a new kind of X-ray machine
David F. Salisbury
Oct. 9, 2001
to the old saying, necessity is the mother of invention. But in
the case of the monochromatic X-ray project, which holds the promise
for significantly improving both the quality and the safety of medical
X-rays, it was not necessity but frustration that provided the impetus.
many years, Frank E. Carroll, chest radiologist and breast cancer
researcher at the Vanderbilt University Medical Center Department
of Radiology, has been frustrated with the poor quality of mammograms.
"I've been reading mammograms for decades and, when I do, I
still feel like I'm standing in quicksand! We find a lot of things,
but miss a lot of them, too," he says.
in 1987 Carroll and several colleagues
studied the problem systematically and identified the quality of
the X-ray beam as the major factor standing in the way of improving
standard X-ray tube used in hospitals produces a beam that contains
a broad spectrum of frequencies .
It generates "soft" X-rays that barely penetrate the skin
at the low end of the spectrum. At the high end, it produces "hard"
X-rays that ricochet off bone and tissue, creating a fog that obscures
subtle features in X-ray images.
X-ray machines do not do a very good job of mammography," Carroll
says flatly. "The radiation dose is high. The accuracy is very
poor. The beam that we use is simply not well suited to what we
a group of Vanderbilt scientists banded together to submit a proposal
to the Department of Defense to create a free-electron laser center
on campus, Carroll joined in because he thought there might be a
way to use the unusual laser to produce better X-rays. When the
Strategic Defense Initiative Organization approved funding for the
Vanderbilt enter, however, they did not support Carroll's proposal
because they thought it was too far out.
the researcher was able to convince The Eastman Kodak Company that
his ideas had merit. Kodak funded his efforts for the first three
years. That allowed Carroll and his colleagues-Charles Brau, professor
of physics; Marcus Mendenhall, a research associate professor; Robert
Traeger, senior research assistant; Glenn Edwards, former FEL center
director now at Duke University; and research physicist James W.
Waters-to create a preliminary design for the monochromatic X-ray
beam line that they wanted to add to the Vanderbilt FEL.
tried several different approaches and finally hit on one that looked
as if it would work. The basic idea is very simple. Generate a beam
of electrons and accelerate them to nearly the speed of light. At
the same time, create a high-powered beam of infrared laser light.
Direct the two beams so that they collide head-on. When you do that
successfully, the infrared photons should bounce off the electrons
and gain the energy required to transform them into X-rays in a
process called the Inverse Compton Effect. Making it work was another
interested Carroll about such a system is that it should produce
monochromatic X-raysX-rays of a single wavelength. This is
very similar to an X-ray laser. Unlike laser light, however, it
is not coherent. That is, the light waves are not all aligned. Despite
this lack, Carroll realized that a monochromatic beam would have
many advantages for medical imaging compared to current "polychromatic"
great deal was already known about the characteristics of monochromatic
X-rays because they are a byproduct of the massive particle accelerators
that have been developed by high energy physicists to study the
basic structure of subatomic matter. Originally, this "synchrotron
radiation" was considered a problem because it siphoned energy
from the beam lines that were central to the physics experiments
being run. Then scientists realized that these X-rays were themselves
a valuable resource. They found a way to control their production
and have set up special laboratories, called synchrotron laboratories,
specifically to give scientists access to these X-rays.
Department of Defense officials continued to dismiss the idea until
John Madey, the inventor of the free-electron laser, stood up in
a meeting and stated publicly that this was a good idea and advised
them to fund it.
support allowed Carroll to modify the Vanderbilt FEL to test the
idea. The changes were made in 1998 and proved the naysayers wrong.
At the same time, the experiment showed that a free-electron laser
was not the ideal instrument for the purpose. For one thing, the
FEL produces so much radiation that it must be operated in a heavily
shielded room. Also, the strength of the X-ray beam that it generated
was so low that extremely long exposure times were required to produce
we thought about it and decided to get rid off all the bad things
about the FEL beam and keep all of the good things: to make a new
kind of machine that we had never seen before," Carroll says.
The key to the new design was a conventional type of infrared laser,
a machine that can produce a beam with about 1,000 times the power
of the FEL called a tabletop terawatt laser developed by Positive
in Los Gatos, CA. The researchers combined this powerful laser with
a similarly sized linear accelerator for producing relativistic
electrons. They estimate that this instrument could be built small
enough to fit in a standard-sized X-ray room and should cost about
$1 million dollars apiece when mass produced. That compares to the
billion dollar price tag for building new synchrotron radiation
and his colleagues went to officials at the Office of Naval Research
(ONR), which had taken over management of the free-electron laser
program, and asked for an additional $10 million in order to begin
producing these monochromatic X-ray machines commercially. ONR agreed
to back the project if the university was willing to invest the
matching funds required to set up a commercial company for this
purpose. Vanderbilt had recently set up the Office of Enterprise
Development to help support the commercialization of technology
based on university research. So the university agreed to use this
fund to meet ONR's conditions and set up a new companyMXISystems,
develop these new machines.
university received the grant in July 1999 and the company began
building a prototype in one of the laboratories at the FEL center.
