# Presentation: 483726

## Peter A. Bandettini

Unit on Functional Imaging Methods
Laboratory of Brain and Cognition
&
Functional MRI Facility

- Unit on Functional Imaging Methods
- Laboratory of Brain and Cognition
- &
- Functional MRI Facility

**Neuronal Current Imaging**

***(GRC: In vivo Magnetic Resonance 2004)***

## 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

**Primary researchers and collaborators:**

## Related Papers

**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).**

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

**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)**

**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).**

**H. Kamei, J, Iramina, K. Yoshikawa, S. Ueno, ***Neuronal current distribution imaging using MR.*** IEEE Trans. On Magnetics, 35: 4109-4111, (1999)**

**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).**

**J. Bodurka, P. A. Bandettini. ***Current induced magnetic resonance phase imaging.*** Journal of Magnetic Resonance, 137: 265-271, (1999).**

**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).**

## Neuronal Dynamics...

**J.P. Wikswo Jr et al.*****  J Clin Neuronphy *****8(2): 170-188, 1991**

- 100 fT at on surface of skull**  **

## 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:

**r****2**

- 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****).**

## Magnetic field associated with 

**B****MRI** ******0.2nT**

- Magnetic field associated with
- bundle of dendrites

## Distance from source (cm)

**Distance from source (cm)**

**∆****B (nT)**

**∆******** ****(Hz)**

**∆******** ****(deg)**

**∆****B = 100fT * (4cm/x)****2**

**∆ ******** ****= ********∆B**

**∆********= ∆ ********TE**************** **

## Is 0.2 nT detectable?

## wire

**wire**

**wire**

- X

- Z

- Current Phantom Experiment

## 

**Measurement**

**Correlation image**

**Single shot GE EPI**

- ****

- 70 A current

****** ****20****0**

**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****). **

## 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****). **

**Distance (m)**

**∆****B (nT)**

## 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...**

## Human Respiration

## GE

**Slice selection**

**Spatial encoding**

**Slice selection**

**Spatial encoding**

**GE**

**SE**

**90****0**

**90****0**

**180****0**

**One strategy for removing low frequency changes...**

## 

**GE**
**spoiled**

- Spectral images

**   ****TR =1.0 sec**

**    ****GE**

**   ****SE**

** ****GE**
**TE=55ms**

** ****SE**
**TE=55ms**

- ****

- M

## 20ms

******20ms**

## 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)****.**

**The use of spin-echo to “tune” to transients..**

## What should we be detecting?

**Phase or Magnitude?**

## Phase vs. Magnitude

## In Vitro Studies

## in vitro model

**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

## Slide 22

## Multi-Electrode Array EEG recording

- Multi-Electrode Array  (MEA)
- EEG Recording
- 1 kHz sampling rate, 20 minutes
- 8x8 electrode configuration

**Multi-Electrode Array EEG recording**

## in vitro MR protocol

**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

## Six Experiments

- two conditions per experiment

**in vitro MR experiment design***** ***

- _Active_ : 10 min (600 images) neuronal activity present

- _Inactive_ : 10 min (600 images) neuronal activity terminated via TTX administration

- Imaging (3T)

- NMR (7T)

- two conditions per experiment

- _Active_ : ~17 min (10,000 images) neuronal activity present

- _Inactive_ : ~17 min (10,000 images) neuronal activity terminated via TTX administration

*Pre- and Post- MR scan electrical recordings*

## 7 Tesla data

**7 Tesla data**

**Power decrease between PRE & TTX EEG : ~ 81%**

**Decrease between PRE & TTX MR phase: ~ 70%**

**Decrease between PRE & TTX MR magnitude: ~ 8%**

## 3 Tesla data

**3 Tesla data**

**A: 0.15 Hz activity, on/off frequency**
**B: activity**
**C: scanner noise (cooling-pump)**

_**Active**_** condition: black line**
_**Inactive**_** condition: red line**

## Strategies for Detection in Humans

**Time shifted sampling**
**Under sampling**

## Time shifted sampling

**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)****.**

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

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

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

**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).**

## Undersampling

**Photodiode**

**MEG**

**8 Hz alternating **
**checkerboard**

**Undersampling**

## Undersampling

**TR**

**Alternating Checkerboard Frequency**

**Undersampling**

## BOLD

**Comparison of phase and magnitude of the MR signal in measuring neuronal activity [for Petes’ sake****1,2****]**
**James M. Kilner, Klaas E. Stephan, Oliver Josephs, Karl J. Friston**
- Wellcome Department of Imaging Neuroscience, 12 Queen Square, London

**BOLD**

**Phase**

**Mag**

## Power spectra

- 0.5 Hz

- 0.5 Hz

**Eyes closed**

**Eyes open**

- Phase 0.12Hz

- Closed

- Open

- Magnitude 0.12 Hz

## Other Methods??

- the Lorentz Effect Imaging

- Song et al ISMRM 2000, p. 54

**Other Methods??**

## i

***i***

***F***

***F***

***B***

- Lorentz Force

## i

***i***

***F***

***F***

***B***

- Lorentz Force

- -G

- G

## Experimental Setup: Phantom Study

**Bo**

- 1 k

- 0.1 – 0.5 V

- MRI Scanner Trigger Pulse

## Slide 41

## Preliminary Experiment on the Optical Nerve

## 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 B****o**** 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.**

**Caution...**

**Despair...**

**Hope...**

## MR Simulations based on EEG

- EEG re-sampled using:
- TR: 1sec
- TE: 60ms (spin-echo)
- Readout :44ms
- Field calculations with
- voxel volume: 27mm3
- Bo : 3T

- EEG re-sampled using:
- TR: 100ms
- TE:30ms
- Readout : 41ms
- (entire FID)
- Field calculations with
- voxel volume: 20mm3
- Bo : 7T

**MR Simulations based on EEG**

*d**B=****  B**neuronal(from EEG)** dVdt; t:82ms, V=27mm**3**  *

**Δ****B (nTesla)**

**Δ****B (nTesla)**

*dB=****  B**neuronal(from EEG)** dVdt; t:71ms, V=20mm**3**  *

*Assuming 100,000 neurons * 1.5nA per neuron*

## Slide 45

## dB=   μo It (neuronal from EEG)  V / 2 π D     dV dt ; t: (TE+Readout) ms, V=(voxel volume)mm3  

*Where:*
*V=sqrt(x**2**+y**2**+z**2**), where x,y,z are the voxel dimensions*
*D= the diameter of the culture (0.5 mm)*
*μo= magnetic permeability of free space*
*I**t** = 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)*