Search

An increase in hyperpolarized (HP) [1‐13C]lactate production has been suggested as a biomarker for cancer occurrence as well as for response monitoring of cancer treatment. Recently, the use of metformin has been suggested as an anticancer or adjuvant treatment. By regulating the cytosolic NAD+/NADH redox state, metformin stimulates lactate production and increases the HP [1‐13C]lactate conversion rate in the kidney, liver, and heart. In general, increased HP [1‐13C]lactate is regarded as a sign of cancer occurrence or tumor growth. Thus, the relationship between the tumor suppression effect of metformin and the change in metabolism monitored by HP [1‐13C]pyruvate MRS in cancer treatment needs to be investigated. The present study was performed using a brain metastasis animal model with MDA‐MB‐231(BR)‐Luc breast cancer cells. HP [1‐13C]pyruvate MRS, T 2‐weighted MRI, and bioluminescence imaging were performed in groups treated with metformin or adjuvant metformin and radiation therapy. Metformin treatment alone did not display a tumor suppression effect, and the HP [1‐13C]lactate conversion rate increased. In radiation therapy, the HP [1‐13C]lactate conversion rate decreased with tumor suppression, with a p‐value of 0.028. In the adjuvant metformin and radiation treatment, the tumor suppression effect increased, with a p‐value of 0.001. However, the apparent HP [1‐13C]lactate conversion rate (K pl) was observed to be offset by two opposite effects: a decrease on radiation therapy and an increase caused by metformin treatment. Although HP [1‐13C]pyruvate MRS could not evaluate the tumor suppression effect of adjuvant metformin and radiation therapy due to the offset phenomenon, metabolic changes following only metformin pre‐treatment could be monitored. Therefore, our results indicate that the interpretation of HP [1‐13C]pyruvate MRS for response monitoring of cancer treatment should be carried out with caution when metformin is used as an adjuvant cancer therapy., 1. Metformin increased HP [1‐13C] lactate/pyruvate (K pl) without tumor suppression. 2. Adjuvant metformin sensitized the radiation‐induced tumor suppression effect. However, the K pl was observed to be offset by two opposite effects: a decrease on radiation therapy and an increase caused by metformin treatment.

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.

This study aims to investigate the feasibility of dynamic hyperpolarized 13 C MR spectroscopic imaging (MRSI) using the SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE) technique and an estimation of the spatially resolved conversion constant rate (kpl ). An acquisition scheme comprising a single training dataset and several imaging datasets was proposed considering hyperpolarized 13 C circumstances. The feasibility and advantage of the scheme were investigated in two parts: (a) consistency of spectral basis over time and (b) accuracy of the estimated kpl . The simulations and in vivo experiments support accurate kpl estimation with consistent spectral bases. The proposed method was implemented in an enzyme phantom and via in vivo experiments. In the enzyme phantom experiments, spatially resolved homogeneous kpl maps were observed. In the in vivo experiments, normal diet (ND) mice and high-fat diet (HFD) mice had kpl (s-1 ) values of medullar (ND: 0.0119 ± 0.0022, HFD: 0.0195 ± 0.0005) and cortical (ND: 0.0148 ±0.0023, HFD: 0.0224 ±0.0054) regions which were higher than vascular (ND: 0.0087 ±0.0013, HFD: 0.0132 ±0.0050) regions. In particular, the kpl value in the medullar region exhibited a significant difference between the two diet groups. In summary, the feasibility of using modified SPICE for dynamic hyperpolarized 13 C MRSI was demonstrated via simulations and in vivo experiments. The consistency of spectral bases over time and the accuracy of the estimated kpl values validate the proposed acquisition scheme, which comprises only a single training dataset. The proposed method improved the spatial resolution of dynamic hyperpolarized 13 C MRSI, which could be used for kpl estimation using high signal-to-noise ratio spectral bases.

Purpose 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. 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 [1-13C] 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

To quantify the accumulation of superparamagnetic iron oxide (SPIO) in patients with and without liver cirrhosis using T2 and T2* mapping.We enrolled 10 patients without liver cirrhosis and 30 patients with liver cirrhosis (Child-Pugh class A, n = 18; and B/C, n = 12). T2 and T2* mapping were performed before and after SPIO administration. The reductions in T2 (DeltaT2) and T2* (DeltaT2*) after SPIO administration were compared between the control and liver cirrhosis groups and the control, Child-Pugh A, and Child Pugh B/C groups.There were significant differences in DeltaT2 (22.2 +/- 4.4 and 15.1 +/- 7.0) and DeltaT2* values (24.3 +/- 3.3 and 16.8 +/- 8.1) (P = 0.005 and P0.001) between the control and the liver cirrhosis groups. There was a significant difference in the DeltaT2* between the Child-Pugh A and Child-Pugh B/C groups (P0.001) and in the DeltaT2 and DeltaT2* between the control and Child-Pugh B/C groups (P = 0.018 and P0.001).DeltaT2 and DeltaT2* are significantly larger in patients without liver cirrhosis than those with liver cirrhosis. DeltaT2* is also significantly larger in Child-Pugh class A patients than those in Child-Pugh B/C.

Purpose We evaluated the sonographic findings in epidermal inclusion cysts and related them to the pathologic findings. Methods We retrospectively reviewed the sonograms and pathology specimens of 24 patients with pathologically proven epidermal inclusion cysts. We evaluated the lesions for shape, size, internal echogenicity, posterior sound enhancement, and presence of color Doppler signals. We classified the masses into 5 sonographic types according to their internal echogenicity. The relationship between the sonographic types and the pathologic findings was examined. Results The masses were ovoid or spherical in 17 cases (71%), lobulated in 5 (21%), and tubular in 2 (8%). The longest diameter ranged from 1 to 6 cm (mean, 3.1 cm). Twenty-three cases (96%) were associated with posterior sound enhancement. Color Doppler signals were absent in 20 cases, but some vascularity was noted in 4 ruptured epidermal cysts, in areas of granulation tissue. The most common sonographic type was a hypoechoic lesion with scattered echogenic reflectors (10 cases). Sonographic findings were related to the lamellation of keratin debris and the granulation tissue secondary to rupture. Most cases with a lobulated configuration (4 of 5) or color Doppler signals (4 of 4) were ruptured cysts. Conclusions Epidermal inclusion cysts most often appeared sonographically as a hypoechoic mass containing variable echogenic foci without color Doppler signals. Ruptured epidermal cysts, however, may have lobulated contours and show color Doppler signals, mimicking a solid mass.

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.