@Article{ HagbergMPBMVKDKL2013, title = {Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex}, journal = {Contrast Media & Molecular Imaging}, year = {2014}, month = {1}, volume = {9}, number = {1}, pages = {71–82}, abstract = {Calcium-sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an MRI-based method capable of determining diffusion properties of conventional and calcium-sensitive agents. Simulations and experiments demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value and for calcium-sensitive contrast agents. The full pharmacokinetic time-course of gadolinium concentration estimates was observed by MRI before, during and after intracerebral administration of the agent, and the effective diffusion coefficient D* was determined by voxel-wise fitting of the solution to the diffusion equation. The method yielded whole brain coverage with a high spatial and temporal sampling. The use of two types of MRI sequences for sampling of the diffusion time courses was investigated: Look–Locker-based quantitative T1 mapping, and T1-weighted MRI. The observation times of the proposed MRI method is long (up to 20 h) and consequently the diffusion distances covered are also long (2–4 mm). Despite this difference, the D* values in vivo were in agreement with previous findings using optical measurement techniques, based on observation times of a few minutes. The effective diffusion coefficient determined for the calcium-sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady state, thereby enabling quantitative sensing of the local calcium concentration.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/cmmi.1535/pdf}, state = {published}, DOI = {10.1002/cmmi.1535}, author = {Hagberg G{ghagberg}{Department High-Field Magnetic Resonance}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Power A{apower}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Kiselev VG; Dhingra K{kirti}{Department Physiology of Cognitive Processes}; Kub{\`i}ček V; Angelovski G{goran}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ DhingraVermaFUBMPBL2013, title = {New Calcium-Selective Smart Contrast Agents for Magnetic Resonance Imaging}, journal = {Chemistry - A European Journal}, year = {2013}, month = {12}, volume = {19}, number = {52}, pages = {18011–18026}, abstract = {Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca2+ levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca2+ in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca2+-sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca2+ in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd3+-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) coupled to a Ca2+ chelator o-amino phenol-N,N,O-triacetate (APTRA). The agents are designed to sense Ca2+ present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2–0.8 mM. The determined dissociation constant of the CAs to Ca2+ falls in the range required to sense and report changes in extracellular Ca2+ levels followed by an increase in neural activity. In buffer, with the addition of Ca2+ the increase in relaxivity ranged from 100–157 %, the highest ever known for any T1-based Ca2+-sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb3+ analogues, nuclear magnetic relaxation dispersion (NMRD), and 17O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca2+ addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/chem.201300169/pdf}, state = {published}, DOI = {10.1002/chem.201300169}, author = {Dhingra Verma K{kirti}{Department Physiology of Cognitive Processes}; Forg{\'a}cs A; Uh H; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Maier ME; Petoud S; Botta M; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ DhingraVermaMEBML2012, title = {Magnetic-Field-Dependent 1H Relaxivity Behavior of Biotin/Avidin-Based Magnetic Resonance Imaging Probes}, journal = {ChemPlusChem}, year = {2012}, month = {9}, volume = {77}, number = {9}, pages = {758–769}, abstract = {One major challenge in noninvasive mapping of various molecular targets is their inherently low in vivo concentration coupled with the insensitivity of imaging modalities, such as the widely used magnetic resonance imaging (MRI). Development of agents with high sensitivity and specificity is of paramount importance for structural and functional noninvasive imaging. The design, synthesis, and physiochemical characterization of two gadolinium-based contrast agents (CAs) for MRI, the sensitivity of which was optimized by exploiting the well-established biotin–avidin amplification strategies, are reported. The relaxivity of these agents showed a large increase if bound to avidin; specifically, the first compound showed an approximately 1000 % increase in transverse proton relaxivity (r2p), whereas the second compound had an approximately 250 % r2p increase. The increase in r2p was magnetic field independent in the range of 1.5–16.4 T whereas the longitudinal proton relaxivity (r1p) showed strong field dependence. The CAs were further characterized by measuring luminescence lifetimes and emission spectral changes upon addition of avidin to their Eu3+ analogues. The difference in relaxation rate behavior of both complexes was explained on the basis of hydration number modulation and the “global/internal motion concept”. The association constant of these CAs with avidin was found to be in the range of approximately 1015 M−1, which shows that the coupling of biotin to Gd-DO3A did not affect its affinity for binding to avidin (DO3A=1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid).}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/cplu.201200064/pdf}, state = {published}, DOI = {10.1002/cplu.201200064}, author = {Dhingra Verma K{kirti}{Department Physiology of Cognitive Processes}; Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Maier ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ MamedovEEBL2011, title = {Dual-functional probes towards in vivo studies of brain connectivity and plasticity}, journal = {Chemical Communications}, year = {2012}, month = {2}, volume = {48}, number = {22}, pages = {2755-2757}, abstract = {A Gd3+ based paramagnetic dextran conjugate has been developed, which enables the tracking of neuroanatomical connectivity in the brain by both MR and optical imaging. Cell studies and subsequent in vivo experiments in rodents demonstrate efficient internalisation and transport properties of the new tracer molecule.