Motion Correction in MRI
Lying absolutely still inside the extremely tight confines of a metal tunnel, surrounded by a terrifying whirring sound, is a difficult task. Unfortunately, it is a necessary one for MRI (magnetic resonance imaging) patients, including the very young, the handicapped, and the mentally ill. Without five minutes of near-complete stillness, doctors cannot obtain high-resolution MRI images. Any motion greater than one-twentieth of an inch can corrupt a scan. The requirement that a subject remain motionless is one of the key obstacles to wider and more effective usage of MRI scans.
Thomas Ernst, of the University of Hawai‘i’s John A. Burns School of Medicine, is in the early design stages of a system to correct that problem. The system would consist of a special reflective marker, a small camera mounted inside or near the MRI chamber, and advanced software. MRI technicians would place the special marker (the size of a coin) on the part of the patient’s body targeted for the scan. The marker would make it possible to measure the six degrees of freedom required to track a moving object through space. Those degrees include the position in space (X, Y, and Z planes) and the rotation in space (pitch, yaw, and roll). “We hope to develop a camera system that would observe the marker and extract its position hundreds of times per second. The camera would feed that information back into the scanner, allowing for continuous position correction,” says Ernst, who is working on the system with colleagues at the University of Wisconsin–Milwaukee, the Medical College of Wisconsin, and the University of Freiburg in Germany. The new motion-correction system would have significant advantages over other available approaches, such as faster tracking speed, better stability, and improved ease of use.
The new system would rely on specialized tracking and image processing software designed to allow the scanner to quickly adjust its target area and compensate for patient movement. Building such a system is a daunting task, says Ernst. Capturing and digitizing dynamic images at rates of hundreds of frames per second is extremely difficult even with simple imaging tasks, let alone the more difficult job of recording the human body in minute detail. Should the team successfully develop the system, this technology could revolutionize the MRI field and allow doctors to use MRI far more often and effectively than ever before.
Cutting-edge technologies track brain function in real time and reveal previously unknown details about the makeup of this most vital organ
Cognitive deficits are a common condition in people who use crystal methamphetamine (meth). The same is true for people infected with human immunodeficiency virus (HIV). Scientists also speculate that children born to active meth users might suffer higher rates of cognitive and behavioral disorders. A joint research effort by Linda Chang and Thomas Ernst at the University of Hawai‘i’s John A. Burns School of Medicine (JABSOM) and The Queen’s Medical Center in Honolulu has started to make crucial inroads into deciphering the root causes of these problems, using novel adaptations of functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS).
Standard magnetic resonance imaging (MRI) scans only capture the structure (i.e., the shape or size) of the brain. In contrast, fMRI goes a step further by using advanced imaging techniques to detect brain function or brain activity in real time. MRS techniques can ascertain not just the presence and location of certain metabolically active chemicals, but also the concentration of these chemicals. With a grant from the White House Office for National Drug Control Policy and other research grants from the National Institute on Drug Abuse, Chang, Ernst and a team of physicists and neuroscientists are adding crucial capabilities to these powerful new MRI technologies.
Despite decades of intensive research directed at decoding the inner workings of the human brain, this most vital organ has remained an enigma. Scientists in recent decades have learned the basic physical functions of the different parts of the brain and gained an understanding of some of the most rudimentary biochemical mechanisms that control this complex mass of nerve cells. But no convenient mechanism existed to study the living brain in detail. Brain chemistry changes at death, so cadaver studies were mainly useful for physical insights. Invasive techniques, such as electrode implantation, were both expensive and dangerous, not to mention totally unacceptable for healthy people required as a control group for any scientific study. As non-invasive techniques that are highly accurate and easily repeated, fMRI and MRS both offer opportunities to examine the living brains of large groups of subjects over long periods of time, with little impact on their well-being and at a low cost.
