Magnetization transfer magic-angle-spinning z-spectroscopy of excised tissues

Avni, Reut; Mangoubi, Oren; Bhattacharyya, Rangeet; Degani, Hadassa; Frydman, Lucio

doi:10.1016/j.jmr.2009.03.007

Cited by 12 publications

(13 citation statements)

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“…A broader peak on the opposite side of the spectrum that approximately spans the frequency range from −2.2 ppm to −5.5 ppm (Figure 1c) was also observed. This broader peak had previously been attributed to NOE transfer of magnetization from aliphatic protons (Avni et al, 2009; Jin et al, 2012a; Jin et al, 2012b; Jones et al, 2012; Ling et al, 2008; Mori et al, 1998; Mougin et al, 2010; Narvainen et al, 2010; van Zijl et al, 2003; Wüthrich 1986; Zhou et al, 2003b). The amide peak appeared somewhat larger in gray matter than white matter.…”

Section: Resultsmentioning

confidence: 76%

“…These effects are typically removed by magnetization transfer ratio asymmetry (MTR asym ) analysis, where an image acquired with saturation at the amide proton frequency is subtracted from a control image acquired with RF saturation on the opposite side of the water line. MTR asym analysis, however, introduces further sources of errors due to the asymmetric macromolecular MTC effect (Hua et al, 2007b; Pekar et al, 1996; Stein et al, 1994) and the presence of saturation peaks attributed to aliphatic protons in a frequency range from approximately -1 ppm to -5 ppm (Avni et al, 2009; Jin et al, 2012a; Jin et al, 2012b; Jones et al, 2012; Ling et al, 2008; Mori et al, 1998; Mougin et al, 2010; Narvainen et al, 2010; van Zijl et al, 2003; Wüthrich 1986; Zhou et al, 2003b). Note that aliphatic protons are believed to exchange magnetization through nuclear Overhauser enhancement (NOE) (Wüthrich 1986; Zhou et al, 2003b), rather than chemical exchange.…”

Section: Introductionmentioning

confidence: 99%

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Contributors to contrast between glioma and brain tissue in chemical exchange saturation transfer sensitive imaging at 3Tesla

2014

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Off-resonance saturation transfer images have shown intriguing differences in intensity in glioma compared to normal brain tissues. Interpretation of these differences is complicated, however, by the presence of multiple sources of exchanging magnetization including amide, amine, and hydroxyl protons, asymmetric magnetization transfer contrast (MTC) from macromolecules, and various protons with resonances in the aliphatic spectral region. We report a study targeted at separating these components and identifying their relative contributions to contrast in glioma. Off-resonance z-spectra at several saturation powers and durations were obtained from 6 healthy controls and 8 patients with high grade glioma. Results indicate that broad macromolecular MTC in normal brain tissue is responsible for the majority of contrast with glioma. Amide exchange could be detected with lower saturation power than has previously been reported in glioma, but it was a weak signal source with no detectable contrast from normal brain tissue. At higher saturation powers, amine proton exchange was a major contributor to the observed signal but showed no significant difference from normal brain. Robust acquisition strategies that effectively isolate the contributions of broad macromolecular MTC asymmetry from amine exchange were demonstrated that may provide improved contrast between glioma and normal tissue.

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Section: Resultsmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Contributors to contrast between glioma and brain tissue in chemical exchange saturation transfer sensitive imaging at 3Tesla

2014

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“…Therefore, the presence of SSB for a solution must depend either on a disruption of the liquid isotropic nature due to the presence of air bubbles and/or on the occurrence of inhomogeneities of the coil radiofrequency field23. In addition, the introduction of sidebands due to wobbling of the rotor around the magic angle during spinning has also been suggested24.…”

Section: Resultsmentioning

confidence: 99%

Slow-spinning low-sideband HR-MAS NMR spectroscopy: delicate analysis of biological samples

Renault

Shintu

Piotto

et al. 2013

Sci Rep

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High-Resolution Magic-Angle Spinning (HR-MAS) NMR spectroscopy has become an extremely versatile analytical tool to study heterogeneous systems endowed with liquid-like dynamics. Spinning frequencies of several kHz are however required to obtain NMR spectra, devoid of spinning sidebands, with a resolution approaching that of purely isotropic liquid samples. An important limitation of the method is the large centrifugal forces that can damage the structure of the sample. In this communication, we show that optimizing the sample preparation, particularly avoiding air bubbles, and the geometry of the sample chamber of the HR-MAS rotor leads to high-quality low-sideband NMR spectra even at very moderate spinning frequencies, thus allowing the use of well-established solution-state NMR procedures for the characterization of small and highly dynamic molecules in the most fragile samples, such as live cells and intact tissues.