}, web_url = {http://pubs.rsc.org/en/Content/ArticleLanding/2012/CC/c1cc15991g}, state = {published}, DOI = {10.1039/C1CC15991G}, author = {Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ EschenkoENBML2011, title = {Tracing of noradrenergic projections using manganese-enhanced MRI}, journal = {NeuroImage}, year = {2012}, month = {2}, volume = {59}, number = {4}, pages = {3252–3265}, abstract = {We examined the applicability of manganese-enhanced MRI (MEMRI) to the in vivo tracing of diffuse neuromodulatory projections by means of simultaneous iontophoretic injections of an extremely low, non-toxic concentration of MnCl2 (10 mM) and fluorescent dextran in the locus coeruleus (LC) in the rat. We validated the use of the iontophoretic injection by reproducing previously reported results from pressure injections of MnCl2 in primary somatosensory cortex. Twenty four hours after injection in LC, Mn2 + labeling was detected in major cortical and subcortical targets of LC projections including predominantly ipsilateral primary motor and somatosensory cortices, hippocampus and amygdala. Although the injections were in most cases centered in the core of LC, the pattern of Mn2 + labeling greatly varied across rats. In addition, despite a certain degree of overlap of the labeling obtained with both MEMRI and classical tracing, MEMRI tracing consistently failed to reliably label not only several minor but also major targets of LC, notably the thalamus. The lack of Mn2 + labeling in thalamus possibly reflected a weaker functional connectivity within coeruleothalamic projections that could not be predicted by anatomical tracing. Inversely, a number of brain regions, particularly contralateral motor cortex, that were not or only sparsely labeled with fluorescent dextran were strongly labeled by Mn2 +. This discrepancy could be partly due to both the activity-dependent and transsynaptic nature of Mn2 + transport. The overall labeling produced using MEMRI with iontophoretic injections in LC indicates that the Mn2 + imaging of highly diffuse projections is in principle feasible. However, the labeling pattern of each individual case needs to be carefully interpreted particularly before submitting data for group analysis or in the case of longitudinal examination of discrete changes in functional connectivity under various physiological or behavioral conditions.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811911013127}, state = {published}, DOI = {10.1016/j.neuroimage.2011.11.031}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Neves RM{ricardo}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ MishraSEBLC2011, title = {Biocytin-derived MRI contrast agent for longitudinal brain connectivity studies}, journal = {ACS Chemical Neuroscience}, year = {2011}, month = {10}, volume = {2}, number = {10}, pages = {578–587}, abstract = {To investigate the connectivity of brain networks noninvasively and dynamically, we have developed a new strategy to functionalize neuronal tracers and designed a biocompatible probe that can be visualized in vivo using magnetic resonance imaging (MRI). Furthermore, the multimodal design used allows combined ex vivo studies with microscopic spatial resolution by conventional histochemical techniques. We present data on the functionalization of biocytin, a well-known neuronal tract tracer, and demonstrate the validity of the approach by showing brain networks of cortical connectivity in live rats under MRI, together with the corresponding microscopic details, such as fibers and neuronal morphology under light microscopy. We further demonstrate that the developed molecule is the first MRI-visible probe to preferentially trace retrograde connections. Our study offers a new platform for the development of multimodal molecular imaging tools of broad interest in neuroscience, that capture in vivo the dynamics of large scale neural networks together with their microscopic characteristics, thereby spanning several organizational levels.}, web_url = {http://pubs.acs.org/doi/pdf/10.1021/cn200022m}, state = {published}, DOI = {10.1021/cn200022m}, author = {Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Canals S{canals}{Department Physiology of Cognitive Processes}} } @Article{ 6854, title = {In Vivo Characterization of a Smart MRI Agent That Displays an Inverse Response to Calcium Concentration}, journal = {ACS Chemical Neuroscience}, year = {2010}, month = {12}, volume = {1}, number = {12}, pages = {819-828}, abstract = {Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd3+ complex linked to an aminobis(methylenephosphonate) group for chelating Ca2+ was synthesized and investigated. The longitudinal relaxivity (r1) of this complex decreases during the relaxometric titration with Ca2+ from 5.76 to 3.57 mM−1 s−1 upon saturation. The r1 is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu3+ complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity of this agent is significantly lower compared with that of gadolinium−diethylenetriaminepentaacetic acid (Gd−DTPA).}, web_url = {http://pubs.acs.org/doi/pdf/10.1021/cn100083a}, state = {published}, DOI = {10.1021/cn100083a}, author = {Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Canals S{canals}{Department Physiology of Cognitive Processes}; Henig J; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Mayer HA; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Article{ 6148, title = {Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies}, journal = {Neuroimage}, year = {2010}, month = {2}, volume = {49}, number = {3}, pages = {2544-2555}, web_url = {http://www.sciencedirect.com/science?_ob=PdfDownloadURL&_uoikey=B6WNP-4XM6K9C-1&_tockey=%23toc%236968%239999%23999999999%2399999%23FLA%23&_orig=search&_acct=C000003178&_version=1&_userid=29041&md5=3bf6091d834384671282cddb6fdb75}, state = {published}, DOI = {10.1016/j.neuroimage.2009.10.079}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Canals S{canals}{Department Physiology of Cognitive Processes}; Simanova I; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ 5682, title = {Functional MRI Evidence for LTP-Induced Neural Network Reorganization}, journal = {Current Biology}, year = {2009}, month = {2}, volume = {19}, number = {5}, pages = {398-403}, abstract = {The hippocampal formation is a region of the forebrain that is important for memory and spatial navigation [1] and [2]. On the basis of a vast amount of literature, the hippocampus is linked with long-term potentiation (LTP), the increased synaptic strength following repeated stimulation of the hippocampal neurons [3] and [4]. LTP is considered to be the experimental demonstration of Hebb‘s postulate on synaptic strength and learning [5], and it is the dominant model of an experience-dependent modification of brain circuits. Yet, despite the importance of this phenomenon for brain physiology and behavior, little is known about how experimentally measured regional synaptic modifications alter the activity of global, widespread networks. Here, we use simultaneous fMRI, microstimulation, and electrophysiology [6], [7] and [8] to unveil global changes in brain activity due to local hippocampal plasticity. Our findings offer the first evidence of an LTP-induced network reorganization that includes increased interhemispheric communication and recruitment of limbic and neocortical circuits after changes in synaptic strength within the hippocampus.