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The first successful nuclear magnetic resonance (NMR) experiments were performed in 1946 by two U.S. scientists. They found that when certain naturally-occurring nuclei were placed in a magnetic field they absorbed energy in the radio frequency range of the electromagnetic spectrum. This energy was re-emitted when the nuclei relaxed back to their original state, a phenomenon termed NMR. With this discovery, NMR spectroscopy became an important analytical method in the study of the composition of chemical compounds. Felix Bloch and Edward Purcell were awarded the Nobel Prize for Physics in 1952 for this discovery.

During the 1950s and 1960s NMR spectroscopy became a widely used technique for the nondestructive analysis of small samples, and many of its applications were at the microscopic level using small-bore, high-field magnets. In 1973, Paul Lauterbur described his research on the high level of contrast that could be realized in nuclear magnetic resonance imaging (MRI). His approach was based on the independent discoveries by Bloch and Purcell of the properties of certain nuclei in the periodic table. Specifically, when some naturally-occurring elements, such as the common hydrogen atom, are exposed to powerful magnetic fields, they emit signals that differ from tissue to tissue. Sir Peter Mansfield developed methodology to analyze the signals and assemble them rapidly into three-dimensional images. Dr. Lauterbur, a long-time NIH grantee, and Dr. Mansfield were recently awarded the 2003 Nobel Prize in Physiology or Medicine for their discoveries in MRI.

Magnetic Resonance Imaging (MRI) in Disease Diagnosis

In 1977, the first MRI exam was performed on a human being. The procedure was long and complicated, taking over 5 hours to produce a single image.  Although researchers had struggled for over 7 years to reach this point, by today’s standards, the image was unrefined and coarse. Critical advances in technology development now allow physicians to image in seconds what used to take hours. MRI has been used successfully for over 15 years to generate soft tissue images of the human body, making it the technique of choice for the routine diagnosis of many diseases and disease processes. Today more than 60 million noninvasive, diagnostic MRI procedures are performed worldwide each year. 

Although there is no doubt that the development of MRI has revolutionized the practice of medicine, one must recognize that individual imaging methods have both intrinsic strengths and weaknesses. NIH researchers are striving to capitalize on these strengths and improve upon known weaknesses to further propel advances that improve medical care. For example, it has long been recognized that tumor oxygenation is a significant factor that influences cancer therapy. Hypoxia, a decrease in oxygen supply, is thought to negatively affect response to radiotherapy and some chemotherapies in solid tumors and may even be a mechanism for malignant progression and metastasis. NIH researchers recently developed a novel in vivo MRI approach for measuring oxygen tension at specific locations within a tumor while observing dynamic changes with respect to intervention. They have now investigated oxygen dynamics in two types of rat tumor models and found considerable intratumoral differences in the distribution of oxygen values between the tumor types. The faster-growing metastatic tumors were more hypoxic than the slow-growing tumors, suggesting that the level of hypoxia may be related to tumor growth rate and poor vascularity. This approach can provide valuable insight into tumor physiology and response to interventions, assisting in the development of novel therapeutic strategies.

 

Image-Guided Surgery

Image-guided surgery systems strive to enhance a surgeon’s ability to utilize medical imagery to decrease the invasiveness of a procedure as well as to increase accuracy and safety. NIH researchers have designed and developed a guidance and visualization system which uniquely integrates data analysis and on-line guidance into the interventional MRI setting. Use of this system enhances and speeds up tissue characterization and precise localization and targeting. To date, this tool has been used in numerous neurosurgical procedures and has been critical in providing surgeons with full access to all available imaging data.  The system’s flexible design will allow its expansion into a highly integrated suite of tools for image analysis and visualization. 

Functional Magnetic Resonance Imaging (fMRI) of the Brain

Functional magnetic resonance imaging (fMRI) is a relatively new technique that builds on the basic properties of MRI to measure quick and tiny metabolic changes that take place in the active brain. Thus, fMRI studies are capable of providing not only an anatomical view of the brain, but a minute-to-minute recording of actual brain activity. This technology is now being used to study and compare the anatomy of the normal, diseased, and injured brain and to assess risks associated with surgery or other invasive treatments. Functional MRI can also help physicians determine exactly which part(s) of the brain is/are responsible for crucial functions such as thought, speech, movement, and sensation. This information can help physicians monitor the growth and function of brain tumors and therefore better plan surgeries and radiation therapies; enable the detection of abnormalities that might be obscured by bone tissue with other imaging methods; develop novel treatment and intervention strategies for brain disorders such as dementia and seizures; and enable detection of a stroke at a very early stage such that physicians can initiate effective treatments earlier.

To date, the most popular fMRI technique utilizes blood oxygenation level-dependent (BOLD) contrast, which is based on the differing magnetic properties of oxygenated and deoxygenated blood. These magnetic susceptibility differences lead to small, but detectable, changes in image intensity. Unfortunately, head movement and physiological sources of variability often make detection of signal changes difficult. NIH investigators have recently introduced a new method for removing movement variability artifacts using a motion sensor system combined with adaptive noise filtering techniques. This computerized filtering approach can be implemented in real-time to allow for continuous monitoring of fMRI during clinical and cognitive studies.

 

Functional MRI to Study Language and Treat Epilepsy

Functional MRI has been used extensively to study language processing in adults, and is being increasingly applied to the study of language function in children. To date, abnormalities in brain structure, cognition, and behavior have been described in children born prematurely. However, there is no direct in vivo evidence demonstrating abnormal neural processing in these children. As language deficits have important and far-reaching implications for academic and social functioning throughout development, researchers compared brain activity associated with phonetic (sounds) and semantic (meaning) processing of language between term and preterm children. Analyses of brain activity associated with the phonologic and semantic processing of a children’s story demonstrated that 8-year old term and preterm children differ in their brain processing of language-based tasks. In addition, brain activity correlated significantly with verbal comprehension IQ scores in preterm but not term children. Additional studies are underway to determine whether the patterns of brain activity observed during language processing tasks can be useful diagnostically or in monitoring educational or therapeutic interventions.

Functional MRI also provides tremendous opportunities for the study and treatment of epilepsy. NIH researchers are using fMRI to integrate information on the suspected location of a brain seizure with information about surrounding brain function in order to improve surgical outcome in epilepsy patients. Initial developments have already been applied to surgical procedures used to alleviate brain seizures in patients with epilepsy. In one case, an early form of surgery employing fMRI strategies was used to treat a patient suffering from as many as 100 seizures daily. Post-surgery, the patient’s seizures have almost completely stopped resulting in a significant increase in quality of life.   

Dr. Lauterbur was recently quoted as saying “I knew it [MRI] would be a useful tool from the very first ideas, but not how useful.” Early research on MRI ignited a spark in the minds of scientists that has led to unforeseen and unimaginable advances in visualization techniques and equipment that have in turn revolutionized the practice of medicine. As we look toward the future, one can only imagine what wondrous advances are yet to come.