From scopes that help premature babies breathe to techniques for imaging live neurons and beating hearts as they develop, the latest optical and laser technology being deployed in medicine and the biosciences will be on display at the Optical Society's (OSA) Annual Meeting, Frontiers in Optics (FiO), which takes place Oct. 11-15 at the Fairmont San Jose Hotel and the Sainte Claire Hotel in San Jose, Calif.
Information on free registration for reporters is contained at the end of this release. Bio-optics research highlights of the meeting include:
- Live Imaging of a Developing Heart
- New Scope to Help Premature Babies Breathe Easier
- Microfine Surgery with Powerful Laser Pulses
- Digital Camera Sees a Sharper Mind
- Following Single Molecules in Live Neurons
- Watching Proteins Fold
LIVE IMAGING OF A DEVELOPING HEART
Approximately one of every 100 babies born in the United States each year comes into the world with a heart defect. Though there is a long history of understanding cardiovascular development and diseases, says Kirill Larin of the University of Houston, very little is known about the dynamics of the normal and abnormal embryonic heart.
Half a century ago, Richard Feynman said that one of the easiest ways to understand a fundamental biological process is to "just look at the thing," and for a highly complicated process like embryonic heart development and dynamics, he may be right. Being able to watch a young heart begin to beat and form chambers would show scientists a lot -- perhaps even revealing the developmental causes of heart abnormalities and other birth defects. But looking at a developing embryo in its womb is easier said than done. Fluorescence microscopes lack the ability to penetrate the skin deeply enough to image an embryo. Medical ultrasound devices can penetrate fully, but they lack the resolution necessary to reveal the details of development.
Now Larin and colleagues at the Baylor College of Medicine in Houston have shown that they can image live mouse embryos cultured outside of the uterus at different stages of development. Using a technique called optical coherence tomography (OCT), they are able to visualize early cardio dynamics and perform blood flow measurements, even from individual cells. OCT works by beaming infrared light on the embryonic tissues and then gating the back-reflected photons from different depths inside the tissues using low-coherence interferometry. The technique is similar to ultrasound imaging, but produces higher resolution images using optical frequencies. The researchers have demonstrated that they can image the heart in its earliest stages, as it first starts to beat and forms chambers. Their hope is to now use this tool to compare how hearts develop in genetically manipulated mice carrying mutations analogous to those that lead to birth defects in people. (Paper FthV2, "Early Mammalian Embryonic Imaging at Different Developmental Stages with Optical Coherence Tomography" is at 4:30 p.m. Thursday, Oct. 15).
NEW SCOPE TO HELP PREMATURE BABIES BREATHE EASIER
Babies born prematurely often find it difficult to breathe on their own. They may require intubation, the insertion of a tube through the nose or mouth into the still-developing lungs to move air in and out. Intubation in adults has a reasonable success rate -- upwards of 80 or 90 percent -- but only about half of first attempts to insert the tube succeed in low-birth-weight babies.
"The size is different and the anatomy is different in infants," says Katherine Baker of the University of California, San Diego.
Baker is working with pediatricians at the university's medical center to create a new piece of equipment suitable for infants, a customized laryngoscope. Its centimeter-wide acrylic tip is tilted to better guide the breathing tube, a light-emitting diode (LED) illuminates the baby's airway and a camera at the end helps medical professionals to maneuver the tube and to teach others how to do the procedure.
The group has successfully tested a prototype on a mannequin and is working to create a second version suitable for testing in clinical trials. (Paper FthP3, "Design and Prototype Fabrication of a Neonatal Video Laryngoscope" is at 2:15 p.m. Thursday, Oct. 15).
MICROFINE SURGERY WITH POWERFUL LASER PULSES
Targeting living cells with laser pulses has been a powerful technique in biology for a number of years. Lasers can punch holes in cell membranes or cut one part of a cell off from another, revealing how the various pieces of a cell function. In recent years, neurobiologists have begun embracing precise laser nanosurgery as a way of revealing the function of individual neurons. Short but powerful laser pulses can deposit considerable energy onto a tiny spot, cleanly cutting a nerve cell without cooking the surrounding tissue. By severing the branches of nerve fibers in creatures like worms or mice, scientists can determine what parts of the body those nerves control.
At the Frontiers in Optics conference, Eric Mazur of Harvard University will describe how laser nanosurgery works, based on his own studies of the worm-like nematode C. elegans. One nematode in particular has a genetic mutation that renders it unable to coordinate its movement. It can wiggle, but it cannot easily move forward or backward. Mazur and his colleagues have shown that they can restore normal motion to this creature by cutting a single neuron. (Paper FWA1, "Nanosurgery with Femtosecond Lasers" is at 8 a.m. Wednesday, Oct. 12).
DIGITAL CAMERA SEES A SHARPER MIND
Try as you might, you can never hold perfectly still -- your body will twitch and jerk with movements nearly invisible to the eye. And if you're a patient in a hospital or the subject of a research study, this squirming will blur the images created by scanning devices like MRI machines, limiting their ability to spot minute details.
