Medicine's new eyes

When something goes seriously wrong inside the body, there's only one course of action: look inside, identify the problem and then figure out how best to fix it. For most of medical history, that crucial first step of making a correct diagnosis has required penetrating the living person's sealed physiological system, inherently a dangerous and complex surgical process. Then, a century ago, the arrival of the X-ray gave medicine the ability to see through the body's surface without cutting it open.

While X-ray images in various forms continue to be one of medicine's diagnostic mainstays, they offer a limited, static portrait of the living human organism. Over the last 10 years, imaging technology has traveled light years from the world in which X-rays were the only means of looking into humans without resorting to the knife. An explosion of advances in other forms of imaging technology has given physicians new eyes, allowing them to peer into the most minute recesses of the body and observe dynamic physiological and biochemical processes in action. As a result, for the first time clinicians and researchers can ask biological questions directly and watch the living, fully awake body as it responds.

For patients, this has meant vast improvements in care and raised hopes for better diagnosis and cure where none existed before. From knee injuries to Parkinson's disease, the advanced imaging technology provides a means of rapidly and precisely measuring the extent of tissue damage and locating functional disturbances. Armed with such knowledge, specialists can then choose the least invasive and most effective treatment option. There is less need for exploratory surgery, less possibility of causing inadvertent harm and increased likelihood of rapid recovery.

Investigators in a wide range of fields now employ a great wealth of advanced imaging tools—computed tomography, functional magnetic resonance imaging, single photon emission computed tomography, and positron emission tomography scans. (See An Imaging Glossary.) Through the eyes of this technology, investigators can visualize human physiology in action and, increasingly, explain how it works at the most basic levels, from thought to movement. "Most people think of imaging as something static," says Bruce L. McClennan, M.D., chair of the medical school Department of Diagnostic Radiology and chief of diagnostic imaging at Yale-New Haven Hospital. "But those days are gone forever. More and more, physicians want not just form but function. And we can deliver it. It's brought about a revolution in how we practice medicine. Already we've cut down drastically on the use of X-rays and X-ray films, and they'll virtually disappear in the next century. And that's just the beginning.

"Just one example: we're now developing interventional imaging magnets to do medical procedures while the patient is actually inside the magnet. The information will be right there for the clinician. For the patient, it means less waiting, more accurate diagnosis and treatment, less surgery and swifter recovery."

For researchers, seeing the body through the new imaging devices has begun to answer ages-old questions about what actually goes on in almost every imaginable bodily functions. Anatomical structures and their respective biological functions can be studied simultaneously. For example, the contracting walls of the heart and the firing cells in the brain can be observed in action so that normal and abnormal behaviors of the body's essential functions can be charted and compared. Equipped with the findings, physicians and scientists can develop new therapies for disorders. The observing eye of the investigator can zoom without resistance through every passage and wall in the body to uncover otherwise hidden disease processes. The imaging technology needed to do this is enormously complex, yet its effect is to simplify treatment and greatly ease and speed the healing process.

While the diagnostic imaging field is now so wide that no institution can command a full range of applications, Yale is a leader in an exceptionally high number. An especially important area is breast needle localization, in which biopsies of suspicious lumps can be accomplished with much greater accuracy. This may prove to be an invaluable tool for cancer patients, most importantly in the diagnosis of breast cancer. "Breast imaging," says Dr. McClennan, "is a huge problem facing our field." Eventually, he believes, the emerging capability to image breast tissue accurately while simultaneously removing suspicious lumps "will obviate the need to go to the operating room. We're going to eventually eliminate the knife."

Improvements in high-speed diagnostic imaging tools have already saved many lives, countless hours of suffering, and enormous amounts of money by shortening the time needed to come up with an explanation for patients' woes. One recent example is a new kidney stone diagnostic procedure, developed at Yale, that has eliminated the need for long waits to determine the cause of severe side pain. (See Throwing Stones.) Patients who only three years ago would have endured as much as 24 hours of unrelieved suffering before the source of their pain could be determined and treatment begun can now begin treatment within five minutes of arrival in the Emergency Department.

