Eunhae Joe

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

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

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

An indirect method for in vivo T2 mapping of 13C–labeled metabolites using T2 and T2* information of water protons obtained a priori is proposed. The T2 values of 13C metabolites are inferred using the relationship to T2′ of coexisting 1H and the T2* of 13C metabolites, which is measured using routine hyperpolarized 13C 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 13C T2* estimation from the 13C 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 13C T2 values within typical experimental settings. The in vivo studies found that the estimated T2 of [1‐13C] 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 13C CSI and can potentially be used with time resolved fast CSI.

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

To optimize and investigate the influence of bipolar gradients for flow suppression in metabolic quantification of hyperpolarized 13C chemical shift imaging (CSI) of mouse liver at 9.4 T.

High resolution hyperpolarized 13C MRSI using SPICE at 9.4T: Hyperpolarized 13C SPICE

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) 13C spectroscopic imaging.

Abstract 2067: Hyperpolarized 13C-pyruvate MRS quantitatively monitor the therapeutic efficacy of adjuvant metformin combined RT in brain metastasis from triple negative breast cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Introduction The hyperpolarized 13C-pyruvate is a robust imaging biomarker to evaluate the metabolic status of cancer to monitor the anti-cancer therapeutic effect and to predict the prognosis as earliest as possible by 10,000 fold increase of MRS sensitivity. According to the clinical epidemiological research, metformin reduces cancer incidence or mortality in type II diabetes patients. In this study, we investigated the anti-cancer metabolic effect of metformin as an adjuvant for the radiation therapy to treat brain metastasis from triple negative breast cancer in nude mouse model by measuring the metabolic flux through the hyperpolarized 13C-pyruvate MRS. Methods Six weeks old BALB/C nude mice were stereotactically implanted 2×105 MDA-MB-231-luciferase breast cancer cells in the striatum of brain. After 1 week from tumor implantation, animals were randomly divided into 4 groups: vehicle (distilled water), oral metformin alone (MET), radiation treatment (RT), and radiation combined with adjuvant oral metformin treatment (METRT). Mice were treated with 300 mg/kg of oral metformin for 5 days in a week from week 1 until when the animals die. MRI and 13C MRS was performed at week 2 and week 3, before and after treatment. Brain tumors were irradiated at week 2 with 3Gy for 5 consecutive days. MRI and MRS was performed at 9.4T Bruker MRI scanner using 20mm surface dual tuned 1H-13C coil. 75mmole of hyperpolarized [1-13C] pyruvate was injected via tail vein in all mice. Metabolic flux was calculated as lactate/pyruvate ratio. The progression and the response to treatment was also monitored by bioluminescence imaging. Paraffin sections were stained with H&E for histological evaluation. Results There was no difference in tumor growth and metabolic flux rate between vehicle and MET alone groups. Vehicle group showed 260% increase in tumor mass, whereas RT group showed only 39% increase in tumor volume. 13C MRS showed 60% decrease in lactate/pyruvate flux ratio in RT group, whereas vehicle group showed 60% increase in metabolic flux ratio. Interestingly, the tumor volume was significantly regressed and 13C-lactate flux was significantly decreased in METRT group after treatment. Bioluminescence imaging showed time-dependent increasing flux in vehicle group, but RT and METRT groups showed decreased photon flux activity. In comparison of METRT with RT alone group, bioluminescence activity was significantly decreased in METRT group. H&E staining of histological sections showed significant tumor necrosis and decreased cellularity in METRT group. Conclusion Hyperpolarized 13C-pyruvate MRS informs the adjuvant therapeutic effect of metformin and RT in brain metastasis from triple negative breast cancer. Citation Format: Young-suk Choi, Han-Sol Lee, Jung-Sung Lee, Hyun-Jin Park, Ju-Hyun Lee, Eun-Kyung Wang, Seung-Wook Yang, Eunhae Joe, Soo Hyeon Lee, Dong-Hyun Kim, Ho-Taek Song. Hyperpolarized 13C-pyruvate MRS quantitatively monitor the therapeutic efficacy of adjuvant metformin combined RT in brain metastasis from triple negative breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2067. doi:10.1158/1538-7445.AM2014-2067