We've all become so accustomed to seeing CT scans and MRI procedures performed on TV medical dramas, or in film, that we rarely give much thought to what happens when the patient, for whatever reason, can't have one of those standard imaging procedures. Babies, for instance, are small, squirmy, and especially vulnerable to the ionizing radiation associated with many medical imaging procedures. Fortunately, researchers all over the world are hard at work developing alternative imaging techniques all the time, many quite similar in concept, but tailored for specific applications -- like imaging the infant brain.
Let's just take the three most common medical imaging technologies as a reference point: X-rays, CT scans, and magnetic resonance imaging (MRI).Conventional X-rays have been around for more than a century, after Wilhelm Roentgen first discovered the invisible rays in the 1890s and realized they could be used to image bone. It took awhile for folks to realize the rays were, in fact, quite dangerous in high doses, but thanks to improved technologies and shielding measures, for normal, healthy adults, X-rays aren't too problematic. CT scans are similar, in that they rely on X-rays, except instead of imaging the outlines of bones and organs, a CT scan machine builds a fully 3D computer model of the inside of a patient's body, by taking a series of images one narrow "slice" at a time and then reconstructing those slices into the final image.
When MRI came along in 1977 -- the first human scan took place on July 3rd of that year, and the machine that took the image, dubbed "Indomitable," is now on display at the Smithsonian Institution -- it became possible to take clear and detailed images of internal organs and soft tissues for the first time, without the use of ionizing radiation. A quick summation (for those who've never taken the time to peruse this handy explanation at How Stuff Works): MRIs use radiofrequency waves combined with a strong magnetic field to take images by manipulating the "magnetic moments" of hydrogen atoms -- one of the most abundant atoms in the human body because of the body's high water content. The rf waves get the protons in the hydrogen atoms all excited (okay, not "excited" in the colloquial sense, but that is the technical term for it), but eventually they relax back into their normal state, and when they do so, they emit powerful radio signals. These are detected and fed into a computer, which translates the data into a high-contrast image showing differences in the water content and distribution in various bodily tissues.
There are some drawbacks to MRI, though, namely the powerful magnetic fields: on the order of 0.5 to 2 tesla (5000 to 20,000 gauss, just to confuse the issue with more scientific units). So any metal object can become a dangerous projectile if it finds its way into the scanning room: paper clips, pens, keys, even medical equipment like stethoscopes, IV poles, or oxygen tanks. In this day of implants and prosthetics, metal objects can actually be inside the body of the prospective patients: certain older dental implants, for example, or aneurysm clips in the brain, or pacemakers. The latter are used to treat arrhythmia (abnormal heart beat), which affects as many as 2.2 million Americans alone, but older models can be made of magnetic materials. There is also a risk of burning heart tissue, because some devices use leads: electrical components capped with metal to connect the device to the heart muscle.
A year or so ago, a team at Johns Hopkins University figured out some ingenious ways to safely perform MRI scans on people with implanted defibrillators and pacemakers. It wasn't a single solution, but rather a combination of methods: some very simple and obvious, like turning off a defibrillator's shocking function for the 30 to 60 minutes it takes to complete the scan; lowering the strength of the electromagnetic field and the amount of electrical energy used at peak MRI scanning; and figuring out how to "blind" the implanted devices to their external environment, making them impervious to misfiring from the MRI machine's rf field.
But babies still present a sticky wicket when it comes to medical imaging. X-rays are just too potentially dangerous to infants because of the ionizing radiation (ditto for pregnant women), so doctors are reluctant to use that tried-and-true technology. Babies tend to find CT scanning equipment big and loud, and therefore upsetting; also, again, the x-ray exposure isn't really a good idea for their tiny developing bodies. MRI is equally big and loud, made more difficult because babies tend to squirm in distress at being confined in the Big Magnetic Donut From Hell. (Heck, plenty of adult patients find the MRI procedure a bit upsetting, and/or have trouble holding still long enough to take a decent set of images.)
If the infant is premature and confined to an incubator, getting a decent brain scan to check for possible damage or irregularities is especially daunting. Doctors understandably want to minimize any time the "preemie" must be handled or exposed to loud noises (or to the germ-laden environment outside the incubator), since either can cause irregular heart rate and breathing patterns -- potentially life-threatening to such a fragile creature. And yet, as many as half of early premature babies suffer from very subtle abnormalities of the brain that can be linked to later developmental problems -- which often don't manifest until at least 10 months of age, at which point it may be too late to medically intervene. It's quite common for premature babies to fall victim to infection from the wall of the uterus or placenta, or have an inflammatory response at birth that affects the brain. Sometimes the damage is caused by something so simple as an under-developed cardiovascular system that just isn't strong enough to pump enough blood to the brain during those crucial few weeks after premature birth.
So getting an MRI scan early on could alert doctors to such conditions much more quickly. Fortunately, a couple of years ago, scientists at the University of California, San Francisco (UCSF) collaborated with General Electric to design a special incubator compatible with MRI machines. 
It's made entirely of plastic, aluminum or brass -- i.e., non-magnetic materials -- and small enough to be easily transported. We're talking about a double-paned Plexiglass capsule, with fresh air piped in from the outside. The infant is usually sedated, since the MRI scan can take an hour or so. Also, it's still very noisy. At least it's now easier to get the images needed to identify potential problems while effective treatment is still an option.
