biomagnetism - uw-madison department of...
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Biomagnetism
Ron WakaiProfessor
Department of Medical Physics
Magnetism in Medicine: A bad beginning
Franz Mesmer (1734-1815)• “discoverer” of “animal
magnetism”
Some current “applications” of magnetism:
Current Medical Applications of Magnetism
Magnetic resonance imaging (MRI)
Transcranial magnetic stimulation (TMS)
Magnetoencephalography (MEG)
Nerve and muscle cells act like tiny
batteries that drive ionic currents
• current dipole, Q (current source)
• volume current, JV
! magnetic field, B
Ionic currents produce electric and magnetic signals:• electrocardiogram (ECG) and magnetocardiogram (MCG)
• electroencephalogram (EEG) and magnetoencephalogram (MEG)
**MEG provides improved source localization
Origin of Surface Electric vs. Magnetic Signals
Extracellular current (volume current) surface electric potentials• topography is distorted by inhomogenous conductivity
Intracellular current (primary current) surface magnetic fields• topography of magnetic signals is distorted much less, allowing accurate source localization
Neuromagnetism
• Dendritic activity gives rise to EEG/MEG• Neurons organized in columnar arrangement• Need >1000 neurons to get detectable signal
• Focal activity produces dipolar spatial pattern
• Source lies below phase inversion
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! geofield
! typical urban magnetic noise
! magnetic field of magnetic contaminants in lung
! magnetocardiogram
! fetal magnetocardiogram
! spontaneous magnetoencephalogram
! evoked magnetic brain responses
Instrumentation Requirements
1. extremely sensitivity detector: SQUID(superconducting quantum interference device)
2. noise rejection: magnetically shielded room (high-magnetic permeability alloy, aluminum)
Whole-head system148 channels
Dual-system system74 channels
SQUID (Superconducting Quantum Interference Device)
Superconducting loopinterrupted by two “weak-links” (Josephson tunnel
junctions)
Current-voltage characteristic• current at zero voltage (supercurrent, Ic)
Modulation of I-V Characteristic by Magnetic Signal
•supercurrent show interferencepattern
Ehrenberg-Siday-Aharonov-Bohm Effect
SQUID1. particle beam divides
2. paths enclose region of flux
3. vector potential, A, alters phase
(B= ∇xA)
phase advancesphase retards
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Current-Biased SQUID: Periodic V vs. Φ
High Magnetic Permeability Shielding
mu-metal
Eddy-Current Shielding
Approximate weight: 7,000 kgApproximate cost: $350,000
Magnetically ShieldedRoom
time-varying magneticinterference
eddy-currents
Essential for low frequency shielding
Highly cost-effective
Magnetic source imaging (MSI)= MEG+MRI
whole-head mapping ofauditory evoked response
isofield contourmap
dipole overlay
Nakasato et al., 1995
Statement of problem: To compute the distributionof brain currents based on measurement ofexternal magnetic field
**Has no unique solution**
Modeling Assumptions• Dipole approximation: signal due to collection of
current dipoles—localized current elements—thatlie on convoluted cortical surface
• Homogeneous sphere model: model head ashomogenous conducting sphere
Inverse Problem
Positron Emission Tomography (PET) Functional Magnetic Resonance Imaging (fMRI)Functional brain imaging techniques
spatial temporal brainmodality resolution resolution region cost
1. positron emission 1 cm minutes whole $3Mtomography (PET) brain
2. functional magnetic 1 cm seconds whole $2Mresonance imaging (fMRI) brain
3. electric source imaging >1cm msec cortex $100k
4. magnetic source imaging 1 cm msec cortex $2M(MEG + MRI)
MSI: records cortical activity directly and with high temporal resolution, butsuffers from an ill-posed inverse problem
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Clinical applications
• presurgical functional mapping– somatosensory, auditory– language
• epilepsy– localization of epileptogenic foci– most useful for neocortical epilepsy
approved for clinical use in 2002
Magnetic Localization of Somatosensory Cortex
sites of mechanical stimulation
sites of cortical response
Nakamura et al., Neuroimage 7(4 Pt 1):377 (1998)
Presurgical mapping of central sulcus
Central sulcus, containing somatosensory cortex, wasat A, not B, allowing surgical resection of tumor
Orrison et al., Perspect Neurol Surg 4:141 (1993)
Language Mapping: Response to Visually Presented Words
Simos et al., J Clin Exp Neuropsych 1998; 5:706
language activity sensory response
Sensory andlanguage responsesare temporallydistinct
Validated viaintraoperativemapping
Magnetoencephalographic mapping of theMagnetoencephalographic mapping of thelanguage-specific cortex.language-specific cortex.Papanicolaou, SimosPapanicolaou, Simos et al. J et al. J NeurosciNeurosci 1997 1997
Language Lateralization
NRNL
NRNLLI
+
!=
Picture Naming
Salmelin et al., Nature 368:463-8 (1994)
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Application of MEG to Epilepsy
• Incidence of about 1%• 10-20% of epilepsy is intractable to drug therapy
Presurgical evaluation• Focal or generalized?• Number and relative timing of foci (primary vs.
