Nowhere are noninvasive diagnostic and surgical techniques more crucial than when the work involves the brain.
One miscue can drastically alter the life of a patient. Doctors and patients alike want highly reliable information before they undertake the delicate, precise surgery involving the brain. No one wants any surprises. And it is no surprise that imaging is taking predictability to a higher plane.
The advances in clinical applications and research in the area of brain imaging continue to make important progress for conditions including stroke, seizures, brain tumors and mental illness. From positron emission tomography with its ability to measure metabolism and to provide early and noninvasive diagnosis of disease (sometimes preceding any clinical indications) to functional MRI with its ability to measure blood flow, brain imaging is going where only the imagination once could take it.
Emerging imaging capabilities are bringing reliable brain imaging and improved outcomes to patients whose conditions previously precluded them from diagnostic benefit. Brain imaging research continues to cross into clinical reality, offering important insight into more diseases.
The early days
In the beginning of the 1990s, brain imaging involved looking at anatomic abnormalities or structural changes. One imaged the disease process by looking at the change in structure on the normal brain.
“In the last 10 years, there has been a dramatic shift more toward not only looking at brain structure, but also looking at brain function,” says William S. Ball, M.D., president of the American Society of Neuroradiology (Oak Brook, Ill.), and chief of the section of pediatric neuroradiology and director of the Imaging Research Center at the University of Cincinnati’s Children’s Hospital Medical Center.
When you talk about disease involving the brain, it involves more than how it affects the structure, but that was not always the case. In the past, physicians were limited in their ability to see pathology by how the structure had changed.
“What has been a dramatic shift in imaging is our ability to look beyond just structure and be able to look at different aspects of pathology, such as what effect does pathology have on blood flow, brain metabolism and actual function,” explains Ball. “Imaging now has shifted to being able to identify those changes that come about, so we can perhaps diagnose earlier. We have a better understanding of a disease by looking at all of its parts, not just one piece, and we have a better way to follow treatment.”
Ball estimates that in his own pediatric practice in the early 1990s, he spent 99 percent of his time looking at images of brain structure. Now, he says that at least 30 percent of his practice looks at physiology in the brain, metabolism, blood flow and altered function.
“That’s what the future of imaging really holds — the ability to look at all the parts of pathology, not just the structural parts,” Ball says.
With PET, Ball can study brain metabolism and look closer at diagnosing metabolic disorders in children for congenital, as well as acquired, alterations in metabolism. “By being able to image metabolism, we can tell more about what type of metabolic disorder we may be dealing with, and we’re able to follow treatment in those metabolic disorders much better than we could just with imaging anatomic [structures] alone,” Ball says.
PET’s contribution
PET also is instrumental in research done by Carolyn Cidis Meltzer, M.D., associate professor of radiology and psychiatry and medical director of the University of Pittsburgh PET Center. Part of Meltzer’s work involves looking at depression, especially in the elderly, and using brain response information to determine the proper medication for patients.
“We’re just starting to scratch the surface in this area, but I’m looking at a serotonin receptor in the brain, the 1-A receptor, which seems to be very much related to the response of the brain to antidepressant medication,” says Meltzer. “If we could show that in some people — depending on what their levels of this receptor are — they may or may not respond to a certain medication. We can use this scan as a screen when we have a depressed patient. If they have a certain pattern, we’ll say they need to be placed on a particular medication. If they have a different pattern, then they’ll do better with another one, as opposed to a six- to eight-week trial of a medication that doesn’t work.”
PET also plays a major role in determining whether a patient with epilepsy will benefit from resecting the epileptic focus area of the brain. Daniel Silverman, M.D., assistant professor in the department of molecular and medical pharmacology at the University of California Los Angeles and head of the Neuronuclear Imaging Research Group at Ahmanson Biological Imaging Center (Los Angeles) uses PET to do interictal imaging between seizures.
“PET has been very reliable in identifying patients who will benefit from surgery; that is, those who have a better than 90 percent of having significant improvement in seizure frequency,” says Silverman. “What it has not traditionally been as good at distinguishing is the patients that will merely benefit vs. the patients who will become entirely free of seizures, which historically occurs in about 68 percent of cases in large inter-institutional studies.”
CT and SPECT imaging
Although the potential of brain imaging with single photon emission computed tomography (SPECT) may not be as great as competing modalities, the technology still serves an important purpose for some.
“We do ictal (injecting the radiopharmaceutical during epileptic seizure) imaging to map where the seizure is,” Meltzer says. “We’ve done that with PET, but it is much more difficult to do, because the drugs have such short half-life. It is difficult to plan when someone has a seizure, whereas with SPECT, you can keep the drug around longer and inject it right at the bedside.”
Yet, the increase in the number of PET scanners may not bode well for the future of SPECT.
“SPECT data for seizure disorder and for dementia are similar to that for PET, but the resolution of PET for detecting abnormalities in the brain is better than SPECT right now,” says Edward Coleman, M.D., professor of radiology at Duke University Medical Center (Durham, N.C.). “Those of us who have PET scanners have not been able to find much indication for SPECT imaging after we’ve done the PET scan. Because there is a higher resolution and sensitivity, most of us who have PET scanners have not done much SPECT brain imaging. Places that don’t have PET scanners do more SPECT brain perfusion imaging, but I think as PET scanners become more widely available, the utility of SPECT brain imaging will diminish.”
