Dr.-Ing. Revathi Appali

Junior Research Group Leader and Principal Investigator

SFB 1270/2 ELAINE – Electrically Active Implants

Raum Ex 139

Tel.: +49 (0) 381 498-7071 
Fax: +49 (0) 381 498-7081

E-Mail: revathi.appali(at)uni-rostock.de
Homepage: http://www.revathiappali.sitew.de

Academic Mentor

Prof. Dr. Ursula van Rienen

Research Group Members

Doctoral Researchers Post-doctoral Researchers Student Assistants
M.Sc. Vishnu Prathapan Dr. rer. nat. Jonathan Dawson Saravana Subramani
M.Sc. Jan Philipp Payonk Dr.-Ing. Sriperumbudur, Kiran Kumar  

Co-Supervision

Doctoral Researchers Post-doctoral Researchers  
M.Sc. Lam Vien Che Dr. Anna Karina Fontes Gomes  
Experience

07/2021 to 06/2025, Co-Principal Investigator of Project A02 in SFB 1270/2 ELAINE

Keywords: Multiscale mathematical modeling, Coupled problems, Deep Brain Stimulation, Osseoinduction, Uncertainty Quantification

02/2019 to 06/2025, Junior Research Group Leader in Project A02 of SFB 1270/1 ELAINE

Keywords: Multiscale mathematical modeling, Coupled problems, Deep Brain Stimulation, Osseoinduction, Uncertainty Quantification

11/2014 to 01/2019, Principal Investigator, Deutsche Forschungsgemeinschaft (DFG) - Project number 260482124

Investigation of Electro-mechanical Coupling in Neuronal Membrane - Towards an Electro-mechanical Model of Nerve Pulse Propagation

Keywords: Multiscale mathematical modeling, Coupled problems

04/2013 to 10/2014, Research Associate

Uncertainty quantification in neuron models, DFG proposal preparation,

Co-supervising an external PhD student

03/2009 to 03/2013, Doctoral Researcher in Research Training Group GRK 1505 welisa

Dissertation on Modeling the coupling of action potential and electrodes

Supervisors: Prof. Dr. Ursula van Rienen, Prof. Dr. Jan Gimsa

03/2008 to 11/2008, Master Thesis Student

Development and simulation of four wheel parallel hybrid drive

IAV GmbH, Gifhorn, Germany

Supervisors: Dr. Thomas Boehme, Prof. Dr. Bernhard Lampe

04/2007 to 03/2008, Student Assistant

Data analysis and automation of western blot experiments

Systems Biology Group, University of Rostock

Supervisors: Dr. Katja Rateitschak, Prof. Dr. Olaf Wolkenhauer    

Research Interests
  • Modeling and simulation of biological systems for implant studies and their interactions
    • Deep Brain Stimulation
    • Bone implants
    • Cochlear implants
  • Biological neural network modeling
  • Physiologically relevant uncertainty quantification in electrically active implants
  • Multiphysics modeling of
    • Stem cell differentiation and proliferation in electrical fields
    • Neuronal signal generation and propagation
  • Multiscale modeling of
    • Bone cell differentiation and proliferation in a bioreactor
    • Deep brain stimulation for Parkinson’s disease and Dystonia

Science Story (Neuronales Netzwerk, deutsch)

Research Projects
Ongoing Projects – Principal Investigator

Project A02 in SFB 1270/2 ELAINE – ELectrically Active ImplaNts

Project A02 : Multi-scale models for studies on electrically active implants in due consideration of uncertainties in the input data

DFG GEPRIS Link

Project A02 investigates microscopic and macroscopic simulations in continuous media in context with the therapeutical electrical stimulation of bone, cartilage or deep brain structures.
Essential is the numerical solution of the relevant partial differential equations (Maxwell’s equations, etc.) with the finite element method to determine the desired quantities, particularly the electric field distribution. For the electrical parameters of the biological tissues, primarily parameterized relaxation models are employed. As already started on a pilot basis in the first funding period of the Collaborative Research Centre, values from project A05 can be used in the project. Electrical and electrochemical effects at the electrode-tissue interface, which depend on the selected type of stimulation, are employed through equivalent circuit models. In the first funding period, suitable theoretical and numerical models were selected. They will be further extended or refined. Results from simulations on a smaller scale are incorporated via homogenization approaches, equivalent circuit models or parameter extraction. Besides extending the multiscale and multiphysical models, establishing stochastic and inverse methods for determining patient-specific optimized recommendations for stimulation parameters presents another focus for the second funding period. To this end, an open-source,  multipurpose simulation platform based on the tissue-specific solutions established in the first funding period will be created. The clinical researchers in the consortium will test the simulation platform utilizing easy-to-use graphical user interfaces.

