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Letter to the Editor - Biomedical Imaging: The Burgeoning Growth of MRI Research

Amit Momaya
Duke University

Letters to the Editor are accepted from any reader, and may address any topic dealing with science or undergraduate issues. They are published at the editor’s discretion. To submit a Letter to the Editor, please write to eic@jyi.org.

To the Editor –

The Nobel Prize committee chose Paul Lauterbur and Peter Mansfield as recipients for the 2003 Nobel Prize in Physiology or Medicine “for their discoveries concerning magnetic resonance imaging.” Undeniably, their discovery has truly altered the method through which doctors and scientists view the inside of the human body, especially the brain. Before the advent of MRI, patients were often forced to undergo painful invasive procedures; if non-invasive methods were available, they often proved pernicious to the patient’s long-term health. With the widespread use of MRI and its myriad applications, not only are patients more comfortable, but, also, doctors and scientists can now combat diseases and map the brain—both anatomically and functionally—with greater competence. MRI, unlike many other imaging procedures, such as X-rays, does not use ionizing radiation. Instead, MRI emits a magnetic field and registers changes in the orientations of nuclei, translating these changes into images. The applications of MRI technology are widespread, ranging from earlier diagnosis of Alzheimer’s disease to the possibility of constructing three-dimensional images of proteins.

Benefits of MRI over other Technologies

X-rays have also helped advance non-invasive procedures; however, X-rays, unlike MRI, can entail detrimental effects to one’s long term health. The use of X-rays has been increasing substantially, and is currently responsible for the largest source of man-made radiation. Additionally, the use of computed tomography (CT) scans, which also employ X-rays (although dosages have dropped considerably), has been on the incline, exasperating the situation. A recent study estimates that approximately 1% of all cancer cases in the United States can be attributed to X-rays, while for Japan the estimate is higher at 3.2% (Darby 2004). The excessive exposure to X-rays may not even be necessary, with an approximate 33% of chest X-rays being superfluous according to Peter Herzog, of Ludwig-Maximilians University in Munich, Germany. He also states, “In everyday practice, those ordering radiological procedures should think carefully about the benefits and risks to their patients for each examination” (Penman 2004).

MRI, on the other hand, does not use ionizing radiation, making it considerably safer. To date, no researchers have found any significant health or safety issues with MRI; however, MRI is limited by its strong magnetic field. For example, patients with cardiac pacemakers or metal implants are precluded from undergoing MRI scans. Also, those who experience claustrophobia may not feel comfortable in an MRI scanner due to the tightly enclosed setting.

How MRI Works

A MRI scanner can, in a rudimentary sense, be thought of as a gigantic magnet approximately 600 times stronger than a refrigerator magnet. Generally, MRI scanners produce magnetic fields between 1.5 T and 3 T. The MRI scanner (Figure 1) applies high strength magnetic fields, often in order to image the brain. The brain is composed of approximately 70% water, which comprises hydrogen and oxygen atoms. The nuclei of hydrogen atoms have nuclear spins, and will take on a high-energy or low-energy state, depending on whether the nuclei orient against or align with the magnetic field, respectively. When the nuclei undergo changes between the two states, they absorb or emit energy in the radiofrequency range, which is subsequently detected by the MRI scanner (Jezzard 2001).



Because different anatomical parts of the brain are composed of varying amounts of water, contrast can be generated in the MR images. For example, the nerve cells are found in a much more aquatic rich environment than the surrounding fatty coating called myelin. Thus, differences between the cortex and underlying white matter can be visualized quite distinctly (Matthews 2002). In addition to the distribution of water, differences in relaxation times—that is, the time it takes for a nucleus to return to its initial low-energy state from the induced high-energy state—generate contrast. In order to quantify the process, researchers use the spin-lattice relaxation time, also referred to as T1. If the frequency of pulses applied by the scanner is too high, and therefore does not allow enough time for the relaxation process to completely occur, then the resonance signal will decrease. The T1 of water is specific to the site due to the dynamic chemical environments in the body. For example, the T1 of tissue will differ from the T1 of cerebrospinal fluid, thus generating contrast in the images.

These concepts allow one to anatomically decipher the brain. Through functional magnetic resonance imaging, or fMRI, however, scientists have taken a step further—that is, they can assign functional roles to different parts of the brain. fMRI experiments, which were first implemented a little over a decade ago, are based upon the fact that increased blood flow parallels increased neuronal activity. Although researchers do not fully understand the exact mechanism, the general idea affords scientists the capability to investigate functional roles in the brain. The images produced in these experiments use the concept of blood oxygen level dependent (BOLD) contrast, first described by Ogawa and Lee (1990). The BOLD contrast is associated with the degree to which an applied magnetic field is distorted. When hemoglobin binds to oxygen it is diamagnetic, thus repelling the magnetic field. In contrast, when hemoglobin is not bound to oxygen it is paramagnetic, thus attracting the magnetic field (Pauling and Coryell 1936). Therefore, changes in the level of oxygenation in the blood will generate changes in the distortions of the magnetic field, and thus produce an image (Figure 2).

Applications of MRI Technology

Doctors can apply MRI technology toward diagnosing injuries, especially those involving musculoskeletal soft tissue injuries, such as anterior cruciate ligament (ACL) tears. Stress is constantly applied to the knee, thus rendering it highly susceptible to injury. MRI affords radiologists a quick and cost effective approach to evaluate not only injuries to the ligament, but also to assess cartilage deficiencies (Freitas 2004).

