Hippocampal MRI volumetrics and temporal lobe substrates in medial temporal lobe epilepsy

Forty-nine consecutive patients undergoing anteromedial temporal lobe resection for medically intractable temporal lobe seizures, and averaging 2 yr (range 6 mo to 4 yr) postoperative follow-up, were selected for a retrospective study. This study correlated magnetic resonance imaging (MRI) derived hippocampal volumetrics, preoperative demographics, postoperative seizure control, and tissue analysis, including hippocampal CA (cornu ammonis) field neuronal, and glial cell counts, and immunohistochemistry (IHC) evidence for dentate sprouting and reorganization. These measures were compared in hippocampi with or without an adjacent presumptive epileptogenic temporal lobe mass. Mesial temporal sclerosis (MTS) was defined as >50% neuronal cell loss averaged across all CA fields with NPY (neuropeptide-y) and somatostatin reorganization. These patients may or may not include granule cell sprouting as determined by dynorphin staining. Patients were divided into two groups based on CA field neuronal cell counts, one averaging >50% cell loss and one averaging <50% cell loss. For the MTS group (N = 38), 89% had significant volumetric atrophy of the ipsilateral hippocampus, 74% had dentate reorganization, and complete seizure control was seen in 76% of these patients. In one subgroup of the <50% cell loss group, patients with medial temporal lobe epilepsy caused by a mass in the medial temporal lobe (mass group) (N = 6), 33% demonstrated significant volumetric atrophy of the hippocampus ipsilateral to the mass, 0% had dentate sprouting, and seizures were completely controlled in 67%. For the second subgroup of the <50% cell loss group, patients without mass lesions (N = 5) who were classified as the paradoxical medial temporal lobe epilepsy group (paradoxical group), 20% had ipsilateral hippocampal atrophy, 0% had dentate reorganization, and complete seizure control was seen in 60% of these patients. In conclusion, for the MTS group, hippocampal atrophy proven by MRI volumetrics was highly predictive of significant neuronal cell loss and an excellent indicator of success. However, in patients who had a foreign mass, hippocampal atrophy was not necessarily indicative of significant neuronal cell loss and MRI volumetrics was not a factor in the determination of a successful outcome. Furthermore, patients without mass lesions who have normal volumetrics but demonstrate hippocampal disease through invasive electrode monitoring, are likely to have paradoxical medial temporal lobe epilepsy, seizures beginning at a later age, and a lower, but not insignificant, success rate than the classical mesial temporal sclerosis group.     

Morphometry in temporal lobe epilepsy

We demonstrate a method for quantitating changes in volume and morphology of the temporal lobe in epilepsy. The temporal lobes of 10 neurologically normal subjects and six subjects with well defined left-sided mesial temporal epilepsy were studied. From high resolution T₁-weighted magnetic resonance images, the grey and white matter were manually segmented over a predetermined extent. The volumes of the grey and white matter were determined. Using the segmented images, the grey matter/CSF surface and the white matter/grey matter surface were reconstructed, allowing estimates of the surface area and calculation of indices of curvature for the two surfaces. The index of curvature was calculated for each vertex of a polygonal mesh that was fitted to the surfaces. An index of grey matter thickness (grey matter volume/white matter surface area) was also calculated. There was a significant bilateral decrease in the total volume (p < .01), grey matter volume (p < .001) and grey matter thickness index (p < .05) in epileptic subjects. In addition, there was a bilateral decrease in white matter surface area (p < .05) and a small left-sided decrease in white matter volume (p < .05) in epileptic subjects. The average distributions of indices of curvature for both surfaces differed significantly (p < .05) between normal and epileptic subjects. In the grey matter/CSF surface of normal subjects, a large peak corresponding to surface concavity was present. The amplitude of this peak was significantly lower in epileptic subjects (p < .05 for the right hemisphere; p < .001 for the left hemisphere).     

