[MURG] [>Htech] Newest imaging methods begin `golden age' of seeing inside body (fwd from oxyryxo@yahoo.com)

[Eugen Leitl]

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From: "oxyryxo" <oxyryxo at yahoo.com>
Date: Mon, 13 Oct 2003 02:47:06 -0000
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Subject: [>Htech] Newest imaging methods begin `golden age' of seeing inside body
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 Posted on Sun, Oct. 12, 2003   
 
Newest imaging methods begin `golden age' of seeing inside body
BY RACHEL EHRENBERG
The Dallas Morning News

DALLAS - (KRT) - For the latest in surveillance technology, you 
wouldn't always want to call the CIA. To spy on the body's innards, 
for example, you might try OCI or SHG. They are among a wave of 
newcomers joining veterans like MRI and PET in the alphabetic arsenal 
of imaging technology.

While agents of the old guard have helped scientists gather 
intelligence about the body's inner workings, new technologies are 
taking reconnaissance to ever-greater depths. X-rays, once used 
mainly to picture broken bones, now capture cartilage, collagen and 
fat. Joystick in hand, researchers can "fly through" a holographic 
image of a tumor. And with the neural equivalent of a traffic 
helicopter, scientists are tracking information flowing along the 
brain's superhighways.

Some of the methods, particularly those exploiting lasers, have 
stimulated scientists to herald a new era of imaging. "It is probably 
the beginning of a golden age of microscopy," says physicist David 
Kleinfeld.

Modern imaging methods date back to 1895, when German physicist 
Wilhelm Rontgen pointed the rays from a gas discharge tube at his 
hand and saw his bones projected on a screen. The rays he called "X," 
for unknown, are still used widely. But today's techniques show a lot 
more than bones. From nerve cells to fat pads to tiny tumors, 
scientists are spying on the body from the outside to better 
understand what goes on within.

Kleinfeld and his colleagues use ultra-fast lasers to precisely slice 
and image sections of brain tissue, a method that will be an 
important tool for mapping the brain. Called two-photon laser 
scanning microscopy, or TPLSM, the technique requires a special laser 
that produces light pulses lasting a millionth of a billionth of a 
second.

"These pulses are very energetic," said Kleinfeld. "They aren't 
around for very long, but when they are there, they do a lot."

The short pulses don't produce damaging heat, but they rip the atoms 
in the samples of brain tissue apart, removing layers that are 
thinner than a human hair. When each new layer is uncovered, a lower-
intensity laser takes an image of the freshly exposed surface, the 
scientists reported recently in the journal Neuron.

Previously, getting microscopic images of the brain was a laborious 
task. For one thing, tissue was hand-sliced, and the slivers of brain 
had to be kept frozen, making them prone to warping and damage. The 
new technique destroys tissue as it is imaged, so samples can't be 
saved for later examination. But TPLSM's impact could be broad, says 
Kleinfeld, who works at the University of California, San Diego. It 
allows precise mapping of structures like blood vessels, and by 
marking proteins with a dye beforehand, scientists can use the laser 
slicing technique to see where in the brain the molecules do their 
stuff.

Another new version of laser I-spy allows Cornell University 
researchers to watch nerve cells as they develop. The technique, 
called second-harmonic generation microscopy, or SHG, takes advantage 
of the way stiff, slender structures called microtubules grow within 
nerve cells. Microtubules are the I-beams and railroad tracks in many 
types of cells, helping to transport goods and provide scaffolding. 
Depending on which part of a nerve cell they are supporting, these 
microtubules grow differently, and that difference can be detected by 
laser beams.

In addition to shedding light on how the brain is wired, the 
technique may help scientists understand which cells are sick in the 
early stages of Alzheimer's disease, or how nerves regrow following 
spinal cord injuries. The scientists and their colleagues at Harvard 
Medical School and Massachusetts General Hospital reported the work 
recently in the Proceedings of the National Academy of Sciences.

Scientists can study cells live and "in action" with SHG, said Daniel 
Dombeck, a physics graduate student at Cornell University and lead 
author of the study. "In the past you had to kill the sample and fix 
it in place," explained Dombeck. "You couldn't look at one cell over 
time."

Other researchers are happy to see scientists tackling new questions 
with SHG. Previously the method was used to study things like the 
distances between molecules, said Kleinfeld. "This is the first 
application to real biology."

The lasers used with SHG shine "coherent light." When you hold a 
flashlight up to your hand, your skin glows red, but you can't see 
any defined structures. This is because the light is scattered into 
jumbled separate paths. With coherent light, all these individual 
light paths are in lockstep.

