Dz Balla

Spatially localized intermolecular zero-quantum coherence spectroscopy for in vivo applications

Magnetic resonance spectroscopy (MRS) techniques that use the distant dipolar field (DDF) to locally refocus inhomogeneous line‐broadening promise improved spectral resolution in spatially varying fields. We investigated three possible implementations of localized DDF spectroscopy. Theoretical analysis and phantom experiments at 17.6 T showed that only localization immediately prior to acquisition provides sufficient spatial selectivity and sensitivity for in vivo applications. Spectra from an (8 mm)3 voxel of the rat brain were acquired in 25 min, and three major metabolites were resolved. In a tumor mouse model, DDF spectra with well‐resolved lines can be obtained from significantly larger voxels compared to conventional localized spectroscopy. From an inhomogeneous voxel, improved spectral resolution can be obtained with DDF techniques when a sufficient number of increments are sampled along the second spectral dimension. With fewer increments, measurement time is significantly shortened, and DDF techniques can provide higher signal‐to‐noise ratio (SNR) efficiency. Magn Reson Med, 2006.

Enhanced neurochemical profile of the rat brain using in vivo 1H NMR spectroscopy at 16.4 T

Single voxel magnetic resonance spectroscopy with ultrashort echo time was implemented at 16.4 T to enhance the neurochemical profile of the rat brain in vivo. A TE of 1.7 msec was achieved by sequence optimization and by using short‐duration asymmetric pulses. Macromolecular signal components were parameterized individually and included in the quantitative analysis, replacing the use of a metabolite‐nulled spectrum. Because of the high spectral dispersion, several signals close to the water line could be detected, and adjacent peaks could be resolved. All 20 metabolites detected in this study were quantified with Cramér‐Rao lower bounds below 20%, implying reliable quantification accuracy. The signal of acetate was detected for the first time in rat brain in vivo with Cramér‐Rao lower bounds of 16% and a concentration of 0.52 μmol/g. The absolute concentrations of most metabolites showed close agreement with values previously measured using in vivo 1H NMR spectroscopy and in vitro biochemical assay. Magn Reson Med, 2010.

Contrast at high field: Relaxation times, magnetization transfer and phase in the rat brain at 16.4 T

As field strength increases, the magnetic resonance imaging contrast parameters like relaxation times, magnetization transfer or image phase change, causing variations in contrast and signal‐to‐noise ratio. To obtain reliable data for these parameters at 16.4 T, high‐resolution measurements of the relaxation times T1, T2 and T2*, as well as of the magnetization transfer ratio and the local frequency in the rat brain were performed. Tissue‐specific values were obtained for up to 17 brain structures to assess image contrast. The measured parameters were compared to those found at different field strengths to estimate contrast and signal behavior at increasing field. T1 values were relatively long with (2272 ± 113) ms in cortex and (2073 ± 97) ms in white matter, but did not show a tendency to converge, leading to an almost linear increase in signal‐to‐noise ratio and still growing contrast‐to‐noise ratio. T2 was short with (25 ± 2) ms in cortex and (20 ± 1) ms in white matter. Magnetization transfer effects increase by around 25% compared to published 4.7 T data, which leads to improved contrast. The image phase, as novel and high‐field specific contrast mechanism, is shown to obtain good contrast in deep brain regions with increasing signal‐to‐noise ratio up to high field strengths. Magn Reson Med, 2011.

Intermolecular zero-quantum coherence NMR spectroscopy in the presence of local dipole fields

