Moderne nicht-invasive Methoden zur Erforschung des menschlichen Gehirns

Moderne nicht-invasive Methoden zur Erforschung des menschlichen Gehirns

Priv.-Doz. Dr. Carsten WoltersPriv.-Doz. Dr. Carsten Wolters

Dr.rer.nat. Harald KugelDr.rer.nat. Harald Kugel

Dr.med. Gabriel MöddelDr.med. Gabriel Möddel

Priv.Doz. Dr. med. Christoph KellinghausPriv.Doz. Dr. med. Christoph Kellinghaus

Priv.-Doz. Dr. Carsten WoltersPriv.-Doz. Dr. Carsten Wolters

Dr.rer.nat. Harald KugelDr.rer.nat. Harald Kugel

Dr.med. Gabriel MöddelDr.med. Gabriel Möddel

Priv.Doz. Dr. med. Christoph KellinghausPriv.Doz. Dr. med. Christoph Kellinghaus

Vorlesung, 15.Oktober 2013Vorlesung, 15.Oktober 2013

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

OutlineOutline

• General planning for this lecture (language? date/time? required knowledge? Participants-Email-List!)

• Literature for this lecture

• Introduction to the lecture (Part 1)

• General planning for this lecture (language? date/time? required knowledge? Participants-Email-List!)

• Literature for this lecture

• Introduction to the lecture (Part 1)

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Aktuelle VorlesungsplanungAktuelle 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)

• 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)

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

OutlineOutline

• Literature for this lecture

• Introduction to the lecture (Part 1)

• Literature for this lecture

• Introduction to the lecture (Part 1)

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Literature for this lectureLiterature for this lecture

• Lecture webside:

http://www.sci.utah.edu/~wolters/LiteraturZurVorlesung/

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

OutlineOutline

• Literature for this lecture

• Introduction to the lecture (Part 1)

• Literature for this lecture

• Introduction to the lecture (Part 1)

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Basics of clinical EEG and MEGBasics of clinical EEG and MEG

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Electro- (EEG) and Magneto-encephalography (MEG)Electro- (EEG) and Magneto-encephalography (MEG)

275 channel axial gradiometer whole-cortex MEG128 channel EEG275 channel axial gradiometer whole-cortex MEG128 channel EEG

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Spatial and temporal resolution of brain imaging methods

Spatial and temporal resolution of brain imaging methods

[Gazzaniga, Ivry & Mangun, Cognitive Neuroscience, 2nd ed., W.W.Norton & Company, 2002]

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

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

• 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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Magnetische Abschirmkammer

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

MEG Interna

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Erfassung des magnetischen Flusses

Magnetometer

Axiales Gradiometer

Planares Gradiometer

Papanicolaou (Ed.): Clinical Magnetoencephalography and Magnetic Source

Imaging

Superconducting quantum interference device

(SQUID)

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

MEG-System am IBB, Uni MünsterMEG-System am IBB, Uni Münster

Finite Elemente Knoten für die MEG Sensor-BeschreibungFinite Elemente Knoten für die MEG Sensor-Beschreibung

[Lanfer, diploma thesis, 2007]

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Epileptic activity as measured with EEG and MEG

Epileptic activity as measured with EEG and MEG

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Source analysis in presurgical epilepsy diagnosisSource analysis in presurgical epilepsy diagnosis

• 0.5%-1% of world population suffers from epilepsy0.5%-1% of world population suffers from epilepsy

• 70-80% of patients successfully treated with drugs70-80% of patients successfully treated with drugs

• For those who are still pharma-resistent after 2-3 drugsFor those who are still pharma-resistent after 2-3 drugs

– Probability of success of a further different drug: 6% Probability of success of a further different drug: 6% (Wiebe et al 2001)(Wiebe et al 2001)

– Probability of success of a surgical treatment: 50% Probability of success of a surgical treatment: 50% (Wiebe et al 2001)(Wiebe et al 2001)

• Indispensable prerequisite for surgery: Focal epilepsy->LocalizationIndispensable prerequisite for surgery: Focal epilepsy->Localization – Gold standard: Video-monitoring and visual inspection of the EEG Gold standard: Video-monitoring and visual inspection of the EEG (Wilson (Wilson

