Proton MRI of (13)C distribution by J and chemical shift editing.

The sensitivity of (13)C NMR imaging can be considerably favored by detecting the (1)H nuclei bound to (13)C nuclei via scalar J-interaction (X-filter). However, the J-editing approaches have difficulty in discriminating between compounds with similar J-constant as, for example, different glucose metabolites. In such cases, it is almost impossible to get J-edited images of a single-compound distribution, since the various molecules are distinguishable only via their chemical shift. In a recent application of J-editing to high-resolution spectroscopy, it has been shown that a more efficient chemical selectivity could be obtained by utilizing the larger chemical shift range of (13)C. This has been made by introducing frequency-selective (13)C pulses that allow a great capability of indirect chemical separation. Here a double-resonance imaging approach is proposed, based on both J-editing and (13)C chemical shift editing, which achieves a powerful chemical selectivity and is able to produce full maps of specific chemical compounds. Results are presented on a multicompartments sample containing solutions of glucose and lactic and glutamic acid in water.     

Fast volumetric spatial-spectral MR imaging of hyperpolarized C-labeled compounds using multiple echo 3D bSSFP

Purpose

The goal of this work was to develop a fast 3D chemical shift imaging technique for the noninvasive measurement of hyperpolarized ¹³C-labeled substrates and metabolic products at low concentration.

Materials and Methods

Multiple echo 3D balanced steady state magnetic resonance imaging (ME-3DbSSFP) was performed in vitro on a syringe containing hyperpolarized [1,3,3-2H3; 1-¹³C]2-hydroxyethylpropionate (HEP) adjacent to a ¹³C-enriched acetate phantom, and in vivo on a rat before and after intravenous injection of hyperpolarized HEP at 1.5 T. Chemical shift images of the hyperpolarized HEP were derived from the multiple echo data by Fourier transformation along the echoes on a voxel by voxel basis for each slice of the 3D data set.

Results

ME-3DbSSFP imaging was able to provide chemical shift images of hyperpolarized HEP in vitro, and in a rat with isotropic 7-mm spatial resolution, 93 Hz spectral resolution and 16-s temporal resolution for a period greater than 45 s.

Conclusion

Multiple echo 3D bSSFP imaging can provide chemical shift images of hyperpolarized ¹³C-labeled compounds in vivo with relatively high spatial resolution and moderate spectral resolution. The increased signal-to-noise ratio of this 3D technique will enable the detection of hyperpolarized ¹³C-labeled metabolites at lower concentrations as compared to a 2D technique.     

Dissociation between lactate accumulation and acidosis in middle cerebral artery-occluded rats assessed by P and H NMR metabolic images under A 2-T magnetic field

The relationships among tissue edema, lactate accumulation, and intracellular pH in middle cerebral artery (MCA)-occluded rats were investigated with multiecho ¹H magnetic resonance imaging and spatially resolved metabolic images constructed by ¹H and ³¹P nuclear magnetic resonance (NMR) chemical shift imaging (CSI). For the effective and sensitive detection of NMR signals from the brain, outer volume suppression (OVS), reduced k-space sampling and proton irradiation were incorporated into the CSI sequences. The consecutive three measurements of calculated T₂ image, lactate image, and pH image which were required for 3.75 h were repeated for four cycles of 1–16 h after MCA occlusion. Tissue edema and lactate accumulation in the infarcted region were gradually and consistently increased during the 15-h observation period. In contrast, severe acidosis was already detected on the first pH image (2–4.7 h after MCA occlusion); thereafter, the degree of acidosis became milder and showed no further progression. The dissociation between the time courses of the lactate accumulation and pH decrease was clearly demonstrated by the NMR metabolic images. Acid-base balance in cerebral infarction might be affected not only by lactate production but also by complicated interactions with tissue edema and some other factors.     

