The Experts below are selected from a list of 1413 Experts worldwide ranked by ideXlab platform

Henryk Barthel - One of the best experts on this subject based on the ideXlab platform.

  • comparison of 18f Florbetaben quantification results using the standard centiloid mr based and mr less capaibl approaches validation against histopathology
    Alzheimers & Dementia, 2019
    Co-Authors: Vincent Dore, Santiago Bullich, Henryk Barthel, Christopher C Rowe, Osama Sabri, Andrew Stephens, Pierrick Bourgeat, Salamata Konate, Jurgen Fripp, Colin L Masters
    Abstract:

    Abstract Introduction 18F-Florbetaben is currently approved for the visual rule out of β-amyloid (Aβ) pathology. It is also used for recruitment and as an outcome measure in therapeutic trials, requiring accurate and reproducible quantification of Aβ burden in the brain. Methods Data from eighty-eight subjects (52 male subjects, aged 79.8 ± 10.6 years) who underwent antemortem 18F-Florbetaben positron emission tomography scan and magnetic resonance imaging less than a year before neuropathological assessment at autopsy were evaluated. Image analysis was performed using the standard Centiloid (CL) statistical parametric mapping approach and CapAIBL®. Imaging results were compared against autopsy data. Results Against combined Bielschowsky silver staining and immunohistochemistry histopathological scores, statistical parametric mapping had 96% sensitivity, 96% specificity, and 95% accuracy, whereas magnetic resonance–less CapAIBL standardized uptake value ratioWhole Cerebellum had 94% sensitivity, 96% specificity, and 95% accuracy. Based on the combined histopathological scores, a CL threshold band of 19 ± 7 CL was determined. Discussion Quantification of 18F-Florbetaben positron emission tomography scans using magnetic resonance–based and magnetic resonance–less CapAIBL® approaches showed high agreement, establishing a pathology-based threshold in CL.

  • validation of noninvasive tracer kinetic analysis of 18f Florbetaben pet using a dual time window acquisition protocol
    The Journal of Nuclear Medicine, 2017
    Co-Authors: Santiago Bullich, Henryk Barthel, Andrew Stephens, Aleksandar Jovalekic, Norman Koglin, Susan De Santi, G Becker, Osama Sabri
    Abstract:

    : Accurate amyloid PET quantification is necessary for monitoring amyloid-β accumulation and response to therapy. Currently, most of the studies are analyzed using the static SUV ratio (SUVR) approach because of its simplicity. However, this approach may be influenced by changes in cerebral blood flow (CBF) or radiotracer clearance. Full tracer kinetic models require arterial blood sampling and dynamic image acquisition. The objectives of this work were, first, to validate a noninvasive kinetic modeling approach for 18F-Florbetaben PET using an acquisition protocol with the best compromise between quantification accuracy and simplicity and, second, to assess the impact of CBF changes and radiotracer clearance on SUVRs and noninvasive kinetic modeling data in 18F-Florbetaben PET. Methods: Using data from 20 subjects (10 patients with probable Alzheimer dementia and 10 healthy volunteers), the nondisplaceable binding potential (BPND) obtained from the full kinetic analysis was compared with the SUVR and with noninvasive tracer kinetic methods (simplified reference tissue model and multilinear reference tissue model 2). Various approaches using shortened or interrupted acquisitions were compared with the results of the full acquisition (0-140 min). Simulations were performed to assess the effect of CBF and radiotracer clearance changes on SUVRs and noninvasive kinetic modeling outputs. Results: An acquisition protocol using time windows of 0-30 and 120-140 min with appropriate interpolation of the missing time points provided the best compromise between patient comfort and quantification accuracy. Excellent agreement was found between BPND obtained using the full protocol and BPND obtained using the dual-window protocol (for multilinear reference tissue model 2, BPND [dual-window] = 0.01 + 1.00·BPND [full], R2 = 0.97; for simplified reference tissue model, BPND [dual-window] = 0.05 + 0.92·BPND [full], R2 = 0.93). Simulations showed a limited impact of CBF and radiotracer clearance changes on multilinear reference tissue model parameters and SUVR. Conclusion: This study demonstrated accurate noninvasive kinetic modeling of 18F-Florbetaben PET data using a dual-window acquisition, thus providing a good compromise between quantification accuracy, scan duration, and patient burden. The influence of CBF and radiotracer clearance changes on amyloid-β load estimates was small. For most clinical research applications, the SUVR approach is appropriate. However, for longitudinal studies in which maximum quantification accuracy is desired, this noninvasive dual-window acquisition with kinetic analysis is recommended.

