Investigating the therapeutic potential of bumetanide in neurodegenerative and neurodevelopmental disorders

Patricia Lam¹, Chitra Vinnakota¹, Beatriz Calvo-Flores Guzmán¹, Julia Newland¹, Oran McNamara², Katie Peppercorn³, Warren P. Tate³, Henry J. Waldvogel¹, Richard L. M. Faull¹ and Andrea Kwakowsky^1,2

¹ Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, New Zealand

² Pharmacology and Therapeutics, Galway Neuroscience Centre, School of Medicine, National University of Galway, Galway, Ireland

³ Department of Biochemistry, University of Otago, Dunedin, New Zealand

Bumetanide, a potent loop-diuretic which antagonizes Na-K-Cl 1 cotransporter (NKCC1), has recently emerged as a potential treatment in both neurodegenerative and neurodevelopmental disorders. It is hypothesized that a significant contributor towards neurological disorders is depolarizing GABAergic activity, whereby activation of the GABA_A ionotropic channel of GABA responsive neurons results in excessive neuronal depolarization, subsequently resulting in dysfunctional network activity and excitotoxicity. A key feature of GABA_A receptor polarity is chloride homeostasis, which is dictated by NKCC1 and potassium-chloride cotransporter 2 (KCC2) within neurons. It is hypothesized that bumetanide exerts efficacy in treating neurological disorders through antagonism of NKCC1, restoring hyperpolarizing GABA_A activity.

We examined the potential neuroprotective effects of bumetanide in an Alzheimer’s disease (AD) mouse model. Primary mouse hippocampal cultures were treated with beta-amyloid (Aβ_1-42) and bumetanide (1µM, 10µM, 100µM, 1mM) to investigate the effect of bumetanide on cell viability. Aβ_1-42 produced 53% cell death after 5 days, which did not improve with bumetanide treatment. Bumetanide at 1µM alone, and higher concentrations, leads to 61.5 ± 1.2% cell death after 5 days, suggesting bumetanide is neurotoxic. In addition, localized NKCC1 upregulation and KCC2 downregulation were apparent in the CA1 subregion of the hippocampus in an in vivo AD mouse model and the human brain.

Our systematic literature review found that bumetanide demonstrated the capacity to significantly restore hyperpolarizing GABAergic activity following in vivo and ex vivo administration, as well as improve behavioral and cognitive abnormalities across disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, autism spectrum disorder, schizophrenia, tuberous sclerosis, fragile X syndrome, Down syndrome, and Angelman’s syndrome. A meta-analysis of childhood autism rating scale (CARS) scoring demonstrated that bumetanide was significantly more efficacious than placebo and provided evidence for responsive patient sub-types.

While these results are promising, the findings suggest that further research is needed to fully elucidate bumetanide's precise role and potential in treating neurological disorders.

Precise control of microtubule structure and intracellular trafficking in living cells and behaving animals

Yu-Chun Lin¹

¹National Tsing Hua University, Institute of Molecular Medicine, HsinChu, Taiwan

Microtubules are essential for regulating cellular processes such as intracellular transport, mitosis, and migration. Dysfunctions in microtubules are implicated in neurodegenerative disorders, cancer, and aging. Their diverse roles stem from variations in tubulin isotypes and post-translational modifications (PTMs), as well as their organization into specialized structures like primary cilia, centrosomes, and mitotic spindles. A major challenge in the field is deciphering how different microtubule subtypes spatiotemporally regulate cellular functions, a task hindered by technical limitations in precise manipulation.

To address this, our team has developed innovative tools that enable precise control over tubulin PTMs, microtubule disassembly, and intracellular trafficking along specific microtubule subtypes (Hong et al., Nat. Commun., 2018; Liu et al., EMBO J., 2022; Lian and Lin, Curr. Opin. Cell Biol., 2024). These approaches allow rapid and reversible perturbation of microtubule dynamics, providing deeper insights into their regulatory mechanisms. Using these tools, we have elucidated the roles of microtubules and intracellular trafficking in shaping cellular architecture and activity. At the organismal level, we demonstrated that targeted modulation of microtubule disassembly and synaptic vesicle transport can reversibly influence locomotion in C. elegans and Drosophila. Moreover, we showed that selective inhibition of ACE2-mediated viral entry can be achieved without disrupting other endocytic pathways, highlighting potential therapeutic applications (Chen et al., Adv. Sci., 2024).

