Hidden imaging data
Magnetic resonance imaging (MRI), which is based on nuclear
magnetic resonance (NMR), has proved to be one of the more
pervasive applications of physics to medical technology. MRI
can probe softtissue characteristics that X-rays and ultrasound
cannot detect because it measures chemical conditions in tissues.
But improving MRI resolution, now around a few millimeters,
poses a major challenge. Higher resolutions require higher
magnetic field gradients, and gradients much higher than those
now used cause side effects on patients nervous systems.
But a collaboration between Valerij G. Kiselev of the section
of medical physics at the University Hospital Freiburg (Germany)
and Dmitry S. Novikov of the physics department at the Massachusetts
Institute of Technology has shown that information
down to the micrometer scale lies hidden in NMR data that
is generally thrown away. Although their new technique
does not directly increase resolution, it gives information
about the shapes of micrometersized cells and capillaries
in a given millimeter- sized region. Such shape information
can be vital for the early detection of several conditions,
|Resolution of magnetic resonance images,
currently around a few millimeters, may be improved down
to the micrometer scale by retrieving shape information
from signal decay rates.
In conventional NMR imaging, a strong magnetic-field gradient allows
only a single millimeter-sized pixel at a time to be identified
by a pulse of radio-frequency (RF) radiation. The radiation flips
the magnetic spins of hydrogen nuclei aligned by the magnet field.
The effect is akin to a hammer hitting a tuning fork, and the nuclei
emit a rapidly fading RF signal as they precess around the field
direction. The rate at which the signal fades depends on the physical
and chemical environment of the nuclei. For example, the fading
time for tumors differs from that for healthy tissue.
The conventional approach assumes that the fading is a steady
exponential decay, and measures the rate after enough time so that
is nearly true, explains Novikov. But our calculations
showed that for relatively short times after the pulse, the decay
rate is slower, and the way the decay rate changes contains valuable
Specifically, the researchers looked at how this early time-fading
changes depending on the microscopic shape of the objects that contain
the nuclei. For fat objects such as spheres, the decay rate increases
rapidly. For thin objects such as rods or thin disks, it increases
more slowly. These changes stem from the different ways that microscopic
objects alter the magnetic fields that affect the nuclei. A
skinny object produces a more uniform field, while a fat objects
field is less uniform, says Novikov.
Experiments and simulations comparing the signals from microscopic
polystyrene spheres and those from disk-shaped red blood cells have
closely agreed with the teams calculations. Potentially, the
ability to distinguish, for example, the average shape of capillaries
in the brain would have great diagnostic value. When a tumor begins
to form, normally straight capillaries become curled, a shape change
that, in theory, the new method would detect.
However, much work remains before physicians can apply the new
analysis in practice. Its much easier to predict the
decay-rate pattern knowing the shape than to determine the shape
from the decay-rate pattern, explains Novikov. More experiments
will be needed to look at the differences in the evolution of decay
rates in tumors and normal tissue, as well as more detailed calculations
of how decay rates vary with different tissue conditions.
|To create three-dimensional integrated
circuits, it is possible to precision-bond two wafers
by first bonding one wafer to glass and removing the silicon
substrate to make it transparent, as in this 200-mm
(Z. Siwy and A. Fulinski)
All computer chips today function as essentially two-dimensional
arrays, with devices placed next to but not atop one another.
Such an arrangement has a significant disadvantage. The number
of devices on a chip grows as the inverse square of the size
of the devices, but the number of connections to the chip
can grow, at most, linearly with the inverse of the size.
As a result, more and more devices compete for the same communication
lines on and off the chip, and communication delays become
more important than processing delays.
One solution to this problem is to manufacture three-dimensional
integrated circuits (3D ICs) with devices stacked in piles. Connections
between one layer and the one underneath can now grow as rapidly
as the number of devices and be very short as well, significantly
increasing overall speed compared with two chips side by side. Manufacturing
such 3D ICs is no easy task using conventional lithographic techniques,
which add one layer of material at a time to a substrate. For one
thing, piling up layers introduces more and more dislocations. For
another, some processes needed for one layer will damage a completed
device in the layer beneath it.
An IBM research team led by Kathryn Guarini, a research staff member
at the Thomas J. Watson Research Center (Yorktown Heights, NY),
has now developed a way that may make 3D ICs practical. It consists
of producing two conventional wafers separately and then bonding
them one on top of the other. Both wafers are produced conventionally,
and then one is bonded with polymer adhesives through its top plane
to a glass wafer. The original silicon substrate of this wafer is
then carefully removed by etching and mechanical grinding, stopping
at the silicon oxide insulating layer. The combined wafer and glass
plate is now transparent, so it can be exactly aligned with the
other chip wafer and bonded to it. Then laser ablation releases
the glass layer and removes the adhesives. In a final step, which
the team has not yet performed, holes can be etched through the
two wafers and filled with metal to produce the large number of
connections that will make each pair of chips function as one.
What we have demonstrated is that this method is gentle
enough to preserve the high performance of the devices, Guarini
says. Performance increases of around 30% are possible using just
two layers, with further increases accruing as subsequent layers
|Scanning electron micrograph of the
500-nm-wide end of a conical pore formed in 12-µm-thick
plastic film, part of a synthetic ion pump that moves
cations against a concentration gradient.
The process of separating chemicals and concentrating desired
species on one side of a barrier is fundamental to industry
and life itself. In industry, separation generally involves
physical processes such as evaporation, chemical reactions that
select specific ions or molecules, or reverse osmosis using
membranes that allow passage of solvents such as water but not
their dissolved substances. Cells, however, rely mainly on ion
pumps, which consist of tiny pores in cell membranes that selectively
move ions from less concentrated to more concentrated regions.