Project duration: 01.07.2021 to 30.06.2025

Principal Investigators: Prof. Dr. Ursula van Rienen, Dr.-Ing. Revathi Appali

Team involved: M.Sc. Jan Philipp Payonk, M.Sc. Lam Vien Che,  Dr. Anna Karina Fontes Gomes

Ongoing Projects – Contributing researcher with supervision tasks

Project S01 in TRR 295 ReTune: Treatment of motor network disorders using neuromodulation

DFG GEPRIS Link

Deep Brain Stimulation (DBS) is a well-accepted treatment option for movement disorders such as Parkinson’s disease. Since DBS target structures are small, exact positioning of surgically-implanted electrodes is crucial to yield optimal outcomes. However, the most effective target position for DBS electrodes is still under debate. To study the relationship between clinical outcomes and electrode placement across patients, the field of DBS imaging evolved. This service project will be based on a widely-used software tool called Lead-DBS, which enables precise localization of DBS electrodes and modelling of their therapeutic effects. Our two primary goals are first, to perform electrode localizations for other projects within the TRR and second to further enhance Leas-DBS and our methodology in DBS modelling. This will involve two research projects, namely (i) a pipeline for multimodal imaging and precise subcortical segmentation of target structures, and (ii) advanced modelling of electric fields and the neural activation around the electrode to study the impact of DBS on surrounding tissue. These efforts will significantly improve imaging methodology for DBS and offer a support structure to answer the central research questions of the TRR 295.

Project duration: 01.07.2020 to 30.06.2024

Principal Investigators: Prof. Dr. Ursula van Rienen, Dr. med. Anna Tietze, Prof. Dr. med. Andreas Horn

Team involved: M.Sc. Arash Golmohammadi, Dr.-Ing. Revathi Appali

Investigating the synergistic effects of spatially resolved biochemical, physicochemical, and physical key stimuli to generate biomimetic niches in perfusion bioreactor and their proficiency to derive large bone-like constructs.

DFG GEPRIS Link

Bioreactors are used increasingly in bone tissue engineering approaches, but the existing homogenous niche applied is generally insufficient to achieve/support formation of bone-like constructs. In physiology, multiple osteochondral cells are present in high cell density and their dynamic interactions are critical for bone development and regeneration processes. This is also complemented with supporting parameters such as oxygen tension (pO2) distribution, biochemical stimuli, and physical/mechanical stimuli to establish the dynamic niches essential for the growth of naïve organs (i.e. cartilage and bone) and attaining their functionalities. In this proposal, we aim to investigate the synergistic potentials of 5 distinct parameters to recapitulate bone developmental processes in a perfusion bioreactor. Through the established dynamic biomimetic niches, the effects on construct development and capability to achieve bone-like tissues in vitro will be assessed. These parameters include 1) medium pH; 2) pO2; 3) Young´s modulus of 3D-printed scaffolds; 4) multi-step osteochondral differentiation regimes and 5) Transformer-like induced electric field (TLC-EF) stimulation to emulate piezoelectric stimuli during movement. Human bone marrow-derived mesenchymal stem cells (hMSC) and human induced pluripotent stem cells (hiPSC) will be used to define the proficiency of biomimetic niches. Their potential to derive different osteochondral cell-types in the biomimetic niches will be critically assessed. Specifically for TLC-EF stimulations, multiscale modelling/simulations that describe EF/Bone construct interactions and the effects on osteogenesis will be combined with experimental validations. This is done with the aim to define an effective range of EF parameters for bone tissue engineering applications. Ultimately, this study will result in a specific set of conditions/stimuli that can recapitulate physiological-like niches in vitro. The approaches applied will also introduce a novel concept to the field of tissue engineering and can be further exploited to derive bone-like constructs with near-physiological properties in a bioreactor.