Most recently, we provide molecular evidience that non-colocalized vesicles preferentially traffic along distinct microtubule subtypes, further advancing our understanding of intracellular transport specificity. Our cutting-edge tools provide a powerful framework for exploring how microtubule subtypes and intracellular trafficking spatiotemporally coordinate cellular architecture and function under physiological and pathological conditions.

Acknowledgment

This research is primarily supported by the National Science and Technology Council, Taiwan (grant number 113-2628-B-007-003).

Promoting the Integration of People with Mental Health Conditions into Orienteering - Flex-O project

Hungarian Orienteering Federation, Budapest, Hungary

The Hungarian Orienteering Federation has initiated a series of programmes called Flex-O, specifically designed for people with special needs. The aim of this initiative is to give people with mental health challenges the opportunity to participate in a sporting activity while benefiting from the positive mental health effects associated with spending time outdoors. The programmes are designed to develop a range of individual and social skills.

Research has demonstrated the positive impact of orienteering on cognitive areas such as perception, information processing, memory, spatial orientation and problem solving. The multiple developmental impacts on different executive functions make it particularly suitable for certain childhood conditions, such as autism spectrum disorder. For children with special educational needs, the Flex-O form of orienteering is psychologically beneficial, having a positive effect on self-confidence, autonomy, stress management and social relationships. Flex-O events are organised in an integrated environment, taking place in the competitive environment of a regular orienteering event, but on a carefully planned, safe and separate course, with additional support available.

The primary target group for Flex-O are children and young people with special educational needs, particularly those with autism spectrum disorders, motor and speech development disorders, learning disabilities and attention deficit hyperactivity disorder. The organisation of Flex-O events is overseen by volunteer facilitators who have expertise in orienteering and are attuned to the individual characteristics and needs of the participants.

Acknowledgements: Our research has been supported by Erasmus+ 2023-1-HU01-KA210-ADU-000156565

Insights into autism etiology

Daniela Ostatníková¹, Silvia Lakatošová¹, Katarína Janšáková¹, Gabriela Repiská¹, and Jaroslava Babková¹

¹Comenius University Faculty of Medicine in Bratislava, Institute of Physiology, Academic Research Centre for Autism, Bratislava, Slovakia

Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions characterized by difficulties in social communication and unusually restricted, repetitive behavior and interests. One of the main features of autism is the unequal sex distribution, with higher prevalence in boys. During critical prenatal period testosterone and its metabolites play crucial role in masculinization of brain with cognitive and behavioral consequences. In general, human population males are more systemized while females are more empathized. The behaviors seen in autistic individuals suppose to be exaggerations of typical sex differences (Baron-Cohen, 2005) and therefore exposure to high levels of prenatal testosterone might be a risk factor for autism. Increased androgen activity has been considered a potential etiological factor in pathogenesis of aggressive behavior. Children with ASD manifest aggression and other behavioral/emotional problems. Oxytocin is considered the prosocial hormone and might be protective in autism development.

Children in our research studies were diagnosed by golden standard ADOS and ADI-R diagnostic tools. Testosterone and oxytocin levels in ASD children were measured in plasma using ELISA method. Testosterone levels were determined in 82 boys with autism and 93 control boys according to standardized procedures. Oxytocin levels were measured in 108 children with autism and compared with a control group of 131 healthy children. Oxytocin levels were lower in autistic boys in comparison with controls, there was no difference in girls. Testosterone levels were higher in boys with autism, moreover genetic analysis revealed increased androgenic affect.

We also have explored testosterone in relation to behavioral problems in 31prepubertal boys with autism. Parents completed the Nisonger Child Behavior Rating Form (NCBRF) to assess specific behavioral/emotional problems. There were positive correlations between testosterone levels and the conduct problems subscale of NCBRF and also between testosterone levels and the hyperactive subscale of NCBRF.

The hormonal factors associated with autism involve complex interactions between genes and environmental influences. Unraveling the pathomechanisms of autism not only enhances our understanding of the disorder but helps to find the way for targeted interventions and personalized approaches to support children with ASD.

