Interictal Positron Emission Tomography Research Articles

Ratio-Images Calculated From Interictal Positron Emission Tomography and Single-Photon Emission Computed Tomography for Quantification of the Uncoupling of Brain Metabolism and Perfusion in Epilepsy

EpilepsiaVolume 41, Issue 1 p. 1560-1566 Free Access Ratio-Images Calculated From Interictal Positron Emission Tomography and Single-Photon Emission Computed Tomography for Quantification of the Uncoupling of Brain Metabolism and Perfusion in Epilepsy First published: 19 September 2008 https://doi.org/10.1111/j.1528-1167.2000.01560.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume41, Issue1December 2000Pages 1560-1566 RelatedInformation

Cortical glucose metabolism positively correlates with gamma-oscillations in nonlesional focal epilepsy

Why do the epileptogenic foci appear hypometabolic on interictal glucose metabolism positron emission tomography (PET) in a substantial proportion of patients with focal epilepsy but appear normo- or even hyper-metabolic in others? Such observations on interictal PET have not been fully explained by the frequency of interictal spike discharges alone. In the present study using digital electrocorticography monitoring system with high-frequency sampling, we determined how well regression models using spectral ECoG measures and spike frequency derived from 651 intracranial electrode sites explained cortical glucose metabolic patterns in six children with nonlesional focal epilepsy. Univariate regression analysis demonstrated that spectral amplitudes at gamma ranges (32–64, 64–100, and 100–200 Hz) were tightly correlated with interictal glucose uptake in the given electrode site in all children. Spike frequency was negatively correlated with interictal glucose uptake in three patients, whose epileptogenic focus appeared hypometabolic and interictal epileptiform discharge often consisted of a spike followed by a subsequent delta-wave. Conversely, spike frequency was positively correlated with interictal glucose uptake in the other three patients, whose epileptogenic foci appeared more hypermetabolic compared to the surrounding regions and associated with frequent interictal spike bursts. The spatial pattern of interictal glucose metabolism in nonlesional focal epilepsy may be better explained by gamma-oscillations derived from epileptiform and physiological neuronal activities rather than the frequency of interictal epileptiform discharges alone.

Functional Imaging in Temporal Lobe Epilepsy

This article highlights the importance of functional imaging methods in the diagnosis and preoperative planning in temporal lobe epilepsy TLE). It starts with a discussion of the role of ictal and interictal single-photon emission computed tomography (SPECT) and interictal positron emission tomography (PET) in lateralizing TLE. The next section discusses the role of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and perfusion MRI, particularly for lateralization of language and memory in TLE patients. The final section explores the relatively new role that the emerging technique of diffusion tensor imaging (DTI) is playing in the evaluation of TLE.

Cortical glucose metabolism correlates negatively with delta‐slowing and spike‐frequency in epilepsy associated with tuberous sclerosis

The mechanism of altered glucose metabolism seen on positron emission tomography (PET) in focal epilepsy is not fully understood. We determined the association between interictal glucose metabolism and interictal neuronal activity, using PET and electrocorticography (ECoG) measures derived from 865 intracranial electrode sites in 11 children with focal epilepsy associated with tuberous sclerosis complex (TSC) (age: 0.5-16 years) undergoing epilepsy surgery. A multiple linear regression analysis was applied to each patient, to determine whether the glucose uptake at each electrode site on interictal PET was predicted by ECoG amplitude powers and interictal spike-frequency measured in the given electrode site. The regression slopes as well as R-square values (an indicator of fitness of the regression models) were finally averaged across the 11 patients. The mean regression slope for delta amplitude power was -0.0025 (95% CI: -0.0045 to -0.0004; P = 0.02 based on one-sample t-test) and that for spike frequency was -0.023 (95% CI: -0.042 to -0.0038; P = 0.02). On the other hand, the mean regression slopes for the remaining ECoG amplitude powers (theta, alpha, sigma, beta, and gamma activities) were not significantly different from zero. The mean R-square value was 0.39. These results suggest that increased delta-slowing and frequent spike activity were independently and additively associated with glucose hypometabolism in children with focal epilepsy associated with TSC. Association between frequent interictal spike activity and low glucose metabolism may be attributed to slow-wave components following spike discharges on ECoG recording, and a substantial proportion of the variance in regional glucose metabolism on PET could be explained by electrophysiological traits derived from conventional subdural ECoG recording.

