Simultaneous surface registration of ictal and interictal SPECT and magnetic resonance images for epilepsy studies

BACKGROUND: Subtraction of ictal and interictal single photon emission computed tomography (SPECT) images is known to be successful in localizing the seizure focus in the pre-surgical evaluation of patients with partial epilepsy. A computer-aided methods for producing subtraction ictal SPECT co-registered to the magnetic resonance image (MRI) (the SISCOM method) is commonly used. The two registrations involved in SISCOM are (1) between the ictal-interictal SPECT images, which was shown to be the more critical, and (2) between the ictal image and MRI. OBJECTIVE: To improve the accuracy of ictal-interictal registration in SISCOM by registering all three images (ictal, interictal SPECT, MRI) simultaneously. METHODS: The registration problem is formulated as the minimization of a cost function between three surfaces. Then, to achieve a global minimum of this cost function, the Powell algorithm with randomly distributed initial configurations is used. This technique is tested by a realistic simulation study, a phantom study and a patient study. RESULTS: The results of the simulation study demonstrate that, in surface-based registration, the triple-registration method results in a smaller ictal-interictal SPECT registration error than the pair-wise registration method (P<0.05) for a range of values of the cost-function parameter. However, the improved registration error is still larger than that obtained by the normalized mutual information method (P<0.001), which is a voxel-based registration algorithm. The phantom and patient studies reveal no observable difference between registration results. CONCLUSIONS: Although the improved accuracy of triple registration is slightly worse than voxel-based registration, it will soon be possible to apply the results of this study in research utilizing the triple-registration principle to improving voxel-based results of ictal-interictal registration.     

Use of subtraction ictal SPECT co-registered to MRI for optimizing the localization of seizure foci in children.

Ictal SPECT studies are increasingly used to localize seizure foci in children with refractory epilepsy, but few studies have reported on ictal-interictal subtraction images co-registered to MRI at this age. METHODS: Twenty-seven children with partial epilepsy (aged 3 mo-18 y) underwent ictal ethyl cysteinate dimer (ECD) SPECT (20 mCi/1.73 m2) combined with video-electroencephalography (EEG) and interictal ECD SPECT followed 2 d later by three-dimensional MRI. Ictal-interictal and interictal-ictal subtraction images were computed by registering and normalizing the ictal to the interictal SPECT scans for each child. The ictal, interictal SPECT and subtraction images were registered to each child's MRI. Difference images (ictal-interictal) were then superimposed on MRI for anatomic localization of the perfusion changes. Intra- and interobserver reproducibility and "facility of interpretation" of overlay images were compared with standard analysis of the non-coregistered ictal and interictal scans. RESULTS: Overlay images allowed the detection of at least one hyperperfused focus in 93% of the children, compared with 74% using ictal and interictal scans separately. Seizure onset was suspected clinically, on EEG or on MRI in 20 children. Overlay images were concordant (n = 11) or larger (n = 7) than the suspected focus in 18 of 20 (90%), whereas these images failed to show any abnormality in 1 child and were discordant with MRI in another patient. In the remaining 7, images showed cortical localization in 6 patients. Among the 5 patients who underwent electrocorticography, overlay images were concordant in 3, larger in 1 and absent in 1. The intra- and interobserver reproducibility and facility of interpretation were significantly higher using overlay images than standard analysis, even when ictal and interictal SPECT were co-registered. CONCLUSION: The co-registration of ictal-interictal subtraction SPECT images to MRI seems to be a helpful technique in localizing the onset of seizure and guiding the intracranial recording in childhood epilepsy. Moreover, this method improves sensitivity, enhances intra- and interobserver reproducibility and makes interpretation easier.     

Computer-aided intrapatient comparison of brain SPECT images: the gray-level normalization issue applied to children with epilepsy.