}, web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6VRT-4VN6FY0-2-2&_cdi=6243&_user=29041&_orig=search&_coverDate=03%2F10%2F2009&_sk=999809994&view=c&wchp=dGLbVzz-zSkWz&md5=d169ef23b3c11c387440f570325c554a&ie=/sdarticle.pdf}, state = {published}, DOI = {10.1016/j.cub.2009.01.037}, author = {Canals S{canals}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ 4909, title = {Electric stimulation fMRI of the perforant pathway to the rat hippocampus}, journal = {Magnetic Resonance Imaging}, year = {2008}, month = {9}, volume = {26}, number = {7}, pages = {978-986}, abstract = {The hippocampal formation is a brain system that is implicated in learning and memory. The major input to the hippocampus arrives from the entorhinal cortex (EC) to the dentate gyrus (DG) through the perforant path. In the present work, we have investigated the functional properties of this connection by concomitantly applying electrophysiological techniques, deep-brain electric microstimulation and functional magnetic resonance imaging in anesthetized rats. We systematically delivered different current intensities at diverse stimulation frequencies to the perforant path while recording electrophysiological and blood-oxygenation-level-dependent (BOLD) signals. We observed a linear relationship between the current intensity used to stimulate the hippocampal formation and the amplitude and extension of the induced BOLD response. In addition, we found a frequency-dependent spatial pattern of activation. With stimulation protocols and train frequencies used for kindling, the activity strongly spreads ipsilaterall y through the hippocampus, DG, subiculum and EC.}, web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T9D-4SH1HXR-B-5&_cdi=5112&_user=29041&_orig=search&_coverDate=09%2F30%2F2008&_sk=999739992&view=c&wchp=dGLzVtb-zSkWz&md5=e7e95446b785f4dd0f51d9b02acb372d&ie=/sdarticle.pdf}, state = {published}, DOI = {10.1016/j.mri.2008.02.018}, author = {Canals S{canals}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ 5128, title = {Synthesis and Characterization of a Smart Contrast Agent Sensitive to Calcium}, journal = {Chemical Communications}, year = {2008}, month = {6}, volume = {29}, pages = {3444-3446}, abstract = {A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.}, web_url = {http://www.rsc.org/ej/CC/2008/b801975d.pdf}, state = {published}, DOI = {10.1039/b801975d}, author = {Dhingra K{kirti}{Department Physiology of Cognitive Processes}; Maier ME; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ 4894, title = {Magnetic Resonance Imaging of Cortical Connectivity in vivo}, journal = {Neuroimage}, year = {2008}, month = {4}, volume = {40}, number = {2}, pages = {458-472}, web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WNP-4RC6R7X-4-S&_cdi=6968&_user=29041&_orig=search&_coverDate=04%2F01%2F2008&_sk=999599997&view=c&wchp=dGLbVtz-zSkzS&md5=dabfb44094d1137121dd895184e159cc&ie=/sdarticle.pdf}, state = {published}, DOI = {10.1016/j.neuroimage.2007.12.007}, author = {Canals S{canals}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Keller AL{akeller}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ 2894, title = {Anatomical and Functional MR Imaging in the Macaque Monkey Using a Vertical Large-bore 7 Tesla Setup}, journal = {Magnetic Resonance Imaging}, year = {2004}, month = {12}, volume = {22}, number = {10}, pages = {1343-1359}, abstract = {Functional magnetic resonance imaging (MRI) in the nonhuman primate promises to provide a much desired link between brain research in humans and the large body of systems neuroscience work in animals. We present here a novel high field, large-bore, vertical MR system (7 T/60 cm, 300 MHz), which was optimized for neuroscientific research in macaque monkeys. A strong magnetic field was applied to increase sensitivity and spatial resolution for both MRI and spectroscopy. Anatomical imaging with voxel sizes as small as 75×150×300 μm3 and with high contrast-to-noise ratios permitted the visualization of the characteristic lamination of some neocortical areas, e.g., Baillarger lines. Relaxation times were determined for different structures: at 7 T, T1 was 2.01/1.84/1.54 s in GM/GM-V1/WM, T2 was 59.1/54.4 ms in GM/WM and T2* was 29 ms. At 4.7 T, T1 was 25% shorter, T2 and T2* 18% longer compared to 7T. Spatiotemporally resolved blood-oxygen-level-dependent (BOLD) signal changes yielded robust activations and deactivations (negative BOLD), with average amplitudes of 4.1% and −2.4%, respectively. Finally, the first high-resolution (500 μm in-plane) images of cerebral blood flow in the anesthetized monkey are presented. On functional activation we observed flow increases of up to 38% (59 to 81 ml/100 g/min) in the primary visual cortex, V1. Compared to BOLD maps, functional CBF maps were found to be localized entirely within the gray matter, providing unequivocal evidence for high spatial specificity. The exquisite sensitivity of the system and the increased specificity of the hemodynamic signals promise further insights into the relationship of the latter to the underlying physiological activity.}, web_url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T9D-4FF9547-2-K&_cdi=5112&_user=29041&_orig=search&_coverDate=12%2F31%2F2004&_sk=999779989&view=c&wchp=dGLzVlz-zSkzk&md5=26f8916c8f8a658f9009cce48bfcedfc&ie=/sdarticle.pdf}, state = {published}, DOI = {10.1016/j.mri.2004.10.004}, author = {Pfeuffer J{josef}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Inbook{ MishraDMSEBCL2011, title = {Biocytin-based contrast agents for molecular imaging: an approach to developing new in vivo neuroanatomical tracers for MRI}, year = {2012}, volume = {1}, pages = {181-204}, abstract = {One of the most striking characteristic of the brain is its profuse neuronal connectivity. Not surprisingly, the function of the nervous system critically depends on the spatiotemporal pattern of intercommunication between different regions of the brain. Both macro- and microscopic aspects of the wiring diagrams of brain circuits are relevant and need to be understood in order to cope with the complexity of the brain function. In this way, for instance, the long-range connections that carry the functional specification of cortical territories need to be studied together with the detailed microcircuits inside a cortical column. Moreover, the temporal dimension of these wiring diagrams must be investigated since neuronal networks are dynamic structures exhibiting context-dependent changes in synaptic weights (Canals et al., 2009) and numbers (Chklovskii et al., 2004). Investigations over the last decades strongly suggest that stimulus or task related neural activity is distributed over large parts of the brain, covering different cortical and sub-cortical areas. For a detailed understanding of brain function, it is of prime importance to understand the organization of the neuronal connections. To chart the anatomical connections between the various components of brain networks, the neuronal tract tracing technique has been proved to be very useful. Thus, experimental tools that allow the exploration of brain circuits at diverse organizational levels are mandatory for the understanding of brain intercommunication and information processing.