Simple compensation method for improved half-pulse excitation profile with rephasing gradient.

PURPOSE: To improve the slice profile quality obtained by RF half-pulse excitation for 2D-UTE applications. METHODS: The overall first-order and zero-order phase errors along the slice-selection direction were obtained with the help of an optimization task to minimize the out-of-slice signal contamination from the calibration 1-dimenisonal (1D) profile data. The time-phase-error evolution was approximated from the k-space readout data, which were acquired primarily for correction of the readout trajectories during data regridding to the rectilinear grids. The correction of the slice profile was achieved by rephasing gradient pulses applied immediately after the end of excitation. The total prescan calibration typically took less than 2 minutes. RESULTS: The improved image quality using the proposed calibration method was demonstrated both on phantoms and on ankle images obtained from healthy volunteers. It was demonstrated that calibration can be performed either as a separate water phantom measurement or directly as a prescan procedure. CONCLUSION: The slice-profile distortion from the half-pulse excitation could substantially affect the overall fidelity of 2D-UTE images. The presented experiments proved that the image quality could be substantially increased by application of the proposed slice-correction method.

Influence of k-space trajectory corrections on proton density mapping with ultrashort echo time imaging: Application for imaging of short T2 components in white matter.

PURPOSE: To evaluate the impact of MR gradient system imperfections and limitations for the quantitative mapping of short T2* signals performed by ultrashort echo time (UTE) acquisition approach. MATERIALS AND METHODS: The measurement of short T2* signals from a phantom and a healthy volunteer study (8 subjects of average age 28 ±â€¯4 years) were performed on a 3T scanner. The characteristics of the gradient system were obtained using calibration method performed directly on the measured subject or phantom. This information was used to calculate the actual sampling trajectory with the help of a parametric eddy current model. The actual sample positions were used to reconstruct corrected images and compared with uncorrected data. RESULTS: Comparison of both approaches, i.e., without and with correction of k-space sampling trajectories revealed substantial improvement when correction was applied. The phantom experiments demonstrate substantial in-plane signal intensity variations for uncorrected sampling trajectories. In the case of the volunteer study, this led to significant differences in relative proton density (RPD) estimation between the uncorrected and corrected data (P = 0.0117 by Wilcoxon matched-pairs test) and provides for about ~15% higher values for short T2* components of white matter (WM) in the case of uncorrected images. CONCLUSION: The imperfection of the applied gradients could induce errors in k-space data sampling which further propagates into the fidelity of the UTE images and jeopardizes precision of quantification. However, the study proved that measurement of gradient errors together with correction of sample positions can contribute to increased accuracy and unbiased characterization of short T2* signals.

K-space trajectory mapping and its application for ultrashort Echo time imaging.

MR images are affected by system delays and gradient field imperfections which induce discrepancies between prescribed and actual k-space trajectories. This could be even more critical for non-Cartesian data acquisitions where even a small deviation from the assumed k-space trajectory results in severe image degradation and artifacts. Knowledge of the actual k-space trajectories is therefore crucial and can be incorporated in the reconstruction of high quality non-Cartesian images. A novel MR method for the calibration of actual gradient waveforms was developed using a combination of phase encoding increments and subsequent detection of the exact time point at which the corresponding trajectory is crossing the k-space origin. The measured sets of points were fitted to a parametrical model to calculate the complete actual acquisition trajectory. Measurements performed on phantoms and volunteers, positioned both in- and off-isocenter of the magnet, clearly demonstrate the improvement in reconstructed ultrashort echo time (UTE) images, when information from calibration of k-space sampling trajectories is employed in the MR image reconstruction procedure. The unique feature of the proposed method is its robustness and simple experimental setup, making it suitable for quick acquisition trajectory calibration procedures e.g. for non-Cartesian radial fast imaging.

Symmetry of the fornix using diffusion tensor imaging.