Proton magnetic resonance spectroscopic images and MRI volumetric studies for lateralization of temporal lobe epilepsy

We obtained 2D magnetic resonance (MR) spectroscopic images (MRSI) and MRI volumetric measurements (MRIV) of amygdala and hippocampus in 30 consecutive patients with temporal lobe epilepsy (TLE) being evaluated for surgical treatment. Both MRSI and MRIV lateralization showed good agreement with the current gold standard of clinical-EEG lateralization. Each exam separately correctly lateralized 25 out of 30 patients with no false lateralization. Combining both exams, lateralization could be achieved in 28 out of 30 patients. The two patients with no significant asymmetry had bitemporal EEG abnormalities, and bilateral damage on both MRIV and MRSI. There was a good correlation between the magnitude of the MRSI and MRIV asymmetry (Pearson COEFFICIENT = 0.83; p < .0001). Both MRSI and MRIV were normal in our patients with seizures originating outside the temporal lobes. Both MRIV and MRSI can lateralize TLE in 83% of patients. Combination of the two modalities allows lateralization in 93% of patients. Patients who cannot be lateralized generally have symmetrical bitemporal abnormalities; they are not incorrectly lateralized. The structural and chemical pathologic abnormalities seen in TLE seem to be associated with the seizure focus, and may be as, or even more, reliable than a few recorded seizures in predicting the side from which most seizures originate.     

MRI of the temporal lobe: normal variations, with special reference toward epilepsy.

Recent investigations of epilepsy, Alzheimer's disease, amnesia, and schizophrenia have used magnetic resonance imaging (MRI) to evaluate changes in temporal lobe structures. Normal variations in these structures need to be defined before one can use these structures to describe abnormal conditions. Twenty-nine normal volunteers were studied by coronal MRI. Frequent findings include notching of the uncus by the tentorium or adjacent vessels (22/29) and asymmetry of the temporal horns (20/29). This finding of uncal notching strengthens the evidence against "incisural sclerosis" as the basis for hippocampal sclerosis. Temporal horn dilatation occurred in four. However, mild asymmetry of the temporal horn was seen frequently at its anterior tip (16/29) and may be related to head rotation. Asymmetry of the choroidal fissure was never marked. Mild asymmetry was common at the hippocampal head (pes). Mild enlargement of the right temporal lobe by visual inspection is not uncommon. Subtle asymmetry of the white matter between the hippocampus and the collateral sulcus occurred in six. The collateral sulcus does not always point to the temporal horn. The occipitotemporal sulcus may point to the temporal horn. Asymmetric uncal protrusion (0/29) and Sylvian fissure dilatation (4/29) occur rarely.     

Cross-frequency network analysis of functional brain connectivity in temporal lobe epilepsy

In this study, we investigate the cross-frequency coupling and functional brain networks in the subjects with temporal lobe epilepsy(TLE) using interictal EEG signals. The phase to phase synchronization within and across frequency bands is calculated and a significant difference between the epilepsy and control groups is observed. Compared with the controls,the epilepsy patients exhibit a stronger within-frequency coupling(WFC) within theta and beta bands, and shows a stronger cross-frequency coupling(CFC) in the delta–alpha and theta–alpha band pairs, but a weakened CFC in alpha–beta band pairs. The weakened coupling between alpha and high frequency band reflects a suppression of phase modulation between the brain regions related to epilepsy. Moreover, WFC and CFC are positively correlated, which is higher in the patients relative to controls. We further reconstruct functional brain connectivity and find that both WFC and CFC networks show small-world properties. For the epilepsy, the small-world efficiency is enhanced in the CFC networks in delta–alpha and theta–alpha band pairs, whereas weakened between alpha and beta bands, which suggests a shift away from the optimal operating point in the epileptic brain with a new balance between WFC and CFC. Our results may help us to understand the important role of information communication across different frequency bands and shed new light on the study of pathology of epilepsy.     

White matter abnormalities in children and adolescents with temporal lobe epilepsy

Background and Purpose

The widespread propagation of synchronized neuronal firing in seizure disorders may affect cortical and subcortical brain regions. Diffusion tensor imaging (DTI) can noninvasively quantify white matter integrity. The purpose of this study was to investigate the abnormal changes of white matter in children and adolescents with focal temporal lobe epilepsy (TLE) using DTI.