Zuzanna Siwy of the Gesellschaft für Schwerionenforschung
(Darmstadt, Germany) and Andrzej Fulinski of the M. Smoluchowski
Institute of Physics at Jagellonian University (Krakow, Poland)
have now developed a synthetic ion pump that is based on tiny conical
pores formed in a 12-µm-thick plastic film (Phys. Rev.
Lett. 2002, 89, 198103-1). The pores act as miniature ratchets,
and an oscillating electrical field preferentially pushes cations
(positively charged ions) from the narrow to the wide ends of the
Siwy and Fulinski were studying biological channels and thought
that synthetic pores would provide a way to model the biological
phenomenon. They got the idea that external field oscillations,
which had been observed in the biological pumps, could be used to
create synthetic ion pumps. We got the hint that a conical
pore could work as a ratchet after we saw an article in Scientific
American about molecular motors, Siwy explains. Molecular-sized
ratchets work on the principle that a random or oscillating impulse
can be converted into useful work if a device can move only in one
A conical pore works as a ratchet because the pore, created in
poly(ethylene terephthalate) film, is lined with negative charges.
These charges are created during the etching of the pores, which
breaks the polymer chains and leaves the negative charges exposed.
A positive ion is attracted to the concentration of negative charge,
which is highest at the narrow end of the pore. In the absence of
an additional field, no flow would result because ions would just
cluster around the pores narrow end until the charge was neutralized.
However, an external field imposes a 0.5-V oscillating potential
on the membrane. Positive ions fall into the deep potential well
near the narrow end, which draws them across the membrane into the
pore. The potential well is asymmetrical, sloping steeply toward
the narrow end and gently toward the wide end of the pore. Inside
the pore, the field created by the oscillating potential occasionally
pushes the ions with enough force to move them out of the well on
the gentle-sloped wide end, but never enough to overcome the steep
narrow end. Thus, the ions are prevented from recrossing the membrane
and must exit out the wide end. A net flow of ionic current of up
to 3 billion ions/s flows through the 2-nm-diameter narrow end of
the pore and out the 500-nm-diameter wide end.
The efficiency of the device is high40% when equal amounts
of ions are on both sides of the membraneand it falls to 10%
for a 7.5-fold difference in concentrations. Some flow is observed
even when the concentration of ions on the receiving side is 100
times higher than on the contributing side.
The conical pores are formed by irradiation through a 100-mm-diameter
mask with a 2.2-GeV beam of gold ions from the UNILAC linear accelerator
in Darmstadt. The irradiation is stopped as soon as a single ion
passes through the membrane. The irradiated material is then etched
away, and the etching is stopped as soon as a breakthrough of the
membrane occurs, producing the atom-sized narrow pore.
We are now working to develop a device that can enrich solutions
on a significant scale, using many pores, says Siwy. This
effort requires a number of improvements: making the pump work faster,
designing pores that work for negative ions as well as positive
ions, and determining if the pores efficiency varies for different
|Transmission electron micrograph of
a new form of copper that is six times as strong and nearly
as ductile as conventional copper and is formed by modifying
( Johns Hopkins University)
Strong, ductile copper
Coppers usefulness is based on its high electrical and
thermal conductivity, and its high ductility: the conventional
form of copper can undergo a strain of almost 70% before breaking.
Such ductility makes copper easy to form and means that it
yields gracefully rather than catastrophically to mechanical
stress. But copper is not strong, with a strength of about
600 kg/cm2 before starting to deform. This relatively
low strength is a drawback for the growing field of microelectromechanical
system (MEMS) devices, which require high strength to compensate
for their tiny size.
As with many materials, coppers mechanical properties
are in part determined by its microstructure, which produces
characteristic defects that strengthen or weaken the metal.
Conventional annealed copper has relatively large grains several
micrometers across. A team of physicists at Johns Hopkins
University has invented a method of modifying its microstructure
to produce a new form of copper that is six times as strong
and nearly as ductile as the conventional metal (Nature
2002, 419, 912). The key is to create a mixture of extremely
small and larger grains.
The research team reasoned that higher strength could be obtained
with nanocrystals smaller than 200 nm in size, so they worked copper
at room temperature without heating it to reduce crystal size. (Such
cold working was the key to the strength of the fabled Arabian steel
swords of the Middle Ages.) However, the team found that although
strength increased greatly, ductility practically disappeared, with
almost no uniform deformation and only 10% strain before failure.
We realized that the dislocations that increase strength were
being eliminated by recrystallization, explains Mingwei Chen,
a member of the team. So we decided to try cold working at
liquid-nitrogen temperature to prevent recrystallization.
This approach increased strength to almost 5,000 kg/cm2
and allowed a small uniform deformation, but ductility was still
The problem was that the large grains, although relatively weak,
allowed the ductile deformation that strong but brittle nanocrystals
could not. So the researchers heated the low-temperature-worked
samples to 200 °C, producing the desirable mix of strong nanocrystals
and ductile large crystals. At this point, strength was still 4,000
kg/cm2 but uniform deformation extended to almost 30%
strain, and failure occurred only at more than 65% strain, almost
as much as for conventional low-strength copper.
Not only could such strong and ductile copper prove useful for
MEMS devices, it could have broader applications where mechanical
strength and high conductivity are required. In addition, the researchers
believe that the same combination of low-temperature working and
high-temperature annealing can improve the toughness of many other