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Moderne nicht-invasive Methoden zur Erforschung des menschlichen Gehirns

Moderne nicht-invasive Methoden zur Erforschung des menschlichen Gehirns. Priv.-Doz. Dr. Carsten Wolters Dr.rer.nat. Harald Kugel Dr.med. Gabriel Möddel Priv.Doz. Dr. med. Christoph Kellinghaus. Vorlesung, 15.Oktober 2013. Outline.

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Moderne nicht-invasive Methoden zur Erforschung des menschlichen Gehirns

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  1. Moderne nicht-invasive Methoden zur Erforschung des menschlichen Gehirns Priv.-Doz. Dr. Carsten Wolters Dr.rer.nat. Harald Kugel Dr.med. Gabriel Möddel Priv.Doz. Dr. med. Christoph Kellinghaus Vorlesung, 15.Oktober 2013

  2. Outline • General planning for this lecture (language? date/time? required knowledge? Participants-Email-List!) • Literature for this lecture • Introduction to the lecture (Part 1)

  3. Aktuelle Vorlesungsplanung • 15.Oktober: Vorbesprechung und Motivation (Wolters) • 22.Oktober: Einführung Magnetresonanztomographie (MRT) (Kugel) • 29.Oktober: Medizinische Grundlagen zur Elektro- (EEG) und Magnetoencephalography (MEG) (Wolters) • 5.Nov.: Mathematisch-physikalische Modellierungsgrundlagen zu EEG und MEG, Teil 1 (Wolters) • 12.Nov.: Mathematisch-physikalische Modellierungsgrundlagen zu EEG und MEG, Teil 2 (Wolters) • 19.Nov.: Grundlagen von Epilepsie und EEG (Kellinghaus) • 26.Nov.: Epileptische Anfälle und ihre Behandlung (Kellinghaus) • 3.Dez.: Registrierung von MRT: Teil 1 (Wolters) • 10.Dez3.: Registrierung von MRT: Teil 2 (Wolters) • 17.Dez.: Segmentierung von MRT (Wolters) • 7.Jan.: Mathematik des EEG/MEG Vorwärtsproblems, Teil 1 (Wolters) • 14.Jan.: Mathematik des EEG/MEG Vorwärtsproblems, Teil 2 (Wolters) • 21.Jan.: Mathematik des EEG/MEG inversen Problems, Teil 1 (Wolters) • 28.Jan.: Mathematik des EEG/MEG inversen Problems, Teil 2 (Wolters) • 4.Feb.: Epilepsiechirurgie, Teil 3 (Möddel)

  4. Outline • Literature for this lecture • Introduction to the lecture (Part 1)

  5. Literature for this lecture • Lecture webside: http://www.sci.utah.edu/~wolters/LiteraturZurVorlesung/

  6. Outline • Literature for this lecture • Introduction to the lecture (Part 1)

  7. Basics of clinical EEG and MEG

  8. Electro- (EEG) and Magneto-encephalography (MEG) 275 channel axial gradiometer whole-cortex MEG 128 channel EEG

  9. Spatial and temporal resolution of brain imaging methods [Gazzaniga, Ivry & Mangun, Cognitive Neuroscience, 2nd ed., W.W.Norton & Company, 2002]

  10. Grundlagen klinischer EEG und MEG Anwendungen => Warum also MEG? • EEG ist Standard in der klinischen Praxis • MEG ist kostenintensiv (Gerätekosten, Wartung, Heliumkühlung…) • Datenauswertung ist komplex (wie auch für EEG, fMRT, …) • In Deutschland bisher keine Vergütung durch die Krankenkassen

  11. Grundlagen - MEG MEG registriert nicht-invasiv magnetische Felder neuronaler Aktivität Ähnlich dem EEG: Ableitung neuronaler Aktivität MEG und EEG messen Aktivität derselben Generatoren PET oder fMRT: Indirekte Erfassung neuronaler Aktivität 4D Neuroimaging, San Diego, CA, USA

  12. Magnetische Abschirmkammer

  13. MEG Interna

  14. Erfassung des magnetischen Flusses Magnetometer Superconducting quantum interference device (SQUID) Axiales Gradiometer Planares Gradiometer Papanicolaou (Ed.): Clinical Magnetoencephalography and Magnetic Source Imaging

  15. [Lanfer, diploma thesis, 2007] MEG-System am IBB, Uni Münster Finite Elemente Knoten für die MEG Sensor-Beschreibung

  16. Epileptic activity as measured with EEG and MEG

  17. Source analysis in presurgical epilepsy diagnosis • 0.5%-1% of world population suffers from epilepsy • 70-80% of patients successfully treated with drugs • For those who are still pharma-resistent after 2-3 drugs • Probability of success of a further different drug: 6% (Wiebe et al 2001) • Probability of success of a surgical treatment: 50% (Wiebe et al 2001) • Indispensable prerequisite for surgery: Focal epilepsy->Localization • Gold standard: Video-monitoring and visual inspection of the EEG (Wilson 1996) • MRI: Identification of an underlying lesion • PET and Neuropsychology: Localization of a functional deficit • Source analysis of • EEG seizure (ictal) activity(Plummer et al., 2008) • EEG/MEG interictal activity: “irritative zone” (Stefan et. al., 2003)