A tool was developed for automated intrapatient comparison of brain SPECT images, with specific emphasis on gray-level normalization. METHODS: Ictal and interictal (99m)Tc-ethyl cysteinate dimer SPECT images were acquired for 6 children with partial epilepsy (age range, 2-10 y). For each patient, 3-dimensional rigid geometric ictal-to-interictal image registration optimizing different classic criteria (correlation coefficient, ratio uniformity) in a multiscale translation-rotation 6-parameter space was first performed. Gray-level normalization was then performed with different methods, using a 1- or 2-parameter linear model. In the 1-parameter case, the scaling factor was equal to the interictal-to-ictal ratio of the maximum, mean, or median values calculated within different reference volumes (whole brain or cerebellum) or obtained by linear regression between ictal and interictal counts in the brain or by maximizing a robust criterion, the number of deterministic sign changes in the subtraction images. In the 2-parameter case, the scaling factor and additive constant were estimated using these last 2 methods. For each patient, registration validity and normalization plausibility were assessed by considering the correlation scatterplot together with the different normalization lines and by comparing interictal and registered normalized ictal images using a twin display (with isocontours) in the 3 orthogonal planes. Three-dimensional volumes of interest could be selected on coupled interictal-subtraction images for further focused numeric comparison. RESULTS: After a satisfactory and stable geometric registration with both criteria, the different normalization methods led to similar subtraction images for 5 of 6 patients, except the maxima ratio, which gave noticeably different results in 2 patients. For the remaining patient, with highly dissimilar ictal-interictal images, the maxima ratio normalization was obviously wrong and the other 1-parameter methods probably better depicted the data than did the 2-parameter methods. CONCLUSION: When comparing intrapatient brain SPECT images, one should be aware of the potential impact of the gray-level normalization method on clinical interpretation. For ictal-interictal images, simple robust scaling should be recommended. In particular, image maximum should generally not be considered a valid reference, and no additive constant is needed in the linear gray-level normalization model.     

Transmission imaging for registration of ictal and interictal single-photon emission tomography, magnetic resonance imaging and electroencephalography

A method developed for registration of ictal and interictal single-photon emission tomography (SPET), magnetic resonance imaging (MRI) and electroencephalography (EEG) is described. For SPET studies, technetium-99m ethyl cysteinate dimer (ECD) was injected intravenously while the patient was monitored on video-EEG to document the ictal or interictal state. Imaging was performed using a triple-head gamma camera equipped with a transmission imaging device using a gadolinium-153 source. The images (128x128 pixels, voxel size 3.7x3.7x3.6 mm3) were reconstructed using an iterative algorithm and postfiltered with a Wiener filter. The gold-plated silver electrodes on the patient's scalp were utilized as markers for registration of the ictal and interictal SPET images, as these metallic markers were clearly seen on the transmission images. Fitting of the marker sets was based on a non-iterative least squares method. The interictal SPET image was subtracted from the ictal image after scaling. The T1-weighted MPRAGE MR images with voxel size of 1.0x1.0x1.0 mm3 were obtained with a 1.5-T scanner. For registration of MR and subtraction SPET images, the external marker set of the ictal SPET study was fitted to the surface of the head segmented from MR images. The SPET registration was tested with a phantom experiment. Registration of ictal and interictal SPET in five patient studies resulted in a 2-mm RMS residual of the marker sets. The estimated RMS error of registration in the final result combining locations of the electrodes, subtraction SPET and MR images was 3-5 mm. In conclusion, transmission imaging can be utilized for an accurate and easily implemented registration procedure for ictal and interictal SPET, MRI and EEG.     

Ictal SPECT in neocortical epilepsies: clinical usefulness and factors affecting the pattern of hyperperfusion

Introduction: The aims of this analysis were to: (1) determine the value of ictal SPECT in the localization of neocortical epileptogenic foci, (2) evaluate the relationships between the results of ictal SPECT and other potential affecting factors, and (3) compare traditional visual analysis and the subtraction method.Methods: We retrospectively analyzed 81 consecutive patients with neocortical epilepsy who underwent epilepsy surgery and achieved a favourable surgical outcome, including 36 patients with normal MRI. Side-by-side visual analysis and subtraction images were classified as correctly localizing,correctly lateralizing, or non-localizing/non-lateralizing images according to the resected lobe.Results: Side-by-side visual analysis and subtraction SPECT correctly localized the epileptogenic lobe in 58.9% and 63.0% of patients, respectively. The two methods were complementary and the diagnostic sensitivity of ictal SPECT using the two methods was 79.0%. Ictal SPECT using the visual method correctly localized the epileptogenic lobe more frequently in patients with a localizing pattern of ictal scalp EEG at the time of radioligand injection. When using subtraction images, an injection delay of less than 20 s after seizure onset was significantly correlated with correct localization. The subtraction method was superior to the visual method for localizing frontal lobe epilepsy (FLE) and parietal lobe epilepsy (PLE), and in patients with non-localizing/non-lateralizing EEG at onset.Conclusions: Ictal SPECT analyses using visual and subtraction methods are useful and complementary for the localization of the epileptogenic foci of neocortical epilepsy. Early radioligand injection and ictal EEG patterns are related to ictal SPECT localization. The subtraction method may be more useful in some epileptic syndromes.     

