High resolution hyperpolarized 13 C MRSI using SPICE at 9.4T.

PURPOSE: To test the feasibility of using the SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation) technique, which uses the partial separability of spectroscopic data, for high resolution hyperpolarized (HP) 13 C spectroscopic imaging. METHODS: Numerical simulations were performed to investigate the impact of transient HP signals on SPICE reconstruction. Furthermore, spectroscopic imaging exams from SPICE and conventional EPSI (echo-planar spectroscopic imaging) were simulated for comparison. For in vivo experiments, HP 13 C SPICE was performed in a mouse kidney by means of the injection of HP [1-13 C] pyruvate at 9.4T. RESULTS: The variation of lactate/pyruvate from the simulated SPICE was less than 4% under various factors that affect the transient HP signal, suggesting that the impact is negligible. We found that while HP 13 C EPSI was limited to the low signal-to-noise ratio (SNR) of lactate, these limitations were mitigated through HP 13 C SPICE, facilitating the improved SNR of lactate and the distinction of tissues. Acquisition of a high resolution HP 13 C spectroscopic image was possible for the in vivo experiments. With the fine structural information, the acquired image showed higher signal of pyruvate and lactate in the renal cortices than in the medullas, which is known to be attributed to higher activity of lactate dehydrogenase. CONCLUSION: The feasibility of HP 13 C SPICE was investigated. Simulation studies were conducted and in vivo experiments were performed in the mouse kidney at 9.4T. Results confirmed that a high resolution HP 13 C spectroscopic image with adequate spectral resolution can be obtained. Magn Reson Med 80:703-710, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

An indirect method for in vivo T2 mapping of [1-13 C] pyruvate using hyperpolarized 13 C CSI.

An indirect method for in vivo T2 mapping of 13 C-labeled metabolites using T2 and T2 * information of water protons obtained a priori is proposed. The T2 values of 13 C metabolites are inferred using the relationship to T2 ' of coexisting 1 H and the T2 * of 13 C metabolites, which is measured using routine hyperpolarized 13 C CSI data. The concept is verified with phantom studies. Simulations were performed to evaluate the extent of T2 estimation accuracy due to errors in the other measurements. Also, bias in the 13 C T2 * estimation from the 13 C CSI data was studied. In vivo experiments were performed from the brains of normal rats and a rat with C6 glioma. Simulation results indicate that the proposed method provides accurate and unbiased 13 C T2 values within typical experimental settings. The in vivo studies found that the estimated T2 of [1-13 C] pyruvate using the indirect method was longer in tumor than in normal tissues and gave values similar to previous reports. This method can estimate localized T2 relaxation times from multiple voxels using conventional hyperpolarized 13 C CSI and can potentially be used with time resolved fast CSI.

Flow-suppressed hyperpolarized 13 C chemical shift imaging using velocity-optimized bipolar gradient in mouse liver tumors at 9.4 T.

PURPOSE: To optimize and investigate the influence of bipolar gradients for flow suppression in metabolic quantification of hyperpolarized 13 C chemical shift imaging (CSI) of mouse liver at 9.4 T. METHODS: The trade-off between the amount of flow suppression using bipolar gradients and T2* effect from static spins was simulated. A free induction decay CSI sequence with alternations between the flow-suppressed and non-flow-suppressed acquisitions for each repetition time was developed and was applied to liver tumor-bearing mice via injection of hyperpolarized [1-13 C] pyruvate. RESULTS: The in vivo results from flow suppression using the velocity-optimized bipolar gradient were comparable with the simulation results. The vascular signal was adequately suppressed and signal loss in stationary tissue was minimized. Application of the velocity-optimized bipolar gradient to tumor-bearing mice showed reduction in the vessel-derived pyruvate signal contamination, and the average lactate/pyruvate ratio increased by 0.095 (P < 0.05) in the tumor region after flow suppression. CONCLUSION: Optimization of the bipolar gradient is essential because of the short 13 C T2* and high signal in venous flow in the mouse liver. The proposed velocity-optimized bipolar gradient can suppress the vascular signal, minimizing T2*-related signal loss in stationary tissues at 9.4 T. Magn Reson Med 78:1674-1682, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Metabolite-selective hyperpolarized (13)C imaging using extended chemical shift displacement at 9.4T.

PURPOSE: To develop a technique for frequency-selective hyperpolarized (13)C metabolic imaging in ultra-high field strength which exploits the broad spatial chemical shift displacement in providing spectral and spatial selectivity. METHODS: The spatial chemical shift displacement caused by the slice-selection gradient was utilized in acquiring metabolite-selective images. Interleaved images of different metabolites were acquired by reversing the polarity of the slice-selection gradient at every repetition time, while using a low-bandwidth radio-frequency excitation pulse to alternatingly shift the displaced excitation bands outside the imaging subject. Demonstration of this technique is presented using (1)H phantom and in vivo mouse renal hyperpolarized (13)C imaging experiments with conventional chemical shift imaging and fast low-angle shot sequences. RESULTS: From phantom and in vivo mouse studies, the spectral selectivity of the proposed method is readily demonstrated using results of chemical shift spectroscopic imaging, which displayed clearly delineated images of different metabolites. Imaging results using the proposed method without spectral encoding also showed effective separation while also providing high spatial resolution. CONCLUSION: This method provides a way to acquire spectrally selective hyperpolarized (13)C metabolic images in a simple implementation, and with potential ability to support combination with more elaborate readout methods for faster imaging.

Effect of combined bevacizumab and temozolomide treatment on intramedullary spinal cord tumor.

STUDY DESIGN: C6 glioma cells and an intramedullary spinal cord tumor model were used to evaluate the effect of bevacizumab (Avastin) or temozolomide (TMZ). OBJECTIVE: In this study, we hypothesized that treatment with bevacizumab accelerates the therapeutic effect of TMZ on intramedullary gliomas in an animal model. SUMMARY OF BACKGROUND DATA: Recently therapies for the management of intramedullary malignant gliomas include surgery, chemotherapy, and radiotherapy. Concurrent or adjuvant TMZ has been considered an emerging new treatment for intramedullary malignant gliomas; however, high-dose application of TMZ has limitation of side effect. METHODS: C6 glioma cells were injected into the T5 level of the spinal cord, and TMZ and bevacizumab were administered 5 days after C6 inoculation (n = 7 for each group). Tumor size was analyzed using histology and magnetic resonance imaging at 13 days after tumor inoculation. RESULTS: Histological analyses and magnetic resonance imaging findings showed that combined treatment with TMZ and bevacizumab reduced tumor mass. The tumor volume of control group was 2.8-fold higher than combined therapy (P < 0.05). Neurological outcomes demonstrated that combined therapy improved hind limb function more than TMZ-alone group or control group (P < 0.05). CONCLUSION: This study shows that bevacizumab could be useful in combination with TMZ to increase the therapeutic benefits of TMZ for intramedullary spinal cord tumors. LEVEL OF EVIDENCE: N/A.