Moderne nicht-invasive Methoden zur Erforschung des menschlichen Gehirns Priv.-Doz. Dr. Carsten...

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!)




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)


• 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)


• 21.Jan.: Mathematik des EEG/MEG inversen Problems, Teil 1 (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)



• 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)





• 4.Feb.: Epilepsiechirurgie, Teil 3 (Möddel)


OutlineOutline






Literature for this lectureLiterature for this lecture

• Lecture webside:

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


OutlineOutline






Basics of clinical EEG and MEGBasics of clinical EEG and MEG


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


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]


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


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


Magnetische Abschirmkammer


MEG Interna


Erfassung des magnetischen Flusses

Magnetometer

Axiales Gradiometer

Planares Gradiometer

Papanicolaou (Ed.): Clinical Magnetoencephalography and Magnetic Source

Imaging

Superconducting quantum interference device

(SQUID)


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]


Epileptic activity as measured with EEG and MEG

Epileptic activity as measured with EEG and MEG


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)


Epileptic spikes in EEG and MEG

Clear spike in EEGNearly no/no signal in MEG



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


• 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



Clear signal in MEG, poor signal in EEG

Explanation?


Sensitivity

• Sensitivity EEG > MEG in deep areas

• But: Sensitivity MEG > EEG in superficial areas

Goldenholz et al., 2009


Spikes in EEG and MEG

Iwasaki et al., 2005

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


Combined EEG and MEGCombined EEG and MEG

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


Source analysis of interictal spikes in presurgical epilepsy diagnosis

Source analysis of interictal spikes in presurgical epilepsy diagnosis


Averaged interictal EEG spikesAveraged interictal EEG spikes

Measure EEG and/or MEGMeasure EEG and/or MEG

[Wolters & Kellinghaus, 2006]


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

Inverse method: Single current dipoleInverse method: Single current dipole


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


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


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


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

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


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


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


T1 MRI segmentation

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


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


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]



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



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


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


Validation result (localization)

sEEG Dipole fit resultsEEG Dipole fit resultiEEG peaking electrodesiEEG peaking electrodes



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)



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

Moderne nicht-invasive Methoden zur Erforschung des menschlichen Gehirns Priv.-Doz. Dr. Carsten...

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