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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

[email protected]

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


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


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.


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


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).


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


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


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


What can MEG measure outside the skull?

Pyramidal cortical neurons: main processing cells. Their dendrites

run parallel, perpendicular to and towards the cortex surface.


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.


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.


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.


Spectral density of typical noise sources*

* Hämäläinen et al., Rev. Mod. Phys. 65, 1993


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.


CTF Systems, Port Coquitlan, BC, CanadaFirst MEG measurements with the

SQUID at MIT (Cohen, 1972).

From first to modern shields


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.


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


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*


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


Latest MEG modelsBiomag 2008, Sapporo, Japan

Elekta Neuromag® NiCT – superconducting shield

•Advanced Technologies Biomagnetics (ATB), Pescara, Italy

•CTF and 4-D Neuroimaging closed!


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


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


•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.


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


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)


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)


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


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


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


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).


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


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!


Thank you!

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Brain's Magnetic Field: a Narrow Window to Brain's Activityworkshop.ee.technion.ac.il/upload/Events/Andrei.pdf · Brain's Magnetic Field: a Narrow Window to ... magnetic fields Poor