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Peter A. Bandettini Unit on Functional Imaging Methods Laboratory of Brain and Cognition &

Neuronal Current Imaging. (GRC: In vivo Magnetic Resonance 2004). Peter A. Bandettini Unit on Functional Imaging Methods Laboratory of Brain and Cognition & Functional MRI Facility. Primary researchers and collaborators:. Natalia Petridou Jerzy Bodurka Peter A. Bandettini

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Peter A. Bandettini Unit on Functional Imaging Methods Laboratory of Brain and Cognition &

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  1. Neuronal Current Imaging (GRC: In vivo Magnetic Resonance 2004) Peter A. Bandettini Unit on Functional Imaging Methods Laboratory of Brain and Cognition & Functional MRI Facility

  2. Primary researchers and collaborators: Natalia Petridou Jerzy Bodurka Peter A. Bandettini Unit on Functional Imaging Methods / Functional MRI Facility, NIMH, NIH Afonso C. Silva Laboratory of Functional and Molecular Imaging, NINDS, NIH Dietmar Plenz Unit of Neural Network Physiology, NIMH, NIH

  3. Related Papers M. L. Joy, G. C. Scott, R. M, Henkelman, In vivo detection of applied electric currents by magnetic resonance imaging. Magn Reson Imaging 7: 89-94, (1989). G. C. Scott, M. L. Joy, R. L. Armstrong, R. M. Henkelman, RF current density imaging homogeneous media. Magn. Reson. Med. 28: 186-201, (1992). M. Singh, Sensitivity of MR phase shift to detect evoked neuromagnetic fields inside the head. IEEE Transactions on Nuclear Science. 41: 349-351, (1994). J. Bodurka, P. A. Bandettini. Current induced magnetic resonance phase imaging. Journal of Magnetic Resonance, 137: 265-271, (1999). H. Kamei, J, Iramina, K. Yoshikawa, S. Ueno, Neuronal current distribution imaging using MR. IEEE Trans. On Magnetics, 35: 4109-4111, (1999) J. Bodurka, P. A. Bandettini. Toward direct mapping of neuronal activity: MRI detection of ultra weak transient magnetic field changes. Magn. Reson. Med. 47: 1052-1058, (2002). D. Konn, P. Gowland, R. Bowtell, MRI detection of weak magnetic fields due to an extended current dipole in a conducting sphere: a model for direct detection of neuronal currents in the brain. Magn. Reson. Med. 50: 40-49, (2003). J. Xiong, P. T. Fox, J.-H. Gao, Direct MRI Mapping of neuronal activity. Human Brain Mapping, 20: 41-49, (2003) R. Chu, J. A. de Zwart, P. van Gelderen, M. Fukunaga, P. Kellman, T. Hollroyd, J. Duyn. Hunting for neuonal currents: absence of rapid MRI signal changes during visual evoked response. NeuroImage (in press).

  4. Neuronal Dynamics… 100 fT at on surface of skull J.P. Wikswo Jr et al. J Clin Neuronphy 8(2): 170-188, 1991

  5. 0 0 d2V Q B= = r2 4 16 Magnetic field associated with single dendrite Single dendrite having a diameter d, and length L behaves like a conductor with conductivity . Resistance is R=V/I, where R=4L/(d2). From Biot-Savart: r2 by substituting d = 4m,   0.25 -1 m-1, V = 10mV and r = 4cm (typical measurement distance when using MEG) the resulting value measured at the surface of a skull is: B0.002 fT J. Bodurka, P. A. Bandettini. Toward direct mapping of neuronal activity: MRI detection of ultra weak transient magnetic field changes. Magn. Reson. Med. 47: 1052-1058, (2002).

  6. Magnetic field associated with bundle of dendrites Because BMEG=100fTis measured by MEG on the scalp, at least50,000 neurons(0.002 fT x 50,000 = 100 fT), must coherently act to generate such field. These bundles of neurons produce, within a typical voxel, 1 mm x 1 mm x 1 mm, a field of order: BMRI0.2nT

  7. 1 0.8 0.6 0.4 0.2 0.04 0.05 0.1 0.15 0.2 0.25 0.3 0.03 0.02 0.01 0.7 0.05 0.1 0.15 0.2 0.25 0.3 0.6 0.5 0.4 0.3 0.2 0.1 0.05 0.15 0.2 0.25 0.3 0.1 ∆B = 100fT * (4cm/x)2 ∆B (nT) ∆  = ∆B ∆ (Hz) ∆ (deg) ∆= ∆ TE  Distance from source (cm)

  8. Is 0.2 nT detectable?

  9. Current Phantom Experiment wire Z wire X

  10. B0 calculated Bc ||B0 Measurement 70 A current   200 Single shot GE EPI Correlation image J. Bodurka, P. A. Bandettini. Toward direct mapping of neuronal activity: MRI detection of ultra weak transient magnetic field changes, Magn. Reson. Med. 47: 1052-1058, (2002).

