Increasing the yield from volumetric MRI in patients with epilepsy

Volumetric magnetic resonance imaging has become a routine investigation in the management of patients with chronic partial epilepsy. However, even with the use of reformatted images, an underlying cause for epileps can-not be found in many of these patients. We show that further processing of the data, including three-dimensional reconstruction and quantitative analysis of the volume and complexity of the images in three dimensions, reveals additional positive information in up to 75% of patients. This may be useful for surgical planning, prognostication, and understanding of the structure and development of the human brain.     

Overview-the role of NMR spectroscopy in epilepsy

Nuclear magnetic resonance (NMR) spectroscopy permits noninvasive, serial measurements of several metabolites with important neurobiologic roles in localized brain regions in vivo. Over the last decade, this technique has been applied to investigations of both animals and humans with epilepsy. Several nuclei that include specific proton, phosphorus, and carbon isotopes provide NMR signals that measure specific compounds in vivo. This paper reviews the studies that have used these multinuclear NMR techniques to investigate the role of these methods in the diagnosis and pathogenesis of epilepsy.     

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).     

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.     

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.     

N-Acetylaspartate and epilepsy

Proton magnetic resonance spectra include signals from N-acetylaspartate, creatine + phosphocreatine, and choline-containing compounds. Abnormalities in these signals can be used in the assessment of patients with intractable epilepsy. In particular, they provide a means of identifying metabolic abnormalities within the temporal lobes, detecting bilateral and diffuse pathology, and aiding lateralization of the seizure focus. The pathology demonstrated on MRS can also be related to cognitive dysfunction.     

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.     

Clinical correlations: MRI and EEG

Main structural correlates of epileptogenesis include hippocampal sclerosis, cortical dysgenesis, foreign tissue lesions, gliosis, and dual pathology (a combination of any two). These structural abnormalities are now increasingly defined with MRI, enabling systematic EEG correlative analyses. Hippocampal atrophy (HA) and increased T₂ signal in medial temporal structures predict the presence of mesial temporal sclerosis with a high degree of sensitivity and specificity. In 50 patients with clinical evidence of temporal lobe epilepsy and isolated HA, ictal scalp EEG was concordant to the atrophic temporal lobe in 33, nonlateralizing in 12, obscured in 3, and bilateral in 2, but it was discordant in none. Earlier reports of higher levels of discordance may be ascribed to the presence of dual pathology or to differing MRI and EEG criteria for localization. In a more inclusive group of 101 patients with unilateral HA, ictal scalp EEG was obtained in 99. It was unlocalized in 53, localized elsewhere in 9, and localized to the atrophic temporal lobe in 38. Of those, 51 patients had intracranial EEG: 12 were unlocalized, 29 were localized to the atrophic hippocampus, and 9 were localized elsewhere. There is thus a rare but definite subgroup of patients with unilateral HA who have EEG localization elsewhere than the atrophy. The successful cure of seizures in half these patients after removal of the EEG focus confirms the importance of this observation and emphasizes the search for more dual pathology that has remained undetected on MRI. About 10% of the patients with HA have significant atrophy bilaterally, and several series have confirmed that surgical success is predicted by removal of the EEG identified seizure onset area, not the more or less atrophic hippocampus. In patients with other kinds of dual pathology, including HA and foreign tissue lesions or cortical dysgenesis, EEG is also paramount in predicting the site of epileptogenesis for surgical intervention. EEG correlates of cortical dysgenesis are heterogeneous, but EEG has potential to provide accurate localization of the site of epileptogenesis in foreign tissue lesions also. In a study of 59 lesional patients, a small number of patients with low grade astrocytomas and oligodendrogliomas consistently localized by EEG to an area elsewhere than the lesion, and failed seizure control when the lesion was removed. Although MRI can demonstrate the structural correlate of the epilepsy in many situations, rare patients, particularly with certain tumors, cortical dysgenesis, and dual pathology, require EEG for accurate localization.     

Magnetic resonance imaging and epilepsy: Neurosurgical decision making

Advances in magnetic resonance imaging (MRI) techniques have had an important impact on the decision-making process leading to surgical resection for chronic seizures. The MRI is now obtained relatively early in the work-up, and, when it shows abnormality, it assumes a crucial role in the detection of specific surgically remediable syndromes. These syndromes, when diagnosed by MR and other confirmatory studies such as electroencephalography (EEG), positron emission tomography (PET), magnetoencephalography (MEG), and neuropsychological testing, define the essential part of the surgical plan; that is, removal of the disease substrate. The availability of a host of MR techniques enable us to investigate epilepsy not only as a structural pathology but as physiological pathology reflected in abnormal blood flow, metabolism, and synaptic transmission. The mainstay of surgical treatment is the removal of the anatomic pathology, but other MR techniques may be helpful in the delineation of dual pathology in lesional cases, in appreciation of the full extent of microscopic pathology in developmental lesions, and in the imposition of restrictions on the resection based upon functional mapping. Finally, functional and anatomic maps obtained preoperatively can be related directly to the spatial coordinates of the exposed brain in the operating room using MRI-based frameless stereotactic methods. The final outcome, then, is the removal of the disease substrate without injury to adjacent, functionally salient cortical regions.     