But what about imaging the brain when we're awake? For decades, even after the invention of CT scans and conventional MRIs, there was no way to image or observe the brain in action. Then came functional MRI. It's pretty much the same technology, with a twist: it identifies those regions of the brain where blood vessels are expanding and other chemical changes are taking place, or perhaps a few extra shots of oxygen are being delivered. That's important information, because it's an indication of metabolic activity: that region of the brain is processing information and issuing "commands" to the body. So by studying which areas show increased activity, scientists can learn which areas of the brain are activated as the patient performs any given task. There have been rather large numbers of fMRI studies performed in recent years, on everything from glossalia (speaking in tongues) and how the brain reacts to chocolate, to the rather breathlessly reported news of an fMRI study of political affiliations that threw some folks in the scientific blogosphere into a tizzy this week over the questionable reporting.
Electroencephalography (EEG) has been the mainstay for infant brain imaging because it's safe and registers changes in brain activity very quickly. Alas, the technique can't reliably and precisely pinpoint where in the brain the activity originates. There have been a few fMRI brain scans of infants performed while said infants were asleep or sedated, but this doesn't tell researchers as much as they'd like to know about the developing infant brain. Ideally, they would like to be able to scan babies' brains as they sit comfortably on a parent's lap and/or interact with their environment. Then they could really see the baby brain in action. Infancy, after all, is a critical developmental period. That's when connections between neurons first form and break, nerve cells branch out to form networks, and various parts of the brain take on their specialized roles in vision, language, and other complex cognitive functions. When that early processing goes wrong, it can lead to learning disabilities of language impairments, among other complications.
In more recent years, high-density diffuse optical tomography (DOT) and its cousin, diffuse optical spectroscopy (DOS) have come into favor for infant brain imaging. This approach was originally developed in the 1990s by various research groups in the US, Europe, and Japan, and innovations have come fast and furious ever since. Last year, researchers at the Washington University School of Medicine in St. Louis (WUSTL), for example, announced they had developed a DOT system specifically to study the infant brain. Their system is much smaller --about the size of a small refrigerator -- quieter and more portable than MRI or CT scanning machines, and the goal is shrink the size down even more, to about the size of a microwave. It's not just useful for basic research, either: the WUSTL system makes it possible to monitor infants with brain injuries in their incubators, making it easier to keep track of their progress and provide better treatment.
Instead of ionizing radiation like x-rays, DOT uses harmless light from the near-infrared portion of the electromagnetic spectrum. Unlike x-rays or ultrasound, near-IR light passes through bone with little attenuation, so scientists can use the diffusing light to determine blood flow and oxygenation in the blood vessels of the brain. When these characteristics increase, it indicates that the particular area of the brain being scanned is contributing in some way to the mental task at hand.
Ah, but how does one scan an infant? You can see the system in action here. It's as simple as attaching a flexible cap to the baby's head, 
covering whatever area the doctors want to image. (I should note that this nifty image isn't the WUSTL system, but a similar approach using near-infrared spectroscopy developed at Helsinki University of Technology in Finland. It's just such a cool, slightly creepy photo, I had to use it.) The cap might look simple on the outside, but inside it contains fiber optic cables. Some of those shed light on the head; by determining how the light is diffused or scattered, researchers can glean useful information about brain activity.
Light passes out of one fiber optic cable, diffuses through the tissue, and is received by another cable. Yes, light does diffuse through tissue, as anyone who has ever held a flashlight up to his hand can attest. According to Joseph Culver, an assistant professor of radiology at WUSTL, "The flashlight's white light becomes visibly reddened because there's a window in the near-IR region of the spectrum where human tissue absorbs relatively little of the light." Anyway, based on this diffusion data, the machine's computer creates a 3D tomographic image based on whether the hemoglobin in the blood is oxygenated or deoxygenated to determine brain activity.
I mentioned the Helsinki NIRS technology above; that's certainly another strong contender in the drive for safer infant brain imaging, although it's pretty much diffuse optical spectroscopy, as far as I can tell. (A rose by any other name, and all...) It's already commonly used to monitor cerebral blood flow in preemies, and now it's moving into studies of brain activity during specific cognitive or sensory tasks. Here in the US, researchers at Texas A&M University worked with neuroscientists at Massachusetts General Hospital to develop a DOT imaging apparatus that also uses a cap or headband. Theirs employs a number of light-emitting diodes and light-sensing detectors to emit and detect near-IR light, looking, as always, for changes in blood oxygen levels to form the images. (Massachusetts General is also developing a DOT system designed to work in conjunction with conventional x-ray mammography to detect breast cancer earlier, with fewer false positives and less need for follow-up biopsies, but that's a bit off-topic for this post.)
The WUSTL system is a little different from other approaches because it combines diffuse optical imaging with tomography -- i.e., a computerized approach to the data analysis that makes it possible to image sections at greater depths. It's thanks to the greater density of the fiber optic cables they used that this is possible. All this is great news, but the WUSTL system isn't quite ready for prime time: it's still being tested for safety and effectiveness. The researchers did conduct one study on human volunteers to demonstrate their system could achieve sufficient resolution for functional brain imaging. They were able to link stimulation of parts of the visual field to the activation of corresponding areas in the brain's visual cortex -- a classic functional brain imaging technique called retinotopic mapping that was also used to test the validity of earlier technologies like fMRI and positron emission tomography (PET).
I think it's safe to say that the innovations will continue to develop. Some day, all those parents wondering, "What is my baby thinking?", might be able to turn to cutting-edge, non-invasive, optical imaging technology for the answer.
Jennifer, you should compile a group of these essays into a book--
BTW, my son is busy trying to work out the imaging algorithms using Monte Carlo simulations and neural nets, for a trapezoidal liquid xenon sensor for a PET scanner
that would improve the resolution markedly.
Posted by: Gordon | November 17, 2007 at 10:55 AM