Acknowledgement:

Supported by grants APVV-20-0139, APVV-20-0070, APVV-20-0114

Autism, Gut and Nutrition

Katarina Babinska, Aleksandra Tomova, Ivan Belica, Barbara Raskova, Maria Kopcikova, Katarina Jansakova, Jaroslava Babkova, Gabriela Repiska, and Daniela Ostatnikova

Comenius University Bratislava, Faculty of Medicine, Institute of Physiology, Academic Research Centre for Autism, Bratislava, Slovakia

Autism spectrum disorders (ASD) are lifelong neurodevelopmental conditions defined by impairments of social communication, social interaction, and restricted or repetitive patterns of behaviour, interests, and activities. ASD are considered to be a serious health problem due to their increasing prevalence, serious clinical presentation, unclear etiology and absence of causal treatment. ASD are associated with numerous health problems, gastrointestinal (GI) dysfunction being one of the most prevalent. Causes of GI problems are not fully clear, one of the factors may be the dysbiosis in the GI tract, that stimulates low grade inflammation of the intestinal mucosa. Processes in the intestine are transmitted via neurohumoral pathways into the central nervous system and may cause behavioural changes.

Results of our studies show a higher prevalence of GI disorders in children and adolescents with ASD. We have observed significantly increased levels of selected inflammatory markers: HMGB1 in plasma and calprotectin in faeces. Interestingly, the plasma cytokine profile of neurotypical siblings of ASD children displayed only a minor difference, indicating possible shared genetic risks, and involvement of additional factors in pathogenesis of the disorder. By the use of 16S rRNA sequencing method, we have revealed bacteria significantly associated with ASD. Distinct types of bacteria were linked to the dietary selectivity of individuals with ASD, indicating that dietary specifics may play role in the observed differences in their microbiome and gut niche. We have observed significant associations between inflammatory markers, GI dysfunction, gut microbiota composition, and severity of autism or challenging behaviours. We have found beneficial effects of probiotic supplementation on the gut microbiota composition and behaviour.

Results of our studies indicate the possible involvement of GI and nutritional factors in pathophysiology of behavioral symptoms of ASD. They highlight, that the multi-professional care of children and adolescents with ASD should include management of gastrointestinal and nutrition-related problems due to their high prevalence and possible adverse effects on their behavior and well-being.

Acknowledgement: Supported by grants APVV-20-0139, APVV-20-0070, APVV-20-0114

Bermuda Triangle: Oxytocin, Dopamine, and GABA in Autism Etiology

Ján Bakoš^1,2, Zuzana Ševčíková Tomašková², Tomáš Havránek^1,2, Denisa Mihalj², Dalibor Putala², Daniela Ostatníková¹ and Zuzana Bačová²

¹ Comenius University in Bratislava, Faculty of Medicine, Bratislava, Slovakia

² Slovak Academy of Sciences, Biomedical Research Center, Bratislava, Slovakia

Despite many studies on dopamine changes in autism, specific alterations in midbrain dopamine neurons projecting to the striatum and cortex remain unclear. Neurons located in dopaminergic brain areas form extensive connections with both GABAergic and oxytocin-producing neurons. Alterations in neurite growth and reciprocal connections between dopamine, GABA, and oxytocin-producing neurons may disrupt the perception and evaluation of social stimuli, affect motivational levels, and lead to abnormal movement patterns. To elucidate these complex changes, we systematically study neuron morphology, neurite outgrowth, and their connections in autism-like animal models. Our recent findings indicate a significantly reduced number of short neurites in GABAergic neurons isolated from the ventral tegmentum of Shank3-deficient mice. A similar trend was observed in neurite arborization following transient Shank3 gene silencing in primary striatal and tegmental neurons. Incubation of neuronal cells in the presence of oxytocin did not significantly affect neurite arborization in primary neurons isolated from the striatum and tegmentum. Increased levels of the postsynaptic protein Neuroligin3 were observed in neurons isolated from the striatum of Shank3-deficient mice, with no differences found after transient Shank3 gene silencing. No change in D2 receptor immunofluorescence was found in primary striatal neurons from Shank3-deficient mice. In contrast, a significant decrease in D2 receptor and Neuroligin 3 immunofluorescence was found following transient Shank3 gene silencing in primary striatal neurons, independent of oxytocin effects. It is likely that the morphology and connections of GABAergic neurons in dopaminergic brain regions contribute to autism-like behavior. Changes in neurite outgrowth are accompanied with alterations in postsynaptic adhesion molecules and dopamine receptors, without additional effects from oxytocin. Changes in the morphology and connections of specific neuron subtypes in dopaminergic brain regions may contribute to autism pathogenesis, at least during certain developmental stages. This work was supported by grants APVV-21-0189, VEGA 2/0057/23, 2/0132/25 and bilateral Hungarian-Slovak collaboration HAS-SAS-2024.

