Hippocampal 1H-MRSI correlates with severity of depression symptoms in temporal lobe epilepsy.

OBJECTIVE: To investigate the association of an indicator of hippocampal function with severity of depression symptoms in temporal lobe epilepsy. METHODS: We evaluated 31 patients with video/EEG-confirmed temporal lobe epilepsy using creatine/N-acetylaspartate ratio maps derived from a previously validated (1)H magnetic resonance spectroscopic imaging ((1)H-MRSI) technique at 4.1 T. We also assessed depression symptoms, epilepsy-related factors, and self-perceived social and vocational disability. We used conservative nonparametric bivariate procedures to determine the correlation of severity of depression symptoms with imaging and clinical variables. RESULTS: The extent of hippocampal (1)H-MRSI abnormalities correlated with severity of depression (Spearman rho = 0.65, p value < 0.001), but other clinical factors did not. CONCLUSION: The extent of hippocampal dysfunction is associated with depression symptoms in temporal lobe epilepsy and may be a more important factor than seizure frequency or degree of disability.

CZT gamma camera for scintimammography.

A high performance prototype gamma camera based on the semiconductor radiation detector Cd(Zn)Te is described. The camera features high spatial resolution, high-energy resolution, a reduced dead space on the edge of the field of view, and a compact format. The camera performance was first examined by comparison of small field of view examinations with those from an Elscint SP6HR standard clinical gamma camera. The new camera was found to give equal or improved image quality. The camera was then used for a systematic phantom study of small lesions in a background as would be found in breast cancer imaging. In this study the camera was able to systematically detect smaller, deeper, and fainter lesions. The camera is presently being used in a clinical trial aimed to assess its value in scintimammography where previous limitations of image quality and detector size have restricted the use of the functional imaging techniques. Preliminary results from 40 patients show high sensitivity and specificity with respect to X-ray mammography and surgery.

A TiO(2) dielectric filled toroidal radio frequency cavity resonator for high-field NMR.

R(F) performance in high-field MRI applications is improved by filling the resonator with material of relative dielectric constant approximating that of human soft tissue. We demonstrate this by filling a toroidal cavity resonator operating in TEM(00) (cyclotron) mode with titanium dioxide (TiO(2)) in powdered rutile form, and acquiring phantom, human lower leg and human breast images of good quality at 4.1 T. Images made with this resonator had unusually high SNR, while the level of R(f) power required to produce a 90 degrees flip angle pulse was about a quartes as high for the filled resonator as for the same resonator before filling. Phantom images obtained with the filled resonator had an SNR of nearly 300 at a resolution of 256 x 256 voxels, nearly three times that of images of the same phantom obtained using a standard volume R(f) coil in frequent use at this laboratory. Breast images made at 256 x 256 voxels resolution had an SNR of 174, also unusually high for a volume coil. High-resolution (512 x 512 voxels) were also obtained, with SNR = 60. Preliminary phantom and in vivo human images are presented in this article. Acquiring the phantom and leg images required significantly less R(f) power than did comparable imaging using a conventional coil. In addition, the field lines were focused as they penetrated into the sample, and this resulted in a more homogeneous B(1)-field. We believe that these improvements occurred because the dielectric presence minimizes the large dielectric mismatch between air and sample.

Visual confrontation naming and hippocampal function: A neural network study using quantitative (1)H magnetic resonance spectroscopy.

Prior research on the relationship between visual confrontation naming and hippocampal function has been inconclusive. The present study examined this relationship using quantitative (1)H magnetic resonance spectroscopy ((1)H-MRS) to operationalize the function of the left and right hippocampi. The 60-item Boston Naming Test (BNT) was used to measure naming. Our sample included 46 patients with medically intractable, focal mesial temporal lobe epilepsy who had been screened for all pathology other than mesial temporal sclerosis. Statistics included Pearson correlations and neural network analysis (multilayer perceptron and radial basis function). Baseline BNT performance correlated significantly with left (1)H-MRS hippocampal ratios. Thirty-six per cent of the variance in baseline BNT performance was explained by a neural network model using left and right (1)H-MRS ratios(creatine/N-acetylaspartate) as input. This was elevated to 49% when input from the right hippocampus was lesioned mathematically. In a second model, left (1)H-MRS hippocampal ratios were modelled using measures of semantic and episodic memory as input (including the BNT). Explained variance in left (1)H-MRS hippocampal ratios fell from 60.8 to 3.6% when input from BNT and another semantic memory measure was degraded mathematically. These results provide evidence that the speech-dominant hippocampus is a significant component of the overall neuroanatomical network of visual confrontation naming. Clinical and theoretical implications are explored.