Evaluating the accuracy of perfusion/metabolism (SPET/PET) ratio in seizure localization

The uncoupling between brain perfusion and metabolism was evaluated as a potential tool for seizure localization by creating an interictal SPET divided by interictal PET functional ratio-image and by evaluating its sensitivity and specificity to areas subsequently surgically resected. The uncoupling between brain perfusion and metabolism was evaluated through the creation of a functional SPET/PET ratio-image relying on interictal single-photon emission computed tomography (SPET) and positron emission tomography (PET) scans in epilepsy patients. The uncoupling of these two physiological brain functions has been demonstrated to be a characteristic of epileptogenic tissue in temporal lobe epilepsy and could potentially serve as a diagnostic measure for localization of seizure onset areas in the brain. The accuracy of hemispheric localization, sensitivity, and specificity of perfusion to metabolism ratio-images were evaluated as compared to standard methods of PET reading. Interictal HMPAO-SPET and FDG-PET scans were obtained from 21 patients who then went on to remain seizure free for a minimum of 1 year post surgical resection. Using Statistical Parametric Mapping (SPM2), the SPET and PET scans were spatially registered and spatially normalized to a standard template (geometric warping). A functional image was created by calculating the ratio of perfusion to metabolism. Discrete areas of uncoupling in the ratio-images were selected, quantified, and compared to visually interpreted PET readings as well as the actual site of subsequent surgical resection. Localization was determined by comparing the hemispheric location of these areas to sites of surgical resection. Sensitivity and specificity of ratio-images and PET readings were calculated by dividing the brains into four sections per hemisphere. When compared to known sites of successful surgical resection, the pre-surgical visually interpreted PET readings had a correct hemispheric localization in 69.6% of cases, while the regions of uncoupling selected in the pre-surgical ratio-images had a correct hemispheric localization of 82.6%. In addition, the regional sensitivity of visually interpreted PET readings was 63.0% with a specificity of 95.7%, while the sensitivity of the ratio-images was 68.0% with a specificity of 96.0%. Compared to the PET readings, the ratio-images yielded similar sensitivity and specificity measures, but had an improved hemispheric localization. Hence, ratio-images may be a valuable diagnostic tool in the hemispheric localization, which could enhance the use of PET readings alone.

5-HT 1A Receptor Binding in Temporal Lobe Epilepsy Patients With and Without Major Depression

Major depressive disorder (MDD) is the most common comorbid psychiatric condition associated with temporal lobe epilepsy (TLE). Preclinical and clinical studies suggest that 5-HT(1A) receptors play a role in the pathophysiology of both TLE and MDD. There is preliminary evidence for an association between decreased 5-HT(1A) receptor binding in limbic brain areas and affective symptoms in TLE patients. The objective of this study was to compare 5-HT(1A) receptor binding between TLE patients with and without MDD. For the first time, 5-HT(1A) receptor binding was measured in a sample large enough to permit sensitive comparisons between TLE patients with and without comorbid MDD diagnosed by clinical and structured psychiatric interviews. Thirty-seven epilepsy patients with temporal lobe foci confirmed by ictal video-electroencephalogram (EEG) monitoring were recruited from the Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke. We performed interictal positron emission tomography scanning, with [(18)F]FCWAY, a fluorinated derivative of WAY100635, on a GE Medical Systems (Waukesha, Wisconsin) Advance scanner with continuous EEG monitoring. The 5-HT(1A) receptor binding was estimated by partial volume-corrected [(18)F]FCWAY V/f(1) values. In addition to decreased 5-HT(1A) receptor binding in the epileptic focus itself, comorbid MDD was associated with a significantly more pronounced reduction in 5-HT(1A) receptor binding in TLE patients, extending into non-lesional limbic brain areas outside the epileptic focus. Focus side and the presence of mesial temporal sclerosis were not associated with the presence of comorbid depression. Reductions in 5-HT(1A) receptor binding might help elucidate the neurobiological mechanisms underlying the TLE-MDD comorbidity.