Establishment of a Cryo-EM Core Facility at the University of Pécs

Péter Horváth^1* and Bianka Kitti Kőhegyi ^1*

¹Cryo-EM Core Facility, University of Pécs, Szentágothai Research Center, Pécs, Hungary

^*Authors contributed equally to this work

Cryo-electron microscopy (cryo-EM) has revolutionized structural biology, enabling the visualization of macromolecular complexes at near-atomic resolution. To support cutting-edge research in life sciences, we are in the process of establishing a state-of-the-art cryo-EM core facility at the University of Pécs in cooperation with Richter Plc. This facility will provide access to high-end instrumentation for researchers in structural biology, drug discovery, and biomaterial sciences, material sciences fostering interdisciplinary collaborations.

The core will be equipped with a 300 keV cryogenic electron microscope featuring automated sample handling, energy-filtered imaging, and direct electron detection. These capabilities allow high-resolution single-particle analysis, cryo-electron tomography (cryo-ET), and microcrystal electron diffraction (MicroED). During our talk, we will introduce these techniques and describe some possibilities that can be achieved by cryo-EM.

Beyond infrastructure, the facility offers expert training, technical support, and data analysis assistance, making cryo-EM accessible to researchers with diverse expertise. Until we can provide a hands-on training, with Cryo-EM lecture series future users may gain the theoretical background necessary to prospective experiments. Collaborations with national and international institutions strengthen the scientific impact of the facility, positioning the University of Pécs as a regional hub for cryo-EM research.

By establishing this core facility, we enable breakthrough discoveries in biomedical sciences, contributing to fundamental research and translational applications. This initiative supports the development of new therapeutics, biomaterials, and nanotechnology solutions, driving scientific excellence and innovation in Hungary and beyond.

Mapping the gating mechanism of the human TRPM2 channel through the investigation of orthologs

Adam Bartok¹²³, Laszlo Csanady¹²³

¹ Semmelweis University, Biochemistry and Molecular Biology Institute, Budapest, Hungary

² HCEMM-SU Molecular Channelopathies Research Group, Budapest, Hungary

³ HUN-REN-SE Ion Channel Research Group, Budapest, Hungary

Transient receptor potential melastatin 2 (TRPM2) is a Ca²⁺ permeable cation channel located in the plasma membrane of various cell types. The activity of the channel is regulated by the simultaneous binding of three ligands: PiP₂, intracellular Ca²⁺ and ADP-ribose (ADPR). The channel is highly temperature-sensitive, as increasing temperature facilitates agonist-driven channel opening. Thus, TRPM2 in hypothalamic neurons plays a role in the central regulation of body temperature, as well as in non-noxious heat detection in peripheral neurons. TRPM2 also participates in the activation of phagocytes and the insulin secretion of pancreatic β-cells.

We investigated the gating mechanism and temperature sensitivity of the zebrafish (drTRPM2) and human (hsTRPM2) orthologs of the channel using the patch-clamp technique and found major differences in their temperature sensitivities and agonist-binding affinities. We identified and characterized a Ca²⁺-dependent inactivation and recovery mechanism in drTRPM2 and constructed a simplified gating scheme that accurately predicts the agonist-dependent channel behavior. Presuming that this gating scheme of drTRPM2 is analogous to that of hsTRPM2, we confirmed that the kinetics of inactivation of hsTRPM2 is indeed Ca²⁺-dependent, and high-affinity Ca²⁺ binding traps the channel in the inactivated state, which, contrary to previous paradigms, is in fact a reversible mechanism.

Acknowledgement: Supported by the EU Horizon 2020 Research and Innovation Program grant 739593 and National Research, Development and Innovation Fund NKFIH KKP_22 grant 144199 and ADVANCED 149640. AB was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00103/20) and the New National Excellence Program (ÚNKP) Bolyai+ scholarship of the Ministry of Human Capacities of Hungary (ÚNKP-20-5-SE-6, ÚNKP-21-5-SE-10, and ÚNKP-22-5-SE-12).

