Horea-Ioan Ioanas

Last Name

Ioanas

First Name

Horea-Ioan

ORCID

0000-0001-7037-2449

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Publications 1 - 10 of 10

Selective amotivation deficits following chronic psychosocial stress in mice
Cabal, Alejandro T.; Ioanas, Horea-Ioan; Seifritz, Erich; et al. (2017)
Behavioural Brain Research
Imaging Monoaminergic Systems and their Pharmacological Control
Ioanas, Horea-Ioan (2019)
The natural sciences always and only enhance the human condition by producing knowledge which empowers us to control the natural world, where otherwise it would control us. Nowhere is the power of uncontrollable natural phenomena to curb or limit human well-being more pervasive than in the human mind itself. Monoamines are a class of neurotransmitters consistently implicated in the etiology of nonvolitional neuropsychological phenomena. They are a cornerstone of those mental functions which humans most desire, but are least able to control. Unsurprisingly, drugs targeting these neurotransmitter systems are widely used in clinical, therapeutic, performance-enhancing, and recreational contexts. To the detriment of patients and users, however, currently available drugs are strongly lacking in terms of effect amplitude, reliability, and persistence, as well as suitability for long-term use. We present novel research, which advances the descriptive understanding of drug-naïve monoaminergic function and of monoaminergic drug effects. Our work includes methods development, the investigation of functional monoaminergic neurophenotypes, and the imaging-based profiling of longitudinal drug treatment. The neurobiological representations we put forward are instrumental to refining the understanding of psychopharmacological intervention profiles and the phenomena which they are able to modulate. Methodologically, we tackle technological impediments to large-scale (longitudinal, multi-cohort, and multi-center) preclinical brain imaging. Our first article deals with the challenge of automatically and reliably preparing preclinical magnetic resonance imaging (MRI) data for sharing and analysis. Our second article deals with the improvement of mouse brain registration and the definition of a reference space. Both of the above, as well as further relevant data analysis, rely heavily on high-level software tools. We consequently make an excursion into neuroscientific software management, which needs to be as accessible, reproducible, and transparent as the research it supports. In our third article we present the first whole-brain read-out of ventral tegmental area (VTA) dopaminergic signalling in the mouse. We perform a multivariate analysis of experiment parameters, and formulate specific guidelines for assay reuse or refinement. In our fourth article we apply a previously established serotonergic activity read-out to a longitudinal selective serotonin reuptake inhibitor (SSRI) drug treatment. We produce the first functional neuroimaging profile of longitudinal serotonergic drug effects, and we identify distinct brain clusters based on longitudinal activation trajectories. Our findings both support the autoinhibition down-regulation theory for the SSRI action mechanism, and complement it, by suggesting a prominent role for brainstem involvement. As all trajectories show significant treatment but no post-treatment effects, we also provide neuroimaging evidence strongly suggesting that the intervention fails to elicit persistent homeostatic shifts in healthy subjects. We openly share all acquired data, and all code required to reproduce our analyses. We suggest that the novel methods and the neurophenotypical profiling concept which we put forward may revitalize psychopharmacological research. Our work ultimately serves to advance the understanding of monoaminergic function and its manipulation, as is needed to fulfill the increasing need for the betterment of the human mind, in and outside of the clinical context.
An in vivo wound healing model for the characterization of the angiogenic process and its modulation by pharmacological interventions
Schneider, Martin K.; Ioanas, Horea-Ioan; Xandry, Jael; et al. (2019)
Scientific Reports
Angiogenesis during wound healing is essential for tissue repair and also affected during cancer treatment by anti-angiogenic drugs. Here, we introduce a minimally invasive wound healing model in the mouse ear to assess angiogenesis with high spatiotemporal resolution in a longitudinal manner in vivo using two-photon microscopy in mice expressing GCaMP2 in arterial endothelial cells. The development of vascular sprouts occurred in a highly orchestrated manner within a time window of 8 days following wounding. Novel sprouts developed exclusively from the distal stump of the transsected arteries, growing towards the proximal arterial stump. This was in line with the incidence of Ca2+ transients in the arterial endothelial cells, most probably a result of VEGF stimulation, which were more numerous on the distal part. Functional analysis revealed perfusion across the wound site via arterial sprouts developed between days 6 and 8 following the incision. At day 8, proximal and distal arteries were structurally and functionally connected, though only 2/3 of all sprouts detected were actually perfused. Treatment with the FDA approved drug, sunitinib, the preclinical drug AZD4547, as well as with the combination of the two agents had significant effects on both structural and functional readouts of neo-angiogenesis. The simplicity and high reproducibility of the model makes it an attractive tool for elucidating migratory activity, phenotype and functionality of endothelial cells during angiogenesis and for evaluating specific anti-angiogenic drug interventions.
Hybrid fiber optic-fMRI for multimodal cell-specific recording and manipulation of neural activity in rodents