Project duration: 3 Years (from 07/2021)

Principal Investigators: Prof. Dr. Ursula van Rienen, Dr.-Ing. Poh Soo Lee, Dr.-Ing. Benjamin Kruppke

Team involved: Post-doctoral researcher (Uni Rostock), Dr.-Ing. Revathi Appali

TU Dresden: Dr.-Ing. Poh Soo Lee (Eigene Stelle), PhD Student: Dipl.-Ing. Franziska Alt – supervised by Dr.-Ing. Benjamin Kruppke

Ongoing Project: State Graduate Funded Doctoral Project

Predicting Spreading of Multiple Sclerosis Demyelination Through a Trans-synaptic Modeling Approach

This project aims at understanding the effects of demyelination and remyelination in Multiple Sclerosis through a trans-synaptic modelling approach. We use neuroVIISAS (https://neuroviisas.med.uni-rostock.de/neuroviisas.shtml) developed by Prof. Dr. Oliver Schmitt to carry out this study. neuroVIISAS (neuro Visualization, Imagemapping, Information System for Analysis and Simulation) is an open framework for integrative data analysis, visualization and population simulations.

Project duration: 2019 – 2021

Supervisors: Prof. Dr. Ursula van Rienen, Prof. Dr. Oliver Schmitt, Dr.-Ing. Revathi Appali

State Graduate Fund Holder: M.Sc. Vishnu Prathapan

Ongoing Research Interest – Contributing Researcher

Modeling the effects of morphological and physiological parameters on the electrical stimulation of the auditory nerve by cochlear implants

Sensorineural deafness is caused by the loss of peripheral neural input to the auditory nerve, resulting from peripheral neural degeneration and/or a loss of inner hair cells. Provided spiral ganglion cells and their central processes are patent, cochlear implants can be used to electrically stimulate the auditory nerve to facilitate hearing in the deaf or severely hard-of-hearing. Neural degeneration is a crucial impediment to the operational success of a cochlear implant. The present, first-of-its-kind two-dimensional finite-element model investigates how the depletion of neural tissues might alter the electrically induced transmembrane potential of spiral ganglion neurons. The study suggests that even as little as 10% of neural tissue degeneration could lead to a disproportionate change in the stimulation profile of the auditory nerve. This result implies that apart from encapsulation layer formation around the cochlear implant electrode, tissue degeneration could also be an essential reason for the apparent inconsistencies in the functionality of cochlear implants.

Team Lead: Prof. Dr. Ursula van Rienen

Team involved: Dr.-Ing. Kiran Sriperumbudur, Dr.-Ing. Revathi Appali

Effect of Electric Field on Stem cells and Bone cells

This project aims at studying the effect of electric field stimulation on human stem cells and bone cells. We use data driven mathematical modelling as a tool to understand the underlying phenomena.

 

Team lead: Dr.-Ing. Revathi Appali, Prof. Dr. Ursula van Rienen

Team involved: Dr. rer. nat. Jonathan Dawson, Dr.-Ing. Revathi Appali

Uncertainty Quantification in Deep Brain Stimulation and Osseoinduction

We are developing physiologically based uncertainty quantification regarding main model parameters. The aim is to optimize the functionality of deep brain stimulation and osseoinduction.

Team Lead: Dr.-Ing. Revathi Appali, Prof. Dr. Ursula van Rienen

Team involved: Dr.-Ing. Kiran Sriperumbudur, Dr.-Ing. Revathi Appali

Completed Projects – Principal Investigator
Finished Research Interest – Contributing Researcher

Study of Electrical Action Potential in Neurons

This project aims to address different factors that influence the action potential in neurons and its activation in any electrically active implants. We focus on the morphology of neurons and the density of neurons in the region of interest as significant factors involved in the optimized stimulation of neurons. 

Team Lead: Prof. Dr. Ursula van Rienen, Prof. Dr. Christiane Thielemann

Team involved: Dr.-Ing. Robert Bestel, Dr.-Ing. Revathi Appali

Teaching Activities
Publications

JOURNAL PAPERS

• J. E. Dawson, T. Sellmann, K. Porath, R. Bader, U. van Rienen, R. Appali, R. Köhling, Cell-cell interactions and fluctuations in the direction of motility promote directed migration of osteoblasts in direct current electrotaxis, Frontiers in Bioengineering and Biotechnology:10, 2022, doi:10.3389/fbioe.2022.995326  ISSN:2296-4185. https://www.frontiersin.org/articles/10.3389/fbioe.2022.995326 

• P. S. Lee, C. Heinemann, K. Zheng, R. Appali, F. Alt, J. Krieghoff, A. Bernhardt, A. R. Boccaccini, U. van Rienen, V. Hintze, The interplay of collagen/bioactive glass nanoparticle coatings and electrical stimulation regimes distinctly enhanced osteogenic differentiation of human mesenchymal stem cells, Acta Biomaterialia, Volume 149, 2022, Pages 373-386, ISSN 1742-7061, https://doi.org/10.1016/j.actbio.2022.06.045.

