Author name cluster

Axel Rominger

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16 papers

1 author row

YNICL Journal 2025 Journal Article

Partial volume effect correction impairs the diagnostic utility of [18F]-THK-5351 PET in nonfluent-agrammatic variant primary progressive aphasia

Patrick J. Sommer
Sebastian Schuster
Oliver Goldhardt
Nobuyuki Okamura
Felix Mueller-Sarnowski
Maximilian Scheifele
Florian Eckenweber
Annika Kreuzer

OBJECTIVES: F]-THK-5351 PET a marker of reactive neuroinflammatory astrogliosis as well as tau-binding. METHODS: F]-THK-5351 PET signal differences between nfv-PPA and controls before and after PVEC. Additionally, a blinded visual read was performed by three nuclear medicine physicians (consensus) before and after PVEC. RESULTS: F]-THK-5351 tracer uptake was significantly higher in the bilateral frontal cortex of patients with nfv-PPA when compared to HC (left > right), despite significant grey matter atrophy in the same brain regions in patients with nfv-PPA. SUVr differences between nfv-PPA and HC were further increased by PVEC in frontal brain regions, but group level variance increased in parallel and reduced the number of significant differences between SUVr of nfv-PPA and HC (uncorrected: 10 significant regions, CoV[nfv-PPA]: 20.8 % ± 4.7 %, CoV[HC]: 7.9 % ± 2.4 %/PVEC: 3 significant regions, CoV[nfv-PPA]: 28.4 % ± 8.9 %, CoV[HC]: 9.8 % ± 2.5 %). Sensitivity/specificity of the visual read for detection of nfv-PPA was 0.85/1.00 without PVEC and 0.85/0.75 with PVEC. CONCLUSIONS: F]-THK-5351 images in patients with nfv-PPA is impaired by PVEC due to loss of specificity and does not support the use of PVEC even in patients with severe atrophy.

YNIMG Journal 2024 Journal Article

Detection of individual brain tau deposition in Alzheimer's disease based on latent feature-enhanced generative adversarial network

Jiehui Jiang
Rong Shi
Jiaying Lu
Min Wang
Qi Zhang
Shuoyan Zhang
Luyao Wang
Ian Alberts

OBJECTIVE: The conventional methods for interpreting tau PET imaging in Alzheimer's disease (AD), including visual assessment and semi-quantitative analysis of fixed hallmark regions, are insensitive to detect individual small lesions because of the spatiotemporal neuropathology's heterogeneity. In this study, we proposed a latent feature-enhanced generative adversarial network model for the automatic extraction of individual brain tau deposition regions. METHODS: The latent feature-enhanced generative adversarial network we propose can learn the distribution characteristics of tau PET images of cognitively normal individuals and output the abnormal distribution regions of patients. This model was trained and validated using 1131 tau PET images from multiple centres (with distinct races, i.e., Caucasian and Mongoloid) with different tau PET ligands. The overall quality of synthetic imaging was evaluated using structural similarity (SSIM), peak signal to noise ratio (PSNR), and mean square error (MSE). The model was compared to the fixed templates method for diagnosing and predicting AD. RESULTS: The reconstructed images archived good quality, with SSIM = 0.967 ± 0.008, PSNR = 31.377 ± 3.633, and MSE = 0.0011 ± 0.0007 in the independent test set. The model showed higher classification accuracy (AUC = 0.843, 95 % CI = 0.796-0.890) and stronger correlation with clinical scales (r = 0.508, P < 0.0001). The model also achieved superior predictive performance in the survival analysis of cognitive decline, with a higher hazard ratio: 3.662, P < 0.001. INTERPRETATION: The LFGAN4Tau model presents a promising new approach for more accurate detection of individualized tau deposition. Its robustness across tracers and races makes it a potentially reliable diagnostic tool for AD in practice.

