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Dr. Ilgar Mamedov

Address: Spemannstr. 41
72076 Tübingen
Room number: 4.B.10
Phone: +49 7071 601 917
Fax: +49 7071 601 919
E-Mail: ilgar.mamedov

 

Picture of Mamedov, Ilgar, Dr.

Ilgar Mamedov

Position: Research Scientist  Unit: Alumni Logothetis

In complex systems like the brain understanding of connectivity is of paramount importance, as the relationship between parts is often more important than the parts themselves. The aim of my research line is to develop an efficient neuronal tracer that can allow a substantially more specific and comprehensive investigation of the neuronal networks using 1H or 19F MR and Optical imaging techniques. This noninvasive technique is invaluable for longitudinal studies, such as those of plasticity and reorganization, or of neurodegenerative processes. The application of MRI-visible paramagnetic tracers to reveal in vivo connectivity can also provide important subject-specific information for multi-site, multi-electrode intracortical recordings combined with behavioral and physiology experiments widely used in the neuroscience.

Development of multimodal imaging probes for neuroanatomical connectivity and plasticity studies in vivo through of 1H or 19F MR and optical imaging.

Introduction and scientific aims

In complex systems like the brain understanding of connectivity is of paramount importance, as the relationship between parts is often more important than the parts themselves. Traditionally, neuronal activity has been studied at different spatio-temporal scales by using methods like intracortical recordings, optical imaging and high-resolution functional magnetic resonance imaging (fMRI). The former techniques can provide no information on large-scale network interactions. Various methods of MRI, on the other hand, including diffusion tensor imaging, measurements of statistical dependence between regions in the resting-state, and graph-theoretical approaches are immensely useful but they too suffer from lack of specificity.

The aim of this research line is to develop an efficient neuronal tracer that can allow a substantially more specific and comprehensive investigation of the neuronal networks using 1H or 19F MR and Optical imaging techniques. This noninvasive technique is invaluable for longitudinal studies, such as those of plasticity and reorganization, or of neurodegenerative processes. The application of MRI-visible paramagnetic tracers to reveal in vivo connectivity can also provide important subject-specific information for multi-site, multi-electrode intracortical recordings combined with behavioral and physiology experiments widely used in the neuroscience.

Methods

We developed and applied different classes of neuroanatomical tracers which can be visualized by 1H or 19F MRI methods as well as with optical imaging techniques. For the initial studies we conjugated MRI and optical reporters with macromolecules that are extensively applied in neuroanatomical research such as dextran amines or cholera toxin subunit B. We performed in cellulo studies on mouse N18 neuroblastoma cells, which have been incubated with the synthesized tracers under physiological conditions. For our in vivo experiments we directly injected the tracer into the primary motor cortex of the rats (Sprague Dawley). After injection, the animals were scanned at different time points (4d, 6d, 9d and 14d post-injection) to study neuronal transport.

Results and Initial Conclusions

We performed fluorescence microscopy to investigate the cellular uptake and transport properties of the developed tracer. The results demonstrated that our molecules were well internalized well and localized mainly in the cell body of the neuronal cells. Less significant amounts of tracer were also observed also in the neuronal processes and their terminals; they could be the result of the anterograde intracellular transport. On the basis of the cell studies we conclude, that the newly developed tracers were efficiently internalized into neuronal cells.

Our in vivo investigations clearly demonstrated that the internalized molecules reduce T1 relaxation times of the brain tissue in the regions of interest. Voxel-wise statistical analysis revealed signal enhancement in several well-known subcortical targets of the primary motor cortex, including the dorsolateral thalamus area (Po) and caudate putamen (CPu). Moreover in the image one can observe a cluster of significant voxels that, most likely, correspond to the pyramidal tract as the trace clearly originated from the injection site in M1 and follows toward the CPu region.

