BOLD

BOLD imaging uses magnetic fields to measure this change in oxygenation. This signal is
often used to infer the activity of brain cells and, thus, which brain areas are involved in a
particular task.
This allows us to investigate complex brain functions such as cognition and consciousness.
Another terrific thing about BOLD is that it measures from the whole brain more or less
simultaneously.

The central limitation is that BOLD is not a direct readout of brain activity, but an indirect
measurement that relies on the change in blood oxygen. Blood oxygenation changes on the
order of seconds. This is very slow relative to the speed of brain activity, which can change
every few milliseconds – that’s one thousandth of one second. Therefore, BOLD cannot
detect rapid changes in neuronal activity, and there is debate amongst scientists about what
speeds of imaging are required to extract meaningful information about the brain.
A second limitation is the resolution – our current techniques allow us to measure BOLD
signals at a millimeter range, but there are thousands, maybe millions of brain cells in this
small space. So BOLD can only measure the collective activity of a large number of neurons.

Blood flow in the brain is highly locally controlled in response to oxygen and carbon
dioxide tension of cortical tissue. When a specific region of the cortex increases its
activity in response to a task, the extraction fraction of oxygen from the local capillaries
leads to an initial drop in oxygenated hemoglobin (oxyHb) and an increase in local
carbon dioxide (CO2) and deoxygenated hemoglobin (deoxyHb). Following a lag of 2-6
seconds, cerebral blood flow (CBF) increases, delivering a surplus of oxygenated
hemoglobin, washing away deoxyhemoglobin 1,2. It is this large rebound in local tissue
oxygenation which is imaged. 

The reason fMRI is able to detect this change is due to a fundamental difference in the
paramagnetic properties of oxyHb and deoxyHb. 

Deoxygenated hemoglobin is paramagnetic whereas oxygenated hemoglobin is not,

and therefore the former will cause local dephasing of protons, and thus reduce the
returned signal from the tissues in the immediate vicinity. Heavily T2* weighted
sequences are used to detect this change, which is in the order of 1-5% 2.

There are a number of limitations of BOLD imaging (and all other techniques which
image function by CBF):

 cerebral blood flow (CBF) is only an indirect marker of activity, rather than
directly visualizing active cortex
 the smallest unit of brain that is able to have its blood flow individually regulated
is in the order of millimeters in diameter
 CBF increases in response to increased activity and there is a 2-6 second lag
What's the Difference Between MRI and FMRI?

FMRI scans use the same basic principles of atomic physics as MRI scans, but MRI scans
image anatomical structure whereas FMRI image metabolic function.  Thus, the images
generated by MRI scans are like three dimensional pictures of anatomic structure.  The
images generated by FMRI scans are images of metabolic activity within these anatomic
structures.

When one causes nuclei to precess their spin will cause them to align themselves with the
magnetic field.  Similarly, all the negative spin atoms align themselves downward on the Z
axis (towards the feet of the subject), and all the positive atoms align upward on the Z axis
(towards the subject's head).   Each atom with a positive spin cancels out (renders
undetectable) an atom with a negative spin.  There remain, however, a few atoms that do
not cancel one another out.  At room temperature, there are always more positive spin
atoms than negative spin atoms.  These unmatched atoms are the important ones for MRI
and FMRI.

Positive spin atoms are in a low energy state.  The atoms achieve and equilibrium
magnetization value along the direction of the magnetic field, i.e., the Z axis.   By introducing
a pulse of magnetic energy perpendicular to the main magnetic field in the form of a radio
frequency pulse that is specific to the type of atom (usually hydrogen), the MRI machine
causes the unmatched atoms to resonate.  Resonating atoms absorb the radio energy as a
photon and go to the higher energy state, i.e., they become negative spin atoms and the
equilibrium magnetization value for the Z axis goes to 0.  When the pulse is stopped, these
atoms release their photon energy and "relax" back into the lower energy positive spin
state.   The signal that the MRI machine detects is the photon energy emitted by these
unmatched atoms as they make a transition from the higher energy state to the lower energy
state after the radio frequency pulse. The amount of time it takes for for the atoms to return
to their equilibrium value is called the "spin lattice relaxation time" or (T1).  T1 is, thus, a
measure of the half-life of inverted spins.

If the technician uses the gradient magnets inside the MRI to alter the local net
magnetization so that it is in the XY plane (cutting a very thin slice across the patient), the
local net magetization rotates the Z axis (takes on positive and negative X and Y values) at a
frequency called the Larmor frequency.  The Lamor frequency equals the frequency of the
photon which would cause a transition between the two energy levels of the nucleic spin.  
By again introducing a pulse of magnetic energy in the form of a radio frequency pulse that
is specific to the type of atom, the MRI machine causes the unmatched atoms to resonate. 
The resonating atoms absorb the radio energy and go to the higher energy state, i.e., they
become negative spin atoms relative to the XY axis (the transverse axis).  The amount of
time it takes for for the atoms to return to their equilibrium magnetization value along  XY
axis (transverse axis) is called the "spin-spin relaxation time" or T2.  T2 is, as a result,
measures the rate of change of spin phases. Whereas a typical T1 (spin lattice relaxation
time) is approximately 1 second, the T2 (spin-spin relaxation time) is usually less than
100ms. This difference in the relative times is what makes T2 better suited than T1 for
functional metabolic imaging.

I’ve been reading about how MRI works, specifically, how BOLD images are taken, the
physics behind it and the advantages and limitations of that technique.