Statistically driven identification of focal metabolic abnormalities in temporal lobe epilepsy with corrections for tissue heterogeneity using 1H spectroscopic imaging.

1H spectroscopic imaging of N-acetyl-aspartate, creatine, and choline has proven to be a sensitive indicator for the lateralization of seizure foci in temporal lobe epilepsy. Previous studies have used right-left comparisons to identify the epileptogenic tissue assuming that alterations due to the disease process outweigh the effects of tissue heterogeneity. To evaluate the effectiveness of tissue heterogeneity corrected analyses, we evaluated three criteria for lateralization of the seizure focus: 1) a statistically driven method adjusted for tissue composition, 2) a single valued threshold, and 3) a single global index of the hippocampus. The statistically driven analysis lateralized all eight patients correctly, whereas the single threshold method incorrectly lateralized one case and the global index failed to identify a significant difference in two cases. These findings indicate that increased accuracy and sensitivity can be obtained by correcting for tissue heterogeneity when analyzing spectroscopy studies of temporal lobe epilepsy.

MRI extrahippocampal volumes and visual memory: correlations independent of MRI hippocampal volumes in temporal lobe epilepsy patients.

Limbic system atrophy and memory dysfunction are common in patients with temporal lobe epilepsy (TLE). However, the relationship between extrahippocampal limbic structures and memory functioning within TLE has received little attention. The present study examined associations of MRI volumetric measurements of the mammillary body, fornix, amygdala, and hippocampus to measures of episodic verbal and visual memory. The Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale were administered to 47 unilateral TLE patients (25 right, 22 left). Normalized right and left MRI volumes were determined for each patient by cursor tracing 1.5 mm slices from 3D-MRI. Significant associations were found between left hippocampal volume and the immediate, delayed, and percent retention scores of the Logical Memory Test; between the left mammillary body volume and the Logical Memory Test delayed and percent retention scores; immediate Visual Reproduction performance was significantly related to the right and left amygdala volumes, and right mammillary body volume; only the right amygdala and right mammillary body volume were associated with the delayed Visual Reproduction trial. However, neither right nor left hippocampal volumes were related to visual memory performance. Multiple limbic system structural volumes were independently associated with verbal and nonverbal memory performance. Results suggest that visual memory, as measured by the Visual Reproduction Test, may be uniquely associated with extrahippocampal volumes in patients with TLE.

Diffusion mapping applied to mesial temporal lobe epilepsy: preliminary observations.

OBJECTIVE: To evaluate whether diffusion mapping could lateralize intractable seizures in mesial temporal lobe epilepsy (MTLE) patients. BACKGROUND: Animal seizure models show acute postictal depression of the apparent diffusion coefficient of water (ADCw), interictal normalization, then chronic elevation. METHODS: The hippocampal plane was imaged with five diffusion weightings along each axis. Three orthogonal ADCw maps were averaged to produce an isotropic ADCw map. RESULTS: In all eight MTLE patients, ADCw was elevated by a mean of 10+/-3% (p<0.01, paired t-test) interictally in the ipsilateral hippocampus, where side of seizure focus was determined electrographically with corroboration by volumetric MRI studies. Measured ADCw values in phantoms and five normal brains agree with published values. CONCLUSIONS: Brain tissue with interictally increased ADCw may represent an epileptogenic region with neuronal loss, gliosis, and expanded extracellular space (hippocampal sclerosis). Thus, diffusion mapping may confirm seizure lateralization.

Relative utility of 1H spectroscopic imaging and hippocampal volumetry in the lateralization of mesial temporal lobe epilepsy.