Fast multivoxel two-dimensional spectroscopic imaging at 3 T

The utility of multivoxel two-dimensional chemical shift imaging in the clinical environment will ultimately be determined by the imaging time and the metabolite peaks that can be detected. Different k-space sampling schemes can be characterized by their minimum required imaging time. The use of spiral-based readout gradients effectively reduces the minimum scan time required due to simultaneous data acquisition in three k-space dimensions (k(x), k(y) and k(f(2))). A 3-T spiral-based multivoxel two-dimensional spectroscopic imaging sequence using the PRESS excitation scheme was implemented. Good performance was demonstrated by acquiring preliminary in vivo data for applications, including brain glutamate imaging, metabolite T(2) quantification and high-spatial-resolution prostate spectroscopic imaging. All protocols were designed to acquire data within a 17-min scan time at a field strength of 3 T.     

Pulsewave velocity measurement using a new real-time MR-method

A new, one-dimensional method for the measurement of pulsewave velocities using real-time magnetic resonance (MR) imaging is presented. The measurement sequence is essentially of a RACE-type (Real Time Acquisition and Evaluation) with interleaved acquisition in two not necessarily parallel slices. In each slice the blood flow velocity perpendicular to the slice orientation was monitored. From the relative time difference of blood flow activity and the slice distance, pulsewave velocities were calculated. With a time resolution of 13 ms an overall acquisition time of 3.3 s was achieved. A method for suppression of signal contributions from stationary tissue along the axis of projection is discussed on the basis of a simplified mathematical model. Preliminary volunteer studies show that pulsewave velocities in the range of 1–10 m/s can be measured with an uncertainty of about 0.6 m/s at a conventional 1.5 T imager with a gradient system of maximal 10 mT/m.     

The first in vivo observation of (13)C-(15)N coupling in mammalian brain.

[5-(13)C,(15)N]Glutamine, with (1)J((13)C-(15)N) of 16 Hz, was observed in vivo in the brain of spontaneously breathing rats by (13)C MRS at 4.7 T. The brain [5-(13)C]glutamine peak consisted of the doublet from [5-(13)C,(15)N]glutamine and the center [5-(13)C,(14)N]glutamine peak, resulting in an apparent triplet with a separation of 8 Hz. The time course of formation of brain [5-(13)C,(15)N]glutamine was monitored in vivo with a time resolution of 20-35 min. This [5-(13)C,(15)N]glutamine was formed by glial uptake of released neurotransmitter [5-(13)C]glutamate and its reaction with (15)NH(3) catalyzed by the glia-specific glutamine synthetase. The neurotransmitter glutamate C5 was selectively (13)C-enriched by intravenous [2,5-(13)C]glucose infusion to (13)C-label whole-brain glutamate C5, followed by [(12)C]glucose infusion to chase (13)C from the small and rapidly turning-over glial glutamate pool, leaving (13)C mainly in the neurotransmitter [5-(13)C]glutamate pool, which is sequestered in vesicles until release. Hence, the observed [5-(13)C,(15)N]glutamine arises from a coupling between (13)C of neuronal origin and (15)N of glial origin. Measurement of the rate of brain [5-(13)C,(15)N]glutamine formation provides a novel noninvasive method of studying the kinetics of neurotransmitter uptake into glia in vivo, a process that is crucial for protecting the brain from glutamate excitotoxicity.     

In vivo dynamic turnover of cerebral 13C isotopomers from [U-13C]glucose

An INEPT-based (13)C MRS method and a cost-effective and widely available 11.7 Tesla 89-mm bore vertical magnet were used to detect dynamic (13)C isotopomer turnover from intravenously infused [U-(13)C]glucose in a 211 microL voxel located in the adult rat brain. The INEPT-based (1)H-->(13)C polarization transfer method is mostly adiabatic and therefore minimizes signal loss due to B(1) inhomogeneity of the surface coils used. High quality and reproducible data were acquired as a result of combined use of outer volume suppression, ISIS, and the single-shot three-dimensional localization scheme built in the INEPT pulse sequence. Isotopomer patterns of both glutamate C4 at 34.00 ppm and glutamine C4 at 31.38 ppm are dominated first by a doublet originated from labeling at C4 and C5 but not at C3 (with (1)J(C4C5) = 51 Hz) and then by a quartet originated from labeling at C3, C4, and C5 (with (1)J(C3C4) = 35 Hz). A lag in the transition of glutamine C4 pattern from doublet-dominance to quartet dominance as compared to glutamate C4 was observed, which provides an independent verification of the precursor-product relationship between neuronal glutamate and glial glutamine and a significant intercompartmental cerebral glutamate-glutamine cycle between neurons and glial cells.     

