Title: MEG Imaging Applications Practical Introduction To Brain Imaging In The Fourth Dimension
1MEG 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)
2Team Work(s)!!!
3Special 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
4Outline
- 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
5What is MEG what it records?
6MEG
- 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).
7IEEG Invasive Electroencephalography, MEG
Magnetoencephalography, MRS Magnetic Resonance
Spectroscopy, fMRI functional MRI, SPECT
Single Photon Emission Cranial Tomography, PET
Positron Emission Tomography,
8Sources of Magnetic Fields
9Sources of Magnetic Signals
http//hyperphysics.phy-astr.gsu.edu/HBASE/magneti
c/magfie.htmlc1
10The Right Hand Rule
http//www.physics.sjsu.edu/facstaff/becker/physic
s51/mag_field.htm
11Electromagnetism
Electric current always generates a magnetic field
H.C. Ørsted, 1820
12Origin of the Magnetic Field
Courtesy of Elekta, Modified by AB
13MEG Generators
104-5 activated cells
(http//www.ctf.com/Pages/page33.html)
14Parallel dendrites
Pyramidal cells parallel orientation gt spatial
summation
15Neural 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
16Currents 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
17Neural 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.
18MEG 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.
19MEG 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
20What can we then see with MEG?
- Almost all of the cortex, fissural activity
emphasized
Hillebrand Barnes, NeuroImage 2002
21MEG 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
22Origin of the Magnetic Field
23Parallel dendrites
Pyramidal cells parallel orientation gt
spatial summation
Courtesy of Elekta, Modified by AB
24Radial vs. Tangential Sources
?
25Radial vs. Tangential Sources
26MEG-EEG MEG Spike With EEG Spike
MEG 275
EEG
27MEG-EEG MEG Spike Without EEG Spike
MEG 275
EEG 18
28Why MEG EEG Spikes are different?
Park et al., Tohoku J Exp Med.
2004203(3)165-74.
29MEG and EEG Generators
http//www.ctf.com/Pages/page33.html
30Orthogonal Relationship Between EEG and MEG
Signals
(Vrba Robinson, 2001)
31Table 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.
32science.nasa.gov
33Magnetic 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)
34http//www.4dneuroimaging.com
35MEG Instrumentation
36Sensing minute magnetic fields
Shielding (repelling) hostile magnetic fields of
the environment
SQUID Superconducting QUantum Interference
Device
Magnetically Shielded Room (MSR)
37The 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).
38John 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!
39Flux Transformer and SQUID-sensor
SQUID Superconducting QUantum Interference Device
40SQUID
- 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)
41The SQUID principle
http//hyperphysics.phy-astr.gsu.edu/HBASE/solids/
squid.htmlc1
42SQUIDs immerged in the sea of helium
http//www.lanl.gov/quarterly/q_spring03/squid_tex
t.shtmlhelmet_assembly
43 Gradiometer Magnetometer
44Flux Transformers
Courtesy of V. Jousmaki, Elekta
45Detector 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)
47Magnetically Shielded Room
(Cohen et al., 2002)
Image Courtesy of Elekta
48A 7-channel MEG recording at the NIH 1986
Sato et al., 1986
49(No Transcript)
50SUBJECT
51PATIENT
52Art vs. Artifact
www.denibonet.com/blog/ images/Face20piercing...
53Aston
1980s
2005
54Data Presentation (1)
55Data Presentation (2)
http//www.ctf.com/Pages/page33.html
56SAM 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.
57Localization of Language Function
CTF MEG, Canada Images courtesy of Dr. Jing
(Hospital for Sick Children)
58A 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
59Magnetic Source Imaging
60Preoperative Identification ofSensorimotor Cortex
Courtesy of V. Jousmaki, Elekta
61Somatosensory Evoked Response for PSFM
Courtesy of VSM-CTF, Work of Jing Xiang, M.D,
Ph.D, Ontario, Cnada
62Operating field
http//www.wkni.org/directions/dv02i02.pdf
63Some logistical technical aspects of MEG
64(No Transcript)
65(No Transcript)
66Sensors
102 Triple-Sensors 102 MAGNETOMITERS 204
GRADIOMETERS 306 Channels
Images Courtesy of Elekta
67Stylete
Receiver
Transmitter
Goggles
Digitizer
Wooden Chair
684 HPI (head position indicator) coils
Machine Coordinate System (Sensor space)
?
3 Cardinal points Head Coordinate System
693 Cardinal Points
Head Coordinate System
?
?
70Machine 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(No Transcript)
72(No Transcript)
73(No Transcript)
74(No Transcript)
75(No Transcript)
76What MEG Can Record?
(Fisher, 2000)
77MEG 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
78Epilepsy Localization
79(No Transcript)
80Biological Price Of Epilepsy
Brains are burning while help is on the way
81Functional Pre-surgical Mapping (FPSM)
82Toe
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
83Example Right Median Nerve Stimulation
Spatial and temporal features combined give an
idea of the number of source areas
Courtesy of MF, Modified by AB
84Courtesy of Funke M, 2005, Modified by Bagic A,
2006
85Somatosensory Mapping Homunculus
LD1
RD5
RD2
Rlip
RD1
CTF MEG, Canada Prepared by Dr. Tim Roberts
86Courtesy of Funke M, 2005
87Right Anterior
M20 Somatosensory Response
Courtesy of Funke M, 2005, Modified by Bagic A,
2006
88Median Nerve Stimulation Index Finger
Movement Tibial Nerve Stimulation
Courtesy of Funke M, 2005, Modified by Bagic A,
2006
89Dipole Model of Right Median Nerve SEF
Courtesy of MF, Modified by AB
90Right Median Nerve Stimulation
91Cortico-Muscular Coherence Spectra
Salenius et al., J Neurophysiol 1997
92Cortico-Muscular Coherence
Bagic, Balish, Sato, unpublished data
93SAM 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
94Memory
95Increased 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
96Estimates (dSPM maps) of the spatiotemporal
patterns of cortical activity during
Ciesielski et al, 2005
97MCI Dementia
98(No Transcript)
99Fernandez et al., 2006
100The 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
101UPMC University of Pittsburgh Center for
Advanced Brain Magnetic Source Imaging
CABMSI
102Education Training
Clinical Care
Clinical Research
CABMSI
Basic Applied Research
103Neurological Surgery
Neurology
Psychiatry
The UPMC U Pitt CMU BRAINS and
minds FOCUSED ON THE BRAIN MIND
Psychology
Welcome Newcomers
CMU
CNBC
Bioengineering
104First 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.
105Ongoing 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
106Oncoming 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
107Externally 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
108Conclusions
- 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.