brain's magnetic field: a narrow window to brain's...
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Brain's Magnetic Field:
a Narrow Window to
Brain's ActivityAndrei Ben-Amar Baranga
Department of Electrical Eng., Ben Gurion University and Physics Department, Nuclear Research Center - Negev
andreib@bgu.ac.il
Electromagnetic field and the human body workshop
Technion, December 2010
Andrei B. Baranga Ben Gurion University
Brain activity exploration
“Exploration of the human brain is
the utmost intellectual interest:
the whole humanity depends on
our minds”.*
1010 neurons: information transmitting and processing units.
1014 synapses: small gaps between neurons’ crossed by nerve impulses.
1011 glial cells: support, ion concentration maintenance and transport of nutrients.
Present understanding of brain functions is based mainly on research on
animals, like microelectrodes inserted into small mammals brain.
* Hämäläinen et al., Rev. Mod. Phys. 65, 1993
Andrei B. Baranga Ben Gurion University
Non-invasive brain activity exploration
Anatomical structures: static pictures of living tissues
• CAT (CT scan): Computer-Assisted x-ray Tomography (1972)
• MRI: Magnetic Resonance Imaging (1973)
Functional metabolic activity / blood flow exploration:
• SPECT: Single-Photon-Emission Computed Tomography (1983)
• PET: Positron-Emission Tomography (1975)
• fMRI: functional MRI (1991)
Subject exposed to X-ray, radioactive tracers and strong
magnetic fields
Poor time resolution: more than one-second
Andrei B. Baranga Ben Gurion University
Real-time, completely non-invasive
techniques for brain activity imaging
• EEG: ElectroEncephaloGraphy: measures electric potential
differences on the scalp (1936)
• MEG: MagnetoEncephaloGraphy: measures weak magnetic fields
produced by currents flow in neural system (1968)
The time resolution of MEG and EEG: milliseconds.
Electrical events of single neurons typically last several tens of milliseconds.
Thousands of neurons should act in concert for a current to be detected.
Magnetic fields, unlike electric potentials, are not affected by surrounding tissues providing a more accurate image than EEG.
Andrei B. Baranga Ben Gurion University
Brain activity imaging
EEG: ElectroEncephaloGraphy
IEEG: Intracranial ElectroEncephaloGraphy
MEG: MagnetoEncephaloGraphy
MRS: Magnetic Resonance Spectroscopy
fMRI: functional Magnetic Resonance Imaging
SPECT: Single-Photon-Emission Computed
Tomography (1983)
PET: Positron-Emission Tomography (1975)
For best results: link between functional MEG to anatomical MRI
Andrei B. Baranga Ben Gurion University
MEG Applications
• Study of brain functions: visual, auditory and somatosensory.
• Study of cognitive processes: face recognition, language perception and production, memory.
• Clinical applications (besides EEG, fMRI and invasive intracranial EEG):
• Treatments of epilepsy for localization of epileptic foci
• Localization and removal of lesions or tumors
• Diagnosis of mild head trauma
• Diagnosis of neurological disorders: schizophrenia, Parkinson's,
Alzheimer's
Wide clinical applications have been limited so far by the high
cost of the systems (~$2M).
Andrei B. Baranga Ben Gurion University
MEG source: the neuron activity
Neurons: the principal brain cells.
– Soma: cell body containing
the nucleus and the
metabolic machinery.
– Dendrites: extensions
receiving stimuli from other
cells.
– Axon: a long fiber carrying
the information far away
from the soma to other
cells.
Axon terminal
Soma-Cell
body
axon
dendrite
Andrei B. Baranga Ben Gurion University
Neurons excitation – ion mechanism
Neuron excitation: change in ions concentration (Potassium
and Sodium).
Action potential: reversal of membrane potential from -70mV
to +40mV (for ~1ms).
Positive impulse current propagates along the axon: pre-
synaptic current, with volume currents closing the loop.
