Regional Hypometabolism Research Articles

Neuropathological investigation of the hypometabolic regions on positron emission tomography with [18F] fluorodeoxyglucose in patients with dementia with Lewy bodies

We performed a quantitative neuropathological examination of the hypometabolic regions on FDG PET in dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and control cases. When the DLB cases were divided into two groups according to concomitant AD pathology (ADP), neuronal loss in the temporo-parietal association area was milder in the DLB groups than in the AD group, although there were no differences between the two DLB groups. Tau and Aβ immunoreactivities were observed in the AD group and the DLB group with ADP, but were rare in the DLB group without ADP. Tau and Aβ immunoreactivities as well as numbers of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) were more common in the AD group than in the DLB group with ADP. There was no difference in neuronal loss in the occipital area among the three groups. α-Synuclein immunoreactivity was observed in the DLB groups but not in the AD group. There were no differences in α-synuclein immunoreactivity and number of Lewy bodies (LBs) between the two DLB groups. These findings indicate that the neuropathological bases of the hypometabolic regions in the temporo-parietal association and occipital area in DLB may be AD pathology and Lewy pathology, respectively.

Multimodality imaging characteristics of dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). Our objective was to determine whether the 11C-Pittsburgh Compound-B (PiB) retention and regional hypometabolism on positron emission tomography (PET) and regional cortical atrophy on magnetic resonance imaging (MRI) are complementary in characterizing patients with DLB and differentiating them from AD. We studied age-, gender-, and education-matched patients with a clinical diagnosis of DLB (n = 21), AD (n = 21), and cognitively normal subjects (n = 42). Hippocampal atrophy, global cortical PiB retention and occipital lobe metabolism in combination distinguished DLB from AD better than any of the measurements alone (area under the receiver operating characteristic = 0.98). Five of the DLB and AD patients who underwent autopsy were distinguished through multimodality imaging. These data demonstrate that magnetic resonance imaging and PiB positron emission tomography contribute to characterizing the distinct pathological mechanisms in patients with AD compared with DLB. Occipital and posterior parietotemporal lobe hypometabolism is a distinguishing feature of DLB and this regional hypometabolic pattern is independent of the amyloid pathology.

Molecular Neuroimaging in the Study of Cognitive Impairment: Contribution of the Cerebral Blood Flow SPECT with 99mTc-HMPAO and 18F-FDG PET/CT Scan

Objective The aim of this study was to analyze cerebral perfusion and glucose metabolism in patients with cognitive impairment using cerebral blood flow 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans. Material and methods Twenty-two patients with cognitive impairment were included: 4 subjective memory complaints (SMC), 8 amnestic mild cognitive impairment (MCI), 5 prodromic Alzheimer's disease (AD) and 5 AD. In each clinical group, 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans were performed. Results 99mTc-HMPAO SPECT showed regions of cerebral hypoperfusion in 15 patients and was normal in 7 of the 22 patients. 18F-FDG PET/CT scan showed cerebral regional hypometabolism in 19 patients and was normal in the other 3 patients. The distribution of abnormalities on 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans was similar in 9 patients (2 SMC, 2 amnestic MCI, 2 prodromic AD, and 3 AD). In 6 patients (1 amnestic MCI, 2 prodromic AD, and 3 AD), FDG hypometabolism was more extensive than the cerebral hypoperfusion. Four patients (1 SMC, 3 amnestic MCI) had an abnormal 18F-FDG PET/CT scan and normal 99mTc-HMPAO SPECT. There were 3 patients (1 SMC, 2 amnestic MCI) with normal 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans. Conclusion 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans showed cerebral hypoperfusion and hypometabolism in patients with cognitive impairment, even in patients with clinical diagnosis of SMC. In patients with a normal cerebral blood flow SPECT, brain glucose cerebral hypometabolism can be detected. In some patients, the extension of FDG hypometabolism is more pronounced than that corresponding to the hypoperfusion area.

