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Title: MEG Imaging Applications Practical Introduction To Brain Imaging In The Fourth Dimension


1
MEG Imaging ApplicationsPractical Introduction
To Brain Imaging In The Fourth Dimension
UPMC
CABMSI Center for Advanced Brain Magnetic Source
Imaging
Anto Bagic, MD, MSc Assistant Professor (Neurology
Neurosurgery) Director, CABMSI (Center for
Advanced Brain Magnetic Source Imaging) Director,
EMU (Epilepsy Monitoring Unit)
2
Team Work(s)!!!
3
Special Thanks
  • All currently active MEG groups
  • Anna Haridis, MEG Coordinator
  • UPMC Administration
  • Elekta (Helsinki, Finland)
  • Michael Funke, MD, PhD (UU, SLC)
  • Steven Stufflebeam, MD (HU/MGH, Boston)
  • Wenyan Jia , Ph.D., Biophysics, U Pitt

4
Outline
  • What is MEG what it records?
  • Some logistical technical aspects of MEG
  • Briefly about clinical applications of MEG
  • A few examples of research applications
  • Center for Advanced Brain Magnetic Source
  • Imaging (CABMSI)
  • Conclusions

5
What is MEG what it records?
6
MEG
  • MEG is the most modern and powerful technique for
    studying brain function non-invasively
  • Based on the recording of magnetic fields induced
    by synchronized neuronal activity as reflected
    outside of the skull
  • MEG can attain a temporal resolution of a few
    milliseconds.
  • MEG can monitor the activation of a neuronal
    population with a spatial resolution of several
    millimeters

(Cohen, 1972 Hamalainen et al., 1993 George et
al., 1995 Vrba Robinson, 2001 Pataraia et
al.,2002).
7
IEEG Invasive Electroencephalography, MEG
Magnetoencephalography, MRS Magnetic Resonance
Spectroscopy, fMRI functional MRI, SPECT
Single Photon Emission Cranial Tomography, PET
Positron Emission Tomography,
8
Sources of Magnetic Fields
9
Sources of Magnetic Signals
http//hyperphysics.phy-astr.gsu.edu/HBASE/magneti
c/magfie.htmlc1
10
The Right Hand Rule
http//www.physics.sjsu.edu/facstaff/becker/physic
s51/mag_field.htm
11
Electromagnetism
Electric current always generates a magnetic field
H.C. Ørsted, 1820
12
Origin of the Magnetic Field
Courtesy of Elekta, Modified by AB
13
MEG Generators
104-5 activated cells
(http//www.ctf.com/Pages/page33.html)
14
Parallel dendrites
Pyramidal cells parallel orientation gt spatial
summation
15
Neural currents Nomenclature
  • Impressed currents Ji(r)
  • due to electrochemical gradients and open ion
    channels across the cell membrane
  • Primary currents Jp(r)
  • due to impressed currents
  • currents inside dendrites and axons
  • decay with distance from the synapse leaky cell
    membrane and resistive conductor
  • Volume currents Jv(r)
  • due to primary currents
  • passive, ohmic current flow

16
Currents in axons and dendrites
Pre-synaptic
Post-synaptic
  • Postsynaptic currents
  • Slow temporal summation
  • Dipolar currents
  • The main surce of MEG EEG!
  • Action potentials
  • Fast no/little temporal summation
  • Cancellation fields diminish rapidly

Courtesy of Elekta, Modified by AB
17
Neural currents and fields
  • All currents generate magnetic field!
  • Skull is a poor conductor gt it distorts and
    blurs electric signals but not magnetic!
  • The primary currents are directly related to the
    neural activation, thus, we may estimate them
    based on the measured MEG/EEG signals.

18
MEG signal strength
Q I d
  • Amount and type of synaptic input
  • excitatory or inhibitory
  • synapses at apical dendrites or close to cell
    body
  • Degree of synchronization
  • Within a cortical patch, 1 of neurons
    signalling synchronously with a stimulus produce
    gt 80 of the signal.

