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 Hawaiµi¶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 noninvasive 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. ³Even 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

Stenger is planning to use these new techniques to measure brain activity and blood flow in the brains of meth users. Ernst says that these limited capabilities are extremely valuable. creatine concentrations in the brain are much higher than glutathione concentrations.´ says Ernst. Regardless. ³It may be partially responsible for causing brain damage and dementia in HIV patients. is developing new fMRI techniques to measure brain function in brain regions that are typically difficult to image with currently available methods. It¶s becoming one of the most important uses of MRI. 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. In parallel. Coupling describes a specific way that hydrogen molecules bond. This allowed them to accurately measure glutathione concentrations in a living brain.cells by preventing oxidative stress. Hydrogen coupling is present in glutathione. Ernst and a UH physicist on his staff. This enhanced . The magnetic detection signal for creatine. the vast majority of the thousands of brain metabolites remain below the detection threshold of even the most cutting-edge MRS systems. Another UH physicist. The researchers hope to elucidate how the brains of meth users are affected by drug use. Ernst relied on complex physics. But that relatively small amount yields a lot of useful information about the status of the brain. Napapon Sailasuta. However. This makes detection of the lowerconcentration biochemical difficult. ³We may be able to measure only 10 to 15 metabolites in the brain. In MRS scans. To date. but not in creatine. Chang and Ernst are using fMRI to study the effects of HIV on brain function. Together with Chang. Andrew Stenger. creatine masks glutathione.´ says Ernst. overlaps with large parts of the signal for glutathione. as well as a marker for brain cell death. a chemical critical to nerve cell function. a process in which oxygenrich compounds (pro-oxidants) damage living cells. Chang and Sailasuta are planning to use this capability in their studies of the brain chemistry of HIV/AIDS patients and meth users. used a quantum mechanical principle called ³coupling´ to devise a way to measure glutathione. HIV patients are living longer due to the efficacy of antiretroviral medications. To extract the magnetic signal for glutathione. Reduced levels of the chemical in the brain may be one of the primary causes of cognitive problems in meth users and HIV patients. Sailasuta and Ernst wrote software that screens out magnetic signatures not attached to the coupling phenomena.

. Over time. MRI could prove to be the ultimate decoding tool for the mysteries of the brain.understanding could prove important in developing new treatment approaches for these individuals. researchers will be able to track more of the real-time chemical and functional activities in the brain. Ernst believes that as fMRI and MRS technologies become more sensitive.

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