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105. Impact of framing scheme optimization and smoking status on binding potential analysis in dynamic PET with [11C]ABP688.

Author

Régio Brambilla, Cláudia, Scheins, Jürgen, Tellmann, Lutz, Issa, Ahlam, Herzog, Hans, Shah, N. Jon, Neuner, Irene, and Lerche, Christoph W.

Subjects
POSITRON emission tomography, SMOKING, G protein coupled receptors
Abstract

Background: For positron emission tomography (PET) ligands, such as [11C]ABP688, to be able to provide more evidence about the glutamatergic hypothesis in schizophrenia (SZ), quantification bias during dynamic PET studies and its propagation into the estimated values of non-displaceable binding potential (BPND) must be addressed. This would enable more accurate quantification during bolus + infusion (BI) neuroreceptor studies and further our understanding of neurological diseases. Previous studies have shown BPND-related biases can often occur due to overestimated cerebellum activity (reference region). This work investigates whether an alternative framing scheme can minimize quantification biases propagated into BPND, whether confounders, such as smoking status, need to be controlled for during the study, and what the consequences for the data interpretation following analysis are. A group of healthy controls (HC) and a group of SZ patients (balanced and unbalanced number of smokers) were investigated with [11C]ABP688 and a BI protocol. Possible differences in BPND quantification as a function of smoking status were tested with constant 5 min ('Const 5 min') and constant true counts ('Const Trues') framing schemes. In order to find biomarkers for SZ, the differences in smoking effects were compared between groups. The normalized BPND and the balanced number of smokers and non-smokers for both framing schemes were evaluated. Results: When applying F-tests to the 'Const 5 min' framing scheme, effect sizes (η2p) and brain regions which showed significant effects fluctuated considerably with F = 50.106 ± 54.948 (9.389 to 112.607), P-values 0.005 to < 0.001 and η2p = 0.514 ± 0.282 (0.238 to 0.801). Conversely, when the 'Const Trues' framing scheme was applied, the results showed much smaller fluctuations with F = 78.038 ± 8.975 (86.450 to 68.590), P < 0.001 for all conditions and η2p = 0.730 ± 0.017 (0.742 to 0.710), and regions with significant effects were more robustly reproduced. Further, differences, which would indicate false positive identifications between HC and SZ groups in five brain regions when using the 'Const 5 min' framing scheme, were not observed with the 'Const Trues' framing. Conclusions: Based on an [11C]ABP688 PET study in SZ patients, the results show that non-consistent BPND outcomes can be propagated by the framing scheme and that potential bias can be minimized using 'Const Trues' framing. [ABSTRACT FROM AUTHOR]

Published
2023
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111. mGluR5 and GABAA receptor‐specific parametric PET atlas construction—PET/MR data processing pipeline, validation, and application

Author

Kaulen, Nicolas, primary, Rajkumar, Ravichandran, additional, Régio Brambilla, Cláudia, additional, Mauler, Jörg, additional, Ramkiran, Shukti, additional, Orth, Linda, additional, Sbaihat, Hasan, additional, Lang, Markus, additional, Wyss, Christine, additional, Rota Kops, Elena, additional, Scheins, Jürgen, additional, Neumaier, Bernd, additional, Ermert, Johannes, additional, Herzog, Hans, additional, Langen, Karl‐Joseph, additional, Lerche, Christoph, additional, Shah, N. Jon, additional, Veselinović, Tanja, additional, and Neuner, Irene, additional

Published
2022
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117. Comparison of the Amyloid Load in the Brains of Two Transgenic Alzheimer’s Disease Mouse Models Quantified by Florbetaben Positron Emission Tomography

Author

Willuweit, Antje, primary, Schöneck, Michael, additional, Schemmert, Sarah, additional, Lohmann, Philipp, additional, Bremen, Saskia, additional, Honold, Dominik, additional, Burda, Nicole, additional, Jiang, Nan, additional, Beer, Simone, additional, Ermert, Johannes, additional, Willbold, Dieter, additional, Shah, N. Jon, additional, and Langen, Karl-Josef, additional

Published
2021
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119. Development of a novel 10‐echo multi‐contrast sequence based on EPIK to deliver simultaneous quantification of T2 and T2* with application to oxygen extraction fraction.