Many of the advances have been made possible by the application of computing technology to imaging devices. In its turn, the computerization of diagnostic imaging is rapidly reshaping the nature of medical communications. Yale is part of a nationwide movement exploring the possibilities for computer networking among physicians, allowing for faster diagnosis, the sharing of information between specialists and clinicians over long distances and improved storage of patient data.

While the newer imaging technologies have opened up new possibilities for investigation and improved clinical care, they also serve the recent priorities of managed care for holding down costs for therapies and preventing more serious, and more expensive, medical problems. For instance, advances made possible by imaging technology, such as the high-speed diagnosis of kidney stones and needle localization biopsies, reduce time patients need to spend in the hospital and often end the need for multiple and redundant procedures. They also potentially lower the number of patients whose conditions worsen, resulting in the need for extended care.

Watching the brain work

In the federally designated Decade of the Brain, it is inside the skull that the frontiers of medicine have been pushed furthest by applications of imaging technology. Perhaps more than any other institution, Yale is noted for using its imaging technology to learn more about how the brain functions. Investigators are mapping out brain structures and exploring the biochemistry of many fundamental mental processes, such as memory, vision, reading, attention, hearing and even smell, as well as disorders in those processes. These conditions include dyslexia, schizophrenia, autism and brain trauma from stroke, alcoholism and epilepsy. "Brain imaging has become one of the hottest fields in the biological sciences. There are always new applications for MR being found," says medical physicist R. Todd Constable, Ph.D., an assistant professor of diagnostic radiology, who works closely with clinicians on magnetic resonance imaging (MRI) projects. "Our research imager is swamped. It's tough to book time."

Much of that work involves mapping out brain anatomy and function. In order to observe the brain in action, study subjects enter the machine and then are given a battery of tests while their brain activity is imaged and recorded. "Any task you can perform on a computer or a video player," says John C. Gore, Ph.D., director of the NMR Physics Research Group and professor of diagnostic radiology and applied physics, "can be projected, controlled and recorded." Study subjects lie down inside the functional MRI (fMRI) machine, which is specially outfitted for research. It may have a video screen placed just outside it from which images are then reflected through a series of mirrors to the supine subject. Headphones can be used for delivering sound tasks, or an air circulation system for olfactory studies. Anyone who has undergone an MR scan knows the magnet's hollow rhythmic beat can be unnerving. Subjects can't move about inside the tube and anyone prone to claustrophobia would be better off skipping the exercise. While the subjects perform tasks, whether it's bending a finger or reading a word, their brain activity can then be imaged and sites mapped for specific activities, from muscle activation to language usage.

With all that data as a baseline for normal brain anatomy and function, investigators then begin to observe differences in the brains of those with cognitive and mental disorders, from learning disabilities, post-traumatic stress syndrome and epilepsy to schizophrenia, alcoholism and stroke. (See What the Brain Thinks While Reading) The investigators hope eventually to develop reliable diagnostic tools and therapies for these disorders that remain among the most difficult to diagnose and most resistant to treatment.

Already, neurosurgeons and neurologists have begun to find practical tools derived from these experimental studies. For instance, Dennis Spencer, M.D., the Harvey and Kate Cushing Professor and chair of neurosurgery, has been testing fMRI as a noninvasive, extremely rapid method of examining the brain prior to surgery. Patients with seizure disorders or tumors who need surgery may soon be able to have their brain anatomy mapped out without the extended preoperative procedures that are now necessary. (See Peeling Back the Skull without a Knife) The potential savings in time, money and pain are almost incalculable.