In addition to evaluating injuries, MRI can dramatically assist pathologists. Early detection is very crucial in the field of pathology, since therapies and medicines are usually most effective while a disease remains in its premature stage.

One promising application of MRI is the early diagnosis of Alzheimer’s disease (AD), a neurodegenerative disease. Symptoms of AD include scattered thoughts and severe memory loss, which could eventually cause the victim to forget how to perform simple vital tasks, such as swallowing. Currently, most doctors use cognitive tests to diagnose AD; however, such tests are often biased, not taking into account educational levels, cultural differences, and random variability. However, neuroimaging with MRI eradicates many of these problems. Also, because many of the symptoms associated with AD often surface after the brain has undergone anatomical changes, MRI can be used to detect AD early by revealing such anatomical changes. For example, the neurodegeneration caused by AD generally begins in the entrohinal cortex and hippocampus, and eventually proceeds to the neocortex. Furthermore, MRI can be a valuable tool in identifying those people who are at risk for AD, since researchers have correlated reduced hippocampal size with the development of AD (Zamrini et al. 2004).

In addition to its applications to AD, MRI can assist surgeons perform their jobs with greater efficiency. Surgeons have already examined the possibility of using MRI with patients who have rectal cancer. In order to treat such a cancer, surgeons perform a resection based on how much the tumor has spread. Often, however, there exists a local recurrence of the tumor, which researchers believe is due to an incomplete removal of the tumor. The recurrence rate drops greatly when a tumor-free circumferential resection margin of greater than 1 mm can be obtained. Using MRI, surgeons can predict the circumferential resection margin with very high accuracy and precision, thus identifying patients who will not reach the 1 mm threshold. Such patients may require preoperative radiotherapy or more extensive surgery (Beets-Tan et al. 2001).



Besides pathology, MRI has broken new grounds in nanotechnology. Just recently, scientists at IBM accomplished a very daunting feat—they detected the faint magnetic signal of a single electron from a solid sample. The nanoscale MRI method employed in the study, referred to as magnetic resonance force microscopy (MRFM), coalesces aspects from both MRI and atomic force microscopy (AFM). The principle feature of an MRFM is the microcantilever, which vibrates at a very high frequency and contains a strong magnetic particle on its tip. The magnetic properties of unpaired electrons in atomic nuclei, often referred to as spin, influence the oscillatory behavior of the microcantilever. Infinitesimal changes in the spin of an electron can be detected by the highly sensitive MRFM (Figure 3). The applications of such technology could widely influence the fields of biology and nanotechnology. For example, with the ability of nanoscale imaging, scientists could soon find themselves with basic three-dimensional images of biomolecules, such as proteins, for the first time. Also, such technology may prove useful in the pharmaceutical industry or even improve how circuits are designed (Biever 2004).

The Future of MRI and its Limitations

The future of MRI research seems very promising for its potential to influence many disciplines of study, ranging from engineering to biology to medicine. Dr. Xiaoping Hu, director of Emory/Georgia Institute of Technology’s Biomedical Imaging Technology Center (BITC) and a Georgia Research Alliance Eminent Scholar, believes “the future lies in applications beyond anatomic imaging, i.e. physiological, functional (more than just brain function) and molecular imaging.”

However, MRI will confront challenges on its path of progression. As with all technologies, money will be required to allow more people access to MRI technology. Furthermore, although most researchers corroborate the general notion of safety with MRI, as higher field strengths are used, there may arise some harmful long-term effects that scientists have failed to foresee. In fact, Dr. Keith Heberlein, another researcher at the BITC, states, “Currently, we are reaching a major limitation in MRI. Gradient coils have become strong enough to cause nerve stimulation in humans during the MR scan. In the future of MRI this will be a hurdle that will need to be overcome.”

Nonetheless, MRI technology has already, and promises to, further revolutionize several cross-disciplinary fields, pushing forth the frontiers of modern medicine.

References

Beets-Tan, R G H et al. Accuracy of magnetic resonance imaging in prediction of tumour-free resection margin in rectal cancer surgery. The Lancet 357 (2001): 497-504.

Biever, Celeste. “MRI used to detect lone electron.” New Scientist. (14 July 2004).

Darby, Sarah and Berrington de Gonzalez, Amy. Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries. The Lancet 363 (2004): 345-351.

Freitas, Alex. “Knee Collateral Ligament Injuries (MRI).” http://www.emedicine.com/radio/topic886.htm (17 July 2004).

Jezzard, Peter, Paul Matthews, and Stephen Smith. Functional MRI-An Introduction to Methods. New York, Oxford University Press, 2001.

Ogawa, S., Lee, T., Kay, A. and Tank, D. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc. Natl. Acad. Sci. U.S.A. 87 (1990): 9868-9872.

Pauling, L. and Coryell, C. The Magnetic Properties and Structure of Hemoglobin, Oxyhemoglobin, and Carbonmonoxyhemoglobin. Proc. Natl. Acad. Sci. U.S.A. 22.4 (1936): 210-216.

Penman, Danny. “Medical X-rays cause thousands of cancers.” New Scientist. (30 January 2004).

Zamrini et al. “Imaging is superior to cognitive testing for early diagnosis of Alzheimer’s disease.” Neurobiology of Aging. 25 (2004): 685-691.