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

Neuroimaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. .
Magnetic Resonance in Medicine (Impact Factor: 3.57). 03/2013; 69(3). DOI: 10.1002/mrm.24315
Source: PubMed


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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Available from: Tao Jin, Sep 10, 2014
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    • "Nevertheless, intracellular changes in pH are supposed to be small in gliomas and only a subtle pH increase (up to approximately 0.1 pH) was reported [23], [24]. Since the increase of NOE was shown to be smaller than 0.7% per pH [14], [25] we assume that pH changes are not the dominant origin of the observed effect. "
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    ABSTRACT: Background and Purpose Nuclear Overhauser Enhancement (NOE) mediated chemical exchange saturation transfer (CEST) is a novel magnetic resonance imaging (MRI) technique on the basis of saturation transfer between exchanging protons of tissue proteins and bulk water. The purpose of this study was to evaluate and compare the information provided by three dimensional NOE mediated CEST at 7 Tesla (7T) and standard MRI in glioblastoma patients. Patients and Methods Twelve patients with newly diagnosed histologically proven glioblastoma were enrolled in this prospective ethics committee–approved study. NOE mediated CEST contrast was acquired with a modified three-dimensional gradient-echo sequence and asymmetry analysis was conducted at 3.3ppm (B1 = 0.7 µT) to calculate the magnetization transfer ratio asymmetry (MTRasym). Contrast enhanced T1 (CE-T1) and T2-weighted images were acquired at 3T and used for data co-registration and comparison. Results Mean NOE mediated CEST signal based on MTRasym values over all patients was significantly increased (p<0.001) in CE-T1 tumor (−1.99±1.22%), tumor necrosis (−1.36±1.30%) and peritumoral CEST hyperintensities (PTCH) within T2 edema margins (−3.56±1.24%) compared to contralateral normal appearing white matter (−8.38±1.19%). In CE-T1 tumor (p = 0.015) and tumor necrosis (p<0.001) mean MTRasym values were significantly higher than in PTCH. Extent of the surrounding tumor hyperintensity was smaller in eight out of 12 patients on CEST than on T2-weighted images, while four displayed at equal size. In all patients, isolated high intensity regions (0.40±2.21%) displayed on CEST within the CE-T1 tumor that were not discernible on CE-T1 or T2-weighted images. Conclusion NOE mediated CEST Imaging at 7T provides additional information on the structure of peritumoral hyperintensities in glioblastoma and displays isolated high intensity regions within the CE-T1 tumor that cannot be acquired on CE-T1 or T2-weighted images. Further research is needed to determine the origin of NOE mediated CEST and possible clinical applications such as therapy assessment or biopsy planning.
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    ABSTRACT: Chemical exchange (CE) sensitive MRI contrast acquired with an off-resonance irradiation pulse is affected by other relaxation mechanisms, such as longitudinal and transverse relaxations. In particular, for intermediate CEs, the effect of transverse relaxation often dominates CE contrast. Since water relaxation rates can change significantly in many pathological conditions or during physiological challenge, it is crucial to separate these relaxation effects in order to obtain pure CE contrast. Here we proposed a novel acquisition scheme in which a toggling inversion pulse is applied prior to the off-resonance irradiation. By combined acquisition of irradiation images with and without an inversion pulse at both the labile proton frequency and the reference frequency, longitudinal and transverse relaxation contributions are cancelled, and the quantification of CE parameters, such as the exchange rate and the labile proton concentration, can be simplified. Furthermore, the CE-mediated relaxation rate can be readily determined with a relatively short irradiation pulse and without approaching the steady state, therefore, reducing the limitations on hardware and specific absorption rate requirements. The signal characteristics of the proposed method are evaluated by numerical simulations and phantom experiments. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
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