A method for recording resistance changes non-invasively during
neuronal depolarization with a view to imaging brain activity with
Electrical Impedance Tomography
Ori Gilad
1,2
, Anthony Ghosh
1
, Dongin Oh
1
, and David S Holder
1
1
Departments of Clinical Neurophysiology and Medical Physics, University College, London, UK
2
Abramson Center for Medical Physics, Sakler Faculty of Exact Sciences, Tel-Aviv University, Tel-
Aviv, Israel
Abstract
Electrical Impedance Tomography (EIT) is a recently developed medical imaging method which has
the potential to produce images of fast neuronal depolarization in the brain. The principle is that
current remains in the extracellular space at rest but passes into the intracellular space during
depolarization through open ion channels. As current passes into the intracellular space across the
capacitance of cell membranes at higher frequencies, applied current needs to be below 100 Hz. A
method is presented for its measurement with subtraction of the contemporaneous evoked potentials
which occur in the same frequency band. Neuronal activity is evoked by stimulation and resistance
is recorded from the potentials resulting from injection of a constant current square wave at 1 Hz
with amplitude less than 25% of the threshold for stimulating neuronal activity. Potentials due to the
evoked activity and the injected square wave are removed by subtraction. The method was validated
with compound action potentials in crab walking leg nerve. Resistance changes of −0.85 ± 0.4 %
(mean±SD) occurred which decreased from −0.97±0.43 % to −0.46±0.16 % with spacing of
impedance current application electrodes from 2 to 8mm but did not vary significantly with applied
currents of 1–10μA. These tallied with biophysical modelling, and so were consistent with a genuine
physiological origin. This method appears to provide a reproducible and artefact free means for
recording resistance changes during neuronal activity which could lead to the long-term goal of
imaging of fast neural activity in the brain.
1. Introduction
Functional neuroimaging has improved greatly in the past two decades but the ‘holy grail’
would be to image neuronal activity non-invasively with a time and spatial resolution of about
1 ms and 1 mm respectively. There has recently been a resurgence of interest in this goal, and
the techniques of source modelling of the EEG (Baillet et al., 2001) and MEG (Hamalainen et
al., 1993; Baillet et al., 2001), their multimodality fusion with MRI (Dale et al., 2001), direct
mapping with MRI (Hagberg et al., 2006; Parkes et al., 2007) and diffuse optical tomography
Corresponding author: Dr Ori Gilad, Address: 29 Inbar Street, Zichron Ya’ackov 30900 Israel, Phone/fax: +972 775035037, Mobile:
+972 525909921, o.gilad@ucl.ac.uk.
Prof David S Holder, Dr Anthony Ghosh and Dr Dongin Oh: Address: Department of Medical Physics & Bioengineering, Malet Place
Engineering Building, University College London, Gower Street, London WC1E 6BT, UK
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Author Manuscript
J Neurosci Methods. Author manuscript; available in PMC 2010 May 30.
Published in final edited form as:
J Neurosci Methods. 2009 May 30; 180(1): 87. doi:10.1016/j.jneumeth.2009.03.012.
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(Syre et al., 2003; Steinbrink et al., 2005) have been investigated but currently cannot achieve
this goal. Electrical impedance Tomography (EIT) is a novel medical imaging method which
has the potential to achieve this revolutionary advance, by imaging electrical impedance
changes over milliseconds (Holder, 1987) which occur when neuronal ion channels open
during activity and the cell membrane resistivity decreases (Cole et al., 1939). The underlying
purpose of this work was to develop a method which could form the basis for tomographic
imaging of resistance changes during neuronal depolarization in the brain.
1.1. Introduction to Electrical Impedance Tomography and its potential use in imaging neural
activity
EIT provides information regarding the internal electrical properties inside a body based on
non-invasive voltage measurements on its boundary. Data acquisition is performed through an
array of electrodes which are attached to the boundary of the imaged object. Sequences of small
insensible currents, typically about of 1 mA, are injected into the object through these electrodes
and the corresponding boundary electric potentials are measured over a predefined set of
electrodes. The process is repeated for numerous different configurations of applied current.
The internal admittivity (or impedivity) distribution can be inferred using this boundary data.
EIT was first proposed as a medical imaging method by Henderson and Webster (1978) and
was initially applied to chest imaging (Brown et al., 1985; Brown et al., 1987; Metherall et al.,
1996). Potential applications of EIT for imaging brain function and pathology include detection
and monitoring of cerebral ischemia and haemorrhage (McArdle et al., 1988; Holder, 1992a;
Gibson et al., 2000; Romsauerova et al., 2006; McEwan et al., 2006), localisation of epileptic
foci (Bagshaw et al., 2003; Fabrizi et al., 2006), normal haemodynamic brain function
(Tidswell et al., 2001) and neuronal activity (Holder, 1987; Boone et al., 1995).
The principle by which EIT could image neuronal activity rests on the application of low
frequency currents below about 100 Hz which remain in the extracellular space under resting
conditions because they cannot enter significantly into the intracellular space across the
capacitative cell membrane. During the action potential or neuronal deploarization, the
membrane resistance diminishes by about 80x (Cole et al., 1939) so that the applied current
enters the intracellular space as well. Over a population of neurones, this will lead to a net
decrease in the resistance during coherent neuronal activity, such as cortical evoked responses,
as the intracellular space will provide additional conductive ions (Boone et al., 1995; Liston
et al., 2000; Liston, 2004).
An important advantage of this potential application of EIT over inverse source modelling of
the EEG or MEG is that this mechanism effectively rectifies the recording of ionic channel
opening – resistance across the membrane can only fall. In this way, impedance falls
irrespective of whether the neurotransmitter giving rise to the change is excitatory or inhibitory.
Neuroelectric or neuromagnetic signals cancel out when measured from a distance unless the
neuronal processes are spatially aligned, as in the dendritic tree of the pyramidal cells. The
rectified resistance change could capture activity in the entire depolarized tissue, regardless of
the spatial arrangement, so the opportunity to record the changes from a distance are much
greater.
In addition, the inverse solution for EIT is in principle unique for the idealised case where there
is complete and noise free knowledge of all boundary potentials with all possible current
injections and sufficient “smoothness” of the unknown conductivity profile (Calderón, 1980;
Isaacson et al., 1989) unlike that for inverse source modelling where a variety of constraints
of indeterminate validity must be employed to give a solution (Bleistein et al., 1977). However,
some constraints are also needed in EIT solutions in practice, where the inverse solution is ill-
posed and there are discrete measurements and instrumentation errors. Nevertheless, in
Gilad et al. Page 2
J Neurosci Methods. Author manuscript; available in PMC 2010 May 30.
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