Is the intracellular pH different from normal in the epileptic focus of patients with temporal lobe epilepsy? A 31P NMR study.

We performed in vivo 31P NMR spectroscopic studies of human brain on a 4.1 T whole-body NMR system. Based on a control group of 20 healthy volunteers, the normal pHi was 7.05 (SD, 0.06; SEM, 0.01) in the left temporal lobe and 7.04 (SD, 0.04; SEM, 0.01) in the right temporal lobe. We also studied a patient group consisting of 13 individuals with unilateral temporal lobe epilepsy. The mean pHi was 7.02 (SD, 0.04; SEM, 0.01) in the ipsilateral lobe and 7.02 (SD, 0.05; SEM, 0.01) in the contralateral lobe. These results clearly show that no statistically significant difference in pHi is observed between the two lobes, either in normal controls or in patients. Also, no significant pHi difference exists between the control group and the patient group. Lateralization in each of the 13 patients with unilateral epilepsy, based on their individual pHi difference between the ipsilateral lobe and contralateral lobe (delta pHi), showed that three patients were nondiagnostic cases because their delta pHis were not significantly different from zero (< or = 0.02), five patients showed small delta pHis consistent with their clinical lateralization, whereas the remaining five patients showed delta pHi-based lateralization opposite to the clinical findings. These results seem to indicate an essentially random distribution around delta pHi = 0 within a very small experimental error of +/-0.02 pH units. pHi obtained from eight different areas in each of the 13 unilateral patients also did not show any significantly nonzero delta pHi values. These results led to the conclusion that even at the excellent spectral resolution and reproducibility of the 4.1 T machine (typical SD of 0.05 pH units), no significant pHi effect, induced by temporal lobe epilepsy, could be detected. Therefore, in this study, delta pHi does not appear to be a clinically useful tool for the lateralization of epileptic foci in patients with temporal lobe epilepsy.

Effects of noise on the determination of ejection fraction from left ventricular time-activity curves.

The effects of Poisson noise on three estimates of ejection fraction made from left-ventricular time-activity curves have been investigated. All three methods are based on a sinusoidal model of left-ventricular volume changes. The first, developed by Schelbert et al., overestimates the ejection fraction for low-activity levels and low ejection fractions. The second estimate, which is merely a first-order correction for the contribution of Poisson noise to the first estimate, appears to be more accurate when both estimators are applied to simulated time-activity curves, and the resulting ejection fractions are compared. A third, "maximum likelihood" estimator, when applied to the same data, is apparently more accurate than the first two.

In vivo phosphorus-31 spectroscopic imaging in patients with global myocardial disease.

The goals of this study were to determine whether abnormalities in phosphorus metabolism could be noninvasively detected using phosphorus-31 nuclear magnetic resonance spectroscopy in patients with dilated cardiomyopathy and left ventricular hypertrophy, and whether these patient groups could be distinguished from each other based on parameters obtained using this technique. Seventeen patients and 14 control subjects were studied using nuclear magnetic resonance spectroscopy. Spectra were obtained from the human heart at rest using 3-dimensional spectroscopic imaging as a localization technique. Data were acquired over an average volume of 48 cc in 26.3 minutes using a 2 tesla imaging and spectroscopy unit. The ratio of phosphocreatine to adenosine triphosphate was 0.89 +/- 0.88 (mean +/- standard error) in normal subjects and did not differ significantly in patients with dilated cardiomyopathy or left ventricular hypertrophy. A prominent peak in the phosphodiester region was seen much more frequently in patients with dilated cardiomyopathy, resulting in significantly higher ratios of phosphodiester to phosphocreatine (1.28 +/- 0.35) and phosphodiester to adenosine triphosphate (0.79 +/- 0.18) in this group compared to normal subjects (0.33 +/- 0.08 and 0.29 +/- 0.08, respectively). However, the various patient groups could not be reliably distinguished from each other based on spectral patterns. These studies demonstrate the feasibility of performing phosphorus-31 nuclear magnetic resonance spectroscopic imaging in patients with myocardial disease. The initial results indicate that, under resting conditions, the ratio of phosphocreatine to adenosine triphosphate is not consistently altered in patients with severe global cardiomyopathies or hypertrophy. Phosphodiesters are elevated in some patients with dilated cardiomyopathy, a finding that may signify abnormal phospholipid metabolism in this condition.

Influence of dobutamine on hemodynamics and coronary blood flow in patients with and without coronary artery disease.