The use of SPECT and PET in routine clinical practice in epilepsy

The aim of this article is to give a subjective review of the usefulness of single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging in clinical practice in epilepsy for 2007. Both ictal perfusion SPECT and interictal fluorodeoxyglucose PET can provide new information in the presurgical evaluation of intractable partial epilepsy. These functional imaging modalities reflect dynamic seizure-related changes in cerebral cellular functions. Although asymmetry of fluorodeoxyglucose PET metabolism has been useful to localize the epileptic temporal lobe, which tends to be more hypometabolic than the contralateral one, both frontal lobes are more hypometabolic than the epileptic temporal lobe, and may represent a region of 'surround inhibition'. Due to its low temporal resolution, ictal perfusion SPECT hyperperfusion patterns often contain both the ictal onset zone and propagation pathways. These patterns often have a multilobulated 'hourglass' appearance. The largest and most intense hyperperfusion cluster often represents ictal propagation, and does not always need to be resected in order to render a patient seizure free. Optimized interictal FDG-PET and ictal perfusion SPECT as part of a multimodality imaging platform will be important tools to better understand the neurobiology of epilepsy and to better define the epileptogenic, ictal onset, functional deficit and surround inhibition zones in refractory partial epilepsy.

Focal Cortical Malformations Can Show Asymmetrically Higher Uptake on Interictal Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography (PET)

Interictal fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a component of the presurgical evaluation of patients with medically intractable epilepsy, including patients with malformations of cortical development. The authors describe 3 cases of focal cortical malformations that displayed asymmetrically higher uptake on FDG-PET performed in the interictal state in patients undergoing evaluation for possible focal resection for refractory localization-related epilepsy. The evaluation included routine and prolonged video electroencephalography (EEG), magnetic resonance imaging (MRI), interictal FDG-PET with concurrent EEG, and single-photon emission computed tomography (SPECT). All 3 patients had focal cortical malformations on MRI corresponding to regions of asymmetrically higher uptake on FDG-PET. EEG confirmed that the FDG-PET studies were performed in the interictal state. The lesions included a large region of subcortical heterotopia in the right frontal lobe, a left temporal lobe dysplasia, and a region of subcortical heterotopia in the right occipital lobe. In both patients with subcortical heterotopia, there were other focal regions of cortical malformation that were not associated with abnormal or asymmetric uptake on FDG-PET. Previous reports describe decreased uptake on interictal PET in most cases of focal cortical malformations. Normal to increased uptake has been reported with band heterotopia. The authors demonstrate that other types of focal malformations of cortical development, including focal subcortical heterotopia and lobar dysplasia, can be associated with asymmetrically higher uptake on interictal FDG-PET.

Avaliação pré-cirúrgica de epilepsia neocortical de lobo temporal com utilização de FDG-18F SPECT: relato de caso

INTRODUÇÃO: Muitos portadores de epilepsias parciais não apresentam foco epileptogênico facilmente identificado na investigação com EEG de superfície e ressonância magnética (RM). Nestes casos o uso de técnicas de neuroimagem funcional como a tomografia por emissão de pósitrons (PET) interictal e a tomografia por emissão de fóton único (SPECT) ictal devem ser considerados, visando evitar a colocação de eletrodos profundos em alguns casos ou guiar o posicionamento destes em outros. O exame de PET, no entanto, não é disponível em grande parte dos centros de epilepsia, principalmente por seu alto custo. OBJETIVO: O nosso objetivo é demonstrar que a utilização de FDG-18F SPECT interictal pode ser uma boa alternativa ao uso do PET na localização do foco e planejamento cirúrgico. MATERIAIS E MÉTODOS: Relato de uma paciente com epilepsia parcial de lobo temporal neocortical, refratária a tratamento clínico, com RM normal e EEG ictal sem localização definida do foco epileptogênico. RESULTADOS: Após a extensa investigação pré cirúrgica sem resultados satisfatórios optou-se pela realização de exame de medicina nuclear FDG-18F SPECT interictal. O exame demonstrou hipometabolismo na região anterior das porções mesial e lateral do lobo temporal direito. A paciente foi, então, submetida à ressecção destas áreas e permanece com excelente controle de crises (Engel IB) 24 meses após a cirurgia. CONCLUSÃO: O FDG-18F SPECT pode tornar-se um substituto do PET nos locais onde esta tecnologia não é disponível.