Cerebral Metabolism, Cognition, and Functional Abilities in Alzheimer Disease

Patients with Alzheimer disease (AD) exhibit profound difficulties in completing instrumental activities of daily living (IADLs), such as managing finances, organizing medications, and food preparation. It is unclear which brain areas underlie IADL deficits in AD. To address this question, we used voxel-based analysis to correlate the performance of IADLs with resting cerebral metabolism as measured during [(18)F] fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in 44 patients with AD. Poorer ability to complete IADLs was associated with hypometabolism in right-sided cortical regions, including the parietal lobe, posterior temporal cortex, dorsolateral prefrontal cortex, and frontal pole. Follow-up path analyses examining anatomically defined regions of interest (ROI) demonstrated that the association between metabolism and IADLs was mediated by global cognition in frontal ROIs, and partially mediated by global cognition in the parietal ROI. Findings suggest that hypometabolism of right sided brain regions involved in executive functioning, visuospatial processing, attention, and working memory underlie functional impairments in patients with AD.

The IMAP* Project: Relative Degrees of Regional Grey Matter Atrophy, Hypometabolism and B-Amyloid Deposition in Alzheimer's Disease Assessed Through Multimodal Neuroimaging

The IMAP* Project: Relative Degrees of Regional Grey Matter Atrophy, Hypometabolism and B-Amyloid Deposition in Alzheimer's Disease Assessed Through Multimodal Neuroimaging

The IMAP* project: Relative degrees of regional grey matter atrophy, hypometabolism and β-amyloid deposition in Alzheimer's disease assessed through multimodal neuroimaging

The IMAP* project: Relative degrees of regional grey matter atrophy, hypometabolism and β-amyloid deposition in Alzheimer's disease assessed through multimodal neuroimaging

A comparison of F-18 FDG-PET imaging in differential diagnosis of Alzheimer's disease and dementia with Lewy body disease

Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease (AD). Clinically it is characterized by attentional fluctuation, recurrent visual hallucinations and motor features of Parkinsonism, while histopathologically by cortical and sub-cortical Lewy bodies. However, due to overlapping clinical features and low sensitivity of clinical diagnostic criteria, the differential diagnosis of AD and DLB remains a major problem in clinical practice. The aim of this study was to investigate the diagnostic value of metabolism in the diagnosis of DLB and AD in comparison with [F-18] fluoro-2-deoxy-D-glucose (FDG)-PET imaging. Investigations which could help improve the accuracy of discrimination between DLB and AD would be a major advance. All subjects underwent 18F-FDG-PET and MRI. We compared regional cerebral metabolic images by a voxel-by-voxel analysis with statistical parametric mapping among DLBD, AD and NC subjects, and evaluated differences of hypometabolic regions. All PET scans be visually rated from equivalent slices, each image volume was registered to match a 18F-FDG-PET template in standard MNI (Montreal Neurological Institute) space using statistical parametric mapping. Accurate normalization is essential for quantitative pattern analysis to neurodegenerative disease; the cerebellum or pons was often used as a reference region in the MR image, which assumed no significant regional influence of physiological fluctuations for quantitative. 18F-FDG-PET revealed evidence of diffuse hypometabolism in both DLBD and AD with Parkinsonism marked declines in association cortices with relative sparing of subcortical structures and primary somatomotor cortex, a pattern reported previously in AD. Unlike AD, DLBD subjects also had hypometabolism in the occipital association cortex and primary visual cortex. Significant changes in hypometabolism in the volume of interest were assessed in the posterior cingulate gyrus, precuneus and parietal cortices. The severity of the decrease in metabolism in AD patients was significantly greater than in vascular dementia and frontotemporal dementia patients and controls. These findings indicate the presence of diffuse cortical abnormalities in DLBD and suggest that FDG-PET may be useful in discriminating DLBD from AD.

