Spatially resolved free-induction decay spectroscopy using a 3D ultra-short echo time multi-echo imaging sequence with systematic echo shifting and compensation of B0 field drifts.

PURPOSE: Biologically interesting signals can exhibit fast transverse relaxation and frequency shifts compared to free water. For spectral assignment, a ultra-short echo time (UTE) imaging sequence was modified to provide pixel-wise free-induction decay (FID) acquisition. METHODS: The UTE-FID approach presented relies on a multi-echo 3D spiral UTE sequence with six echoes per radiofrequency (RF) excitation (TEmin 0.05 ms, echo spacing 3 ms). A complex pixel-wise raw data set for FID spectroscopy is obtained by several multi-echo UTE measurements with systematic shifting of the readout by 0.25 or 0.5 ms, until the time domain is filled for 18 or 45 ms. B0 drifts are compensated by mapping and according phase correction. Autoregressive extrapolation of the signal is performed before Gaussian filtering. This method was applied to a phantom containing collagen-water solutions of different concentrations. To calculate the collagen content, a 19-peak collagen model was extracted from a non-selective FID spectrum (50% collagen solution). Proton-density-collagen-fraction (PDCF) was calculated for 10 collagen solutions (2%-50%). Furthermore, an in vivo UTE-FID spectrum of adipose tissue was recorded. RESULTS: UTE-FID signal patterns agreed well with the non-spatially selective pulse-acquire FID spectrum from a sphere filled with 50% collagen. Differentiation of collagen solution from distilled water in the PDCF map was possible from 4% collagen concentration for a UTE-FID sequence with 128 × 128 × 64 matrix (voxel size 1 × 1 × 2.85 mm3 ). The mean values of the PDCF correlate linearly with collagen concentration. CONCLUSION: The presented UTE-FID approach allows pixel-wise raw data acquisition similar to non-spatially selective pulse-acquire spectroscopy. Spatially resolved applications for assessment of spectra of rapidly decaying signals seem feasible.

Three-dimensional Hadamard-encoded proton spectroscopic imaging in the human brain using time-cascaded pulses at 3 Tesla.

PURPOSE: To reduce the specific-absorption-rate (SAR) and chemical shift displacement (CSD) of three-dimensional (3D) Hadamard spectroscopic imaging (HSI) and maintain its point spread function (PSF) benefits. METHODS: A 3D hybrid of 2D longitudinal, 1D transverse HSI (L-HSI, T-HSI) sequence is introduced and demonstrated in a phantom and the human brain at 3 Tesla (T). Instead of superimposing each of the selective Hadamard radiofrequency (RF) pulses with its N single-slice components, they are cascaded in time, allowing N-fold stronger gradients, reducing the CSD. A spatially refocusing 180° RF pulse following the T-HSI encoding block provides variable, arbitrary echo time (TE) to eliminate undesirable short T2 species' signals, e.g., lipids. RESULTS: The sequence yields 10-15% better signal-to-noise ratio (SNR) and 8-16% less signal bleed than 3D chemical shift imaging of equal repetition time, spatial resolution and grid size. The 13 ± 6, 22 ± 7, 24 ± 8, and 31 ± 14 in vivo SNRs for myo-inositol, choline, creatine, and N-acetylaspartate were obtained in 21 min from 1 cm(3) voxels at TE ≈ 20 ms. Maximum CSD was 0.3 mm/ppm in each direction. CONCLUSION: The new hybrid HSI sequence offers a better localized PSF at reduced CSD and SAR at 3T. The short and variable TE permits acquisition of short T2 and J-coupled metabolites with higher SNR.

Efficient method for in situ agitation of liquids directly inside NMR spectrometer.

