A detailed analysis of localized J-difference GABA editing: theoretical and experimental study at 4 T.

The problem of low signal-to-noise ratio for gamma-aminobutyric acid (GABA) in vivo is exacerbated by inefficient detection schemes and non-optimal experimental parameters. To analyze the mechanisms for GABA signal loss of a MEGA-PRESS J-difference sequence at 4 T, numerical simulations were performed ranging from ideal to realistic experimental implementation, including volume selection and experimental radio frequency (RF) pulse shapes with a macromolecular minimization scheme. The simulations were found to be in good agreement with phantom and in vivo data from human brain. The overall GABA signal intensity for the simulations with realistic conditions for the MEGA-PRESS difference spectrum was calculated to be almost half of the signal simulated under ideal conditions (~43% signal loss). In contrast, creatine was reduced significantly less then GABA (~19% signal loss). The 'four-compartment' distribution due to J-coupling in the PRESS-based localization was one of the most significant sources of GABA signal loss, in addition to imperfect RF profiles for volume selection and editing. An alternative strategy that reduces signal loss due to the four-compartment distribution is suggested. In summary, a detailed analysis of J-difference editing is provided with estimates of the relative amounts of GABA signal losses due to various mechanisms. The numerical simulations presented in this study should facilitate both implementation of the more efficient acquisition and quantification process of J-coupled systems.

Metabolic characteristics of cortical malformations causing epilepsy.

PURPOSE: Cortical malformations (CMs) are increasingly recognized as the epileptogenic substrate in patients with medically refractory neocortical epilepsy (NE). The aim of this study was to test the hypotheses that: 1. CMs are metabolically heterogeneous. 2. The structurally normal appearing perilesional zone is characterized by similar metabolic abnormalities as the CM. METHODS: Magnetic resonance spectroscopic imaging (MRSI) in combination with tissue segmentation was performed on eight patients with NE and CMs and 19 age matched controls. In controls, NAA, Cr, Cho,NAA/Cr and NAA/Cho of all voxels of a given lobe were expressed as a function of white matter content and thresholds for pathological values determined by calculating the 95% prediction intervals. These thresholds were used to identify metabolically abnormal voxels within the CM and in the perilesional zone. RESULTS: 30% of all voxels in the CMs were abnormal, most frequently because of decreases of NAA or increases of Cho. Abnormal voxels tended to form metabolically heterogeneous clusters interspersed in metabolically normal regions. Furthermore, 15% of all voxels in the perilesional zone were abnormal, the most frequent being decreases of NAA and Cr. CONCLUSION: In CMs metabolically normal regions are interspersed with metabolically heterogeneous abnormal regions. Metabolic abnormalities in the perilesional zone share several characteristics of CMs and might therefore represent areas with microscopic malformations and/or intrinsic epileptogenicity.

Temporal lobectomy for epilepsy: recovery of the contralateral hippocampus measured by (1)H MRS.

(1)H MRS imaging was obtained from 10 patients with mesial temporal lobe epilepsy before and after surgery. After surgery, metabolic recovery in the contralateral hippocampus was detected. Preoperatively, reduced N-acetylaspartate (p < 0.04) increased after surgery nonsignificantly to equal control values. Cholines increased after surgery (p < 0.02) and creatine-phosphocreatine showed a trend to higher values. The results suggest that the contralateral hippocampus is affected by repeated seizure activity in the ipsilateral hippocampus, rather than presence of bilateral mesial temporal sclerosis.

1H MRSI predicts surgical outcome in MRI-negative temporal lobe epilepsy.

1H MRS imaging (MRSI) was performed on 15 patients with MRI-negative temporal lobe epilepsy (TLE) who underwent seizure surgery. The non-seizure-free patients (NSF) ipsilateral hippocampal N-acetylaspartate (NAA)/(Cr+Cho) z scores were lower than the contralateral scores (p = 0.04), and the NSF ipsilateral z scores were lower than the seizure-free patients' (SF) ipsilateral z scores (p = 0.0049). Similarly, NSF contralateral scores were lower than contralateral SF (p = 0.02). These findings suggest NAA predicts the surgical outcome in patients with TLE without evidence of mesial temporal sclerosis on MRI.

Short echo time multislice proton magnetic resonance spectroscopic imaging in human brain: metabolite distributions and reliability.