}, web_url = {http://www.intechopen.com/articles/show/title/biocytin-based-contrast-agents-for-molecular-imaging-an-approach-to-developing-new-in-vivo-neuroanat}, editor = {Bright, P.}, publisher = {InTech}, address = {Rijeka, Croatia}, booktitle = {Neuroimaging - Methods}, state = {published}, ISBN = {978-953-51-0097-3}, DOI = {10.5772/23806}, author = {Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Mishra R{ritu}{Department High-Field Magnetic Resonance}; Canals S{canals}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}; Dhingra K{kirti}{Department Physiology of Cognitive Processes}} } @Poster{ BallaPSENSMOMMBELS2015, title = {500 ms temporal and 750 μm spatial inplane resolution for whole-brain fMRI applications in the macaque at 7T}, year = {2015}, month = {6}, day = {2}, volume = {23}, number = {3910}, abstract = {We developed fast MRI methods facilitating concurrent electrophysiological recordings and fMRI with high spatio-temporal resolution (500ms / 750µm) and full brain coverage in macaques. The significant improvements in MR signal sampling efficiency without and with the use of parallel imaging are demonstrated by presenting activation maps and time-courses of fMRI experiments using a simple visual stimulation paradigm.}, file_url = {fileadmin/user_upload/files/publications/2015/ISMRM-2015-Balla.pdf}, web_url = {http://www.ismrm.org/15/program_files/TueEPS04.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {accepted}, author = {Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Pohmann R{rolf}{Department High-Field Magnetic Resonance}; Shajan G{shajang}{Department High-Field Magnetic Resonance}; Ehses P{ehses}{Department High-Field Magnetic Resonance}; Nauerth A{arno}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}; Munk MH{munk}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}} } @Poster{ GoenseBHSSSLM2014, title = {Novel RF-Coil Assembly to Simultaneously Investigate fMRI and Electrophysiology in Non-Human Primates in a Large Bore Vertical Magnet}, year = {2014}, month = {5}, day = {12}, number = {1348}, abstract = {RF-coil design for combined electrophysiology and fMRI in non-human primates is challenging because any coil design needs to be sufficiently open to allow for electrode access to the brain. Patch antennas allow for a more open design, but since our bore is too small for a 300 MHz traveling wave, we developed an open quadrature transmit coil/antenna placed in-situ. The transmit coil/antenna is capable of producing a sufficiently homogenous B1 field. This device can be used alone in transceiver mode or in combination with dedicated receive arrays which allow for maximum flexibility while maintaining a very high SNR.}, web_url = {http://www.ismrm.org/14/program_files/TP04.htm}, event_name = {Joint Annual Meeting ISMRM-ESMRMB 2014}, event_place = {Milano, Italy}, state = {published}, author = {Goense J{jozien}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Hoffmann J{tatum}{Department High-Field Magnetic Resonance}; Shajan G{shajang}{Department High-Field Magnetic Resonance}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}} } @Poster{ EschenkoBMEBOL2013, title = {BOLD responses associated with hippocampal ripples in the rat brain}, year = {2013}, month = {11}, day = {13}, volume = {43}, number = {863.09}, abstract = {Hippocampal ripples, brief high-frequency oscillations, occur during behavioral states that are not associated with active sensory processing. The ripple event represents a simultaneous burst of a large neuronal population that is synchronized across the entire hippocampus. Reactivation of neuronal ensembles that were active during learning predominantly occurs during ripples. The number of ripples is increased after learning and this increase is predictive for memory recall. Ripple suppression is unfavorable for memory consolidation. Ripples have been suggested to provide a neurophysiological substrate for ‘off-line’ memory consolidation by facilitating synaptic plasticity within the learning-associated neuronal ensembles. The neuronal activity in other brain regions that is time-locked to hippocampal ripples may underlie a cross-regional information transfer. We exploited the methodology allowing simultaneous extracellular recording combined with fMRI. An anesthetized rat was fixed in the MRI scanner and MRI-compatible linear electrode array was placed with electrode contacts in cortex, hippocampus, and thalamus using a custom-made movable drive. Spontaneous whole-brain BOLD activity was acquired along with multi-site electrophysiological recording. The ripple events were detected and classified off-line using a custom software. The time series of BOLD responses were extracted for each voxel according to the event-triggered design, where the ripple onset was used as an event, and the statistical maps were generated indicating the voxels with positive and negative BOLD responses. The voxels were subsequently grouped according to the anatomical brain regions by co-registration of the functional images with the digital rat brain atlas. The positive BOLD response was detected within the direct proximity to the ripple recording site in the CA1 region of hippocampus. The most of the hippocampal volume was also co-activated. In addition, a number of cortical regions including sensory and associative cortices contained a substantial proportion of voxels showing positive BOLD responses. Several brain regions consistently showed negative BOLD responses. These included many of the thalamic nuclei, neuromodulatory nuclei of the midbrain and brain stem and cerebellum. The fMRI findings were further confirmed by electrophysiological recordings in multiple brain areas. Our results identify a brain network that possibly supports hippocampal-dependent memory consolidation. Besides, hippocampal ripples may cause a transient inhibition within competing functional networks to enable more efficient intra brain region communication.