PURPOSE: To: 1) Present fornix tractography in its entirety for 20 healthy individuals to assess variability. 2) Provide individual and groupwise whole tract diffusion parameter symmetry assessments prior to clinical application. 3) Compare whole tract diffusion parameter assessments with tract-based spatial statistics (TBSS). MATERIALS AND METHODS: Diffusion tensor imaging (DTI) data were acquired on a 3T Siemens magnetic resonance imaging (MRI) system using a single-shot spin echo planar imaging (EPI) sequence. Individual fornix tractography was conducted and whole tract diffusion parameter symmetries assessed. Whole tract results were compared with asymmetry contrasts conducted with voxelwise statistical analysis of diffusion parameters using TBSS. RESULTS: The fornix tract could be visualized in its entirety including the columns, body, crura, and fimbria. Contrary to the crus and body, there were some tractography inconsistencies of the columns and fimbria across subjects. Although whole tract diffusion parameter asymmetries were nonsignificant, fractional anisotropy (FA) values bordered on statistical significance (P = 0.052). Using TBSS, significant FA asymmetries were identified (P ≤ 0.01, corrected). CONCLUSION: The findings demonstrate consistency of fornix tractography as well as some variability in the columns and fimbria. While parametric assessment demonstrates diffusion parameter symmetry, permutation-based TBSS analysis reveals significant FA asymmetries in the crura and fimbriae.

Tractography of Meyer's Loop asymmetries.

PURPOSE: The purpose of the current study was to use diffusion tensor imaging (DTI) to conduct tractography of the optic radiations (OR) and its component bundles and to assess both the degree of hemispheric asymmetry and the inter-subject variability of Meyer's Loop (ML). We hypothesized that there are significant left versus right differences in the anterior extent of ML to the temporal pole (TP) in healthy subjects. MATERIALS AND METHODS: DTI data were acquired on a 3T Siemens MRI system using a single-shot Spin Echo EPI sequence. The dorsal, central and ML bundles of the OR were tracked and visualized in forty hemispheres of twenty healthy volunteers. The uncinate fasciculus (UF) was also tracked in these subjects so that it could be used as a distinct anatomical reference. Measurements were derived for the distance between ML-TP, ML and the temporal horn (ML-TH) and ML and the uncinate fasciculus (ML-UF). Paired difference t-tests were carried out with SPSS 14.0. RESULTS: ML and the UF were successfully tracked and visualized in all 20 volunteers. Significant hemispheric asymmetries were found for all measurements with left distances shorter than the right (P<0.005). In 50% of the subjects the left ML-UF distance was ≤1.9 mm. CONCLUSION: The results support our hypothesis and demonstrate that left ML-TP distances are significantly shorter than right ML-TP distances. These asymmetries are also reflected in shorter left distances between ML-TH and ML-UF. Moreover, these results are of interest to left-sided temporal lobe epilepsy surgery because it is not only more likely to disturb the anterior extent of ML but also renders the often closely located posterior aspect of the left UF more vulnerable to potential surgical impact.

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethylcellulose matrix tablets in situ-is it possible to detect phenomena related to drug dissolution within the hydrated matrices?

PURPOSE: So far, the hydrated part of the HPMC matrix has commonly been denoted as a "gel" or "pseudogel" layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. METHODS: Multiparametric, spatially and temporally resolved T2 MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T2 signals. RESULTS: Two components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external "gel-like" layer. CONCLUSIONS: We have introduced a new paradigm in the characterization of hydrating matrices using (1)H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods.

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethyl cellulose matrix tablets in situ.

PURPOSE: To resolve contradictions found in morphology of hydrating hydroxypropylmethyl cellulose (HPMC) matrix as studied using Magnetic Resonance Imaging (MRI) techniques. Until now, two approaches were used in the literature: either two or three regions that differ in physicochemical properties were identified. METHODS: Multiparametric, spatially and temporally resolved T(2) MR relaxometry in situ was applied to study the hydration progress in HPMC matrix tablets using a 11.7 T MRI system. Two spin-echo based pulse sequences-one of them designed to specifically study short T(2) signals-were used. RESULTS: Two components in the T(2) decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T(2) values, were obtained. Based on the data, five different regions and their temporal evolution were identified: dry glassy, hydrated solid like, two interface layers and gel layer. The regions were found to be separated by four evolving fronts identified as penetration, full hydration, total gelification and apparent erosion. CONCLUSIONS: The MRI results showed morphological details of the hydrating HPMC matrices matching compound theoretical models. The proposed method will allow for adequate evaluation of controlled release polymeric matrix systems loaded with drug substances of different solubility.