NMR experiments detecting intermolecular zero-quantum coherences (iZQCs) allow for observation of homogeneous line shapes under inhomogeneous magnetic fields. Local dipole fields impair the refocusing capacity of such experiments and render the available theoretical description of signal evolution invalid. In this article, the impact of local dipole fields on two-dimensional iZQC spectroscopy experiments was assessed by performing extensive numerical simulations, which solved the nonlinear Bloch equations for a binary solution in a magnetization array of 64(3) spatial points. Local dipole fields were simulated using spherical volumes with different magnetic susceptibility values corresponding to either a glass sphere or an air inclusion with a diameter of 100 microm. The local field resulted in a broadened distribution of difference frequencies between locally interacting spins and led to the dominating effect of decreasing the amplitude of the solute peak, before line broadening was observed in the spectra. From simulations using a magnetic field strength of 17.6 T, the smallest ratio of sample to inclusion volume that still allowed for observation of the solute peak was determined to be eta(limit)=215 and eta(limit)=392 for glass and air inclusions, respectively. Experimental data acquired with a 100 microm diameter glass sphere embedded in agar gel yielded a value of eta(limit)=252 and confirmed the order of magnitude obtained from the simulations. From these data, it was concluded that iZQC spectroscopy is possible as long as the relative volume occupied by air inclusions does not exceed the order of 0.1% of the sample volume. This limit, in contrast to the previous speculations, strongly excludes materials or tissues with high density of strong inhomogeneities from the investigation by iZQC spectroscopy.

Assessing White Matter Microstructure in Brain Regions with Different Myelin Architecture Using MRI

Objective We investigate how known differences in myelin architecture between regions along the cortico-spinal tract and frontal white matter (WM) in 19 healthy adolescents are reflected in several quantitative MRI parameters that have been proposed to non-invasively probe WM microstructure. In a clinically feasible scan time, both conventional imaging sequences as well as microstructural MRI parameters were assessed in order to quantitatively characterise WM regions that are known to differ in the thickness of their myelin sheaths, and in the presence of crossing or parallel fibre organisation. Results We found that diffusion imaging, MR spectroscopy (MRS), myelin water fraction (MWF), Magnetization Transfer Imaging, and Quantitative Susceptibility Mapping were myelin-sensitive in different ways, giving complementary information for characterising WM microstructure with different underlying fibre architecture. From the diffusion parameters, neurite density (NODDI) was found to be more sensitive than fractional anisotropy (FA), underlining the limitation of FA in WM crossing fibre regions. In terms of sensitivity to different myelin content, we found that MWF, the mean diffusivity and chemical-shift imaging based MRS yielded the best discrimination between areas. Conclusion Multimodal assessment of WM microstructure was possible within clinically feasible scan times using a broad combination of quantitative microstructural MRI sequences. By assessing new microstructural WM parameters we were able to provide normative data and discuss their interpretation in regions with different myelin architecture, as well as their possible application as biomarker for WM disorders.

Widespread and Opponent fMRI Signals Represent Sound Location in Macaque Auditory Cortex

In primates, posterior auditory cortical areas are thought to be part of a dorsal auditory pathway that processes spatial information. But how posterior (and other) auditory areas represent acoustic space remains a matter of debate. Here we provide new evidence based on functional magnetic resonance imaging (fMRI) of the macaque indicating that space is predominantly represented by a distributed hemifield code rather than by a local spatial topography. Hemifield tuning in cortical and subcortical regions emerges from an opponent hemispheric pattern of activation and deactivation that depends on the availability of interaural delay cues. Importantly, these opponent signals allow responses in posterior regions to segregate space similarly to a hemifield code representation. Taken together, our results reconcile seemingly contradictory views by showing that the representation of space follows closely a hemifield code and suggest that enhanced posterior-dorsal spatial specificity in primates might emerge from this form of coding.

In vivo visualization of single native pancreatic islets in the mouse

The purpose of this study was to investigate the potential of a novel targeted contrast agent (CA) for the in vivo visualization of single native pancreatic islets, the sites of insulin production, in the pancreas of mice using magnetic resonance imaging (MRI). The CA for intravenous administration was composed of the β-cell-specific single-chain antibody fragment, SCA B1, and ferromagnetic carbon-coated cobalt nanoparticles. MRI experiments were performed at 7, 9.4 and 16.4 T in excised organs (pancreas, liver, kidney, spleen), at 7 T in mice fixed in formalin and at 9.4 and 16.4 T in living mice. Image contrast in untreated control animals was compared with images from mice treated with unspecific and specific CA. For the validation of MRI results, selected pancreases were subjected to immunohistochemical staining and numerical contrast simulations were performed. Ex vivo results and the outcome of immunohistochemistry suggest that islets are marked only by the CA containing SCA B1. Strong accumulation of particles was found also in other investigated organs owing to the uptake by the reticuloendothelial system, but the contrast in the MR images is clearly distinguishable from the islet specific contrast in pancreases and numerical predictions. In vivo experiments based on averaged dynamic sampling with 66 × 66 × 100 µm³ and triggered acquisition with 90 × 90 × 200 µm³ nominal resolution resulted in similar particle contrast to in in vitro measurements. The newly developed CA and MRI strategies have the potential to be used for studying mouse diabetes models by visualizing single native pancreatic islets.

