Magnetic resonance microscopy of the equine hoof wall: a study of resolution and potential.

REASONS FOR PERFORMING STUDY: Obtaining magnetic resonance images of the inner hoof wall tissue at the microscopic level would enable early accurate diagnosis of laminitis and therefore more effective therapy. OBJECTIVES: To optimise magnetic resonance imaging (MRI) parameters in order to obtain the highest possible resolution of the structures beneath the equine hoof wall. METHODS: Magnetic resonance microscopy (MRM) was performed in front feet from 6 cadaver horses using T2-weighted fast spin echo (FSE-T2), and T1-weighted gradient echo (GRE-T1) sequences. RESULTS: In T2 weighted FSE images most of the stratum medium showed no signal, however the coronary, terminal and sole papillae were visible. The stratum lamellatum was clearly visible and primary epidermal lamellae could be differentiated from dermal lamellae. CONCLUSION: Most structures beneath the hoof wall were differentiated. Conventional scanners for diagnostic MRI in horses are low or high field. However this study used ultra-high field scanners currently not available for clinical use. Signal-to-noise ratio (S/N) increases as a function of field strength. An increase of spatial resolution of the image results in a decreased S/N. S/N can also be improved with better coils and the resolution of high field MRI scanners will increase as technology develops and surface array coils become more readily available. POTENTIAL RELEVANCE: Although MR images with microscopic resolution were obtained ex vivo, this study demonstrates the potential for detection of lamellar pathology as it occurs. Early recognition of the development of laminitis to instigate effective therapy at an earlier stage and may improve the outcome for laminitic horses. Clinical MR is now readily available at 3 T, while 4 T, 7 T and 9 T systems are being used for human whole body applications.

Magnetic resonance imaging analysis of the upper cervical spine extensor musculature in an asymptomatic cohort: an index of fat within muscle.

AIM: To establish a simple method to quantify muscle/fat constituents in cervical muscles of asymptomatic women using magnetic resonance imaging (MRI), and to determine whether there is an age effect within a defined age range. MATERIALS AND METHODS: MRI of the upper cervical spine was performed for 42 asymptomatic women aged 18-45 years. The muscle and fat signal intensities on axial spin echo T1-weighted images were quantitatively classified by taking a ratio of the pixel intensity profiles of muscle against those of intermuscular fat for the rectus capitis posterior major and minor and inferior obliquus capitis muscles bilaterally. Inter- and intra-examiner agreement was scrutinized. RESULTS: The average relative values of fat within the upper cervical musculature compared with intermuscular fat indicated that there were only slight variations in indices between the three sets of muscles. There was no significant correlation between age and fat indices. There were significant differences for the relative fat within the muscle compared with intermuscular fat and body mass index for the right rectus capitis posterior major and right and left inferior obliquus capitis muscles (p=0.032). Intraclass correlation coefficients for intraobserver agreement ranged from 0.94 to 0.98. Inter-rater agreement of the measurements ranged from 0.75 to 0.97. CONCLUSION: A quantitative measure of muscle/fat constituents has been developed, and results of this study indicate that relative fatty infiltration is not a feature of age in the upper cervical extensor muscles of women aged 18-45 years.

Magnetization transfer imaging for polymer gel dosimetry.

Off-resonance RF pre-saturation was used to obtain contrast in MRI images of polymer gel dosimeters irradiated to doses up to 50 Gy. Two different polymer gel dosimeters composed of 2-hydroxyethyl-acrylate or methacrylic acid monomers mixed with N, N'-methylene-bisacrylamide (BIS), dispersed in an aqueous gelatin matrix were evaluated. Radiation-induced polymerization of the co-monomers generates a fast-relaxing insoluble polymer. Saturation of the polymer using off-resonance Gaussian RF pulses prior to a spin-echo readout with a short echo time leads to contrast that is dependent on the absorbed dose. This contrast is attributed to magnetization transfer (MT) between free water and the polymer, and direct saturation of water was found to be negligible under the prevailing experimental conditions. The usefulness of MT imaging was assessed by computing the dose resolution obtained with this technique. We found a low value of dose resolution over a wide range of doses could be obtained with a single experiment. This is an advantage over multiple spin echo (MSE) experiments using a single echo spacing where an optimal dose resolution is achieved over only very limited ranges of doses. The results suggest MT imaging protocols may be developed into a useful tool for polymer gel dosimetry.