Convertible pneumatic actuator for magnetic resonance elastography of the brain.

Here we present a novel pneumatic actuator design for brain magnetic resonance elastography (MRE). Magnetic resonance elastography is a phase contrast technique capable of tracing strain wave propagation and utilizing this information for the calculation of mechanical properties of materials and living tissues. In MRE experiments, the acoustic waves are generated in a synchronized way with respect to image acquisition, using various types of mechanical actuators. The unique feature of the design is its simplicity and flexibility, which allows reconfiguration of the actuator for different applications ranging from in vivo brain MRE to experiments with phantoms. Phantom and in vivo data are presented to demonstrate actuator performance.

Bloch simulations with intra-voxel spin dephasing.

A common problem in simulations of MRI-experiments based on the numerical solution of the Bloch equations is the finite number of isochromats used in the calculations. This usually results in false or spurious signals and is a source of various differences between calculated and experimentally obtained data. In this paper, we are proposing a technique representing each sample voxel by a central and three additional isochromats, slightly shifted in orthogonal directions from center, thus providing a linear approximation of intra-voxel dephasing. This approach allows for further improvement and precision of the calculated NMR signal and virtually avoids the problem related to an finite set of isochromats. Here we provide details of the algorithm together with examples of simulations which prove the efficiency of this approach.

Mass spectrometric study of N-glycans from serum of woodchucks with liver cancer.

Woodchucks have been a preferred lab animal model of chronic hepatitis B viral infection. The model recapitulates the disease progression of HBV infection to hepatocellular carcinoma (HCC) and has documented similarities in protein glycosylation with human HCC. This study examined N-glycans in serum of animals with(out) HCC. Oligosaccharides were released enzymatically using PNGaseF from total serum or from serum partially fractionated by extraction. Two different extraction procedures - reversed-phase high-performance liquid chromatography (RP-HPLC) and solid-phase extraction (SPE) on a cation-exchange/reversed-phase STRATA-XC cartridge - were used with the purpose of confirming glycosylation profiles. Oligosaccharides were analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) after derivatization with phenylhydrazine and/or permethylation. Characteristic fragment ions produced under MS/MS conditions allowed discrimination between isomeric structures of oligosaccharides, including those sialylated with two types of acidic residues. The complementary methods allowed structural characterization of oligosaccharides from various N-glycan classes. Furthermore, to validate results, glycosylation profiles of woodchuck sera were compared to glycans obtained from mouse serum on the same conditions. In summary, we have identified 40 N-glycan structures in the serum of woodchucks and some types of oligosaccharide structures appeared to increase in HCC samples following protease digest. The study provides improved tools for the characterization of N-glycans from total serum in the progression of liver disease.

Functional magnetic resonance imaging of the spinal cord during sensory stimulation in diabetic rats.

PURPOSE: To determine if differences exist between control and diabetic rats in functional magnetic resonance imaging (fMRI) activity of the spinal cord and if fMRI can provide a means of early detection of diabetic neuropathy. MATERIALS AND METHODS: fMRI of the spinal cord, using noxious electrical stimulation (15 V ( approximately 8 mA), 0.3 msec, 3 Hz) of the hind paw, was performed in groups of control and streptozotocin (STZ)-induced type 1 diabetic rats. RESULTS: Diabetic rats were lighter, hyperglycemic, and had lower blood pH than controls. fMRI activity at the lumbar enlargement of the spinal cord was identified in the dorsal horn ipsilateral to stimulus of all animals. Signal intensity changes across the lumbar spinal cord during periods of activity were not significantly different between control and diabetic rats, with a trend toward greater signal changes in controls. When specific regions of the spinal cord were analyzed, control rats exhibited significantly increased blood-oxygen level-dependent (BOLD) fMRI activity in both ipsilateral and contralateral dorsal horn compared to diabetic rats. CONCLUSION: The results of this study are consistent with reports that primary afferent input to the spinal cord is diminished by diabetes, and suggest that BOLD fMRI may be useful in early detection of diabetic neuropathy.

Magnetic resonance imaging tracking of alginate beads used for drug delivery of growth factors at sites of cardiac damage.