19
MEG signal strength
  • Depth
  • more attenuation the deeper the primary current
  • no magnetic signal from the center of a
    conducting sphere
  • Cancellation
  • close-by areas with simultaneous, opposing
    current flow decrease the signal

20
What can we then see with MEG?
  • Almost all of the cortex, fissural activity
    emphasized

Hillebrand Barnes, NeuroImage 2002
21
MEG Signal generation - Summary
  • MEG noninvasively detects the magnetic fields due
    to synchronously active neuron populations
  • Excitatory postsynaptic potentials/currents in
    pyramidal cells produce most of the MEG signals
  • MEG is most sensitive to fissural activity
  • MEG can follow the neural events down to
    submillisecond timescales
  • Magnetic signals are not distorted by the skull
    gt generators can be localized much better than
    from EEG

22
Origin of the Magnetic Field
23
Parallel dendrites
Pyramidal cells parallel orientation gt
spatial summation
Courtesy of Elekta, Modified by AB
24
Radial vs. Tangential Sources
?

25
Radial vs. Tangential Sources
26
MEG-EEG MEG Spike With EEG Spike
MEG 275
EEG
27
MEG-EEG MEG Spike Without EEG Spike
MEG 275
EEG 18
28
Why MEG EEG Spikes are different?
Park et al., Tohoku J Exp Med.
2004203(3)165-74.
29
MEG and EEG Generators
http//www.ctf.com/Pages/page33.html
30
Orthogonal Relationship Between EEG and MEG
Signals
(Vrba Robinson, 2001)
31
Table 1 Comparative summary of the key features
of MEG and EEG (Vrba Robinson, 2001 Barkley,
2004 Baumgartner, 2004)
There is a prospect of having a system
operational outside of a shielded room in the
near future , iEEG invasive EEG, vEEG
video EEG cm centimeter, Ks thousands,
Sato, Bagic 2005, in press.
32
science.nasa.gov
33
Magnetic Field Measurements
  • Frequency
  • 10 mHz (as low as 1 mHz for sleep spindles) to 1
    kHz.
  • Field magnitudes
  • 10 fT (10-15 T) for spinal cord signals to about
    several picotesla (10-12 T) for brain rhythms.
  • The Earth 0.5 mT, the urban magnetic noise 1
    nT 1 ?T.
  • The Environment/Brain Ratio 1 million 1
    billion.

(Nakaya Mori, 1992 Vrba Robinson, 2001)
34
http//www.4dneuroimaging.com
35
MEG Instrumentation
36
Sensing minute magnetic fields
Shielding (repelling) hostile magnetic fields of
the environment
SQUID Superconducting QUantum Interference
Device
Magnetically Shielded Room (MSR)
37
The man who made it possible!
Brian David Josephson (Cardiff, UK, 01/04/1940)
is a British physicist whose discovery of the
Josephson effect while a 22-year-old graduate
student won him a share (with Leo Esaki and Ivar
Giaever) of the 1973 Nobel Prize for Physics.
(1962)
  • A Josephson junction is an superconductor-
  • insulator-superconductor (SIS) layer structure
  • placed between two electrodes.
  • (As the temperature is lowered), superconducting
  • current flows through it even in the absence of
  • voltage between the electrodes (part of the
  • Josephson effect).

38
John Clarke, Ph. D. Professor of physics
Materials Sciences Division Lawrence Berkeley
National Laboratory University of California at
Berkeley
  • SQUID
  • Magnetometer Sensitivity
  • The most sensitive measurement device known to
    man
  • It can measure magnetic flux on the order of
    one flux quantum.

A flux quantum can be visualized as the magnetic
flux of the Earth's magnetic field (0.5 Gauss
0.5 x 10-4 Tesla) through a single human red
blood cell (diameter about 7 microns).
It can measure extremely tiny magnetic fields.
The energy associated with the smallest
detectable change in a second, about 10-32
Joules, is about equivalent to the work required
to raise a single electron 1 millimeter in the
Earth's gravitational field!
39
Flux Transformer and SQUID-sensor
SQUID Superconducting QUantum Interference Device
40
SQUID
  • SQUID is the only sensor sensitive enough for MEG
  • Superconducting loop broken by two Josephson
    junctions
  • Superconductivity low temperature required
    immersion in liquid helium (-269 Celsius)

41
The SQUID principle
http//hyperphysics.phy-astr.gsu.edu/HBASE/solids/
squid.htmlc1
42
SQUIDs immerged in the sea of helium
  • 269 ºC
  • 452 ºF
  • 4.2 ºK

http//www.lanl.gov/quarterly/q_spring03/squid_tex
t.shtmlhelmet_assembly
43
Gradiometer Magnetometer
44
Flux Transformers
Courtesy of V. Jousmaki, Elekta
45
Detector Array
Triple Sensor
Images Courtesy of Elekta
46
(Science 1968161784-6.)
The man who did it!
  • The first SQUID
  • measurement at the MIT
  • (Cohen, Science 1972)

