-3-phosphate in vivo.

Conclusions

Application of ¹ H decoupling provides significant sensitivity enhancement for detection of HP ¹³ C metabolic products with large ¹ H spin couplings, and is therefore expected to be useful for preclinical and potentially clinical HP ¹³ C MR studies. Magn Reson Med 80:36-41, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-¹³C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo ¹³C MR data, it is possible to evaluate the distribution of agents such as [1-¹³C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-¹³C]lactate in tumor, with the ratio of [1-¹³C]lactate/[1-¹³C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect ¹³C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-¹³C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-¹³C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-¹³C]lactate/[1-¹³C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.

Purpose

With the initiation of human hyperpolarized ¹³ C (HP-¹³ C) trials at multiple sites and the development of improved acquisition methods, there is an imminent need to maximally extract diagnostic information to facilitate clinical interpretation. This study aims to improve human HP-¹³ C MR spectroscopic imaging through means of Tensor Rank truncation-Image enhancement (TRI) and optimal receiver combination (ORC).

Methods

A data-driven processing framework for dynamic HP ¹³ C MR spectroscopic imaging (MRSI) was developed. Using patient data sets acquired with both multichannel arrays and single-element receivers from the brain, abdomen, and pelvis, we examined the theory and application of TRI, as well as 2 ORC techniques: whitened singular value decomposition (WSVD) and first-point phasing. Optimal conditions for TRI were derived based on bias-variance trade-off.

Results

TRI and ORC techniques together provided a 63-fold mean apparent signal-to-noise ratio (aSNR) gain for receiver arrays and a 31-fold gain for single-element configurations, which particularly improved quantification of the lower-SNR-[¹³ C]bicarbonate and [1-¹³ C]alanine signals that were otherwise not detectable in many cases. Substantial SNR enhancements were observed for data sets that were acquired even with suboptimal experimental conditions, including delayed (114 s) injection (8× aSNR gain solely by TRI), or from challenging anatomy or geometry, as in the case of a pediatric patient with brainstem tumor (597× using combined TRI and WSVD). Improved correlation between elevated pyruvate-to-lactate conversion, biopsy-confirmed cancer, and mp-MRI lesions demonstrated that TRI recovered quantitative diagnostic information.

Conclusion

Overall, this combined approach was effective across imaging targets and receiver configurations and could greatly benefit ongoing and future HP ¹³ C MRI research through major aSNR improvements.