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SQUID sensors a successful complementary electrophysiological instrument for imaging brain and nerve activities Zvonko Trontelj Physics Dept., University.

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Presentation on theme: "SQUID sensors a successful complementary electrophysiological instrument for imaging brain and nerve activities Zvonko Trontelj Physics Dept., University."— Presentation transcript:

1 SQUID sensors a successful complementary electrophysiological instrument for imaging brain and nerve activities Zvonko Trontelj Physics Dept., University of Ljubljana and Institute for Mathematics, Physics and Mechanics, Ljubljana

2 Participating Researchers University of Ljubljana: Vojko Jazbinsek, Matjaz Slibar, Ales Stampfl, Robert Zorec PTB Berlin: Sergio Erné, Lutz Trahms, Martin Burghoff Wolfgang Mueller, Gerd Wuebbeler. FU Berlin: Gabriel Curio, Peter Aust TU Darmstadt: Gerhard Thiel, Michael Wacke Vanderbilt University: Franz Baudenbacher, Luis Fong, Jenny Holzer, John Wikswo Producers of instrumentation: Neuromag-Electa, CTF

3 Outline of talk Introduction Introduction On SQUID sensor On SQUID sensor Measuring systems Measuring systems Basic steps in data analysis and modeling of sources of bioelectric activity Basic steps in data analysis and modeling of sources of bioelectric activity Examples: Examples: a)Peripheral nerve studies a)Peripheral nerve studies b) Some examples of brain studies b) Some examples of brain studies Conclusions Conclusions

4 Objectives: To apply SQUID(s) in order to obtain the noninvasive information on: To apply SQUID(s) in order to obtain the noninvasive information on: a) Ionic currents in electrically stimulated peripheral nerve medianus. b) Localizations of epileptical focus. c) Localization and functional information on some parts of brain cortex. To demonstrate the pre-diagnostic capabilities of SQUID(s) To demonstrate the pre-diagnostic capabilities of SQUID(s) To model the intracellular curent (m. field) and its relation to AP To model the intracellular curent (m. field) and its relation to AP

5 SQUID sensors 1.What is SQUID? 2.What they offer to us? 3.Where we can use them? 4.Why SQUID sensors in electrophysiology?

6 Ad 1 and Ad 2 Superconducting QUantum Interference Device Superconducting QUantum Interference Device Magnetic flux-to-voltage convertor (the most sensitive sensor for quasi dc magnet. fields m.) Magnetic flux-to-voltage convertor (the most sensitive sensor for quasi dc magnet. fields m.) Measured m. field; via Ampers law the source Measured m. field; via Ampers law the source Based on 3 facts described by QM Based on 3 facts described by QM - superconductivity with Cooper pairs - superconductivity with Cooper pairs - C. pair tunneling - C. pair tunneling - m. flux quantization - m. flux quantization

7 From Josephson jct. to closed sc. circuit

8 Dc SQUID configuration

9 Outer magnetic field is present at the SQUID

10 Ad 3 and ad Ad 4 -M. flux has to be transp.to SQUID - SQUID has to be in m. shielded env. -High sensitivity and spatio.temp. r.

11 Multichannel SQUID system for brain studies

12 Multichannel SQUID system for brain staudies

13 Part of SQUID microscope and C.c. internodal cell holder We measure: We measure: Electric AP Electric AP K + anesthesia technique K + anesthesia technique Magnetic field Magnetic field SQUID Microscope SQUID Microscope Both measurements are simultaneous Both measurements are simultaneous

14 SQUID microscope prepared for the C.c. inernodal cell studies (schematically)

15 Basic steps in analysis and modelling of current sources in living matter Distribution of ionic currents in tissue. Complicated Distribution of ionic currents in tissue. Complicated Direct and inverse problem Direct and inverse problem The direct problem – a unique solution The direct problem – a unique solution T Z T E T Z T E The inverse problem is ill-posed problem The inverse problem is ill-posed problem E Z ET T E Z ET T Simple geometry – analyt. solutions, otherweise modeling Simple geometry – analyt. solutions, otherweise modeling