Chester Wildey of the University of Texas, Dallas, is working on a way to detect and compensate for these slight movements using a modified digital camera. The camera tracks a pair of glasses worn by the subject and records minute movements of the head.
"Using a regular 640 by 480 camera, we can detect movement down to a micron," says Wildey. "You can't see movement that small with your eye." Image processing software developed by his group crunches this data in real time, allowing scanners to be adjusted and achieve better resolutions.
The technology has been used by researchers in Texas looking for evidence in the brain for Gulf War syndrome, a controversial physical illness thought to be connected to service in the Gulf War. He believes that the technology could help researchers looking for other subtle changes in the brain -- such as those studying the neurological basis of attention deficit disorder.
The camera is also being adapted to measure a person's heartbeat from a distance by recording slight movements in tabs attached to the pulsing skin. Wildey hopes that this may lead to a way to detect atherosclerosis by comparing heartbeats in different parts of the body. (Paper FWR3, "Head tracking for Real-Time Motion Correction in the MRI Environment Using a Single Camera" is at 2:30 p.m. Wednesday, October 14; Paper JWC9, "Real Time Optical Vibrocardiography Using Image Processing" is at noon on Wednesday, October 12).
FOLLOWING SINGLE MOLECULES IN LIVE NEURONS
Peripheral nerves are the organic wires that connect the command centers in the brain to the muscles and other tissues they control. Understanding how these nerves function is of critical importance because of their central role in many human diseases. Now a group of researchers at Stanford University has designed a way to observe one critical aspect of peripheral nerve function -- the transport of essential proteins and other materials from one end of a nerve fiber to another.
Because they can snake several feet from the spinal cord to the extremities, peripheral nerves are often quite long -- sometimes 100,000 times longer than other cells in the body. The transportation of materials along this entire length is an extremely long and complicated process that can take days or even weeks. Studying this process has always been a complicated proposition, but Bianxiao Cui and her Stanford colleagues have demonstrated a new way of observing this transport by tagging single molecules, called nerve growth factors, with "quantum dots" that can be followed with a powerful microscope as they move along live neurons.
The researchers' technique is analogous to looking at a dark highway from the window of an airplane. The dark, invisible lanes of roads are microtubules, the skeleton of the cell. The nerve growth factor molecules ride in the cars that are illuminated by their quantum dot headlights. One thing Cui and her colleagues have observed, which has never been seen before, is that packages in transport can jump from one microtubule to another as they move along -- like cars switching lanes as they roll down the highway. They also discovered that the majority of those cars are single passenger; they only contain a single nerve growth factor molecule.
Scientists have known for a long time that these proteins are essential, since they help the nerve cells survive by regulating gene expression. But Cui and her colleagues showed that even a single molecule of nerve growth factor is enough to trigger the transport process and sustain signaling during axonal transport to the cell body. (Paper LSThB3, "Single Molecule Imaging of Axonal Transport in Live Neurons" is at 9 a.m. Thursday, Oct. 15).
WATCHING PROTEINS FOLD
One of the most important biological actions is the folding and unfolding of protein molecules. But getting hold of single protein molecules is difficult, and monitoring their gymnastic gyrations is even more so. Scientists at Harvard University have produced new video-based "optical tweezers" techniques for doing just this, enabling ultra-precise measurements to be made in a way that is simple and effective. The current U.S. secretary of energy, Steven Chu, won a Nobel Prize for his contribution toward controlling atoms with laser beams inside an enclosed trap; he later pioneered the use of laser beams for actually holding tiny objects -- even biological molecules -- in place. The Harvard device is among the latest and most versatile use of this optical tweezers approach.
Wesley Wong of the Rowland Institute at Harvard and his colleagues have developed a unique optical tweezers system that uses a combination of interference imaging, light modulation and custom software algorithms to achieve the necessary resolution and stability to watch proteins fold. This system, which employs already-existing optical technology components, utilizes 3-D video tracking to measure the lengths of short molecular tethers with angstrom resolution (less than 1 billionth of a meter) and active feedback control for a force stability of femtoNewtons (10^-15 Newtons). Fluctuations can be glimpsed at rates faster than 100,000 frames per second -- all with inexpensive video-imaging. The act of protein folding is quantified by measuring the end-to-end distance of a single molecule while the strength of the tweezers' grip is varied.
The Wong group uses optical tweezers to study the behavior of single molecules under force in order to reveal the nanoscopic workings of biological systems. Together with their collaborators, they have used this approach to expose the molecular feedback mechanism behind the regulation of blood clotting and to determine the dynamic mechanical properties of spectrin, a structural molecule largely responsible for the amazing material properties of red blood cells. (Paper FWS1, High-Resolution, High-Stability, "High-Frequency Optical Tweezers Method with a Simple Video Camera" is at 1:30 p.m. Wednesday, Oct. 14).
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