Author

Küppers, Fabian, Yun, Seong Dae, and Shah, N. Jon

Subjects
MAGNETIC resonance imaging, GRAY matter (Nerve tissue), WHITE matter (Nerve tissue), OXYGEN, CLINICAL medicine
Abstract

Purpose: The simultaneous quantification of T2 and T2* maps based on fast sequences for combined GE and SE acquisition has rekindled research and clinical interest by offering a wide range of attractive applications, e.g., dynamic tracking of oxygen extraction fraction (OEF). However, previously published methods based on EPI‐readouts have been hindered by resolution and the number of acquired echoes. Methods: This work presents a novel 10‐echo GE‐SE EPIK (EPI with keyhole) sequence for the rapid quantification of T2'. T2/T2* maps from the GE‐SE EPIK sequence were validated using three phantoms and 15 volunteers at 3T. The incorporation of a sliding window approach, combined with the full sampling of the k‐space center inherent to EPIK, enables a high effective temporal resolution. That is, for an eight‐slice breath‐hold experiment, a temporal sampling rate of eight reconstructed slices per 1.1 s. Results: In comparison with repeated single‐echo SE, multi‐echo GE, and spectroscopy methods, the GE‐SE EPIK sequence shows good agreement in quantifying T2/T2* values, while the gray matter/white matter separation yielded the expected contrast differentiation. The OEF was calculated with a view to an initial application with clinical relevance, producing results comparable to those in the literature and with good sensitivity in breath‐hold experiments. Conclusions: GE‐SE EPIK provides increased resolution and more echoes, including two SEs, than comparable sequences. Moreover, GE‐SE EPIK achieves this within an acquisition time of 57 s for 20 slices (matrix size = 128×128; FOV = 24 cm) and with a reasonably short TE for the final echo (114 ms). The sequence can dynamically track OEF changes in a breath‐hold experiment. [ABSTRACT FROM AUTHOR]

Published
2022
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126. Sex-Related Motor Deficits in the Tau-P301L Mouse Model

Author

Camargo, Luana Cristina, primary, Honold, Dominik, additional, Bauer, Robert, additional, Shah, N. Jon, additional, Langen, Karl-Josef, additional, Willbold, Dieter, additional, Kutzsche, Janine, additional, Willuweit, Antje, additional, and Schemmert, Sarah, additional

Published
2021
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130. Microglial activation and blood-brain barrier permeability in cerebral small vessel disease

Author

Walsh, Jessica, Tozer, Dan J, Sari, Hasan, Hong, Young T, Drazyk, Anna, Williams, Guy, Shah, N Jon, O'Brien, John T, Aigbirhio, Franklin I, Rosenberg, Gary, Fryer, Tim D, Markus, Hugh S, Walsh, Jessica [0000-0001-9723-3043], Sari, Hasan [0000-0002-1504-1767], and Apollo - University of Cambridge Repository

Subjects
Male, cerebral small vessel disease, CADASIL, lacunar stroke, Neuroimaging, Middle Aged, blood–brain barrier, Magnetic Resonance Imaging, neuroinflammation, Capillary Permeability, Blood-Brain Barrier, Case-Control Studies, Cerebral Small Vessel Diseases, Positron-Emission Tomography, Humans, Female, Microglia, Aged
Abstract

Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. The underlying pathogenesis is poorly understood, but both neuroinflammation and increased blood-brain barrier permeability have been hypothesized to play a role, and preclinical studies suggest the two processes may be linked. We used PET magnetic resonance to simultaneously measure microglial activation using the translocator protein radioligand 11C-PK11195, and blood-brain barrier permeability using dynamic contrast enhanced MRI. A case control design was used with two disease groups with sporadic SVD (n = 20), monogenic SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL), and normal controls (n = 20) were studied. Hotspots of increased glial activation and blood-brain barrier permeability were identified as values greater than the 95th percentile of the distribution in controls. In sporadic SVD there was an increase in the volume of hotspots of both 11C-PK11195 binding (P = 0.003) and blood-brain barrier permeability (P = 0.007) in the normal appearing white matter, in addition to increased mean blood-brain barrier permeability (P

Published
2021
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131. Bias evaluation and reduction in 3D OP-OSEM reconstruction in dynamic equilibrium PET studies with 11C-labeled for binding potential analysis

Author

Brambilla, Cláudia Régio, Scheins, Jürgen, Issa, Ahlam, Tellmann, Lutz, Herzog, Hans, Rota Kops, Elena, Shah, N. Jon, Neuner, Irene, and Lerche, Christoph W.