La neuroimagen molecular en el estudio del deterioro cognitivo: contribución de la SPECT de perfusión cerebral con 99mTc-HMPAO y la 18F-FDG PET/TAC

Objective The aim of this study was to analyze cerebral perfusion and glucose metabolism in patients with cognitive impairment using cerebral blood flow 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans. Material and methods Twenty-two patients with cognitive impairment were included: 4 subjective memory complaints (SMC), 8 amnestic mild cognitive impairment (MCI), 5 prodromic Alzheimer's disease (AD) and 5 AD. In each clinical group, 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans were performed. Results 99mTc-HMPAO SPECT showed regions of cerebral hypoperfusion in 15 patients and was normal in 7 of the 22 patients. 18F-FDG PET/CT scan showed cerebral regional hypometabolism in 19 patients and was normal in the other 3 patients. The distribution of abnormalities on 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans was similar in 9 patients (2 SMC, 2 amnestic MCI, 2 prodromic AD, and 3 AD). In 6 patients (1 amnestic MCI, 2 prodromic AD, and 3 AD), FDG hypometabolism was more extensive than the cerebral hypoperfusion. Four patients (1SMC, 3 amnestic MCI) had an abnormal 18F-FDG PET/CT scan and normal 99mTc-HMPAO SPECT. There were 3 patients (1 SMC 2, amnestic MCI) with normal 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans. Conclusion 99mTc-HMPAO SPECT and 18F-FDG PET/CT scans showed cerebral hypoperfusion and hypometabolism in patients with cognitive impairment, even in patients with clinical diagnosis of SMC. In patients with a normal cerebral blood flow SPECT, brain glucose cerebral hypometabolism can be detected. In some patients, the extension of FDG hypometabolism is more pronounced than that corresponding to the hypoperfusion area.

The concept of FDG-PET endophenotype in Alzheimer’s disease

Often viewed as a potential tool for preclinical diagnosis in early asymptomatic stages of Alzheimer's disease (AD), the term "endophenotype" has acquired a recent popularity in the field. In this review, we analyze the construct of endophenotype-originally designed to discover genes, and examine the literature on potential endophenotypes for the late-onset form of AD (LOAD). We focus on the [18F]-fluoro-2-deoxyglucose (FDG) PET technique, which shows a characteristic pattern of hypometabolism in AD-related regions in asymptomatic carriers of the ApoE E4 allele and in children of AD mothers. We discuss the pathophysiological significance and the positive predictive accuracy of an FDG-endophenotype for LOAD in asymptomatic subjects, and discuss several applications of this endophenotype in the identification of both promoting and protective factors. Finally, we suggest that the term "endophenotype" should be reserved to the study of risk factors, and not to the preclinical diagnosis of LOAD.

Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden

Disruption of functional connectivity between brain regions may represent an early functional consequence of β-amyloid pathology prior to clinical Alzheimer's disease. We aimed to investigate if non-demented older individuals with increased amyloid burden demonstrate disruptions of functional whole-brain connectivity in cortical hubs (brain regions typically highly connected to multiple other brain areas) and if these disruptions are associated with neuronal dysfunction as measured with fluorodeoxyglucose-positron emission tomography. In healthy subjects without cognitive symptoms and patients with mild cognitive impairment, we used positron emission tomography to assess amyloid burden and cerebral glucose metabolism, structural magnetic resonance imaging to quantify atrophy and novel resting state functional magnetic resonance imaging processing methods to calculate whole-brain connectivity. Significant disruptions of whole-brain connectivity were found in amyloid-positive patients with mild cognitive impairment in typical cortical hubs (posterior cingulate cortex/precuneus), strongly overlapping with regional hypometabolism. Subtle connectivity disruptions and hypometabolism were already present in amyloid-positive asymptomatic subjects. Voxel-based morphometry measures indicate that these findings were not solely a consequence of regional atrophy. Whole-brain connectivity values and metabolism showed a positive correlation with each other and a negative correlation with amyloid burden. These results indicate that disruption of functional connectivity and hypometabolism may represent early functional consequences of emerging molecular Alzheimer's disease pathology, evolving prior to clinical onset of dementia. The spatial overlap between hypometabolism and disruption of connectivity in cortical hubs points to a particular susceptibility of these regions to early Alzheimer's-type neurodegeneration and may reflect a link between synaptic dysfunction and functional disconnection.