Preliminary in vivo experiments on the Dextran based paramagnetic tracers demonstrated the high potential of the method. However, in the future, a broad spectrum of existing neuroanatomical tracers will be used depending on the desired application for given project in neuroscience. Further fine-tuning of the target molecule, injection technique and MRI methods will help to improve in vivo visualization of the tracer.

We are aware that sensitivity of the MR method will never approach that of optical imaging, but it will remain one of the few methods able to achieve the whole brain imaging of living subjects. The high impact of MR-active tracers cannot be overestimated. These molecules will facilitate a variety of new experimental studies on different issues associated with longitudinal research on brain plasticity.

In the context of this and other projects in my group I have been having interaction and collaboration with Oxana Eschenko (Neuromodulation), Henry Evrard (Neuroanotomy), Gisela Hagberg (MRI), Joern Engelmann (Cell Biology), Aneta Keliris (Chemistry)  and Anthony Power (Biochemistry).

 

References

[1] Mamedov, I., J. Engelmann, O. Eschenko, M. Beyerlein, N.K. Logothetis 'Dual-functional probes towards in vivo studies of brain connectivity and plasticity, ChemComm., 2012, DOI:10.1039/C1CC15991G.

[2] C.W-H. Wu, O. Vasalatiy, N. Liu, H. Wu, S. Cheal, D.-Y. Chen, A.P. Koretsky, G.L. Griffiths, R.B.H. Tootell, L.G. Ungerleider, Neuron, 2011, 70, 229-243;

 

Figure 1.   Injection of the GdAAZTA-Dextran into the primary motor cortex of the rat. Tracing ability and accumulation in the area of interest (CPu - Caudate putamen, Po- Dorsolateral thalamus).

Figure 1.

Injection of the GdAAZTA-Dextran into the primary motor cortex of the rat. Tracing ability and accumulation in the area of interest (CPu - Caudate putamen, Po- Dorsolateral thalamus).

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Articles (12):

Hagberg G Person, Mamedov I Person, Power A Person, Beyerlein M Person, Merkle H Person, Kiselev VG , Dhingra K Person, Kubìček V , Angelovski G Person and Logothetis NK Person (January-2014) Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex Contrast Media & Molecular Imaging 9(1) 71–82.
Gambino G , Engelmann J Person, Tei L , Botta M , Logothetis NK Person and Mamedov I Person (September-2013) Multimodal contrast agents for in vivo neuroanatomical analysis of monosynaptic connections Biomaterials 34(29) 7135–7142.
Keliris A Person, Mamedov I Person, Hagberg GE Person, Logothetis NK Person, Scheffler K Person and Engelmann J Person (September-2012) A smart 19F and 1H MRI probe with self-immolative linker as a versatile tool for detection of enzymes Contrast Media & Molecular Imaging 7(5) 478–483.
Mamedov I Person, Engelmann J Person, Eschenko O Person, Beyerlein M Person and Logothetis NK Person (February-2012) Dual-functional probes towards in vivo studies of brain connectivity and plasticity Chemical Communications 48(22) 2755-2757.
Henig J , Mamedov I Person, Fousková P , Toth E , Logothetis NK Person, Angelovski G Person and Meyer HA (July-2011) Influence of Calcium-Induced Aggregation on the Sensitivity of Aminobis(methylenephosphonate)-Containing Potential MRI Contrast Agents Inorganic Chemistry 50(14) 6472–6481.
Mamdedov I Person, Logothetis NK Person and Angelovski G Person (July-2011) Structure-related variable responses of calcium sensitive MRI probes Organic & Biomolecular Chemistry 9(16) 5816-5824.
Angelovski G Person and Mamedov I Person (May-2011) Cation-Responsive MRI Contrast Agents Based on Gadolinium(III) Current Inorganic Chemistry 1(1) 76-90.
Mamedov I Person, Canals S Person, Henig J , Beyerlein M Person, Murayama Y Person, Mayer HA , Logothetis NK Person and Angelovski G Person (December-2010) In Vivo Characterization of a Smart MRI Agent That Displays an Inverse Response to Calcium Concentration ACS Chemical Neuroscience 1(12) 819-828.
Mamedov I Person, Parac-Vogt TN , Logothetis NK Person and Angelovski G Person (May-2010) Synthesis and characterization of dinuclear heterometallic lanthanide complexes exhibiting MRI and luminescence response Dalton Transactions 39(24) 5721-5727.
Mamedov I Person, Táborský P , Lubal P , Laurent S , Elst LV , Mayer HA , Logothetis NK Person and Angelovski G Person (August-2009) Relaxometric, Thermodynamic and Kinetic Studies of Lanthanide(III) Complexes of DO3A-Based Propylphosphonates European Journal of Inorganic Chemistry 2009(22) 3298-3306.
Angelovski G Person, Fousková P , Mamedov I Person, Canals S Person, Tóth É and Logothetis NK Person (July-2008) Smart Magnetic Resonance Imaging Agents that Sense Extracellular Calcium Fluctuations ChemBioChem 9(11) 1729-1734.
Mamedov I Person, Mishra A Person, Angelovski G Person, Mayer HA , L-O , Parker D and Logothetis NK Person (December-2007) Synthesis and Characterization of Lanthanide Complexes of DO3A-Alkylphosphonates Dalton Transactions 45 5260-5267.

