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Background and Purposes: We recently proposed the existence of neurotoxic interactions between the cannabinoid type 1 (CB(1)) receptor and transient receptor potential vanilloid 1 (TRPV1) channels in rat mesencephalic cultures. This study seeks evidence for the mediator(s) and mechanisms underlying the neurotoxic interactions between CB(1) receptors and TRPV1 in vitro and in vivo., Experimental Approach: The mediator(s) and mechanism(s) for the interactions between CB(1) receptors and TRPV1 were evaluated by cell viability assays, immunocytochemistry, Fura-2 calcium imaging, mitochondrial morphology assay, ELISA and Western blot assay in vitro in neuron-enriched mesencephalic cultures. Injections into the substantia nigra and subsequent cell counts were also used to confirm these interactions in vivo., Key Results: The neurotoxic interactions were mediated by 12(S)-hydroperoxyeicosatetraenoic acid (12(S)-HPETE), an endogenous TRPV1 agonist. CB(1) receptor agonists (HU210 and WIN55,212-2) increased the level of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a downstream metabolite of 12(S)-HPETE, which stimulates TRPV1-mediated death of mesencephalic neurons, both in vitro and in vivo. The neurotoxicity was mediated by increased intracellular Ca(2+) concentration ([Ca(2+)](i)) through TRPV1, consequently leading to mitochondrial damage and was attenuated by baicalein, a 12-lipoxygenase inhibitor., Conclusion and Implications: Activation of CB(1) receptors in rat mesencephalic neurons was associated with biosynthesis of 12(S)-HPETE, which in turn stimulated TRPV1 activity, leading to increased [Ca(2+)](i), mitochondrial damage and neuronal death.

Echo shifted (ES) gradient-recalled echo sequences (whose TE > TR) have found important applications in fMRI and MR thermometry since their introduction. The technique increases T *(2) weighting in BOLD imaging and temperature change sensitivity in phase-based temperature imaging compared to FLASH sequences. Yet, inconsistent observations have previously been reported when variants of this technique were used in various MRI experiments. Previous understanding of the ES sequences (the "FLASH-like" postulation) was not sufficient to explain these observations. This work provides an in-depth study on the various ES sequences. It was found that there are two types of ES sequences: ES-FLASH that spoils coherent transverse magnetization and ES-GRE, which is based on SSFP signals. A signal expression was derived for the clinically popular TR-periodic ES-GRE sequence with one echo shift. This signal expression reduced to the "FLASH-like" postulation under certain conditions. The new knowledge about the echo formation mechanism in ES sequences helps explain the experimental observations previously reported. Moreover, the resonance offset angle based analysis demonstrates an elegant methodology to analyze short TR imaging sequences. Magn Reson Med 42:864-875, 1999., (Copyright 1999 Wiley-Liss, Inc.)

Rapid T(2) weighted (T(2)W) images would facilitate physicians being able to distinguish normal tissues, vessels, tumors, and thermal lesions from therapeutic devices throughout interventional MRI procedures commonly performed in open low-field scanners (e.g., 0.2 T). Conventional diagnostic MRI techniques have not been successful at low-field strength for fast T(2)W imaging during the guidance phase of interventional MRI (I-MRI) procedures. FISP and true-FISP methods yield T(1)/T(2)-weighted images and do not always provide sufficient contrast for device guidance or lesion assessment. As such, a variant of PSIF (a gradient reversed form of FISP) which collects the T(2)-weighted spin echo of the SSFP signal was developed and implemented at 0.2 T for use in I-MRI procedures. The sequence has a balanced readout gradient to reduce motion sensitivity. Asymmetric sampling toward the end of the TR cycle reduces T(2)* decay of the spin echo component in the SSFP signal. The sequence gives one image in 5-7 s in vivo with adequate SNR and T(2) contrast for interventional applications. Patient studies showed that the PSIF sequence variant demarcates many tumors not detectable by either FISP or true-FISP. Results from animal experiments suggested that it has potential to monitor thermal lesions during interstitial thermal ablation procedures. Magn Reson Med 42:335-344, 1999., (Copyright 1999 Wiley-Liss, Inc.)

Successful radiofrequency (RF) thermal ablation was performed on VX2 tumors implanted in 23 rabbit livers under magnetic resonance (MR) guidance using a C-arm-shaped low-field 0.2 T system. RF application and immediate postprocedure MRI of all animals was performed [T2-weighted, turbo short tau inversion recovery (STIR), T1-weighted before and after gadopentetate dimeglumine administration). Follow-up MRI with a superparamagnetic iron oxide (SPIO) contrast medium was performed in nine rabbits at 2 weeks and in four rabbits at 1 month post RF ablation. All livers were harvested for pathologic examination. T2-weighted and turbo-STIR images demonstrated the highest tumor-to-RF-thermal lesion contrast-to-noise ratios (CNRs; means 4.5 and 3.8, respectively) on postprocedure images; this was redemonstrated at 2- and 4-week follow-up imaging. T2-weighted imaging never overestimated pathologic lesion size by more than 2 mm, and the radiologic-pathologic correlation coefficient was not less than 0.90. In conclusion, MRI-guided RF thermal ablation in implanted liver tumor is feasible using a C-arm-shaped low-field 0.2 T system. The thermal lesion size can be most accurately monitored with T2-weighted and turbo-STIR images.

Background: An increase in resting energy expenditure (REE) is considered to contribute to the weight loss experienced by patients with cancer. However, alternations in basal metabolism vary among patients with different neoplasms. REE in patients with hepatocellular carcinoma (HCC), a common malignant tumor in Taiwan, was evaluated., Methods: Fifty-seven male patients with HCC and 60 male control subjects without known cancer were entered in the study. The groups did not differ significantly in age, body weight, and height. Indirect calorimetry was used to measure REE. Oxidative rates of endogenous substrates also were calculated., Results: REE was significantly higher in the HCC group than the control group (22.12 +/- 0.36 kcal/kg/day versus 20.99 +/- 0.27 kcal/kg/day, P < 0.05; and 115.3 +/- 4.3 kcal/100 mg creatinine versus 102.2 +/- 3.8 kcal/100 mg creatinine, P < 0.05). A higher measured-to-predicted-REE ratio also was observed in the HCC group (101.5% +/- 1.4% versus 93.6% +/- 1.0%; P < 0.005). REE in patients with HCC did not differ according to whether patients had liver cirrhosis or ascites. In addition, REE of patients with large and medium tumors were higher than were those of patients with small tumors, but no difference was found between the REE of patients with small tumors and the control subjects. Also observed were an increase in oxidation of fat with a decrease in oxidation of protein in patients with HCC and a relative decrease in the contribution of fat with an increase in the contribution of carbohydrates to REE after the increase of tumor size., Conclusions: The results suggest that patients with HCC are hypermetabolic and the elevation in REE is related to tumor size, not to the presence of liver cirrhosis or ascites.