Multislice proton magnetic resonance spectroscopic imaging (1H MRSI) at 25 ms echo time was used to measure concentrations of myo-inositol (mI), N-acetylaspartate (NAA), and creatine (Cr) and choline (Cho) in ten normal subjects between 22 and 84 years of age (mean age 44 +/- 18 years). By co-analysis with MRI based tissue segmentation results, metabolite distributions were analyzed for each tissue type and for different brain regions. Measurement reliability was evaluated using intraclass correlation coefficients (ICC). Significant differences in metabolite distributions were found for all metabolites. mI of frontal gray matter was 84% of parietal gray matter and 87% of white matter. NAA of frontal gray matter was 86% of parietal gray matter and 85% of white matter. Cho of frontal gray matter was 125% of parietal gray matter and 59% of white matter and Cho of parietal gray matter was 47% of white matter. Cr of parietal gray matter was 113% of white matter. Reliability was relatively high (ICC from.70 to.93) for all metabolites in white matter and for NAA and Cr in gray matter, though limited (ICC less than.63) for mI and Cho in gray matter. These findings indicate that voxel gray/white matter contributions, regional variations in metabolite concentrations, and reliability limitations must be considered when interpreting 1H MR spectra of the brain.

Effects of abstinence from alcohol on the broad phospholipid signal in human brain: an in vivo 31P magnetic resonance spectroscopy study.

BACKGROUND: In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a magnetic field strength of 1.5 T allows measurement of fairly mobile membrane phospholipids in the human brain. We previously showed that subjects who are heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2) of white matter phospholipids than light drinkers, which suggested lower concentrations and molecular mobility of phospholipids in heavy drinkers. The purpose of the present study was to measure if such chronic alcohol-induced white matter tissue changes are persistent in long-term abstinent alcoholics. METHODS: Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were studied by localized 31P MRS in the centrum semiovale and were compared with 13 male, alcohol-dependent, heavy drinkers and 23 nondependent light drinkers (17 men, 6 women) of similar age. Methods for measurements of the broad membrane phospholipid signal and its relaxation time were described previously. RESULTS: Phospholipid concentrations and relaxation times in alcoholics abstinent for an average of 31 months were not significantly different from those measured in light drinkers. The contribution of fast and slowly relaxing signal components to the broad phospholipid signal, however, was still different in abstinent alcoholics compared with light drinkers. No effects of sex or of family history of alcoholism were noted on any of our spectroscopic measures within the light-drinking or abstinent groups. CONCLUSIONS: Most of our results suggest at least partial recovery of chronic alcohol-induced white matter phospholipid damage with long-term abstinence. They offer myelination changes and/or dendritic rearborization as a possible mechanism for the commonly observed white matter volume gain with prolonged abstinence. But the results also suggest a persistent abnormality in the nature and/or physical properties of white matter phospholipids in long-term abstinent alcoholics.

Effects of chronic alcohol consumption on the broad phospholipid signal in human brain: an in vivo 31P MRS study.

BACKGROUND: Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the measurement of phospholipids and their breakdown products in the human brain. Fairly mobile membrane phospholipids give rise to a broad signal that co-resonates with metabolic phosphodiesters. Chronic alcohol exposure increases the rigidity of isolated brain membranes and, thus, may affect the amount and transverse relaxation times (T2) of MRS-detectable phospholipids. We tested the hypothesis that subjects who were heavy drinkers have stiffer membranes than controls who were light drinkers, as reflected in a smaller broad signal component and a shorter T2 of the broad signal in 31P MR spectra of the brain. METHODS: Thirteen alcohol-dependent heavy drinkers (mean age 44 years) were studied by localized 31P MRS in the centrum semiovale and compared with 17 nondependent light drinkers of similar age. The broad component signal was separated from the metabolite signal by convolution difference, which is based on the large difference in line widths of these two signals. Longitudinal and T2 relaxation times were measured using standard methods. RESULTS: The broad component integral was 13% lower in the brain of heavy drinkers compared with light drinkers (p < 0.001) and remained significantly smaller after corrections for both longitudinal and transverse relaxations (p < 0.01). The T2 distribution of the broad component consistently showed two resolvable components in both groups. The fast relaxing component had the same T2 in both groups (T2 = 1.9 msec). The slower relaxing component T2 was 0.6 msec shorter in heavy drinkers compared with light drinkers (p = 0.08). CONCLUSIONS: These results, observed in the absence of white matter volume loss, are consistent with biochemical alterations and higher rigidity of white matter phospholipids associated with long-term chronic alcohol abuse. The observed smaller broad signal component in these relatively young heavy drinkers is a sensitive measure of white matter phospholipid damage.