Materials and Methods

Eight patients with clinically diagnosed TLE and eight age- and sex-matched healthy controls were studied. DTI images were obtained with a 3-T magnetic resonance imaging scanner. The epileptic foci were localized with magnetoencephalography. Fractional anisotropy (FA), mean diffusivity (MD), parallel (λ_||) and perpendicular (λ_⊥) diffusivities in the genu of the corpus callosum, splenium of the corpus callosum (SCC), external capsule (EC), anterior limbs of the internal capsule (AIC), and the posterior limbs of the internal capsule (PIC) were calculated. The DTI parameters between patients and controls were statistically compared. Correlations of these DTI parameters of each selected structure with age of seizure onset and duration of epilepsy were analysed.

Results

In comparison to controls, both patients' seizure ipsilateral and contralateral had significantly lower FA in the AIC; PIC and SCC and higher MD, λ_|| and λ_⊥ in the EC, AIC, PIC and SCC. The MD, λ_|| and λ_⊥ were significantly correlated with age of seizure onset in the EC and PIC. λ_|| was significantly correlated with the duration of epilepsy in the EC and PIC.

Conclusion

The results of the present study indicate that children and adolescents with TLE had significant abnormalities in the white matter in the hemisphere with seizure foci. Furthermore, these abnormalities may extend to the other brain hemisphere. The age of seizure onset and duration of epilepsy may be important factors in determining the extent of influence of children and adolescents TLE on white matter.     

Diffusion tensor MRI to investigate dementias: a brief review

Diffusion tensor magnetic resonance imaging (DT-MRI) is a powerful quantitative technique with the ability to detect in vivo microscopic characteristics and abnormalities of brain tissue. It has been successfully applied to a number of neurological conditions, such as stroke, multiple sclerosis and brain tumors, providing information otherwise inaccessible on the pathological substrates. DT-MRI has also been used to study patients with cognitive decline, mainly those with Alzheimer's disease. Several image-analysis approaches have been employed, including region of interest, histogram, voxel-based analyses and DT-MRI-based tractography. Specific patterns of spatial distribution of tissue damage and correlations with neuropsychological measures have been reported. This review focuses on the use of DT-MRI to investigate dementias. The main clinical results and the different methods of image analysis will be overviewed and discussed.     

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.     

Quantitative 1H MRS in the evaluation of mesial temporal lobe epilepsy in vivo

Hippocampal metabolite concentrations were determined by localized in vivo proton magnetic resonance spectroscopy (¹H MRS) in eleven patients suffering from refractory mesial temporal lobe epilepsy (MTLE), as well as in eleven age-matched healthy volunteers, and compared with patient history, postoperative outcome and histopathology. Main results are: 1) In patients, the decrease in N-acetylaspartate (NAA) concentrations was highly significant ipsilateral, and less but still significant contralateral to the electroencephalogram-defined focus, as compared to controls. 2) The decrease in ipsilateral NAA measured preoperatively correlates with the degree of hippocampal sclerosis but 3) does not reliably predict postoperative outcome, although there is a trend toward better outcome in patients with a marked decrease of NAA. 4) Hippocampal NAA decrease (ipsi- and contralateral) is highly correlated with early onset age of epileptic seizures. 5) Among patients with similar onset age in early childhood, there is a strong association between duration of the disease and contralateral (and, though less clear-cut, ipsilateral) NAA loss. These results are concordant with the notion of a generally progressive worsening and complicating course of symptoms in poorly controlled MTLE.     

Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

Background

Recent studies have shown that the human right-hemispheric auditory cortex is particularly sensitive to reduction in sound quality, with an increase in distortion resulting in an amplification of the auditory N1m response measured in the magnetoencephalography (MEG). Here, we examined whether this sensitivity is specific to the processing of acoustic properties of speech or whether it can be observed also in the processing of sounds with a simple spectral structure. We degraded speech stimuli (vowel /a/), complex non-speech stimuli (a composite of five sinusoidals), and sinusoidal tones by decreasing the amplitude resolution of the signal waveform. The amplitude resolution was impoverished by reducing the number of bits to represent the signal samples. Auditory evoked magnetic fields (AEFs) were measured in the left and right hemisphere of sixteen healthy subjects.

Results

We found that the AEF amplitudes increased significantly with stimulus distortion for all stimulus types, which indicates that the right-hemispheric N1m sensitivity is not related exclusively to degradation of acoustic properties of speech. In addition, the P1m and P2m responses were amplified with increasing distortion similarly in both hemispheres. The AEF latencies were not systematically affected by the distortion.

Conclusions

We propose that the increased activity of AEFs reflects cortical processing of acoustic properties common to both speech and non-speech stimuli. More specifically, the enhancement is most likely caused by spectral changes brought about by the decrease of amplitude resolution, in particular the introduction of periodic, signal-dependent distortion to the original sound. Converging evidence suggests that the observed AEF amplification could reflect cortical sensitivity to periodic sounds.     

Quantitative magnetic resonance imaging in consecutive patients evaluated for surgical treatment of temporal lobe epilepsy

We present the results of quantitative Magnetic Resonance Imaging (MRI) in 55 consecutively referred patients with clinical evidence of temporal lobe epilepsy (TLE). The Cavalieri method was used in combination with point counting to provide unbiased estimates of the volume of the left and right hippocampus, amygdala, temporal lobe, lateral ventricles and cerebral hemisphere, and pixel by pixel maps of the T2 relaxation time were computed for both central and anterior sections of the hippocampus. The 99th centiles of hippocampal volume, hippocampal volume asymmetry and T2 relaxation times in 20 control subjects provided limits which identified the presence of MTS. The results of the quantitative MRI were compared with the results of conventional diagnostic MRI, foramen ovale (FO) recording and the WADA test. Thirty-one patients were found to have unilateral MTS (17 left and 14 right) and 7 bilateral MTS. No evidence of MTS was detected in 16 patients. Of the 31 patients diagnosed with unilateral MTS on the basis of hippocampal volume and T2 measurement, 74% and 77% would respectively have received the same diagnosis on the basis of hippocampal volume and T2 measurements alone. In comparison to FO recording, quantitative MRI has a sensitivity of 55% and a specificity of 86%, while conventional diagnostic MRI has a sensitivity of 42% and a specificity of 80% for detection of MTS. Unilateral abnormalities were detected by FO recording in 30% cent of patients who appeared normal on quantitative MRI. WADA test results were available for 40 patients. The findings were consistent with quantitative MRI showing reduced memory function ipsilateral to unilateral MTS in 18 patients, but reduced memory function contralateral to unilateral MTS in two patients, and reduced memory function without MR abnormality in seven patients. WADA testing revealed unilateral memory impairments where MRI found bilateral pathology in 4 patients and in 4 patients in whom quantitative MRI detected unilateral MTS there was no evidence of reduced memory during WADA testing of the corresponding cerebral hemisphere. In the patients with unilateral right MTS a highly significant negative correlation (p = 0.0003) was observed between age of onset and the volume of the contralateral temporal lobe.

Quantitative MR imaging of the hippocampus (i.e. volume and T2 measurement) is preferable to conventional radiological reporting for providing objective evidence of the presence of MTS on which to base the referral of patients for surgery, and since it has associated morbidity FO recording is now only being used in selected patients. Furthermore, stereology provides a convenient method for estimating the volume of other brain structures, which is relevant to obtaining a better understanding of the effects of laterality and age of onset of TLE.     