FMRI language dominance and FDG-PET hypometabolism

Atypical language dominance is common in patients with temporal lobe epilepsy. We examined the association of left temporal hypometabolism with laterality of fMRI activation in a language task in a cross-sectional study. Thirty patients with temporal lobe epilepsy (mean age 32.4 ± 11.0 years [range 18-55]; epilepsy onset 15.3 ± 11.3 years [range 0.8-40]; 22 left focus, 8 right focus) had (18)fluoro-deoxyglucose (FDG)-PET using noninvasive cardiac input function. After MRI-based partial volume correction, regional glucose metabolism (CMRglc) was measured and asymmetry index, AI = 2(l - R)/(L + R), calculated. fMRI language dominance was assessed with an auditory definition decision paradigm at 3 T. fMRI data were analyzed in SPM2 using regions of interest from Wake Forest PickAtlas (Wernicke area [WA], inferior frontal gyrus [IFG], middle frontal gyrus [MFG]) and bootstrap laterality index, LI = (l - R/L + R). Nineteen patients had ipsilateral temporal hypometabolism; 3 of 4 patients with atypical language had abnormal FDG-PET. Increasing left midtemporal hypometabolism correlated with decreased MFG LI (r = -0.41, p < 0.05) and showed trends with WA LI (r = -0.37, p = 0.055) and IFG LI (r = -0.31, p = 0.099); these relationships became more significant after controlling for age at onset. Increasing hypometabolism was associated with fewer activated voxels in WA ipsilateral to the focus and more activated voxels contralaterally, but overall, activation amount in left WA was similar to subjects without left temporal hypometabolism (t = -1.39, p > 0.10). We did not find evidence of impaired blood oxygenation level-dependent response in hypometabolic cortex. Regional hypometabolism appears to be a marker for the temporal lobe dysfunction that leads to displacement of language function.

Temporoparietal Hypometabolism in Frontotemporal Lobar Degeneration and Associated Imaging Diagnostic Errors

To evaluate the cause of diagnostic errors in the visual interpretation of positron emission tomographic scans with fludeoxyglucose F 18 (FDG-PET) in patients with frontotemporal lobar degeneration (FTLD) and patients with Alzheimer disease (AD). Twelve trained raters unaware of clinical and autopsy information independently reviewed FDG-PET scans and provided their diagnostic impression and confidence of either FTLD or AD. Six of these raters also recorded whether metabolism appeared normal or abnormal in 5 predefined brain regions in each hemisphere-frontal cortex, anterior cingulate cortex, anterior temporal cortex, temporoparietal cortex, and posterior cingulate cortex. Results were compared with neuropathological diagnoses. Academic medical centers. Forty-five patients with pathologically confirmed FTLD (n=14) or AD (n=31). Raters had a high degree of diagnostic accuracy in the interpretation of FDG-PET scans; however, raters consistently found some scans more difficult to interpret than others. Unanimity of diagnosis among the raters was more frequent in patients with AD (27 of 31 patients [87%]) than in patients with FTLD (7 of 14 patients [50%]) (P=.02). Disagreements in interpretation of scans in patients with FTLD largely occurred when there was temporoparietal hypometabolism, which was present in 7 of the 14 FTLD scans and 6 of the 7 scans lacking unanimity. Hypometabolism of anterior cingulate and anterior temporal regions had higher specificities and positive likelihood ratios for FTLD than temporoparietal hypometabolism had for AD. Temporoparietal hypometabolism in FTLD is common and may cause inaccurate interpretation of FDG-PET scans. An interpretation paradigm that focuses on the absence of hypometabolism in regions typically affected in AD before considering FTLD is likely to misclassify a significant portion of FTLD scans. Anterior cingulate and/or anterior temporal hypometabolism indicates a high likelihood of FTLD, even when temporoparietal hypometabolism is present. Ultimately, the accurate interpretation of FDG-PET scans in patients with dementia cannot rest on the presence or absence of a single region of hypometabolism but rather must take into account the relative hypometabolism of all brain regions.

