J. Biomedical Science and Engineering, 2009, 2, 173-176
Published Online June 2009 in SciRes. http://www.scirp.org/journal/jbise
Functional brain imaging with use of a new and
powerful neuroimaging technique
Mohammad Karimi Moridani1
1Biomedical Engineering Department, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Email: Karimi.m@srbiau.ac.ir
Received 19 November 2008; revised 21 March 2009; accepted 16 April 2009.
Most of the information available on the human
brain came from subjects who had sustained
major head wounds, or who suffered from
various mental disorders. By determining the
extent of brain damage, and the nature of the
loss of function, it was possible to infer which
regions of the brain were responsible for which
function. With the development of the imaging
techniques of computerised tomography (CT)
and magnetic resonance imaging it was possi-
ble to be more specific as to the location of
damage in brain injured patients. The meas-
urement of the electrical signals on the scalp,
arising from the synchronous firing of the neu-
rons in response to a stimulus, known as elec-
troencephalography (EEG), opened up new
possibilities in studying brain function in nor-
mal subjects. However it was the advent of the
functional imaging modalities of positron emis-
sion tomography (PET), single photon emission
computed tomography (SPECT), functional
magnetic resonance imaging (fMRI), and mag-
netoencephalography (MEG) that led to a new
era in the study of brain function. In this paper
the mechanisms of the techniques mentioned
above are outlined, together with an assess-
ment of their strengths and weaknesses. Then
an introduction to the Metabolism and Blood
Flow in the Brain is given. This is followed by a
more detailed explanation of functional MRI and
how such experiments are perfo rmed.
Keywords: Functional Magnetic Resonance Imaging;
Brain Function; EEG
Functional brain imaging using MRI (functional MRI or
fMRI) has become a valuable tool for studying function/
structure relationships in the human brain in both normal
and clinical populations. This paper describes the
physiological changes associated brain with activity,
including changes in blood flow, volume, and oxygena-
tion. The latter of these, known as Blood Oxygenation
Level Depended (BOLD) contrast, is the most common
approach for functional MRI, but it is related to brain
activity via a variety of complex mechanisms. Blood
oxygenation level dependent functional MRI and near
infrared optical tomography have been widely used to
investigate hemodynamic responses to functional stimu-
lation in the human brain. The temporal hemodynamic
response shows an increased total hemoglobin concen-
tration, which indicates an increased cerebral blood
volume (CBV) during physiological activation. Blood
Oxygenation Level Dependent signal indirect measure of
neural activity. The signal variations induced by respira-
tion and cardiac motion decrease the statistical signifi-
cance in functional MRI data analysis. Physiological
noise can be estimated and removed adaptively using
signal projecting technique with the actual functional
signal preserved. We estimate and remove the physio-
logical noise from the magnitude images. This method is
a fully data-driven method, which can efficiently and
effectively reduce the overall signal fluctuation of func-
tional MRI data. Assumes that the MRI data recorded on
each trial are composed of a signal added with noise
Signal (random) is present on every trial, so it remains
constant through averaging and Noise randomly varies
across trials, so it decreases with averaging Thus, Sig-
nal-to-Noise Ratio (SNR) increases with averaging.
The brain imaging techniques that had been presented in
this paper all measure slightly different properties of the
brain as it carries out cognitive tasks. Because of th is the
techniques should be seen as complementary rather than
competitive. All of them have the potential to reveal
much about the function of the brain and they will no
doubt develop in clinical usefulness as more about the
underlying mechanisms of each are understood, and the
hardware becomes more available. A summary of the
174 M. K. Moridani / J. Biomedical Science and Engineering 2 (2009) 173-176
SciRes Copyright © 2009 JBiSE
strengths and weaknesses of the techniques is presented
in Table 1 [5].
2.1. SPECT and PET
The imaging modalities of single photon emission com-
puted tomography (SPECT) and positron emission to-
mography (PET) both involve the use of radioactive
nuclides either from natural or synthetic sources. Their
strength is in the fact that, since the radioactivity is in-
troduced, they can be used in tracer studies where a ra-
diopharmaceutical is selectively absorbed in a region of
the brain. The main aim of SPECT as used in brain im-
aging, is to measure the regional cerebral blood flow
(rCBF). The earliest experiments to measure cerebral
blood flow were performed in 1948 by Kety and
Schmidt [1]. They used nitrous oxide as an indicator in
the blood, measuring the differences between the arterial
input and venous outflow, from which the cellular up-
take could be determined.
