MR imaging of the amide-proton transfer effect and the pH-insensitive nuclear overhauser effect at 9.4 T.

Neuroimaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. .
Magnetic Resonance in Medicine (Impact Factor: 3.27). 05/2012; DOI: 10.1002/mrm.24315
Source: PubMed

ABSTRACT The amide proton transfer (APT) effect has emerged as a unique endogenous molecular imaging contrast mechanism with great clinical potentials. However, in vivo quantitative mapping of APT using the conventional asymmetry analysis is difficult due to the confounding nuclear Overhauser effect (NOE) and the asymmetry of the magnetization transfer effect. Here, we showed that the asymmetry of magnetization transfer contrast from immobile macromolecules is highly significant, and the wide spectral separation associated with a high magnetic field of 9.4 T delineates APT and NOE peaks in a Z-spectrum. Therefore, high-resolution apparent APT and NOE maps can be obtained from measurements at three offsets. The apparent APT value was greater in gray matter compared to white matter in normal rat brain and was sensitive to tissue acidosis and correlated well with apparent diffusion coefficient in the rat focal ischemic brain. In contrast, no ischemia-induced contrast was observed in the apparent NOE map. The concentration dependence and the pH insensitivity of NOE were confirmed in phantom experiments. Our results demonstrate that in vivo apparent APT and NOE maps can be easily obtained at high magnetic fields and the pH-insensitive NOE may be a useful indicator of mobile macromolecular contents. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

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    ABSTRACT: PurposeTo investigate the characteristics of nuclear Overhauser enhancement (NOE) imaging signals in the brain at 7T.Methods Fresh hen eggs, as well as six healthy, and six C6 glioma-bearing Wistar rats were scanned using chemical exchange saturation transfer-magnetic resonance imaging (CEST-MRI) and chemical exchange saturation transfer-magnetic resonance spectroscopy (CEST-MRS) sequences (saturation duration 3 s, power 1.47 µT) with and without lipid suppression. CEST data were acquired over an offset range of −6 to +6 ppm relative to the water resonance in 0.5 ppm steps.ResultsThe water signals were not disrupted by other protons during the CEST-MRS sequences, and true NOE signals could be observed. Using the CEST-MRI sequence without lipid suppression, pseudo NOE imaging signals were observed in the lipid-containing regions (egg yolk, scalp, and even white matter). These pseudo NOE signals were almost (but incompletely) removed with the lipid suppression. Egg yolk results indicated the presence of the NOE to olefinic protons overlapping with the water signal. In vivo experiments showed that the amide proton transfer signal was larger in the tumor, whereas the NOE signal was larger in the normal white matter.Conclusions True NOE signals can be detected using MRS sequences, and considerable pseudo NOE imaging signals may be observed using MRI sequences. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 05/2014; · 3.27 Impact Factor
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    ABSTRACT: Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading to irreversible cellular damage. Chemical exchange saturation transfer (CEST) effects can be used to generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been used to delineate the ischemic penumbra after ischemic stroke. In the current study, a novel MRI ratiometric technique is presented to measure absolute pH using the ratio of CEST-mediated contrast from amine and amide protons: amine/amide concentration-independent detection (AACID). Effects of CEST were observed at 2.75 parts per million (p.p.m.) for amine protons and at 3.50 p.p.m. for amide protons downfield (i.e., higher frequency) from bulk water. Using numerical simulations and in vitro MRI experiments, we showed that pH measured using AACID was independent of tissue relaxation time constants, macromolecular magnetization transfer effects, protein concentration, and temperature within the physiologic range. After in vivo pH calibration using phosphorus ((31)P) magnetic resonance spectroscopy ((31)P-MRS), local acidosis is detected in mouse brain after focal permanent middle cerebral artery occlusion. In summary, our results suggest that AACID represents a noninvasive method to directly measure the spatial distribution of absolute pH in vivo using CEST MRI.Journal of Cerebral Blood Flow & Metabolism advance online publication, 5 February 2014; doi:10.1038/jcbfm.2014.12.
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    ABSTRACT: Amide proton transfer (APT) imaging is a pH mapping method based on the chemical exchange saturation transfer phenomenon that has potential for penumbra identification following stroke. The majority of the literature thus far has focused on generating pH-weighted contrast using magnetization transfer ratio asymmetry analysis instead of quantitative pH mapping. In this study, the widely used asymmetry analysis and a model-based analysis were both assessed on APT data collected from healthy subjects (n = 2) and hyperacute stroke patients (n = 6, median imaging time after onset = 2 hours 59 minutes). It was found that the model-based approach was able to quantify the APT effect with the lowest variation in grey and white matter (≤ 13.8 %) and the smallest average contrast between these two tissue types (3.48 %) in the healthy volunteers. The model-based approach also performed quantitatively better than the other measures in the hyperacute stroke patient APT data, where the quantified APT effect in the infarct core was consistently lower than in the contralateral normal appearing tissue for all the patients recruited, with the group average of the quantified APT effect being 1.5 ± 0.3 % (infarct core) and 1.9 ± 0.4 % (contralateral). Based on the fitted parameters from the model-based analysis and a previously published pH and amide proton exchange rate relationship, quantitative pH maps for hyperacute stroke patients were generated, for the first time, using APT imaging. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.
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