Age-Related Metabolic Profiles in Cognitively Healthy Elders: Results from a Voxel-Based [18F]Fluorodeoxyglucose–Positron-Emission Tomography Study with Partial Volume Effects Correction: Fig 1.

Functional brain variability has been scarcely investigated in cognitively healthy elderly subjects, and it is currently debated whether previous findings of regional metabolic variability are artifacts associated with brain atrophy. The primary purpose of this study was to test whether there is regional cerebral age-related hypometabolism specifically in later stages of life. MR imaging and FDG-PET data were acquired from 55 cognitively healthy elderly subjects, and voxel-based linear correlations between age and GM volume or regional cerebral metabolism were conducted by using SPM5 in images with and without correction for PVE. To investigate sex-specific differences in the pattern of brain aging, we repeated the above voxelwise calculations after dividing our sample by sex. Our analysis revealed 2 large clusters of age-related metabolic decrease in the overall sample, 1 in the left orbitofrontal cortex and the other in the right temporolimbic region, encompassing the hippocampus, the parahippocampal gyrus, and the amygdala. The division of our sample by sex revealed significant sex-specific age-related metabolic decrease in the left temporolimbic region of men and in the left dorsolateral frontal cortex of women. When we applied atrophy correction to our PET data, none of the above-mentioned correlations remained significant. Our findings suggest that age-related functional brain variability in cognitively healthy elderly individuals is largely secondary to the degree of regional brain atrophy, and the findings provide support to the notion that appropriate PVE correction is a key tool in neuroimaging investigations.

Time Course of Glucose Metabolism in Relation to Cognitive Performance and Postmortem Neuropathology in Met146Val PSEN1 Mutation Carriers

Studies in carriers of mutations that cause early-onset familial Alzheimer’s disease (eoFAD) are of significant interest.We showed previously that regional glucose hypometabolism could be detected many years before disease onset in presenilin 1(PSEN1) mutation carriers. Here we studied four members of a family with a Met146Val PSEN1 mutation, two symptomatic carriers and two non-carriers, longitudinally with 18F-FDG PET over a period of about two and four years, respectively. The two mutation carriers showed global cortical glucose hypometabolism over time with the most distinct decline occurring in the posterior cingulate, the parietal and parietotemporal cortex, which was also observed when compared with a group of 23 healthy controls and a group of 27 sporadic Alzheimer’s disease (sAD) patients. This decline correlated with cognitive deterioration overtime as measured by neuropsychological tests. Postmortem examination of brain tissue revealed substantially elevated levels of AD type neuropathology in terms of neuritic plaques and neurofibrillary tangles in the two mutation carriers compared with a reference group of 249 sAD patients. In the mutation carriers, the amount of neuritic plaques but not neurofibrillary tangles correlated hereby significantly with regional glucose metabolism as measured by 18F-FDG on the last scanning occasions, which were performed four and approximately five years before death, respectively. We here show that FDG PET can depict in vivo the aggressive disease progression in eoFAD mutation carriers in relationship to neuropathology.