Posters (17):

Hagberg GE Person, Keliris A Person, Mamedov I Person, Placidi M Person, Merkle H Person, Logothetis NK Person and Scheffler K Person (April-2013): 19F-Lanthanide Complexes: T1 - and T2 - Dependent Signal Gain Using Gradient Echoes, 21st Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2013), Salt Lake City, UT, USA.
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Hagberg GE Person, Mamedov I Person, Power A Person, Beyerlein M Person, Merckle H , Dhingra K Person, Kubicek V and Logothetis NK Person (September-2012): Diffusion of conventional and calcium sensitive MRI contrast agents in the rat cerebral cortex, Fifth Annual World Molecular Imaging Congress (WMIC 2012), Dublin, Ireland.
Keliris A Person, Mamedov I Person, Hagberg GE Person, Logothetis NK Person, Scheffler K Person and Engelmann J Person (September-2012): Dual 1H/19F MR imaging approach for detection of enzyme activity, Fifth Annual World Molecular Imaging Congress (WMIC 2012), Dublin, Ireland.
Hagberg GE Person, Mamedov I Person, Power A Person, Beyerlein M Person, Merkle H Person, Angelovski G Person and Logothetis NK Person (May-9-2012): Diffusion in the extra-cellular space of the rat cerebral cortex probed by MRI and direct infusion of contrast agents, 20th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2012), Melbourne, Australia.
Mamedov I Person, Engelmann J Person, Hagberg G Person, Eschenko O Person and Logothetis NK Person (May-8-2012): Development of multimodal imaging probes for neuroanatomical connectivity studies in vivo by means of MRI, 20th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2012), Melbourne, Australia.
Angelovski G Person, Mamdeov I Person, Engelmann J Person, Gottschalk S Person, Balla DZ Person, Pohmann R Person and Logothetis NK Person (September-2010): The Use of Gadolinium-based Contrast Agents for Molecular and Cellular MRI: Quantitative Considerations, 2010 World Molecular Imaging Congress (WMIC), Kyoto, Japan.
Mamedov I Person, Parac-Vogt T , Logothetis NK Person and Angelovski G Person (September-2010): Title Dinuclear Heterometallic Lanthanide Complexes Exhibiting MRI and Luminescence Response, 2010 World Molecular Imaging Congress (WMIC), Kyoto, Japan.
Angelovski G Person, Chauvin T , Fousková P , Mamedov I Person, Canals S Person, Pohmann R Person, Tóth É and Logothetis NK Person (October-2009): Smart Calcium-sensitive MRI Agents, 442. Wilhelm und Else Heraeus-Seminar "Molecular Imaging", Bad Honnef, Germany.
Mamedov I Person, Henig J , Angelovski G Person, Tóth É , Logothetis NK Person and Mayer HA Person (September-2009): Unusual Calcium Sensitivity of Aminobis(methylenephosphonate)-Containing MRI Contrast Agents, 2009 World Molecular Imaging Congress (WMIC), Montréal, Canada.
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Mamedov I Person, Táborský P , Lubal P , Laurent S , Elst LV , Logothetis N Person and Angelovski G Person (April-2009): Relaxometric, Thermodynamic and Kinetic Studies of Lanthanide(III) Complexes of DO3A-based Propylphosphonates, CMST COST Action D38: Metal-Based Systems for Molecular Imaging Applications, Tübingen, Germany.