YNICL Journal 2023 Journal Article

The heterogeneity of asymmetric tau distribution is associated with an early age at onset and poor prognosis in Alzheimer’s disease

Jiaying Lu
Zhengwei Zhang
Ping Wu
Xiaoniu Liang
Huiwei Zhang
Jimin Hong
Christoph Clement
Tzu-Chen Yen

PURPOSE: Left-right asymmetry, an important feature of brain development, has been implicated in neurodegenerative diseases, although it's less discussed in typical Alzheimer's disease (AD). We sought to investigate whether asymmetric tau deposition plays a potential role in AD heterogeneity. METHODS: F-Florzolotau]. Based on the absolute global tau interhemispheric differences, each cohort was divided into two groups (asymmetric versus symmetric tau distribution). The two groups were cross-sectionally compared in terms of demographic, cognitive characteristics, and pathological burden. The cognitive decline trajectories were analyzed longitudinally. RESULTS: Fourteen (23.3%) and 42 (48.3%) patients in the ADNI and SMS cohorts showed an asymmetric tau distribution, respectively. An asymmetric tau distribution was associated with an earlier age at disease onset (proportion of early-onset AD: ADNI/SMS/combined cohorts, p = 0.093/0.026/0.001) and more severe pathological burden (i.e., global tau burden: ADNI/SMS cohorts, p < 0.001/= 0.007). And patients with an asymmetric tau distribution were characterized by a steeper cognitive decline longitudinally (i.e., the annual decline of Mini-Mental Status Examination score: ADNI/SMS/combined cohorts, p = 0.053 / 0.035 / < 0.001). CONCLUSIONS: Asymmetry in tau deposition, which may be associated with an earlier age at onset, more severe pathological burden, and a steeper cognitive decline, is potentially an important characteristic of AD heterogeneity.

JBHI Journal 2022 Journal Article

Non-Invasive Glucose Metabolism Quantification Method Based on Unilateral ICA Image Derived Input Function by Hybrid PET/MR in Ischemic Cerebrovascular Disease

Min Wang
Bixiao Cui
Yi Shan
Hongwei Yang
Zhuangzhi Yan
Lalith Kumar Shiyam Sundar
Ian Alberts
Axel Rominger

The non-invasive quantification of the cerebral metabolic rate for glucose (CMRGlc) and the characterization of cerebral metabolism in the cerebrovascular territories are helpful in understanding ischemic cerebrovascular disease (ICVD). Firstly, we investigated a non-invasive quantification approach based on an image-derived input function (IDIF) in ICVD. Second, we studied the metabolic changes in CMRGlc after surgical intervention. We evaluated the hypothesis that the IDIF method based on the unilateral internal carotid artery could address challenges in ICVD quantification. The CMRGlc and standardized uptake value ratio (SUVR) were used to measure glucose metabolism activity. Healthy controls showed no significant differences in CMRGlc values between bilateral and unilateral IDIF measurements (intraclass correlation coefficient [ICC]: 0. 91–0. 98). Patients with ICVD showed significantly increased CMRGlc values after surgical intervention for all territories (percentage changes: 7. 4%–22. 5%). In contrast, SUVR showed minor differences between postoperative and preoperative patients, indicating that it was a poor biomarker for the diagnosis of ICVD. A significant association between CMRGlc and the National Institutes of Health Stroke Scale (NIHSS) scores was observed ( r =-0. 54). Our findings suggested that IDIF could be a valuable tool for CMRGlc quantification in patients with ICVD and may advance personalized precision interventions.

YNICL Journal 2021 Journal Article

Cognitive reserve hypothesis in frontotemporal dementia: A FDG-PET study

Leonie Beyer
Johanna Meyer-Wilmes
Sonja Schönecker
Jonas Schnabel
Julia Sauerbeck
Maximilian Scheifele
Catharina Prix
Marcus Unterrainer

