Advances in imaging technology have brought about a revolution in the diagnosis and treatment of diseases and disorders. One of the best applications of this is in neuroradiology where advanced techniques, as well as tried-and-true modalities such as structural MRI, are now capable of monitoring a wide range of cognitive and physiologic activities in the brain. Structural MRI, as well as advanced brain scanning methods such as functional MRI (fMRI), MR spectroscopy (MRS), diffusion-weighted imaging, perfusion-weighted imaging, electroencephalography (EEG), magnetoencephalography (MEG), and positron emission tomography (PET) are all being used in countless research studies, as well as in clinical situations.
“The way the field is shifting is that in the past when you would do a CT scan or MRI of the brain, you were actually looking at an anatomic image of the brain,” explains Suresh Mukherji, MD, chief of neuroradiology and head and neck radiology, University of Michigan Health System, Ann Arbor. “Now we’re actually seeing how the brain works in terms of electrical activity, blood flow, and enzymatic pathways.” This has opened the door for a wide range of studies, assessing everything from bipolar disorder and Alzheimer’s disease to attention-deficit hyperactivity disorder (ADHD) and addictive behaviors. Beyond research, Mukherji points out that this new technology is even available in clinical situations such as when diffusion-weighted imaging is used to diagnose acute strokes.
IMPROVED IMAGING TECHNOLOGIES
Higher resolution imaging systems and a better understanding of science have contributed to the tremendous growth in the field of noninvasive imaging of brain function, says A. Gregory Sorensen, MD, associate director of the Charlestown, Mass-based Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital. “The standard among MRI systems used to be 1.5 tesla, but now some research facilities such as ours are using 7 tesla scanners,” says Sorensen. As a collaboration among Massachusetts General Hospital’s Department of Radiology, Massachusetts Institute of Technology (MIT), and the Harvard-MIT Division of Health Science and Technology, the research center creates and applies advanced imaging technologies in a myriad of applications. The center’s 7T MRI allows researchers to image the brain with sufficient resolution to identify miniscule anatomic details and to localize regions important for specific brain functions such as memory, language, and reward. In addition, a 306-channel MEG scanner is used to image the brain’s electrical activities with very high temporal resolution in real time. (MEG is a noninvasive method for the recording of electromagnetic cerebral activity capable of measuring temporal resolution in milliseconds. Whole head MEG measures the magnetic fields generated by the brain using a set of sensors mounted on an anatomically shaped helmet. The sensors are positioned about 3 cm from the patient’s head.) Combined data from both these systems have enabled researchers to understand how parts of the brain communicate with each other. “Although MEG has existed in a rudimentary to a very advanced way at a number of institutions for some time, the idea of combining it with MRI is new and has resulted in a powerful tool,” says Sorensen.
|In a study designed to detect cognitive impairment, a 72-year-old man’s baseline brain MRI is shown in black/white; the area of brain atrophy is in reddish color; the medial temporal lobe region found to be diagnostic for future cognitive decline is in yellow (only the left side of the medial temporal brain is outlined). Courtesy of Henry Rusinek, PhD, New York University School of Medicine.
While radiologists have always historically debated which imaging modality is most effective, Sorensen reports that much of this type of thinking has changed as researchers and clinicians recognize the value of each of these new technologies for different applications. “I think increasingly people are realizing that some techniques are naturally better at answering certain questions,” he says.
Radiologists are in agreement that the technologies have their own strengths and weaknesses. While MRI can see the whole brain, MEG and EEG are more useful in scanning specific parts of the brain. “Some of these technologies are more effective in scanning areas closer to the surface of the brain while others are better for deeper regions,” explains Sorensen. “Because each of these cameras has different strengths, we naturally want to combine their technologies.”
AN INTERDISCIPLINARY APPROACH
As researchers continue to discover new applications for this technology, the need for an interdisciplinary focus has been apparent. Most institutions encourage strong working relationships between radiologists, neurologists, psychiatrists, oncologists, and other physicians and medical professionals that may be involved in these types of studies. Sorensen notes that his center even has a psychiatrist on the radiology payroll because of his role in understanding the brain. “Our chairman has recognized for a long time that it pays to hire people with very disparate backgrounds to focus on imaging problems,” he says.
Mukherji concurs that this growing field requires specialists from many different areas working together. His work with brain tumors keeps him in direct contact with the hospital’s radiation and medical oncologists. He also is closely involved with psychiatrists in evaluating patients with schizophrenia.
