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Detection of inflammatory arthritis by using hyperpolarized 13C-pyruvate with MR imaging and spectroscopy.

ABSTRACT: To examine the feasibility of using magnetic resonance (MR) spectroscopy with hyperpolarized carbon 13 ((13)C)-labeled pyruvate to detect inflammation.The animal care and use committee approved all work with animals. Arthritis was induced in the right hind paw of six rats; the left hind paw served as an internal control. The lactate dehydrogenase-catalyzed conversion of pyruvate to lactate was measured in inflamed and control paws by using (13)C MR spectroscopy. Clinical and histologic data were obtained to confirm the presence and severity of arthritis. Hyperpolarized (13)C-pyruvate was intravenously injected into the rats before simultaneous imaging of both paws with (13)C MR spectroscopy. The Wilcoxon signed rank test was used to test for differences in metabolites between the control and arthritic paws.All animals showed findings of inflammation in the affected paws and no signs of arthritis in the control paws at both visible inspection (clinical index of 3 for arthritic paws and 0 for control paws) and histologic examination (histologic score of 3-5 for arthritic paws and 0 for control paws). Analysis of the spectroscopic profiles of (13)C-pyruvate and converted (13)C-lactate showed an increase in the amount of (13)C-lactate in inflamed paws (median lactate-to-pyruvate ratio, 0.50; mean lactate-to-pyruvate ratio ± standard deviation, 0.52 ± 0.16) versus control paws (median lactate-to-pyruvate ratio, 0.27; mean lactate-to-pyruvate ratio, 0.32 ± 0.11) (P < .03). The ratio of (13)C-lactate to total (13)C was also significantly increased in inflamed paws compared with control paws (P < .03).These results suggest that alterations in the conversion of pyruvate to lactate as detected with (13)C-MR spectroscopy may be indicative of the presence of inflammatory arthritis.

SUBMITTER: MacKenzie JD

PROVIDER: S-EPMC3079121 | biostudies-other | 2011 May

REPOSITORIES: biostudies-other

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Project description:Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer's disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6?months, hyperpolarized [1-13C] pyruvate MR spectroscopy showed decreased perfusion (p?<?0.01) and increased conversion from pyruvate to lactate (p?<?0.001) in the brain. The hippocampus and striatum showed the highest conversion ratio. The functional integrity of the blood-brain barrier tested by dynamic contrast-enhanced MR imaging showed no difference to the control. Lactate was increased in the cortex (p?<?0.01) and striatum (p?<?0.05), while PDH activity was decreased in the cortex (p?<?0.01) and striatum (p?<?0.001) and the phosphorylated PDH was increased in the striatum (p?<?0.05). Mice fed HFD showed less efficiency in learning memory compared with control (p?<?0.05). To determine whether hyperpolarized 13C-pyruvate magnetic resonance (MR) spectroscopy could detect a much earier event in the brain. Mice fed HFD for 3?months did not show a detectable cognitive decline in water maze based learning memory. Hyperpolarized [1-13C] pyruvate MR spectroscopy showed increased lactate conversion (P?<?.001), but no difference in cerebral perfusion. These results suggest that the increased hyperpolarized [1-13C] lactate signal in the brain of HFD-fed mice represent that altered metabolic alteration toward to glycolysis and hypoperfusion by the long-term metabolic stress by HFD further promote to glycolysis. The hyperpolarized [1-13C] pyruvate MR spectroscopy can be used to monitor the brain metabolism and will provide information helpful to understand the disease process.

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Detection of inflammatory arthritis by using hyperpolarized 13C-pyruvate with MR imaging and spectroscopy.

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