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Empirical Inference}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Evrard H{evrard}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ EschenkoBOL2013, title = {BOLD responses evoked by electrical stimulation of Locus Coeruleus in rats under anesthesia}, year = {2013}, month = {3}, abstract = {We performed a whole-brain fMRI imaging in the rat under urethane anesthesia and studied BOLD responses induced by electrical stimulation of the brain stem noradrenergic nucleus Locus Coeruleus (LC). The rat was first implanted with a MRI-compatible custom-made iridium electrode into LC under electrophysiological guidance. A 7T (300 MHz) magnet with a 30-cm horizontal bore (Bruker BioSpec 70/30, Ettlingen, Germany) equipped with a 20cm inner diameter gradient (Bruker BGA-20S Ettlingen, Germany) was used for MRI scanning. The experimental paradigm consisted of 6s base line sampling, followed by 4s of unilateral LC stimulation and 10s of post-stimulus sampling. Biphasic square pulses (0.05-0.4mA) were delivered to LC at 20-100Hz either continuously for 4s or grouped in 100-500ms trains. These stimulation parameters were efficient in eliciting LC burst firing bilaterally. We also collected BOLD responses induced by peripheral sensory stimulation in the same animal and using the same experimental design (6/4/10s). For visual stimulation we used a luminance flicker presented to both eyes at 16Hz and delivered via fiber optic cables. A mild electrical stimulation (1-5mA) of a forepaw was used as somatosensory stimulation. The fMRI images were collected with spatial resolution of 0.4x0.4x1.0mm and temporal resolution of 1s. BOLD maps were generated by using GLM with standard (HRF-convolved boxcar functions) or neural regressors. We observed a remarkable dichotomy between BOLD responses of cortical and subcortical structures. Specifically, LC stimulation produced positive BOLD responses in the majority of structures belonging to metencephalon, mesencephalon and diencephalon, while negative BOLD responses in the entire neocortex. The robust neuronal activation in thalamic projections of LC was further confirmed by electrophysiological recordings. The cortical inhibition as a result of LC stimulation and associated NE release in cortical targets of LC has been reported in earlier studies. The peripheral sensory stimulation evoked both sensory-specific and non-specific activation/deactivation pattern. Strikingly, the regions of non-specific BOLD responses were common for both sensory modalities and largely overlapped with brain regions that showed responses to LC stimulation. We hypothesize that sensory stimulation activates modality-specific sensory pathways along with LC-NE system; and the LC co-activation produces the observed non-specific BOLD responses.}, web_url = {http://www.ewcbr.eu/files/2013/Abstracts/Eschenko.pdf}, event_name = {33rd European Winter Conference on Brain Research and European Brain and Behaviour Society (EWCBR/EBBS 2013)}, event_place = {Brides-les-Bains, France}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ HagbergMPBM2013, title = {Diffusion of conventional and calcium sensitive MRI contrast agents in the rat cerebral cortex}, journal = {Molecular Imaging and Biology}, year = {2012}, month = {11}, volume = {14}, number = {Supplement 2}, pages = {S1544}, abstract = {Calcium sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an in vivo MRI based method capable of determining diffusion properties of conventional and calcium sensitive agents. Simulations and experiment demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value, and for calcium sensitive contrast agents. Sprague-Dawley rats (N=19, 220-300g) were used as approved by the local authorities in compliance with guidelines EUVD 86/609/EEC. Physiological signs were monitored throughout the experiment and remained within physiological limits. Surgery was performed after anesthesia (2.0%isoflurane, Forene, urethane (1.5 g/kg, i.p.) and xylocain (locally)). A burr hole was made above the primary sensory cortex (S1) and a guiding cannula was implanted and fixed prior to positioning in a stereotaxic holder and insertion of a glass capillary (tip: OD: 21-30μm, ID: 6-10μm) in the center of S1. The glass capillary was connected to an injection pump via 6.5m long fused silica tubes and the rat positioned in the center of a 7T Bruker Biospec 70/30 scanner (BGA-9S, Helmholtz RF volume transmission coil, 2cm single loop receiving surface coil). Biodistribution and diffusion of the contrast agents were imaged continuously before, during and after a 1.1±0.3µl slow bolus infusion, with a rate of 32±9nl/min by a T1-weighted RARE sequence (TE/TR 9/290ms) and by quantitative mapping of T1 times by a Look-Locker inversion recovery sequence with a single-shot EPI read out (11.5/8000ms; TI1=35ms, TIdelay=250ms, total of 18 LL images). Data analysis consisted of estimation of the Gadolinium concentration from the images and non-linear fitting of the diffusion equation (Figure). The D* values observed for conventional and responsive contrast agents[1-3] in vivo by MRI were in agreement with model predictions for extra-cellular diffusion and previous findings using other measurement techniques[4], the only exception being Dextran10k (Table 1). This compound has been used both as an extra-cellular tracer for diffusion measurements, and as a neuroanatomical connectivity tracer. The MRI method described is based on long observation times (up to 20h) and assessed both extra-cellular diffusion and intra-cellular transport across extended brain regions of Dextran10k. The apparent diffusion coefficient determined for the calcium sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady-state, hereby enabling quantitative sensing of the local calcium concentration.