BACKGROUND AND OBJECTIVE: F]-fluorodeoxyglucose positron-emission-tomography (FDG-PET) hypometabolism in FTD. METHODS: Sixty-six FTD subjects (age 67 ± 8 years) and twenty-four cognitively healthy controls (HC) were evaluated. Brain regions with FTD-related glucose hypometabolism in the contrast against HC and brain regions that correlate with the cognitive function were defined by a voxel-based analysis and individual FDG-PET values were extracted from all frontotemporal brain areas. Linear regression analysis served to test if education is associated with residualized cognitive performance and regional FDG-PET hypometabolism after controlling for global cognition. RESULTS: Compared to healthy controls, patients with FTD showed glucose hypometabolism in bilateral frontal and temporal brain areas whereas cognition was only associated with deteriorated glucose metabolism in the left temporal lobe. The education level was significantly correlated with the residualized cognitive performance (residuals from regression analysis between hypometabolism and cognitive function as a quantitative index of reserve) and also negatively correlated with left temporal FDG-PET hypometabolism after controlling for cognition. CONCLUSIONS: In patients with FTD, the education level predicts the existing left temporal FDG-PET hypometabolism at the same cognition level, supporting the cognitive reserve hypothesis in FTD.

YNIMG Journal 2021 Journal Article

Microglial activation in the right amygdala-entorhinal-hippocampal complex is associated with preserved spatial learning in App mice

Gloria Biechele
Karin Wind
Tanja Blume
Christian Sacher
Leonie Beyer
Florian Eckenweber
Nicolai Franzmeier
Michael Ewers

BACKGROUND: In Alzheimer`s disease (AD), regional heterogeneity of β-amyloid burden and microglial activation of individual patients is a well-known phenomenon. Recently, we described a high incidence of inter-individual regional heterogeneity in terms of asymmetry of plaque burden and microglial activation in β-amyloid mouse models of AD as assessed by positron-emission-tomography (PET). We now investigate the regional associations between amyloid plaque burden, microglial activation, and impaired spatial learning performance in transgenic mice in vivo. METHODS: mice, controlled for age and sex. In order to assess the effects of hemispheric asymmetry, we also analyzed correlations of spatial learning performance with tracer uptake in bilateral regions of interest for frontal cortex, entorhinal/piriform cortex, amygdala, and hippocampus, using a regression model. We tested the correlation between regional asymmetry of PET biomarkers with individual spatial learning performance. RESULTS: mice revealed that higher TSPO-PET signal in the amygdala, entorhinal and piriform cortices, the hippocampus and the hypothalamus correlated with spatial learning performance. Region-based analysis showed significant correlations between TSPO expression in the right entorhinal/piriform cortex and the right amygdala and spatial learning performance, whereas there were no such correlations in the left hemisphere. Right lateralized TSPO expression in the amygdala predicted better performance in the Morris water maze (β = -0.470, p = 0.013), irrespective of the global microglial activation and amyloid level. Region-based results for amyloid-PET showed no significant associations with spatial learning. CONCLUSION: mice is associated with better spatial learning. Our findings support a protective role of microglia on cognitive function when they highly express TSPO in specific brain regions involved in spatial memory.

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.

YNICL Journal 2019 Journal Article

Neuronal injury biomarkers for assessment of the individual cognitive reserve in clinically suspected Alzheimer's disease

Leonie Beyer
Jonas Schnabel
Philipp Kazmierczak
Michael Ewers
Sonja Schönecker
Catharina Prix
Johanna Meyer-Wilmes
Marcus Unterrainer

OBJECTIVES: ), all according to the A/T/N-classification. The aim of this study was to calculate residual cognitive performance based on neuronal injury biomarkers as a surrogate of cognitive reserve, and to test the predictive value of this index for the individual clinical course. METHODS: . All neuronal injury markers were tested for an association with clinical MMSE and the resulting residuals were correlated with years of education. We used multiple regression analysis to calculate the expected MMSE score based on neuronal injury biomarkers and covariates. The residuals of the partial correlation for each biomarker and the predicted residualized memory function were correlated with individual cognitive changes measured during clinical follow-up (27 ± 13 months). RESULTS: (R = -0.12, p = .22) showed only weak correlations. Residuals of all neuronal injury biomarker regressions correlated significantly with education level, indicating them to be surrogates of cognitive reserve. A positive residual was associated with faster cognitive deterioration at follow-up for the residuals of stand-alone FDG-PET (R = -0.36, p = .01) and the combined residualized memory function model (R = -0.35, p = .02). CONCLUSIONS: These findings suggest that subjects with higher cognitive reserve had accumulated more pathology, which subsequently caused a faster cognitive decline over time. Together with previous findings suggesting that higher reserve is associated with slower cognitive decline, we propose a biphasic reserve effect, with an initially protective phase followed by more rapid decompensation once the protection is overwhelmed.