Stroke is another area in which new applications of imaging technology hold great promise. By understanding which areas of the brain have been damaged by trauma or stroke, more appropriate therapies can be prescribed for individuals. Assistant professor of neuroradiology Robert K. Fulbright, M.D., director of clinical fMRI, has shown that stroke, epileptic seizures and other neuronal activity change the way water molecules move in the brain. Diffusion weighted imaging, an MRI technique that measures these changes, is now regarded as the most sensitive way to detect stroke in patients during the first few hours after symptoms occur. Actual scanning can take less than a minute, with results following within a half hour. "We can rule out hemorrhages and tumors and detect stroke very, very early. This gives us a tool for rapid treatment and for developing new treatments. New drugs are now in development to limit damage from, or even prevent stroke."

New ways to improve care

The advantages for clinical care and medical research the newer technologies offer are easy to imagine. The reality of their application is much tougher.

Much about how MRI works is simply not understood, and the process of getting readable images from machines can be enormously complex. It's not like an X-ray in which the tube shoots, film gets exposed to radiation on the other side of the body and a photographic negative of anatomical structures follows. Even the most basic MRI scan requires a highly specialized team to operate it and process the data emerging from it. The more complex the question the less certain are the data and the more post-processing must take place to clarify just what the eye of the scanner has seen. "You don't just get an area of the brain to light up," says medical physicist Dr. Constable of studies of brain activation. "Nobody knows why functional MRI works or why images change," adds Dr. Gore.

That is why many of the frontiers of diagnostic imaging are being explored as much by physicists as by radiologists. Dr. Gore, who is himself a physicist, directs a large team comprising physicists, neuroscientists, radiologists and computer scientists who work with researchers throughout the School of Medicine and indeed the entire University using MRI for their research. Biological investigators need Gore's group to help them develop imaging methods and then explain just what it is they're seeing. Says Dr. Gore: "We continually find that what we think are simple tasks—like listening to a tone in the ear for example—may also evoke a transient response in areas of the brain that we were not expecting." Figuring out what causes those responses and eliminating "noise" from small movements or individual variations in brain structure require complex calculations.

The future of imaging technology promises to alter medicine radically, from diagnostic and treatment methods to administration of care. Some of the most speculative uses already developed for the new imaging technologies seem to have jumped from the screens of science fiction movies.

Eventually, patients will very likely be able to walk into a clinic, get a complete body scan in a matter of minutes, have it diagnosed for problems and then stored away for future reference. Kevin M. Johnson, M.D., a diagnostic radiologist doing MR research, has already perfected a new technique for rapid total body MRI, in which a patient's entire body can be imaged without great blurring in as little as a scant 18 seconds. Using an adaptation to the scanner, Johnson can move his study subjects on a sliding table swiftly through the MRI machine, getting 180 cross-sectional images along the way. The complete picture gives a much wider scope for diagnosis than current procedures. The images can also be stacked for animated tours. While many questions remain, Dr. Johnson believes that the new technique is especially promising for detecting the spread of cancers, which now is usually done in limited regions using a CT (computed tomography) body scanner and an ingested or injected nuclear tracer. "We can do a workup faster and with less inconvenience and suffering for the patient," says Dr. Johnson, assistant professor of diagnostic radiology. "And you get to see the entire body and not just a limited area." He believes that, when coupled with existing tests, the rapid total body MRI will eventually provide better cancer detection.

The three-dimensional quality of computer animated graphics has given viewers playing video games or watching movies a feeling of entering into a world of virtual reality. A similar experience is now possible in traveling at high speed through the body. Where now a viewing scope must be inserted into the partially anesthetized body and passed through the colon, aortic vessels or bronchial tubes until an obstruction is encountered, radiologists will soon rely upon virtual equivalents. And the virtual tour will be a better diagnostic tool than current invasive procedures. Colorized, animated, volumetric renderings on the computer of CT scans provide a realistic image of the interior of the body's passages. Using a joystick, the viewer can travel up and down or zoom in on sites, such as polyps, atherosclerotic plaque buildup or ulcers. There are major advantages to the virtual colonoscopy, angioscopy and bronchoscopy beside not subjecting patients to unpleasant, invasive and potentially hazardous procedures. When an obstruction is encountered that would halt an actual physical exam, the virtual examination simply passes right through it. Using color processing, blood can be "drained" from the heart and vessels to examine walls and valves, which would otherwise be obscured, for damage. Eventually, a completely animated, virtual tour of the body may be possible. "The potential is great," says James Brink, M.D., vice chair for clinical affairs and associate professor of diagnostic radiology, who is working with the technology. "Is it ready for primetime? It's too early to tell."