Contribution of subtraction ictal SPECT coregistered to MRI to epilepsy surgery: a multicenter study

Objective  A multicenter prospective study was performed to assess the additional value of a subtraction ictal SPECT coregistered to MRI (SISCOM) technique to traditional side-by-side comparison of ictal- and interictal SPECT images in epilepsy surgery. Methods  One hundred and twenty-three patients with temporal and extratemporal lobe epilepsy who had undergone epilepsy surgery after evaluation of scalp ictal and interictal electroencephalogram (EEG), MRI, and ictal and interictal SPECT scans were followed up in terms of postsurgical outcome for a period of at least 1 year. Three reviewers localized the epileptogenic focus using ictal and interictal SPECT images first by side-by-side comparison and subsequently by SISCOM. Concordance of the localization of the epileptogenic focus by SPECT diagnosis with the surgical site and inter-observer agreement between reviewers was compared between side-by-side comparison and SISCOM. Logistic regression analysis was performed in predicting the surgical outcome with the dependent variable being the achievement of a good postsurgical outcome and the independent variables using the SISCOM, side-by-side comparison of ictal and interictal SPECT images, MRI, and scalp ictal EEG. Results  The SISCOM presented better concordance in extratemporal lobe epilepsy and less concordance in temporal lobe epilepsy than side-by-side comparison. Inter-observer concordance was higher in SISCOM than in side-by-side comparison. Much higher concordance of the epileptogenic focus by SPECT diagnosis with the surgical site was obtained in patients with good surgical outcome than in those with poor surgical outcome. These differences in concordance between good and poor surgical outcomes were greater in SISCOM than in side-by-side comparison. Logistic regression analysis showed the highest odds ratio of 12.391 (95% confidence interval; 3.319, 46.254) by SISCOM evaluation for concordance of the epileptogenic focus with the surgical site in predicting good surgical outcome. Conclusions  A SISCOM technique of ictal and interictal SPECT images provides higher predictive value of good surgical outcome and more reliability on the diagnosis of the epileptogenic focus than side-by-side comparison in medically intractable partial epilepsy.     

Transmission imaging for registration of ictal and interictal single-photon emission tomography, magnetic resonance imaging and electroencephalography

A method developed for registration of ictal and interictal single-photon emission tomography (SPET), magnetic resonance imaging (MRI) and electroencephalography (EEG) is described. For SPET studies, technetium-99m ethyl cysteinate dimer (ECD) was injected intravenously while the patient was monitored on video-EEG to document the ictal or interictal state. Imaging was performed using a triple-head gamma camera equipped with a transmission imaging device using a gadolinium-153 source. The images (128×128 pixels, voxel size 3.7×3.7×3.6 mm³) were reconstructed using an iterative algorithm and postfiltered with a Wiener filter. The gold-plated silver electrodes on the patient’s scalp were utilized as markers for registration of the ictal and interictal SPET images, as these metallic markers were clearly seen on the transmission images. Fitting of the marker sets was based on a non-iterative least squares method. The interictal SPET image was subtracted from the ictal image after scaling. The T1-weighted MPRAGE MR images with voxel size of 1.0×1.0×1.0 mm³ were obtained with a 1.5-T scanner. For registration of MR and subtraction SPET images, the external marker set of the ictal SPET study was fitted to the surface of the head segmented from MR images. The SPET registration was tested with a phantom experiment. Registration of ictal and interictal SPET in five patient studies resulted in a 2-mm RMS residual of the marker sets. The estimated RMS error of registration in the final result combining locations of the electrodes, subtraction SPET and MR images was 3–5 mm. In conclusion, transmission imaging can be utilized for an accurate and easily implemented registration procedure for ictal and interictal SPET, MRI and EEG. Received 20 September and in revised form 16 October 1999     

Sensitivity and specificity of quantitative difference SPECT analysis in seizure localization.