The influence of dobutamine on hemodynamics and coronary blood flow was studied in patients after routine cardiac catheterization. The data demonstrated that dobutamine is a powerful inotropic agent at a dose that has a relatively small influence on heart rate. In patients without coronary artery disease dobutamine greatly increased coronary arterial perfusion. In patients with severe coronary artery diseases dobutamine resulted in a much smaller increase in coronary perfusion, and the pattern of perfusion became more inhomogeneous. The results suggest that dobutamine has a potential inotropic value but raise concern about its influence on regional myocardial perfusion in patients with serious coronary artery disease.

Clinical MRS studies of the brain.

Image-guided 31P and 1H magnetic resonance localized spectroscopy was performed on patients with brain tumors, temporal lobe epilepsy, chronic brain stroke, and deep white matter lesions. Absolute molar concentrations of metabolites, peak area ratios, and pH were obtained. The important findings were that 31P metabolite concentrations were significantly reduced in tumors, infarcts, and deep white matter lesions. Similarly, 1H metabolite intensities were reduced in chronic stroke. In the seizure foci of epilepsy patients, in tumors, and in chronic stroke, the pH was more alkaline than the normal pH. Peak area ratios were altered in tumors (reduction of phosphocreatine/inorganic phosphate (PCr/Pi) and in chronic stroke (large increases in Cr/NAA and Cho/NAA). Finally, the spectroscopic imaging technique offers a versatile alternative to the "single point" techniques, producing spectra or images of the spatial distribution of individual 31P metabolites.

The k-trajectory formulation of the NMR imaging process with applications in analysis and synthesis of imaging methods.

The fundamental operations of nuclear magnetic resonance (NMR) imaging can be formulated, for a large number of methods, as sampling the object distribution in the Fourier spatial-frequency domain, followed by processing the digitized data (often simply by Fourier transformation) to produce a digital image. In these methods, which include reconstruction from projections, Fourier imaging, spin-warp imaging, and echo-planar imaging, controllable gradient fields determine the points in the spatial-frequency domain which are sampled at any given time during the acquisition of data (the free induction decay, or FID). The detailed time dependence of the resulting trajectory of sample points (the k trajectory) determines the relative weight and accuracy with which image information at each spatial frequency is measured, establishing theoretical limitations on image quality achievable with a given imaging method. We demonstrate here that these considerations may be used to compare the theoretical capabilities of NMR imaging methods, and to derive new imaging methods with optimal theoretical imaging properties.

Iterative reconstruction of single-shot spiral MRI with off resonance.

A variety of applications and research directions in magnetic resonance imaging which require fast scan times have recently become popular. In order to satisfy many of the requirements of these applications, snapshot imaging methods, which acquire an entire image in one excitation, are often used. These snapshot techniques are relatively insensitive to motion and can allow rapidly occurring processes to be imaged. However, snapshot imaging techniques acquire data over a relatively long period, during which off-resonance phase can accumulate, leading to image degradation. This degradation often limits the usefulness of the images. Presented here is a method to iteratively reconstruct an image acquired by a spiral snapshot technique and to remove image degradation due to off resonance. This iterative method does not assume that the inhomogeneity is slowly varying within the image, allowing better results than with deblurring techniques which do not take abrupt changes into account. Although presented here with a spiral imaging technique, the iterative algorithm is general enough to be applied to a variety of snapshot imaging techniques.

Phosphorus-31 MR spectroscopic imaging (MRSI) of normal and pathological human brains.

The goals of this study were to evaluate 31P MR spectroscopic imaging (MRSI) for clinical studies and to survey potentially significant spatial variations of 31P metabolite signals in normal and pathological human brains. In normal brains, chemical shifts and metabolite ratios corrected for saturation were similar to previous studies using single-volume localization techniques (n = 10; pH = 7.01 +/- 0.02; PCr/Pi = 2.0 +/- 0.4; PCr/ATP = 1.4 +/- 0.2; ATP/Pi = 1.6 +/- 0.2; PCr/PDE = 0.52 +/- 0.06; PCr/PME = 1.3 +/- 0.2; [Mg2+]free = 0.26 +/- 0.02 mM.) In 17 pathological case studies, ratios of 31P metabolite signals between the pathological regions and normal-appearing (usually homologous contralateral) regions were obtained. First, in subacute and chronic infarctions (n = 9) decreased Pi (65 +/- 12%), PCr (38 +/- 6%), ATP (55 +/- 6%), PDE (47 +/- 9%), and total 31P metabolite signals (50 +/- 8%) were observed. Second, regions of decreased total 31P metabolite signals were observed in normal pressure hydrocephalus (NPH, n = 2), glioblastoma (n = 2), temporal lobe epilepsy (n = 2), and transient ischemic attacks (TIAs, n = 2). Third, alkalosis was detected in the NPH periventricular tissue, glioblastoma, epilepsy ipsilateral ictal foci, and chronic infarction regions; acidosis was detected in subacute infarction regions. Fourth, in TIAs with no MRI-detected infarction, regions consistent with transient neurological deficits were detected with decreased Pi, ATP, and total 31P metabolite signals. These results demonstrate an advantage of 31P MRSI over single-volume 31P MRS techniques in that metabolite information is derived simultaneously from multiple regions of brain, including those outside the primary pathological region of interest. These preliminary findings also suggest that abnormal metabolite distributions may be detected in regions that appear normal on MR images.