Ioanas, Horea-Ioan; Schlegel, Felix; Skachokova, Zhiva; et al. (2022)
Neurophotonics
Significance: Multiscale imaging holds particular relevance to neuroscience, where it helps integrate the cellular and molecular biological scale, which is most accessible to interventions, with holistic organ-level evaluations, most relevant with respect to function. Being inextricably interdisciplinary, multiscale imaging benefits substantially from incremental technology adoption, and a detailed overview of the state-of-the-art is vital to an informed application of imaging methods. Aim: In this article, we lay out the background and methodological aspects of multimodal approaches combining functional magnetic resonance imaging (fMRI) with simultaneous optical measurement or stimulation. Approach: We focus on optical techniques as these allow, in conjunction with genetically encoded proteins (e.g. calcium indicators or optical signal transducers), unprecedented read-out and control specificity for individual cell-types during fMRI experiments, while leveraging non-interfering modalities. Results: A variety of different solutions for optical/fMRI methods has been reported ranging from bulk fluorescence recordings via fiber photometry to high resolution microscopy. In particular, the plethora of optogenetic tools has enabled the transformation of stimulus-evoked fMRI into a cell biological interrogation method. We discuss the capabilities and limitations of these genetically encoded molecular tools in the study of brain phenomena of great methodological and neuropsychiatric interest—such as neurovascular coupling (NVC) and neuronal network mapping. We provide a methodological description of this interdisciplinary field of study, and focus in particular on the limitations of the widely used blood oxygen level dependent (BOLD) signal and how multimodal readouts can shed light on the contributions arising from neurons, astrocytes, or the vasculature. Conclusion: We conclude that information from multiple signaling pathways must be incorporated in future forward models of the BOLD response to prevent erroneous conclusions when using fMRI as a surrogate measure for neural activity. Further, we highlight the potential of direct neuronal stimulation via genetically defined brain networks towards advancing neurophysiological understanding and better estimating effective connectivity.
An Automated Open-Source Workflow for Standards-Compliant Integration of Small Animal Magnetic Resonance Imaging Data
Ioanas, Horea-Ioan; Marks, Markus; Garin, Clément M.; et al. (2020)
Frontiers in Neuroinformatics
Large-scale research integration is contingent on seamless access to data in standardized formats. Standards enable researchers to understand external experiment structures, pool results, and apply homogeneous preprocessing and analysis workflows. Particularly, they facilitate these features without the need for numerous potentially confounding compatibility add-ons. In small animal magnetic resonance imaging, an overwhelming proportion of data is acquired via the ParaVision software of the Bruker Corporation. The original data structure is predominantly transparent, but fundamentally incompatible with modern pipelines. Additionally, it sources metadata from free-field operator input, which diverges strongly between laboratories and researchers. In this article we present an open-source workflow which automatically converts and reposits data from the ParaVision structure into the widely supported and openly documented Brain Imaging Data Structure (BIDS). Complementing this workflow we also present operator guidelines for appropriate ParaVision data input, and a programmatic walk-through detailing how preexisting scans with uninterpretable metadata records can easily be made compliant after the acquisition.
Using Tandem Behaviour-PET to Examine Dopaminergic Signalling Underlying Exploration
Müller Herde, Adrienne; Ioanas, Horea-Ioan; Boss, Silvan D.; et al. (2017)
Matters
Here, we examine the potential of positron emission tomography (PET), a non-invasive technique that detects the location of a small molecule within a subject in real-time with resolution in the micrometre range, in providing insight into the role of dopaminergic signalling in exploratory behaviours. Using a pilot of five adult mice, we recorded the behaviour of each subject during a 15-min free exploration period and then performed PET imaging with the F-labelled high affinity dopamine D2/D3 receptor antagonist 18 F- fallypride. A correlation matrix of behaviours and brain regions of interest revealed some interesting correlations. In particular, we find a decreased standardised uptake value (SUV) for 18 F-fallypride in the hippocampal formation and amygdala in subjects that exhibited high levels of unassisted rearing. This finding suggests that either a higher concentration of dopamine in these areas, or lower D2/D3 receptor availability, is associated with increased exploratory behaviour. In contrast, we found that high SUVs for 18 F-fallypride throughout the brain correlated most strongly with immobility and body grooming, suggesting these behaviours dominate during times of low global dopamine/dopamine receptor binding. This pilot study serves as an example of the potential for using tandem behaviour-PET to identify novel brain-behaviour interactions, but additional refinements to the methods are warranted before full-scale studies are engaged.
An Optimized Registration Workflow and Standard Geometric Space for Small Animal Brain Imaging
Ioanas, Horea-Ioan; Marks, Markus; Yanik, Mehmet Fatih; et al. (2019)
bioRxiv