True ictal SPECT can accurately demonstrate perfusion increases in the epileptogenic area but often requires dedicated personnel waiting at the bedside to accomplish the injection. We investigated the value of perfusion changes as measured by ictal or immediate postictal SPECT in localizing the epileptogenic region in refractory partial epilepsy. METHODS: Quantitative perfusion difference images were calculated by registering, normalizing and subtracting ictal (or immediate postictal) from interictal SPECT for 53 patients with refractory epilepsy. Perfusion difference SPECT results were compared with visually interpreted SPECT, scalp electroencephalography (EEG), MRI, PET and intracranial EEG. RESULTS: In 43 patients (81%), discrete areas of increased perfusion (with ictal injections) or decreased perfusion (with postictal injections) were noted. Interictal scalp EEG was localizing in 28 patients (53%), ictal scalp EEG was localizing in 35 patients (66%) and intracranial EEG was localizing in 22 patients (85%) (of 26 patients who underwent invasive study). MRI was localizing in 34 patients (64%), PET was localizing in 32 of 45 patients (71%), interictal SPECT was localizing in 26 patients (49%) and peri-ictal SPECT (visual interpretation) was localizing in 30 patients (57%). By comparison with an intracranial EEG standard of localization, SPECT subtraction analysis had 86% sensitivity and 75% specificity. CONCLUSION: Our data provide evidence that SPECT perfusion difference analysis has higher sensitivity and specificity than any other noninvasive localizing criterion and can localize epileptogenic regions with accuracy comparable with that of intracranial EEG. To obtain these results, one must apply knowledge of the timing of the ictal injection relative to seizure occurrence.     

癫痫发作期与发作间期脑血流灌注显像减影法定位致痫灶的价值

目的:研究癫痫发作期与发作间期脑血流灌注显像减影法定位致癫灶的价值.材料和方法:14例癫痫患者在癫痫发作期和发作间期分别进行脑血流灌注显像,两次所得图像进行空间匹配后相减得到减影像,并与EEG、MRI、手术结果及临床表现比较.结果:与发作间期相比,13/14例发作期局部脑血流有不同程度的增高,减影像可显示血流改变的具体部位及形态;1例发作期血流低于发作间期,但病灶区表现明显.手术后病灶病理诊断包括胶质细胞增生、疤痕组织及胶质细胞瘤.术后13例患者发作次数明显减少,1例效果不显著.结论:发作期与发作间期显像减影法定位致痫灶有较高的准确性,有助于术前制定合理的手术方案.     

Evaluation of ictal brain SPET using statistical parametric mapping in temporal lobe epilepsy

An automated voxel-based analysis of brain images using statistical parametric mapping (SPM) is accepted as a standard approach in the analysis of activation studies in positron emission tomography and functional magnetic resonance imaging. This study aimed to investigate whether or not SPM would increase the diagnostic yield of ictal brain single-photon emission tomography (SPET) in temporal lobe epilepsy (TLE). Twenty-one patients (age 27.14 +/- 5.79 years) with temporal lobe epilepsy (right in 8, left in 13) who had a successful seizure outcome after surgery and nine normal subjects were included in the study. The data of ictal and interictal brain SPET of the patients and baseline SPET of the normal control group were analysed using SPM96 software. The t statistic SPM?t? was transformed to SPM?Z? with various thresholds of P<0.05, 0.005 and 0.001, and corrected extent threshold P value of 0.05. The SPM data were compared with the conventional ictal and interictal subtraction method. On group comparison, ictal SPET showed increased uptake within the epileptogenic mesial temporal lobe. On single case analysis, ictal SPET images correctly lateralized the epileptogenic temporal lobe in 18 cases, falsely lateralized it in one and failed to lateralize it in two as compared with the mean image of the normal group at a significance level of P<0.05. Comparing the individual ictal images with the corresponding interictal group, 15 patients were correctly lateralized, one was falsely lateralized and four were not lateralized. At significance levels of P<0.005 and P<0.001, correct lateralization of the epileptogenic temporal lobe was achieved in 15 and 13 patients, respectively, as compared with the normal group. On the other hand, when comparison was made with the corresponding interictal group, only 7 out of 21 patients were correctly lateralized at the threshold of P<0.005 and five at P<0.001. The result of the subtraction method was close to the single case analysis on SPM at P<0.05. However, at higher thresholds (P<0.005 and 0.001) the subtraction method was comparable to the SPM results only when individual ictal images were compared with the normal control group, and not when comparison was with the interictal group. It is concluded that SPM is an alternative diagnostic method for the localization or lateralization of the seizure focus in temporal lobe epilepsy and that interictal SPET could be omitted if a normal brain SPET database were to be established. The medical cost of seizure localization would thereby be reduced.     