Determination of regional variations and reproducibility in in vivo 1H NMR spectroscopy of the rat brain at 16.4 T

In vivo 1H NMR spectroscopy was used to obtain the neurochemical profile in the posterior parts of the brain, the cerebellum and the medulla oblongata in comparison to the hippocampus and the thalamus. Using small voxel sizes between 16 and 32 μl to avoid partial volume effects, most metabolites demonstrated significant regional differences except acetate, γ‐aminobutyric acid, and phosphorylcholine. Noticeable regional differences in metabolite concentrations were the significant increase of total creatine in the cerebellum and the substantial decrease of taurine in thalamus and medulla oblongata. In particular, the glycine concentration in the medulla oblongata was determined to be 4.37 ± 0.68 μmol/g (Cramér‐Rao lower bounds 7%) and thus significantly higher than in the other regions, consistent with findings reported in both in vivo 1H NMR spectroscopy and in vitro biochemical assays. Intraindividual reproducibility and interindividual variability were investigated by acquiring spectra from the thalamus of the same rats in two sessions. No prominent influence on measurement session was observed in metabolite concentrations with coefficients of variations being below 20% in 16 metabolites. Magn Reson Med, 2011.

Rat brain MRI at 16.4T using a capacitively tunable patch antenna in combination with a receive array

For MRI at 16.4T, with a proton Larmor frequency of 698 MHz, one of the principal RF engineering challenges is to generate a spatially homogeneous transmit field over a larger volume of interest for spin excitation. Constructing volume coils large enough to house a receive array along with the subject and to maintain the quadrature symmetry for different loading conditions is difficult at this frequency. This calls for new approaches to RF coil design for ultra‐high field MR systems. A remotely placed capacitively tunable patch antenna, which can easily be adjusted to different loading conditions, was used to generate a relatively homogeneous excitation field covering a large imaging volume with a transversal profile similar to that of a birdcage coil. Since it was placed in front of the animal, this created valuable free space in the narrow magnet bore around the subject for additional hardware. To enhance the reception sensitivity, the patch antenna was combined with an actively detunable 3‐channel receive coil array. In addition to increased SNR compared to a quadrature transceive surface coil, we were able to get high quality gradient echo and spin‐echo images covering the whole rat brain. Copyright

Rat strain-dependent variations in brain metabolites detected by in vivo (1) H NMR spectroscopy at 16.4T.

Localized in vivo 1H NMR spectroscopy is playing an increasing role in preclinical studies, because of its ability to quantify the concentrations of up to 20 metabolites in rat brain. To assess the differences between often‐used rat strains, the neurochemical profiles of Sprague‐Dawley, Wistar and Fischer rats were determined at ultrashort TE at 16.4 T. To ascertain high‐qualitative quantification, a first experiment examined the dependence of the measuring time on the quantification results and precision by precisely the number of averages between 16 and 320. It was shown that most metabolites can be quantified accurately within a short scan time, yielding Cramér–Rao lower bounds below 20% and stable concentrations for 16 metabolites with as few as 32 or 64 averages in the thalamus and hippocampus, respectively. Interstrain differences in metabolite concentrations were shown to be moderate, with taurine varying significantly between Sprague‐Dawley and Wistar rats, and slightly more distinct differences from Fischer rats, including variations in glutamate and myo‐inositol. The high spectral quality and quantification precision of all data again demonstrated the potential of in vivo 1H NMR spectroscopy at ultrahigh field. Copyright