Images without film

The most far-reaching impact from diagnostic imaging advances, however, may be through communication technology. Digitizing imaging allows for high-speed computer link ups among specialists and clinicians. Doctors on opposite sides of the world will be able to work together to come up with the best diagnosis and treatment for patients. Digital imaging also reduces the space needed for storage of images and the number of personnel necessary for maintaining film archives. At the same time, it enhances access by allowing those with appropriate entry codes to download information. "Theoretically," says Pradeep G. Mutalik, M.D., who is director of radiology information technology and is developing medical communications systems for the Department of Diagnostic Radiology, "the day has arrived when we can dispense with film." Already some military hospitals have gone entirely filmless. Since 1993, digital transfer of images has been possible to the intensive care units at Yale-New Haven Hospital. Eventually, the entire hospital complex will be wired for digital information sharing.

Dr. Mutalik and his colleague Vladimir P. Neklesa, M.D., are responsible for setting up Yale's Picture Archiving and Communications System (PACS), including a Web-based system in which authorized physicians will be able to log on from their office workstation and download archived images. (See A Virtual Image Bank) The future of radiology as a profession and medicine as a whole will be radically altered by so-called "teleradiology," in which radiologists will provide service to a large region from a single center. "People now see the world through their computers," says Howard P. Forman, M.D., vice chair for finance and administration in diagnostic radiology. "We constantly ask ourselves, How can we deliver information and images to physicians in a seamless manner?"

Software versus hardware

While the tremendous value of many of the technologies is now readily apparent, not all high-tech medical equipment has proven its worth. For many years, promising and extremely expensive new imaging technology seemed to arrive at the medical marketplace every few months. Medical centers invested huge sums to acquire advanced equipment and systems, in some cases only to see it superseded within months. The almost crazed pace of imaging technology development that took place in the 1980s has slowed considerably as the hardware revolution seems to have crested for the moment. Most recent advances have come about through development of software, new applications of existing technologies and the convergence of a variety of techniques rather than the creation of another new generation of machines. "It used to be," explains Dr. Forman, "the field developed things in what could be seen as a backward way. A new technology came along and we looked for ways to apply it. Now, we develop applications from the technology that has stabilized. The cutting edge has slowed down."

Part of that slowing has occurred because of economics. The arrival of managed care has meant that the high cost of purchasing high-tech care systems must be justified through improved patient outcomes over existing forms of treatment. With a new, high-power fMRI machine costing more than $4 million just to purchase and millions more to operate, clinicians and researchers need to prove that it will not only provide better clinical outcomes for patients, but will pay its own way. Clinicians must now think both like healers and like business managers. Says department chair Dr. McClennan: "It's a different world. The assessment of technology is much more demanding because there is such a constraint on resources. The powers that be say, 'How much faster is it?' 'How much cheaper?' and 'Show me the outcome studies before I'll spend a dollar.' We're constantly sorting out the hype from what will really bear fruit."

Given the enormous costs of equipment and the rapid sweep of technological change in diagnostic imaging, the risks of doing a high-tech belly flop are great. The School of Medicine is continuously bombarded by companies seeking testing and adaptation of their equipment. The capabilities claimed by the manufacturers of these new technological wonders sometimes vastly outpace reality. There are occasions when new systems can do more than the current state of patient care and academic research actually demand. Says Dr. McClennan: "We need to ask, where is the technology leading us and who is in charge? The challenge is to keep medicine and technology married and not get distracted." Like most marriages, the road has sometimes been bumpy, but it's a marriage that all believe will continue. YM