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.

Magnetic resonance spectroscopic imaging in temporal lobe epilepsy: neuronal dysfunction or cell loss?

BACKGROUND: Magnetic resonance spectroscopy (MRS) has demonstrated consistent metabolic abnormalities in temporal lobe epilepsy. The reason for decreases in N-acetylated compounds are thought to be related to neuronal hippocampal cell loss as observed in hippocampal sclerosis. However, mounting evidence suggest that the N-acetylated compound decreases may be functional and reversible. OBJECTIVE: To establish whether the metabolic changes measured by MRS correlate to hippocampal cell loss in temporal lobe epilepsy. SUBJECTS AND METHODS: We prospectively performed quantitative hippocampal MR imaging volumetry and MRS imaging in 33 patients with intractable mesial temporal lobe epilepsy who were undergoing surgery. A neuronal-glial ratio of cornu ammonis and fascia dentata was obtained and correlated while validating the pathologic analysis by comparisons with specimens of age-matched autopsy control-case hippocampus (n = 14). RESULTS: The neuronal-glial ratio of the patient group was statistically significantly lower than in the control group for the cornu ammonis region (P<.001). Correlations of hippocampal volumes with cornu ammonis and neuronal-glial ratios revealed a significant interdependence (P<.01). However, correlations of the resected hippocampal creatine-N-acetylated compound ratio with the cornu ammonis or fascia dentata neuronal-glial ratios showed no significant interdependence (P>.8). CONCLUSIONS: Our findings support the concept that the metabolic dysfunction measured by MRS imaging and the hippocampal volume loss detected by MR imaging volumetry do not have the same neuropathologic basis. These findings suggest that the MRS imaging metabolic measures reflect neuronal and glial dysfunction rather than neuronal cell loss as previously assumed.

Correlation of scalp EEG and 1H-MRS metabolic abnormalities in temporal lobe epilepsy.

PURPOSE: To correlate the interictal spike field and region of seizure onset with the distribution of 1H-MRS abnormalities in temporal lobe epilepsy (TLE) and improve our understanding of the clinical significance of 1H-MRS abnormalities. METHODS: Scalp electroencephalogram (EEG) monitoring and proton magnetic resonance spectroscopy (1H-MRS) results were correlated in 31 consecutive patients with TLE. RESULTS: Lateralized 1H-MRS-based hippocampal abnormalities were recorded in 95% of the patients with unilateral interictal spikes, with a high degree of concordance for the lateralization side (90%). In 64% of the patients with normal or bilateral interictal EEG spikes, 1H-MRS provided lateralizing information. Bilateral 1H-MRS abnormalities, with or without lateralization, were 3 times more frequent than bitemporal EEG spikes. Anterior predominance of the 1H-MRS abnormalities was more frequent in patients with anterior temporal EEG spiking (50%), than in patients without this EEG distribution (18%). Similar association was noted between distribution of 1H-MRS abnormalities and region of EEG seizure onset. CONCLUSIONS: Our results show a moderate level of concordance between the distribution of 1H-MRS and EEG abnormalities. 1H-MRS identifies abnormalities contralateral to the predominant seizure focus more often than does EEG and may provide lateralizing information in patients with nonlateralizing interictal EEG.

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.

Cognitive correlates of 1H MRSI-detected hippocampal abnormalities in temporal lobe epilepsy.