Functional neuroimaging in the preoperative evaluation of children with drug-resistant epilepsy

FUNCTIONAL NEUROIMAGING: Although the primary imaging modality in the management of epilepsy is magnetic resonance imaging MRI, functional neuroimaging with positron-emission tomography (PET) and single photon emission computed tomography (SPECT) often provides complementary information and, in a number of situations, provides unique information that cannot be obtained with MRI. The most commonly used PET tracers used for epilepsy evaluation are 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG) and [(11)C]flumazenil (FMZ). Recently, interictal PET with alpha-[(11)C]methyl-L: -tryptophan was found to be highly specific for the epileptic focus and can differentiate between epileptogenic and nonepileptogenic lesions in the same patient (e.g., in patients with tuberous sclerosis). In this review, we discuss clinical applications of these three PET tracers in drug-resistant temporal and extratemporal lobe epilepsy, selected epilepsy syndromes of childhood, lesional and nonlesional epilepsy, and the challenges of imaging secondary epileptic foci. A brief discussion of SPECT applications in epilepsy is also included. With further development of new tracers highly sensitive and specific for epileptogenic brain regions, the presurgical evaluation of refractory epilepsy will be greatly facilitated. Approximately 0.5 to 1.0% of the population suffer from epilepsy, of which 15-20% are intractable. Infants and children, whose seizures have a focal onset are refractory to anticonvulsants and are prolonged, tend to have the worst cognitive outcome [Meador KJ, Neurology 58 (Suppl 5):S21-S26, 2002]. Seizures themselves affect the developing brain and contribute to an adverse neurologic outcome (Holmes, Pediatric Neurology 33:1-110, 2005). Therefore, in treating children with intractable epilepsy, it is important to consider seizure control and to give allowance for normal cognitive development.

Tc-99m ECD SPECT and FDG PET in Partial Status Epilepticus Resulting From Cerebral Sparganosis

Sparganosis is a rare intracranial parasitic disease caused by the infestation of a plerocercoid tapeworm larva of Spirometra mansoni. According to previous studies of cerebral sparganosis, common clinical features are seizure, hemiparesis, and chronic headache. We report a case of cerebral sparganosis in which the patient presented with a first attack of sustained unilateral jerky involuntary movements that concluded as a partial status epilepsy based on the ictal and interictal brain Tc-99m ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) and interictal FGD positron emission tomography (PET) studies.

Positron emission tomography and single photon emission computed tomography in epilepsy care

Radiopharmaceutical brain imaging is clinically applied in planning resective epilepsy surgery. Cerebral sites of seizure generation-propagation are highly associated with regions of hyperperfusion during seizures, and with glucose hypometabolism interictally. For surgical planning in epilepsy, the functional imaging modalities currently established are ictal single photon emission computed tomography (SPECT) with [ 99mTc]technetium-hexamethylpropyleneamine oxime (HMPAO) or with [ 99mTc]technetium-ethylene cysteine dimer (ECD), and interictal positron emission tomography (PET) with 2-[ 18F]fluoro-2-deoxyglucose (FDG). Ictal SPECT and interictal FDG PET can be used in presurgical epilepsy evaluations to reliably: 1) determine the side of anterior temporal lobectomy, and in children the area of multilobar resection, without intracranial electroencephalographic recording of seizures; 2) select high-probability sites of intracranial electrode placement for recording ictal onsets; and, 3) determine the prognosis for complete seizure control following anterior temporal lobe resection. Coregistration of a patient's structural (magnetic resonance) and functional images, and statistical comparison of a patient's data with a normal data set, can increase the sensitivity and specificity of these SPECT and PET applications to the presurgical evaluation. © 2003 Elsevier Inc. All rights reserved.