David Cohen, Ph.D. (MIT, 1968)
47
Magnetically Shielded Room
(Cohen et al., 2002)
Image Courtesy of Elekta
48
A 7-channel MEG recording at the NIH 1986
Sato et al., 1986
49
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50
SUBJECT
51
PATIENT
52
Art vs. Artifact
www.denibonet.com/blog/ images/Face20piercing...
53
Aston
1980s
2005
54
Data Presentation (1)
55
Data Presentation (2)
http//www.ctf.com/Pages/page33.html
56
SAM Display of a Language Task
subjects were presented with a single letter and
instructed to sub-vocalize words beginning with
the given letter
http//vsm.gssiwebs.com/products/meg/overview/faq.
htm
Courtesy Dr. Krish Singh et. al., Wellcome
Laboratory for MEG Studies, Aston University,
U.K.
57
Localization of Language Function
CTF MEG, Canada Images courtesy of Dr. Jing
(Hospital for Sick Children)
58
A representation of the magnetic fields measured
by sensors as superimposed on the surface of
the subject's head.
Modeling of cortical activations during a
visual experiment
John George http//www.firstscience.com/SITE/ARTI
CLES/imaging.asp
59
Magnetic Source Imaging
60
Preoperative Identification ofSensorimotor Cortex
Courtesy of V. Jousmaki, Elekta
61
Somatosensory Evoked Response for PSFM
Courtesy of VSM-CTF, Work of Jing Xiang, M.D,
Ph.D, Ontario, Cnada
62
Operating field
http//www.wkni.org/directions/dv02i02.pdf
63
Some logistical technical aspects of MEG
64
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65
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66
Sensors
102 Triple-Sensors 102 MAGNETOMITERS 204
GRADIOMETERS 306 Channels
Images Courtesy of Elekta
67
Stylete
Receiver
Transmitter
Goggles
Digitizer
Wooden Chair
68
4 HPI (head position indicator) coils
Machine Coordinate System (Sensor space)
?
3 Cardinal points Head Coordinate System
69
3 Cardinal Points
Head Coordinate System
?
?
70
Machine Coordinate System (Sensor space, fixed)
4 HPI (head position indicator) coils
4. X,Y,Z
2. X,Y,Z
?
1. X,Y,Z
3. X,Y,Z
71
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72
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73
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74
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75
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76
What MEG Can Record?
(Fisher, 2000)
77
MEG Applications
  • Clinical applications of MEG
  • 1. Localization of epileptic foci and surgical
    planning
  • 2. Functional pre-surgical mapping (FPSM)
  • Selected research applications of MEG in
    studying
  • 1. Mental activity and memory
  • 2. Various aspects of language
  • 3. Cortical plasticity
  • 4. Movement physiology
  • 5. Neurological disorders
  • 6. Psychiatric disorders
  • 7. Pain
  • 8. Fetal MEG
  • 9. High frequency oscillations (HFOs)

