Comparison of statistical parametric mapping and SPECT difference imaging in patients with temporal lobe epilepsy

PURPOSE: Statistical parametric mapping (SPM) is an image-analysis tool that assesses the statistical significance of cerebral blood flow (CBF) changes on a voxel-by-voxel basis, thereby removing the subjectivity inherent in conventional region-of-interest (ROI) analysis. Our platform of single-photon emission computed tomography (SPECT) ictal-interictal difference imaging in clinical epilepsy has been validated for localizing seizure onset. We extend the tools of SPM by further applying statistical measures for the significance of perfusion changes in individual patients to localize epileptogenic foci in patients with defined temporal lobe epilepsy by using paired scans in this preliminary study. METHODS: Twelve patients with pairs of periictal and interictal SPECT scans were analyzed in this comparison study between SPECT difference imaging and SPM difference analysis by using a reference database of paired normal healthy images. These 12 patients possessed seizure foci localized to the mesial temporal lobe as confirmed by surgical outcome and by hippocampal sclerosis on pathology. SPM was used to identify clusters of increased or decreased CBF in each patient in contrast to our control group. RESULTS: The regions having the most significant increased or decreased CBF by SPM analysis were in agreement with regions identified by conventional difference imaging and visual analysis by viewers blinded to the results of the SPM analysis. Differentiated further by time of radiopharmaceutical injection, six of seven patients injected within 100 s of seizure onset displayed hyperperfusion changes localized to the corresponding epileptogenic temporal lobe by both techniques. Among patients receiving injections after 100 s, both techniques showed primarily regions of hypoperfusion, which again were similar between these two methods. CONCLUSIONS: The results provide strong evidence supporting SPM difference analysis in assessing regions of significant CBF change from baseline in concordance with our current clinically used technique of SPECT ictal--interictal difference imaging in epilepsy patients. Difference analysis using SPM could serve as a useful diagnostic tool in the evaluation of seizure focus in temporal lobe epilepsy.     

Coherence analysis in the myoclonus of corticobasal degeneration.

We investigated whether myoclonus in corticobasal degeneration (CBD) is cortical or subcortical in origin. Many authors have suggested that the myoclonus in CBD is a subtype of cortical myoclonus, despite the fact that back-averaging fails to detect a cortical correlate to spontaneous or action induced jerks and giant sensory evoked potentials are seldom found. Electroencephalographic-electromyographic (EEG-EMG) and EMG-EMG frequency analysis may be more sensitive to cortical drives when EMG bursts occur at a high frequency and at low amplitudes as in CBD. We evaluated EEG-EMG and EMG-EMG coherence and phase in 5 patients with clinically probable CBD and unilateral, action-induced and stimulus-sensitive myoclonus. We found negligible corticomuscular coherence despite a dramatically exaggerated EMG-EMG coherence. We conclude that an inflated EMG-EMG coherence is found in some patients with CBD and that this is unlikely to be due to an exaggerated cortical drive.     

Dopamine transporters, D2 receptors, and glucose metabolism in corticobasal degeneration.

Alterations in presynaptic and postsynaptic dopaminergic system and cerebral glucose metabolism in corticobasal degeneration (CBD) were assessed to evaluate the potential usefulness of different imaging methods for CBD. (123)I-FP-CIT/(123)I-beta-CIT SPECT and (123)I-IBZM SPECT as well as (18)F-FDG PET were performed in eight CBD patients. Decreased presynaptic dopamine transporter binding was found in all CBD patients while D2 receptor binding was reduced in only one patient. (18)F-FDG PET displayed a contralateral hypometabolism in cortical and subcortical areas in seven out of eight patients. Our results demonstrate that glucose metabolism and DAT are reduced, while D2 receptors may be frequently preserved in CBD.     

Asymmetrical alien hands in corticobasal degeneration.

There are several forms of alien limb, but alien limb in corticobasal degeneration (CBD) is not well understood. We studied a patient with CBD who demonstrated two different types of alien limb. With his right hand he demonstrated a tactile avoidance response with levitation. With his left hand, he demonstrated continuous tactile pursuit of the examiner's hand ("tactile mitgehen"). Mitgehen is often associated with frontal dysfunction, but avoidance response and levitation are often associated with parietal dysfunction.     