Volume currents’ electric potential is monitored by EEG
+40mV++++++++++++ - - -Na+ ions
K+ ions
Neuron excitation
- - - - - - - - - - -+++-70mV
Action potential
Andrei B. Baranga Ben Gurion University
Stimulated neuron currents: the current
dipole
Bi-directional, millisecond current Uni-directional, tens of milliseconds current
Volume currents
At axon terminals, the impulse induces the release of
neurotransmitter molecules through the synaptic cleft to the
post-synaptic cell: post-synaptic current (tens of milliseconds).
Post-synaptic currents’ magnetic field is monitored by MEG
Andrei B. Baranga Ben Gurion University
What can MEG measure outside the skull?
Pyramidal cortical neurons: main processing cells. Their dendrites
run parallel, perpendicular to and towards the cortex surface.
Andrei B. Baranga Ben Gurion University
MEG challenges to be addressed
• Very low magnetic signals, <100 fT:
– 8 to 9 orders of magnitude below earth magnetic field.
• Environmental and human body noise:
– the magnetic noise is several orders of magnitude
higher than the biomagnetic signals in the same
frequency band.
• Measurements’ interpretation - the inverse problem:
– Source localization in the brain might have multiple
solution.
Andrei B. Baranga Ben Gurion University
Magnetic Field Strengths
Human brain : activity
Atotesla
Chip transistor @ 2m
Microtesla
Nanotesla
Picotesla
Femtotesla
10-15
10-12
10-9
10-6
10-3
Earth's field
Power lines
Automobile at 50m
Screwdriver @ 5m
Lung particles
Human heart
Skeletal musclesFetal heartHuman eye
Human brain : evoked
responses
SQUID system
noise level1
10
100
1
10
100
1
10
100
0
10
100
1
10-18 1
10
100
SERF atomic
magnetometer
Atomic magnetometer
Car @ 2 km
Biomagnetic fieldsEnvironmental fieldsB (tesla)
Magnetic fields generated by brain: ~100fT, <100Hz.
Andrei B. Baranga Ben Gurion University
Noise in MEG
• Laboratory environment:
– Outside the building: cars, railways, power lines.
– Inside the building: elevators, fluorescent lamps, general equipment (MRI produces fields 14-15 orders of magnitude higher than the brain signals).
• Mechanical movements of the magnetometer relative to the measured subject produce noise.
• Geomagnetic fluctuations at low frequency: for f<1 Hz, noise of ~ I pT/√Hz.
• Noise from human body:
– Eye movements and blinks.
– Cardiac activity.
– Electric currents in muscles.
Andrei B. Baranga Ben Gurion University
Spectral density of typical noise sources*
* Hämäläinen et al., Rev. Mod. Phys. 65, 1993
Andrei B. Baranga Ben Gurion University
Noise reduction - Shielding• Passive 50-100 dB
– Flux-entrapment shields (low frequency noise):
• Ferromagnetic, highly permeable m-metal (Nickel, Copper, Iron alloy).
• Ferrite materials.
– Lossy magnetic shields based on induced eddy currents (high frequency):
• highly conductive materials (Copper, Aluminum, Iron, etc.).
• High Tc superconducting shields.
• Active 10-20 dB
– Zeroing coils: orthogonal Helmoltz coils around the room to eliminate external fields.
– Gradiometers: two or more coaxial pick-up coils connected in series.
• Logic
– Filters:
• band pass adequate to biomagnetic signals (1-100 Hz) to avoid wideband thermal noise,
• rf filters on all cables.
– Averaging repetitive signals.
Andrei B. Baranga Ben Gurion University
CTF Systems, Port Coquitlan, BC, CanadaFirst MEG measurements with the
SQUID at MIT (Cohen, 1972).
From first to modern shields
Andrei B. Baranga Ben Gurion University
Stimulations delivery
• Sounds are delivered by plastic tubes with mechanical
earphones.
• Visual stimuli by fibers or mirrors.
• Electric stimuli in Somatosensory experiments through
tightly twisted pairs of wires.
Stimulus generators may produce false signals and noise.