Other scientists are using coherent light to create holographic 
movies of tumors. At Purdue University, scientists have developed 
technology that allows visual "fly-throughs" of the cellular galaxy. 
Steering with a joystick, the researchers can swoop through a rat 
tumor, backing up in real time when they see a structure they want to 
stop and examine. The technology, called Optical Coherence Imaging, 
or OCI, could allow scientists to study a tumor's inner cells, from 
the outside.

A key to OCI's success is specially designed holographic film. Unlike 
the human eye, the film is sensitive to coherent light and the film 
rejects incoherent, scattered light. Shining two laser beams onto the 
film, the researchers created a video of the interior of a tiny 
tumor. The team reported the work recently in Applied Physics Letters.

"The benefit is this film is dynamic, it is just like a movie," said 
physicist Ping Yu, now at the University of Missouri-Columbia. "It 
has a very fast response time; if you find something interesting, you 
can just move back."

OCI can only image shallow structures, because light penetrates to a 
maximum of about 2 millimeters below the skin. But the technology may 
be used to monitor how well a tumor's inner cells respond to drugs by 
allowing scientists to study growth without cutting the tumors up.

Other scientists are developing new ways of tweaking older 
technologies. Brookhaven National Laboratory's Zhong Zhong is using 
high-intensity X-rays to image soft tissues such as tendons and skin. 
The technique, called Diffraction Enhanced Imaging, or DEI, may help 
detect diseases such as lung and breast cancers, or cartilage damage 
in osteoarthritic patients, Zhong and his colleagues reported 
recently in the journal Anatomy.

Conventional X-rays are absorbed by the large atoms that make up 
dense tissue, like the calcium in bones and teeth, but such X-rays 
mostly pass through softer tissues such as skin or fat. Higher-
intensity X-rays are absorbed even less, so the team used a high 
powered X-ray machine called a synchrotron.

"The higher the energy, the less it is absorbed," says Zhong. "We 
just upped the energy."

The scientists calibrate the synchrotron's beams, which are a 
thousand times brighter than those made by conventional machines, by 
aiming them at a silicon crystal. When directed at the body part of 
choice, the beams bend and scatter, hitting the film on the other 
side at different intensities and creating an image. DEI scans on 
cadavers show a variety of tissues; there are fat pads, blood 
vessels, tendons and skin. And the radiation exposure is 
significantly less than that of conventional X-rays, says Zhong.

Another old imaging technique that's being tweaked into doing new 
tricks is MRI, or magnetic resonance imaging. Conventional MRI uses a 
combination of radio waves and a strong magnetic field to spur the 
hydrogen atoms in your body to send out signals that are collected 
and transformed into an image. Today, one of the most popular 
versions of MRI is functional magnetic resonance imaging, or fMRI. 
The technique detects blood flow, and scientists are using it to 
learn about what parts of the brain go to work when a person smells 
or thinks or feel certain things. "fMRI is the 600-pound gorilla of 
imaging," says Michael Moseley, a professor of radiology at Stanford 
University's School of Medicine and president of the International 
Society for Magnetic Resonance in Medicine.

Today there are still other variations on MRI that scientists are 
using to understand the brain's structure and function. In the early 
1990s, Moseley did pioneering work using diffusion or dMRI, a method 
that detects water flowing out of brain cells. He was one of the 
first to show that in the minutes following a stroke, water flowing 
across damaged brain tissue slows considerably.

Usually water moves across brain cells at about 1 millimeter per 
minute, but when cells die or are stressed, the water movement slows 
down, and the sluggish flow can be detected with dMRI. A recent study 
led by doctors at Massachusetts General Hospital found dMRI to be 90 
percent accurate at detecting strokes.

A newer variation on dMRI is diffusion tensor, or DT-MRI. Using this 
technique, scientists are building elaborate road maps of the brain's 
white matter, the pathways that bring information from one area of 
the brain to another. DT-MRI is helping scientists understand a 
multitude of ills, from Alzheimer's to dyslexia. Diffusion tensor MRI 
also tracks water movement, but from many more directions than 
regular dMRI. Like people moving about in a city, water diffuses 
randomly in the brain's gray matter. But on the white matter tracks, 
the highways taking information to and from the cities, water 
movement is very directed. Scientists track this flow with DT-MRI.

Moseley says a combination of techniques will probably yield the most 
intriguing information. "fMRI combined with tensor will you show you 
the road map underneath all that activation - people with dyslexia or 
schizophrenics might have altered road maps," he said.

In 10 years scientists will probably "be imaging the actual processes 
that occur when cells are active," said Moseley. "It is stunning to 
see what is going on right now in molecular imaging right now. 
Everyone is in an absolute frenzy."
 
http://www.centredaily.com/mld/centredaily/news/6997064.htm


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