Orbito-frontal epilepsy masquerading as temporal lobe epilepsy—a case report

Temporal lobectomy fails to control seizures in a considerable percentage of patients who do not have hippocampal sclerosis. One theoretical reason for failure of surgery is that some of these patients may in fact have extratemporal epilepsy. We present a 28-year-old woman with clinical and scalp electroencephalogram (EEG) evidence of right temporal lobe epilepsy (TLE) supported by functional imaging with interictal positron emission tomography (PET) and ictal single-photon emission computerized tomography (SPECT). An invasive EEG monitoring was prompted by the discovery of a small right orbito-frontal lesion on MRI. Monitoring documented seizure onset at the lesion, with rapid right temporal involvement. The patient was almost seizure-free after a lesionectomy. The index of suspicion of orbito-frontal epilepsy should be high in patients with apparent TLE when the scalp EEG and neuroimaging data are not congruent, or if temporal lobe pathology cannot be identified on structural imaging.

Ratio-images calculated from interictal positron emission tomography and single-photon emission computed tomography for quantification of the uncoupling of brain metabolism and perfusion in epilepsy.

Image processing techniques were applied to interictal positron emission tomography (PET) and single-photon emission computed tomography (SPECT) brain images to aid in the localization of epileptogenic foci by calculating a functional image that represents the degree of coupling between perfusion and metabolism. Uncoupling of these two functions has been demonstrated to be a characteristic of epileptogenic tissue in temporal lobe epilepsy and has the potential to serve as a diagnostic measure for localization in other areas as well. Interictal PET ((18)F-FDG) and interictal SPECT ((99m)Tc-HMPAO) scans were acquired from 11 epilepsy patients. The metabolism and perfusion images were three-dimensionally spatially registered, and a functional ratio-image was computed. These functional maps are overlaid onto a three-dimensional rendering of the same patient's magnetic resonance imaging anatomy. In all patients, an average uniform perfusion-to-metabolism ratio showed approximately constant values throughout most of the whole brain. However, the epileptogenic area (confirmed on surgery) demonstrated an area of elevated perfusion/metabolism in the grey matter. Although hypometabolism in the PET image was observed in most of these patients, the calculation of a functional ratio-image demonstrated localized foci that in some cases could not be observed on the PET image alone. The ratio-image also yields a quantitative measure of the uncoupling phenomenon.

Is epileptogenic cortex truly hypometabolic on interictal positron emission tomography?

Positron emission tomography (PET) of glucose metabolism is often applied for the localization of epileptogenic brain regions, but hypometabolic areas are often larger than or can miss epileptogenic cortex in nonlesional neocortical epilepsy. The present study is a three-dimensional brain surface analysis designed to demonstrate the functional relation between glucose PET abnormalities and epileptogenic cortical regions. Twelve young patients (mean age, 10.8 years) with intractable epilepsy of neocortical origin underwent chronic intracranial electroencephalographic monitoring. The exact location of the subdural electrodes was determined on high-resolution three-dimensional reconstructed magnetic resonance imaging scan volumes. The electrodes were classified according to their locations over cortical areas, which were defined as hypometabolic, normometabolic, or at the border between hypometabolic and normal cortex (metabolic "border zones") based on interictal glucose PET. Electrodes with seizure onset were located over metabolic border zones significantly more frequently than over hypometabolic or normometabolic regions. Seizure spread electrodes also more frequently overlay metabolic border zones than hypometabolic regions. These findings suggest that cortical areas with hypometabolism should be interpreted as regions mostly not involved in seizure activity, although epileptic activity commonly occurs in the surrounding cortex. This feature of hypometabolic cortex is remarkably similar to that of structural brain lesions surrounded by epileptogenic cortex. Cortical areas bordering hypometabolic regions can be highly epileptogenic and should be carefully assessed in presurgical evaluations.