One salvation of SPECT very well may be its ability to do PET-type imaging on gamma cameras. For hospitals that do not have or cannot afford a PET scanner, but have SPECT, the ability to do PET-like imaging serves an important purpose and probably will continue to do so until PET becomes a more affordable option at more locations. The increasing availability and affordability of FDG (fluorodeoxyglucose) has played a major role in PET’s growth.
Computed tomography (CT) continues to offer rapid imaging of the brain with multidetector spiral CT. “[The ability] to image contrast at the time of injection is bringing back a resurgence of interest in CT of the brain,” adds Coleman. “I think there was a tendency to go away from CT toward MR as MR became very good for looking at vascular lesions. With the newer CT scanners, there is going to be further interest in CT of the brain. It is a modality that will continue to be used to provide clinical information.”
Some cancer hospitals use CT for the basic screening of the brain for metastatic disease or hemorrhages and other complications, such as stroke. Surgeons also frequently use 3D models based on CT imaging to see tumors and blood vessels related to the bone in head and neck surgery to see what they are getting into prior to surgery.
Miraculous MRI
Using functional MRI or cortical activation imaging, Children’s Hospital Medical Center’s Ball can look at the brain reacting or activating in response to some type of movement or sensory input.
“We’re using that to [examine] language development in children,” he adds. “We’re able to identify those areas of the brain that are responsible for language, and we’re able to [study] how those areas develop.”
The result of that is the ability to better diagnose and understand disorders in children that involve language development, such as autism, and other types of abnormalities, both for psychiatric and other disease processes that may have a direct effect on how language develops in children.
Count among the advancements of functional MRI the ability to begin to look at what represents pathology, including the ability to do cortical activation studies, and much higher-resolution studies looking at blood flow and blood vessels, but the progress includes another aspect as well.
“The technology continues to advance to improve our ability to see things in a more timely fashion,” Ball asserts. “The major breakthroughs are as much how we use that technology as it is the technology [advancements themselves].”
Of mice and men
At the Center for Advanced Brain Imaging at the Nathan S. Kline Research Institute (Orangeburg, N.Y.), researchers use functional MRI to study different aspects of brain imaging, ranging from imaging transgenic mice, which express different aspects of disease (such as Alzheimer’s disease and drug abuse) to the study of normal brain function and the investigation of cognitive functions of memory and anxiety.
Functional MRI assists in the study of drug abuse by identifying regions of the brain that are involved in the addiction and trying to identify regions of the brain that respond differently in a person who suffers from an addiction to drugs, as opposed to a person who does not. By identifying what aspects of the brain are involved, researchers can look deeper and further into more of the mechanistic parts of the disease. That may involve changes in blood flow and in metabolism.
Joseph Helpern, Ph.D., is a professor of psychiatry, radiology and physiology and neuroscience at New York University Medical Center (New York City) and chief of the division of medical physics and director of the Center for Advanced Brain Imaging at the Kline Research Institute. He and his colleagues are making headway in unraveling the tangle of Alzheimer’s disease. Using functional MRI, Helpern is studying deposits of beta-amyloid protein in the brain of a mouse.
“We can use the mouse to study what effect this beta-amyloid deposition has on the brain, and in that regard we have been able to start to understand how
the [protein] may affect the biophysical properties in a way we can detect with MRI,” Helpern explains. “If I can tease out the information that I need as a medical physicist to improve the ability to image the effects of beta-amyloid in the mouse brain, it increases the probability that I then will be able to turn to the clinical world and try to apply that knowledge to be able to image or to investigate patients with Alzheimer’s disease. Possibly we can use the types of measure we are developing in imaging as a means of looking at therapeutic intervention in humans.”
More magnets
Higher magnetic field strengths have been a significant breakthrough in MRI for brain imaging. “There’s quite a strong move when [hospitals] need a replacement to acquire high-field systems, 3 tesla systems,” Helpern says. “Things get better at higher field. The signal to noise improves with field strength. When you have more signal to deal with, you can do more things and do [them] at a higher resolution. You can improve the imaging. MR angiography, for example, is far superior at 3 teslas than it is at 1.5 tesla.”
Helpern says the reason functional MRI is coupled to magnetic strength is that the techniques currently developed for looking at brain function using that technique are more sensitive to higher field. As the FDA clears 3T systems for use, higher field systems exist now in research systems. Will they eventually trickle down to the clinic?
“It is possible,” Helpern says, “but I think the next level of increase in field strength from 3 Tesla is going to be quite a long time. It will have to be a compelling reason to do so.”
The fact remains: As one increases the field strength of magnets, not everything gets better. “Most of the things you want [do] get better, but it gets harder to place them,” Helpern explains. “As field strength of the magnet increases, so do the magnets themselves and the stray fields they produce that extend outside to areas you don’t want get larger. They become physically more difficult to place in congested places like hospitals.”