Spectral editing for in vivo ¹³C magnetic resonance spectroscopy

In vivo detection of carboxylic/amide carbons is a promising technique for studying cerebral metabolism and neurotransmission due to the very low RF power required for proton decoupling. In the carboxylic/amide region, however, there is severe spectral overlap between acetate C1 and glutamate C5, complicating studies that use acetate as an astroglia-specific substrate. There are no known in vivo MRS techniques that can spectrally resolve acetate C1 and glutamate C5 singlets. In this study, we propose to spectrally separate acetate C1 and glutamate C5 by a two-step J-editing technique after introducing homonuclear (13)C-(13)C scalar coupling between carboxylic/amide carbons and aliphatic carbons. By infusing [1,2-(13)C(2)]acetate instead of [1-(13)C]acetate the acetate doublet can be spectrally edited because of the large separation between acetate C2 and glutamate C4 in the aliphatic region. This technique can be applied to studying acetate transport and metabolism in brain in the carboxylic/amide region without spectral interference.     

Magnetic resonance imaging dynamic contrast enhancement (DCE) characteristics of healed myocardial infarction differ from viable myocardium

Purpose

To determine whether healed myocardial infarction alters dynamic contrast-enhancement (DCE) curve shapes as well as late gadolinium-enhancement (LGE).

Materials and methods

Twenty patients with chronic myocardial infarction underwent MR imaging at 1.5 T with blood and myocardial T1 measurements before and after contrast administration for forty minutes. Viable and infarcted myocardial partition coefficients were calculated using multipoint slope methods for ten different DCE sampling intervals and windows. Partition coefficients and coefficients of determination were compared with paired statistical tests to assess the linearity of DCE curve shapes over the 40 min time period.

Results

Calculated partition coefficients did not vary significantly between methods (p = 0.325) for viable myocardium but did differ for infarcted myocardium (p < 0.001), indicating a difference in infarcted DCE. There was a significant difference between viable and infarcted myocardial partition coefficients estimates for all methods with the exception of methods that included measurements during the first 10 min after contrast agent administration.

Conclusion

Myocardial partition coefficients calculated from a slope calculation vary in healed myocardial infarction based on the selection of samples due to non-linear DCE curve shapes. Partition coefficient calculations are insensitive to data sampling effects in viable myocardium due to linear DCE curve shapes.     

Towards hyperpolarized (13)C-succinate imaging of brain cancer

We describe a novel (13)C enriched precursor molecule, sodium 1-(13)C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized (13)C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized (13)C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized (13)C sodium succinate, contained significant concentrations of the injected substrate, (13)C sodium succinate, together with (13)C maleate and succinate metabolites 1-(13)C-glutamate, 5-(13)C-glutamate, 1-(13)C-glutamine and 5-(13)C-glutamine. The (13)C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized (13)C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in (13)C MR spectral-spatial images.     

Video-rate near-infrared optical tomography using spectrally encoded parallel light delivery

A novel parallel source implementation approach to near-infrared tomography is demonstrated through spectral encoding of the light delivery. This new technique allows many sources to be input into the tissue at the same time, and a high-resolution spectrometer is used to spatially spread out the signals from each spectrally encoded source. The parallel sampling of all sources at all detection locations renders rapid imaging. Acquisition of complete tomographic data sets at a video rate of 35 frames/s is achieved for imaging of a 6.35 mm diameter inclusion with an absorption coefficient of 0.01 mm(-1) and a reduced scattering coefficient of 1.5 mm(-1) that is moving along a circular path inside a 1% Intralipid solution.     

Proton decoupled 13C NMR imaging

Proton decoupled 13C images were obtained at 2.1 Tesla. 13C[1H] images showed an increase in sensitivity over nondecoupled 13C images because of the nuclear Overhauser effect and elimination of multiple lines from scalar 13C-1H spin-spin couplings. The improvement in S/N for 13C[1H] images was smaller than expected because of a significant decrease in decoupling efficiency when 13C spin echoes were acquired in a readout gradient. Images of 13C compounds that had a wide range of chemical shifts showed separated and/or overlapping images, which is consistent with chemical shift imaging artifacts seen in 1H images. This work examines the technical constraints of acquiring and the difficulties of interpreting 13C[1H] images.     