Temporal lobe epilepsy: qualitative reading of 1H MR spectroscopic images for presurgical evaluation.

PURPOSE: To study the feasibility and clinical potential of visual inspection of hydrogen 1 magnetic resonance (MR) spectroscopic metabolite images for the lateralization of unilateral nonlesional temporal lobe epilepsy (TLE). MATERIALS AND METHODS: MR imaging and 1H MR spectroscopic imaging were performed of the temporal lobes in 50 patients with TLE and 23 age-matched healthy volunteers. N-acetylaspartate (NAA) and creatine plus choline metabolite images were read by two neuroradiologists who determined lateralization according to the side of lower NAA signal intensity. Quantitative estimates of NAA were calculated by using an automated fitting program. RESULTS: Agreement in lateralization between readers was significant with a kappa score of 0.53 for all patients with TLE and 0.63 for patients displaying mild or marked NAA asymmetry. Among the 50 patients with TLE, lateralization was determined correctly by reader 1 in 38 (76%) patients and by reader 2 in 31 (62%) patients. If limited to patients with mild or marked NAA asymmetry, correct lateralization improved to 30 (77%) of 39 and 16 (80%) of 20 patients, respectively. Combined qualitative reading and quantitative spectral fitting enabled lateralization in 34 (85%) of 40 patients with TLE for reader 1 and 30 (77%) of 39 for reader 2, including nine of 14 patients with TLE with negative MR images. CONCLUSION: Reading of metabolite images is a feasible and fast means for noninvasive evaluation of patients with TLE who are candidates for surgery and enables lateralization in some patients with negative MR images.

Hippocampal structures: anteroposterior N-acetylaspartate differences in patients with epilepsy and control subjects as shown with proton MR spectroscopic imaging.

PURPOSE: To determine the distribution of proton metabolites along the long axis of the hippocampus. MATERIALS AND METHODS: Proton magnetic resonance (MR) spectroscopic imaging measurements were performed in the hippocampi of 14 control subjects and nine patients with unilateral mesial temporal lobe epilepsy. RESULTS: Control subjects showed significantly lower ratios of N-acetylaspartate (NAA) to choline-containing compounds (Ch) and creatine plus phosphocreatine (CR) (NAA/[Cr + Ch]) in the anterior as compared with the posterior part of the hippocampus. Furthermore, a similar anteroposterior (AP) difference in NAA/(Cr + Ch) values was found in both ipsilateral and contralateral hippocampi of patients. In the patients compared with the control subjects, ipsilateral NAA/(Cr + Ch) levels were reduced in every part of hippocampal tissue with an average reduction of 17%, and contralateral NAA/(Cr + Ch) was reduced by about 10%. In the patients compared with the control subjects, the proportional reduction in ipsilateral NAA/(Cr + Ch) was greatest in voxels from anterior hippocampal regions. CONCLUSION: AP differences could be a result of fewer neurons in the anterior compared with the posterior hippocampus or of the increasing thickness of the hippocampus from posterior to anterior, which leads to different contributions from adjacent tissue. Measurements of T2 showed that T2 differences are probably not responsible for these changes.

Spectral simulations incorporating gradient coherence selection.

Computer-aided methods can considerably simplify the use of the product operator formalism for theoretical analysis of NMR phenomena, which otherwise becomes unwieldy for anything but simple spin systems and pulse sequences. In this report, two previously available programming approaches using symbolic algebra (J. Shriver, Concepts Magn. Reson. 4, 1-33, 1992) and numerical simulation using object-oriented programming (S. A. Smith, T. O. Levante, B. H. Meier, and R. R. Ernst, J. Magn. Reson. A 106, 75-105, 1994) have been extended to include the use of gradient operators for simulation of spatially localized NMR spectroscopy and gradient coherence selection. These methods are demonstrated using an analysis of the response of an AX(3) spin system to the STEAM pulse sequence and verified with experimental measurements on lactate.

A practical double-tuned 1H/31P quadrature birdcage headcoil optimized for 31P operation.