Diffusion tensor imaging at low SNR: nonmonotonic behaviors of tensor contrasts

Diffusion tensor imaging (DTI) provides measurements of directional diffusivities and has been widely used to characterize changes in the tissue microarchitecture of the brain. DTI is gaining prominence in applications outside of the brain, where resolution, motion and short T2 values often limit the achievable signal-to-noise ratio (SNR). Consequently, it is important to revisit the topic of tensor estimation in low-SNR regimes. A theoretical framework is developed to model noise in DTI, and by using simulations based on this theory, the degree to which the noise, tensor estimation method and acquisition protocol affect tensor-derived quantities, such as fractional anisotropy and apparent diffusion coefficient, is clarified. These results are then validated against clinical data. It is shown that reliability of tensor contrasts depends on the noise level, estimation method, diffusion-weighting scheme and underlying anatomy. The propensity for bias and errors does not monotonically increase with noise. Comparative results are shown in both graphical and tabular forms, so that decisions about suitable acquisition protocols and processing methods can be made on a case-by-case basis without exhaustive experimentation.     

Diffusion tensor imaging in horizontal gaze palsywith progressive scoliosis

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare disorder characterized by absence of conjugate horizontal eye movements, preservation of vertical gaze and convergence, progressive scoliosis developing in childhood and adolescence. It is caused by mutations in the ROBO3 gene which are critical for the crossing of long ascending medial lemniscal and descending corticospinal tracts in the medulla. Diffusion tensor imaging on a 14-year-old boy with HGPPS revealed ipsilateral ascending and descending connectivity in the brainstem without any crossing over of the major tracts although normal interhemispheric connections in the corpus callosum was demonstrable. Absent decussation of smaller sized superior cerebellar peduncles but with normal crossing over of the middle cerebellar peduncle was also observed. Tractography is a valuable investigative modality to assess neuronal connections in the brain and is a useful adjunct to the structural magnetic resonance imaging in confirming the diagnosis of HGPPS.     

Diffusion tensor fiber tractography of the olfactory tract

Magnetic resonance diffusion tensor imaging with fiber tracking is used for 3-dimensional visualization of the nervous system. Peripheral nerves and all cranial nerves, except for the olfactory tract, have previously been visualized. The olfactory tracts are difficult to depict with diffusion-weighted imaging due to the high sensitivity to susceptibility artifacts at the base of the skull. Here we report an optimized single-shot diffusion-weighted echo planar imaging sequence that can visualize the olfactory tracts with fiber tracking. Five healthy individuals were examined, and the olfactory tracts could be fiber tracked with the diffusion-weighted sequence. For comparison and as a negative control, an anosmic patient was examined. No olfactory tracts were visualized on T2-weighted nor diffusion-weighted fiber tracking images. Measuring diffusion in the olfactory tracts promise to facilitate the identification of different hyposmic and anosmic conditions.     

Diffusion tensor image up-sampling: a registration-based approach

Diffusion weighted images (DWI), from which the corresponding diffusion tensor images (DTI) are estimated, are commonly acquired with anisotropic discretizations. Traditional methods to up-sample diffusion weighted images generally rely on scene-based interpolation and do not exploit structural information from the images. In this study, a DTI up-sampling framework is presented that incorporates the underlying anatomical shape information by means of non-rigid inter-slice registration. A strategy is proposed to reorient the interpolated tensor in order to maintain its proper orientation. Tests on phantom as well as on real data sets show that the proposed method is able to produce better results compared to scene based interpolation methods in terms of the accuracy of DWI/DTI interpolation, especially when diffusion tensor orientation is taken into account.     

Efficient cardiac diffusion tensor MRI by three-dimensional reconstruction of solenoidal tensor fields