Acquisition time reduction in magnetic resonance spectroscopic imaging using discrete wavelet encoding

This paper describes a new magnetic resonance spectroscopic imaging (MRSI) technique based upon the discrete wavelet transform to reduce acquisition time and cross voxel contamination. Prototype functions called wavelets are used in wavelet encoding to localize defined regions in localized space by dilations and translations. Wavelet encoding in MRSI is achieved by matching the slice selective RF pulse profiles to a set of dilated and translated wavelets. Single and dual band slice selective excitation and refocusing pulses, with profiles resembling Haar wavelets, are used in a spin-echo sequence to acquire 2D-MRSI wavelet encoding data. The 2D space region is spanned up to the desired resolution by a proportional number of dilations (increases in the localization gradients) and translations (frequency shift) of the Haar wavelets (RF pulses). Acquisition time is reduced by acquiring successive MR signals from regions of space with variable size and different locations with no requirement for a TR waiting time between acquisitions. An inverse wavelet transform is performed on the data to produce the correct spatial MR signal distribution.     

Novel peak assignments of in vivo (13)C MRS in human brain at 1.5 T

(13)C MRS studies at natural abundance and after intravenous 1-(13)C glucose infusion were performed on a 1.5-T clinical scanner in four subjects. Localization to the occipital cortex was achieved by a surface coil. In natural abundance spectra glucose C(3beta,5beta), myo-inositol, glutamate C(1,2,5), glutamine C(1,2,5), N-acetyl-aspartate C(1-4,C=O), creatine CH(2), CH(3), and C(C=N), taurine C(2,3), bicarbonate HCO(-)(3) were identified. After glucose infusion (13)C enrichment of glucose C(1alpha,1beta), glutamate C(1-4), glutamine C(1-4), aspartate C(2,3), N-acetyl-aspartate C(2,3), lactate C(3), alanine C(3), and HCO(-)(3) were observed. The observation of (13)C enrichment of resonances resonating at >150 ppm is an extension of previously published studies and will provide a more precise determination of metabolic rates and substrate decarboxylation in human brain.     

Transfer of hyperpolarization from long T1 storage nuclei to short T1 neighbors using FLOPSY-8

Nuclei with long T1s are optimal targets for dynamic nuclear polarization (DNP). Therefore, most of the agents used in metabolic imaging and spectroscopy studies are based on carboxylic acid moieties that lack protons, a strong source of dipolar relaxation. Metabolic flux information encoded into spectra of small molecule metabolites in the form of the 13C isotopomer data cannot be accessed using standard 13C hyperpolarization methods because protonated carbons relax too quickly through T1 dipolar relaxation. It is shown here that the longitudinal mixing sequence FLOPSY-8 can be used to transfer polarization from a long T1 storage nucleus to adjacent protonated carbons so that they may be detected with high sensitivity. We demonstrate that FLOPSY-8 allows a direct readout of isotopomer populations in butyrate and glutamate in vitro.     

Improved proton spectroscopic U-FLARE imaging for the detection of coupled resonances in the rat brain in vivo

Modifications of the pulse sequence for spectroscopic U-FLARE imaging are discussed to detect not only the predominant singlet signals of N-acetylaspartate, total creatine, and choline containing compounds or the doublet signal of lactate, but also the coupled resonances of glutamate, glutamine, taurine and myo-inositol. Effective homonuclear decoupling is achieved by use of constant time chemical shift encoding. A maximum signal-to-noise ratio (SNR) can be obtained for a certain coupled resonance of interest by optimizing the evolution period t(c) of the J modulated spin echo. Good reproducibility and a high SNR were achieved by combining several methods for water suppression and by using the displaced variant of U-FLARE. Measurements of a 3 mm slice of the rat brain were performed in vivo within 4 min, giving a nominal voxel size of 1.5 x 1.5 x 3.0 mm3 or 1.5 x 0.75 x 3.0 mm3. Thus, optimized spectroscopic U-FLARE is a powerful tool for proton spectroscopic imaging with high spectral, spatial and temporal resolution.     