New technical developments in magnetic resonance imaging of epilepsy

Within the last several years a number of technical developments have been made in magnetic resonance imaging (MRI) that can potentially impact clinical and research MR imaging applications in epilepsy. These include developments in instrumentation and in pulse sequences. Advances in instrumentation include higher capacity gradient systems and multiple receiver coils as directed to brain imaging. Advances in pulse sequence include use of fast or turbo-spin-echo techniques, variants of echo-planar imaging, and sequences such as fluid-attenuation inversion recovery (FLAIR) targeted to specific applications of brain imaging. The purpose of this paper is to review several of these developments.     

MRI hippocampal volume and neuropsychology in epilepsy surgery

A review is provided of recent findings on relationships between neurocognitive test data and magnetic resonance imaging (MRI)-determined hippocampal volumes in nonlesional temporal lobectomy patients. The difference between the right and left hippocampal volumes is correlated with postoperative verbal memory in left temporal lobectomy patients who do not have lesional pathology. MRI hippocampal volume data are not associated with measures of executive functioning or naming. Sex differences have been found for verbal memory outcome as women have better verbal memory following left temporal lobectomy. Sex differences have also been found in the relationships between verbal and visual memory, and hippocampal volume data. The systematic combination of MRI-acquired morphological data and neuropsychological test data may further our understanding of neurocognitive function, and provide clinically useful data for counseling epilepsy surgery patients. The current data are promising with regard to prediction of memory outcome following temporal lobectomy, but they do not yet allow for prediction of specific individual patient outcomes. Rather, the currently available data support counseling patients based on the memory outcome of others with similar characteristics.     

Curvilinear reconstruction of 3D magnetic resonance imaging in patients with partial epilepsy: A pilot study

In an attempt to better delineate the abnormalities associated with focal cortical dysgenesis, we performed curvilinear reformatting of the cortex from 3D magnetic resonance (MR) images. Illustrative patients with partial seizures and conventional orthogonal MRI evaluation show that small regions of cortical thickening suggestive of focal dysplastic lesions may not be recognized. In three such patients the curvilinear reformatting demonstrated two additional focal abnormalities of the cortical gyri and better defined the two focal lesions found on conventional orthogonal MR images. This method promises to a be useful tool in the evaluation of epileptic patients with proven or suspected subtle structural cortical abnormalities, particularly focal neuronal migration disorders where cortical thickening, abnormal gyral pattern, and poor delineation of the gray-white matter transition are the main findings.     

Identification of patients with hereditary haemochromatosis by magnetic resonance imaging and spectroscopic relaxation time measurements

A total of 4302 healthy blood donors were screened for elevated serum ferritin and transferrin saturation. Fifteen had increased serum ferritin at a follow-up examination. Five relatives of these donors also entered the study. Eleven patients had elevated liver iron concentrations, while five had normal liver iron concentrations. The R₂ relaxation rate in the liver was first measured with a conventional multi-spin-echo imaging sequence, and then by a volume-selective spectroscopic multi-spin-echo sequence, in order to achieve a minimum echo time of 4 msec. No correlation was found between the relaxation rate R₂ and the liver iron concentration, when R₂ was calculated from the imaging data. Multi-exponential transverse relaxation could be resolved when the spectroscopic sequence was used. A strong correlation between the initial slope of the relaxation curve and the liver iron concentration was found (r = 0.90, p < 0.001). Signal intensity ratios between liver and muscle were calculated from the first three echoes in the multi-echo imaging sequence, and from a gradient echo sequence. A strong correlation between the logarithm of the signal intensity ratios and the liver iron concentration was found. Although both spectroscopic T₂ relaxation time measurements and signal intensity ratios could be used to quantify liver iron concentration, the gradient echo imaging seemed to be the best choice. Gradient echo imaging could be performed during a single breath hold, so motion artifacts could be avoided. The accuracy of liver iron concentration estimates from signal intensity ratios in the gradient echo images was about 35%.     