YNIMG Journal 2018 Journal Article

Coupling between physiological TSPO expression in brain and myocardium allows stabilization of late-phase cerebral [18F]GE180 PET quantification

Maximilian Deussing
Tanja Blume
Lena Vomacka
Christoph Mahler
Carola Focke
Andrei Todica
Marcus Unterrainer
Nathalie L. Albert

Objectives PET imaging of the 18 kDa translocator protein (TSPO), a biomarker of microglial activity, receives growing interest in clinical and preclinical applications of neuroinflammatory and neurodegenerative brain diseases. In globally affected brains, intra-cerebral pseudo reference regions are not feasible. Consequently, many brain-independent approaches have been attempted, including SUV analysis and normalization to muscle- or heart uptake, aiming to stabilize quantitative analysis. In this study, we systematically compared different image normalization methods for static late phase TSPO-PET imaging of rodent brain. Methods We first obtained gamma counter measurements for gold standard quantitation of [18F]GE180 uptake in brain of C57Bl/6 mice (N = 10) after PET, aiming to identify factors contributing significantly to the quantitative results. Subsequently, data from a large cohort of C57Bl/6 mice (N = 79) were compiled to precisely determine the weighted influence and variance attributable these factors by regression analysis. Scan-rescan variability and agreement with histology were used to validate the tested normalization methods in an Alzheimer's disease (AD) mouse model with pathologically increased TSPO expression (PS2APP; N = 24). Longitudinal data from AD model mice (N = 10) scanned at four different ages were used to challenge and validate the different normalization methods in a practical application. Results Gamma counter results revealed that injected dose, body weight and PET-measured radioactivity concentration in the ventral myocardium all significantly accounted for [18F]GE180 activity in the brain. Skeletal muscle activity had high test-retest variance in this PET only application and was therefore pursued no further. Regression analysis of the large scale evaluation showed that scaling to injected dose or SUV analysis accounted for little variance in brain activity (R2 < 0. 5), but inclusion of myocardial activity together with injected dose and body weight in the regression model accounted for most of the variance in brain uptake (R2 = 0. 94). Scan-rescan stability, correlation with histology and applicability for longitudinal examination in the disease model were also significantly improved by inclusion of myocadial uptake in the quantitative model. Conclusion Cerebral and myocardial TSPO expression are highly coupled under physiological conditions. Myocardial uptake has great potential for stabilization of static late phase [18F]GE180 quantification in brain in the absence of a valid intra-cerebral pseudo-reference region.

YNICL Journal 2017 Journal Article

Evaluation of early-phase [18F]-florbetaben PET acquisition in clinical routine cases

Sonja Daerr
Matthias Brendel
Christian Zach
Erik Mille
Dorothee Schilling
Mathias Johannes Zacherl
Katharina Bürger
Adrian Danek

OBJECTIVES: F]-fluorodeoxyglucose (FDG) PET in a clinical setting. METHODS: All subjects were recruited with clinical suspicion of dementia due to neurodegenerative disease. FDG PET was undertaken by conventional methods, and amyloid PET was performed with FBB, with early recordings for the initial 10 min (early-phase FBB), and late recordings at 90-110 min p.i. (late-phase FBB). Regional SUVR with cerebellar and global mean normalization were calculated for early-phase FBB and FDG PET. Pearson correlation coefficients between FDG and early-phase FBB were calculated for predefined cortical brain regions. Furthermore, a visual interpretation of disease pattern using 3-dimensional stereotactic surface projections (3D-SSP) was performed, with assessment of intra-reader agreement. RESULTS: Among a total of 33 patients (mean age 67.5 ± 11.0 years) included in the study, 18 were visually rated amyloid-positive, and 15 amyloid-negative based on late-phase FBB scans. Correlation coefficients for early-phase FBB vs. FDG scans displayed excellent agreement in all target brain regions for global mean normalization. Cerebellar normalization gave strong, but significantly lower correlations. 3D representations of early-phase FBB visually resembled the corresponding FDG PET images, irrespective of the amyloid-status of the late FBB scans. CONCLUSIONS: Early-phase FBB acquisitions correlate on a relative quantitative and visual level with FDG PET scans, irrespective of the amyloid plaque density assessed in late FBB imaging. Thus, early-phase FBB uptake depicts a metabolism-like image, suggesting it as a valid surrogate marker for synaptic dysfunction, which could ultimately circumvent the need for additional FDG PET investigation in diagnosis of dementia.