A uniqueness theorem for the anti-de Sitter soliton.

The stability of physical systems depends on the existence of a state of least energy. In gravity, this is guaranteed by the positive energy theorem. For topological reasons, this fails for nonsupersymmetric Kaluza-Klein compactifications, which can decay to arbitrarily negative energy. For related reasons, this also fails for the anti-de Sitter (AdS) soliton, a globally static, asymptotically toroidal Lambda<0 spacetime with negative mass. Nonetheless, arguing from the AdS conformal field theory (AdS/CFT) correspondence, Horowitz and Myers proposed a new positive energy conjecture, which asserts that the AdS soliton is the unique state of least energy in its asymptotic class. We give a new structure theorem for static Lambda<0 spacetimes and use it to prove uniqueness of the AdS soliton. Our results offer significant support for the new positive energy conjecture and add to the body of rigorous results inspired by the AdS/CFT correspondence.

4D deformation modeling of cortical disease progression in Alzheimer's dementia.

This work describes the development of a model of cerebral atrophic changes associated with the progression of Alzheimer's disease (AD). Linear registration, region-of-interest analysis, and voxel-based morphometry methods have all been employed to elucidate the changes observed at discrete intervals during a disease process. In addition to describing the nature of the changes, modeling disease-related changes via deformations can also provide information on temporal characteristics. In order to continuously model changes associated with AD, deformation maps from 21 patients were averaged across a novel z-score disease progression dimension based on Mini Mental State Examination (MMSE) scores. The resulting deformation maps are presented via three metrics: local volume loss (atrophy), volume (CSF) increase, and translation (interpreted as representing collapse of cortical structures). Inspection of the maps revealed significant perturbations in the deformation fields corresponding to the entorhinal cortex (EC) and hippocampus, orbitofrontal and parietal cortex, and regions surrounding the sulci and ventricular spaces, with earlier changes predominantly lateralized to the left hemisphere. These changes are consistent with results from post-mortem studies of AD.

Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy.

We wish to report the detection of dimethyl sulfone (methylsulfonylmethane, C2H6O2S) in the brain of a normal 62-year-old male using in vivo proton magnetic resonance spectroscopy. The presence of this exogenous metabolite resulted from ingestion of a dietary supplement containing dimethyl sulfone. The concentration of this compound in the brain was measured to be 2.4 mmol, with a washout "half life" of approximately 7.5 days. The in vivo T1 and T2 relaxation times of dimethyl sulfone were measured to be 2180 ms and 385 ms, respectively. The concentration of major brain metabolites, namely N-acetylaspartate, total Creatine and Choline, and myo-Inositol were within normal limits.

A 1H MRS study of probable Alzheimer's disease and normal aging: implications for longitudinal monitoring of dementia progression.

In order to evaluate the capability of 1H MRS to monitor longitudinal changes in subjects with probable Alzheimer's disease (AD), the temporal stability of the metabolite measures N-acetylaspartate and N-acetylaspartylglutamate (NA), total Creatine (Cr), myo-Inositol (mI), total Choline (Chol), NA/Cr, mI/Cr, Chol/Cr and NA/mI were investigated in a cohort of normal older adults. Only the metabolite measures NA, mI, Cr, NA/Cr, mI/Cr, and NA/mI were found to be stable after a mean interval of 260 days. Relative and absolute metabolite measures from a cohort of patients with probable AD were subsequently compared with data from a sample of normal older adult control subjects, and correlated with mental status and the degree of atrophy in the localized voxel. Concentrations of NA, NA/Cr, and NA/mI were significantly reduced in the AD group with concomitant significant increases in mI and mI/Cr. There were no differences between the two groups in measures of Cr, Chol, or Chol/Cr. Significant correlations between mental status as measured by the Mini-Mental State Examination and NA/mI, mI/Cr and NA were found. These metabolite measures were also significantly correlated with the extent of atrophy (as measured by CSF and GM composition) in the spectroscopy voxel.