Trpm4 in Hilar Mossy Cells, A Role in Epilepsy

Erzsébet Kövesdi¹, Laura Mundrucz¹, Angela Kecskes⁷, Attila Gyéresi¹, Máté Deák¹, Balázs Gaszner², Cecília Szekeres-Paraczky⁴, Zsófia Maglóczky⁴, Rudi Vennekens³ Viktória Kormos⁷ and Miklós Kecskés¹

¹ Institute of Physiology, Medical School, University of Pécs, Pécs, Hungary

² Department of Anatomy, Medical School and Research Group for Mood Disorders, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, Pécs, Hungary^.

³ Laboratory of Ion Channel Research, Biomedical Sciences Group, Department of Cellular and Molecular Medicine, VIB‑KU Leuven Center for Brain & Disease Research, KU Leuven, Leuven, Belgium

⁴ Human Brain Research Laboratory, HUN-REN Institute of Experimental Medicine, Budapest, Hungary

⁷ Department of Pharmacology and Pharmacotherapy, Centre for Neuroscience, Medical School, University of Pécs, Pécs, Hungary

Mossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus, and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients; however, the mechanisms leading to cellular death is unclear.

Transient receptor potential melastatin 4 (TRPM4) is a Ca²⁺-activated non-selective cation channel regulating diverse physiological functions of excitable cells. Here, we identified that TRPM4 is present in hilar mossy cells and regulates their intrinsic electrophysiological properties including spontaneous activity and action potential dynamics. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits. Finally, we demonstrated that in vivo application of meclofenamate a novel antagonist of TRPM4 before the induction of status epilepticus reduces the frequency and duration of seizures in mice.

Our results provide evidence for the role of TRPM4 in MC excitability both in physiological and pathological conditions.

TRP channels in human dental pulp-derived cells and their role in pulpitis

Márk Racskó^1,2, Judit Bohács^1,2,3, Árpád Kunka^1,2,4, Erika Lisztes¹, Nóra Henn-Mike⁵, Rita Marincsák³, Balázs István Tóth^1,5

¹ University of Debrecen, Faculty of Medicine, Department of Physiology, Debrecen, Hungary

² University of Debrecen, Doctoral School of Molecular Medicine, Debrecen, Hungary

³ University of Debrecen, Faculty of Dentistry, Department of Operative Dentistry and Endodontics, Debrecen, Hungary

⁴ University of Debrecen, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Debrecen, Hungary

⁵ University of Pécs, Medical School, Institute of Physiology, Pécs, Hungary

Pulpitis, the most common inflammatory disease of the teeth, is often associated with hyperalgesia toward mechanical and thermal stimuli. In the transduction of the algogenic physical stimuli, transient receptor potential (TRP) ion channels of the somatosensory fibers play a crucial role. Changes in their expression and sensitivity contribute to the development of hyperalgesia or allodynia. However, TRP channels are also expressed in non-neuronal cells of the dental pulp which can also shape sensory and inflammatory processes. In this study, we investigated sensory TRP channels in human dental pulp-derived cells isolated from healthy molar teeth.

We investigated the expression of various warm- and cold-sensitive TRP channels in primary human dental pulp cells (hDPCs) and the expression of mechanosensitive ion channels in odontoblast-like cells (OBLCs) differentiated from hDPCs in vitro. The functionality of TRP channels was investigated by measuring changes in intracellular Ca²⁺ concentration upon applying pharmacological agonists and antagonists. The mechanosensitivity of OBLCs was also investigated.

We established inflammatory conditions in hDPC cultures by applying various ligands representing pathogen and damage-associated molecular patterns activating pattern recognition Toll-like receptors. Poly(I:C), a ligand of Toll-like receptor 3 (TLR3), induced robust inflammatory responses, whereas other PAMPs were less effective. Poly(I:C) stimulated the production of pro-inflammatory cytokines, induced oxidative stress and highly upregulated TRPA1, a multimodal nociceptor of the TRP family. In poly(I:C) induced inflammatory conditions, intracellular Ca²⁺ signals evoked by TRPA1 ligands were highly potentiated. Poly(I:C)-treated cells displayed increased Ca²⁺ responses to H₂O₂ which was abolished by TRPA1 antagonism. Moreover, poly(I:C) resulted in diminished cellular viability and mitochondrial functions. Mitochondrial dysfunctions were alleviated by the antioxidant glutathione and partly by TRPA1 antagonism or silencing. Our running experiments investigate novel pharmacological tools to alleviate poly(I:C) induced pulpal inflammation.