Application of high field spectroscopic imaging in the evaluation of temporal lobe epilepsy.

Previous spectroscopic imaging studies of temporal lobe epilepsy have used comparisons of metabolite content or ratios to lateralize the seizure focus. Although highly successful, these studies have shown significant variations within each of the groups of healthy subjects and patients. This variation may arise from the natural differences seen in metabolite concentration in gray and white matter, the complex anatomy seen about the hippocampus, and the large voxels typically employed at 1.5 T. Using a 4.1 T whole body system, we have acquired spectroscopic images with 0.5 cc nominal voxels (1 cc after filtering) to evaluate the regional variation in metabolite content of the hippocampus, temporal gray and white matter, midbrain, and cerebellar vermis. Using a threshold value of 0.90 for CR/NAA, a value 90% of all normal hippocampal voxels lay below, we have correctly identified the presence of epileptogenic tissue in patients with unilateral as well as bilateral seizures. By using comparisons to healthy values of the CR/NAA ratio, this method enables the visualization of bilateral disease and provides information on the extent of gray matter involvement.

Multiple-output chemical shift imaging (MOCSI): a practical technique for rapid spectroscopic imaging.

A new technique for rapid multiple-frame chemical shift imaging and localized spectroscopy is reported. Unlike phase-encoding techniques and multiple-delay chemical shift imaging techniques, this technique permits spectroscopic imaging at high spatial resolution and moderately high spectral resolution with acquisition times as short as 10 min or less. Unlike other rapid spectroscopic imaging techniques which have been reported, it uses cyclic trapezoidal gradient waveforms achievable in standard clinical magnetic resonance imaging systems. Multiple-output chemical shift imaging images and spectra from a human study are shown.

Acquisition and accuracy in rapid NMR imaging methods.

The echo-planar imaging method (EPI) and its variants can acquire data sufficient to form an image in a much shorter time than the Fourier or projection-reconstruction methods. Fundamental requirements on gradient waveforms and signal sampling are discussed for EPI and SEPI (a variant using sinusoidal gradient waveforms), based on the k-trajectory formulation of acquisition in NMR imaging. Using a new simulation method, image defects in EPI and SEPI are demonstrated which result from failure to meet these requirements. Faithful rendition of theoretically ideal gradient waveforms places severe demands on gradient system response in rapid imaging. It is shown, however, that nonideal gradient system response need not degrade images if appropriate reconstruction computations are used. Transfer functions and noise power spectra are derived for EPI and SEPI, and the ratio of these two functions is used to derive ideal observer signal-to-noise ratios for simple visual interpretive tasks. It is shown that ideal observer performance can differ significantly between EPI and SEPI for some visual tasks, using the same NMR imaging system.

A general treatment of NMR imaging with chemical shifts and motion.

A general treatment of nuclear magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI), which takes into account the effects of chemical shift, motion, field inhomogeneity, and relaxation times, is presented. A graphical representation based on the k trajectory formalism which includes these effects is then developed for MRI and MRSI acquisition processes. These considerations should be useful in the study and design of flow-sensitive MRI and MRSI methods and the accurate prediction of motion artifacts in conventional MRI and MRSI techniques. We conclude by presenting examples illustrating applications of the general theory to specific MRSI and flow imaging methods.

Flow SS-PARSE: a new method for rapid imaging and mapping of blood flow velocity.

A new method for flow velocity mapping of blood is presented here. Instead of the conventional approach of employing two images (velocity sensitive and control) to generate velocity information, in the new method the velocity is determined directly by solving an inverse problem. This technique is an application of single shot - parameter assessment by retrieval from signal encoding (SS-PARSE). Simulations have been done to demonstrate the feasibility of the method. The velocity measurement range of the prototype version is from -50cm/s to 50cm/s, roughly appropriate for future applications in blood flow measurement of carotid arteries.

Quantitative spectroscopic imaging of the human brain.