secondary focus)• Location with respect to eloquent cortex
Mirror focus
Primary focus
Transmission of electric and magnetic fetal signals
primary currents→ fMCG,fMEGvolume currents → fECG,fEEG
•fECG is attenuated strongly by thepoor conductivity of vernix caseosa
•fMCG is affected much less
Fetal Magnetocardiography (fMCG)
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FMCG FROM 17-38 WEEKS FROM SAME SUBJECT Information Content of fMCG
RR interval fetal heart rate (FHR), FHR variabilityQRS amplitude variations fetal (trunk) movementP-, QRS-, T-wave timing and morphology fetal rhythm
•R
RR
QRSamp
PR
QT
QRS
Fetal Heart Rate (FHR) Monitoring
• Primary clinical method• Specific for hypoxia
Reassuring FHR patterns• reactivity: FHR accelerations associated with movement• normal FHR variability
Ominous FHR patterns• decelerations that are late or variable with respect to
uterine contractions• absent variability
Movement-related Signal Amplitude Variation:fMCG Actography
• fetal trunk movement results in prominent movement artifact• instantaneous QRS amplitude serves as actogram tracing
Assessing fetal activity from the fMCG:fMCG Actocardiography
• 2 pumps: left (systemic), right (pulmonary)• 4 chambers: 2 atria, 2 ventricles
valves at inlet and outlet of ventricles
The Heart
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Unique Electrical Properties of Cardiac Tissue
!threshold
1. rhythmic self-excitation - pacemaker tissue
3. continuous conducting surface- myocardial syncytium
2. long refractory period- 250 ms (vs. 2 ms for neurons)
repolarizationdepolarization
refractory period
Mechanisms of Arrhythmia
1. Abnormal impulse formation– ectopy– altered automaticity
2. Abnormal impulse conduction
– accessory connection
– conduction block
– reentry
Ventricular Fibrillation (V-fib)chaotic, ineffective beating (heart quivers)
• most common immediate cause of sudden death• due to abnormal automaticity and/or “reentry” (impulsepropagates through same tissue more than once)
Initiation of V-fib• QT dispersion (inhomogeneous repolarization)• impulses divide around patches of refractory tissue
ECG during transition from normalsinus rhythm to V-tach to V-fib
• ~1-2% incidence, but most are benign• ~10% of these are serious, sustained arrhythmias
Sustained fetal arrhythmia• rare, but high mortality and morbidity• most common types:
1) sustained tachyarrhythmia, usually SVT2) complete congenital heart block (CCHB)
Fetal Arrhythmia
Drug Therapy for Fetal Arrhythmia
• Aggressive drug therapy is used often
• Adverse side effects: toxic, proarrhythmic
Accurate diagnosis and follow-up are critical, especiallywhen drug therapy is used
Rationale for fMCG:• MCG/ECG is gold standard for rhythm assessment
• Ultrasound is less precise and indirect for rhythm assessment,but can also assess heart function and blood flow
Echo/Doppler Ultrasound
fMCG
echo/Doppler
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145 146 147 148 149 150
-2500
-1500
-500
500
1500
2500
P
R
P TP
R
P
T
P
R
PT
time (sec)
amplitude (fT) 115 116 117 118 119 120
-2000
-1000
0
1000
time (sec)
amplitude (fT)
Long QT Syndrome (LQTS)
fMCG diagnosed LQTS and torsade due to proarrhythmic drug effect
polymorphic ventriculartachycardia: torsade depointes
• prolonged QT interval
• 2nd-degree AV block
• LQTS: prolonged repolarization, undetectable with ultrasound
P-wave: atria depolarization
QRS complex: ventricular depolarization
T-wave: ventricular repolarization
Depolarization of Heart
• atria and ventricles are isolated except via the AV node
Atrioventricular Block• impulse is slowed or blocked at AV node• second most common serious fetal arrhythmia
60% maternal lupus antibodies, 40% structural disease
264.0 265.0 266.0 267.0 268.0
CCAVB
congenital complete AV block• SA node paces atria• AV node paces ventricles at much lower rate• atrial and ventricular rhythms are dissociated
P-wave
Supraventricular Tachycardia (SVT)
109 110 111 112 113 114
Initiation of supraventricular tachycardia:
• “accessory” pathway (extra connection) exists between atria andventricles• most common serious fetal arrhythmia
circusmovement
Initiation and Termination of SVT:Association with Fetal Movement
300 400 500 600
-2000
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4000
0
50
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350subject 2
time (sec)
fetal QRS amplitude (fT)
fetal heart rate (bpm)
0 100 200 300
0
2000
4000
0
50
100
150
200
250
time (sec)
fetal QRS amplitude (fT)
fetal heart rate (bpm)
subject 3
SVT SVTSVT
SVT
quiescence activity
quiescence
activity
0 100 200 300 400 500 600
50
100
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atrial
ventricular
time (sec)
fetal heart rate (bpm)
Subject 2: GA= 33 wks, ventricular rate= 75 bpm
Heart Rate Patterns in Congenital AV Block
0 100 200 300
50
100
150
ventricular
atrial
time (sec)
fetal heart rate (bpm)
High ventricular rate (>60 bpm)atrial and ventricular rates arereactive and highly correlated
Low ventricular rate (< 55 bpm):ventricular tracings become flat
Subject 3: GA= 28 wks, ventricular rate= 52 bpm
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Subject 3: GA= 25-4/7 weeks; mean ventricular rate= 71 bpm
Tachycardia in Congenital AV Block
Subject 4: GA= 34 weeks; ventricular rate= 50 bpmbigeminy tachycardia
Subject 4: GA= 34 weeks; ventricular rate= 50 bpm
• 20% show tachycardia; generally not detected by ultrasound
• predictive of need for with neonatal pacing