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Stefan Förster

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6 papers

1 author row

YNICL Journal 2020 Journal Article

Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder

Xianhua Han
Ping Wu
Ian Alberts
Hucheng Zhou
Huan Yu
Panagiotis Bargiotas
Igor Yakushev
Jian Wang

OBJECTIVE: F-FDG reveals metabolic perturbations, which are scored by spatial covariance analysis. However, the resultant pattern scores do not capture the spatially heterogeneous trajectories of metabolic changes between individual brain regions. Assuming metabolic progression occurs as a continuum from the healthy control (HC) condition to iRBD and then PD, we investigated spatial dynamics of progressively perturbed glucose metabolism in a cross-sectional study. METHODS: F-FDG uptake and the Unified Parkinson's Disease Rating Scale motor (UPDRS III) scores in the PD group. RESULTS: F-FDG metabolism and disease duration in the iRBD group. Regional hyper- and hypo-metabolism in the PD patients correlated with disease duration or clinical UPDRS III scores. CONCLUSION: Cerebral metabolism changes heterogeneously in a continuum extending from HC to iRBD and PD groups in this preliminary study. The distinctive metabolic trajectories point towards a potential neuroimaging biomarker for conversion of iRBD to frank PD, which should be amenable to advanced pattern recognition analysis in future longitudinal studies.

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YNIMG Journal 2017 Journal Article

Data-driven identification of intensity normalization region based on longitudinal coherency of 18F-FDG metabolism in the healthy brain

Huiwei Zhang
Ping Wu
Sibylle I. Ziegler
Yihui Guan
Yuetao Wang
Jingjie Ge
Markus Schwaiger
Sung-Cheng Huang

Objectives In brain 18F-FDG PET data intensity normalization is usually applied to control for unwanted factors confounding brain metabolism. However, it can be difficult to determine a proper intensity normalization region as a reference for the identification of abnormal metabolism in diseased brains. In neurodegenerative disorders, differentiating disease-related changes in brain metabolism from age-associated natural changes remains challenging. This study proposes a new data-driven method to identify proper intensity normalization regions in order to improve separation of age-associated natural changes from disease related changes in brain metabolism. Methods 127 female and 128 male healthy subjects (age: 20 to 79) with brain18F-FDG PET/CT in the course of a whole body cancer screening were included. Brain PET images were processed using SPM8 and were parcellated into 116 anatomical regions according to the AAL template. It is assumed that normal brain 18F-FDG metabolism has longitudinal coherency and this coherency leads to better model fitting. The coefficient of determination R2 was proposed as the coherence coefficient, and the total coherence coefficient (overall fitting quality) was employed as an index to assess proper intensity normalization strategies on single subjects and age-cohort averaged data. Age-associated longitudinal changes of normal subjects were derived using the identified intensity normalization method correspondingly. In addition, 15 subjects with clinically diagnosed Parkinson's disease were assessed to evaluate the clinical potential of the proposed new method. Results Intensity normalizations by paracentral lobule and cerebellar tonsil, both regions derived from the new data-driven coherency method, showed significantly better coherence coefficients than other intensity normalization regions, and especially better than the most widely used global mean normalization. Intensity normalization by paracentral lobule was the most consistent method within both analysis strategies (subject-based and age-cohort averaging). In addition, the proposed new intensity normalization method using the paracentral lobule generates significantly higher differentiation from the age-associated changes than other intensity normalization methods. Conclusion Proper intensity normalization can enhance the longitudinal coherency of normal brain glucose metabolism. The paracentral lobule followed by the cerebellar tonsil are shown to be the two most stable intensity normalization regions concerning age-dependent brain metabolism. This may provide the potential to better differentiate disease-related changes from age-related changes in brain metabolism, which is of relevance in the diagnosis of neurodegenerative disorders.

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YNICL Journal 2014 Journal Article

LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo

Timo Grimmer
Oliver Goldhardt
Liang-Hao Guo
Behrooz H. Yousefi
Stefan Förster
Alexander Drzezga
Christian Sorg
Panagiotis Alexopoulos

OBJECTIVE: Impaired amyloid clearance has been proposed to contribute to β-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of β-amyloid across the blood-brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in genetic studies. We aimed to elucidate the association of this polymorphism with in-vivo brain amyloid load of AD patients using amyloid PET with [(11)C]PiB. MATERIALS AND METHODS: 72 patients with very mild to moderate AD were examined with amyloid PET and C667T polymorphism was obtained using TaqMan PCR assays. The association of C667T polymorphism with global and regional amyloid load was calculated using linear regression and voxel based analysis, respectively. The effect of the previously identified modulator of amyloid uptake, the apolipoprotein E genotype, on this association was also determined. RESULTS: The regression analysis between amyloid load and C667T polymorphism was statistically significant (p = 0.046, β = 0.236). In an additional analysis ApoE genotype and gender were identified to explain further variability of amyloid load. Voxel based analysis revealed a significant (p < 0.05) association between C667T polymorphism and amyloid uptake in the temporo-parietal cortex bilaterally. ApoE did not interact significantly with the LRP-1 polymorphism. DISCUSSION: In conclusion, C667T polymorphism of LRP-1 is moderately but significantly associated with global and regional amyloid deposition in AD. The relationship appears to be independent of the ApoE genotype. This finding is compatible with the hypothesis that impaired amyloid clearance contributes to amyloid deposition in late-onset sporadic AD.