  • correlation of Florbetaben pet imaging and the amyloid peptide as42 in cerebrospinal fluid
    Psychiatry Research-neuroimaging, 2017
    Co-Authors: Carola G Schipke, Santiago Bullich, Henryk Barthel, Osama Sabri, John Seibyl, Norman Koglin, Lisa Katharina Joachim, Brigitte Haas, Oliver Peters
    Abstract:

    Abstract Today, the use of biomarkers such as amyloid-specific positron emission tomography (PET) tracers and information derived from cerebrospinal fluid (CSF) can support the diagnosis of Alzheimer's disease (AD) as an indicator for the presence of amyloid pathology. We here show that the PET signal of the 18 F-labelled tracer Florbetaben (NeuraCeq™), that binds to amyloid-beta plaques, inversely correlates with CSF levels of As42, another biomarker for AD. Results from the two biomarkers were concordant in 35 out of 38 subjects. In 7 AD subjects (20%) at least one biomarker was inconsistent with the clinical diagnosis. This confirms known limitations of the clinical AD diagnosis and highlights the potential of biomarker-assisted diagnosis to improve accuracy.

  • Feasibility of in vivo ^18F-Florbetaben PET/MR imaging of human carotid amyloid-β
    European Journal of Nuclear Medicine and Molecular Imaging, 2017
    Co-Authors: Jan Bucerius, Henryk Barthel, Solveig Tiepolt, Peter Werner, Judith C. Sluimer, Joachim E. Wildberger, Marianne Patt, Swen Hesse, Hermann-josef Gertz, Erik A. L. Biessen
    Abstract:

    Purpose Amyloid-beta (Aβ) peptides are involved in the inflammatory pathology of atherosclerosis. ^18F-Florbetaben is a PET tracer for clinical imaging of cerebral Aβ plaques in Alzheimer’s disease (AD). We sought to determine whether specific uptake of ^18F-Florbetaben in the carotid arteries can be identified using a fully integrated hybrid PET/MRI system and whether this uptake is associated with clinical cardiovascular disease (CVD) risk factors. Methods Carotid ^18F-Florbetaben uptake was quantified as the mean of the maximum target-to-background ratio (_meanTBR_max) in 40 cognitively impaired subjects (age 68.2 ± 9.5 years) undergoing ^18F-Florbetaben PET/MRI to diagnose AD. Associations between carotid ^18F-Florbetaben uptake and several CVD risk factors were assessed by univariate analysis followed by a multivariate linear regression analysis. Furthermore, carotid ^18F-Florbetaben uptake was compared between patients with and without a positive cerebral Aβ PET scan. Results ^18F-Florbetaben uptake was clearly visualized in the carotid arteries. Values of _meanTBR_max corrected for the blood pool activity of the tracer showed specific ^18F-Florbetaben uptake in the carotid wall. Male gender was associated with carotid ^18F-Florbetaben uptake in the univariate analysis, and was found to be an independent predictor of ^18F-Florbetaben uptake in the multivariate regression analysis (standardized regression coefficient β  = 0.407, p  = 0.009). Carotid ^18F-Florbetaben _meanTBR_max in patients with a positive cerebral Aβ scan did not differ from that in patients without cerebral Aβ deposits. Conclusion Specific ^18F-Florbetaben uptake in human carotid arteries was detected. Male gender was identified as an independent clinical risk factor. Therefore, ^18F-Florbetaben PET/MRI might provide new insights into the pathophysiological process in atherosclerosis.

  • feasibility of in vivo 18f Florbetaben pet mr imaging of human carotid amyloid β
    European Journal of Nuclear Medicine and Molecular Imaging, 2017
    Co-Authors: Jan Bucerius, Henryk Barthel, Solveig Tiepolt, Peter Werner, Judith C. Sluimer, Joachim E. Wildberger, Marianne Patt, Swen Hesse, Hermann-josef Gertz, Erik A. L. Biessen
    Abstract:

    Purpose Amyloid-beta (Aβ) peptides are involved in the inflammatory pathology of atherosclerosis. 18F-Florbetaben is a PET tracer for clinical imaging of cerebral Aβ plaques in Alzheimer’s disease (AD). We sought to determine whether specific uptake of 18F-Florbetaben in the carotid arteries can be identified using a fully integrated hybrid PET/MRI system and whether this uptake is associated with clinical cardiovascular disease (CVD) risk factors.

Osama Sabri - One of the best experts on this subject based on the ideXlab platform.

  • comparison of 18f Florbetaben quantification results using the standard centiloid mr based and mr less capaibl approaches validation against histopathology
    Alzheimers & Dementia, 2019
    Co-Authors: Vincent Dore, Santiago Bullich, Henryk Barthel, Christopher C Rowe, Osama Sabri, Andrew Stephens, Pierrick Bourgeat, Salamata Konate, Jurgen Fripp, Colin L Masters
    Abstract:

    Abstract Introduction 18F-Florbetaben is currently approved for the visual rule out of β-amyloid (Aβ) pathology. It is also used for recruitment and as an outcome measure in therapeutic trials, requiring accurate and reproducible quantification of Aβ burden in the brain. Methods Data from eighty-eight subjects (52 male subjects, aged 79.8 ± 10.6 years) who underwent antemortem 18F-Florbetaben positron emission tomography scan and magnetic resonance imaging less than a year before neuropathological assessment at autopsy were evaluated. Image analysis was performed using the standard Centiloid (CL) statistical parametric mapping approach and CapAIBL®. Imaging results were compared against autopsy data. Results Against combined Bielschowsky silver staining and immunohistochemistry histopathological scores, statistical parametric mapping had 96% sensitivity, 96% specificity, and 95% accuracy, whereas magnetic resonance–less CapAIBL standardized uptake value ratioWhole Cerebellum had 94% sensitivity, 96% specificity, and 95% accuracy. Based on the combined histopathological scores, a CL threshold band of 19 ± 7 CL was determined. Discussion Quantification of 18F-Florbetaben positron emission tomography scans using magnetic resonance–based and magnetic resonance–less CapAIBL® approaches showed high agreement, establishing a pathology-based threshold in CL.

  • validation of noninvasive tracer kinetic analysis of 18f Florbetaben pet using a dual time window acquisition protocol
    The Journal of Nuclear Medicine, 2017
    Co-Authors: Santiago Bullich, Henryk Barthel, Andrew Stephens, Aleksandar Jovalekic, Norman Koglin, Susan De Santi, G Becker, Osama Sabri
    Abstract:

    : Accurate amyloid PET quantification is necessary for monitoring amyloid-β accumulation and response to therapy. Currently, most of the studies are analyzed using the static SUV ratio (SUVR) approach because of its simplicity. However, this approach may be influenced by changes in cerebral blood flow (CBF) or radiotracer clearance. Full tracer kinetic models require arterial blood sampling and dynamic image acquisition. The objectives of this work were, first, to validate a noninvasive kinetic modeling approach for 18F-Florbetaben PET using an acquisition protocol with the best compromise between quantification accuracy and simplicity and, second, to assess the impact of CBF changes and radiotracer clearance on SUVRs and noninvasive kinetic modeling data in 18F-Florbetaben PET. Methods: Using data from 20 subjects (10 patients with probable Alzheimer dementia and 10 healthy volunteers), the nondisplaceable binding potential (BPND) obtained from the full kinetic analysis was compared with the SUVR and with noninvasive tracer kinetic methods (simplified reference tissue model and multilinear reference tissue model 2). Various approaches using shortened or interrupted acquisitions were compared with the results of the full acquisition (0-140 min). Simulations were performed to assess the effect of CBF and radiotracer clearance changes on SUVRs and noninvasive kinetic modeling outputs. Results: An acquisition protocol using time windows of 0-30 and 120-140 min with appropriate interpolation of the missing time points provided the best compromise between patient comfort and quantification accuracy. Excellent agreement was found between BPND obtained using the full protocol and BPND obtained using the dual-window protocol (for multilinear reference tissue model 2, BPND [dual-window] = 0.01 + 1.00·BPND [full], R2 = 0.97; for simplified reference tissue model, BPND [dual-window] = 0.05 + 0.92·BPND [full], R2 = 0.93). Simulations showed a limited impact of CBF and radiotracer clearance changes on multilinear reference tissue model parameters and SUVR. Conclusion: This study demonstrated accurate noninvasive kinetic modeling of 18F-Florbetaben PET data using a dual-window acquisition, thus providing a good compromise between quantification accuracy, scan duration, and patient burden. The influence of CBF and radiotracer clearance changes on amyloid-β load estimates was small. For most clinical research applications, the SUVR approach is appropriate. However, for longitudinal studies in which maximum quantification accuracy is desired, this noninvasive dual-window acquisition with kinetic analysis is recommended.

  • correlation of Florbetaben pet imaging and the amyloid peptide as42 in cerebrospinal fluid
    Psychiatry Research-neuroimaging, 2017
    Co-Authors: Carola G Schipke, Santiago Bullich, Henryk Barthel, Osama Sabri, John Seibyl, Norman Koglin, Lisa Katharina Joachim, Brigitte Haas, Oliver Peters
    Abstract:

    Abstract Today, the use of biomarkers such as amyloid-specific positron emission tomography (PET) tracers and information derived from cerebrospinal fluid (CSF) can support the diagnosis of Alzheimer's disease (AD) as an indicator for the presence of amyloid pathology. We here show that the PET signal of the 18 F-labelled tracer Florbetaben (NeuraCeq™), that binds to amyloid-beta plaques, inversely correlates with CSF levels of As42, another biomarker for AD. Results from the two biomarkers were concordant in 35 out of 38 subjects. In 7 AD subjects (20%) at least one biomarker was inconsistent with the clinical diagnosis. This confirms known limitations of the clinical AD diagnosis and highlights the potential of biomarker-assisted diagnosis to improve accuracy.