Alginate-based beads labeled with contrast agent and loaded with vascular growth hormones were used for site-specific chronic delivery of hormones at the site of myocardial damage in a porcine model. Position of the beads within the pericardium could be monitored by MRI for optimal hormone delivery due to the presence of contrast agent. The beads facilitate the slow release of cytochrome c, myoglobin and methemoglobin used as protein models of growth factors. This application allows for site-specific delivery of hormones while the incorporated contrast agent in the beads provides a tool for MRI tracking in chronic studies.

On the diffusion constant of water in wheat.

Diffusion-weighted magnetic resonance imaging (MRI) was used to obtain diffusion constants for water in the embryo and endosperm of wheat. Our experiments showed a significant difference between the diffusion constant for the two components. It was also shown that water diffusion in both the endosperm and embryo deviates from the typically observed Gaussian behavior in bulk fluids, showing a time-dependent diffusion constant. Diffusion constants for the embryo and endosperm were shown to differ by an order of magnitude. Using a model for restricted diffusion, information on the endosperm pore size and the embryo cell dimensions could be obtained.

Single-point imaging with a variable phase encoding interval.

A modified single-point imaging (SPI) technique using a variable phase encoding interval is proposed. This method is based on the minimization of the phase encoding interval for further signal-to-noise ratio (SNR) optimization. This is particularly beneficial when the maximum gradient amplitude limits an optimal phase encoding interval, and the resulting SNR suffers from T(2)-related signal attenuation. Theoretical calculation of the SNR and simulation of the point spread function (PSF) for the different experimental parameters are presented. Experiments using a rubber sample (T(2)* approximately 73 micros) and a tooth (bi-exponential relaxation: T(2,1)*=111 micros and T(2,1)*=872 micros) showed a significant increase in SNR (>3 and >2, respectively) when compared with images acquired with conventional SPI.

Simple phase method for measurement of magnetic field gradient waveforms.

Magnetic field gradients play a fundamental role in MR imaging and localized spectroscopy. The MRI experiment, in particular fast MRI, relies on precise gradient switching, which has become more demanding with the constantly growing number of fast imaging techniques. Here we present a simple MR method to measure the behavior of a magnetic field gradient waveform in an MR scanner. The method employs excitation of a thin slice, followed by application of the studied gradient and simultaneous FID acquisition. Measurements of different gradient waveforms were performed with a spherical phantom filled with doped water and positioned at the isocenter of the gradient set. The presented experiments demonstrate the capability of the technique to measure different gradient waveforms with an estimated error of less than 200 microT/m.

Monitoring the development of hepatocellular carcinoma in woodchucks using 31P-MRS.

The woodchuck is one of the only lab animal models of chronic viral hepatitis infection and the development of hepatocellular carcinoma. Using this model, changes in tissue energetics in the liver due to the development of hepatocellular carcinoma can be monitored by repeated magnetic resonance imaging and localized phosphorus spectroscopy. Age- and sex-matched control (n=5) and chronically infected (n=5) adult woodchucks were imaged four times in a six-month period in a 7-T horizontal-bore magnet. Using a custom-built doubly tunable quadrature volume coil, sagittal and axial FLASH images (128 x 128, slice thickness = 5 mm, TR/TE=1000/4.1, 8 averages) were acquired to locate the largest portion of the liver with the least amount of signal contamination from surrounding abdominal muscle. Two-dimensional 31P chemical-shift imaging (2D-CSI) was acquired (16 x 16 data matrix, 24 x 24 x 2 cm3, 1024 data points, 16 averages) for all animals. The extent of liver injury was determined using serum gamma glutamyltransferase (GGT). The livers of infected woodchucks showed a significant increase (p=0.01) in phosphomonoesters (PME):beta-adenosine triphosphate (NTP). Chronically infected woodchucks had higher levels of serum GGT compared to uninfected woodchucks (p=0.002). An increase in the PME:beta-NTP ratio indicates cellular proliferation within the malignant tumor.

Rubidium-87 magnetic resonance spectroscopy and imaging for analysis of mammalian K+ transport.

