A new strategy for in vivo spectral editing. Application to GABA editing using selective homonuclear polarization transfer spectroscopy

2007

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Lactate dehydrogenase (LDH, EC 1.1.1.27) catalyzes an exchange reaction between pyruvate and lactate. It is demonstrated here that this reaction is sufficiently fast to cause a significant magnetization (saturation) transfer effect when the 13 C resonance of pyruvate is saturated by a continuous-wave (CW) RF pulse. Infusion of [2-13 C]glucose was used to allow labeling of pyruvate C2 at 207.9 ppm to determine the pseudo first-order rate constant of the unidirectional lactate 3 pyruvate flux in vivo. During systemic administration of GABA A receptor antagonist bicuculline, this pseudo first-order rate constant was determined to be 0.08 ؎ 0.01 s ؊1 (mean ؎ SD, N ‫؍‬ 4) in halothane-anesthetized adult rat brains. In 9L and C6 rat glioma models, the 13 C saturation transfer effect of the LDH reaction was also detected in vivo. Our results demonstrate that the 13 C magnetization transfer effect of the LDH reaction may be useful as a novel marker for utilizing noninvasive in vivo MRS to study many physiological and pathological conditions, such as cancer. Magn Reson Med 57:258 -264, 2007.

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Section: Discussionmentioning

confidence: 93%

In vivo ¹³C saturation transfer effect of the lactate dehydrogenase reaction

Yang

2007

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“…Recently we have demonstrated a new GABA editing method based on presaturation and selective homonuclear polarization transfer from the C3 to the C4 methylene protons of GABA (11). Population transfer using NOE or ROE in vivo, however, is not feasible since the transfer yield is only a few percent for small molecules.…”

Section: Discussionmentioning

confidence: 99%

“…A range of spectral editing techniques using various MR properties has been proposed in an attempt to select low concentration metabolites with J-coupled spins such as ␥-aminobutyric acid (GABA) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), glutathione (GSH) (13)(14)(15)(16), alanine (17), lactate (12,18), ␤-hydroxybutyrate (12), and taurine (19). Essentially all previously proposed editing techniques are based on pulse-interrupted freeprecession of J-coupling interactions to differentiate the signal of interest (SOI) from overlapping resonances.…”

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confidence: 99%

“…For in vivo spectral editing, the HartmannHahn transfer can be exploited by selectively matching the SOI with a remote resonance to which it is J-coupled (23)(24)(25)(26). Prior to the selective Hartmann-Hahn transfer process, the thermal equilibrium SOI together with overlapping resonances can be presaturated (11). Then the SOI can be regenerated anew from the remote resonance via the selective homonuclear Hartmann-Hahn transfer process.…”

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confidence: 99%

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Selective homonuclear Hartmann–Hahn transfer method for in vivo spectral editing in the human brain

Choi

Lee

2005

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A novel selective homonuclear Hartmann-Hahn transfer method for in vivo spectral editing is proposed and applied to measurements of ␥-aminobutyric acid (GABA) in the human brain at 3 T. The proposed method utilizes a new concept for in vivo spectral editing, the spectral selectivity of which is not based on a conventional editing pulse but based on the stringent requirement of the doubly selective Hartmann-Hahn match. The sensitivity and spectral selectivity of GABA detection achieved by this doubly selective Hartmann-Hahn match scheme was superior to that achievable by conventional in vivo spectral editing techniques providing both sensitivity enhancement and excellent suppression of overlapping resonances in a single shot. Since double-quantum filtering gradients were not employed, singlets such as the NAA methyl group at 2.02 ppm and the creatine methylene group at 3.92 ppm were detected simultaneously. These singlets may serve as navigators for the spectral phase of GABA and for frequency shifts during measurements. The estimated concentration of GABA in the frontoparietal region of the human brain in vivo was 0.7 ؎ 0.2 mol/g (mean ؎ SD, n ‫؍‬ 12 A range of spectral editing techniques using various MR properties has been proposed in an attempt to select low concentration metabolites with J-coupled spins such as ␥-aminobutyric acid (GABA) (1-12), glutathione (GSH) (13-16), alanine (17), lactate (12,18), ␤-hydroxybutyrate (12), and taurine (19). Essentially all previously proposed editing techniques are based on pulse-interrupted freeprecession of J-coupling interactions to differentiate the signal of interest (SOI) from overlapping resonances. For example, the two-step J-editing techniques utilize Hahn spin-echo subtraction (1)(2)(3)(4)(5)12,17). The multiple quantum (MQ) coherence transfer method utilizes coherence transfer between different spin quantum states as well as gradient filtering (6,8 -10,13-15,18 -21). Many editing methods suffer sizable sensitivity loss during the editing process because of the conflicting needs of preserving the thermal equilibrium SOI and simultaneously suppressing the overlapping signals. The spectral selectivity is critically dependent on the bandwidth and profile of the selective editing pulse [e.g., (1-6,8 -11)].There is, however, a fundamentally different method, the Hartmann-Hahn transfer, to reveal the SOI from those based on pulse-interrupted free precession. The Hartmann-Hahn transfer was initially proposed for heteronuclear cross-polarization of dipole-coupled spins in solids by simultaneous application of spin-locking radiofrequency (RF) fields to both nuclei. When the HartmannHahn condition (␥ 1 B SL1 ϭ ␥ 2 B SL2 , where ␥ is the gyromagnetic ratio and B SL is the spin-locking RF fields) is fulfilled, polarization is transferred between heteronuclear spins. Both the heteronuclear and the homonuclear Hartmann-Hahn transfer methods have been widely used in high-resolution NMR spectroscopy of liquids (22)(23)(24)(25)(26)(27). Broadband Hartmann-Hahn match leads to pro...

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“…Prior to acute inhibition of GABA-T, a short-TE spectrum using a previously described 3D localization method (21-23) was acquired from a 4.5 ϫ 2.5 ϫ 4.5 mm 3 spectroscopy voxel (NS ϭ 128, TR/TE ϭ 2700 ms/15 ms). Then the basal GABA concentration in the same voxel was measured using a 1D doubly selective homonuclear polarization transfer method (24). Briefly, the thermal equilibrium GABA-4 signal at 3.0 ppm and the overlapping creatine, glutathione, and macromolecules were suppressed first using the chemical shift selective (CHESS) method.…”

Section: Methodsmentioning

confidence: 99%

In vivo detection of cortical GABA turnover from intravenously infused [1‐¹³C]D‐glucose

Yang

2005

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