  • amyloid positronenemissionstomographie mit 18 f Florbetaben in der demenzdiagnostik
    Nervenarzt, 2017
    Co-Authors: Sonja Schönecker, Osama Sabri, Matthias Brendel, Erik Mille, C. Prix, Theresa Raiser, Nibal Ackl, Elisabeth Wlasich, Gisela Stengleinkrapf, Marianne Patt
    Abstract:

    Hintergrund Eine gesicherte Diagnose der Alzheimer-Krankheit beruht auf dem histologischen Nachweis von Neurofibrillen und β‑Amyloid-Ablagerungen. Amyloid-Positronenemissionstomographie (Amyloid-PET) ist eine neue diagnostische Technik, welche die In-vivo-Quantifizierung pathologischer β‑Amyloid-Ablagerungen ermoglicht. Ziel dieser Studie war, zu evaluieren, inwiefern die Durchfuhrung einer [18F]-Florbetaben-PET (FBB-PET) die Diagnosestellung bei Patienten mit demenziellem Syndrom beeinflusst.

  • optimized classification of 18f Florbetaben pet scans as positive and negative using an suvr quantitative approach and comparison to visual assessment
    NeuroImage: Clinical, 2017
    Co-Authors: Santiago Bullich, Henryk Barthel, Osama Sabri, John Seibyl, Ana M Catafau, Aleksandar Jovalekic, Norman Koglin, Susan De Santi
    Abstract:

    Introduction Standardized uptake value ratios (SUVRs) calculated from cerebral cortical areas can be used to categorize 18F-Florbetaben (FBB) PET scans by applying appropriate cutoffs. The objective of this work was first to generate FBB SUVR cutoffs using visual assessment (VA) as standard of truth (SoT) for a number of reference regions (RR) (cerebellar gray matter (GCER), whole cerebellum (WCER), pons (PONS), and subcortical white matter (SWM)). Secondly, to validate the FBB PET scan categorization performed by SUVR cutoffs against the categorization made by post-mortem histopathological confirmation of the Aβ presence. Finally, to evaluate the added value of SUVR cutoff categorization to VA.

John Seibyl - One of the best experts on this subject based on the ideXlab platform.

  • correlation of Florbetaben pet imaging and the amyloid peptide as42 in cerebrospinal fluid
    Psychiatry Research-neuroimaging, 2017
    Co-Authors: Carola G Schipke, Santiago Bullich, Henryk Barthel, Osama Sabri, John Seibyl, Norman Koglin, Lisa Katharina Joachim, Brigitte Haas, Oliver Peters
    Abstract:

    Abstract Today, the use of biomarkers such as amyloid-specific positron emission tomography (PET) tracers and information derived from cerebrospinal fluid (CSF) can support the diagnosis of Alzheimer's disease (AD) as an indicator for the presence of amyloid pathology. We here show that the PET signal of the 18 F-labelled tracer Florbetaben (NeuraCeq™), that binds to amyloid-beta plaques, inversely correlates with CSF levels of As42, another biomarker for AD. Results from the two biomarkers were concordant in 35 out of 38 subjects. In 7 AD subjects (20%) at least one biomarker was inconsistent with the clinical diagnosis. This confirms known limitations of the clinical AD diagnosis and highlights the potential of biomarker-assisted diagnosis to improve accuracy.

  • optimized classification of 18f Florbetaben pet scans as positive and negative using an suvr quantitative approach and comparison to visual assessment
    NeuroImage: Clinical, 2017
    Co-Authors: Santiago Bullich, Henryk Barthel, Osama Sabri, John Seibyl, Ana M Catafau, Aleksandar Jovalekic, Norman Koglin, Susan De Santi
    Abstract:

    Introduction Standardized uptake value ratios (SUVRs) calculated from cerebral cortical areas can be used to categorize 18F-Florbetaben (FBB) PET scans by applying appropriate cutoffs. The objective of this work was first to generate FBB SUVR cutoffs using visual assessment (VA) as standard of truth (SoT) for a number of reference regions (RR) (cerebellar gray matter (GCER), whole cerebellum (WCER), pons (PONS), and subcortical white matter (SWM)). Secondly, to validate the FBB PET scan categorization performed by SUVR cutoffs against the categorization made by post-mortem histopathological confirmation of the Aβ presence. Finally, to evaluate the added value of SUVR cutoff categorization to VA.

  • cerebellar amyloid β plaques how frequent are they and do they influence 18f Florbetaben suv ratios
    The Journal of Nuclear Medicine, 2016
    Co-Authors: Ana M Catafau, Santiago Bullich, Henryk Barthel, John Seibyl, Bernardino Ghetti, James B Leverenz, James W Ironside, Walter J Schulzschaeffer, Anja Hoffmann, Osama Sabri
    Abstract:

    : SUV ratios (SUVRs) are used for relative quantification of 18F-Florbetaben scans. The cerebellar cortex can be used as a reference region for quantification. However, cerebellar amyloid-β (Aβ) plaques may be present in Alzheimer disease (AD). The aim of this study was to assess the influence of Aβ pathology, including neuritic plaques, diffuse plaques, and vascular deposits, in 18F-Florbetaben SUVR when cerebellum is used as the reference. METHODS: Using immunohistochemistry to demonstrate Aβ plaques and vascular deposits, and using the Bielschowsky method to demonstrate neuritic plaques, we performed a neuropathologic assessment of the frontal, occipital, anterior cingulate, and posterior cingulate cerebral cortices and the cerebellar cortex of 87 end-of-life patients (64 with AD, 14 with other types of dementia, and 9 nondemented aged volunteers; mean age ± SD, 80.4 ± 10.2 y) who had undergone 18F-Florbetaben PET before death. The lesions were rated as absent (none or sparse) or present (moderate or frequent). Mean cortical SUVRs were compared among cases with different cerebellar Aβ loads. RESULTS: None of the 83 evaluable cerebellar samples showed frequent diffuse Aβ or neuritic plaques; 8 samples showed frequent vascular Aβ deposits. Diffuse Aβ plaques were rated as absent in 78 samples (94%) and present in 5 samples (6%). Vascular Aβ was rated as absent in 62 samples (74.7%) and present in 21 samples (25.3%). No significant differences in cerebellar SUVs were found among cases with different amounts or types of Aβ deposits in the cerebral cortex. Both diffuse and neuritic plaques were found in the cerebral cortex of 26-44 cases. No significant SUVR differences were found between these brains with different cerebellar Aβ loads. CONCLUSION: The effect of cerebellar plaques on cortical 18F-Florbetaben SUVRs appears to be negligible even in advanced stages of AD with a higher cerebellar Aβ load.

  • impact of training method on the robustness of the visual assessment of 18f Florbetaben pet scans results from a phase 3 study
    The Journal of Nuclear Medicine, 2016
    Co-Authors: John Seibyl, Henryk Barthel, Christopher C Rowe, Ana M Catafau, Masaki Takao, Bernardino Ghetti, James B Leverenz, James W Ironside, Kenji Ishii
    Abstract:

    UNLABELLED: Training for accurate image interpretation is essential for the clinical use of β-amyloid PET imaging, but the role of interpreter training and the accuracy of the algorithm for routine visual assessment of Florbetaben PET scans are unclear. The aim of this study was to test the robustness of the visual assessment method for Florbetaben scans, comparing efficacy readouts across different interpreters and training methods and against a histopathology standard of truth (SoT). METHODS: Analysis was based on data from an international open-label, nonrandomized, multicenter phase-3 study in patients with or without dementia (ClinicalTrials.gov: NCT01020838). Florbetaben scans were assessed visually and quantitatively, and results were compared with amyloid plaque scores. For visual assessment, either in-person training (n = 3 expert interpreters) or an electronic training method (n = 5 naive interpreters) was used. Brain samples from participants who died during the study were used to determine the histopathologic SoT using Bielschowsky silver staining (BSS) and immunohistochemistry for β-amyloid plaques. RESULTS: Data were available from 82 patients who died and underwent postmortem histopathology. When visual assessment results were compared with BSS + immunohistochemistry as SoT, median sensitivity was 98.2% for the in-person-trained interpreters and 96.4% for the e-trained interpreters, and median specificity was 92.3% and 88.5%, respectively. Median accuracy was 95.1% and 91.5%, respectively. On the basis of BSS only as the SoT, median sensitivity was 98.1% and 96.2%, respectively; median specificity was 80.0% and 76.7%, respectively; and median accuracy was 91.5% and 86.6%, respectively. Interinterpreter agreement (Fleiss κ) was excellent (0.89) for in-person-trained interpreters and very good (0.71) for e-trained interpreters. Median intrainterpreter agreement was 0.9 for both in-person-trained and e-trained interpreters. Visual and quantitative assessments were concordant in 88.9% of scans for in-person-trained interpreters and in 87.7% of scans for e-trained interpreters. CONCLUSION: Visual assessment of Florbetaben images was robust in challenging scans from elderly end-of-life individuals. Sensitivity, specificity, and interinterpreter agreement were high, independent of expertise and training method. Visual assessment was accurate and reliable for detection of plaques using BSS and immunohistochemistry and well correlated with quantitative assessments.

  • partial volume effect correction improves quantitative analysis of 18f Florbetaben β amyloid pet scans
    The Journal of Nuclear Medicine, 2016
    Co-Authors: Michael Rullmann, Solveig Tiepolt, Marianne Patt, Hermann-josef Gertz, Julia Luthardt, Juergen Dukart, Karltitus Hoffmann, Matthias L Schroeter, John Seibyl
    Abstract:

    UNLABELLED: Neocortical atrophy reduces PET signal intensity, potentially affecting the diagnostic efficacy of β-amyloid (Aβ) brain PET imaging. This study investigated whether partial-volume effect correction (PVEC), adjusting for this atrophy bias, improves the accuracy of (18)F-Florbetaben Aβ PET. METHODS: We analyzed (18)F-Florbetaben PET and MRI data obtained from 3 cohorts. The first was 10 patients with probable Alzheimer disease (AD) and 10 age-matched healthy controls (HCs), the second was 31 subjects who underwent in vivo imaging and postmortem histopathology for Aβ plaques, and the third was 5 subjects who underwent PET and MRI at baseline and 1 y later. The imaging data were coregistered and segmented. PVEC was performed using the voxel-based modified Muller-Gartner method (PVELab, SPM8). From the PET data, regional and composite SUV ratios (SUVRs) with and without PVEC were obtained. In the MRI data, mesial temporal lobe atrophy was determined by the Scheltens mesial temporal atrophy scale and gray matter volumes by voxel-based morphometry. RESULTS: In cohort 1, PVEC increased the effect on AD-versus-HC discrimination from a Cohen d value of 1.68 to 2.0 for composite SUVRs and from 0.04 to 1.04 for mesial temporal cortex SUVRs. The PVEC-related increase in mesial temporal cortex SUVR correlated with the Scheltens score (r = 0.84, P < 0.001), and that of composite SUVR correlated with the composite gray matter volume (r = -0.75, P < 0.001). In cohort 2, PVEC increased the correlation coefficient between mesial temporal cortex SUVR and histopathology score for Aβ plaque load from 0.28 (P = 0.09) to 0.37 (P = 0.03). In cohort 3, PVEC did not affect the composite SUVR dynamics over time for the Aβ-negative subject. This finding was in contrast to the 4 Aβ-positive subjects, in 2 of whom PVEC changed the composite SUVR dynamics. CONCLUSION: The influence of PVEC on (18)F-Florbetaben PET data is associated with the degree of brain atrophy. Thus, PVEC increases the ability of (18)F-Florbetaben PET to discriminate between AD patients and HCs, to detect Aβ plaques in the atrophic mesial temporal cortex, and potentially to evaluate changes in brain Aβ load over time. As such, the use of PVEC should be considered for quantitative (18)F-Florbetaben PET scans, especially in assessing patients with brain atrophy.

Santiago Bullich - One of the best experts on this subject based on the ideXlab platform.

  • comparison of 18f Florbetaben quantification results using the standard centiloid mr based and mr less capaibl approaches validation against histopathology
    Alzheimers & Dementia, 2019
    Co-Authors: Vincent Dore, Santiago Bullich, Henryk Barthel, Christopher C Rowe, Osama Sabri, Andrew Stephens, Pierrick Bourgeat, Salamata Konate, Jurgen Fripp, Colin L Masters
    Abstract:

    Abstract Introduction 18F-Florbetaben is currently approved for the visual rule out of β-amyloid (Aβ) pathology. It is also used for recruitment and as an outcome measure in therapeutic trials, requiring accurate and reproducible quantification of Aβ burden in the brain. Methods Data from eighty-eight subjects (52 male subjects, aged 79.8 ± 10.6 years) who underwent antemortem 18F-Florbetaben positron emission tomography scan and magnetic resonance imaging less than a year before neuropathological assessment at autopsy were evaluated. Image analysis was performed using the standard Centiloid (CL) statistical parametric mapping approach and CapAIBL®. Imaging results were compared against autopsy data. Results Against combined Bielschowsky silver staining and immunohistochemistry histopathological scores, statistical parametric mapping had 96% sensitivity, 96% specificity, and 95% accuracy, whereas magnetic resonance–less CapAIBL standardized uptake value ratioWhole Cerebellum had 94% sensitivity, 96% specificity, and 95% accuracy. Based on the combined histopathological scores, a CL threshold band of 19 ± 7 CL was determined. Discussion Quantification of 18F-Florbetaben positron emission tomography scans using magnetic resonance–based and magnetic resonance–less CapAIBL® approaches showed high agreement, establishing a pathology-based threshold in CL.

  • validation of noninvasive tracer kinetic analysis of 18f Florbetaben pet using a dual time window acquisition protocol
    The Journal of Nuclear Medicine, 2017
    Co-Authors: Santiago Bullich, Henryk Barthel, Andrew Stephens, Aleksandar Jovalekic, Norman Koglin, Susan De Santi, G Becker, Osama Sabri
    Abstract:

    : Accurate amyloid PET quantification is necessary for monitoring amyloid-β accumulation and response to therapy. Currently, most of the studies are analyzed using the static SUV ratio (SUVR) approach because of its simplicity. However, this approach may be influenced by changes in cerebral blood flow (CBF) or radiotracer clearance. Full tracer kinetic models require arterial blood sampling and dynamic image acquisition. The objectives of this work were, first, to validate a noninvasive kinetic modeling approach for 18F-Florbetaben PET using an acquisition protocol with the best compromise between quantification accuracy and simplicity and, second, to assess the impact of CBF changes and radiotracer clearance on SUVRs and noninvasive kinetic modeling data in 18F-Florbetaben PET. Methods: Using data from 20 subjects (10 patients with probable Alzheimer dementia and 10 healthy volunteers), the nondisplaceable binding potential (BPND) obtained from the full kinetic analysis was compared with the SUVR and with noninvasive tracer kinetic methods (simplified reference tissue model and multilinear reference tissue model 2). Various approaches using shortened or interrupted acquisitions were compared with the results of the full acquisition (0-140 min). Simulations were performed to assess the effect of CBF and radiotracer clearance changes on SUVRs and noninvasive kinetic modeling outputs. Results: An acquisition protocol using time windows of 0-30 and 120-140 min with appropriate interpolation of the missing time points provided the best compromise between patient comfort and quantification accuracy. Excellent agreement was found between BPND obtained using the full protocol and BPND obtained using the dual-window protocol (for multilinear reference tissue model 2, BPND [dual-window] = 0.01 + 1.00·BPND [full], R2 = 0.97; for simplified reference tissue model, BPND [dual-window] = 0.05 + 0.92·BPND [full], R2 = 0.93). Simulations showed a limited impact of CBF and radiotracer clearance changes on multilinear reference tissue model parameters and SUVR. Conclusion: This study demonstrated accurate noninvasive kinetic modeling of 18F-Florbetaben PET data using a dual-window acquisition, thus providing a good compromise between quantification accuracy, scan duration, and patient burden. The influence of CBF and radiotracer clearance changes on amyloid-β load estimates was small. For most clinical research applications, the SUVR approach is appropriate. However, for longitudinal studies in which maximum quantification accuracy is desired, this noninvasive dual-window acquisition with kinetic analysis is recommended.

  • Added value of 18F-Florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study.
    Alzheimers & Dementia, 2017
    Co-Authors: Mathieu Ceccaldi, Thérèse Rivasseau Jonveaux, Antoine Verger, Pierre Krolak-salmon, Claire Houzard, Olivier Godefroy, Trevor Shields, Audrey Perrotin, Rossella Gismondi, Santiago Bullich
    Abstract:

    Abstract Introduction Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting. Methods This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172). Results Two hundred five patients were enrolled with evaluable Florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases. Discussion High-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of Florbetaben PET into current standard practices for the most complex dementia cases.

  • 18f Florbetaben pet beta amyloid binding expressed in centiloids
    European Journal of Nuclear Medicine and Molecular Imaging, 2017
    Co-Authors: Christopher C Rowe, Santiago Bullich, Andrew Stephens, Rachel S Mulligan, Gareth Jones, Vincent Dore, Colin L Masters, Susan De Santi, David Baxendale, Ludger Dinkelborg
    Abstract:

    Purpose The Centiloid (CL) method enables quantitative values from Aβ-amyloid (Aβ) imaging to be expressed in a universal unit providing pathological, diagnostic and prognostic thresholds in clinical practice and research and allowing integration of multiple tracers and methods. The method was developed for 11C-PiB scans with zero CL set as the average in young normal subjects and 100 CL the average in subjects with mild Alzheimer’s disease (AD). The method allows derivation of equations to convert the uptake value of any tracer into the same standard CL units but first requires head-to-head comparison with 11C-PiB results. We derived the equation to express 18F-Florbetaben (FBB) binding in CL units.

  • correlation of Florbetaben pet imaging and the amyloid peptide as42 in cerebrospinal fluid
    Psychiatry Research-neuroimaging, 2017
    Co-Authors: Carola G Schipke, Santiago Bullich, Henryk Barthel, Osama Sabri, John Seibyl, Norman Koglin, Lisa Katharina Joachim, Brigitte Haas, Oliver Peters
    Abstract:

    Abstract Today, the use of biomarkers such as amyloid-specific positron emission tomography (PET) tracers and information derived from cerebrospinal fluid (CSF) can support the diagnosis of Alzheimer's disease (AD) as an indicator for the presence of amyloid pathology. We here show that the PET signal of the 18 F-labelled tracer Florbetaben (NeuraCeq™), that binds to amyloid-beta plaques, inversely correlates with CSF levels of As42, another biomarker for AD. Results from the two biomarkers were concordant in 35 out of 38 subjects. In 7 AD subjects (20%) at least one biomarker was inconsistent with the clinical diagnosis. This confirms known limitations of the clinical AD diagnosis and highlights the potential of biomarker-assisted diagnosis to improve accuracy.

Matthias Brendel - One of the best experts on this subject based on the ideXlab platform.

  • Additive value of amyloid-PET in routine cases of clinical dementia work-up after FDG-PET.
    European Journal of Nuclear Medicine and Molecular Imaging, 2017
    Co-Authors: Matthias Brendel, Marianne Patt, Andreas Schildan, Jonas Schnabel, Sonja Schönecker, Leonie Wagner, Eva Brendel, Johanna Meyer-wilmes, Marcus Unterrainer, C. Prix
    Abstract:

    Purpose In recent years, several [18F]-labeled amyloid-PET tracers have been developed and have obtained clinical approval. Despite their widespread scientific use, studies in routine clinical settings are limited. We therefore investigated the impact of [18F]-Florbetaben (FBB)-PET on the diagnostic management of patients with suspected dementia that was still unclarified after [18F]-fluordeoxyglucose (FDG)-PET.