Our results suggest that TRP channels in the dental pulp are not only important players in dental sensory transduction, but also promising pharmacological targets to combat pulpitis and alleviate inflammation-related pulpal tissue damage.

The research was supported by NKFI 134725, 134791, EKÖP-24-4-II-DE-19, EKÖP-24-3-II-DE-384, and EKÖP-24-3-I-DE-420.

Investigation the effect of antibiotics on E. coli cells using different microscopical methods

Szilvia Barkó¹, Beáta Longauer¹, Emőke Bódis¹, Tamás Huber¹, Miklós Nyitrai ¹, Géza Makkai² Tibor Jánosi² and András Lukács¹

¹ Medical School, Department of Biophysics, University of Pécs, Pécs, Hungary

²Medical School, Nano-Bio-Imaging Core Facility, University of Pécs, Pécs, Hungary

The MreB protein plays a crucial role in bacterial cell wall synthesis. The cellular function of MreB can be specifically inhibited by the antibacterial agent A22, which was found to be effective only against Gram-negative bacteria. The antibiotic vancomycin is used for infections caused by Gram-positive bacteria, as it cannot penetrate easily through the outer lipid layer of Gram-negative bacteria.

Our observation is that vancomycin enhances the effect of A22 on MreB. This is confirmed by both our microbiological and microscopic results. Using the fluorescent analogue of vancomycin, we believe that not only the cell wall synthesis apparatus already identified as a binding partner, but also the MreB molecule itself can be visualized. For our studies we used confocal, FLIM and SIM microscopes of the Ábrahám István Nanobio Imaging Center.

Introducing the Medical and Preclinical Imaging Subnode of Euro-BioImaging at the University of Pécs

Bálint Botz¹, Ádám István Horváth^2,3 and Zsuzsanna Helyes^2,3,4

¹ Department of Medical Imaging, Medical School, University of Pécs, Pécs, Hungary

² Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary

³ National Laboratory for Drug Research and Development, Budapest, Hungary

⁴ Hungarian Research Network, HUN-REN-PTE Chronic Pain Research Group, Pécs, Hungary

The Medical and Preclinical Imaging Subnode at the University of Pécs possesses the most complex in vivo imaging platform in Hungary. The preclinical imaging platform was established in 2012 at the Department of Pharmacology and Pharmacotherapy of the Medical School. It involves a luminescent and fluorescent in vivo optical imaging system (IVIS Lumina III, PerkinElmer), a fluorescent molecular tomograph (FMT 2000, PerkinElmer), a Laser Speckle Imaging System (PeriCam PSI, Perimed) and an in vivo micro-CT (SkyScan 1176, Bruker). These equipments provide valuable tools for investigating pathophysiological processes and identifying novel drug targets in inflammatory diseases, which is one of the main research profiles of the department. IVIS Lumina III and FMT 2000 are suitable for functional imaging of the brain and peripheral organs in rodents, as well as investigating cellular and vascular responses of inflammatory processes. PeriCam PSI allows the real-time measurement of blood perfusion changes in tissues at the microcirculation level. Furthermore, in vivo micro-CT visualizes structural alterations of the bone microarchitecture associated with inflammatory and degenerative joint diseases, lung structural changes related to inflammation, emphysema and fibrosis, as well as body fat composition.

Our clinical imaging research group focuses on the role of contrast-enhanced ultrasound (CEUS) and Doppler-based microvascular flow imaging (MVFI) in the assessment of solid tissue lesions and inflammatory conditions in a variety of clinical conditions. These methods aid the assessment of tissue vascular architecture and small vessel organization with excellent temporal and spatial resolution. Approximately 700 CEUS exams are conducted in our department annually, and we are the largest performing such studies in Hungary. Our research focuses on the quantitative assessment of liver lesion enhancement kinetics, and its role in lesion characterization. Our aim is to develop a vendor-neutral CEUS analysis software, that could be better integrated into the clinical diagnostic workflow. We also actively study the role of CEUS in the characterization of cystic renal lesions, the predictive value and diagnostic performance of both CEUS and MVFI.

Acknowledgement: RRF-2.3.1-21-2022-00015, Hungarian Research Network (Chronic Pain Research Group), National Brain Research Program 3.0