Sato, Bagic 2005
78
Epilepsy Localization
79
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80
Biological Price Of Epilepsy
Brains are burning while help is on the way
81
Functional Pre-surgical Mapping (FPSM)
82
Toe
Hand Digits
Tumor
Thumb Lip
Pre-surgical Brain Mapping Somatosensory Source
Localizations In Reference To The Tumor
Courtesy of VSM-CTF, Canada Prepared by Dr. Tim
Roberts, Modified by AB
Bagic 2006
83
Example Right Median Nerve Stimulation
Spatial and temporal features combined give an
idea of the number of source areas
Courtesy of MF, Modified by AB
84
Courtesy of Funke M, 2005, Modified by Bagic A,
2006
85
Somatosensory Mapping Homunculus
LD1
RD5
RD2
Rlip
RD1
CTF MEG, Canada Prepared by Dr. Tim Roberts
86
Courtesy of Funke M, 2005
87
Right Anterior
M20 Somatosensory Response
Courtesy of Funke M, 2005, Modified by Bagic A,
2006
88
Median Nerve Stimulation Index Finger
Movement Tibial Nerve Stimulation
Courtesy of Funke M, 2005, Modified by Bagic A,
2006
89
Dipole Model of Right Median Nerve SEF
Courtesy of MF, Modified by AB
90
Right Median Nerve Stimulation
91
Cortico-Muscular Coherence Spectra
Salenius et al., J Neurophysiol 1997
92
Cortico-Muscular Coherence
Bagic, Balish, Sato, unpublished data
93
SAM statistical images in left-handed patients
clearly show language dominance right dominant
(case 1, left, LI 0.33), bilateral (case 4,
right, LI 0.08) and left dominant (case 3,
center, LI 0.41). The results were congruent
with the Wada test.
Hirata et al., NeuroImage 2004 23 4653
94
Memory
95
Increased MEG activation in OCD reflects a
compensatory mechanism specific to the phase of a
visual working memory task
Estimates dynamic Statistical Parametric Mapping
(dSPM maps) of the spatiotemporal patterns of
cortical activity during
Ciesielski et al, 2005
96
Estimates (dSPM maps) of the spatiotemporal
patterns of cortical activity during
Ciesielski et al, 2005
97
MCI Dementia
98
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99
Fernandez et al., 2006
100
The estimated relative risk of conversion to AD
was increased by 350 in those MCI patients with
high left parietal dipole density scores.
Fernandez et al., 2006
101
UPMC University of Pittsburgh Center for
Advanced Brain Magnetic Source Imaging
CABMSI
102
Education Training
Clinical Care
Clinical Research
CABMSI
Basic Applied Research
103
Neurological Surgery
Neurology
Psychiatry
The UPMC U Pitt CMU BRAINS and
minds FOCUSED ON THE BRAIN MIND
Psychology
Welcome Newcomers
CMU
CNBC
Bioengineering
104
First UPMC MEG Data in Stentor
CABMSI Center for Advanced Brain Magnetic Source
Imaging
A dipole fit in the left pre-central gyrus
indicating a corresponding source localization
of a N20m after the Right Median Nerve (RMN)
stimulation of our first volunteer whose data
were posted in Stentor on December 15, 2005.
105
Ongoing CABMSI Pilot Studies
  • PI Mark R. Lovell, Ph. D., Orthopedic Surgery
  • (IRB 0603162 (Approval Date June 2, 2006)
  • MEG and Sports-Related Concussion
  • PI Charles A. Perfetti, Ph.D., LRDC
  • (IRB 0600839 Approval Date June 29, 2006)
  • Electrophysiological Studies of Reading and
    Language
  • PI Ellen Frank, Ph.D., Psychiatry
  • (IRB IRB 0607024 Approval Date July 11,
    2006)
  • Using Magnetoencephalography (MEG) to
    Investigate Patterns of Neural Responses Prior to
    and Following Interpersonal Psychotherapy

106
Oncoming CABMSI Pilot Studies
  • PI James McClelland. Ph.D., CMU/Stanford
  • (IRB 0606115 Approval Date October 18, 2006)
  • MEG-EEG Studies of Mental Coherence
  • PI Matthew Shtrahman, Ph.D. (MD/PHD Program)
  • (Approval Date In submission, 2006)
  • Elucidating the Electrophysiological Basis of
    Perception Using Magnetoencephalography (MEG) and
    Electroencephalography (EEG)
  • IN PREPARATION
  • David Wolk, M.D., Neurology
  • Mark Wheeler, PhD, Psychology

107
Externally Funded Or Submitted Proposals
  • PI Bill Eddy, Ph.D., CMU/CNBC
  • (NSF Grant DMS-0527141)
  • Magnetoencephalography (MEG) -Analysis of very
    noisy spatially and temporally varying fields
  • PIs Seong-Gi Kim, Ph.D., William Eddy, Ph.D.,
  • (NIH Training Grant Funded)
  • The Multimodal Neuroimaging Training Program
    (T90/R90)
  • PI Sasa Zivkovic, M.D., Neurology VA
  • (VA Study, Funded)
  • Cognitive Function in Veterans with ALS
  • PI Stefanie Hassel, Ph.D., Psychiatry
  • (NARSAD Proposal, Pending)
  • Processing facial affect in bipolar disorder  a
    magnetoencephalography study

108
Conclusions
  • MEG is temporally and spatially most accurate
    non-invasive real-time reading of brain activity.
  • MEG is a very potent research tool that is
    increasingly incorporated into complex multimodal
    imaging approaches.
  • The CABMSI is a resource center established to
    facilitate all clinical applications as well as
    the broadest spectrum of research applications of
    MEG.
  • The limits are only set by our creativity and
    enthusiasm.
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