This could only be used to m easure t he gl oba l cerebral
blood flow, and so in 1963 G l as s and Harper[2], building
on the work of Ingvar and Lassen, used the radioisotope
Xe-133, which emits gamma rays, to measure the re-
gional cerebral blood flow. The development of com-
puted tomography in the 1970’s allowed mapping of the
distribution of the radioisotopes in the brain, and led to
the technique now called SPECT [3].
2.2. EEG and MEG
Measuring the electrical signals from the brain has been
carried out for several decades [4], but it is only more
recently that attempts have been made to map electrical
and magnetic activity. The electroencephalogram is re-
corded using electrodes, usually silver coated with silver
chloride, attached to the scalp and kept in good electrical
contact using conductive electrode jelly. One or more ac-
tive sites may be monitored relative to a reference elec-
trode placed on an area of low response activity such as
the earlobe. The signals are of the order of 50 microvolts,
Table 1. Comparison of modalities for studying brain function.
Technique Resolution Advantages Disadvantages
SPECT 10 mm
Low cost
Available Invasive, Limited
PET 5 mm
Sensitive, Good resolu-
tion, Metabolic studies,
Receptor mapping
Invasive, Ve ry
EEG poor
Very low cost, Sleep
and operation moni-
Not an imaging
MEG 5 mm
High temporal resolu-
Very Expensive,
Limited resolution
for deep structures
fMRI 3 mm
Excellent resolution
Expensive, Limited
to activation stud-
MRS low
metabolic studies Expensive, Low
and so care must be taken to reduce interference from
external sources, eye movement and muscle activity.
Several characteristic frequencies are detected in the
human EEG. For example, when the subject is relaxed
the EEG consists mainly of frequen cies in the range 8 to
13 Hz, called alpha waves, but when the subject is more
alert the frequencies detected in the signal rise above
13Hz, called beta waves. Measurements of the EEG dur-
ing sleep have revealed periods of high frequency
waves, known as rapid eye movement (REM) sleep
which has been associated with dreaming [5].
MEG experiments are carried out in much the same
way as their EEG counterpart. Having identified the
peak of interest, the signals from all the detectors are
analysed to obtain a field map. From this map an attempt
can be made to ascertain the source of the si gna l by s ol v-
ing the inverse problem. Since the inverse problem has
no unique solution, assumptions need to be made, but
providing there are only a few activated sites, close to
the scalp then relatively accurate localization is possible,
giving a resolution of the order of a few millimeters.
MEG has the advantage over EEG that signal local-
isation is, to an extent, po ssible, and over PET and fMRI
in that it has excellent temporal resolution of neuronal
events. However MEG is costly and its ability to accu-
rately detect events in deeper brain structures is li mited.
2.3. Functional MRI and MRS
Since functional magnetic resonance imaging is the sub-
ject of this paper, little will be said in this section as to
the mechanisms and applications of the technique. The
purpose of this section is to compare fMRI to the other
modalities already mentioned, and also to consider the
related, but distinct technique of magnetic resonance
spectroscopy (MRS) [5].
During an fMRI experiment, the brain of the subject is
scanned repeatedly, usually using the fast imaging tech-
nique of echo planar imaging (EPI). The subject is re-
quired to carry out some task consisting of periods of
activity and periods of rest. During the activity, the MR
signal from the region of the brain involved in the task
normally increases due to the flow of oxygenated blood
into that region. Signal processing is then used to reveal
these regions. The main advantage of MRI over its clos-
est counterpart, PET, is that it requires no contrast agent
to be administered, and so is considerably safer. In addi-
tion, high quality anatomical images can be obtained in
the same session as the functional studies, giving greater
confidence as to the source of the activation. However,
the function that is mapped is ba sed on bl o od f l ow, and i t
is not yet possible to directly map neuroreceptors as PET
can. The technique is relatively expensive, although
comparable with PET, however since many hospitals
now have an MRI scanner the availability of the tech-
nique is more widespread [5].
M. K. Moridani et al. / J. Biomedical Science and Engineering 2 (2009) 173-176 175
SciRes Copyright © 2009 JBiSE
FMRI is limited to activation studies, which it per-
forms with good spatial resolution. If the resolution is
reduced somewhat then it is also possible to carry out
spectroscopy, which is chemically specific, and can fol-
low many metabolic processes. Since fMRS can give the
rate of glucose utilisation, it provides useful additional
information to the blood flow and oxygenation measure-
ments from fMRI, in the st udy of brai n metabolis m [5].