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YNIMG Journal 2010 Journal Article

Real versus imagined locomotion: A [18F]-FDG PET-fMRI comparison

Christian la Fougère
Andreas Zwergal
Axel Rominger
Stefan Förster
Gunther Fesl
Marianne Dieterich
Thomas Brandt
Michael Strupp

The cortical, cerebellar and brainstem BOLD-signal changes have been identified with fMRI in humans during mental imagery of walking. In this study the whole brain activation and deactivation pattern during real locomotion was investigated by [18F]-FDG-PET and compared to BOLD-signal changes during imagined locomotion in the same subjects using fMRI. Sixteen healthy subjects were scanned at locomotion and rest with [18F]-FDG-PET. In the locomotion paradigm subjects walked at constant velocity for 10 min. Then [18F]-FDG was injected intravenously while subjects continued walking for another 10 min. For comparison fMRI was performed in the same subjects during imagined walking. During real and imagined locomotion a basic locomotion network including activations in the frontal cortex, cerebellum, pontomesencephalic tegmentum, parahippocampal, fusiform and occipital gyri, and deactivations in the multisensory vestibular cortices (esp. superior temporal gyrus, inferior parietal lobule) was shown. As a difference, the primary motor and somatosensory cortices were activated during real locomotion as distinct to the supplementary motor cortex and basal ganglia during imagined locomotion. Activations of the brainstem locomotor centers were more prominent in imagined locomotion. In conclusion, basic activation and deactivation patterns of real locomotion correspond to that of imagined locomotion. The differences may be due to distinct patterns of locomotion tested. Contrary to constant velocity real locomotion (10 min) in [18F]-FDG-PET, mental imagery of locomotion over repeated 20-s periods includes gait initiation and velocity changes. Real steady-state locomotion seems to use a direct pathway via the primary motor cortex, whereas imagined modulatory locomotion an indirect pathway via a supplementary motor cortex and basal ganglia loop.

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YNIMG Journal 2010 Journal Article

Uptake and binding of the serotonin 5-HT1A antagonist [18F]-MPPF in brain of rats: Effects of the novel P-glycoprotein inhibitor tariquidar

Christian la Fougère
Guido Böning
Hero Bartmann
Björn Wängler
Sebastian Nowak
Theresa Just
Erika Wagner
Petra Winter

We used microPET to map the dose–response to the novel P-glycoprotein (P-gp) inhibitor tariquidar (TQD) of the initial influx of the P-gp substrate [18F]-MPPF in rat brain, and to test for effects of P-gp inhibition on the subsequent binding of [18F]-MPPF to serotonin 5-HT1A receptors. Summation maps of [18F]-MPPF uptake during the first 100 seconds after intravenous injection were calculated in groups of rats with vehicle (glucose 5%) pretreatment, or following pretreatment with TQD at doses of 5, 15, or 30 mg/kg. The early summation image (K 1-weighted), were validated as a surrogate marker for the physiological blood–brain clearance (K 1; ml g− 1 min−1) by linear graphic analysis of the unidirectional blood–brain clearance relative to an image-based arterial input measured in the left ventricle of the heart. In the same animals, parametric maps of the [18F]-MPPF binding potential (BPND) were calculated from the entire 60-minute emission recordings using conventional reference tissue methods. All [18F]-MPPF recordings were followed by an [18F]-FDG emission recording, the summation of which was used for spatial normalization to a rat brain atlas. Test–retest variability of K 1-weighted uptake and BPND was 25%. TQD treatment evoked a global dose-dependent increase in K 1-weighted summation, which increased 2. 5-fold with TQD (30 mg/kg), suggesting an IC50 of 5 mg/kg TQD. All TQD doses increased the apparent [18F]-MPPF BPND calculated by the Logan method by 30%–40%, a bias likely arising due to increased free [18F]-MPPF concentrations in brain. TQD (15 mg/kg) evoked a 45% global increase in [18F]-FDG uptake, suggesting perturbation of brain energy metabolism due to P-gp blockade.

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YNIMG Journal 2009 Journal Article

Subcortical elevation of metabolism in Parkinson's disease — A critical reappraisal in the context of global mean normalization

Per Borghammer
Paul Cumming
Joel Aanerud
Stefan Förster
Albert Gjedde

In a recent issue of NeuroImage, we presented evidence that biased global mean (GM) normalization of brain PET data can generate the appearance of subcortical foci with relative hypermetabolism in patients with Parkinson's disease (PD), and other degenerative disorders. In a commentary to our article, Ma and colleagues presented a study seeking to establish that a pattern of widespread hypermetabolism, known as the Parkinson's disease related pattern (PDRP) is a genuine metabolic feature of PD. In the present paper, we respond to the arguments presented by Ma et al. , and we provide a critical reappraisal of the evidence for the existence of the PDRP. To this end, we present new analyses of PET data sets, which demonstrate that very similar patterns of relative subcortical increases are seen in PD, Alzheimer's disease, hepatic encephalopathy, healthy aging, and simulation data. Furthermore, longitudinal studies of PD previously reported relative hypermetabolism in very small anatomical structures such as the subthalamic nucleus. We now demonstrate how focal hypermetabolism attributed to small nuclei can similarly arise as a consequence of GM normalization. Finally, we give a comprehensive summary of the entire deoxyglucose autoradiography literature on acquired parkinsonism in experimental animals. Based on this evidence, we conclude that (1) there is no quantitative evidence for widespread subcortical hypermetabolism in PD, (2) very similar patterns of subcortical hyperactivity are evident in various other brain disorders whenever GM normalization is utilized, and (3) the PDRP is not evident in animal models of PD. In the absence of quantitative evidence for the PDRP, our alternative interpretation of normalization bias seems the more parsimonious explanation for the reports of relative hypermetabolism in PD.

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