On April 10, 2001 they turned on the new machine and made X-rays
for the first time. They are currently in the process of improving
the machine's performance and making it easier to produce full X-ray
now we have a beam no one has ever had before. It is basically one
frequency, although it is not truly monochromatic. And it is tunable.
Now we have to convince people that we can use this to make better
images," says Carroll.
initial effort is to use the new beam to produce conventional X-ray
images. Because the beam can be tuned to produce X-rays ranging
from 15 to 50 KeV, operators can pick the frequency that does the
best job of imaging the part of the body of interest. MXISystems
and Vanderbilt scientists believe that they can produce images with
greater detail than conventional X-ray machines using half the dosage.
Also, the device produces X-rays in extremely short pulses .
As a result, it can take sharp pictures of subjects even if they
are moving rapidly.
this mode, the monochromatic X-ray machine should also go a substantial
way toward meeting Carroll's initial objective. Tumors should stand
out much more clearly. He estimates that tumor tissue should be
11 percent lighter than normal tissue using monochromatic X-rays
compared to the half a percent difference with conventional X-ray
this is only the beginning. There are several ways to use monochromatic
X-rays that have even greater medical potential.
such approach is called "time-of-flight imaging." In normal
imaging, all the photons that make it through the body contribute
to the final image. This includes photons that have bounced around
in the body before emerging and so blur the image. With the extremely
short pulses generated by the new X-ray source, the scientists can
install electronic detectors that only measure the photons that
pass through the body directly. This has the potential for reducing
dosages by another factor of ten.
in conventional absorption X-ray imaging actually deliver very little
information. Photons that pass through the body strike the X-ray
plate, while those that are absorbed don't. Physicists know that
photons contain hundreds to thousands of times more information
than that. As the X-ray photons travel through tissue they undergo
subtle changes in phase. With a monochromatic light source, scientists
can tap into this information through a process called phase contrast
imaging. Research done with synchrotron radiation has shown that
this approach can provide valuable information about changes in
tissue density and edges between different organs and body parts
show up clearly. For example, phase contrast images can show individual
muscles which are completely invisible to conventional X-rays.
monochromatic X-ray machine will also foster another technique,
called K-edge imaging, that Carroll predicts will become a "whole
new field of radiology."
great deal of anatomical imaging, like angiography ,
is done by injecting special compounds into the body that show up
clearly with X-rays. One commonly used contrast agent is iodine.
But it that has a greater degree of toxicity than radiologists would
like, over and above the basic damage done by the X-ray beam itself.
imaging provides a way to reduce both contrast agent toxicity and
the energy of the beam to a value equal to the binding energy of
the electrons in the inner (K) shell of the contrast agent creates
absorption effects that can greatly increase the effectiveness of
such compounds. That means that they can be used at much lower dosages.
Being able to tune the X-ray beam also means that researchers can
choose among many more compounds.
higher energy levels, the body becomes increasingly transparent
to X-rays. That means a higher percentage of the X-ray photons pass
through the body without doing any damage. So, by identifying contrast
agents of lower toxicity that work at higher energy levels, the
adverse side-effects of this type of radiology can be substantially
reduced, Carroll says.
the same time, it should be possible to use K-edge imaging to view
a new level of detail within the body. For example, an experiment
performed by two of Carroll's graduate students
has shown that this approach can see microcirculation channels in
blood vessels that are invisible in conventional angiography while
reducing both the radiation dose and the concentration of the contrast
materials given to the patient.
addition to its radiological applications, the monochromatic X-ray
may have an important role in the basic research efforts made possible
by the mapping of the human genome. Many of the scientists involved
say that the next step is "proteomics" - that is mapping
and determining the functions of the millions of proteins that act
as the basic molecular machinery of living organisms. One of the
key techniques for determining the structure of complex molecules
like proteins is X-ray crystallography.
characterization efforts are currently done primarily at the big
synchrotron laboratories because monochromatic X-ray beams are far
superior to polychromatic beams for this purpose. Demand for time
on these beam lines is far greater than the time available, however.
So researchers must prepare lengthy proposals and wait long periods
of time before they can analyze their samples.
imagine! With this technology we will be able to put 100,000 monochromatic
X-ray sources in 100,000 universities around the world for the cost
of building just one centralized synchrotron lab," says FEL
center director, David Piston.