Rapid solid-state NMR of deuterated proteins by interleaved cross-polarization from ¹H and ²H nuclei

We present a novel sampling strategy, interleaving acquisition of multiple NMR spectra by exploiting initial polarization subsequently from (1)H and (2)H spins, taking advantage of their different T(1) relaxation times. Different (1)H- and (2)H-polarization based spectra are in this way simultaneously recorded improving either information content or sensitivity by adding spectra. The so-called Relaxation-optimized Acquisition of Proton Interleaved with Deuterium (RAPID) (1)H→(13)C/(2)H→(13)C CP/MAS multiple-acquisition method is demonstrated by 1D and 2D experiments using a uniformly (2)H, (15)N,(13)C-labeled α-spectrin SH3 domain sample with all or 30% back-exchanged labile (2)H to (1)H. It is demonstrated how 1D (13)C CP/MAS or 2D (13)C-(13)C correlation spectra initialized with polarization from either (1)H or (2)H may be recorded simultaneously with flexibility to be added or used individually for spectral editing. It is also shown how 2D (13)C-(13)C correlation spectra may be recorded interleaved with (2)H-(13)C correlation spectra to obtain (13)C-(13)C correlations along with information about dynamics from (2)H sideband patterns.     

西洋参皂甙的核磁共振波谱研究——Ⅰ.西洋参叶中 Ocotillol型皂甙的结构分析

本文用常规一维~1H、~(13)C核磁共振波谱和远程异核化学位移相关谱。异核化学位移相关谱和同核化学位移相关谱技术研究了西洋参叶中首次分离出的一种Ocotillol型皂甙,确认了化学结构,并对其~(13)C、~1H NMR谱线进行了归属。     

Effect of hyperosmotic mannitol on magnetic resonance relaxation parameters in reperfused canine myocardial infarction

To determine how administration of a hyperosmotic agent alters regional nuclear magnetic resonance (NMR) relaxation parameters and imaging characteristics in ischemic-reperfused myocardium, 7 dogs were infused with mannitol for 15 minutes before and after the release of a 3 hour left anterior descending coronary artery (LAD) occlusion. Nine control animals received normal saline during the 3 hour occlusion and 1 hour reperfusion periods. Normal posterior left ventricular (LV) wall and the ischemic anterior LV wall (risk area) myocardium was sampled for calculation of segmental microsphere myocardial blood flow, % tissue water content, NMR relaxation times (T1, T2) and myocyte ultrastructure using electron microscopy. Mean infarct T1 values were 14% greater than normal segments in saline-treated controls, but only 5% greater after mannitol. The difference in tissue water content between infarcted and normal segments was 4% in saline-treated (83 vs. 79%) compared to 2% in mannitol-treated dogs (79 vs. 77%). T1, T2 and % water content of control infarct segments were greater than treated infarcts (p less than 0.01). T1 and T2 rose as occlusion flow fell below 0.5 ml/min/g in control hearts but did not rise until flows were reduced to 0.1 ml/min/g in mannitol-treated hearts. Areas of increased signal in T1 and T2 NMR images correlated well with histochemical infarct volume (r = 0.98, SEE = 1.1 cc) in mannitol-treated dogs, but infarct borders were qualitatively less well-defined than in controls. We concluded that mannitol (1) diminishes tissue edema and reduces NMR relaxation parameters (T1, T2) in infarcted myocardium; and (2) attenuates the rise in T1 and T2 and ultrastructural myocyte injury in ischemic-reperfused myocardium.     

A four-element phased array coil for high resolution and parallel MR imaging of the knee

A four-element phased array coil for MR imaging of the knee was designed, built and tested for clinical use at 1.5 Tesla. In routine imaging, it provides over twofold increase in signal-to-noise (SNR) compared to two commercially available knee coils, and supports higher spatial image resolution. The phased array knee coil was also tested for its compatibility with parallel MR imaging that reduces imaging time by several folds over conventional MR technique. Results obtained using SiMultaneous Acquisition of Spatial Harmonics (SMASH) technique shows that our phased array knee coil can be used with parallel MR imaging. These improvements may enhance knee diagnosis with higher image quality and reduced scan time.