The biochemical reactions that transmit neural informa-
tion via action potentials and neurotransmitters, all re-
quire energy.
This energy is provided in the form of ATP, which in
turn is produced from glucose by oxidative phosphoryla-
tion and the Kreb’s cycle (Figure 1) [5].
As ATP is hydrolysed to ADP, energy is given up,
which can be used to drive biochemical reactions that
require free energy. The production of ATP from ADP by
oxidative phosphorylation is governed by demand, so
that the energy reserves are kept constant. That is to say,
the rate of this reaction depends mainly on the level of
ADP present.
This means that the rate of oxygen consumption by
oxidative phosphorylation is a good measure of the rate
of use of energy in that area [5].
The oxygen required by metab olism is supplied in the
blood. Since oxygen is not very soluble in water, the
blood contains a protein that oxygen can bind to, called
haemoglobin. The important part of the haemoglobin
molecule is an iron atom, bound in an organic structure,
and it is this iron atom which gives blood it’s colour.
When an oxygen molecule binds to haemoglobin, it is
said to be oxyhaemoglobin, and when no oxygen is
bound it is called deoxyhaemoglobin.
To keep up with the high energy demand of the brain,
oxygen delivery and blood flow to this organ is quite
large. Although the brain’s weight is only 2% of the
body’s, its oxygen consumption rate is 20% of the
body’s and blood flow 15%. The blood flow to the grey
matter, which is a synapse rich area, is about 10 times
Figure 1. Overview of the aerobic metabolism of glucose to
ATP following the Kreb’s cycle.
that to the white matter per unit volume. Regulation of
the regional blood flow is poorly understood, but it is
known that localised neural activity results in a rapid
selective increase in blood flow to that area [5].
Since regional blood flow is closely related to neural
activity, measurement of the rCBF is useful in studying
brain function. It is possible to measure blood perfusion
with MRI, using techniques similar to those mentioned.
However there is another, more sensitive, contrast
mechanism which depends on the blood oxygenation
level, known as blood oxygen level dependent (BOLD)
contrast. The mechanisms behind the BOLD contrast are
still to be determined, however there are hypotheses to
explain the observed signal changes.
Deoxyhaemoglobin is a paramagnetic molecule whereas
oxyhaemoglobin is diamagnetic. The presence of de-
oxyhaemoglobin in a blood vessel causes a suscep tibility
difference between the vessel and its surrounding tis-
sue.Such susceptibility differences cause dephasing of
the MR proton signal [6],leading to a reduction in the
value of T2*. In a T2* weighted imaging experiment,the
presence of deoxyhaemoglobin in the blood vessels [7,
8]causes a darkening of the image in those voxels con-
taining vessels. Since oxyhaemoglobin is diamagnetic
and does not produce the same dephasing, changes in
oxygenation of the blood can be observed as the signal
changes in T2*weighted images [5].
It would be expected that upon neural activity, since
oxygen consumption is increased, that the level of de-
oxyhaemoglobin in the blood would also increase, and
the MR signal would decrease. However what is ob-
served is an increase in signal, implying a decrease in
deoxyhaemoglobin. This is because upon neural activity,
as well as the slight increase in oxygen extraction from
the blood, there is a much larger increase in cerebral
blood flow, bringing with it more oxyhaemoglobin (Fig-
ure 2). Thus the bulk effect upon neural activity is a
regional decrease in paramagnetic deoxyhaemoglobin,
and an increase in signal [5].
The study of these mechanisms are helped by results
from PET and near-infrared spectroscopy (NIRS) studies.
PET has shown that changes in cerebral blood flow and
cerebral blood volume upon activation, are not accom-
panied by any significant increase in tissue oxygen con-
sumption [9].
NIRS can measure the changes in concentrations of
oxy- and deoxyhaemoglobin, by looking at the absor-
bency at different frequencies. Such studies have shown
an increase in oxyhaemoglobin, and a decrease deoxy-
haemoglobin upon activation. An increase in the total
amount of haemoglobin is also observed, reflecting the
increase in blood volume upon activation [2].