Subjects
Central Nervous System, Imaging Techniques, Science, Neuroimaging, Research and Analysis Methods, Nervous System, Diagnostic Radiology, Binding Analysis, Imaging, Three-Dimensional, Diagnostic Medicine, Medicine and Health Sciences, ddc:610, Carbon Radioisotopes, Tomography, Chemical Characterization, Cingulate Cortex, Phantoms, Imaging, Radiology and Imaging, Applied Mathematics, Simulation and Modeling, Biology and Life Sciences, Brain, Magnetic Resonance Imaging, Noise Reduction, Isotope Labeling, Positron-Emission Tomography, Physical Sciences, Signal Processing, Engineering and Technology, Medicine, Anatomy, Positron Emission Tomography, Mathematics, Algorithms, Research Article, Neuroscience
Abstract

PLOS ONE 16(1), 1-18 (2021). doi:10.1371/journal.pone.0245580, Published by PLOS, San Francisco, California, US

Published
2021

136. Putaminal y ‐Aminobutyric Acid Modulates Motor Response to Dopaminergic Therapy in Parkinson's Disease

Author

Seger, Aline D., primary, Farrher, Ezequiel, additional, Doppler, Christopher E.J., additional, Gogishvili, Ana, additional, Worthoff, Wieland A., additional, Filss, Christian P., additional, Barbe, Michael T., additional, Holtbernd, Florian, additional, Shah, N. Jon, additional, Fink, Gereon R., additional, and Sommerauer, Michael, additional

Published
2021
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139. Application of Evolution Strategies to the Design of SAR Efficient Parallel Transmit Multi-Spoke Pulses for Ultra-High Field MRI

Author

Eberhardt, Boris, Poser, Benedikt A., Shah, N. Jon, Felder, Jorg, MRI, RS: FPN CN 5, RS: FPN CN 1, and Audition

Subjects
Optimization, PHASE, POWER, Trajectory, Parallel transmission, Magnetic resonance imaging, Hardware, RADIOFREQUENCY PULSE, Radio frequency, EXCITATION, ultra-high field, ALGORITHM, Least-Squares Analysis, Nonhomogeneous media, Phantoms, Imaging, ABSORPTION RATE, Brain, INHOMOGENEITY, RF PULSES, evolution strategies, ARRAY, ddc:620, Algorithms, Neuroscience, SAR, LEAST-SQUARES OPTIMIZATION
Abstract

We present an evolution-strategy based approach to solve the magnitude least squares (MLS) design problem of low flip-angle slice-selective parallel transmit RF pulses for ultra-high field MRI using SAR and peak-RF-constraints. A combined transmit k-space trajectory and RF pulse weight optimization is proposed in two algorithmic steps. The first step is a coarse grid search to find an initial solution that fulfills all constraints for the subsequent multistage optimization. This avoids convergence to the next nearest local minimum. The second step attempts to refine the results using multiple evolution strategies. We compare the performance of our approach with the non-convex optimization methods described in the literature. The proposed algorithm converges for phantom and in vivo data and only requires an initial estimate of the range of suitable regularization parameters. It demonstrates improved excitation homogeneity compared to published spoke-design methods and allows optimization for homogeneity with a subsequent reduction in the SAR burden. Moreover, excitation homogeneity and the SAR burden can be balanced against each other, enabling a further reduction in SAR at the cost of minor relaxations in excitation homogeneity. This feature makes the algorithm a good candidate for SAR limited sequences in ultra-high field imaging. The algorithm is validated using phantom and in vivo measurements obtained with a 16-channel transmit array at 9.4 T.

Published
2020

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