Neuronuclear assessment of patients with epilepsy

Epilepsy is a common chronic neurological disorder that is controlled with medication in approximately 70% of cases. When partial seizures are recurrent despite the use of antiepileptic drugs, resection of the epileptogenic cortex may be considered. Nuclear medicine plays an important role in the presurgical assessment of patients with refractory epilepsy. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques are used to determine the seizure onset zone, which needs to be resected to render a patient seizure free. Correct localization of the ictal onset zone with the use of SPECT or PET is associated with a better surgical outcome. Ictal perfusion SPECT imaging with (99m)Tc-ethyl cysteinate dimer (ECD) or (99m)Tc-hexamethylpropyleneamine oxime (HMPAO) enables one to detect the seizure onset zone in a majority of cases, especially in patients with temporal lobe epilepsy. Interictal SPECT imaging, which is more widely available, is unreliable to determine the ictal onset zone and is usually only used for comparison with ictal SPECT images. Assessment of the ictal onset zone using subtracted ictal and interictal studies, overlayed on structural imaging has proven to be more sensitive and more specific compared with visual assessment. Video-electroencephalography monitoring in combination with ictal SPECT imaging, however, is only available in specialized centers. It is important to inject the perfusion tracer as early as possible after the beginning of a seizure and to be aware of patterns of seizure propagation. Interictal (18)F-fluorodeoxyglucose (FDG)-PET is routinely used to detect brain areas of hypometabolism, which usually encompass, but tend to be larger than, the seizure onset zone. Also, for assessment of FDG-PET, it is advisable to use an automated technique comparing the patient's images to a normal database in addition to visual interpretation of the images, since automated techniques have proven to be more accurate. In view of the thickness of the cortical ribbon, which may be below the resolution of the PET camera, posthoc partial volume correction or PET reconstruction incorporating the anatomical information of magnetic resonance imaging (MRI), may be useful for optimal assessment of glucose metabolism. Perfusion SPECT and interictal FDG-PET are able to demonstrate areas of abnormal perfusion and metabolism at a distance from the ictal onset zone, which may be associated with cognitive and psychiatric comorbidities, and may represent the functional deficit zone in epilepsy. Part of the functional deficit zone is a dynamic seizure-related process, which may resolve with cessation of seizures. In recent years, novel PET tracers have been developed to visualize not only glucose metabolism but also a wide variety of specific receptor systems. In patients with epilepsy, changes in the gamma-amino-butyric acid(A) receptor, opioid receptor, 5-HT(1A) serotonin receptor, nicotinic acetylcholine receptor systems, and others have been described. Because these tracers are not widely available and the superiority of studying these receptor systems over glucose metabolism in the presurgical evaluation of patients with refractory epilepsy remains to be proven, their use in clinical practice is limited at the moment. Finally, advances in small animal PET scanning allow the in vivo study of the process of epileptogenesis, starting from an initial brain insult to the development of seizures, in animal models of epilepsy. Potential new therapeutic targets may be discovered using this translational approach.     

Does performing image registration and subtraction in ictal brain SPECT help localize neocortical seizures?

Ictal brain SPECT (IS) findings in neocortical epilepsy (patients without mesiotemporal sclerosis) can be subtle. This study is aimed at assessing how the seizure focus identification was improved by the inclusion of individual IS and interictal brain SPECT (ITS)-MRI image registration as well as performing IS - ITS image subtraction. METHODS: The study involved the posthoc analysis of 64 IS scans using 99mTc-ethyl cysteinate dimer that were obtained in 38 patients without mesiotemporal sclerosis but with or without other abnormalities on MRI. Radiotracer injection occurred during video-electroencephalographic (EEG) monitoring. Patients were injected 2-80 s (median time, 13 s) after clinical or EEG seizure onset. All patients had sufficient follow-up to correlate findings with the SPECT results. All patients had ITS and MRI, including a coronal volume sequence used for registration. Image registration (IS and ITS to MRI) was performed using automated software. After normalization, IS - ITS subtraction was performed. The IS, ITS, and subtraction studies were read by 2 experienced observers who were unaware of the clinical data and who assessed the presence and localization of an identifiable seizure focus before and after image registration and subtraction. Correlation was made with video-EEG (surface and invasive) and clinical and surgical follow-up. RESULTS: Probable or definite foci were identified in 38 (59%) studies in 33 (87%) patients. In 52% of the studies, the image registration aided localization, and in 58% the subtraction images contributed additional information. In 9%, the subtraction images confused the interpretation. In follow-up after surgery, intracranial EEG or video-EEG monitoring (or both) has confirmed close or reasonable localization in 28 (74%) patients. In 6 (16%) patients, SPECT indicated false seizure localization. CONCLUSION: Image registration and image subtraction improve the localization of neocortical seizure foci using IS, but close correlation with the original images is required. False localizations occur in a minority of patients.     