176 M. K. Moridani / J. Biomedical Science and Engineering 2 (2009) 173-176
SciRes Copyright © 2009
Figure 2. Upon activation, oxygen is extracted by the cells,
thereby increasing the level of deoxyhaemoglobin in the blood.
This is compensated for by an increase in blood flow in the
vicinity of the active cells, leading to a net increase in oxy-
Functional magnetic resonance imaging can accurately
represent cerebral topography, cortical venous structures
and underlying lesions. Functional activation appears to
accurately localize appropriate cortical areas and these
studies are feasible in the presence of local pathology. It
is extremely useful in presurgical planning as well as
assessment of operability. Intra-operatively, it shows a
great promise in being able to define the exact location
and extent of lesions with respect to surrounding func-
tional cortex.
Functional MRI is a new and powerful neuroimaging
technique that can create an anatomical and functional
model of an individual patient's brain. The concurrent 3-D
rendering of cerebral topography, cortical veins and re-
lated pathology gives an unprecedented display of critical
relational anatomy. Since stereotaxy means simply the
three dimensional arrangement of objects, then fMRI may
be the ultimate stereotactic system. It allows us to see
through the scalp and cortex into subcortical areas which
are not visually apparent. It accurately predicts cortical
gyral and venous anatomy as well as the subcortical loca-
tion and extent of lesions. But most importantly, it is ca-
pable of mapping specific cortical functions to anatomical
regions thereby combining form and function.
We have described the physiological bases of func-
tional MRI and introduced a physiologically relevant
model of the vascular response to fMRI. We described
the major optimization goals in fMRI and several fMRI
acquisition approaches. Substantial progress is being
made to reduce artifacts in fMRI as well as to improve
the measurement of alternate physiological phenomena
using MRI.
The spatial activation pattern of changes indeoxyhe-
moglobin concentration is consistent with the BOLD
signal map. The patterns of oxy-and deoxyhemoglobin
concentrations are very similar to one another. The tem-
poral hemodynamic response shows an increased total
hemoglobin concentration, which indicates an increment
of CBV during physiological activation. It has now been
firmly established that magnetic resonance imaging can
be used to map brain function.
The main impetus of research and development of the
technique, needs to be directed in several areas if fMRI
is to become more than ’colour phrenology’, intriguing
in its results yet having little clinical value. The mecha-
nisms behind the BOLD effect need to be better under-
stood, as does the physiological basis of the observed
blood flow and oxygenation changes. The combination
of the functional imaging modalities needs attention,
since it is unlikely that any one method will provide the
full picture. Finally, robust and simple techniques for
data analysis need to be developed, allowing those who
do not specialise in fMRI, to carry out experiments and
interpret results.
[1] S. S. Kety and C. F. Schmidt, (1948) The nitrous oxide
method for the quantitative determination of cerebral
blood flow in man: Theory, procedure and normal values,
J. Clin. Invest. 27, 476-483.
[2] H. I. Glass and A. M. Harper, (1963) Measurement of
regional blood flow in cerebral cortex of man through in-
tact skull, Br. Med. J., 1, 593.
[3] D. E. Kuhl and R. Q. Edwards, (1963) Image separation
radioisotope scanning, Radiology, 80, 653-661.
[4] H. Berger, (1929) Über das elektrenkephalogramm des
menschen, Arch. Psychiatr Nervenkr, 87, 527-570.
[5] Veopen, (1995) Magnetic resonance imaging of brain
function, Magn. Reson. Med., 22, 149-166.
[6] K. R. Thulborn, J. C. Waterton, P. M. Matthews, and G.
K. Radda, (1982) Oxygen dependence of the transverse
relaxation time of water protons in whole blood at high
field, Biochim. Biophys. Acta., 714, 265-270.
[7] S. Ogawa, T. M. Lee, A. S. Nay ak, and P. Glynn, (1990)
Oxygenation-sensitive contrast in magnetic resonance im-
age of rodent brain at high magnetic fields, Magn. Reson.
Med., 14, 68-78.
[8] S. Ogawa and T. M. Lee, (1990) Magnetic resonance
imaging of blood vessels at high fields: In vivo and in vi-
tro measurements and image simulation, Magn. Reson.
Med., 16, 9-18.
[9] P. T. Fox, M. E. Raichle, M. A. Mintun, and C. Dence,
(1988) Nonoxidative glucose consumption during physi-
ologic neural activity, Science, 241, 462-464.