  18. Epileptic spikes in EEG and MEG Clear spike in EEG Nearly no/no signal in MEG

  19. Epileptic spikes in EEG and MEG • Clear spike in EEG • Nearly no/no signal in MEG • Deep source • Strongly radially oriented source

  20. MEG registers mainly tangential source components: Sulci-walls: tangential pyramidal cells -> High amplitudes „Diagonal“ orientation-> Medium amplitude Radial sources hardly produce an MEG: Depth and crown of sulci: radial pyramidal cells -> Low contribution Sensitivity for radial and tangential sources

  21. Epileptic spikes in EEG and MEG Clear signal in MEG, poor signal in EEG Explanation?

  22. Sensitivity Sensitivity EEG > MEG in deep areas But: Sensitivity MEG > EEG in superficial areas Goldenholz et al., 2009

  23. Spikes in EEG and MEG What should we use? MEG instead of EEG? Only EEG? Iwasaki et al., 2005

  24. Combined EEG and MEG 275 channel axial gradiometer whole-cortex MEG 128 channel EEG

  25. Source analysis of interictal spikes in presurgical epilepsy diagnosis

  26. Averaged interictal EEG spikes [Wolters & Kellinghaus, 2006] Measure EEG and/or MEG

  27. Results of combined EEG/MEG dipole fit [Wolters & Kellinghaus, 2006] EEG data and (transparent) cortex MEG data and (transparent) cortex Inverse method: Single current dipole

  28. Results of combined EEG/MEG L1 norm current density reconstruction [Wolters & Kellinghaus, 2006] EEG data and (nontransparent) cortex MEG data and (nontransparent) cortex Inverse method: L1 norm current density

  29. Source analysis of seizure (ictal) spikes in presurgical epilepsy diagnosis

  30. [Gazzaniga, Ivry & Mangun, Cognitive Neuroscience, 2nd ed., W.W.Norton & Company, 2002] Typical EEG signals Gamma(30-70Hz): Starke Konzentr., Lernphase Beta (14-30Hz): Hellwach, gute Intelligenzleistung Alpha (8-13Hz): Entspannte Wachheit Theta (4-7Hz): Leichte Schlafphasen Delta (0.3-3.5Hz): Traumlose Tiefschlafphase

  31. EEG Preprocessing [Rullmann, Anwander, Dannhauer, Warfield, Duffy & Wolters, NeuroImage, 44(2), 2009]

  32. [Rullmann, Anwander, Dannhauer, Warfield, Duffy & Wolters, NeuroImage, 44(2), 2009] T1 MRI segmentation

  33. [Rullmann, Anwander, Dannhauer, Warfield, Duffy & Wolters, NeuroImage, 44(2), 2009] FE mesh generation

  34. Brain conductivity anisotropy modeling [Rullmann, Anwander, Dannhauer, Warfield, Duffy & Wolters, NeuroImage, 44(2), 2009] FA map after registration Original DTI data FA map on T1-MRI Effective medium approach model (DTI <-> CTI): Model DTI<->Conductivity Tensor Image (CTI)[Tuch et al., Ann. NYAS, 1999] Linear model DTI<->CTI [Tuch et al., PNAS, 2001] Validation of DTI<->CTI model in silk yarn phantom[Oh et al., ISMRM, 2006]

  35. Presurgical EEG source analysis [Rullmann, Anwander, Dannhauer, Warfield, Duffy & Wolters, NeuroImage, 44(2), 2009] Goal function scan (Mosher, 1992; Knösche, 1997) MNLS (Hämäläinen & Ilmoniemi, 1984) sLORETA (Pascual-Marqui, 2002) Dipole fit (Scherg and von Cramon, 1985) Result: Behind the lesion in lateral premotor cortex

  36. [Rullmann, Anwander, Dannhauer, Warfield, Duffy & Wolters, NeuroImage, 44(2), 2009] Validation: Intracranial EEG (iEEG)

  37. [Rullmann, Anwander, Dannhauer, Warfield, Duffy & Wolters, NeuroImage, 44(2), 2009] CT and iEEG electrode positions

  38. [Rullmann, Anwander, Dannhauer, Warfield, Duffy & Wolters, NeuroImage, 44(2), 2009] Validation result (localization) iEEG peaking electrodes sEEG Dipole fit result

  39. [Rullmann, Anwander, Dannhauer, Warfield, Duffy & Wolters, NeuroImage, 44(2), 2009] Validation result (orientation) sEEG dipole fit result: Source orientation away from the lesion towards the epileptogenic tissue (Salayev et al., 2006; Plummer et al., 2008)

  40. Thank you for your attention!

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