Andrei B. Baranga Ben Gurion University
MEG Instrumentation
High sensitive magnetometers:
• Copper induction coil (1968)1
• SQUID (1972)2
• SERF Atomic magnetometer (2006)3
1. Cohen D. "Magnetoencephalography: evidence of magnetic fields produced by alpha rhythm currents." Science 1968;161:784-6
2. Cohen D. "Magnetoencephalography: detection of the brain's electrical activity with a superconducting magnetometer.“ Science 1972;175:664-66
3. H. Xia, A. Ben-Amar Baranga, D. Hoffman, and M. V. Romalis, “Magnetoencephalography with an atomic magnetometer”, Appl. Phys. Lett. 89, 211104 2006
Andrei B. Baranga Ben Gurion University
SQUID consists of two superconductors separated by thin insulating layers to form
two parallel Josephson junctions (superconductor-insulator-superconductor tunnel
junctions).
* Zimmerman et al., J. Appl. Phys., 41, 1572 (1970)
Signal to SQUID connection:
an inductively-matched
superconducting pickup
detection coil connected to
the input coil directly or
through a superconducting
flux transporter.
SQUID
Input coil Pickup coil
SQUID
Input coil Pickup coilFlux transformer
SQUID area: ~0.01-0.05 mm2, <1 nH
SQUID: Superconducting Quantum
Interference Device*
Andrei B. Baranga Ben Gurion University
SQUID MEG
Most sensitive commercial magnetometers, 1 fT·Hz-1/2 @ 4oK
* Zimmerman et al., J. Appl Phys., 41, 1572 (1970)
Gradiometer
configurations:
(b) ΔBz/Δz
(c) ΔBz/Δx
pickup coil
compensation coil
Andrei B. Baranga Ben Gurion University
Latest MEG modelsBiomag 2008, Sapporo, Japan
Elekta Neuromag® NiCT – superconducting shield
•Advanced Technologies Biomagnetics (ATB), Pescara, Italy
•CTF and 4-D Neuroimaging closed!
Andrei B. Baranga Ben Gurion University
SQUID MEG specs
• Liquid He cryostat of non-magnetic materials.
• SQUID pick-up coils as first order gradiometers to eliminate magnetic fields from distant sources such as heart.
• Superconducting helmet for shielding external noise.
• 200-300 SQUIDS in a single layer, 2cm above skull surface, 2-3 cm separation.
• Localization of electric dipoles at a resolution of 3-10 mm.
• Static fields can cause flux trapping in SQUID superconductors, decreasing SQUID gain and increasing noise.
Needed: a more sensitive, more accurate and less
expensive technology to investigate brain activity
Andrei B. Baranga Ben Gurion University
All-optical atomic-magnetometer: principle
of operation – 1. optical pumping
•High density alkali metal vapor (Rb, K, Cs) is produced in a glass cell by
heating it up.
•Each alkali atom has a small magnetic-dipole, the spin.
•By optical pumping the spins are aligned along an incoming circularly
polarized resonantly-tuned pump laser beam.
Vapor cell
Pump
beamx
y
z
Andrei B. Baranga Ben Gurion University
•In a high density vapor cell, a
magnetic field B perpendicular
to the pump beam, rotates the
spins by an angle proportional
to the magnetic field intensity.
All optical atomic magnetometer: principle
of operation – 2. field measurement
•A linearly polarized probe beam, slightly detuned, perpendicular to
both the pump beam and the magnetic field, measures the angle of
spin rotation and, hence, the absolute intensity of the magnetic field by
monitoring its linear polarization rotation (Faraday effect).
•An atomic magnetometer
measures the Larmor frequency
of an atom-spin precession into
an external magnetic field.
Andrei B. Baranga Ben Gurion University
Sensitivity of atomic magnetometers
Limitation: spin-exchange process between two alkali atoms
leading to spin relaxation
• Fundamental sensitivity of an atomic magnetometer:
VtnTB
2
1
n the number density of atoms,
the gyromagnetic ratio,
T2 the transverse spin relaxation time,
V the measurement volume,
t the measurement time.
• T2 is usually limited by the spin exchange collisions between alkali atoms:
n, the thermal velocity
sSE=2×10-14cm2 the spin-
exchange cross-section, similar
for all alkali atoms
• Achievable sensitivity:
T2≈TSE=(nnsSE)-1
B = 1fTcm3
Hz
Andrei B. Baranga Ben Gurion University
SERF: Spin-Exchange Relaxation-Free
• SERF magnetometer eliminates SE relaxation operating in high density alkali vapor and very low magnetic field, B<<1nT; 104 times longer relaxation time!*
– 180oC for [K]~1014cm-3 alkali vapor density.