A method to provide B1 correction and cerebrospinal fluid (CSF) referencing is developed and applied to spectroscopic imaging of the human brain at 4.1 T using a volume head coil. The B1 image allows rapid determination of the spatially dependent B1 that is then used to compensate for the B1 sensitivity of the spectroscopic sequence. The reference signal is acquired from CSF located in a lateral ventricular position using a point-resolved echo spectroscopy (PRESS) acquisition. The CSF spectrum is also corrected for B1 dependence. Together with T2 and T1 corrections, this method is used to provide quantitative values of N-acetylaspartate (NAA), creatine (Cr), and choline (Ch). The metabolite concentrations obtained from a spectroscopic imaging slice through the ventricles in seven normal controls are in good agreement with previously published literature values. This method is applied in a patient with secondary progressive multiple sclerosis, showing separate areas of abnormalities in both NAA and Cr.

Baseline conditions and subtractive logic in neuroimaging.

Discrepancies in the patterns of cortical activation across studies may be attributable, in part, to differences in baseline tasks, and hence, reflect the limits of the subtractive logic underlying much of neuroimaging. To assess the extent of these effects, three of the most commonly used baseline conditions (rest, tone monitoring, and passive listening) were compared using phoneme discrimination as the experimental task. Eight participants were studied in a fMRI study with a 4.1 T system. The three baseline conditions systematically affected the amount of activation observed in the identical phoneme task with major affects in Broca's area, the left posterior superior temporal gyrus, and the left and right inferior parietal regions. Two central findings were: 1) a differential effect of baseline within each region, with the rest baseline condition producing the greatest amount of activation and the passive listening condition producing the least, and 2) systematic baseline task activation in the inferior parietal regions. These results emphasize the relativity of activation patterns observed in functional neuroimaging, and the necessity to specify the baseline processes in context to the experimental task processes.

A novel k-space trajectory measurement technique.

A new k-space trajectory measurement technique is proposed and demonstrated. This technique measures the k-space trajectory, in seconds, using only a few readout lines, using phase values of acquired MR signals. As a result of the technique's efficiency, k-space trajectory measurement using patient data becomes possible. The utility of this techniques is demonstrated in phantom and human studies at 4.1 T.

Spatial resolution in 31P metabolite imaging of the human brain at 4.1 T.

In studies of 31P metabolite imaging in the human brain using a high-field 4.1 T NMR system, resolution and signal-to-noise ratios were measured to determine the potential for spatial-resolution improvements. The results suggest that spatial resolution of FWHM of 2 cm or less, similar to that of radionuclide tomographic functional images, may be feasible.

Detection of motion using B1 gradients.

An NMR method which makes use of a radiofrequency (RF) field gradient to detect diffusion, perfusion, or flow is demonstrated. The technique is analogous to the detection of motion using pulsed B0 gradients. The simplest form of the experiment is as follows: A spatially imhomogeneous RF field generated by a surface coil produces dispersal of magnetization in the Y Z plane. After a delay, the RF field is applied within reversed phase to restore polarization along +Z, which is then sampled using an observe pulse or pulse sequence. If molecular motion occurs during the delay period the amplitude of Z magnetization will be reduced. The lengths of the RF pulses and the delay period are varied so that the effects of relaxation, flow, and diffusion or perfusion can be distinguished. The present study demonstrates the use of this method to detect slow fluid flow. Advantages of this method include the availability of large RF gradients, and the avoidance of eddy currents. It is suggested that the method may have application to the study of perfusion and flow in vivo.

A method to measure arbitrary k-space trajectories for rapid MR imaging.

A method to measure arbitrary k-space trajectories was developed to compensate for nonideal gradient performance during rapid magnetic resonance (MR) imaging with actively or nonactively shielded gradients at a magnetic field strength of 4.1 T. Accurate MR image reconstruction requires knowledge of the k-trajectory produced by the gradient waveforms during k-space sampling. Even with shielded gradients, residual eddy currents and imperfections in gradient amplifier performance can cause the true k-space trajectory to deviate from the ideal trajectory. The k-space determination was used for spiral gradient-echo imaging fo the human brain. While individual calibrations are needed for new pulse sequences, the method of k-space determination can be used for any sequence of preparation pulses and readout gradient waveforms and should prove useful for other trajectories, including the rastered lines of echo-planar imaging.

Detection of brain glutamate and glutamine in spectroscopic images at 4.1 T.

Brain glutamate and glutamine were detected in healthy human volunteers in spectroscopic images with a nominal voxel size of 2.25 cm3 at an echo time of 15 ms. Due to the increased frequency separation and simplification of J-coupling patterns, the separate detection of brain glutamate and glutamine at short echo times was possible. Creatine, choline, and N-acetylaspartate with other N-acetylated compounds were also detected. The ratios of the metabolite resonance intensities were in agreement with previously published values.