YNICL Journal 2017 Journal Article

Identification of brain regions predicting epileptogenesis by serial [18F]GE-180 positron emission tomography imaging of neuroinflammation in a rat model of temporal lobe epilepsy

Vera Russmann
Matthias Brendel
Erik Mille
Angela Helm-Vicidomini
Roswitha Beck
Lisa Günther
Simon Lindner
Axel Rominger

F]GE-180 PET brain imaging can serve as a biomarker of epileptogenesis. The identification of brain regions with predictive value might facilitate the development of preventive concepts as well as the early assessment of the interventional success. Future studies are necessary to further confirm the predictivity of the approach.

YNIMG Journal 2015 Journal Article

Improved longitudinal [18F]-AV45 amyloid PET by white matter reference and VOI-based partial volume effect correction

Matthias Brendel
Marcus Högenauer
Andreas Delker
Julia Sauerbeck
Peter Bartenstein
John Seibyl
Axel Rominger

Amyloid positron-emission-tomography (PET) offers an important research and diagnostic tool for investigating Alzheimer's disease (AD). The majority of amyloid PET studies have used the cerebellum as a reference region, and clinical studies have not accounted for atrophy-based partial volume effects (PVE). Longitudinal studies using cerebellum as reference tissue have revealed only small mean increases and high inter-subject variability in amyloid binding. We aimed to test the effects of different reference regions and PVE-correction (PVEC) on the discriminatory power and longitudinal performance of amyloid PET. We analyzed [18F]-AV45 PET and T1-weighted MRI data of 962 subjects at baseline and two-year follow-up data of 258 subjects. Cortical composite volume-of-interest (VOI) values (COMP) for tracer uptake were generated using either full brain atlas VOIs, gray matter segmented VOIs or gray matter segmented VOIs after VOI-based PVEC. Standard-uptake-value ratios (SUVR) were calculated by scaling the COMP values to uptake in cerebellum (SUVRCBL), brainstem (SUVRBST) or white matter (SUVRWM). Mean SUV, SUVR, and changes after PVEC were compared at baseline between diagnostic groups of healthy controls (HC; N=316), mild cognitive impairment (MCI; N=483) and AD (N=163). Receiver operating characteristics (ROC) were calculated for the discriminations between HC, MCI and AD, and expressed as area under the curve (AUC). Finally, the longitudinal [18F]-AV45-PET data were used to analyze the impact of quantitation procedures on apparent changes in amyloid load over time. Reference region SUV was most constant between diagnosis groups for the white matter. PVEC led to decreases of COMP-SUV in HC (−18%) and MCI (−10%), but increases in AD (+7%). Highest AUCs were found when using PVEC with white matter scaling for the contrast between HC/AD (0. 907) or with brainstem scaling for the contrast between HC/MCI (0. 658). Longitudinal increases were greatest in all diagnosis groups with application of PVEC, and inter-subject variability was lowest for the white matter reference. Thus, discriminatory power of [18F]-AV45-PET was improved by use of a VOI-based PVEC and white matter or brainstem rather than cerebellum reference region. Detection of longitudinal amyloid increases was optimized with PVEC and white matter reference tissue.