Still Mukherji points out that some radiologists may worry in the years ahead about this overlapping of specialties, particularly since increasing numbers of nonradiologists are acquiring imaging equipment for their studies. “One can almost see a scenario play out in which neurologists or psychiatrists who start performing their own functional imaging then go on to do their own anatomical studies,” he says. “If they start believing they don’t need the radiologist to perform these studies, you can see where some uneasiness could develop,” says Mukherji.
Currently, however, the interdisciplinary approach to brain imaging can be seen only as an asset. The following profiles demonstrate that many physicians and researchers with diverse backgrounds work closely with radiologists in establishing these research studies and assessing the findings.
RESEARCH AT MARTINOS CENTER
Sorensen and his team of researchers are working on a variety of biomedical imaging studies involving brain scanning. Thanks to a grant from the Office of National Drug Control Policy, which funded the center’s 7T MRI system, scientists are developing a better understanding of the biological basis of addiction, which they hope will contribute to better treatments and deterrents for addiction. Specifically, these studies have helped researchers pinpoint specific brain regions that need to be targeted by medications for countering cocaine’s effects.
The Martinos Center has also spent considerable resources on studying the brain areas activated by pain. To track brain activity in response to pain, the center’s researchers have studied fMRI images that reveal that brain structures previously shown to react to rewarding experiences are also activated by pain. This research has been used to advance the understanding of the effects of pain within the brain and will hopefully some day lead to new ways to diagnose and treat pain.
In addition to these types of research studies, the Martinos Center also provides advanced clinical work for a variety of patients being treated at Massachusetts General Hospital. In cases in which routine neuroimaging is limited or has even failed, physicians will consult with the center’s radiologists. For example, Sorensen notes that many patients with epilepsy will initially get MRI scans that are read as normal at 1.5T, yet when they are scanned on the center’s 3T MRI, abnormalities appear. “We combine 3T MRI with MEG to pinpoint the source of their seizures,” says Sorensen. “This combination of technologies can provide more accurate information for the surgeon.”
DELAYED SPEECH IN CHILDREN
Another brain imaging study that has received considerable attention recently involves abnormal brain activity in children with delayed speech. Conducted by Nolan R. Altman, MD, chief of radiology at Miami Children’s Hospital, the study was published in the December issue of Radiology. 1 This research represents the first time fMRI has been used to investigate brain activity associated with speech delay.
According to Altman, fMRI was selected because it is capable of imaging regions of the brain (in this case the cortex) that are activated by certain tasks. “The ability to superimpose the activation maps on an MRI image performed at the same time allows a marked improvement in the spatial resolution not possible with any other modality,” says Altman.
The researchers completed fMRI studies on 17 abnormally speech-delayed children and 35 age-matched children without delayed speech to compare the brain activation patterns between the two groups. The findings indicated that children with seriously delayed speech have higher levels of right brain lobe activity than children without delayed speech, who tend to use the left side of their brains when they listen. “These findings suggest that with fMRI, these children could be diagnosed earlier, resulting in earlier intervention, and early intervention has proven to be critical in treating these speech disorders,” says Altman. “This type of screening may also be a way to monitor these children to see which type of intervention is most effective.” Altman adds that he hopes this research will lead to other studies involving learning disabilities in children.
MEMORY LOSS AND CHEMOTHERAPY
Neuroscientists at the University of California, Los Angeles (UCLA), have used PET to study metabolic activities in the brains of chemotherapy patients who complain of memory problems. Although the term “chemo brain” has been used loosely for many years in referring to chemotherapy-treated patients who suffer from cognitive problems, studies such as this are confirming the reality of this situation.
The UCLA study involved 200 breast cancer patients who had undergone chemotherapy. A smaller subset of this group then went on to have PET scans, which revealed important findings. Specifically, in the women who had underwent chemotherapy, the images showed a difference in metabolic activity in the parts of the brain involved in language, and some areas of the brains of the chemotherapy-treated women looked 25 years older than they actually were. “From a clinical perspective, one of the things our subjects got out of this was that the PET scan validated their feelings,” says Dan Silverman, MD, chief of neuronuclear imaging at UCLA and chief investigator of the study. “Many had thought they were crazy for feeling this way,” he says.
The results of this study are particularly helpful since increasing numbers of individuals have normal life expectancies after being treated with chemotherapy for cancer. “Although these patients may end up being cured of breast cancer, years later many of them claim that the single leading impediment in the quality of their lives is cognitive problems and fatigue,” says Silverman. This condition has been tested primarily in breast cancer patients because many of them are relatively young, have high survival rates, and have professional careers that require cognitive skills. Studies are currently under way to determine if certain drugs or cognitive therapy can help prevent or offset this side effect. Silverman has also applied for additional research monies to conduct a larger longitudinal study in which patients are studied before starting tamoxifen and then followed up over a period of years to determine what metabolic and psychological changes take place.