Quantification and improvement of the signal-to-noise ratio in a magnetic resonance image acquisition procedure

A procedure is developed to quantify and improve the signal-to-noise ratio (SNR) of magnetic resonance images. The image SNR is quantified using the correlation function of two independent acquisitions of an image. To test the performance of the quantification, SNR measurement data are fitted to theoretically expected curves. The proposed correlation technique is also used to improve the SNR by estimating the amplitude of the signal spectrum. The technique is applied to a set of MR images, and its performance in terms of gain in SNR, contrast-to-noise ratio (CNR), and resolution loss is compared to that of classical noise filters. The SNR as well as the CNR is improved significantly with minor loss of resolution. Finally, it is shown that the correlation technique can be implemented in a highly efficient way in almost any acquisition procedure of a magnetic resonance imaging system.     

Magnetic resonance imaging with superparamagnetic iron oxide particles for the detection of myocardial reperfusion

The effect of superparamagnetic iron oxide particles on magnetic resonance myocardial signal intensity was examined in order to define the ability of this agent to identify normal, ischemic, and reperfused myocardium. Data were obtained from 6 normal rats (group 1) and from 6 heterotopic isogenic rat heart transplants (group 2) at 4.7 T with a multislice spin-echo sequence. Images were acquired in (a) normal rats before and after the infusion of 36 μmol Fe/kg of AMI-25 (group 1) and (b) rat heart transplants during control, global myocardial ischemia (before and after the injection of 72 μmol Fe/kg of AMI-25), and following reperfusion (group 2). Myocardial signal intensity decreased by 36 ± 4%, p < 0.001, following contrast infusion in normal hearts (group 1). The intensity remained constant in the rat heart transplants (group 2) during coronary occlusion, both before and after the infusion of AMI-25 and decreased by 61 ± 7%, p < 0.001, upon reperfusion. The larger effect of AMI-25 in reperfused as compared to normal myocardium suggests the presence of ischemia-induced hyperemia. There was no significant difference (analysis of variance) among intensities from different myocardial regions in either group at any stage of the experiment. We conclude that the use of AMI-25 permits identification of normal, ischemic, and reperfused myocardium and may therefore be helpful for the early detection of reperfusion following thrombolytic therapy for acute myocardial infarction.     

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.     

Determination of velum opening for french nasal vowels by magnetic resonance imaging

MRI techniques have been used to describe velum opening of French vowels. Data based on 18 joined axial slices of 4 mm thickness were recorded with four subjects. Differences in velum opening are calculated from areas measured in the tract between the lowered velum and the back pharynx wall. Results show that for all subjects, the back vowel / / has the smallest opening, while some variations are observed for the other vowels.     

The application of proton nuclear magnetic resonance imaging for the in vivo characterisation of chemically induced renal lesions in rats over a prolonged time study

Renal cortical and medullary spin-lattice (T₁) relaxation times were measured at various time points over a period of 56 days following the administration of a single i.p. injection of 100 mg/kg 2-bromoethanamine hydrobromide (BEA), 200 mg/kg hexachloro-1,3-butadiene (HCBD) or 100 mg/kg puromycin aminonucleoside (PAN) to male Wistar rats. Administration of a single injection of HCBD caused a dramatic, immediate rise in the cortical T₁ values above control values, and these levels remained elevated until, by Day 28 postinjection the levels were back to control values. Administration of BEA also caused an elevation in cortical T₁ values, but in this case these values remained above control values for the rest of the study. The administration of PAN did not produce any significant increases in cortical T₁ values until 14 days postinjection. The elevated T₁ values remained above control values for the rest of the study. These increases observed in cortical T₁ values appeared to be mirrored by decreases in medullary T₁ values. Increases in cortical T₁ values were accompanied by visual changes in the NMR images and enlargement of the kidneys. The histological findings were consistent with the NMR data, confirming that morphologically the tissues did show a full recovery by Day 28 in the HCBD-treated animals. This was not the case following injection of both BEA and PAN, where necrosis was not reversible and there was no recovery of the tissues.     

A technique for flow-enhanced magnetic resonance angiography of the lower extremities

A two-dimensional, flow-enhanced gradient echo pulse sequence for nuclear magnetic resonance angiography is described. It employs interleaved, presaturated slices to acquire data efficiently on imagers which favor interleaved acquisition over sequential acquisition for multislice imaging. It is useful on any imager when the effective TR is extended to enhance the sensitivity to slow flow. The technique was applied to the region from aortic bifurcation to the iliac bifurcations of three normal volunteers. The right and left common iliac arteries and veins, the separation of the external and internal iliac arteries, and secondary branches were clearly depicted.     

Site location and requirements for the installation of a nuclear magnetic resonance scanning unit

The installation of a nuclear magnetic resonance unit in any diagnostic facility involves certain location and environmental requirements. Based on our experience with the FONAR QED 80 system, we have delineated the major factors which must be considered when planning for such an installation. The major requirements are location and space. Suggested layouts for the suite and the control room are included. Certain environmental specifications will vary depending on the location of the facility and the type of unit installed.