Clinical advantages of interictal SPECT coregistered to magnetic resonance imaging in patients with epilepsy

PURPOSE: The aim of this study was to investigate the clinical value of coregistration of interictal SPECT and magnetic resonance imaging (MRI) in patients with partial epilepsy. MATERIALS AND METHODS: Seventeen patients with partial epilepsy were examined with I-123 IMP or Tc-99m ethyl cysteinate dimer SPECT during the interictal phase. The SPECT images were automatically coregistered to axial T1 weighted MRIs. Asymmetry indexes (AIs) were calculated in both nonregistered images and coregistered images. RESULTS: SPECT images showed areas of decreased tracer uptake in 12 patients. In two patients, the relation between the tumor and the extent of decreased uptake became more accurate in the coregistered images. In five cases, the coregistered images clearly showed that the decreased uptake was located in the sulcus. The AIs were significantly reduced from 14.29 +/- 7.23 to 5.86 +/- 3.48 (P < 0.001) after the images were coregistered in these cases. In five cases, the coregistered images indicated that the decreased areas were in agreement with the cortical findings. No significant differences in the AIs were observed in these cases (16.50 +/- 6.19 versus 17.83 +/- 4.45). Thus, the coregistered images were useful not only to differentiate actual hypoperfusion from artificial hypoperfusion resulting from partial volume effects but also to improve the accuracy of AIs. CONCLUSION: The coregistration of interictal perfusion SPECT and MRI is useful not only to provide precise functional and anatomic mapping but also to improve the accuracy of calculations of the semiquantitative analysis of regional cerebral blood flow parameters during the interictal state of epilepsy.     

The relative localizing value of interictal and immediate postictal SPECT in seizures of temporal lobe origin.

Although interictal hypoperfusion and ictal hyperperfusion are established localizing findings in partial epilepsy, their relative value is disputed. After a meta analysis of several published articles on SPECT brain imaging in patients with epilepsy (with extractable data on at least 6 patients per article), institutions using SPECT for evaluation of epilepsy have been encouraged to perform ictal scanning or interictal and postictal SPECT studies. METHODS: We compared the relative localizing values of hypoperfusion in video-electroencephalographically (EEG) monitored interictal SPECT (IISPECT) and hyperperfusion in immediate postictal or periictal SPECT (PISPECT) in nonlesional patients who underwent temporal lobectomies in our epilepsy center from 1995 to 1998. We also evaluated the usefulness of combined interpretation of IISPECT and PISPECT when available. RESULTS: Our experience with continuous cerebral blood-flow monitoring, published elsewhere, and SPECT results indicate that these recommendations are valid, but obtaining ictal SPECT is often serendipitous. We found that (a) interictal hypoperfusion was easier to demonstrate by SPECT but was less often concordant with the EEG focus than hyperperfusion in PISPECT, but not significantly (P = 0.11) so; (b) the lower incidence of hyperperfusion in PISPECT in our series was due to the occurrence of hypoperfusion in PISPECT, which was seen in 34.5% of our patients; and (c) hypoperfusion in PISPECT did have localizing value when it occurred on the same side as the hypoperfusion noted in IISPECT. CONCLUSION: On the basis of our findings, we recommend the use of 3 distinct perfusion patterns that emerge from the combined interpretation of IISPECT and PISPECT we proposed earlier (patterns 1-3), for localization purposes when possible, rather than ictal SPECT, IISPECT, or PISPECT by itself.     