The reliability of scientific results critically depends on reproducible and transparent data processing. Cross-subject and cross-study comparability of imaging data in general, and magnetic resonance imaging (MRI) data in particular, is contingent on the quality of registration to a standard reference space. In small animal MRI this is not adequately provided by currently used processing workflows, which utilize high-level scripts optimized for human data, and adapt animal data to fit the scripts, rather than vice-versa. In this fully reproducible article we showcase a generic workflow optimized for the mouse brain, alongside a standard reference space suited to harmonize data between analysis and operation. We present four separate metrics for automated quality control (QC), and a visualization method to aid operator inspection. Benchmarking this workflow against common legacy practices reveals that it performs more consistently, better preserves variance across subjects while minimizing variance across sessions, and improves both volume and smoothness conservation RMSE approximately 3-fold. We propose this open source workflow and the QC metrics as a new standard for small animal MRI registration, ensuring workflow robustness, data comparability, and region assignment validity, important criteria for the comparability of scientific results across experiments and centers.
Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations
Ioanas, Horea-Ioan; Saab, Bechara John; Rudin, Markus (2022)
Translational Psychiatry
Ascending dopaminergic projections from neurons located in the Ventral Tegmental Area (VTA) are key to the etiology, dysfunction, and control of motivation, learning, and addiction. Due to the evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an assay for VTA dopaminergic signaling in the mouse brain is crucial for the translational investigation of motivational control as well as of neuronal function phenotypes for diseases and interventions. In this article we use optogenetic stimulation directed at VTA dopaminergic neurons in combination with functional Magnetic Resonance Imaging (fMRI), a method widely used in human deep brain imaging. We present a comprehensive assay producing the first whole-brain opto-fMRI map of dopaminergic activation in the mouse, and show that VTA dopaminergic system function is consistent with its structural VTA projections, diverging only in a few key aspects. While the activation map predominantly highlights target areas according to their relative projection densities (e.g., strong activation of the nucleus accumbens and low activation of the hippocampus), it also includes areas for which a structural connection is not well established (such as the dorsomedial striatum). We further detail the variability of the assay with regard to multiple experimental parameters, including stimulation protocol and implant position, and provide evidence-based recommendations for assay reuse, publishing both reference results and a reference analysis workflow implementation.
An optimized registration workflow and standard geometric space for small animal brain imaging
Ioanas, Horea-Ioan; Marks, Markus; Zerbi, Valerio; et al. (2021)
NeuroImage
The reliability of scientific results critically depends on reproducible and transparent data processing. Cross-subject and cross-study comparability of imaging data in general, and magnetic resonance imaging (MRI) data in particular, is contingent on the quality of registration to a standard reference space. In small animal MRI this is not adequately provided by currently used processing workflows, which utilize high-level scripts optimized for human data, and adapt animal data to fit the scripts, rather than vice-versa. In this fully reproducible article we showcase a generic workflow optimized for the mouse brain, alongside a standard reference space suited to harmonize data between analysis and operation. We introduce four separate metrics for automated quality control (QC), and a visualization method to aid operator inspection. Benchmarking this workflow against common legacy practices reveals that it performs more consistently, better preserves variance across subjects while minimizing variance across sessions, and improves both volume and smoothness conservation RMSE approximately 2-fold. We propose this open source workflow and the QC metrics as a new standard for small animal MRI registration, ensuring workflow robustness, data comparability, and region assignment validity, all of which are indispensable prerequisites for the comparability of scientific results across experiments and centers.
An Automated Open-Source Workflow for Standards-Compliant Integration of Small Animal Magnetic Resonance Imaging Data
Ioanas, Horea-Ioan; Marks, Markus; Garin, Clément M.; et al. (2019)
bioRxiv
Large-scale research integration is contingent on seamless access to data in standardized formats. Standards enable researchers to understand external experiment structures, pool results, and apply homogeneous preprocessing and analysis workflows. Particularly, they facilitate these features without the need for numerous potentially confounding compatibility add-ons. In small animal magnetic resonance imaging, an overwhelming proportion of data is acquired via the ParaVision software of the Bruker Corporation. The original data structure is predominantly transparent, but fundamentally incompatible with modern pipelines. Additionally, it sources metadata from free-field operator input, which diverges strongly between laboratories and researchers. In this article we present an open-source workflow which automatically converts and reposits data from the ParaVision structure into the widely supported and openly documented Brain Imaging Data Structure (BIDS). Complementing this workflow we also present operator guidelines for appropriate ParaVision data input, and a programmatic walk-through detailing how preexisting scans with uninterpretable metadata records can easily be made compliant after the acquisition.

Publications 1 - 10 of 10

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