This review summarizes results 87Rb MRS/I studies of K+ transport in mammalian cells, organs and in vivo. It provides a brief description of K+ transport systems, their interactions with Rb+ and evidence that Rb+ is a best K+ congener. 87Rb MR studies have focused mostly on isolated perfused rat and pig hearts and to a lesser extent on kidney, skeletal muscle, salivary gland and red blood cells. The method has been used for three purposes: measurements of kinetics of unidirectional Rb+ uptake and efflux and steady-state Rb+ levels. In cardiovascular studies Rb+ has been used in the absence of shift reagent taking advantage of the predominantly intracellular Rb+/K+ distribution (approximately 20:1). Pharmacological analysis of Rb+ uptake and efflux allowed assessment of the contributions of various transporters to the total Rb+ fluxes in rat hearts. It was confirmed that Na+/K+ ATPase is responsible for the majority of K+ influx since Rb+ uptake is 80% ouabain-sensitive and dependent on the intracellular [Na+]. Energy deprivation caused by low-flow ischemia or metabolic inhibition reduced Rb+ uptake rate. Under normal conditions, Rb+ efflux is mediated mainly by voltage-gated K+ channels with a small contribution from the K+/Na+/2Cl- cotransporter. Intracellular alkalosis and osmotic swelling stimulated Rb+ efflux by activation of the putative K+/H+ antiporter. Activity of ATP-sensitive K+ (K(ATP)) channels was revealed by metabolic (2,4-dinitrophenol, ischemia) or pharmacological (K(ATP) opener, P-1075) stimulation of Rb+ efflux, which was reversed by the K(ATP) blocker, glibenclamide. Mitochondrial K+ transport was evaluated in hearts with saponin-permeabilized myocytes and under hypothermic conditions.Three-dimensional (3-D) spectroscopic MRI of isolated beating pig hearts has been used to obtain time series of Rb+ maps of normal and ischemic/infarcted hearts, which showed lower image intensity in the damaged area. Kinetics of Rb+ uptake in the ischemic areas depended on both regional flow and metabolism. The adrenergic agonist dobutamine stimulated Rb+ uptake in normal areas and did not affect uptake in ischemic areas. Drugs that may affect passive Rb+ transport (bumetanide, pinacidil, glibenclamide) did not change Rb+ uptake either in the normal or ischemic zones. 87Rb-MRI was also able to localize ischemia and infarction in blood-perfused hearts. 87Rb MRS/I is an excellent non-invasive research tool for studies of K+ transport in isolated organs and in vivo.

Single point imaging with suppressed sound pressure levels through gradient-shape adjustment.

Acoustic noise produced during single point imaging (SPI) experiments was modulated by changes in the spatial encoding gradients. Parameters of both linear and sine-shaped gradient ramps were modified to minimize the acoustic noise levels. Acoustic noise measurements during SPI were measured on three different gradient systems and revealed that for small gradient-bore systems a considerable acoustic noise reduction of more than 20 dB can easily be achieved. SPI in conjunction with an optimized gradient waveform can be a superb alternative to the previously introduced single point ramped imaging with T(1) enhancement (SPRITE) method when sound levels and overheating of gradients are a concern.

Magnetic resonance imaging of seeds by use of single point acquisition.

In general, magnetic resonance imaging (MRI) is used to obtain a spatial representation of the water distribution in an object. Water in soft materials (living matter) often shows a high degree of translational mobility, giving rise to relatively long magnetic relaxation times. This allows the use of conventional MRI techniques such as the spin-echo, to acquire an image. However, when hydration levels become low, water becomes less mobile, resulting in much shorter magnetic relaxation times and a corresponding signal loss. To avoid problems arising from rapid decaying signals, we investigated the use of single point imaging (SPI) in the study of seeds. We were able to obtain SPI images of nonimbibed and imbibed seeds. Using SPI with shaped gradients significantly reduced the acoustic noise level.

Barley viability during storage: use of magnetic resonance as a potential tool to study viability loss.

Malting-quality barley samples of the varieties Harrington, Manley, and TR118, each from two locations in Saskatchewan, were collected directly from the producers and sent to China for storage. At regular intervals samples were shipped back to Canada for analysis consisting of germination studies, alpha-amylase tests, magnetic resonance imaging (MRI), and magnetic relaxation (NMR) studies. Samples showing a decrease in germinative energy and elevated levels of alpha-amylase also showed a rapid uptake of water in the area between the embryo and the endosperm as observed by MRI. Using NMR relaxation experiments, viable and nonviable barley samples could be distinguished after 2 h of imbibition.