YNIMG Journal 2014 Journal Article

Impact of partial volume effect correction on cerebral β-amyloid imaging in APP-Swe mice using [18F]-florbetaben PET

Matthias Brendel
Andreas Delker
Christina Rötzer
Guido Böning
Janette Carlsen
Clemens Cyran
Erik Mille
Franz Josef Gildehaus

We previously investigated the progression of β-amyloid deposition in brain of mice over-expressing amyloid-precursor protein (APP-Swe), a model of Alzheimer's disease (AD), in a longitudinal PET study with the novel β-amyloid tracer [18F]-florbetaben. There were certain discrepancies between PET and autoradiographic findings, which seemed to arise from partial volume effects (PVE). Since this phenomenon can lead to bias, most especially in the quantitation of brain microPET studies of mice, we aimed in the present study to investigate the magnitude of PVE on [18F]-florbetaben quantitation in murine brain, and to establish and validate a useful correction method (PVEC). Phantom studies with solutions of known radioactivity concentration were performed to measure the full-width-at-half-maximum (FWHM) resolution of the Siemens Inveon DPET and to validate a volume-of-interest (VOI)-based PVEC algorithm. Several VOI-brain-masks were applied to perform in vivo PVEC on [18F]-florbetaben data from C57BL/6(N=6) mice, while uncorrected and PVE-corrected data were cross-validated with gamma counting and autoradiography. Next, PVEC was performed on longitudinal PET data set consisting of 43 PET scans in APP-Swe (13–20months) and age-matched wild-type (WT) mice using the previously defined masks. VOI-based cortex-to-cerebellum ratios (SUVR) were compared for uncorrected and PVE-corrected results. Brains from a subset of transgenic mice were ultimately examined by autoradiography ex vivo and histochemistry in vitro as gold standard assessments, and compared to VOI-based PET results. The phantom study indicated a FWHM of 1. 72mm. Applying a VOI-brain-mask including extracerebral regions gave robust PVEC, with increased precision of the SUVR results. Cortical SUVR increased with age in APP-Swe mice compared to baseline measurements (16months: +5. 5%, p<0. 005; 20months: +15. 5%, p<0. 05) with uncorrected data, and to a substantially greater extent with PVEC (16months: +12. 2% p<0. 005; 20months: +36. 4% p<0. 05). WT animals showed no binding changes, irrespective of PVEC. Relative to autoradiographic results, the error [%] for uncorrected cortical SUVR was 18. 9% for native PET data, and declined to 4. 8% upon PVEC, in high correlation with histochemistry results. We calculate that PVEC increases by 10% statistical power for detecting altered [18F]-florbetaben uptake in aging APP-Swe mice in planned studies of disease modifying treatments on amyloidogenesis.

YNICL Journal 2014 Journal Article

Reduced FDG-PET brain metabolism and executive function predict clinical progression in elderly healthy subjects

Michael Ewers
Matthias Brendel
Angela Rizk-Jackson
Axel Rominger
Peter Bartenstein
Norbert Schuff
Michael W. Weiner

Brain changes reminiscent of Alzheimer disease (AD) have been previously reported in a substantial portion of elderly cognitive healthy (HC) subjects. The major aim was to evaluate the accuracy of MRI assessed regional gray matter (GM) volume, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and neuropsychological test scores to identify those HC subjects who subsequently convert to mild cognitive impairment (MCI) or AD dementia. We obtained in 54 healthy control (HC) subjects a priori defined region of interest (ROI) values of medial temporal and parietal FDG-PET and medial temporal GM volume. In logistic regression analyses, these ROI values were tested together with neuropsychological test scores (free recall, trail making test B (TMT-B)) as predictors of HC conversion during a clinical follow-up between 3 and 4 years. In voxel-based analyses, FDG-PET and MRI GM maps were compared between HC converters and HC non-converters. Out of the 54 HC subjects, 11 subjects converted to MCI or AD dementia. Lower FDG-PET ROI values were associated with higher likelihood of conversion (p = 0.004), with the area under the curve (AUC) yielding 82.0% (95% CI = (95.5%, 68.5%)). The GM volume ROI was not a significant predictor (p = 0.07). TMT-B but not the free recall tests were a significant predictor (AUC = 71% (95% CI = 50.4%, 91.7%)). For the combination of FDG-PET and TMT-B, the AUC was 93.4% (sensitivity = 82%, specificity = 93%). Voxel-based group comparison showed reduced FDG-PET metabolism within the temporo-parietal and prefrontal cortex in HC converters. In conclusion, medial temporal and-parietal FDG-PET and executive function show a clinically acceptable accuracy for predicting clinical progression in elderly HC subjects.

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.

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.