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Metal ion sensing using ion chemical exchange saturation transfer 19F magnetic resonance imaging.

ABSTRACT: Although metal ions are involved in a myriad of biological processes, noninvasive detection of free metal ions in deep tissue remains a formidable challenge. We present an approach for specific sensing of the presence of Ca(2+) in which the amplification strategy of chemical exchange saturation transfer (CEST) is combined with the broad range of chemical shifts found in (19)F NMR spectroscopy to obtain magnetic resonance images of Ca(2+). We exploited the chemical shift change (??) of (19)F upon binding of Ca(2+) to the 5,5'-difluoro derivative of 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA) by radiofrequency labeling at the Ca(2+)-bound (19)F frequency and detection of the label transfer to the Ca(2+)-free (19)F frequency. Through the substrate binding kinetics we were able to amplify the signal of Ca(2+) onto free 5F-BAPTA and thus indirectly detect low Ca(2+) concentrations with high sensitivity.

SUBMITTER: Bar-Shir A

PROVIDER: S-EPMC3786336 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Metal ion sensing using ion chemical exchange saturation transfer 19F magnetic resonance imaging.

Bar-Shir Amnon A Gilad Assaf A AA Chan Kannie W Y KW Liu Guanshu G van Zijl Peter C M PC Bulte Jeff W M JW McMahon Michael T MT

Journal of the American Chemical Society 20130806 33

Although metal ions are involved in a myriad of biological processes, noninvasive detection of free metal ions in deep tissue remains a formidable challenge. We present an approach for specific sensing of the presence of Ca(2+) in which the amplification strategy of chemical exchange saturation transfer (CEST) is combined with the broad range of chemical shifts found in (19)F NMR spectroscopy to obtain magnetic resonance images of Ca(2+). We exploited the chemical shift change (Δω) of (19)F upon ...[more]

PMID: 23905693

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Project description:Background:Encephalitis is a common central nervous system inflammatory disease that seriously endangers human health owing to the lack of effective diagnostic methods, which leads to a high rate of misdiagnosis and mortality. Glutamate is implicated closely in microglial activation, and activated microglia are key players in encephalitis. Hence, using glutamate chemical exchange saturation transfer (GluCEST) imaging for the early diagnosis of encephalitis holds promise. Methods:The sensitivity of GluCEST imaging with different concentrations of glutamate and other major metabolites in the brain was validated in phantoms. Twenty-seven Sprague-Dawley (SD) rats with encephalitis induced by Staphylococcus aureus infection were used for preclinical research of GluCEST imaging in a 7.0-Tesla scanner. For the clinical study, six patients with encephalitis, six patients with lacunar infarction, and six healthy volunteers underwent GluCEST imaging in a 3.0-Tesla scanner. Results:The number of amine protons on glutamate that had a chemical shift of 3.0 ppm away from bulk water and the signal intensity of GluCEST were concentration-dependent. Under physiological conditions, glutamate is the main contributor to the GluCEST signal. Compared with normal tissue, in both rats and patients with encephalitis, the encephalitis areas demonstrated a hyper-intense GluCEST signal, while the lacunar infarction had a decreased GluCEST signal intensity. After intravenous immunoglobulin therapy, patients with encephalitis lesions showed a decrease in GluCEST signal, and the results were significantly different from the pre-treatment signal (1.34 ± 0.31 vs 5.0 ± 0.27%, respectively; p = 0.000). Conclusion:Glutamate plays a role in encephalitis, and the GluCEST imaging signal has potential as an in vivo imaging biomarker for the early diagnosis of encephalitis. GluCEST will provide new insight into encephalitis and help improve the differential diagnosis of brain disorders.

Dataset Information

Metal ion sensing using ion chemical exchange saturation transfer 19F magnetic resonance imaging.

Publications

Metal ion sensing using ion chemical exchange saturation transfer 19F magnetic resonance imaging.

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