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs11307-012-0598-3.pdf}, event_name = {Fifth Annual World Molecular Imaging Congress (WMIC 2012)}, event_place = {Dublin, Ireland}, state = {published}, DOI = {10.1007/s11307-012-0598-3}, author = {Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Power A{apower}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Merckle H; Dhingra K{kirti}{Department Physiology of Cognitive Processes}; Kubicek V; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ EschenkoBOL2012, title = {BOLD responses evoked by electrical stimulation of Locus Coeruleus in rats under anesthesia}, year = {2012}, month = {10}, day = {16}, volume = {42}, pages = {674.15}, abstract = {We performed a whole-brain fMRI imaging in the rat under urethane anesthesia and studied BOLD responses induced by electrical stimulation of the brain stem noradrenergic nucleus Locus Coeruleus (LC). The rat was implanted with a MRI-compatible custom-made iridium electrode into LC under electrophysiological guidance. A 7T (300 MHz) magnet with a 30-cm horizontal bore (Bruker BioSpec 70/30, Ettlingen, Germany) equipped with a 20cm inner diameter gradient (Bruker BGA-20S Ettlingen, Germany) was used for MRI scanning. The experimental paradigm consisted of 6s baseline sampling, followed by 4s of unilateral LC stimulation and 10s of post-stimulus sampling. Biphasic square pulses (0.05-0.4mA) were delivered to LC at 20-100Hz either continuously for 4s or grouped in 100-500ms trains. These stimulation parameters were efficient in eliciting LC burst firing bilaterally. We also collected BOLD responses induced by peripheral sensory stimulation in the same animal and using the same experimental design (6/4/10s). For visual stimulation we used a luminance flicker presented to both eyes at 16Hz and delivered via fiber optic cables. A mild electrical stimulation (1-5mA) of a forepaw was used as somatosensory stimulation. The fMRI images were collected with spatial resolution of 0.4x0.4x1.0mm and temporal resolution of 1s. BOLD maps were generated by using GLM with standard (HRF-convolved boxcar functions) or neural regressors. We observed a remarkable dichotomy between BOLD responses of cortical and subcortical structures. Specifically, LC stimulation produced positive BOLD responses in the majority of structures belonging to metencephalon, mesencephalon and diencephalon, while negative BOLD responses in the entire neocortex. The robust neuronal activation in thalamic projections of LC was further confirmed by electrophysiological recordings. The cortical inhibition as a result of LC stimulation and associated NE release in cortical targets of LC has been reported in earlier studies. The peripheral sensory stimulation evoked both sensory-specific and non-specific activation/deactivation pattern. Strikingly, the regions of non-specific BOLD responses were common for both sensory modalities and largely overlapped with brain regions that showed responses to LC stimulation. We hypothesize that sensory stimulation activates modality-specific sensory pathways along with LC-NE system; and the LC co-activation produces the observed non-specific BOLD responses.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=56e5a2a5-ea9a-475f-a0a5-90bc1015fd1b&cKey=24dcc369-8c88-4e2b-9178-d2498997deed&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ HagbergMPBMAL2012, title = {Diffusion in the extra-cellular space of the rat cerebral cortex probed by MRI and direct infusion of contrast agents}, year = {2012}, month = {5}, day = {9}, volume = {20}, pages = {1841}, abstract = {Measurements of the diffusion properties of substances in the cerebral extra-cellular space (ECS) can be used to study drug delivery/clearance and brain tissue structure. Currently used methods have high sensitivity, but are limited to single spatial points or are performed post mortem, or has a limited depth penetration. Here we explore the use of MRI during direct infusion of T1 relaxating agents and mathematical modelling for investigating ECS diffusion.}, web_url = {http://www.ismrm.org/12/tp_11.htm}, event_name = {20th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2012)}, event_place = {Melbourne, Australia}, state = {published}, author = {Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Power A{apower}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Angelovski G{goran}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ NevesEEBL2010, title = {Mapping noradrenergic projections from locus coeruleus using classical fluorescent tracer and MRI-visible contrast agent}, year = {2010}, month = {7}, volume = {7}, number = {087.13}, abstract = {We examined anterograde labeling of noradrenergic terminals originating from the neurons of brain stem neuromodulatory nucleus Locus Coeruleus (LC), a major course of noradrenaline in the rat forebrain, by means of simultaneous iontophoretic injection of paramagnetic (Mn2+) and classical (fluorescent dextran) tracers in the LC. In order to detect Mn2+ transport, MRI scanning was performed in each rat before and 24h after injection and, subsequently, MR images were compared using voxel-based t-test (voxel size: 0.25x0.25x0.25mm). Fluorescent dextran monosynaptic anterograde transport was analysed 5 days after injection. Iontophoretic injection of Mn2+ did not produce neurotoxic effects as there were no signs of neuronal death or glial inflammatory reaction at the injection site 5 days after injection. Both methods revealed reliable labeling in major subcortical terminal fields of LC neurons (Swanson and Hartman, 1975; Ungerstedt, 1971) including central nucleus of amygdala, internal capsule, anterior part of bed nucleus of the stria terminalis, and mesencephalic region. Consistent with previous studies, labeling was predominantly ipsilateral to the injection site. Classical tracer readily detected terminals like fibers of passage typical for noradrenergic innervation of cortical regions. In contrast, manganese-enhanced MRI (MEMRI) method failed to visualize such dispersed noradrenergic innervation in the cortex. On the other hand, MEMRI might be more sensitive for detecting patterns of functional connectivity. Consistent and strong Mn-labeling in hippocampus was observed, which was not proportional to anatomical connectivity labeled by dextran. Thus, the tract-tracing using MEMRI preferentially maps the target sites of rather strong and highly concentrated projections, but not dispersed terminal fields. Despite the relatively low resolution of MEMRI technique compared to florescent microscopy, this novel tract-tracing method can be successfully applied for visualization of major neural pathways and their reorganization in the same animal in longitudinal studies including those concentrating on development, aging, plasticity, or disease-related neurodegeneration.