Peter B. Brown

High magnetic field water and metabolite proton T1 and T2 relaxation in rat brain in vivo

Comprehensive and quantitative measurements of T1 and T2 relaxation times of water, metabolites, and macromolecules in rat brain under similar experimental conditions at three high magnetic field strengths (4.0 T, 9.4 T, and 11.7 T) are presented. Water relaxation showed a highly significant increase (T1) and decrease (T2) with increasing field strength for all nine analyzed brain structures. Similar but less pronounced effects were observed for all metabolites. Macromolecules displayed field‐independent T2 relaxation and a strong increase of T1 with field strength. Among other features, these data show that while spectral resolution continues to increase with field strength, the absolute signal‐to‐noise ratio (SNR) in T1/T2‐based anatomical MRI quickly levels off beyond ∼7 T and may actually decrease at higher magnetic fields. Magn Reson Med, 2006.

Differentiation of Glucose transport in human brain gray and white matter

Localized 1H nuclear magnetic resonance spectroscopy has been applied to determine human brain gray matter and white matter glucose transport kinetics by measuring the steady-state glucose concentration under normoglycemia and two levels of hyperglycemia. Nuclear magnetic resonance spectroscopic measurements were simultaneously performed on three 12-mL volumes, containing predominantly gray or white matter. The exact volume compositions were determined from quantitative T1 relaxation magnetic resonance images. The absolute brain glucose concentration as a function of the plasma glucose level was fitted with two kinetic transport models, based on standard (irreversible) or reversible Michaelis-Menten kinetics. The steady-state brain glucose levels were similar for cerebral gray and white matter, although the white matter levels were consistently 15% to 20% higher. The ratio of the maximum glucose transport rate, Vmax, to the cerebral metabolic utilization rate of glucose, CMRGlc, was 3.2 ± 0.10 and 3.9 ± 0.15 for gray matter and white matter using the standard transport model and 1.8 ± 0.10 and 2.2 ± 0.12 for gray matter and white matter using the reversible transport model. The Michaelis-Menten constant Km was 6.2 ± 0.85 and 7.3 ± 1.1 mmol/L for gray matter and white matter in the standard model and 1.1 ± 0.66 and 1.7 ± 0.88 mmol/L in the reversible model. Taking into account the threefold lower rate of CMRGlc in white matter, this finding suggests that blood–brain barrier glucose transport activity is lower by a similar amount in white matter. The regulation of glucose transport activity at the blood–brain barrier may be an important mechanism for maintaining glucose homeostasis throughout the cerebral cortex.

Dynamic shim updating (DSU) for multislice signal acquisition.

Dynamic shim updating (DSU) is a technique for achieving optimal magnetic field homogeneity over extended volumes by dynamically updating an optimal shim setting for each individual slice in a multislice acquisition protocol. Here the practical implementation of DSU using all first‐ and second‐order shims is described. In particular, the hardware modifications and software requirements are demonstrated. Furthermore, the temporal effects of dynamically switching shim currents are investigated and a Z2‐to‐Z0 compensation unit is described and implemented to counteract the temporal Z0 variations following a change in the Z2 shim current. The optimal shim settings for all slices are determined with a quantitative and user‐independent, multislice phase‐mapping sequence. The performance of DSU is evaluated from multislice phase maps and spectroscopic images acquired on rat brain in vivo. DSU improved the magnetic field homogeneity over all spatial slices, with a more pronounced effect on the slices positioned away from the magnet isocenter, thereby making the magnetic field homogeneity highly uniform over an extended volume. Magn Reson Med 49:409–416, 2003.

Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H-[13C]-NMR spectroscopy

Localized, water‐suppressed 1H‐[13C]‐NMR spectroscopy was used to detect 13C‐label accumulation in cerebral metabolites following the intravenous infusion of [1,6‐13C2]‐glucose (Glc). The 1H‐[13C]‐NMR method, based on adiabatic RF pulses, 3D image‐selected in vivo spectroscopy (ISIS) localization, and optimal shimming, yielded high‐quality 1H‐[13C]‐NMR spectra with optimal NMR sensitivity. As a result, the 13C labeling of [4‐13C]‐glutamate (Glu) and [4‐13C]‐glutamine (Gln) could be detected from relatively small volumes (100 μL) with a high temporal resolution. The formation of [n‐13C]‐Glu, [n‐13C]‐Gln (n = 2 or 3), [2‐13C]‐aspartate (Asp), [3‐13C]‐Asp, [3‐13C]‐alanine (Ala), and [3‐13C]‐lactate (Lac) was also observed to be reproducible. The 13C‐label incorporation curves of [4‐13C]‐Glu and [4‐13C]‐Gln provided direct information on metabolic pathways. Using a two‐compartment metabolic model, the tricarboxylic acid (TCA) cycle flux was determined as 0.52 ± 0.04 μmol/min/g, while the glutamatergic neurotransmitter flux equaled 0.25 ± 0.05 μmol/min/g, in good correspondence with previously determined values. Magn Reson Med 49:37–46, 2003.

Spectroscopic imaging of glutamate C4 turnover in human brain.

One‐dimensional spectroscopic imaging of 13C‐4‐glutamate turnover is performed in the human brain with a 6 cc nominal voxel resolution at 4T. Data were acquired with an indirect detection approach using a short spin echo single quantum 1H‐13C heteronuclear editing method and a 7 cm surface coil with quadrature 13C decoupling coils. To analyze the data as a function of tissue type, T1‐based image segmentation through the surface coil was performed to determine the gray and white matter contributions to each voxel. The tricarboxylic acid (TCA) cycle rate in gray and white matter was then determined using a two‐compartment model with the tissue fractionation derived from the image segmentation. The mean values for the TCA cycle rate for occipital gray and white matter from three volunteers was 0.88 ± 0.12 and 0.28 ± 0.13 respectively, in agreement with literature data. Magn Reson Med 44:673–679, 2000.

In vivo GABA editing using a novel doubly selective multiple quantum filter

A novel multiple quantum filtering method is proposed that uses a doubly selective pulse termed Delays Alternating with Nutations for Tailored Excitation (DANTE) for multiple quantum preparation. This method selectively prepares GABA‐3 and GABA‐4 into a multiple quantum state and suppresses all other resonances at 3.0 ppm in each single scan. Phantom tests demonstrated excellent GABA signal retention and complete suppression of overlapping metabolites. It is shown using numerical simulations that overlapping macromolecules are suppressed because the frequency of the first upfield 2π rotation of the doubly selective DANTE pulse coincides with that of the macromolecules at 1.72 ppm. Excellent suppression of overlapping macromolecules was demonstrated in vivo. Using this method the concentration of GABA in the occipital lobe of healthy volunteers was measured to be 1.21 ± 0.28 μmol/mL (mean ± SD, N = 9). Magn Reson Med 47:447–454, 2002.

Multicoil shimming of the mouse brain.

MR imaging and spectroscopy allow the noninvasive measurement of brain function and physiology, but excellent magnetic field homogeneity is required for meaningful results. The homogenization of the magnetic field distribution in the mouse brain (i.e., shimming) is a difficult task due to complex susceptibility‐induced field distortions combined with the small size of the object. To date, the achievement of satisfactory whole brain shimming in the mouse remains a major challenge. The magnetic fields generated by a set of 48 circular coils (diameter 13 mm) that were arranged in a cylinder‐shaped pattern of 32 mm diameter and driven with individual dynamic current ranges of ±1 A are shown to be capable of substantially reducing the field distortions encountered in the mouse brain at 9.4 Tesla. Static multicoil shim fields allowed the reduction of the standard deviation of Larmor frequencies by 31% compared to second order spherical harmonics shimming and a 66% narrowing was achieved with the slice‐specific application of the multicoil shimming with a dynamic approach. For gradient echo imaging, multicoil shimming minimized shim‐related signal voids in the brain periphery and allowed overall signal gains of up to 51% compared to spherical harmonics shimming. Magn Reson Med, 2011.