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“…Besides direct RF saturation, there are concomitant RF irradiation effects, such as semisolid macromolecular magnetization transfer (MT) and nuclear overhauser effects (NOE) (14,15). As the mechanism of the intrinsically asymmetric shift (MTR' asym ) is not well understood, the conventional asymmetry analysis is often calculated as the apparent APT contrast (16,17). Because it has been shown that the semisolid macromolecular MT changes negligibly immediately upon ischemia (18,19).…”

Section: Introductionmentioning

confidence: 99%

Quantification ofin vivopH-weighted amide proton transfer (APT) MRI in acute ischemic stroke

et al. 2015

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Amide proton transfer (APT) imaging is a specific form of chemical exchange saturation transfer (CEST) MRI that probes the pH-dependent amide proton exchange.The endogenous APT MRI is sensitive to tissue acidosis, which may complement the commonly used perfusion and diffusion scans for characterizing heterogeneous ischemic tissue damage. Whereas the saturation transfer asymmetry analysis (MTR asym ) may reasonably compensate for direct RF saturation, in vivo MTR asym is however, susceptible to an intrinsically asymmetric shift (MTR' asym ). Specifically, the reference scan for the endogenous APT MRI is 7 ppm upfield from that of the label scan, and subjects to concomitant RF irradiation effects, including nuclear overhauser effect (NOE)-mediated saturation transfer and semisolid macromolecular magnetization transfer. As such, the commonly used asymmetry analysis could not fully compensate for such slightly asymmetric concomitant RF irradiation effects, and MTR asym has to be delineated in order to properly characterize the pH-weighted APT MRI contrast. Given that there is very little change in relaxation time immediately after ischemia and the concomitant RF irradiation effects only minimally depends on pH, the APT contrast can be obtained as the difference of MTR asym between the normal and ischemic regions. Thereby, the endogenous amide proton concentration and exchange rate can be solved using a dual 2-pool model, and the in vivo MTR' asym can be calculated by subtracting the solved APT contrast from asymmetry analysis (i.e., MTR' asym =MTR asym -APTR). In addition, MTR' asym can be quantified using the classical 2-pool exchange model. In sum, our study delineated the conventional in vivo pH-sensitive MTR asym contrast so that pHspecific contrast can be obtained for imaging ischemic tissue acidosis. SUMMARYAmide proton transfer (APT) imaging is pH sensitive, and has been shown promising to complement perfusion and diffusion MRI for stratifying heterogeneous ischemic tissue injury. Whereas conventional asymmetry analysis (MTR asym ) reasonably compensates for the direct RF saturation effect, it is susceptible to an intrinsically asymmetric shift (MTR' asym ). To improve tissue acidosis mapping, we delineated pHsensitive APT effect from confounding factors using an animal model of stroke. We quantified concentration and exchange rate for both APT and nuclear overhauser effects (NOE). Our study elucidated conventional pH-weighted MTR asym contrast so that more specific pH-sensitive images can be obtained for characterizing ischemic acidosis.

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Magnetization transfer magic-angle-spinning z-spectroscopy of excised tissues

Cited by 12 publications

References 50 publications

Contributors to contrast between glioma and brain tissue in chemical exchange saturation transfer sensitive imaging at 3Tesla

Contributors to contrast between glioma and brain tissue in chemical exchange saturation transfer sensitive imaging at 3Tesla

Slow-spinning low-sideband HR-MAS NMR spectroscopy: delicate analysis of biological samples

Quantification ofin vivopH-weighted amide proton transfer (APT) MRI in acute ischemic stroke

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