16 Simple geometry Single cylindrically shaped cell (1D case) Single cylindrically shaped cell (1D case) Bound. cond.: m (z) = i a,z) – e a,z) Bound. cond.: m (z) = i a,z) – e a,z) n.J i (a,z) = n.J e (a,z) n.J i (a,z) = n.J e (a,z)

17 Simple geometry (contin.) From Ampere law: From Ampere law: B i = Integr. [G( a,z – z)J i (a,z)]dz B i = Integr. [G( a,z – z)J i (a,z)]dz Applying the Fourier and the inverse Fourier transformations one can come from potential to mag. field and v.a.v. Applying the Fourier and the inverse Fourier transformations one can come from potential to mag. field and v.a.v.

18 Some methods in modeling of current sources Current multipole expansion Current multipole expansion Current distribution with the minimum norm estimation Current distribution with the minimum norm estimation Covariance method (to extract the dc component of the measured modulated magnetic field data) Covariance method (to extract the dc component of the measured modulated magnetic field data)

19 Part of an axon or(C.Corallina intern. Cell): stimulus location and measuring points; intra-,extracell. curr.; m. field

20 The time evolution of magnetic field (vert. comp.) measured in 37 points above the C. corallina

21 Examples: Electrically stimulated peripheral nerve medianus. Simultaneus electrical and magnetic measurements. Electrically stimulated peripheral nerve medianus. Simultaneus electrical and magnetic measurements.

22 Sketch of experimental setup

23 Mag. field after stimulation at t=0, x=0: a) propagation, traces at y=30mm, x=285mm, 335mm, 385mm b) polarity reversal: x=335mm, y= -30mm and 30mm

24 Linear scan of the magnetic recordings along the y-axis (a) Elec. pot. rec. simult. at y=0 and x=335mm (b) Linear scan of the magnetic recordings along the y-axis (a) Elec. pot. rec. simult. at y=0 and x=335mm (b)

25 Isofield pattern in the x-y plane with 20 fT steps between two isofield lines. Crosses indicates the positins of input data points. The calculated equivalent current dipol is shown.

26 CT cross-section of the right upper arm at x=335mm as seen in the distal direction. The encircled dot at the edge of median nerve is the position of equivalent cur. dipole.

27 The model calculation of the cmpound action current

28 Results of peripheral nerve study: The point-like current dipole is a suitable model for a simple geometry as it is in this case. The point-like current dipole is a suitable model for a simple geometry as it is in this case. The localization of the nerve was within 2 mm (based on the CT). The localization of the nerve was within 2 mm (based on the CT).

29 Examples: Determination of epileptical focus in the case of focal epilepsy Determination of epileptical focus in the case of focal epilepsy

30 The flowchart of the current approach to localizing epileptic focus. A: Time domain waveforms showing epileptic spikes. B: Spectrogram showing focal increases of spectral power. C: Magnetic source image (MSI) showing an epileptic focus. The flowchart of the current approach to localizing epileptic focus. A: Time domain waveforms showing epileptic spikes. B: Spectrogram showing focal increases of spectral power. C: Magnetic source image (MSI) showing an epileptic focus.

31 Spread non-normal (epileptic) activity

32 The location of epileptical discharges

33 Examples: Study of functional stimulation Study of functional stimulation

34 FUNCTIONAL IMAGING: Evoked response to median nerve stimulation (not clear in the average of MEG sensors (the top overlay).The earliest peak is from the ACG. Followed by the events in the CS. The cerebellum response is seen as well.

35 Conclusions Magnetic measurements offer also in the world of living state valuable noninvasive information. Magnetic measurements offer also in the world of living state valuable noninvasive information. Both, multichannel SQUID system and SQUID microscope can be applied. The last option offers good spatial resolution. Both, multichannel SQUID system and SQUID microscope can be applied. The last option offers good spatial resolution. Results from magnetic measurements can be considered as complementary to the existing electric measurements in many cases. They can be combined with different imaging modalities. Results from magnetic measurements can be considered as complementary to the existing electric measurements in many cases. They can be combined with different imaging modalities. SQUID measurements provide direct information on the behavior of ionic currents. SQUID measurements provide direct information on the behavior of ionic currents. The highest spatial resolution. The highest spatial resolution.