The objective of the method is to allow agitation and fast homogenization of liquid systems in NMR tubes, directly inside the NMR spectrometer. The setup makes it possible to record spectra of samples that are macroscopically not stable, as dispersions of large particles. It makes also possible to fasten the homogeneization of liquid during a reaction or a phase transition. In the present paper, the method has been evaluated using homogeneous liquid extraction (HLLE). This configuration can also be used to introduce gases in different systems to perform various types of experiments. The set up consists in a Teflon tube inserted in the NMR tube bringing gas that yields agitation by bubbling. The gas flow is tuned using an electronically operated valve connected to gas line and to the NMR console. The method details how to reach proper homogenization without any perturbation, as liquid leaks.•An easy method for agitation of liquids inside NMR spectrometers.•The set up can be used for the insertion of gases in the NMR tube inside the spectrometer.•The method allows the study of the mixing of biphasic systems by NMR techniques.

Towards a better mechanistic comprehension of drug permeation and absorption: Introducing the diffusion-partitioning interplay.

The process of passive drug absorption from the gastrointestinal tract is still poorly understood and modelled. Additionally, the rapidly evolving field of pharmaceutics demands efficient, affordable and reliable in vitro tools for predicting in vivo performance. In this work, we combined established methods for quantifying drug diffusivity (localized UV-spectroscopy) and permeability (Permeapad® plate) in order to gain a better understanding of the role of unstirred water layers (UWLs) in drug absorption. The effect of diffusion/permeability media composition and viscosity on the apparent permeation resistance (Rapp) of model drugs caffeine (CAF) and hydrocortisone (HC) were tested and evaluated by varying the type and concentration of viscosity-enhancing agent - glycerol or a poly(ethylene glycol) (PEG) with different average molecular weights. For all types of media, increased viscosity lead to reduction in diffusivity but could not alone explain the observed effect, which was attributed to intermolecular polymer-drug interactions. Additionally, for both drugs, smaller hydrophilic viscosity-enhancing agents (glycerol and PEG 400) had larger influence than larger ones (PEG 3350 and 6000). The results highlighted the role of UWL as an additive barrier to permeation and indicated that diffusion through UWL is the rate-limiting step to CAF's permeation, whilst HC permeability is a partition-driven process.

Impact of Mucin on Drug Diffusion: Development of a Straightforward in Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin.

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin-drug interaction was investigated by measuring the drug relative diffusivity (Drel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus-PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin-drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption.

In Vivo 1H Magnetic Resonance Spectroscopy.

In vivo Magnetic Resonance Spectroscopy (MRS) allows the non-invasive detection and quantification of a number of metabolites from localized volumes within a living organism. MRS localization techniques can be divided into two main groups, single voxel and multi-voxel. Single voxel techniques provide the metabolic profile from a specific small volume, whereas multi-voxel techniques are used to obtain the spatial distribution of metabolites throughout a large volume subdivided into small contiguous voxels. This chapter describes standard protocols for the acquisition and processing of in vivo single voxel1H MRS data from the rodent brain.

Measurement of fat fraction in the human thymus by localized NMR and three-point Dixon MRI techniques.

PURPOSE: To develop a protocol to non-invasively measure and map fat fraction, fat/(fat+water), as a function of age in the adult thymus for future studies monitoring the effects of interventions aimed at promoting thymic rejuvenation and preservation of immunity in older adults. MATERIALS AND METHODS: Three-dimensional spoiled gradient echo 3T MRI with 3-point Dixon fat-water separation was performed at full inspiration for thymus conspicuity in 36 volunteers 19 to 56 years old. Reproducible breath-holding was facilitated by real-time pressure recording external to the console. The MRI method was validated against localized spectroscopy in vivo, with ECG triggering to compensate for stretching during the cardiac cycle. Fat fractions were corrected for T1 and T2 bias using relaxation times measured using inversion recovery-prepared PRESS with incremented echo time. RESULTS: In thymus at 3 T, T1water = 978 ±â€¯75 ms, T1fat = 323 ±â€¯37 ms, T2water = 43.4 ±â€¯9.7 ms and T2fat = 52.1 ±â€¯7.6 ms were measured. Mean T1-corrected MRI fat fractions varied from 0.2 to 0.8 and were positively correlated with age, weight and body mass index (BMI). In subjects with matching MRI and MRS fat fraction measurements, the difference between these measurements exhibited a mean of -0.008 with a 95% confidence interval of (0.123, -0.138). CONCLUSIONS: 3-point Dixon MRI of the thymus with T1 bias correction produces quantitative fat fraction maps that correlate with T2-corrected MRS measurements and show age trends consistent with thymic involution.