FDG-PET improves surgical outcome in negative MRI Taylor-type focal cortical dysplasias

To determine the diagnostic accuracy and prognostic value of ¹⁸FDG-PET in a recent series of patients operated for intractable partial epilepsy associated with histologically proven Taylor-type focal cortical dysplasia (TTFCD) and negative MRI. Of 23 consecutive patients (12 male, 7-38 years old) with negative 1.5-Tesla MRI, 10 exhibited subtle nonspecific abnormalities (e.g., unusual sulcus depth or gyral pattern) and the 13 others had strictly normal MRI. FDG-PET was analyzed both visually after coregistration on MRI and using SPM5 software. Metabolic data were compared with the epileptogenic zone (EZ) determined by stereo-EEG (SEEG) and surgical outcome. Visual PET analysis disclosed a focal or regional hypometabolism in 18 cases (78%) corresponding to a single gyrus (n = 9) or a larger cortical region (n = 9). PET/MRI coregistration detected a partially hypometabolic gyrus in 4 additional cases. SPM5 PET analysis (n = 18) was concordant with visual analysis in 13 cases. Location of PET abnormalities was extratemporal in all cases, involving eloquent cortex in 15 (65%). Correlations between SEEG, PET/MRI, and histologic findings (n = 20) demonstrated that single hypometabolic gyri (n = 11) corresponded to EZ and TTFCD, which was localized at the bottom of the sulcus. Larger hypometabolic areas (n = 9) also included the EZ and the dysplastic cortex but were more extensive. Following limited cortical resection (mean follow-up 4 years), seizure freedom without permanent motor deficit was obtained in 20/23 patients (87%). ¹⁸FDG-PET coregistered with MRI is highly sensitive to detect TTFCD and greatly improves diagnosis and surgical prognosis of patients with negative MRI.

18F]FDG-PET as a Biomarker for Early Alzheimer`s Disease

Fluorine)fluorodeoxiglucose-Positron Emission Tomgraphy ( 18 F FDG-PET) has gained a leading role in the diagnostic assessment of patients with cognitive complaints, notably Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). Together with morphological Magnetic Resonance Imaging (MRI) and cerebrospinal fluid biomarker assays it allows early identification of subjects with neurodegeneration of the AD-type, which is crucial in view of effective disease-modifying drugs. (18F)FDG-PET identifies hypometabolic regions in posterior cingulate-precuneus, posterior lateral and medial temporal-parietal association cortex, and in lateral frontal cortex. Hypometabolism in posterior cingulate-precuneus may be found even in MCI patients not yet converted to AD after a reasonable follow-up time and thus it might be a marker of memory deficit rather than of AD conversion. As (18F)FDG-PET is sensitive to synaptic dysfunction and depletion, hypometabolic areas can be detected before atrophy is highlighted by MRI in the same regions. The interpretation of the pathophysiological meaning of hypometabolism is discussed also in view of the most recent theory on the brain 'default mode network'. In longitudinal 1-year studies, (18F)FDG-PET has been shown an adequate tool to detect metabolic deterioration in AD patients better than amyloid-PET. It has been proposed as a surrogate biomarker to evaluate the effect of disease-modifying drugs in AD with a five times higher power than the commonly used neuropsychological scales. A flow-chart on the clinical use of (18F)FDG-PET is proposed, in which it is strongly recommended in MCI patients with suspected neurodegeneration.

Amygdalar enlargement in patients with temporal lobe epilepsy

ObjectiveThe purpose of the study was to clarify the significance of amygdalar enlargement (AE) in patients with temporal lobe epilepsy (TLE) detected by MRI.Methods11 TLE patients (eight men, mean age...

Vascular diseases and old age mental disorders: an update of neuroimaging findings

To review neuroimaging findings that have been reported in samples of patients with cardiovascular disorders and their association with the onset of Alzheimer's disease, vascular dementia, depression and bipolar disorder in the elderly and to highlight the implications of these findings to the knowledge about the pathophysiology of psychiatric disorders in old age, as well as their potential clinical implications. Vascular risk factors, such as hypertension, diabetes, dyslipidemia, smoking habits and heart failure, have all been associated with signs of cerebrovascular dysfunction, including structural MRI findings of signal hyperintensities, lacunes and stroke and functional imaging findings of brain regional hypoperfusion and hypometabolism. Such brain abnormalities have been found to increase the risk of onset of psychiatric disorder (depression, bipolar and dementia) in old age. As vascular risk factors are potentially modifiable when detected in midlife, the early characterization of brain changes associated with the presence of cardiovascular diseases holds promise to afford clinical applications in psychiatry, providing new perspectives for the prevention of old age psychiatric disorders.