}, web_url = {http://fens2010.neurosciences.asso.fr/}, event_name = {7th Forum of European Neuroscience (FENS 2010)}, event_place = {Amsterdam, Netherlands}, state = {published}, author = {Neves RM{ricardo}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Evrard H{evrard}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ DhingraMESCPBML2009, title = {Development of Bio-responsive Contrast Agents for Magnetic Resonance Imaging: Potential Applications of a Novel Precursor}, journal = {Molecular Imaging and Biology}, year = {2010}, month = {2}, volume = {12}, number = {Supplement 1}, pages = {S44}, abstract = {Magnetic resonance imaging (MRI) is one of the powerful imaging modality. To circumvent its low sensitivity, there has been a substantial interest on the development of the contrast agents. In the present scenario, there is a need to develop contrast agents which are target specific and can report the changes in the physiological environment around them. On the similar lines we are reporting here a novel precursor (tris-tert-Bu-(Z)-Ser-DO3A (Figure 1)). This precursor contains an amine and a carboxylate groups in an orthogonally protected condition, which allows their selective de-protection and coupling to different moieties. Out of the various possibilities, we explored two strategies of coupling that lead to a potential targeted CA and another CA with potential of tracing neuroanatomy in the brain. The special design of these agents not only provides the stability against their enzymatic degradation which is important for their in vivo applicability but also has the possibility to amplify its signal once recognized by the target site. This could be done by exploiting the biotin/strept(avidin) high affinity and the pretargeting strategy, which is well established in nuclear medicine. The CA when bound to avidin showed an enhancement in the relaxivity (r1 and r2) at 1.5T. A substantial increase of ≥1000% in r2 was observed at all magnetic fields studied (1.5T, 3T, 7T, 9.4T) while r1 showed an increase of 260% at 1.5T and an expected decrease with further increase of field strength. The relaxivity changes at 1.5T suggest the structural requirement of a CA to fit in to avidin and optimize the parameters determining relaxivity of the complex matches well with our synthesized agent. Using the same precursor, we have also synthesized a CA which can potentially be used for tracing the neuronal tracks in the brain. Biocytin was used as the basic tracer. Coupling an MR detectable moiety to a well known neuroanatomical tracer would open up new possibilities to noninvasively study the neuronal networks by MRI.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs11307-009-0251-y.pdf}, event_name = {2009 World Molecular Imaging Congress (WMIC)}, event_place = {Montréal, Canada}, state = {published}, DOI = {10.1007/s11307-009-0251-y}, author = {Dhingra K{kirti}{Department Physiology of Cognitive Processes}; Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}; Canals S{canals}{Department Physiology of Cognitive Processes}; Pohmann R{rolf}{Department High-Field Magnetic Resonance}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Maier ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ NevesEEBL2009, title = {Anterograde analysis of noradrenergic projections in the rat forebrain using classical and manganese-enhanced MRI (MEMRI) tract-tracing}, year = {2009}, month = {11}, volume = {10}, number = {10}, pages = {29}, abstract = {We examined anterograde labeling of noradrenergic terminals originating from the neurons of brain stem neuromodulatory nucleus Locus Coeruleus (LC), a major course of noradrenaline in the rat forebrain, by means of simultaneous iontophoretic injection of paramagnetic (Mn2 +) and classical (fluorescent dextran) tracers in the LC. Both MEMRI and fluorescent microscopy revealed anterograde labeling in major terminal fields of LC neurons (Swanson and Hartman, 1975; Ungerstedt, 1971) 24 h and 5 d after injection, respectively. Predominantly ipsilateral labeling of thalamic nuclei, primary sensory cortices, medial prefrontal cortex, and olfactory bulbs reflected previously demonstrated monosynaptic projections of the LC neurons in multiple target brain regions. The labeling patterns of both paramagnetic and classical tracers were strikingly similar. Importantly, iontophoretic injection of Mn2+ did not produce neurotoxic effects as there were no signs of neuronal death or glial inflammatory reaction at the injection site 5 days after injection. The reported results further validate MEMRI tract-tracing technique allowing visualization a highly distributed and distal efferent projections arising from the brain stem nucleus. Thus, MEMRI may be used for mapping convergent target brain regions of different neuromodulatory systems in the same animal and their functional reorganization in longitudinal studies.}, web_url = {http://www.neuroschool-tuebingen-nena.de/}, event_name = {10th Conference of Junior Neuroscientists of Tübingen (NeNa 2009)}, event_place = {Ellwangen, Germany}, state = {published}, author = {Neves RM{ricardo}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Evrard H{evrard}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ 5311, title = {Novel Calcium Sensitive MRI Contrast Agent: A Potential Agent for in vivo testing}, year = {2008}, month = {9}, number = {1502}, abstract = {Ca2+ plays an important dual role as a carrier of electrical current and as a second messenger in the brain. Its effects are much more diverse than of other second messengers such as cAMP (3',5'-cyclic adenosine monophosphate) and DAG (Diacylglycerol) as its actions are mediated by large array of proteins including protein kinases. Optical imaging with the help of fluorescent dyes has revealed the important role played by Ca2+; however it is limited by depth penetration and photobleaching side product. Magnetic Resonance Imaging (MRI), owing to its noninvasive characteristics together with its high spatial and temporal resolution doesn’t possess such limitations. In order to exploit these characteristics of MRI, Li. et al. (JACS comm. 1999) have proposed a smart contrast agent based on the high affinity chelator BAPTA, showing sensitivity to Ca2+ concentration in the range of 0.1 to 10 µM with an apparent dissociation constant of 0.96 µM. Contrast agents with such a strong affinity Ca2+ chelator are likely to be saturated once the Ca2+ concentration exceeds 1µM. We report here the synthesis of a Ca2+ sensitive smart contrast agent based on a low affinity chelator APTRA (o-aminophenol-N,N,O-triacetate). The agent showed 100% relaxivity enhancement in presence of Ca2+. Besides its excellent sensitivity, the agent was found Ca2+ selective in the presence of Mg2+ and Zn2+. Its relaxivity response in physiological media such as artificial cerebro-spinal fluid (ACSF) and artificial extracellular matrix (AECM) was found to be 37 % and 27 % respectively. CSF is the fluid that occupies the subarachnoid space and ventricular system around and inside the brain while ECM materials are mostly present in intercellular spaces between neurons and glia. The observed relaxivity changes in these physiological media prove the prospects of the agent for in vivo tests.