• R. Bestel, U. van Rienen, C. Thielemann and R. Appali. Influence of Neuronal Morphology on the Shape of Extracellular Recordings With Microelectrode Arrays: A Finite Element Analysis. IEEE Transactions on Biomedical Engineering, vol. 68, no. 4, pp. 1317-1329, April 2021.  doi: 10.1109/TBME.2020.3026635

• K. K. Sriperumbudur, R. Appali, A. W. Gummer, U. van Rienen. Neural Tissue Degeneration in Rosenthal’s Canal and Its Impact on Electrical Stimulation of the Auditory Nerve by Cochlear Implants: An Image-Based Modeling Study. Int. J. Mol. Sci. 2020, 21, 8511. https://doi.org/10.3390/ijms21228511

• J.E. Dawson, P. S. Lee, U. van Rienen and R. Appali. A general theoretical framework to study the influence of electric fields on mesenchymal stem cells. Frontiers in Bioengineering and Biotechnology, 2020, 8, 1144. https://doi.org/10.3389/fbioe.2020.557447

• R. Bestel, R. Appali, U. van Rienen and C. Thielemann. Effect of Morphologic Features of Neurons on the Extracellular Electric Potential a Simulation Study Using Cable Theory and Electro-Quasistatic Equations", Neural Computation 29:11, pp. 2955-2978, 2017. DOI: 10.1162/neco_a_01019.

• Lautrup, B. et al., 2011. The stability of solitons in biomembranes and nerves. The European physical journal. E, Soft matter, 34(6), pp.1–9. https://doi.org/10.1140/epje/i2011-11057-0

• Appali, R., Petersen, S. & Van Rienen, U., 2010. A comparision of Hodgkin-Huxley and soliton neural theories. Advances in Radio Science, 8, pp.75–79. https://doi.org/10.5194/ars-8-75-2010 

BOOK CHAPTERS

• Appali, R. et al., 2012. Soliton Collision in Biomembranes and Nerves – A Stability Study. In B. Michielsen & J. R. Poirier, eds. Scientific Computing in Electrical Engineering, Mathematics in Industry. Springer, pp. 205–212. https://doi.org/10.1007/978-3-642-22453-9_22 

• Appali, R., van Rienen, U. & Heimburg, T., 2012. A Comparison of the Hodgkin-Huxley Model and the Soliton Theory for the Action Potential in Nerves. Advances in Planar Lipid Bilayers and Liposomes, 16, pp.275–299. https://doi.org/10.1016/B978-0-12-396534-9.00009-X

TECHNICAL REPORTS

• Tavangarian, D. et al., 2014. Communication Systems in Aircraft with IEEE 802.11ac - EMF Effects of IEEE 802.11ac for In-Flight Communication Systems D. Tavangarian, ed., University of Rostock. ISBN: 978-3-86009-437-2

CONFERENCE PAPERS (PEER-REVIEWED)

• R. Appali, K. K. Sriperumbudur and U. van Rienen. Extracellular Stimulation of Neural Tissues: Activating Function and Sub-threshold Potential Perspective, 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Berlin, Germany, 2019, pp. 6273-6277. doi: 10.1109/EMBC.2019.8857113

• R. Appali, K. K. Sriperumbudur and U. van Rienen. Challenges in modeling nerve-electrode interactions of neuronal implants. 2016 URSI International Symposium on Electromagnetic Theory (EMTS), Espoo, 2016, pp. 534-537. https://doi.org/10.1109/URSI-EMTS.2016.7571447 

• R. Appali, K. K. Sriperumbudur and U. van Rienen. 3D Axonal Networks Coupled to Microelectrode Arrays: A Simulation Model to Study Neuronal Dynamics. 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Milan, 2015, pp. 4700-4704. https://doi.org/10.1109/EMBC.2015.7319443 

• R. Appali, C. Schmidt, and U. van Rienen. Some Uncertainty Aspects in Models for Neural Engineering. In IEEE International Conference on Electromagnetics in Advanced Applications (ICEAA), 2013,
pp. 289-292. https://doi.org/10.1109/ICEAA.2013.6632239 

• R. Appali et al.. Thermodynamic Theory of Nerve Signal Propagation and First Simulation of Soliton Model. In Biomedical Engineering BMT. 2010, pp. 186-189. https://doi.org/10.1515/bmt.2010.712

