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Thinking
Inside
the
Voxel
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Mark Does is interested in what’s
/really/ going on inside that 1 millimeter cube of MRI space
called a “voxel.”* A voxel is like a 3-D pixel in a Magnetic
Resonance Imaging (MRI) scan and is the smallest spatial unit an
MRI scanner is able to resolve.
“MRI was developed only 30 years ago,” the assistant professor
of biomedical engineering at Vanderbilt said. “While it has
become a mainstay in clinical radiology, it is rich in
capabilities, and we are far from utilizing it to its full
potential.”
The MRI imaging modality is very good at distinguishing |
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between
different types of soft body tissues, but Does
wants to get a closer look at what’s happening to the cells,
themselves.
Does has won a
National Science Foundation (NSF) CAREER award for his research to
develop MRI techniques that can tease out information about bodily
tissues at the cellular, sub-voxel level.
His techniques will have immediate application to diagnosis and
treatment of multiple sclerosis but ultimately will be applicable to
a variety of other tissues, as well.
Multiple sclerosis involves degeneration of the sheath of myelin
that insulates the nerve cells and causes the cells to short out and
fail to communicate with each other.
“MRI cannot visualize myelin directly, so we are looking at ways to
infer its presence,” Does said. “Our immediate objective is simply
to measure how much myelin is present, with a longer term goal of
distinguishing between healthy myelin and myelin that has broken
down.”
Unlocking the secrets of myelin content contained within a single
heterogeneous voxel of MRI space is just the beginning. Does’ work
will help advance the application of MRI technology to more
precisely analyze the cellular level of a wide range of tissues,
particularly in the brain, the spinal cord and the heart.
Like most MRI techniques, Does’ approach targets water. “We want to
get as complete a picture as we can of how water behaves inside the
myelin,”
Does said.
A single voxel imaging nerve and white matter in the brain might
contain hundreds or thousands of myelinated axons, which are the
connecting components of nerve cells. There is water around these
cells as well as water within them. How is one to distinguish the
water within ultra-thin myelin from the water everywhere else in the
space depicted by the voxel?
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Part of the trick lies in
manipulating and rearranging the precise “pulse sequences” that make
up MRI scans.
Unlike the comparatively straightforward point-and-shoot techniques
of X-ray and CT scans, MRI scans are obtained by subjecting bodily
tissues to a variety of magnetic and radio energies and
discriminating between different tissues based on how they respond
to these stimuli.
The large magnet people commonly identify as the “MRI scanner”
serves the purpose of creating a magnetic field such that the
protons of hydrogen (in water, which pervades the body) aligns with
it. You won’t feel it if you’re having an MRI
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scan done, but all those
hydrogen cells are abandoning their usual random orientation in the
body and are lining up north-south with the magnet. Three smaller
magnets called gradients then swing into action, each one
representing the x, y, and z axes of a three-dimensional graph.
These three magnets align so that an area of interest, or slice, can
be imaged, because the protons in that area are affected differently
from protons outside the slice.
Next the aligned protons
are zapped with a radio frequency that is precisely tuned to make
hydrogen protons wobble (“precess” is the correct term) at a higher
energy level for a short time.
As the stimulated protons relax back to their preferred precession
level, they emit energy in the radio frequency range. Protons relax
at different rates, depending on the type of tissue they are
embedded in and how quickly the surrounding tissue can absorb the
released energy.
An MRI receiver picks up the released energy signal, which is
transmitted to the computer that plots the relaxation times and
other data. This information is then compared with MRI data
libraries that have been developed to identify different types of
tissue based on these relaxation rates.
As you might imagine, the sequence and precision of these sets of
stimuli to the protons must be exquisitely timed and finely tuned in
order to achieve the desired precision in the image. If the sequence
is altered, different information is gained. Does and his associates
are taking advantage of that ultra sensitivity and precision to
discern what’s contained within single voxels, based on the
relaxation patterns that emerge from different pulse sequences.
“Water in myelin ‘relaxes’ more quickly than the other water in
nerve.
We collect a series of images, each at a different time point of
this relaxation process,” Does said. “From these we can extract a
time course of the relaxation of the combination of all signal
within a voxel, which can be mathematically transformed how much
signal exists at different relaxation rates.”
In addition to altering the radio frequency pulse sequences to
better quantify the amount of myelin at a sub-voxel level, Does is
using manganese, a contrast agent readily taken up by calcium
channels used to transmit electrical signals through nerve cells.
Manganese is a metal ion strongly imaged by MRI equipment.
Does is currently testing his techniques on rats in the Center for
Small Animal Imaging, which he directs. The Center is part of the
Vanderbilt University Institute of Imaging Science (VUIIS). “This
gives us the opportunity to explore the potential of small animal
MRI as a research tool,” Does said. |
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