Sensory alien hand syndrome in corticobasal degeneration: A cerebral blood flow study

The presence of alien hand syndrome (AHS) is suggestive of the diagnosis of corticobasal degeneration when it develops in a progressive way. Sensory AHS (sAHS) should be distinguished from the motor form described more commonly. The physiopathology of sAHS remains unclear. The aim of this study is to determine cerebral regions involved in sAHS. We compared perfusion single photon emission computer tomography scans of patients with sAHS (n = 3) and without (n = 4). We observed significant decrease of regional cerebral blood flow over the nondominant thalamus in sAHS+ compared to sAHS? patients. This result suggests the involvement of the nondominant thalamus in sAHS. © 2010 Movement Disorder Society     

Brain perfusion differences in Parkinsonian disorders

We aimed to objectively examine the brain perfusion differences between PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy. ^99mTc ethylcysteinate dimer single‐photon emission CT (SPECT) was performed in 28 patients with PD, 12 with Parkinson variant of multiple system atrophy, 19 with progressive supranuclear palsy, and 17 age‐ and sex‐matched control subjects. A voxel‐by‐voxel group analysis, using statistical parametric mapping 8, was performed to detect the differences of regional cerebral blood flow among three diseases and control groups. Regional cerebral blood flow was measured using the noninvasive Patlak plot method and calculated using a fully automated region of interest technique. Progressive supranuclear palsy showed decreased regional cerebral blood flow in the cingulate gyrus and thalamus, whereas Parkinson variant of multiple system atrophy showed decreased regional cerebral blood flow in the cerebellum, compared with other patients and controls. Regional cerebral blood flow in the thalamus could be used to discriminate progressive supranuclear palsy from other diseases and control subjects with high sensitivity. These findings suggest that parkinsonian disorders, such as PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy show a distinct SPECT pattern in the frontal cortex, thalamus, and cerebellum. Moreover, the measurements of regional cerebral blood flow in the thalamus and cerebellum may be helpful in screening for the differential diagnosis of parkinsonian syndrome. © 2011 Movement Disorder Society     

Depressive mood in pre-dialytic chronic kidney disease: Statistical parametric mapping analysis of Tc-99m ECD brain SPECT

The purpose of this study was to investigate depression-related regions in pre-dialytic patients with chronic kidney disease (CKD) patients. Participants comprised 33 patients with stage 4 and 5 CKD (age, 55 [42–63]) and 32 healthy volunteers (age, 53.5 [49.5–57]). Depressed mood was assessed in the patients, and both groups underwent Tc-99m-labeled ethylcysteinate dimer (Tc-99m ECD) single photon emission computed tomograpy (SPECT). Statistical parametric mapping identified 18 areas of hypoperfusion in the patients in comparison with the normal controls. The largest clusters were areas including left precentral gyrus, right superior and middle temporal gyrus, both cerebellar posterior lobes, both inferior frontal gyrus, right superior and middle frontal gyrus, right cuneus, right inferior parietal lobule, and right putamen. However, there were no specific hypoperfusion areas in CKD patients with depression compared with CKD patients without depression. Interestingly, several hypoperfusion areas in CKD patients (inferior frontal gyrus [BA46], superior temporal gyrus [BA42], anterior cingulate gyrus [BA24]) were concordant with hypoperfusion areas found in patients with major depression who were free of kidney disease. In conclusion, this study did not demonstrate specific depression-related cerebral hypoperfusion areas. However, the cerebral blood flow pattern in CKD patients was similar to that of patients with major depression in some areas. Although further investigations are needed in the future, we suggest that the causes of the higher prevalence of depression in CKD might be associated with this finding.     

Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis

Alzheimer's disease (AD) is clinically characterized by cognitive symptoms that, in combination with behavioral disturbances, significantly interfere with activities of daily living. These behavioral disorders contribute to the clinical heterogeneity of the disease and probably express different pathophysiological processes. Apathy is one of the most frequent behavioral disorders in AD. The aim of this study was to evaluate brain perfusion of AD patients with and without apathy (as determined by the Neuropsychiatric Inventory) compared with that in healthy elderly subjects. A total of 15 AD patients without apathy (AD/NA; mean age 76.6) and 15 AD patients with apathy (AD/A; mean age 77.6) were studied. Brain perfusion was measured by 99mTc-labeled bicisate (ECD) single-photon emission tomography (ECD SPECT). The images of the two AD subgroups were compared by means of statistical parametric mapping (SPM 99) to corresponding images of 11 healthy elderly control subjects (obtained from the Society of Nuclear Medicine database). Compared with the healthy elderly subjects, the apathy-free AD subgroup had significantly lower perfusion of inferior temporal regions (left fusiform gyrus, left parahippocampal area) and occipital regions (left gyrus lingualis). The apathy subgroup had significantly decreased perfusion of the left anterior cingulate, the right inferior and medial gyrus frontalis, the left orbitofrontal gyrus and the right gyrus lingualis. The differences in the brain areas with reduced perfusion between the apathy-free subjects (mainly the posterior regions) and the apathetic subjects (mainly the anterior regions) indicate that behavioral disorders such as apathy participate in the heterogeneity of brain perfusion in AD.     