The beauty of the technology, of course, is that MRI is noninvasive and safe. “But you are working on very high magnetic fields, strong enough to suck a floor polisher into the magnet,” Helpern asserts. Still, the higher field magnets provide more sensitivity in detecting smaller changes in blood flow.
“It is not impossible to think there may be other brain functions that would occur at a level that might not change blood flow enough for me to detect it,” he adds. “There is a limit in my detection, hence [the need] for higher magnetic fields.”
The future of functional MRI and brain imaging holds great promise, opines Helpern.
“Many of my colleagues in the field and I have a vision of a system where a patient is lying in the magnet and the imaging session becomes much more interactive with the technologist or physician,” he adds. “The console controls are adjusted by the physician, and he is interacting with the patient, [directing] the patient to rotate her head to the right. While the images are coming off in real time, [you are] possibly doing some brain mapping functions, cognitive tasks of people’s brains. The high-speed aspect of the technology is what is very exciting.”
MR angiography and MR spectroscopy
One breakthrough in MRI has been the use of contrast-based MR angiography. “[The technology] has the ability to create very high-quality accurate representation of a vessel in a short time period,” says Ronald Alberico, M.D., director of the neuroradiology division in the department of radiation medicine at Roswell Park Cancer Institute (Buffalo, N.Y.). “Before, in order to get a very good picture of MRI of the blood vessels of the neck, you had to spend 10 to 15 minutes. During that period the patient would swallow, and you would have trouble with motion artifact in the accuracy due to other physical problems acquiring the data.”
If there is a lot of calcium around the blood vessel, you might get inaccurate distortion of the magnetic field and the vessels. Or if there is turbulent flow within the blood vessel, you might lose some signal, but these problems are avoided for the most part with the new contrast-enhanced images, according to Alberico.
“I find that now for a stroke evaluation, I can do an MR angiogram of the head and the neck and fully evaluate the brain for stroke in the same setting, and the patient’s cooperation is less important for the angiogram,” Alberico says. He considers the improvement in the quality of the studies to be a big advance.
The facility also uses MR spectroscopy to measure the chemical composition of specific areas of the brain. “In a cancer hospital, that can help me distinguish areas of scar tissue from the treatment effect from areas of recurrent disease or regrowth of tumor, and that’s very important for the surgeons here,” Alberico says.
Some hospitals are considering the use of MR spectroscopy to help detect changes in a patient’s tumor metabolic or biochemical makeup before the tumor actually changes size.
“Maybe we will be able to predict whether the ongoing treatment is going to work or fail before we have to wait for the tumor to grow or shrink,” Alberico explains. That would offer a valuable time advantage to both doctors and patients.
The ability to measure blood flow enables physicians to see which areas of the brain receive increased blood flow with various activities. “For patients with psychiatric or other
disorders, you can design different techniques to activate and map out areas of activation in their brain that differ from the general population or that may change with exposure to different drugs,” Alberico says. “There’s the potential to look at how the brain rewires itself after infarction or after diseases like multiple sclerosis.”
MR spectroscopy primarily looks at protons, the most common element in the brain and the easiest to detect
with spectroscopy. As magnets get stronger, the accuracy of spectroscopy will increase and the capability to image more compounds will increase. The technology is particularly good at detecting early changes in tumors that one may not be able to see.
“People are already doing phosphorous, which has to do with energy metabolism in the brain and the application of the combination of spectroscopy techniques where you measure proton spectroscopy and phosphorus spectroscopy,” Alberico says.
“Maybe spectroscopy in another element could potentially give us the ability to make histological diagnosis of tumors, not only to say there is a tumor there but to say what kind it is without taking a piece of it,” he continues. “That would be a big advance that I see on the horizon in the next decade or two.”
Magneto encephalography
Instead of MRI, in which the magnet actively perturbs the brain to get information, biomagnetometry or magneto encephalography is a valuable tool to record electrical activity in the brain. The patient is placed in the machine and the electrical activity that goes on in the brain, which induces a change in the magnetic field, is recorded.
“Its primary potential will be in the evaluation of patients with seizures, which is an alternation of electrical activity within the brain,” Ball says. “Biomagnetometry is capable of potentially mapping out the course of a seizure or looking specifically for a seizure focus that other images might not be able to identify.”
The technology remains in its early stages.
Optical scanning
As an emerging technology still in its infancy, infrared or optical scanning is believed to hold its share of potential. When neurons activate in the brain, they change blood flow within the brain, and that change in blood flow may induce an optical change. With that change, optical techniques may have strong potential to be able to guide surgery, for instance.
“Just imagine the surgeon who is facing the brain and must cut out only a certain part of a tumor, but he wants to spare all the normal function around it,” Ball says. “That can be done with the patient awake, performing the function and the optical changes can be identified by the change in blood flow to identify the sensitive area you should avoid.”
Optical scanning has the potential role in the future of helping direct the surgeon to identify what tissue to remove and also identify the good tissue to leave behind.
Knowledge is power and neuroradiologists and physicians have in their hands powerful technology to understand more about the brain than ever before.