A reproducible method for automated extraction of brain volumes from 3D human head MR images.

An automated method for extracting brain volumes from three commonly acquired three-dimensional (3D) MR images (proton density, T1 weighted, and T2-weighted) of the human head is described. The procedure is divided into four levels: preprocessing, segmentation, scalp removal, and postprocessing. A user-provided reference point is the sole operator-dependent input required. The method's parameters were first optimized and then fixed and applied to 30 repeat data sets from 15 normal older adult subjects to investigate its reproducibility. Percent differences between total brain volumes (TBVs) for the subjects' repeated data sets ranged from .5% to 2.2%. We conclude that the method is both robust and reproducible and has the potential for wide application.

Localized two-dimensional shift correlated spectroscopy in humans at 2 Tesla.

A method for the acquisition of localized 2D shift-correlated spectra, based on the combination of the stimulated-echo volume-selection and gradient-enhanced COSY experiments, is described. The sequence can be modified to perform a number of localized experiments including HOHAHA and DQF-COSY. The method is demonstrated in vivo by presentation of localized COSY and HOHAHA spectra of human tibia marrow, and a localized COSY spectrum of human brain acquired at a field strength of 2 Tesla. Cross peaks corresponding to correlations between coupled groups along the acyl chains of triglycerides are observed in the spectra of marrow. The major cerebral metabolites are represented in the in vivo COSY brain spectrum, including N-acetylaspartate, glutamate/glutamine, total creatine, aspartate, and myo-inositol. Difficulties in the implementation of localized shift-correlation spectroscopy, including water suppression and T2 relaxation, are discussed.

Measurement of the T2 relaxation time of ethanol and cerebral metabolites, in vivo.

The SPACE volume selection technique was combined with a spin-echo sequence to measure the transverse relaxation time of the resonances of ethanol and cerebral metabolites in the dog brain, in vivo. The method was extended to measure brain metabolite T2 values in the rat using 1H NMR microspectroscopy. The T2 decays for the resonances of the metabolites N-acetylaspartate, creatine/phosphocreatine, and choline/phosphorylcholine were found to be biexponential with long T2 components of 490, 260, and 350 ms for the dog and 490, 220, and 355 ms for the rat brain, respectively. The existence of a second T2 component may originate from J-coupled nonresolved metabolite resonances. The relaxation decay for the ethanol triplet could be fitted to a single exponential giving a T2 relaxation time of 335 ms. However, given the large errors in the measurement of ethanol peak intensities at short echo times because of overlapping lipid signal and the effects of J-modulation, a biexponential decay with a long T2 component of 335 ms cannot be ruled out. Ambiguities regarding the reported partial detection of the 1H NMR signal of ethanol in the brain are discussed.

The visibility of the 1H NMR signal of ethanol in the dog brain.

In vivo, high-resolution, volume-selected 1H NMR spectroscopy was used to monitor the concentration of ethanol in the dog brain following intravenous injection of ethanol. Equilibration of ethanol in the body water should result in approximately equivalent concentrations of ethanol in the blood and brain. However, the mean equilibrium brain ethanol concentration determined using N-acetylaspartate as an internal standard was only 23 +/- 5% of the blood ethanol concentration. The disparity between blood and brain ethanol concentrations was attributed to underestimation of the ethanol concentration due to overlapping resonances with NAA and to T2 attenuation or possible nondetection of the 1H signal from ethanol bound at the surface of cell membranes and partitioned into the hydrophobic core of membrane lipids.

In vivo volume-selective metabolite editing via correlated z-order.

Volume-selected 1H NMR spectroscopy was combined with spectral editing to selectively detect brain metabolites. The SPACE localization sequence was used to create a voxel of zeta-magnetization which could then be edited for any scalar coupled metabolite by the use of selective excitation in the ECZOTIC sequence to generate longitudinal spin order. The sequence returns an edited signal with no intrinsic loss of magnetization. The method was applied to observe approximately 10 mM ethanol and 17 mM lactate in the brain of a dog.

Study of human liver disease with P-31 magnetic resonance spectroscopy.