The value of interictal brain SPECT in epilepsy patients without mesial-temporal sclerosis

PURPOSE: Most of the literature concerning interictal SPECT brain scanning in patients with seizures has involved the evaluation of those with temporal lobe epilepsy. The authors' aim was to determine the utility of interictal SPECT in patients with neocortical epilepsy. MATERIALS AND METHODS: Eighty-four patients with neocortical epilepsy were evaluated with 95 interictal SPECT scans and magnetic resonance imaging (MRI). RESULTS: Fifty-four percent of studies with normal MRI findings had SPECT images without regions of hypoperfusion. Sixty-one percent of patients with abnormal MRI results had matching defects visible on SPECT images. Fourteen scans (only 24%) had focal hypoperfusion by SPECT and no obvious matching MRI finding. CONCLUSIONS: Interictal SPECT, without a comparison ictal study, is of potentially limited value in localizing neocortical seizure foci. SPECT findings usually match MRI findings. Interictal SPECT, however, may still be of value in confirming abnormalities detected by ictal examination.     

Voxel significance mapping using local image variances in subtraction ictal SPET

Subtraction ictal SPET co-registered to MRI (SISCOM) has been shown to aid epileptogenic localization and improve surgical outcome in partial epilepsy patients. This paper reports a method of identifying significant areas of epileptogenic activation in the SISCOM subtraction image, taking into account normal variation between sequential 99Tcm-ethyl cysteinate diethylester SPET scans of single individuals, and attempts to assess the clinical value of statistical mapping in subtraction SPET. Non-linear inter-subject registration is used to combine a group of subtraction images into a common anatomical framework. A map of the pixel intensity standard deviation values in the subtraction images is created, and this map is non-linearly registered to a patient's SISCOM subtraction image. Pixels in the patient subtraction image were then evaluated based upon the statistical characteristics of corresponding pixels in the atlas. SISCOM images created with the voxel variance method were rated higher in quality than the conventional image variance method in 15 patients. No difference in localization rate was observed between the voxel variance mapping and image variance methods. The voxel significance mapping method was shown to improve the quality of clinical SISCOM images.     

Evaluation of ictal brain SPET using statistical parametric mapping in temporal lobe epilepsy

An automated voxel-based analysis of brain images using statistical parametric mapping (SPM) is accepted as a standard approach in the analysis of activation studies in positron emission tomography and functional magnetic resonance imaging. This study aimed to investigate whether or not SPM would increase the diagnostic yield of ictal brain single-photon emission tomography (SPET) in temporal lobe epilepsy (TLE). Twenty-one patients (age 27.14LJ.79 years) with temporal lobe epilepsy (right in 8, left in 13) who had a successful seizure outcome after surgery and nine normal subjects were included in the study. The data of ictal and interictal brain SPET of the patients and baseline SPET of the normal control group were analysed using SPM96 software. The t statistic SPM{t} was transformed to SPM{Z} with various thresholds of P<0.05, 0.005 and 0.001, and corrected extent threshold P value of 0.05. The SPM data were compared with the conventional ictal and interictal subtraction method. On group comparison, ictal SPET showed increased uptake within the epileptogenic mesial temporal lobe. On single case analysis, ictal SPET images correctly lateralized the epileptogenic temporal lobe in 18 cases, falsely lateralized it in one and failed to lateralize it in two as compared with the mean image of the normal group at a significance level of P<0.05. Comparing the individual ictal images with the corresponding interictal group, 15 patients were correctly lateralized, one was falsely lateralized and four were not lateralized. At significance levels of P<0.005 and P<0.001, correct lateralization of the epileptogenic temporal lobe was achieved in 15 and 13 patients, respectively, as compared with the normal group. On the other hand, when comparison was made with the corresponding interictal group, only 7 out of 21 patients were correctly lateralized at the threshold of P<0.005 and five at P<0.001. The result of the subtraction method was close to the single case analysis on SPM at P<0.05. However, at higher thresholds (P<0.005 and 0.001) the subtraction method was comparable to the SPM results only when individual ictal images were compared with the normal control group, and not when comparison was with the interictal group. It is concluded that SPM is an alternative diagnostic method for the localization or lateralization of the seizure focus in temporal lobe epilepsy and that interictal SPET could be omitted if a normal brain SPET database were to be established. The medical cost of seizure localization would thereby be reduced.     