A double-tuned 1H/31P birdcage head coil for use with humans at 1.5 T is described. The coil was designed for proton-decoupled 31P excitation and reception and incorporated a number of practical features including optimized sensitivity for 31P, quadrature operation at 1H and 31P frequencies, and a radiofrequency (RF) mirror for improved B1 homogeneity. The design achieved similar B1 homogeneity at both 31P and 1H frequencies. Inductive matching was used to accommodate samples with large loading differences. A facile method for tuning and matching over a variety of sample loadings is presented, along with capacitively shortened bazookas for suppression of cable braid currents. The proton sensitivity, although down by approximately a factor of two compared with an optimized 1H birdcage head coil, was still ample for shimming and generation of scout images. Advantages of the design are discussed and proton-decoupled 31P spectra of human brain are presented.

Measurement of chemical shifts and coupling constants for glutamate and glutamine.

Proton chemical shifts and coupling constants were obtained for glutamate and glutamine in water (D2O) at pH = 6.6. Initial chemical shift and coupling constant values obtained from experimental spectra were refined using a spectral simulation and optimization program to get a complete set of values that could not otherwise be measured directly from the experimental spectra due to strong spin-spin couplings. These values are essential for automated spectral fitting procedures that require a priori information.

Regional distribution of interictal 31P metabolic changes in patients with temporal lobe epilepsy.

PURPOSE: We compared the 31P metabolites in different brain regions of patients with temporal lobe epilepsy (TLE) with those from controls. METHODS: Ten control subjects and 11 patients with TLE were investigated with magnetic resonance imaging (MRI) and [31P]MR spectroscopic imaging (MRSI). [31P]MR spectra were selected from a variety of brain regions inside and outside the temporal lobe. RESULTS: There were no asymmetries of inorganic phosphate (Pi), pH, or phosphomonoesters (PME) between regions in the left and right hemispheres of controls. In patients with TLE, Pi and pH were higher and PME was lower throughout the entire ipsilateral temporal lobe as compared with the contralateral side and there were no significant asymmetries outside the temporal lobe. The degree of ipsilateral/contralateral asymmetry for all three metabolites was substantially greater for the temporal lobe than for the frontal, occipital, and parietal lobes, and these asymmetries provided additional data for seizure localization. As compared with levels in controls, Pi and pH were increased and PME were decreased on the ipsilateral side in patients with TLE. There were changes in Pi, pH, and PME on the contralateral side in persons with epilepsy as compared with controls, contrary to changes on the ipsilateral side. CONCLUSIONS: Our findings provide some insight into the metabolic changes that occur in TLE and may prove useful adjuncts for seizure focus lateralization or localization.

Multiple-echo proton spectroscopic imaging using time domain parametric spectral analysis.

A multiple-echo MR spectroscopic imaging (MRSI) method is presented that enables improved metabolite imaging in the presence of local field inhomogeneities and measurement of transverse relaxation parameters. Short echo spacing is used to maximize signal energy from inhomogeneously line-broadened resonances, and time domain parametric spectral analysis of the entire echo train is used to obtain sufficient spectral resolution from the shortened sampling periods. Optimal sequence parameters for 1H MRSI are determined by computer simulation, and performance is compared with conventional single-echo acquisition using phantom studies at a field strength of 4.7 T. A preliminary example for use at 1.5 T is also presented using phantom and human brain MRSI studies. This technique is shown to offer improved performance relative to single-echo MRSI for imaging of metabolites with shortened T2* values due to the presence of local field inhomogeneities. Additional advantages are the intrinsic measurement of metabolite T2 values and determination of metabolite integrals without T2 weighting, thereby facilitating quantitative metabolite imaging.

Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy.

The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.

Hippocampal N-acetylaspartate in neocortical epilepsy and mesial temporal lobe epilepsy.

Previous magnetic resonance spectroscopy (MRS) studies have shown that N-acetylaspartate (NAA) is reduced not only in the ipsilateral but also in the contralateral hippocampus of many patients with mesial temporal lobe epilepsy (mTLE). The reason for the contralateral damage is not clear. To test whether the hippocampus is also damaged if the focus is outside the hippocampus, we have measured patients with neocortical epilepsy (NE). Therefore, the goals of this study were to determine if hippocampal NAA is reduced in NE and if hippocampal NAA discriminates NE from mTLE. MRS imaging (MRSI) studies were performed on 10 NE patients and compared with MRSI results in 23 unilateral mTLE patients and 16 controls. The results show that, in contrast to mTLE, NAA was not reduced in the hippocampus of NE patients, neither ipsilateral nor contralateral to the seizure focus. These results suggest that repeated seizures do not cause secondary damage to the hippocampus. The absence of spectroscopic differences in NE may help to distinguish NE from mTLE.