Volume localized spin echo correlation spectroscopy with suppression of 'diagonal' peaks.

Two dimensional homonuclear (1)H correlation spectroscopy is of considerable interest for volume localized spectral studies, both in vivo and in vitro, of biological as well as material objects. The information principally sought from correlation spectra resides in the cross-peaks, which are often masked however by the presence of diagonal peaks in COSY, or 'pseudo-diagonal' peaks at F1=0 in SECSY. It has therefore been a concern to suppress these diagonal or 'pseudo-diagonal' peaks, in order to ensure that cross-peak information is fully discernible. We present here a report of our work on volume localized DIagonal Suppressed Spin Echo Correlation specTroscopy (LDISSECT) and demonstrate its performance in comparison to the standard volume localized SECSY experiment, employing brain metabolite phantoms in a gel. The sequence works in the inhomogeneous, multi-component environment by exploiting the short acquisition time to suppress undesired information by employing an additional rf pulse. A brief description of the pulse sequence, its theory, and simulations are also included, besides experimental benchmarking on two brain metabolite phantoms in gel phase.

Highly-accelerated quantitative 2D and 3D localized spectroscopy with linear algebraic modeling (SLAM) and sensitivity encoding.

Noninvasive magnetic resonance spectroscopy (MRS) with chemical shift imaging (CSI) provides valuable metabolic information for research and clinical studies, but is often limited by long scan times. Recently, spectroscopy with linear algebraic modeling (SLAM) was shown to provide compartment-averaged spectra resolved in one spatial dimension with many-fold reductions in scan-time. This was achieved using a small subset of the CSI phase-encoding steps from central image k-space that maximized the signal-to-noise ratio. Here, SLAM is extended to two- and three-dimensions (2D, 3D). In addition, SLAM is combined with sensitivity-encoded (SENSE) parallel imaging techniques, enabling the replacement of even more CSI phase-encoding steps to further accelerate scan-speed. A modified SLAM reconstruction algorithm is introduced that significantly reduces the effects of signal nonuniformity within compartments. Finally, main-field inhomogeneity corrections are provided, analogous to CSI. These methods are all tested on brain proton MRS data from a total of 24 patients with brain tumors, and in a human cardiac phosphorus 3D SLAM study at 3T. Acceleration factors of up to 120-fold versus CSI are demonstrated, including speed-up factors of 5-fold relative to already-accelerated SENSE CSI. Brain metabolites are quantified in SLAM and SENSE SLAM spectra and found to be indistinguishable from CSI measures from the same compartments. The modified reconstruction algorithm demonstrated immunity to maladjusted segmentation and errors from signal heterogeneity in brain data. In conclusion, SLAM demonstrates the potential to supplant CSI in studies requiring compartment-average spectra or large volume coverage, by dramatically reducing scan-time while providing essentially the same quantitative results.

Initial in vivo rodent sodium and proton MR imaging at 21.1 T.

The first in vivo sodium and proton magnetic resonance (MR) images and localized spectra of rodents were attained using the wide bore (105 mm) high resolution 21.1-T magnet, built and operated at the National High Magnetic Field Laboratory (Tallahassee, FL, USA). Head images of normal mice (C57BL/6J) and Fisher rats (approximately 250 g) were acquired with custom designed radiofrequency probes at frequencies of 237/900 MHz for sodium and proton, respectively. Sodium MR imaging resolutions of approximately 0.125 microl for mouse and rat heads were achieved by using a 3D back-projection pulse sequence. A gain in SNR of approximately 3 for sodium and approximately 2 times for proton were found relative to corresponding MR images acquired at 9.4 T. 3D Fast Low Angle Shot (FLASH) proton mouse images (50x50x50 microm(3)) were acquired in 90 min and corresponding rat images (100x100x100 microm(3)) within a total time of 120 min. Both in vivo large rodent MR imaging and localized spectroscopy at the extremely high field of 21.1 T are feasible and demonstrate improved resolution and sensitivity valuable for structural and functional brain analysis.