  11. Z X 2 1.5 1 BR<2nT 0.5 0.004 0.006 0.008 0.01 0.002 BR<0.2nT ∆B (nT) Distance (m) J. Bodurka, P. A. Bandettini. Toward direct mapping of neuronal activity: MRI detection of ultra weak transient magnetic field changes, Magn. Reson. Med. 47: 1052-1058, (2002).

  12. Main issues/obstacles: • The effect is small • Artifactual changes (respiration, cardiac) are order of mag larger • The effect itself depends on geometry (phase/magnitude) • The timing of the effect is variable • BOLD still ubiquitous…

  13. Human Respiration 400 BR10 nT o B =90 DF B0 TIME=110 s 200 3 2x10 00 0.0 0.1 0.2 0.3 0.4 0.5 frequency ( Hz )

  14. One strategy for removing low frequency changes… 900 GE Slice selection Spatial encoding 900 1800 SE Slice selection Spatial encoding

  15. Experiment (human respiration) Spectral images GE TE=55ms SE TE=55ms  TR =1.0 sec SE GE GE spoiled M

  16. S1 S2 S1: Optimal temporal position for 180 pulse; net phase shift induce by EMF>0 S1: For this 180 pulse temporal position net phase shift induce by EMF is close to zero 20ms

  17. The use of spin-echo to “tune” to transients.. M. Singh, Sensitivity of MR phase shift to detect evoked neuromagnetic fields inside the head. IEEE Transactions on Nuclear Science. 41: 349-351, (1994).

  18. What should we be detecting? Phase or Magnitude?

  19. ∆ phase ∆ magnitude, ?∆ phase ? ∆ magnitude, ? ∆ phase Phase vs. Magnitude

  20. In Vitro Studies

  21. Cortex Basal Ganglia 100 mm Plenz, D. et al. Neurosci 70(4): 861-924, 1996 in vitro model Organotypic (no blood supply or hemoglobin traces) sections of newborn-rat somato-sensory Cortex, or somato-sensory Cortex & Basal Ganglia • Size: in-plane:~1-2mm2, thickness: 60-100m • Neuronal Population: 10,000-100,000 • Spontaneous synchronized activity < 2Hz • Epileptiform activity • Spontaneous beta freq. activity (20-30Hz) • Network Activity Range: ~ 0.5-15V

  22. ~100ms Transient Event Multi-Electrode Array EEG recording Multi-Electrode Array (MEA) EEG Recording 1 kHz sampling rate, 20 minutes 8x8 electrode configuration

  23. in vitro MR protocol Imaging (3T) NMR (7T) • Spin-Echo EchoPlanar Imaging • free induction decay (FID) • acquisition SE EPI image FID • voxel size: ~3x3x3 mm • Sampling Rate :1 Hz (TR: 1sec) • TE: 60 ms • Readout :44 ms • slab size: ~2x10x1mm • Sampling Rate :10 Hz (TR: 100ms) • TE : 30 ms • Readout : 41 ms

  24. in vitro MR experiment design Imaging (3T) NMR (7T) Six Experiments two conditions per experiment Six Experiments two conditions per experiment Active : 10 min (600 images) neuronal activity present Active : ~17 min (10,000 images) neuronal activity present Inactive : ~17 min (10,000 images) neuronal activity terminated via TTX administration Inactive : 10 min (600 images) neuronal activity terminated via TTX administration Pre- and Post- MR scan electrical recordings

  25. 7 Tesla data Power decrease between PRE & TTX EEG : ~ 81% Decrease between PRE & TTX MR phase: ~ 70% Decrease between PRE & TTX MR magnitude: ~ 8%

  26. 1: culture 2: ACSF ACSF Culture C C A A B B FSE image Hz Hz 0.15Hz map 1 2 3 Tesla data Active condition: black line Inactive condition: red line A: 0.15 Hz activity, on/off frequency B: activity C: scanner noise (cooling-pump)

  27. Strategies for Detection in Humans • Time shifted sampling • Under sampling

  28. Time shifted sampling M. Singh, Sensitivity of MR phase shift to detect evoked neuromagnetic fields inside the head. IEEE Transactions on Nuclear Science. 41: 349-351, (1994).