1996)1996)– MRI: Identification of an underlying lesionMRI: Identification of an underlying lesion– PET and Neuropsychology: Localization of a functional deficitPET and Neuropsychology: Localization of a functional deficit– Source analysis ofSource analysis of

• EEG EEG seizure (ictal) activityseizure (ictal) activity (Plummer et al., 2008)(Plummer et al., 2008)• EEG/MEG EEG/MEG interictal activityinterictal activity: “irritative zone” : “irritative zone” (Stefan et. al., 2003)(Stefan et. al., 2003)

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Epileptic spikes in EEG and MEG

Clear spike in EEGNearly no/no signal in MEG

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Epileptic spikes in EEG and MEG

Clear spike in EEGNearly no/no signal in MEG Deep source Strongly radially oriented source

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

• 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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Epileptic spikes in EEG and MEG

Clear signal in MEG, poor signal in EEG

Explanation?

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Sensitivity

• Sensitivity EEG > MEG in deep areas

• But: Sensitivity MEG > EEG in superficial areas

Goldenholz et al., 2009

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Spikes in EEG and MEG

Iwasaki et al., 2005

What should we use? MEG instead of EEG? Only EEG?

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Combined EEG and MEGCombined EEG and MEG

275 channel axial gradiometer whole-cortex MEG128 channel EEG275 channel axial gradiometer whole-cortex MEG128 channel EEG

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Source analysis of interictal spikes in presurgical epilepsy diagnosis

Source analysis of interictal spikes in presurgical epilepsy diagnosis

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Averaged interictal EEG spikesAveraged interictal EEG spikes

Measure EEG and/or MEGMeasure EEG and/or MEG

[Wolters & Kellinghaus, 2006]

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Results of combined EEG/MEG dipole fit Results of combined EEG/MEG dipole fit

Inverse method: Single current dipoleInverse method: Single current dipole

[Wolters & Kellinghaus, 2006]

EEG data and (transparent) cortexEEG data and (transparent) cortex MEG data and (transparent) cortexMEG data and (transparent) cortex

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Results of combined EEG/MEG L1 norm current density reconstruction

Results of combined EEG/MEG L1 norm current density reconstruction

Inverse method: L1 norm current densityInverse method: L1 norm current density

[Wolters & Kellinghaus, 2006]

EEG data and (nontransparent) cortexEEG data and (nontransparent) cortex MEG data and (nontransparent) cortexMEG data and (nontransparent) cortex

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

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

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Typical EEG signalsTypical EEG signals

[Gazzaniga, Ivry & Mangun, Cognitive Neuroscience, 2nd ed., W.W.Norton & Company, 2002]

Delta (0.3-3.5Hz): Traumlose Tiefschlafphase

Gamma(30-70Hz): Starke Konzentr., Lernphase

Alpha (8-13Hz): Entspannte Wachheit

Theta (4-7Hz): Leichte Schlafphasen

Beta (14-30Hz): Hellwach, gute Intelligenzleistung

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

T1 MRI segmentation

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Brain conductivity anisotropy modelingBrain conductivity anisotropy modeling

FA map on T1-MRIFA map on T1-MRIOriginal DTI dataOriginal DTI data FA map after registration

FA map after registration

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]

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Presurgical EEG source analysisPresurgical EEG source analysis

Goal function scan

MNLS

Dipole fit

(Hämäläinen & Ilmoniemi, 1984)(Hämäläinen & Ilmoniemi, 1984)

(Mosher, 1992; Knösche, 1997)(Mosher, 1992; Knösche, 1997)

(Scherg and von Cramon, 1985)(Scherg and von Cramon, 1985)

sLORETA

(Pascual-Marqui, 2002)(Pascual-Marqui, 2002)

Result: Behind the lesion in lateral premotor cortex

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Validation result (localization)

sEEG Dipole fit resultsEEG Dipole fit resultiEEG peaking electrodesiEEG peaking electrodes

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

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)

sEEG dipole fit result: Source orientation away from the lesion towards the epileptogenic tissue (Salayev et al., 2006; Plummer et al., 2008)

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

Carsten Wolters, IBB, WWU MünsterCarsten Wolters, IBB, WWU Münster

Thank you for your attention!Thank you for your attention!