Scientists in the United Kingdom first applied MRS to measure chemical compositions in living humans us ing an MRI scanner two decades ago. Five years ago, these devices bec ame us e ful i n diagnosing human medical conditions. However, the capability of these devices has remained limited. “Even though the technique is available commercially, the software from the manufacturers does not allow you to do many quantitative measurements. So we are developing new methods of detecting certain important chemicals in the brain,” says Chang.
Chang and Ernst are among the first researchers to convert theoretical detection mechanisms of the key neurochemical glutathione into a real-world detection and measurement capability. They performed this work using a research- dedicated Siemens 3 Tesla MRI device at The Queen’s Medical Center. Glutathione is believed to play a critical role in protecting brain cells by preventing oxidative stress, a process in which oxygenrich compounds (pro-oxidants) damage living cells. Reduced levels of the chemical in the brain may be one of the primary causes of cognitive problems in meth users and HIV patients, as well as a marker for brain cell death. “It may be partially responsible for causing brain damage and dementia in HIV patients,” says Ernst.
To extract the magnetic signal for glutathione, Ernst relied on complex physics. The magnetic detection signal for creatine, a chemical critical to nerve cell function, overlaps with large parts of the signal for glutathione. However, creatine concentrations in the brain are much higher than glutathione concentrations. In MRS scans, creatine masks glutathione. This makes detection of the lower-concentration biochemical difficult. Ernst and a UH physicist on his staff, Napapon Sailasuta, used a quantum mechanical principle called “coupling” to devise a way to measure glutathione. Coupling describes a specific way that hydrogen molecules bond. Hydrogen coupling is present in glutathione, but not in creatine.
Sailasuta and Ernst wrote software that screens out magnetic signatures not attached to the coupling phenomena. This allowed them to accurately measure glutathione concentrations in a living brain. Chang and Sailasuta are planning to use this capability in their studies of the brain chemistry of HIV/AIDS patients and meth users. To date, the vast majority of the thousands of brain metabolites remain below the detection threshold of even the most cutting-edge MRS systems. Regardless, Ernst says that these limited capabilities are extremely valuable. “We may be able to measure only 10 to 15 metabolites in the brain. But that relatively small amount yields a lot of useful information about the status of the brain. It’s becoming one of the most important uses of MRI,” says Ernst.
In parallel, Chang and Ernst are using fMRI to study the effects of HIV on brain function. HIV patients are living longer due to the efficacy of antiretroviral medications. Chang is using fMRI to follow a group of HIV patients as they age to determine whether aging exacerbates HIV’s effect on brain activity. Another UH physicist, Andrew Stenger, is developing new fMRI techniques to measure brain function in brain regions that are typically difficult to image with currently available methods. Together with Chang, Stenger is planning to use these new techniques to measure brain activity and blood flow in the brains of meth users. The researchers hope to elucidate how the brains of meth users are affected by drug use. This enhanced understanding could prove important in developing new treatment approaches for these individuals. Ernst believes that as fMRI and MRS technologies become more sensitive, researchers will be able to track more of the real-time chemical and functional activities in the brain. Over time, MRI could prove to be the ultimate decoding tool for the mysteries of the brain.
Linda Chang is a neurologist and professor of Medicine at JABSOM. Her research centers on the use of advanced imaging systems, including not only MRI and MR spectroscopy but also PET scanning, to study brain changes resulting from drug abuse, aging, and chronic disease. She came to the University of Hawai‘i from Brookhaven National Laboratory. Thomas Ernst is a physicist and professor at JABSOM, and serves as the technical director of the MRI laboratory. He was formerly the director of the Department of Medical Physics at Brookhaven, where he also worked with Chang. Their research into meth addiction is particularly critical to Hawai‘i as the state has one of the highest meth addiction rates in the country.
Photo Credits: Images courtesy of Dr. Thomas Ernst, UH John A. Burns School of Medicine
MAGNETOM Trio 3T System courtesy of Siemens Medical Solutions