  • amyloid positronenemissionstomographie mit 18 f Florbetaben in der demenzdiagnostik
    Nervenarzt, 2017
    Co-Authors: Sonja Schönecker, Osama Sabri, Matthias Brendel, Erik Mille, C. Prix, Theresa Raiser, Nibal Ackl, Elisabeth Wlasich, Gisela Stengleinkrapf, Marianne Patt
    Abstract:

    Hintergrund Eine gesicherte Diagnose der Alzheimer-Krankheit beruht auf dem histologischen Nachweis von Neurofibrillen und β‑Amyloid-Ablagerungen. Amyloid-Positronenemissionstomographie (Amyloid-PET) ist eine neue diagnostische Technik, welche die In-vivo-Quantifizierung pathologischer β‑Amyloid-Ablagerungen ermoglicht. Ziel dieser Studie war, zu evaluieren, inwiefern die Durchfuhrung einer [18F]-Florbetaben-PET (FBB-PET) die Diagnosestellung bei Patienten mit demenziellem Syndrom beeinflusst.

  • evaluation of early phase 18f Florbetaben pet acquisition in clinical routine cases
    NeuroImage: Clinical, 2017
    Co-Authors: Sonja Daerr, Matthias Brendel, Erik Mille, Christian Zach, Dorothee Schilling, Mathias Zacherl, Katharina Burger, Adrian Danek, Oliver Pogarell
    Abstract:

    Objectives: In recent years several [F-18]-labelled amyloid PET tracers have been developed and have obtained clinical approval. There is accumulating evidence that early (post injection) acquisitionswith these tracers are equally informative as conventional blood flow andmetabolismstudies for diagnosis of Alzheimer's disease, but there have been few side-by-side studies. Therefore, we investigated the performance of early acquisitions of [F-18]Florbetaben (FBB) PET compared to [F-18]-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 globalmean 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 (3DSSP) 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 earlyphase 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 surrogatemarker for synaptic dysfunction, which could ultimately circumvent the need for additional FDG PET investigation in diagnosis of dementia. (C) 2016 The Author(s). Published by Elsevier Inc.

  • automated spatial brain normalization and hindbrain white matter reference tissue give improved 18f Florbetaben pet quantitation in alzheimer s model mice
    Frontiers in Neuroscience, 2016
    Co-Authors: Felix Overhoff, Matthias Brendel, Andreas Delker, Franz Josef Gildehaus, Anna Jaworska, Viktoria Korzhova, Federico Probst, Carola Focke, Janette Carlsen
    Abstract:

    Preclinical PET studies of β-amyloid (Aβ) accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore we aimed to evaluate systematically the 1) impact of an automated algorithm for spatial brain normalization, and 2) intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a six week longitudinal setting (N = 37) and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40) were investigated by [18F]-Florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ). For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX/REF), relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen’s d), and in reference to gold standard histopathological quantitation (Pearson’s R). Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ ≥ 0.99) between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX/REF. All SUVRCTX/REF methods performed better than SUVCTX both with regard to longitudinal stability (d ≥ 1.21 vs. d = 0.23) and histological gold standard agreement (R ≥ 0.66 vs. R ≥ 0.31). Voxel-wise analysis suggested a physiologically implausible longitudinal decrease of global mean scaling. The hindbrain white matter reference (Rmean = 0.75) was slightly superior to the brainstem (Rmean = 0.74) and the cerebellum (Rmean = 0.73). Automated brain normalization with reference region templates presents an excellent method to avoid the inter-reader variability in preclinical Aβ-PET scans. Intracerebral reference regions lacking Aβ pathology serve for precise longitudinal in vivo quantification of [18F]-Florbetaben PET. Hindbrain white matter reference performed best when considering the composite of quality criteria.

  • Cross-Sectional Comparison of Small Animal [18F]-Florbetaben Amyloid-PET between Transgenic AD Mouse Models
    PLOS ONE, 2015
    Co-Authors: Matthias Brendel, Christina Rotzer, Janette Carlsen, Franz Josef Gildehaus, Paul Cumming, Karlheinz Baumann, Steffen Burgold, Anna Jaworska, Eric Grießinger, Christian Haass
    Abstract:

    We aimed to compare [18F]-Florbetaben PET imaging in four transgenic mouse strains modelling Alzheimer’s disease (AD), with the main focus on APPswe/PS2 mice and C57Bl/6 mice serving as controls (WT). A consistent PET protocol (N = 82 PET scans) was used, with cortical standardized uptake value ratio (SUVR) relative to cerebellum as the endpoint. We correlated methoxy-X04 staining of β-amyloid with PET results, and undertook ex vivo autoradiography for further validation of a partial volume effect correction (PVEC) of PET data. The SUVR in APPswe/PS2 increased from 0.95±0.04 at five months (N = 5) and 1.04±0.03 (p