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Angelovski G Person, Fousková P , Mamedov I Person, Canals S Person, Tóth É and Logothetis NK Person (September-2008): Smart MRI Agents Sensing Extracellular Calcium Fluctuations, 2008 World Molecular Imaging Congress (WMIC), Nice, France.
Mamedov I Person, Angelovski G Person, Henig J , Mayer HA and Logothetis NK Person (September-2007): Azamacrocyclic Ca2+ Sensitive Contrast Agents for MR Imaging, AMI/SMI Joint Molecular Imaging Conference 2007, Providence, RI, USA.
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Mamedov I Person, Pfeuffer J Person, Logothetis NK Person and Mayer HA (September-2005): Assessment of Bis-macrocyclic Compounds as Calcium-sensitive MR Contrast Agents, 4th Annual Meeting of the Society for Molecular Imaging (SMI 2005), Köln, Germany.
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Mamedov I Person, Pfeuffer J Person, Logotethis NK Person and Mayer HA (September-2005): Azamacrocyclic Ca2+ Sensitive Contrast Agents for MR Imaging, 4th Annual Meeting of the Society for Molecular Imaging (SMI 2005), Köln, Germany.
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Mamedov I Person, Mishra A Person, Pfeuffer J Person and Logothetis NK Person (September-2005): Novel Azamacrocyclic Conjugates in the Development of “Smart” and Targeted Contrast Agents for MR Imaging, 4th Annual Meeting of the Society for Molecular Imaging (SMI 2005), Köln, Germany.
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Mammadova S , Mamedov I Person and Mayer HA (July-2005): Design of multifunctional macrocyclic compounds, XXX. International Symposium on Macrocyclic Chemistry (ISMC 2005), Dresden, Germany.
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Mamedov I Person, Pfeuffer J Person, Logothetis NK Person and Mayer HA (July-2005): Functionalized azamacrocyclic compounds as Ca2+ sensitive contrast agents for MR imaging, XXX. International Symposium on Macrocyclic Chemistry (ISMC 2005), Dresden, Germany.
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Talks (3):

Mamedov I Person, Engelmann J Person, Hagberg GE Person, Logothetis NK Person, Gambino G , Tei L and Botta M (September-7-2012) Abstract Talk: Development of multimodal imaging probes for neuroanatomical connectivity studies in vivo, Fifth Annual World Molecular Imaging Congress (WMIC 2012), Dublin, Ireland(S113).
Mamedov I Person (March-3-2008): Phosphonate-Containing Azamacrocycles in the Development of "Smart" Contrast Agents for MRI, "Frontiers in Medicinal Chemistry" Meeting, Regensburg, Germany.
Mishra A Person, Mamedov I Person, Pfeuffer J Person, Angelovski G Person, Laurent S , van der Elst L , Müller R , Lubal P , Logothetis NK Person and Mayer H (June-2006) Abstract Talk: DO3A-Based mono(alkylphosphonate) complexes as potential pH-sensitive contrast agents for MR Imaging, 10th Bi-Annual Conference of the European Magnetic Resonance Forum (EMRF 2006), Vilnius, Lithuania.

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Last updated: Tuesday, 18.11.2014