36 Thank you for your attention!

37 Examples from the world of plants: a) Simple plant cell – Internodal cell of a) Simple plant cell – Internodal cell of green algae Chara corallina green algae Chara corallina

38 Our cell culture

39 Chara corallina internodal cell

40 Multi-SQUID measuring configuration (37 channels) - schematically

41 The isofield lines representation 3 particular time values (1.3s, 1.6s, 1.9s) after the stimulus 3 particular time values (1.3s, 1.6s, 1.9s) after the stimulus

42 The isof. representation (at 1.4s, 2.5s, 3.6s); model. calc. of current dipol and current density along the C.c. intern. c.

43 Measured and calculated AP and B

44 Some results Spreading of excitation along the cell: v ~ 4cm/s Spreading of excitation along the cell: v ~ 4cm/s Conductivity: i = m -1, ex = m -1 Conductivity: i = m -1, ex = m -1 Length of the depolarized area: l ~ 50 mm Length of the depolarized area: l ~ 50 mm Maximal intracellular current: I i = 1 A Maximal intracellular current: I i = 1 A

45 Examples from the world of plants: b) the influence of visible light on AP and on B in Chara corallina: The chemical nature of AP obtained from the non- invasive observation (by SQUID microscope) of the intracellular current under the influence of light

46 Protocol of the C.c. experiment with white light illumination Light OFF reference Light ON 10 min Light ON 20 min Light ON 60min AP as function of light exposure

47 The influence of ilumination on the measured B and AP of electrically stimulated C.c. internodal cell

48 Model which explains the illumination experiment in the context of 2nd messenger system [Ca 2+ ] c is altered under the influence of light/dark transitions 1987) [Ca 2+ ] c is altered under the influence of light/dark transitions AP can be described by an electrically stimulated release of Ca 2+ from internal store: AP can be described by an electrically stimulated release of Ca 2+ from internal store: -a) the voltage depend. synthesis/breakdown of the 2nd mesenger IP 3. -b) the joint action of IP 3 and Ca 2+ on the gating of the receptor channels, which conduct Ca 2+ release from internal stores. -c) modification: cells move excess Ca 2+ from the cytoplasm back into internal stores by an endogeneous Ca 2+ pump system (described by the Hill function. - Quantitative evaluation follows the Othmer model.

49 Simulated [Ca +2 ] c transients in response to a single electrical stimulation

50 Some results Assuming that the activation of the Cl - channels, that cause the depolarization, Assuming that the activation of the Cl - channels, that cause the depolarization, is the direct consequence of the change in [Ca 2+ ] c, the measurements quantitavely agree well with the model. is the direct consequence of the change in [Ca 2+ ] c, the measurements quantitavely agree well with the model.

51 Examples from the world of plants: c) the injury induced ionic currents in the plant organs - leaves in the higher developed plant Vicia faba, detected magnetically by the multichannel SQUID system.

52 Measuring setup

53 The position of injury (panel B cut)

54 Time evolution of magnetic field in all channels: panel A 15 min. before injury, panel B 1-16 min after injury, panel C time evolution of field RMS value, panels D end E isofield maps 10 min before and 1.5 min after injury.

55 Some results Some results All measured injured Vicia f. plants responded to All measured injured Vicia f. plants responded to injuries with detectable quasi-d.c. magnetic signals. injuries with detectable quasi-d.c. magnetic signals. Large injury leads to easily localizable current source Large injury leads to easily localizable current source of dipolar pattern. The characteristic time delay is of dipolar pattern. The characteristic time delay is about 10 min. about 10 min. No long-distance spreading of electrical activity was No long-distance spreading of electrical activity was generally observed. generally observed.

56 The flowchart of the current approach to localizing epileptic focus. A: Time domain waveforms showing epileptic spikes. B: Spectrogram showing focal increases of spectral power. C: Magnetic source image (MSI) showing an epileptic focus. The flowchart of the current approach to localizing epileptic focus. A: Time domain waveforms showing epileptic spikes. B: Spectrogram showing focal increases of spectral power. C: Magnetic source image (MSI) showing an epileptic focus.


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