OBJECTIVES: To determine the relative utility of 1H MRSI and hippocampal volumetry for the lateralization of mesial temporal lobe epilepsy (MTLE) in patients with intractable epilepsy. BACKGROUND: MTLE is the most common partial-onset seizure disorder in patients undergoing temporal lobe epilepsy surgery. MR volumetry and spectroscopy are reliable preoperative imaging techniques for the lateralization of MTLE. METHODS: We analyzed the 1H MRSI and hippocampal formation volumes preoperatively in 30 consecutive patients who had undergone temporal lobectomy. RESULTS: Volumetry correctly lateralized the side of surgery in 93% of patients and 1H MRSI did so in 97% of patients. Incorrect lateralization occurred by volumetry in two patients and by 1H MRSI in one patient. Concordance between all MRI modalities was 73%. Pearson's analysis revealed no correlation between the degree of hippocampal volume loss and the creatine-to-N-acetylated-compounds ratio. CONCLUSIONS: Volumetry and 1H MRSI correctly lateralized most patients with MTLE and complement each other in final lateralization. The lack of correlation between the severity of volume loss and the degree of metabolic disturbance suggests that the techniques examine distinct pathophysiologic processes in MTLE.

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.

Preliminary clinical-radiological assessment of a MR tissue signature model in human stroke.

We evaluated the ability of an MR signature model (SM) of cerebral ischemic injury to stage the evolution of cellular damage in human stroke. In 19 patients with ischemic stroke of presumed embolic or non-embolic cause we carried out diffusion-weighted and T2-weighted MR imaging within 48 h of onset, and obtained apparent diffusion coefficient of water (ADCw), and T2 weighted images. We used the signatures obtained from these ADCw/T2 maps to formulate two patterns of damage signifying accelerated or non-accelerated progression of cellular death after stroke onset. Those patients with the accelerated pattern corresponded to those with the neuroradiological (NRC) and clinical diagnosis (TOAST.1 and TOAST.2) of presumed embolic stroke, with clinical diagnosis performed blinded both to NRC and to SM. Agreement between the SM and NRC was substantial (kappa=0.62), moderate (0.60

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.

Frequency offset corrected inversion (FOCI) pulses for use in localized spectroscopy.

Gradient localized spectroscopy techniques suffer from a well documented spatial localization error caused by the difference in chemical shifts between resonances. This results in the acquisition of spectra from partially overlapping spatial regions of the sample, with each resonance representing a different region. The image-selected in vivo spectroscopy technique uses hyperbolic secant inversion pulses, where the main limitation in reducing this error is in the RF power available for application of the selective RF pulse. This spatial localization error may be dramatically reduced by increasing, and temporally shaping, the gradient pulse during slice-selective spin inversion. The performance of these RF pulses have been experimentally verified.

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.

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.

Normalization of contralateral metabolic function following temporal lobectomy demonstrated by 1H magnetic resonance spectroscopic imaging.

We studied 10 medically intractable temporal lobe epilepsy (TLE) patients prior to surgery using proton magnetic resonance spectroscopic imaging (MRSI) to localize seizure foci. We found significantly elevated creatine/N-acetylaspartate (Cr/NAA) unilaterally in 8 and bilaterally in 2 patients. Five patients have been studied again 1 year after surgery. In the 2 patients with bilateral temporal seizure onsets, MRSI showed normalization of Cr/NAA in the unoperated contralateral tissue following surgical elimination of seizures. This study suggests that metabolic recovery can occur in contralateral temporal areas following surgical treatment of partial epilepsy.