OBJECTIVES: To examine associations between 1H magnetic resonance spectroscopic imaging (1H MRSI)-detected hippocampal creatine to N-acetylaspartate (Cr/NAA) ratios and neuropsychological measures sensitive to mesial temporal lobe function. BACKGROUND: The measurement of 1H MRSI-detected hippocampal metabolites has proved effective in determining extent and lateralization of neuronal damage. However, relationships between 1H MRSI-detected hippocampal metabolic abnormalities and specific areas of cognitive functioning have received limited attention compared to other studies using MRI volumetry or cerebral blood flow techniques. METHODS: We analyzed right and left hippocampal Cr/NAA ratios in 46 adult mesial temporal lobe epilepsy patients (32 left, 14 right) by 1H MRSI at high magnetic field (4.1 T). We examined the relationship between the right and left Cr/NAA hippocampal ratios to measures of verbal and visual memory, intelligence, attention, visuoperception, and confrontation naming. RESULTS: Measures of episodic verbal memory (n = 33) and visual confrontation naming (n = 46) were selectively associated with left hippocampal metabolic function (p<0.004), whereas neuronal function of the right hippocampal region was strongly associated with performance on a measure of facial recognition (n = 46; p<0.02). CONCLUSIONS: This study shows that specific areas of cognitive function are related to hippocampal neuronal metabolic abnormalities as detected by spectroscopic imaging. The current study indicates that 1H MRSI offers a complimentary technique to structural imaging studies in the study of mesial temporal lobe epilepsy and may enhance understanding of the role of hippocampal function in complex cognitive systems.

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.

Predictive value of 1H MRSI for outcome in temporal lobectomy.

OBJECTIVE: To investigate the predictive value of 1H MRSI for outcome in patients with mesial temporal lobe epilepsy (MTLE). BACKGROUND: 1H MRSI has been shown to be highly sensitive in the lateralization of temporal lob epilepsy. METHODS: The authors analyzed the relationship between the 1H MRSI findings and surgical outcome in 40 consecutive patients who underwent temporal lobe surgery for MTLE. Outcome at a mean of 24 months (range 18 to 40 months) was classified as seizure free or not seizure free. RESULTS: At follow-up, 78% of patients were seizure free. Correlations showed no predictive value for the creatine/N-acetylated compound (Cr/NA) ratio of the operated temporal lobe and outcome. However, a relationship was found between surgical failure and the Cr/NA ratio of the nonoperated temporal lobe and with a Cr/NA ratio in the nonoperated lobe above 1.21 in patients with bilateral abnormalities (p < 0.01). CONCLUSIONS: Preoperative elevations in the Cr/NA ratio in the nonoperated temporal lobe or the presence of higher metabolic ratios contralateral to the proposed surgery are associated with surgical failure. The predictive value of 1H MRSI absolute metabolite concentrations for outcome in MTLE requires further investigation.

Quantitative MRI in temporal lobe epilepsy: evidence for fornix atrophy.

OBJECTIVE: To investigate whether the fornix and mamillary bodies, being part of the limbic system, are abnormal in patients with mesial temporal lobe epilepsy (MTLE). BACKGROUND: The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. This system is implicated in complex functions, including memory and emotion, and in diseases such as MTLE. METHODS: The authors performed volumetric measurements of hippocampus, amygdala, fornix, and mamillary bodies in 50 patients with MTLE and compared the results with normal controls and patients with extratemporal lobe epilepsy. RESULTS: Control (n = 17) measurements of the amygdala, hippocampus, and fornix revealed larger volumes of the right hemisphere structures (p < 0.001). Normalized fornix volumes revealed atrophy in 86% of studies concordant with hippocampal atrophy in all cases but one. Similarly, the mean hippocampal and fornix volumes for the group discriminated the epileptogenic temporal lobe (p < 0.001). Limbic volumes were normal in all patients with extratemporal lobe epilepsy. CONCLUSIONS: Quantitative MRI findings support the concept that MTLE is not a process limited to the hippocampus but also involves other interrelated limbic system structures, in particular, the fornix.

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.

Topiramate increases cerebral GABA in healthy humans.

Topiramate (TOP) is a novel anticonvulsant drug with multiple mechanisms of action used in the treatment of epilepsy. Measurements of cerebral GABA were obtained in six controls using 1H MRS at baseline and at 3 and 6 hours following the administration of 3 mg/kg of TOP. Brain GABA concentrations rose by 72% at 3 hours and by 64% at 6 hours compared with baseline (p < 0.004). This study demonstrates that TOP significantly increases human cerebral GABA concentrations in healthy individuals.