Is epileptogenic cortex truly hypometabolic on interictal positron emission tomography?

Is epileptogenic cortex truly hypometabolic on interictal positron emission tomography?

Temporal Lobe Hypometabolism Ipsilateral to a Hypothalamic Mass: Relationship to Gelastic Seizures

The purpose of this study was to investigate metabolic changes associated with a right hypothalamic mass in a 26-year-old gelastic seizure patient. Positron emission tomography (PET) imaging of the brain was performed in the interictal state using 18F-fluorodeoxyglucose (18F-FDG) in this patient. Temporal lobe hypometabolism was noted ipsilateral to the hypothalamic lesion. The mass itself had little to no uptake of 18F-FDG. This is the first known PET imaging report of temporal lobe hypometabolism ipsilateral to a presumed hypothalamic hamartoma causing gelastic seizures. Further studies are needed in other patients to test whether interictal PET imaging may help plan the removal of epileptogenic hypothalamic lesions.

Planned Ictal FDG PET Imaging for Localization of Extratemporal Epileptic Foci

This work demonstrates the feasibility of planned ictal positron emission tomography (PET) with [18F]fluoro-2-deoxy-glucose (FDG) for localization of epileptic activity in patients with frequent partial seizures of extratemporal origin. Ictal PET imaging was performed in four patients (two men and two women, ages 28-61) with continuous or very frequent (every 3-15 min) partial seizures. All patients had abnormalities apparent on magnetic resonance (MR) or computed tomographic (CT) imaging, two with extensive brain lesions that precluded precise localization of the seizure focus with interictal PET or single-photon emission tomography (SPECT) imaging. Ictal PET imaging demonstrated a restricted area of focal hypermetabolism concordant with surface electroencephalographic (EEG) recording in all cases. The PET images were registered to MR imaging data for further anatomic localization of hypermetabolic regions in three cases. The ictal PET data were used to guide neurosurgical intervention in one case. We conclude that planned ictal PET imaging may be a useful and potentially superior approach to ictal SPECT for identifying the epileptic focus in a selected group of patients with continuous or frequent simple partial seizures.

Noninvasive protocol for surgical treatment of focal epilepsies

We present a non-invasive epilepsy surgery protocol, which includes EEG-video-monitoring, magnetic resonance imaging (MRI), interictal positron emission tomography (PET) and ictal single photon emission computerized tomography (SPECT). According to this non-invasive protocol 50 of 173 patients with medically intractable focal epilepsy underwent resective surgery. The localization of the epileptogenic zone was based on the congruence of the localizing results of EEG-video-monitoring, MRI, interictal PET and ictal SPECT. 46 (92%) of the patients had temporal and 4 (8%) had extratemporal epilepsies. 78% (n = 39) of all patients operated according to our non-invasive protocol were postoperatively completely or almost seizure free. Extramesiotemporal resections could be carried out without invasive EEG-recording if the epileptogenic zone was not adjacent to the eloquent cortex. We conclude from our results that in a considerable number of patients with medically intractable particularly temporal focal epilepsies, resective epilepsy surgery can be based on non-invasive EEG-evaluations and the risk of invasive recordings can be avoided.

A case of parietal lobe epilepsy with distinctive clinical and neuroradiological features

We present a case of parietal lobe epilepsy, the epileptogenic focus of which was conspicuously demonstrated on magnetoencephalography (MEG). The remarkable fluctuation in the seizure frequency and the presence of atonic seizures were suggestive of atypical partial benign epilepsy of childhood (APBEC). An interictal positron emission tomography (PET) scan performed during the cluster of fits revealed hypermetabolism around the epileptogenic focus, which might be related to the marked tendency of clustering of seizures in this patient.