Liver metabolism and energetics of 24 patients with liver disease were studied using phosphorus-31 magnetic resonance spectroscopy. Significant abnormalities were detected in the majority of these patients. A striking diversity in metabolic patterns was observed. Patients with acute viral hepatitis had low liver phosphodiesters and high phosphomonoesters, possibly phosphocholine and phosphoethanolamine. In alcoholic hepatitis phosphomonoesters were raised. Intracellular inorganic phosphate and inorganic phosphate/ATP ratios were decreased in primary biliary cirrhosis and in some patients with hepatitis. These spectroscopic results were evaluated in respect of the pattern of liver damage and cellular regeneration. Liver tumours had raised phosphomonoesters and also showed evidence for altered spin-lattice relaxation of the phosphorus nucleus in various metabolites. In iron overload the liver ATP resonances were broadened. The line broadening correlated with the degree of iron overload suggesting the potential use of P-31 magnetic resonance spectroscopy for measuring liver iron.

High-field localized in vivo proton spectroscopy on micro volumes.

A water-suppressed volume-selected in vivo 1H spectrum of 0.2 ml of a rat brain has been obtained at 200 MHz using the SPACE localization method. Good signal-to-noise and spectral resolution were obtained by averaging 256 acquisitions. The spectrum shows little T2 weighting effect.

In vivo high-resolution volume-selected proton spectroscopy and T1 measurements in the dog brain.

Successful in vivo NMR spectroscopy requires a combination of techniques to address the problems of volume selection, water suppression, and resolution. All this needs to be done in the very heterogeneous environment found in living organisms. Previously published techniques are used to obtain 1H spectra from a dog brain, observing metabolites with concentrations below 1 mM. Measurements of spin-lattice relaxation times (T1) are also presented. The 1H relaxation times are long (T1 greater than 1.0 s) yielding information about the fluidity of the molecular environment. Comments are made concerning the achievable linewidth in vivo and the deficiencies that phase-encoding spectroscopic methods may have in obtaining high-resolution 1H spectra.

The unequivocal determination of lactic acid using a one-dimensional zero-quantum coherence-transfer technique.

A method based on zero-quantum coherence transfer for spectral editing of metabolites in aqueous solution in a one-dimensional experiment is described. Water suppression factors of approximately 8000 were achieved by the use of pulsed B0 field gradients and excellent editing was obtained in a single acquisition. The methyl resonances of both lactate and acetaldehyde were readily observed in a mouse brain homogenate by generating zero-quantum coherence using Gaussian pulses for selective excitation of the respective CH resonances.

Nodal inhomogeneity mapping by localized excitation--the "NIMBLE" shimming technique for high-resolution in vivo NMR spectroscopy.

A method (NIMBLE) for obtaining optimum B0 field homogeneity at voxels located away from the magnet isocenter for use in volume-selected NMR spectroscopy is described. Voxels may be shimmed using only first-order X, Y, and Z shims to produce three-dimensional shim current maps, thus avoiding shim coupling problems. NIMBLE shimming prior to volume selection ensures optimum spectral resolution and improves the efficiency and accuracy of the volume-selection experiment. The benefits of the technique are illustrated by a high-resolution volume-selected spectrum of human tibia marrow.

On the calculation of magnetization slice profiles for NMR imaging and in vivo spectroscopy.

When developing new techniques for NMR imaging and in vivo spectroscopy it is a major advantage to be able to calculate the magnetization slice profiles, at any point during a pulse sequence in the presence of a field gradient. While this has frequently been done by treating the problem as a number of discrete resonances, it is sometimes necessary to consider the continuous nature of the magnetization profiles. This paper describes a method used to simulate the free-induction decay at any point during the NMR experiment.

Water-suppressed volume-selected 1H NMR spectroscopy in vivo: application to study tumor metabolism.

Volume selection using SPACE has been combined with water suppression techniques to provide high-resolution 1H NMR spectra from aqueous solutions. The technique developed was used to obtain spectra from a tumor growing on the hind leg of a rat. Water suppression factors of between 1000 and 2000 were achieved simultaneously with excellent volume selection.