Assessing the reliability to detect cerebral hypometabolism in probable Alzheimer's disease and amnestic mild cognitive impairment

Fluorodeoxyglucose positron emission tomography (FDG-PET) studies report characteristic patterns of cerebral hypometabolism in probable Alzheimer's disease (pAD) and amnestic mild cognitive impairment (aMCI). This study aims to characterize the consistency of regional hypometabolism in pAD and aMCI patients enrolled in the AD neuroimaging initiative (ADNI) using statistical parametric mapping (SPM) and bootstrap resampling, and to compare bootstrap-based reliability index to the commonly used type-I error approach with or without correction for multiple comparisons. Batched SPM5 was run for each of 1000 bootstrap iterations to compare FDG-PET images from 74 pAD and 142 aMCI patients, respectively, to 82 normal controls. Maps of the hypometabolic voxels detected for at least a specific percentage of times over the 1000 runs were examined and compared to an overlap of the hypometabolic maps obtained from 3 randomly partitioned independent sub-datasets. The results from the bootstrap derived reliability of regional hypometabolism in the overall data set were similar to that observed in each of the three non-overlapping sub-sets using family-wise error. Strong but non-linear association was found between the bootstrap-based reliability index and the type-I error. For threshold p=0.0005, pAD was associated with extensive hypometabolic voxels in the posterior cingulate/precuneus and parietotemporal regions with reliability between 90% and 100%. Bootstrap analysis provides an alternative to the parametric family-wise error approach used to examine consistency of hypometabolic brain voxels in pAD and aMCI patients. These results provide a foundation for the use of bootstrap analysis characterize statistical ROIs or search regions in both cross-sectional and longitudinal FDG-PET studies. This approach offers promise in the early detection and tracking of AD, the evaluation of AD-modifying treatments, and other biologically or clinical important measurements using brain images and voxel-based data analysis techniques.

The topography and significance of extratemporal hypometabolism in refractory mesial temporal lobe epilepsy examined by FDG‐PET

This study aims to map the temporal and extratemporal 18-fluorodeoxyglucose positron emission tomography (FDG-PET)-defined hypometabolism in mesial temporal lobe epilepsy (MTLE). We hypothesize that quantitative analysis will reveal extensive extratemporal glucose hypometabolism (EH), that the EH is related to seizure propagation beyond the temporal lobe, hypometabolism restricted to one temporal lobe predicts a good outcome following surgery, and EH predicts a poor outcome. Sixty-four patients were studied who had undergone temporal lobectomy for intractable MTLE and had at least 2 years of postoperative follow-up. Spatial preprocessing and statistical analysis on preoperative interictal FDG-PET using statistical parametric mapping (SPM 2) identified significant regions of hypometabolism compared to normal controls. The predictors of outcome were determined by univariable and multiple logistic regression analyses. EH was common and widespread, occurring most frequently in the ipsilateral insula and frontal lobe. The extent of EH was not significantly associated with age of onset or the duration of epilepsy. Presence of secondarily generalized tonic--clonic seizures (SGTCS) was associated with a larger extent of remote hypometabolism (RH, p < 0.005). Multiple logistic regression analysis identified the extent of RH and the age at surgery as independent predictors of seizure outcome. Our results indicate that RH in MTLE is associated with a poorer surgical outcome, especially if seen in the contralateral hemisphere. The extent of RH relates to SGTCS but not to duration of epilepsy.