PROPELLER allowed simultaneous acquisition of artifact-reduced T2 - and diffusion-weighted images of multiple hepatoma-bearing rats. This technique can promote high-throughput preclinical MR research for liver cancer.
Purpose: We explored a recovery correction technique that can correct metabolite loss during perchloric acid (PCA) extraction and minimize inter-assay variance in quantitative 1 H nuclear magnetic resonance (NMR) spectroscopy of the brain and evaluated its efficacy in 5-fluorouracil (5-FU)-and saline-administered rats.Methods: We measured the recovery of creatine and DL-valine-2,3-d 2 from PCA extract containing both compounds (0.5 to 8 mM). We intravenously administered either 5-FU for 4 days (total, 100 mg/kg body weight) or saline into 2 groups of 11 rats each. We subsequently performed PCA extraction of the whole brain on Day 9, externally adding 7 µmol of DL-valine-2,3-d 2 . We estimated metabolite concentrations using an NMR spectrometer with recovery correction, correcting metabolite concentrations based on the recovery factor of DL-valine-2,3-d 2 . For each metabolite concentration, we calculated the coefficient of variation (CEV) and compared differences between the 2 groups using unpaired t-test.Results: Equivalent recoveries of DL-valine-2,3-d 2 (89.4 « 3.9%) and creatine (89.7 « 3.9%) in the PCA extract of the mixed solution indicated the suitability of DL-valine-2,3-d 2 as an internal reference. In the rat study, recovery of DL-valine-2,3-d 2 was 90.6 « 9.2%. Nine major metabolite concentrations adjusted by recovery of DL-valine-2,3-d 2 in saline-administered rats were comparable to data in the literature. CEVs of these metabolites were reduced from 10 to 17% before to 7 to 16% after correction. The significance of differences in alanine and taurine between the 5-FU-and salineadministered groups was determined only after recovery correction (0.75 « 0.12 versus 0.86 « 0.07 for alanine; 5.17 « 0.59 versus 5.66 « 0.42 for taurine [µmol/g brain tissue]; P < 0.05).Conclusion: A new recovery correction technique corrected metabolite loss during PCA extraction, minimized inter-assay variance in quantitative 1 H NMR spectroscopy of brain tissue, and effectively detected inter-group differences in concentrations of brain metabolites between 5-FU-and saline-administered rats.
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