  29. J. Xiong, P. T. Fox, J.-H. Gao, Direct MRI Mapping of neuronal activity. Human Brain Mapping, 20: 41-49, (2003)

  30. J. Xiong, P. T. Fox, J.-H. Gao, Direct MRI Mapping of neuronal activity. Human Brain Mapping, 20: 41-49, (2003)

  31. R. Chu, J. A. de Zwart, P. van Gelderen, M. Fukunaga, P. Kellman, T. Hollroyd, J. Duyn. Hunting for neuonal currents: absence of rapid MRI signal changes during visual evoked response. NeuroImage, (in press).

  32. Undersampling 8 Hz alternating checkerboard MEG Photodiode

  33. Undersampling Alternating Checkerboard Frequency TR

  34. Comparison of phase and magnitude of the MR signal in measuring neuronal activity [for Petes’ sake1,2] James M. Kilner, Klaas E. Stephan, Oliver Josephs, Karl J. Friston Wellcome Department of Imaging Neuroscience, 12 Queen Square, London Phase BOLD Mag

  35. Closed Open Phase 0.12Hz Magnitude 0.12 Hz Power spectra Eyes closed Eyes open 0.5 Hz 0.5 Hz

  36. Other Methods?? The principle and application of the Lorentz Effect Imaging Song et al ISMRM 2000, p. 54

  37. Lorentz Force i F B F

  38. Lorentz Force i F B F -G G

  39. Experimental Setup: Phantom Study Bo 0.1 – 0.5 V 1 k MRI Scanner Trigger Pulse

  40. Rapid-flashing checkerboard Image Acquisition encoding decoding Schematic illustration of the data acquisition. A B rest active Optic Chiasm EPI images without visual stimuli (A) and with visual stimuli (B). Preliminary Experiment on the Optical Nerve

  41. Caution… • Need to rule out BOLD or other mechanisms • Noise is larger than effect • MR sampling rate is slow • Neuronal activation timing is variable and unspecified • Models describing spatial distribution of ∆B across spatial scales are crude…could be off by up to an order of magnitude. • We are understanding more about precise effects of stimuli. • “Transient-tuned” pulse sequences (spin-echo, multi-echo) • Sensitivity and/or resolution improvements • Lower field strengths? (effect not Bo dependent) • Simultaneous electrophysiology – animal models? • Synchronization improvements. • Again..models describing spatial distribution of ∆B across spatial scales are crude…could be off by up to an order of magnitude. Despair… Hope…

  42. MR Simulations based on EEG Assuming 100,000 neurons * 1.5nA per neuron EEG re-sampled using: TR: 1sec TE: 60ms (spin-echo) Readout :44ms Field calculations with voxel volume: 27mm3 Bo : 3T ΔB (nTesla) dB= Bneuronal(from EEG)dVdt; t:82ms, V=27mm3 EEG re-sampled using: TR: 100ms TE:30ms Readout : 41ms (entire FID) Field calculations with voxel volume: 20mm3 Bo : 7T ΔB (nTesla) dB= Bneuronal(from EEG)dVdt; t:71ms, V=20mm3

  43. Simulated MR spectrum calculated using sliding window FFT. Simulation based on previously shown electrical recording data

  44. dB=µo It (neuronal from EEG) V / 2 π D dV dt ; t: (TE+Readout) ms, V=(voxel volume)mm3 Where: V=sqrt(x2+y2+z2), where x,y,z are the voxel dimensions D= the diameter of the culture (0.5 mm) µo= magnetic permeability of free space It = the current produced from the neuronal network at a given point in time, t this is calculated from the EEG as follows: maximum current possible for the given culture (here 100,000 neurons * 1.5nA per neuron - reference: Nicholls JG, Martin AR, Wallace BG. From Neuron to Brain. 3rd ed. Sinauer, 1992.) multiplied by the following weighting function ( normalized EEG): resulting fields are consistent with those expected (checked with Dietmar and literature – will give you ref. papers)

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