In situ 3D magnetic resonance metabolic imaging of microwave-irradiated rodent brain : a new tool for metabolomics research

The rapid elevation in rat brain temperature achieveable with focused beam microwave irradiation (FBMI) leads to a permanent inactivation of enzymes, thereby minimizing enzyme‐dependent post‐mortem metabolic changes. An additional characteristic of FBMI is that the NMR properties of the tissue are close to those of the in vivo condition and remain so for at least 12 h. These features create an opportunity to develop magnetic resonance spectroscopy and imaging on microwave‐irradiated samples into a technique with a resolution, coverage and sensitivity superior to any experiment performed directly in vivo. Furthermore, when combined with pre‐FBMI infusion of 13C‐labeled substrates, like [1‐13C]‐glucose, the technique can generate maps of metabolic fluxes, like the tricarboxylic acid and glutamate‐glutamine neurotransmitter cycle fluxes at an unprecedented spatial resolution.

DYNAmic Multi-coIl TEchnique (DYNAMITE) shimming of the rat brain at 11.7 T.

The in vivo rat model is a workhorse in neuroscience research, preclinical studies and drug development. A repertoire of MR tools has been developed for its investigation; however, high levels of B0 magnetic field homogeneity are required for meaningful results. The homogenization of magnetic fields in the rat brain, i.e. shimming, is a difficult task because of a multitude of complex, susceptibility‐induced field distortions. Conventional shimming with spherical harmonic (SH) functions is capable of compensating for shallow field distortions in limited areas, e.g. in the cortex, but performs poorly in difficult‐to‐shim subcortical structures or for the entire brain. Based on the recently introduced multi‐coil approach for magnetic field modeling, the DYNAmic Multi‐coIl TEchnique (DYNAMITE) is introduced for magnetic field shimming of the in vivo rat brain and its benefits for gradient‐echo echo‐planar imaging (EPI) are demonstrated. An integrated multi‐coil/radiofrequency (MC/RF) system comprising 48 individual localized DC coils for B0 shimming and a surface transceive RF coil has been developed that allows MR investigations of the anesthetized rat brain in vivo. DYNAMITE shimming with this MC/RF set‐up is shown to reduce the B0 standard deviation to a third of that achieved with current shim technology employing static first‐ through third‐order SH shapes. The EPI signal over the rat brain increased by 31%, and a 24% gain in usable EPI voxels could be realized. DYNAMITE shimming is expected to critically benefit a wide range of preclinical and neuroscientific MR research. Improved magnetic field homogeneity, together with the achievable large brain coverage of this method, will be crucial when signal pathways, cortical circuitry or the brains default network are studied. Together with the efficiency gains of MC‐based shimming compared with SH approaches demonstrated recently, DYNAMITE shimming has the potential to replace conventional SH shim systems in small‐bore animal scanners. Copyright

Natural abundance 17O NMR spectroscopy of rat brain in vivo

Oxygen is an abundant element that is present in almost all biologically relevant molecules. NMR observation of oxygen has been relatively limited since the NMR-active isotope, oxygen-17, is only present at a 0.037% natural abundance. Furthermore, as a spin 5/2 nucleus oxygen-17 has a moderately strong quadrupole moment which leads to fairly broad resonances (T(2)=1-4 ms). However, the similarly short T(1) relaxation constants allow substantial signal averaging, whereas the large chemical shift range (>300 ppm) improves the spectral resolution of (17)O NMR. Here it is shown that high-quality, natural abundance (17)O NMR spectra can be obtained from rat brain in vivo at 11.74 T. The chemical shifts and line widths of more than 20 oxygen-containing metabolites are established and the sensitivity and potential for (17)O-enriched NMR studies are estimated.