Silverman’s study can also be applied to a wide range of other disorders involving cognitive impairment. “People can become cognitively impaired from something toxic like chemotherapy, but they can also be affected in similar ways because of medical problems such as hyperthyroidism, depression, or neurological diseases like Alzheimer’s,” says Silverman.
MEMORY LOSS IN HEALTHY ADULTS
Another brain study involving cognitive impairment was conducted by Henry Rusinek, PhD, professor of radiology at New York University (NYU) School of Medicine in New York City. Rusinek’s study, which was published in the December issue of Radiology, looked at healthy adults, between the ages of 65 and 85, using structural MRI to assess subtle changes in the medial temporal lobes over 6 years. 2 “This study demonstrated that we are capable of detecting cognitive impairment, which may lead to Alzheimer’s disease, before the patient shows clinical symptoms,” says Rusinek.
The NYU researchers studied 45 healthy patients and compared images of their brains from year to year. Over 6 years, 13 of the patients showed cognitive decline, and the rate of loss of mass in the medial temporal lobe was the most significant predictor of decline. According to Rusinek, the value of these findings is that measuring brain shrinkage can be used to test the effectiveness of drugs that may delay or prevent Alzheimer’s disease.
At a time when newer forms of imaging technology exist, Rusinek used MRI for the study. “Some could say that we’re performing a crude assessment of neuronal loss, but it’s important to point out that MRI is relatively inexpensive and is capable of detecting very subtle changes,” says Rusinek. He adds that MR spectroscopy would not have been as effective for this study because it is not capable of acquiring data close to the sinuses. However, he points out that researchers at the Mayo Clinic have discovered how to use MRS successfully in studying cognitive impairment. As in Silverman’s study, PET could have been effective in detecting cognitive impairment but was not selected as a research tool due to its high cost.
CHILDREN WITH ADHD
During the past several years, brain scanning has been used in a number of studies related to ADHD in children. A study conducted by researchers at the Laboratory of Neuro Imaging at UCLA, published in The Lancet last fall, provides details of the underlying causes of ADHD with reductions in size of some of the areas of the brain as well as an increase in grey matter proportions. 3 Elizabeth Sowell, PhD, assistant professor of neurology, UCLA, and colleagues undertook the first detailed morphological study using high-resolution MRI and sophisticated computational systems to more accurately determine the specific areas of the brain related to ADHD. Brain assessments of 27 children and adolescents with ADHD were compared with those of 46 control children without the disorder.
The findings indicated abnormal brain structure in the frontal cortices (on both sides of the brain) of children with ADHD, with reduced regional brain size localized mainly to small areas of dorsal prefrontal cortices. The children with ADHD also had reduced brain size in anterior temporal areas on both sides of the brain. Significant increases in grey matter were recorded in large portions of the posterior temporal and inferior parietal cortices in children with ADHD. The researchers stress that these findings may help researchers and physicians to understand the sites of action of the medications used to treat ADHD, particularly stimulant medications. It may also help researchers develop new therapeutic agents that can be effective in treating this disorder.
LOOKING TO THE FUTURE
Continued advancements in the field of neuroimaging are sure to have a major impact on research as well as on clinical practice. Using high-speed and high-field MR imaging, MR spectroscopy, optical imaging, MEG, and EEG, scientists across a wide range of disciplines will explore the properties of biological systems to help understand and devise new treatments for pathologies such as cancer, neurological diseases, and cardiovascular disorders.
One of the areas that will see explosive growth is the use of these imaging technologies as predictors for certain disorders, as well as for actual diagnoses. As Mukherji points out, “Some of these imaging techniques that measure physiologic and metabolic conditions are already capable of providing certain diagnoses,” he says. “Everyone in the field can envision a day in which a relative or friend with something like bipolar disorder or Alzheimer’s disease can be diagnosed earlier with one of these tests, allowing them to receive the appropriate therapies earlier.”
Carol Daus is a contributing writer for Decisions in Axis Imaging News.
- Bernal B, Altman N. Speech delay in children: a functional MR imaging study. Radiology. 2003;229:651-658.
- Rusinek H, De Santi S, Frid D, et al. Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging. Radiology. 2003;229:691-696.
- Sowell ER, Thompson PM, Welcome SE, Henkenius AL, Toga AW, Peterson BS. Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder. Lancet. 2003;362:1699-707.