}, web_url = {http://www.abstractsonline.com/viewer/viewAbstract.asp?CKey={D8AE58D9-C2EA-4152-BA98-1137F8656F49}&MKey={B47BAE74-CCA9-4C27-80FB-0005AFC9E5C0}&AKey={A4C6DD8F-4BF2-400D-97ED-20C14381CDBB}&SKey={EB48FD2C-03BC-414B-8733-3C12AFA98531}}, event_name = {2008 World Molecular Imaging Congress (WMIC)}, event_place = {Nice, France}, state = {published}, author = {Dhingra K{kirti}{Department Physiology of Cognitive Processes}; Maier ME; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ CanalsBL2008, title = {Functional magnetic resonance imaging (fMRI) of synaptic plasticity}, year = {2008}, month = {7}, volume = {6}, number = {079.4}, abstract = {Repetitive stimulation of hippocampal neurons induce a fast and prolonged increase in local synaptic strength, which is known as LTP (long-term potentiation). LTP is currently considered as being the cellular model of associative learning and memory. Despite the relevance of such phenomenon in the healthy and diseased brain, and all valuable information gained in the study of its cellular and molecular mechanisms, little is known about its role in whole-brain functional connectivity. The lack of a better understanding of the context-dependent network organization most likely reflects the fact that most current methodologies are not really suited for the study of mass action. In an attempt to overcome this limitation, we previously combined electrophysiological techniques and electrical microstimulation of the rat perforant path with functional magnetic resonance imaging (fMRI) (Canals et al. 2008, in press) and showed that the fMRI signal (BOLD) in this model is a good surrogate of the neuronal activity as measured electrophysiologically. Here, we investigate the functional patterns produced as a result of long-term potentiation of synaptic transmission in the rat hippocampus. FMRI maps of the entire brain were obtained before, during and after the induction of LTP, demonstrating changes in functional connectivity due to synaptic potentiation. Furthermore, our results demonstrate that the magnitude of the potentiation is heterogeneously distributed across different hippocampal areas, and that interhemispheric communication is also potentiated after LTP induction. The present model (BOLD-LTP) represents the first demonstration of synaptic plasticity using fMRI and will allow us to further study the information transfer between the hippocampus, the cerebral cortex and subcortical structures, providing new data for the understanding of memory and learning processes.}, web_url = {http://fens2008.neurosciences.asso.fr/}, event_name = {6th Forum of European Neuroscience (FENS 2008)}, event_place = {Geneva, Switzerland}, state = {published}, author = {Canals S{canals}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ 4616, title = {In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing}, year = {2007}, month = {5}, day = {23}, volume = {2007}, pages = {481}, abstract = {One of the main problems in systems biology is to obtain information between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge the applicability of this technique. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. On the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to produce detectable contrast and reliable connectivity maps.Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps.}, web_url = {http://www.ismrm.org/07/}, event_name = {2007 Joint Annual Meeting ISMRM-ESMRMB}, event_place = {Berlin, Germany}, state = {published}, author = {Canals S{canals}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Keller AL{akeller}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ 4302, title = {In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing}, journal = {Neuroforum}, year = {2007}, month = {4}, volume = {13}, number = {Supplement}, pages = {1221}, abstract = {One of the main problems in systems biology is to obtain information on signal processing between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge its applicability. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. In the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to produce detectable contrast and reliable connectivity maps. Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps. The somatosensory cortex of male SD rats was stereotaxically injected with different Mn2+-containing solutions. Total amount of injected Mn2+ ranged between 1 and 16 nmol and the injected volumes between 10 and 80 nL. Osmolarity and pH effects were investigated injecting pH buffered solutions of Mn2+ (pH 7.3 in Tris-HCl buffer vs. 5.5 in H2O) at different concentration (0.05, 0.1 and 0.8 M MnCl2). Same amounts of Mn2+ (8nmol) delivered to the tissue at different infusion rates were also compared. Following the injection, T1-weighted MR imaging (250 mm isotropic resolution) was performed in a 7T scanner at different time points. Fifteen days after the injection animals were sacrificed and brains processed for histology. Nissl staining as well as GFAP and NeuN immunohistochemistry (selective staining for astrocytes and neurons, respectively) were performed in the brain sections to examine cellular toxicity. All injections produced connectivity maps consistent with the known anterograde projections of SI cortex based on classical neuronal tract-tracing techniques. Our results show that pH buffered solution improve the effectiveness of MEMRI, increasing T1 contrast in the projection sites. In addition, injections of pH buffered and isotonic solutions of 50 and 100 mM MnCl2 yielded more extensive connectivity maps, in particular, ipsiand contra-lateral corticocortical connections were evident in all animal injected with those solutions but not with the more usual MEMRI protocol (0.8M MnCl2 in H2O). Hypertonic and non-buffered solutions containing 8nmol Mn2+ resulted in neuronal death and astrogliosis in extensive areas around the injection point. In sharp contrast, no neuronal toxicity was observed with injections containing up to 8nmol of Mn2+ in isotonic solutions of up to 100 mM MnCl2 and pH 7.3. Slow infusion rates demonstrated also to be advantageous and permitted application of larger amounts of Mn2+ without toxic effects, resulting in better T1 contrast in the low density projection fields. Any sign of toxicity was observed in any condition in the projection fields. We conclude that refined protocols for MEMRI improve the quality and extension of connectivity maps and preserves tissue viability, assuring the application of this technique in longitudinal experiments.}, file_url = {/fileadmin/user_upload/files/publications/T38-4C_4302[0].pdf}, web_url = {http://nwg.glia.mdc-berlin.de/media/pdf/conference/Proceedings-Goettingen2007.pdf}, event_name = {7th Meeting of the German Neuroscience Society, 31st Göttingen Neurobiology Conference}, event_place = {Göttingen, Germany}, state = {published}, author = {Canals S{canals}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Keller AL{akeller}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} }