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.

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

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.

Volumetric MRI of the limbic system: anatomic determinants.

The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. It is involved in complex functions including memory and emotion and in diseases such as temporal lobe epilepsy. Volume measurements of the amygdala and hippocampus have been used reliably to study patients with temporal lobe epilepsy but have not extended to other limbic structures. We performed volume measurements of hippocampus, amygdala, fornix and mamillary bodies in healthy individuals. Measurements of the amygdala, hippocampus, fornix and mamillary bodies revealed significant differences in volume between right and left sides (P < 0.001). The intraclass coefficient of variation for measurements was high for all structures except the mamillary bodies. Qualitative image assessment of the same structures revealed no asymmetries between the hemispheres. This technique can be applied to the study of disorders affecting the limbic system.

Proton spectroscopic imaging at 4.1 tesla in patients with malformations of cortical development and epilepsy.

We used proton magnetic resonance spectroscopic imaging (MRSI) at 4.1 tesla in patients with malformations of cortical development (MCDs) and epilepsy. We compared the spectroscopic results with normative data using 2 SDs (95% confidence) above normal values for detection of significant abnormalities for creatine-N-acetylated compounds (Cr/NA) ratio and choline-N-acetylated compounds (Cho/NA). The results were correlated with clinical, EEG, and histologic findings. Patients with focal cortical dysplasia showed significant metabolic abnormalities in correspondence with the structural lesions, whereas patients with heterotopia and polymicrogyria demonstrated no subcortical MRSI abnormalities. Significant correlations were found between the metabolic abnormalities and the frequency of seizures but not with the degree of interictal EEG discharges. Quantitative neuronal and glial cell counts revealed no statistically significant correlation between cell loss and the abnormal metabolic ratios in those who underwent surgery. These preliminary findings suggest that MRSI-based metabolic abnormalities in patients with MCDs are variable and are likely to be associated with complex cellular mechanisms involving the regulation of NA, total Cr content, and Cho.

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.

Association of combined MRI, interictal EEG, and ictal EEG results with outcome and pathology after temporal lobectomy.

PURPOSE: Magnetic resonance imaging, interictal scalp EEG, and ictal scalp EEG each have been shown to localize the primary epileptic region in most patients with mesial-basal temporal lobe epilepsy (MBTLE), but the association of surgical outcome and pathology with each combination of these test results is not known. METHODS: We reviewed the MRI, interictal scalp EEG, and ictal scalp EEG results of 90 consecutive patients with MBTLE. Twelve patients were excluded from the analysis because inconclusive bitemporal intracranial EEG results precluded anterior temporal lobectomy (ATL); none had concordant MRI and interictal scalp EEG results. We compared all combinations of presurgical MRI, interictal EEG, and ictal EEG results to seizure outcome and tissue pathology in the 78 patients who underwent an ATL. RESULTS: Forty-eight (61%) patients had concordant lateralized MRI and interictal EEG temporal lobe abnormalities, with no discordant ictal EEG results; 77% of these patients were seizure-free after ATL. Concordance of MRI and interictal EEG abnormalities correlated with seizure cessation (p < 0.05), compared to all combinations with discordant or nonlateralizing MRI and interictal EEG results. Mesial temporal sclerosis (MTS) was confirmed pathologically in about 80% of both groups (p = 0.5). Outcome in patients with concordant MRI and ictal EEG with nonlateralizing interictal EEG was significantly worse than combinations with concordant MRI and interictal EEG (p < 0.02). CONCLUSIONS: Compared to other combinations of test results, concordance of MRI and interictal EEG is most closely associated with surgical outcome in MBTLE. However, most selected patients have pathologic confirmation of MTS regardless of test results or outcome. This information may be useful for planning the presurgical evaluation of patients with medically intractable MBTLE.