Tensor tomography is being investigated as a technique for reconstruction of in vivo diffusion tensor fields that can potentially be used to reduce the number of magnetic resonance imaging (MRI) measurements. Specifically, assessments are being made of the reconstruction of cardiac diffusion tensor fields from 3D Radon planar projections using a filtered backprojection algorithm in order to specify the helical fiber structure of myocardial tissue. Helmholtz type decomposition is proposed for 3D second order tensor fields. Using this decomposition a Fourier projection theorem is formulated in terms of the solenoidal and irrotational components of the tensor field. From the Fourier projection theorem, two sets of Radon directional measurements, one that reconstructs the solenoidal component and one that reconstructs the irrotational component of the tensor field, are prescribed. Based on these observations filtered backprojection reconstruction formulae are given for the reconstruction of a 3D second order tensor field and its solenoidal and irrotational components from Radon projection measurements. Computer simulations demonstrate the validity of the mathematical formulations and demonstrate that a realistic model of the helical fiber structure of the myocardial tissue specifies a diffusion tensor field for which the first principal vector (the vector associated with the maximum eigenvalue) of the solenoidal component accurately approximates the first principal vector of the diffusion tensor. A priori knowledge of this allows the orientation of the myocardial fiber structure to be specified utilizing one half of the number of MRI measurements of a normal diffusion tensor field study.     

MRI in cerebral developmental malformations and epilepsy

Cerebral developmental malformations are increasingly recognized as a major cause of developmental delay and epilepsy. The incidence of these developmental malformations in patients with epilepsy is not known, but epilepsy surgery data suggest that this pathology is commonly seen in children who undergo epilepsy surgery for intractable epilepsy. These malformations can be diagnosed by a combination of clinical, neurophysiological, and imaging techniques. However, imaging techniques such as MRI have been able to provide in vivo recognition of many of these malformations and have contributed to the recognition of specific syndromes. These malformations can be classified on an anatomical basis either into diffuse, unilateral, or generalized. However, a combination of imaging data in conjunction with genetics and embryology may be more appropriate in the future. Further technical developments promise to increase the sensitivity of MRI in detecting these malformations and may help to delineate the possible biology of these disorders.     

Diffusion tensor magnetic resonance imaging of the normal breast

Purpose

The objective of this study was to evaluate diffusion anisotropy of the breast parenchyma and assess the range and repeatability of diffusion tensor imaging (DTI) parameters in normal breast tissue.

Materials and Methods

The study was approved by our institutional review board and included 12 healthy females (median age, 36 years). Diffusion tensor imaging was performed at 1.5 T using a diffusion-weighted echo planar imaging sequence. Diffusion tensor imaging parameters including tensor eigenvalues (λ₁, λ₂, λ₃), fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured for anterior, central and posterior breast regions.

Results

Mean normal breast DTI measures were λ₁=2.51×10⁻³ mm²/s, λ₂=1.89×10⁻³ mm²/s, λ₃=1.39×10⁻³ mm²/s, ADC=1.95±0.24×10⁻³ mm²/s and FA=0.29±0.05 for b=600 s/mm². Significant regional differences were observed for both FA and ADC (P<.05), with higher ADC in the central breast and higher FA in the posterior breast. Comparison of DTI values calculated using b=0, 600 s/mm² vs. b=0, 1000 s/mm², showed significant differences in ADC (P<.001), but not FA. Repeatability assessment produced within-subject coefficient of variations of 4.5% for ADC and 11.4% for FA measures.

Conclusion

This study demonstrates anisotropy of water diffusion in normal breast tissue and establishes a normative range of breast FA values. Attention to the influence of breast region and b value on breast DTI measurements may be important for clinical interpretation and standardization of techniques.     

MRI diffusion tensor reconstruction with PROPELLER data acquisition

MRI diffusion imaging is effective in measuring the diffusion tensor in brain, cardiac, liver, and spinal tissue. Diffusion tensor tomography MRI (DTT MRI) method is based on reconstructing the diffusion tensor field from measurements of projections of the tensor field. Projections are obtained by appropriate application of rotated diffusion gradients. In the present paper, the potential of a novel data acquisition scheme, PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction), is examined in combination with DTT MRI for its capability and sufficiency for diffusion imaging. An iterative reconstruction algorithm is used to reconstruct the diffusion tensor field from rotated diffusion weighted blades by appropriate rotated diffusion gradients. DTT MRI with PROPELLER data acquisition shows significant potential to reduce the number of weighted measurements, avoid ambiguity in reconstructing diffusion tensor parameters, increase signal-to-noise ratio, and decrease the influence of signal distortion.