– shielding of m-metal to reduce any external field by a factor of 106
– zeroing coils to actively eliminate any residual magnetic fields.
B=0.01 fTcm3
Hz• He buffer gas added to K vapor slows the diffusion of atoms suppressing
spin relaxation due to collisions with the walls.
• Achievable sensitivity with SERF:
• N2 molecules prevent radiation trapping by quenching the fluorescence
of excited alkali atoms.
For best performance: high pressure vapor and very low
external magnetic field.
*W. Happer and H. Tang, PRL 31, 273 (1973); W. Happer and A. C. Tam, Phys. Rev. A 16, 1877 (1977)
Andrei B. Baranga Ben Gurion University
Multichannel operation• In a high pressure cell, a volume as small as 1mm3 is an independent detector.*
•1000 field measurements per cm3 are possible.
•The number of simultaneous channels is the number of detectors in the two-dimensional photo-diode array.
•3-D imaging by scanning the pump beam
photodiode
arrayoptics
vapor
cube
probe
beam
pump
beam
*A. Ben-Amar Baranga, S. Appelt, C. J. Erickson, A. R. Young and
W. Happer, Phys. Rew. A 58, 2282 (1998)
Andrei B. Baranga Ben Gurion University
Accuracy of Source Localization
Simulation for a cubic 3-D grid, 100 fT field on edge
3 cm from source, measurement noise 1 fT
– 3-D localization resolution ~ 0.02 mm
– 2-D array resolution ~ 0.2 mm
– SQUID array resolution ~ 2 mm
Atomic Magnetometer
Array
Typical
SQUID Array
Andrei B. Baranga Ben Gurion University
SERF magnetometer advantages• High-sensitivity critical to biomedical applications (noise limitation below 0.01
fT/√Hz)
• Fast data acquisition required by medical applications and research (<100msec).
• Does not require cryogenic cooling as SQUIDS:
– Smaller magnetic shields
– No magnetic dewar noise
– Accommodates head-size variation
• Allows independent and simultaneous measurement of all 3 components of the
magnetic field.
• Simultaneous 3-D magnetic field measurement.
• Multi-channel photodetector technology well developed and inexpensive.
• Higher resolution: up to 1000 field measurements per cm3 (1mm spacing).
• No danger of flux trapping like in SQUID
Andrei B. Baranga Ben Gurion University
1 m
3 m-metal layers
1 m diameter
2 m length
10 measurement positions
18 magnetic coils for zeroingProbe beam
Pump beam
K vapor cell
and oven
Measured Shielding Factor
Transverse 7000
Longitudinal 1000
Princeton Magnetic shielding
Andrei B. Baranga Ben Gurion UniversityAccessible and more spacious than MRI
Andrei B. Baranga Ben Gurion University
First brain magnetic field signals
detected with a SERF magnetometer
H. Xia, A. Ben-Amar Baranga, D.
Hoffman, and M. V. Romalis,
"Magnetoencephalography with an atomic
magnetometer", Appl. Phys. Lett. 89,
211104 (2006).
Andrei B. Baranga Ben Gurion University
The “ill posed” inverse problem
• EEG and MEG measurements might have multiple solutions for source localization.
• Additional contextual information is necessary to complement the theoretical model.
• Few solutions are compatible with constraints from cortical anatomy and multimodal investigations (MEG+EEG+fMRI+…) making MEG/EEG a modeling problem.
• Only cortex is modeled.
• Two main models for the inverse problem:
– Equivalent current dipole
– Distributed source imaging
Andrei B. Baranga Ben Gurion University
Summary
• MEG allows brain activity investigation with good time
resolution and source localization.
• SQUID now and SERF Atomic Magnetometers in the
near future for commercial MEG systems.
• Hybrid technologies are required: MEG, EEG and MRI.
• Better shielding and lower system price for larger scale
span.
• More research towards clinical applications
Can we read thoughts? Not yet!
Andrei B. Baranga Ben Gurion University
Thank you!
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