Quantitative single photon emission tomography analysis for the diagnosis of transient global amnesia: adaptation of statistical parametric mapping

We report two cases of transient global amnesia (TGA) diagnosed using a clinical criteria and single photon emission tomography (SPECT) with the aid of Statistical Parametric Mapping (SPM). Both patients underwent an initial SPECT study about 20 h after the disappearance of the amnesic episode, and a second study 3 weeks after the episode. We conducted quantitative cerebral blood flow (CBF) analyses using SPM on Matlab. This revealed regions with abnormal CBF in the first studies but not in the second. This method appears to be useful for diagnosis of TGA, especially in patients with suspected TGA in whom the amnesic episode disappears within a few days.     

Analysis of family‐wise error rates in statistical parametric mapping using random field theory

This technical report revisits the analysis of family‐wise error rates in statistical parametric mapping—using random field theory—reported in (Eklund et al. [ 2015 ]: arXiv 1511.01863). Contrary to the understandable spin that these sorts of analyses attract, a review of their results suggests that they endorse the use of parametric assumptions—and random field theory—in the analysis of functional neuroimaging data. We briefly rehearse the advantages parametric analyses offer over nonparametric alternatives and then unpack the implications of (Eklund et al. [ 2015 ]: arXiv 1511.01863) for parametric procedures. Hum Brain Mapp, 40:2052–2054, 2019. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Regional cerebral perfusion abnormalities in developmental language disorder

Objective A voxel based investigation of cerebral blood flow was conducted to identify brain functional differences during resting state between children with developmental language disorder (DLD) and normal controls. Method Using DSM–IV criteria, we selected 21 children with DLD.All children were examined by technetium–99m–HMPAO Brain SPECT. Using SPM analyses, we compared the SPECT images of children with DLD and those of 17 control subjects on a voxel by voxel basis using ANCOVA covarying for age. Results Reduced cerebral blood flow in the right putamen,the right inferior parietal cortex, and the left globus pallidus were found in children with DLD versus the controls. However, no area of increased cerebral blood flow was observed in children with DLD compared to the controls. Conclusion Though results should be interpreted cautiously, this study confirms the presence of functional defects in the basal ganglia and the inferior parietal lobe during the resting state of the brains of children with DLD. It also gives further evidence for functional deficits in basal ganglia as an important factor in the etiology of DLD.     

Neurodegenerative disease and the evolution of art: the effects of presumed corticobasal degeneration in a professional artist.

Production of art is a complex process involving a combination of technical skill and a unique talent. Changes in artistic ability may accompany neurodegenerative disorders when they occur in an artist. The nature of these changes in the context of definable regional neuropathological disturbances may provide insight into the structural basis of the creative process. We describe a professional artist in whom presumed corticobasal degeneration (CBD) was associated with an alteration of his artistic judgement and production. Disinhibition, perseveration, and left hemispatial neglect, features of his cognitive profile were readily discernible in his work. The differences in his style are examined with respect to his main neuroanatomic abnormalities, namely right cerebral hemiatrophy as defined by magnetic resonance and single-photon emission computed tomography imaging. Cognitive deficits, including visuoconstructive and motor neglect, apathy, perseveration, and disinhibition as determined by neuropsychological testing, contributed to the dissolution of his artistic skills. Our case study adds to the growing literature on the effects of brain damage on artistic expression in the graphic arts.     

MRI correlates of alien leg-like phenomenon in corticobasal degeneration.

We describe the clinical and neuroradiologic correlates in two patients with the clinical picture of CBD and alien leg phenomena. The MRI brain scan in both had unique focal abnormalities in the corresponding leg area of the homunculus that may be the substrate for the alien limb features.     