• U. van Rienen et al.. Analysis and simulation of electrical interactions of implants with biosystems. In Biomedical Engineering BMT. 2010, pp. 167-170. https://doi.org/10.1515/bmt.2010.712

• R. Appali et al.. 3D-Simulation of Action Potential Propagation in a Squid Giant Axon. In COMSOL Conference, Bangalore, India, 2010, pp. 1-6. https://www.comsol.de/paper/

ABSTRACTS

• R. Appali. Comparison of FitzHugh-Nagumo Model and Heimburg-Jackson Models for Nerve Pulse Propagation. In ELAINE 2020 conference, Rostock, Germany, September 29-30, 2020. https://doi.org/10.18453/rosdok_id00002752

• J. Dawson, U. van Rienen, R. Appali. Theoretical framework to study the influence of electric field on the mesenchymal osteogenic differentiation and osteoblast migration. In ELAINE 2020 conference, Rostock, Germany, September 29-30, 2020. https://doi.org/10.18453/rosdok_id00002752

• P.S. Lee, A. R. Boccaccini, R. Appali, U. van Rienen, V. Hintze. Investigating the potential of electric field stimulations and bio-active glass nanoparticles to enhance osteogenic differentiation of human mesenchymal stem cells. In ELAINE 2020 conference, Rostock, Germany, September 29-30, 2020. https://doi.org/10.18453/rosdok_id00002752

• V. Prathapan, P. Eipert, R. Appali, U. van Rienen, O. Schmitt. Modeling and simulation of neural signal activity in a connectome for the study on Multiple Sclerosis. In ELAINE 2020 conference, Rostock, Germany, September 29-30, 2020. https://doi.org/10.18453/rosdok_id00002752

• K.K. Sriperumbudur, R. Appali, R. Bader,U. van Rienen. Modeling Anisotropic Electric Conductivity of Porous Bone Using Image-Based methods. In ELAINE 2020 conference, Rostock, Germany, September 29-30, 2020. https://doi.org/10.18453/rosdok_id00002752

• J. Dawson, U. van Rienen and R. Appali: A theoretical framework to describe influence of electric field on Mesenchymal cell differentiation, Focus session: Physics of Stem Cells, DPG Spring Meeting, Dresden,March 2020 (cancelled due to corona).

• R. Appali, U. van Rienen. Modeling and simulation of nerve-electrode interactions in neuronal implants In: International Multigrid Conference-Bio-Math-Symposium, December 5-9, 2016.

• R. Appali, U. van Rienen: Towards a Multiphysical Model for Signaling in Nerves and Biomembranes. 8th International Conference on Porous Media and Annual Meeting (Interpore 2016), Cincinnati, OH, USA, May 9-12, 2016.

• R. Appali, T. Heimburg, S. Petersen, J. Gimsa, U. van Rienen. Collision of Nerve Pulses in the nerve Fibre. 22nd Workshop on “Advances in Electromagnetic Research”, Aug. 8-13, 2010, p.25.

• R. Appali, S. Petersen, J. Gimsa, U. van Rienen. Modelling the Neuronal Signals Recorded by Electrons – First Impressions. 21st Workshop on “Advances in Electromagnetic Research”, Aug. 22-28, 2009, p34.

• R. Appali, S. Petersen, U. van Rienen. A comparison of Hodgkin-Huxley and Soliton Neural Theories. U.R.S.I. Landesausschuss in der Bundesrepublik Deutschland e.V. Kleinheubacher Tagung, Miltenberg, 2009.

FURTHER PUBLICATIONS

• R. Appali, "Start zu interdisziplinärem Forschungsprojekt zu künstlichen Knochen – Rostocker Elektrotechnik und TU Dresden kooperieren". Press release of the University of Rostock, August 2021. https://www.elektrotechnik.uni-rostock.de/presse/

• R. Appali, "Inderin als Spitzen-Forscherin an Universität Rostock". Press release of the University of Rostock, June 2021. https://www.elektrotechnik.uni-rostock.de/presse/

• Appali, R. et al., 2012. Implantate zur Stimulation des Hörnervs und des tiefen Hirns. Traditio et Innovatio, Forschungsmagazin der Universität Rostock, ISSN 1432-1513 (Heft 2), pp.19-25.

• Appali, R., 2011. Zwischen Rostock und Kopenhagen. Profile – Das Magazin der Universität Rostock, ISSN: 1866-1440, pp. 50-51.

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