Composite SISCOM images in mesial temporal lobe epilepsy: technique and illustration of regions of hyperperfusion

OBJECTIVE: To outline and validate a technique for subtraction ictal single photon emission tomography (SPET) co-registered to magnetic resonance imaging (MRI) (SISCOM), which allows non-linear co-registration of groups of subtraction SPET images to a single, template image. METHODS: In patients with mesial temporal lobe epilepsy, we used linear and non-linear transformation steps to co-register ictal and interictal images to a template SPET, then used the resultant ictal and interictal images to produce subtraction images. Statistical changes in subtraction SPET before and after the transformation steps in individual subjects were documented to validate the technique. Subtraction SPET images were thresholded to include pixel values 1 standard deviation (SD) above zero, and converted to binary. Images were combined by simple addition of images to form the final composite image. Final results were co-registered to a template MRI to demonstrate the regions most commonly hyperperfused in mesial temporal lobe epilepsy. RESULTS: Linear and non-linear transformation steps induced only small changes in standard deviations of subtraction SPET, typically approximately 1 pixel value. The final composite SISCOM images showed the anterior temporal lobe, insula and basal ganglia as the most commonly hyperperfused regions during mesial temporal lobe epileptic seizures. CONCLUSION: Our technique resulted in only small changes in statistical characteristics of individual subtraction SPET studies, and was acceptable for the purpose of creating composite SISCOM images.     

Subtraction SPECT for parathyroid scintigraphy based on maximization of mutual information

Our objective was to investigate the feasibility of subtraction for SPECT images of (99m)Tc-MIBI double-phase parathyroid scintigraphy. METHODS: Fourteen patients with hyperparathyroidism were enrolled in the present study. Histopathologically, excised tissue specimens showed hyperplasia in 11 patients and adenoma in 3 patients. Both ultrasonography and (99m)Tc-sestamibi (MIBI) SPECT images were obtained from all patients. As standard lines to ensure that patient positioning remained identical between the different phases, we used the cross-marker produced by a pair of laser pointers, the orbitomeatal line, and the vertical midline through the patient's nose. Data processing was performed with software that enables image registration by maximization of mutual information. The results of subtraction SPECT imaging were compared with those of ultrasonography. RESULTS: The registration of double-phase SPECT images was successful in all patients when the salivary glands were excluded from the image reconstruction region. The overall sensitivities of scintigraphy and ultrasonography were 90.9% (40/44) and 70.5% (31/44), respectively, with respective specificities of 83.3% (10/12) and 75.0% (9/12). Scintigraphy and ultrasonography showed accuracies of 92.8% (52/56) and 71.4% (40/56), respectively. CONCLUSION: The new technique used in the present study allowed the subtraction for SPECT images. The sensitivity of parathyroid lesion detection using this technique was superior to that of ultrasonography.     

Comparative analysis of MR imaging,Ictal SPECT and EEG in temporal lobe epilepsy: a prospective IAEA multi-center study

Background and purpose MR imaging, ictal single-photon emission CT (SPECT) and ictal EEG play important roles in the presurgical localization of epileptic foci. This multi-center study was established to investigate whether the complementary role of perfusion SPECT, MRI and EEG for presurgical localization of temporal lobe epilepsy could be confirmed in a prospective setting involving centers from India, Thailand, Italy and Argentina. Methods We studied 74 patients who underwent interictal and ictal EEG, interictal and ictal SPECT and MRI before surgery of the temporal lobe. In all but three patients, histology was reported. The clinical outcome was assessed using Engel’s classification. Sensitivity values of all imaging modalities were calculated, and the add-on value of SPECT was assessed. Results Outcome (Engel’s classification) in 74 patients was class I, 89%; class II, 7%; class III, 3%; and IV, 1%. Regarding the localization of seizure origin, sensitivity was 84% for ictal SPECT, 70% for ictal EEG, 86% for MRI, 55% for interictal SPECT and 40% for interictal EEG. Add-on value of ictal SPECT was shown by its ability to correctly localize 17/22 (77%) of the seizure foci missed by ictal EEG and 8/10 (80%) of the seizure foci not detected by MRI. Conclusions This prospective multi-center trial, involving centers from different parts of the world, confirms that ictal perfusion SPECT is an effective diagnostic modality for correctly identifying seizure origin in temporal lobe epilepsy, providing complementary information to ictal EEG and MRI. Part of this work was presented at the 2005 SNM meeting in Toronto, Canada.