Cerebral glucose metabolism abnormalities in patients with major depressive symptoms in pre-dialytic chronic kidney disease: statistical parametric mapping analysis of F-18-FDG PET, a preliminary study

Aims: The aim of the present study was to investigate the relationship between depressive symptoms and cerebral glucose metabolism in pre‐dialytic chronic kidney disease (PDCKD) patients. Methods: Twenty‐one patients with stage 5 CKD and 21 healthy volunteers underwent depressive mood assessment and statistical parametric mapping (SPM) using F‐18‐fluorodeoxyglucose (FDG) positron emission tomography (PET). Results: Several voxel clusters of significantly decreased cerebral glucose metabolism were found in PDCKD patients. The largest cluster was left prefrontal cortex (Brodmann area [BA] 9). The second largest cluster was also left prefrontal cortex (BA 9). The third largest clusters were right prefrontal cortex (BA 10) and right basolateral prefrontal cortex (BA 46). Other brain areas also showed decreased cerebral glucose metabolism including left anterior cingulate gyrus (BA 32), left premotor cortex (BA 6), left transverse temporal gyrus (BA 41), left superior temporal gyrus (BA 42), right basolateral prefrontal cortex (BA 44), right inferior parietal lobule (BA 39), left middle temporal gyrus (BA 19), and left angular gyrus (BA 39). Hypermetabolized brain areas, however, were not found in PDCKD patients compared to normal controls. For the right orbitofrontal cortex there was a negative correlation of cerebral glucose metabolism with Hamilton Depression Rating Scale (HDRS) in PDCKD patients (BA 11). Conclusion: PDCKD patients with depressive symptoms had decreased cerebral glucose metabolism in several brain areas. For the right orbitofrontal cortex there was a negative correlation with HDRS in PDCKD patients. The present findings provide functional neuroimaging support for abnormal cerebral glucose metabolism in PDCKD patients with depressive symptoms.     

Imaging of activated microglia with PET and [11C]PK 11195 in corticobasal degeneration.

Positron emission tomography (PET) using [(11)C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left-sided symptoms was studied using fluorodeoxyglucose (FDG) and [(11)C]PK 11195 PET. We found a marked right hemispheric hypometabolism and asymmetric microglial activation in corresponding areas of the basal ganglia and right temporal and parietal cortex. [(11)C]PK 11195 PET suggests involvement of microglial activation in the pathogenesis of CBD.     

Asymmetric changes in somatosensory evoked potentials correlate with limb apraxia in corticobasal degeneration

To clarify the underlying mechanism of limb apraxia in corticobasal degeneration (CBD), we investigated somatosensory evoked potentials in 5 patients with CBD, as compared with 12 age-matched control subjects. All patients presented with asymmetric limb apraxia, particularly of limb-kinetic type. N20 latencies were significantly prolonged following median nerve stimulation on the more apraxic side, but not on the less apraxic side. These results suggest that limb apraxia in CBD may, at least in part, be due to a disorder of somatosensory information processing involving the parietal cortex.     

Statistical parametric mapping demonstrates asymmetric uptake with Tc-99m ECD and Tc-99m HMPAO SPECT in normal brain

Tc-99m ethyl cysteinate diethylester (ECD) and Tc-99m hexamethyl propylene amine oxime (HMPAO) are commonly used for single-photon emission computed tomography (SPECT) studies of a variety of neurologic disorders. Although these tracers have been very helpful in diagnosing and guiding treatment of neurologic disease, data describing the distribution and laterality of these tracers in normal resting brain are limited. Advances in quantitative functional imaging have demonstrated the value of using resting studies from control populations as a baseline to account for physiologic fluctuations in cerebral perfusion. Here, we report results from 30 resting Tc-99m ECD SPECT scans and 14 resting Tc-99m HMPAO scans of normal volunteers with no history of neurologic disease. Scans were analyzed with regions of interest and with statistical parametric mapping, with comparisons performed laterally (left vs. right), as well as for age, gender, and handedness. The results show regions of significant asymmetry in the normal controls affecting widespread areas in the cerebral hemispheres, but most marked in superior parietotemporal region and frontal lobes. The results have important implications for the use of normal control SPECT images in the evaluation of patients with neurologic disease.     

Advanced dynamic statistical parametric mapping with MEG in localizing epileptogenicity of the bottom of sulcus dysplasia

Objective

To investigate whether advanced dynamic statistical parametric mapping (AdSPM) using magnetoencephalography (MEG) can better localize focal cortical dysplasia at bottom of sulcus (FCDB).