Temporal lobe epilepsy: bilateral hippocampal metabolite changes revealed at proton MR spectroscopic imaging.

PURPOSE: To determine which proton magnetic resonance (MR) spectroscopic imaging measures are best for lateralizing the seizure focus in patients who have temporal lobe epilepsy with and in those without hippocampal atrophy on MR images, the extent of contralateral abnormalities, and whether there is a correlation between MR spectroscopic imaging findings and surgical outcome. MATERIALS AND METHODS: MR spectroscopic imaging was performed in 16 adult patients with temporal lobe epilepsy and unilateral electroencephalographic findings and in 16 adult control subjects. Eleven patients underwent surgery; all patients underwent MR imaging. RESULTS: Nine patients had hippocampal atrophy on MR images. An ipsilateral decrease in the N-acetylaspartate concentration or the ratio of N-acetylaspartate to the sum of creatine and choline (N-acetylaspartate/ [creatine + choline]) was found in all patients. Decreased contralateral N-acetylaspartate concentration, N-acetylaspartate/(creatine + choline), or N-acetylaspartate concentration and N-acetylaspartate/(creatine + choline) were detected in eight patients (50%), which suggests bilateral abnormalities not detected with MR imaging. In the five patients who underwent surgery and did not show hippocampal atrophy on MR images, successful and unsuccessful outcomes were correctly predicted with N-acetylaspartate concentration. CONCLUSION: Decreased N-acetylaspartate concentration is not due solely to hippocampal atrophy. Contralateral abnormalities are much more frequent than expected. MR spectroscopic imaging is valuable in the presurgical evaluation of epilepsy.

Correlation of seizure frequency with N-acetyl-aspartate levels determined by 1H magnetic resonance spectroscopic imaging.

Using 1H MRSI, we measured N-acetyl-aspartate (NAA), a neuronal marker, in the seizure focus of 16 patients with partial epilepsy. Decreasing NAA correlated with increasing seizure frequency in frontal lobe epilepsy (r = -0.72, p < 0.02) and a similar trend was present in temporal lobe epilepsy (r = -.60, p < 0.06). NAA was not related to the duration of epilepsy. We conclude that patients with higher seizure frequency have evidence of greater neuron loss or dysfunction.

Comparison of k-space sampling schemes for multidimensional MR spectroscopic imaging.

For clinical 31P MR spectroscopic imaging (MRSI) studies, where signal averaging is necessary, some improvement of sensitivity and spatial response function may be achieved by acquiring data over a spherical k-space volume and varying the number of averages acquired in proportion to the desired spatial filter. Eight different k-space sampling schemes are compared through simulations that provide graphs of the spatial response functions (SRF), and tabulations of voxel volumes, relative signal-to-noise ratios (SNR), and relative data collection efficiencies (SNR per unit volume over the same time). All schemes were based on practical experiments, each of which could be implemented in the same length of time. The results show that in comparison with cubic k-space sampling with the same number of signal averages at each point, spherical and acquisition-weighted k-space sampling can be used to achieve reduced Gibbs ringing along the principal axes directions, and thus reduced contamination from adjacent tissue in these directions, without degradation of voxel volume or SNR.

Proton magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy.

Proton magnetic resonance spectroscopic imaging (1H MRSI) has demonstrated decreased N-acetyl compounds (NA) in the epileptogenic hippocampus in patients with temporal lobe epilepsy. We studied 8 patients with frontal lobe epilepsy and found mean NA/creatine (Cr) in the epileptogenic frontal lobe decreased by 27% compared with that of the contralateral homologous region (1.81 +/- 0.36 vs 2.49 +/- 0.60, p < 0.008). In every patient, NA/Cr was decreased in the epileptogenic region by at least 5%. These findings suggest that 1H MRSI may be useful in the presurgical evaluation of patients with frontal lobe epilepsy.