A model to predict the histopathology of human stroke using diffusion and T2-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: We sought to identify MRI measures that have high probability in a short acquisition time to predict, at early time points after onset of ischemia, the eventual development of cerebral infarction in clinical patients who suffer occlusion of a cerebral artery. METHODS: We developed an MR tissue signature model based on experimentally derived relationships of the apparent diffusion coefficient of water (ADCw) and T2 to ischemic brain tissue histopathology. In eight stroke patients we measured ADCw and T2 intensity using diffusion-weighted echo-planar imaging (DW-EPI). Tissue signature regions were defined, and theme maps of the ischemic focus at subacute time points after stroke onset were generated. RESULTS: Five MR signatures were identified in human stroke foci: two that may predict either cell recovery or progression to necrosis, one that may mark the transition to cell necrosis, and two that may be markers of established cell necrosis. CONCLUSIONS: An MR tissue signature model of ischemic histopathology using ADCw and T2 can now be tested for its potential to predict reversible and identify irreversible cellular damage in human ischemic brain regions.

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.

Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging.

The goals of the current study were threefold: first, to confirm previous single volume proton (1H) magnetic resonance spectroscopy results of reduced N-acetyl aspartate (NAA, a putative marker of neurons) in multiple sclerosis (MS) white matter lesions using multiple volume 1H magnetic resonance spectroscopic imaging (MRSI); second, to measure the phospholipid metabolites phosphomonoesters and phosphodiesters in such lesions using phosphorus (31P) MRSI; and third, to test the hypothesis that biochemical changes occur in the normal-appearing (on spin echo T2-weighted magnetic resonance images) white matter in patients with MS. Thirteen subjects with clinically definite MS were studied with both 1H and 31P MRSI, and 19 controls were studied with either 1H MRSI, 31P MRSI, or both. MS lesion, MS normal-appearing white matter, and region-matched control spectra from the centrum semiovale were analyzed. The major findings of this study were that in both white matter lesions and normal-appearing white matter in patients with MS, the metabolite ratio NAA/creatine and the total 31P peak integrals were significantly reduced compared with controls. In addition, in MS lesions NAA/choline and phosphodiesters/total 31P were significantly reduced compared with controls, and in MS normal-appearing white matter there was a trend for NAA/choline to be reduced compared with controls. In normal-appearing white matter in patients with MS, total creatine and phosphocreatine were significantly increased compared to controls, as detected with both 1H (total creatine peak integrals) and 31P (phosphocreatine/total 31P) MRSI techniques. These results suggest reduced neuronal density and altered phospholipid metabolites in white matter lesions in patients with MS.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced phase encoding in spectroscopic imaging.

The effect of different spatial-encoding (k-space) sampling distributions are evaluated for magnetic resonance spectroscopic imaging (MRSI) using Fourier reconstruction. Previously, most MRSI studies have used square or cubic k-space functions, symmetrically distributed. These studies examine the conventional k-space distribution with spherical distribution, and 1/2 k-space acquisition, using computer simulation studies of the MRSI acquisition for three spatial dimensions and experimental results. Results compare the spatial response function, Gibbs ringing effects, and signal contamination for different spatial-encoding distribution functions. Results indicate that spherical encoding, in comparison with cubic encoding, results in a modest improvement of the response function with approximately equivalent spatial resolution for the same acquisition time. For spin-echo acquired data, reduced acquisition times can readily be obtained using 1/2 k-space methods, with a concomitant reduction in signal to noise ratio.

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

Phosphorus magnetic resonance spectroscopic imaging has previously demonstrated localized metabolic abnormalities within the epileptogenic region in patients with temporal lobe epilepsy, including alkalosis, increased inorganic phosphate level, and decreased phosphomonoester levels. We studied 8 patients with frontal lobe epilepsy, finding interictal alkalosis in the epileptogenic region compared to the contralateral frontal lobe in all patients (7.10 +/- 0.05 vs 7.00 +/- 0.06, p < 0.001). Seven patients exhibited decreased phosphomonoester levels in the epileptogenic frontal lobe compared to the contralateral frontal lobe (16.0 +/- 6.0 vs 23.0 +/- 4.0, p < 0.01). In contrast to findings in temporal lobe epilepsy, inorganic phosphate level was not increased in the epileptogenic region. Based on values derived from normal control subjects, 5 patients had elevated pH in the seizure focus and 2 patients had decreased phosphomonoesters while none had abnormalities in the contralateral frontal lobe. These data suggest that magnetic resonance spectroscopy will be useful in the presurgical evaluation of patients with frontal lobe epilepsy.