Striatal and prefrontal D2R and SERT distributions contrastingly correlate with default-mode connectivity

Ionescu, Tudor M.; Amend, Mario; Hafiz, Rakibul; Biswal, Bharat B.; Maurer, Andreas; Pichler, Bernd J.; Wehrl, Hans F.; Herfert, Kristina

doi:10.1016/j.neuroimage.2021.118501

Cited by 12 publications

(5 citation statements)

References 63 publications

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“…Our study reevaluates two distinct datasets previously published by our group [11,12], to simultaneously explore FC and MC both at baseline conditions [12] and following MDMA administration [11]. For detailed descriptions on animal handling, experimental setups, and data acquisition procedures, please refer to these earlier publications.…”

Section: Methodsmentioning

confidence: 99%

Mapping Serotonergic Dynamics using Drug-Modulated Molecular Connectivity

Ionescu,

Amend,

Hafiz

et al. 2024

Preprint

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Brain imaging plays a critical role in unraveling the complex functional architecture of animal and human brains. However, individual imaging modalities often face limitations confining them to narrow physiological perspectives. Our study introduces molecular connectivity (MC), a novel concept in imaging that provides a detailed view of molecular interactions and their implications for brain functionality. This research bridges the gap between functional magnetic resonance imaging (fMRI) which tracks neurovascular dynamics, and positron emission tomography (PET), revealing molecular changes at the receptor level. The integration of these techniques can enhance our comprehension of brain-wide effects of drugs. In this study, we delve deeper into this integration by extracting molecular connectivity (MC) at the individual subject level using dynamic [11C]DASB PET scans, which map serotonin transporters (SERT). We particularly focus on assessing the ability of this method to track pharmacological alterations introduced by methylenedioxymethamphetamine (MDMA). Our comprehensive analysis involves a comparison between MC and functional connectivity (FC), utilizing seed-based and independent component analysis (ICA) during resting states. We identified significant, physiologically pertinent independent components with the [11C]DASB data, thereby enhancing the interpretation of FC results. Remarkably, we observed pronounced changes in MC following a single MDMA administration with strong correlations between resting state MC and the spatial-temporal patterns of MDMA's effect on SERT occupancy. This research marks a pioneering effort in investigating subject-level MC using PET imaging. Our findings suggests that these advanced imaging techniques can substantially refine our understanding of how drugs influence the overarching functional organization of the brain.

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Section: Methodsmentioning

confidence: 99%

Mapping Serotonergic Dynamics using Drug-Modulated Molecular Connectivity

Ionescu,

Amend,

Hafiz

et al. 2024

Preprint

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“… 30 , 46 rs-fMRI sequences were obtained at baseline, 24 h, and 1 month. The imaging data were pre-processed and analyzed as previously described by Ionescu et al 47 Subsets of animals were sacrificed at every imaging time point and excised brains were preserved either for histology or metabolomic analyses. Precise details on MRI acquisition and post-processing are provided in the Supplementary materials .…”

Section: Methodsmentioning

confidence: 99%

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke

Patzwaldt

Berezhnoy

Ionescu

et al. 2023

Brain Communications

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Ambroxol is a well-known mucolytic expectorant, which has gained much attention in Amyotrophic lateral sclerosis, Parkinson’s and Gaucher’s disease. A specific focus has been placed on Ambroxol’s glucocerebrosidase-stimulating activity, on grounds that the point mutation of the gba1 gene, which codes for this enzyme, is a risk factor for developing Parkinson’s disease. However, Ambroxol has been attributed other characteristics, such as the potent inhibition of sodium channels, modification of calcium homeostasis, anti-inflammatory effects and modifications of oxygen radical scavengers. We hypothesized that Ambroxol could have a direct impact on neuronal rescue if administered directly after ischemic stroke induction. We longitudinally evaluated 53 rats using magnetic resonance imaging to examine stroke volume, edema, white matter integrity, resting state functional magnetic resonance imaging and behavior for one month after ischemic stroke onset. For closer mechanistic insights, we evaluated tissue metabolomics of different brain regions in a subgroup of animals using ex-vivo nuclear magnetic resonance spectroscopy. Ambroxol-treated animals presented reduced stroke volumes, reduced cytotoxic edema, reduced white matter degeneration, reduced necrosis, improved behavioral outcomes and complex changes in functional brain connectivity. Nuclear magnetic resonance spectroscopy tissue metabolomic data at 24 h post stroke proposes several metabolites that are capable of minimizing post-ischemic damage and that presented prominent shifts during Ambroxol treatment in comparison to controls. Taking everything together, we propose that Ambroxol catalyzes recovery in energy metabolism, cellular homeostasis, membrane repair mechanisms and redox balance. One week of Ambroxol administration following stroke onset reduced ischemic stroke severity and improved functional outcome in the subacute phase followed by reduced necrosis in the chronic stroke phase.

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“…Hybrid PET/MRI has been successfully used in preclinical neuroimaging to correlate changes in neuronal activity using fMRI and changes in receptor expression and neurotransmitter binding [66][67][68][69]. Simultaneous PET/MRI imaging is essential for these examinations, as neuronal activations in temporally separate examinations are not comparable and do not permit any reliable conclusions.…”

Section: Hybrid Pet/mri In Animal Researchmentioning

confidence: 99%

Hybrid PET/MRI in Cerebral Glioma: Current Status and Perspectives

Langen

Galldiks

Mauler

et al. 2023

Cancers

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Advanced MRI methods and PET using radiolabelled amino acids provide valuable information, in addition to conventional MR imaging, for brain tumour diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumour progression from treatment-related changes, and the early assessment of responses to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing, and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other, leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods, but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumours. PET is only required in equivocal situations, and the spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumours compared with a single modality. This review focuses on studies investigating the diagnostic value of combined amino acid PET and ‘advanced’ MRI in patients with cerebral gliomas. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterisation of newly diagnosed tumours. Few data are available concerning the delineation of tumour extent. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumour recurrence from treatment-related changes. Here, the PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of cerebral gliomas, for which hybrid PET/MRI offers optimal conditions.

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Striatal and prefrontal D2R and SERT distributions contrastingly correlate with default-mode connectivity

Cited by 12 publications

References 63 publications

Mapping Serotonergic Dynamics using Drug-Modulated Molecular Connectivity

Mapping Serotonergic Dynamics using Drug-Modulated Molecular Connectivity

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke

Hybrid PET/MRI in Cerebral Glioma: Current Status and Perspectives

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