Barbara Vogt

Differential effects of global and cerebellar normalization on detection and differentiation of dementia in FDG-PET studies

FDG-PET ([18F]fluorodeoxyglucose positron emission tomography) is frequently used to improve the differential diagnosis of dementia. However, a fundamental methodological issue of the reference area for the intensity normalization procedure is still unsolved. Here, we systematically compared the two most commonly used normalization methods to the cerebral and to the cerebellar metabolic rate for glucose with regard to detection and differentiation of dementia syndromes. FDG-PET imaging was performed on 19 subjects with early Alzheimers disease, 13 subjects with early frontotemporal lobar degeneration and 10 subjects complaining of memory impairment, which had not been confirmed by comprehensive clinical testing. Images were normalized to either the cerebral or the cerebellar metabolic rate for glucose. Differences in relative regional glucose metabolism were assessed by voxelwise comparison. Analysis using the two normalization procedures revealed remarkable differential effects. Whereas cerebellar normalization was superior in identifying dementia patients in comparison to control subjects, cerebral normalization showed better results for differential diagnosis between types of dementia. These effects were shown for both, Alzheimers disease and frontotemporal lobar degeneration. Relative hypermetabolism in comparison to the control group was only detected in both kinds of dementia using global normalization. The results indicate that normalization has a decisive impact on diagnostic accuracy in dementia. While cerebellar normalization seems to be more sensitive for early diagnosis, cerebral global normalization might be superior for differential diagnostic purposes in dementia syndromes.

Dissociating memory networks in early Alzheimer’s disease and frontotemporal lobar degeneration: A combined study of hypometabolism and atrophy

Introduction We aimed at dissociating the neural correlates of memory disorders in Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). Methods We included patients with AD (n = 19, 11 female, mean age 61 years) and FTLD (n = 11, 5 female, mean age 61 years) in early stages of their diseases. Memory performance was assessed by means of verbal and visual memory subtests from the Wechsler Memory Scale (WMS-R), including forgetting rates. Brain glucose utilization was measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and brain atrophy by voxel-based morphometry (VBM) of T1-weighted magnetic resonance imaging (MRI) scans. Using a whole brain approach, correlations between test performance and imaging data were computed separately in each dementia group, including a group of control subjects (n = 13, 6 female, mean age 54 years) in both analyses. The three groups did not differ with respect to education and gender. Results Patients in both dementia groups generally performed worse than controls, but AD and FTLD patients did not differ from each other in any of the test parameters. However, memory performance was associated with different brain regions in the patient groups, with respect to both hypometabolism and atrophy: Whereas in AD patients test performance was mainly correlated with changes in the parieto-mesial cortex, performance in FTLD patients was correlated with changes in frontal cortical as well as subcortical regions. There were practically no overlapping regions associated with memory disorders in AD and FTLD as revealed by a conjunction analysis. Conclusion Memory test performance may not distinguish between both dementia syndromes. In clinical practice, this may lead to misdiagnosis of FTLD patients with poor memory performance. Nevertheless, memory problems are associated with almost completely different neural correlates in both dementia syndromes. Obviously, memory functions are carried out by distributed networks which break down in brain degeneration.

Dissociating behavioral disorders in early dementia - An FDG-PET study

Behavioral impairments occur frequently in dementia. Studies with magnetic resonance imaging, measuring atrophy, have systematically investigated their neural correlates. Such a systematic approach has not yet been applied to imaging with [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET), although regional hypometabolism may precede and exceed atrophy in dementia. The present study related all behavioral disorders as assessed with the Neuropsychiatric Inventory to reductions in brain glucose utilization as measured by FDG-PET with Statistical Parametric Mapping (SPM5). It included 54 subjects mainly with early Alzheimers disease, frontotemporal lobar degeneration, and subjective cognitive impairment. Apathy, disinhibition and eating disorders - most frequent in frontotemporal lobar degeneration - correlated significantly with regional brain hypometabolism. Whereas a single regressor analysis and conjunction analysis revealed largely overlapping frontomedian regions that were associated with all three behavioral domains, a disjunction analysis identified three specific neural networks for each behavioral disorder, independent of dementia severity. Apathy was related to the ventral tegmental area, a component of the motivational dopaminergic network; disinhibition to both anterior temporal lobes including the anterior hippocampi and left amygdala, caudate head, orbitofrontal cortex and insulae; and eating disorders to the right lateral (orbito) frontal cortex/insula. Our study contributes to the understanding of behavioral deficits in early dementia and suggests specific diagnostic and therapeutic approaches.

Functional Regions of Interest in Electrical Impedance Tomography: A Secondary Analysis of Two Clinical Studies

Introduction Patients with acute respiratory distress syndrome (ARDS) typically show a high degree of ventilation inhomogeneity, which is associated with morbidity and unfavorable outcomes. Electrical impedance tomography (EIT) is able to detect ventilation inhomogeneity, but it is unclear which method for defining the region of interest (ROI) should be used for this purpose. The aim of our study was to compare the functional region of interest (fROI) method to both the lung area estimation method (LAEM) and no ROI when analysing global parameters of ventilation inhomogeneity. We assumed that a good method for ROI determination would lead to a high discriminatory power for ventilation inhomogeneity, as defined by the area under the receiver operating characteristics curve (AUC), comparing patients suffering from ARDS and control patients without pulmonary pathologies. Methods We retrospectively analysed EIT data from 24 ARDS patients and 12 control patients without pulmonary pathology. In all patients, a standardized low-flow-pressure volume maneuver had been performed and was used for EIT image generation. We compared the AUC for global inhomogeneity (GI) index and coefficient of variation (CV) between ARDS and control patients using all EIT image pixels, the fROI method and the LAEM for ROI determination. Results When analysing all EIT image pixels, we found an acceptable AUC both for the GI index (AUC = 0.76; 95% confidence interval (CI) 0.58–0.94) and the CV (AUC = 0.74; 95% CI 0.55–0.92). With the fROI method, we found a deteriorating AUC with increasing threshold criteria. With the LAEM, we found the best AUC both for the GI index (AUC = 0.89; 95% CI 0.78–1.0) and the CV (AUC = 0.89; 95% CI 0.78–1.0) using a threshold criterion of 50% of the maximum tidal impedance change. Conclusion In the assessment of ventilation inhomogeneity with EIT, functional regions of interest obscure the difference between patients with ARDS and control patients without pulmonary pathologies. The LAEM is preferable to the fROI method when assessing ventilation inhomogeneity.

Regional lung function testing in children using electrical impedance tomography

To evaluate regional lung function in lung‐healthy children before and after exercise challenge using electrical impedance tomography (EIT).