Functional Magnetic Resonance Imaging - Case Study Example

Functional Magnetic Resonance Imaging (fMRI Past, Present & Future E-mail Publication This paper summarises the history of functional MRI (fMRI) technology, the scientific discoveries that led to its development, and the uses to which it has been applied. Whilst the technology is fairly recent, the basic scientific principles and the underlying research for fMRI have been known for years. Since its inception, fMRI has developed tremendous potential to improve not only the quality of medical diagnosis and practice but, perhaps more important, by improving our understanding of the human brain, fMRI opens a window into the human soul, with serious implications on other fields such as law, education, and philosophy. KEYWORDS: BOLD, brain, fMRI, hemodynamic response, imaging. 1. Introduction Functional Magnetic Resonance Imaging (fMRI) is the application of magnetic resonance imaging (MRI) technology to capture images of brain activity with the goal of understanding how the brain is affected by or affects physical or mental activity. In contrast with a structural MRI scan that slices the topography of the brain or other body part and takes images of each slice, useful for determining the presence of tumours or other abnormalities, fMRI is a type of specialised MRI scan that measures hemodynamic response, the change in blood flow and blood oxygenation related to brain activity. Popularity and usefulness of fMRI in neuroimaging is due to its low invasiveness, absence of exposure to radiation, and greater availability compared to other neuroimaging technologies. 2. Basic Science of fMRI In the late 19th century, Roy and Sherrington [1] observed the relation between hemodynamics and neural activity. Active cells need more oxygen, resulting in increased blood flow in the region of increased activity, reaching a peak before subsiding after a few seconds. In addition to this hemodynamic response, there are changes in the relative concentrations of oxyhemoglobin and deoxyhemoglobin. Pauling and Coryell [2] discovered that oxyhemoglobin or oxygen-bound hemoglobin has a low spin rate (S = 0) and is diamagnetic. In contrast, deoxyhemoglobin, i.e., hemoglobin without bound oxygen molecules, is paramagnetic because of the high spin state (S = 2) of the iron content. The magnetic properties of deoxyhemoglobin in blood cells differ from the diamagnetic plasma in blood. This results in a difference in the magnetic properties between the blood and the surrounding tissue. The fMRI scan detects the image caused by changes in deoxyhemoglobin content from the modification of the relaxation process of water protons in the blood. This variation of image intensity from changes in deoxyhemoglobin content was first detected by Ogawa et al. [3] and termed Blood Oxygenation Level Dependent or BOLD. Building on earlier findings by Thulborn et al. [4] that spin echo (T2) or gradient echo (T2*) relaxation show the signal decay process as field distortions in blood water protons leading to the conclusion that blood water T2 varies with deoxyhemoglobin content, Ogawa and his team were the first to suggest the use of BOLD in the functional study of the brain. With deoxyhemoglobin as the contrast agent, MRI can detect changes from the modification of the relaxation of water protons in blood. These basic principles formed the scientific foundations of BOLD-based functional MRI. Equally interesting and important were the developments in neuroscience and medical imaging technology. 3. Developments in Neuroscience and Imaging Technology The nervous system is the interconnected network of nerves and nerve cells found in most invertebrates and all vertebrates. Neural science or neuroscience is the scientific study of this nervous system to understand the workings and interactions of each component. The range of studies is broad and complex, from the processes within the neuron or nerve cell (molecular and cellular levels) to how these networks of nerve cells interact (system level) and how humans are capable of intelligent human behaviour, cognition, emotion and physiological responses (physiological and cognitive levels). The brain, and not the heart as was previously thought before Hippocrates, is the centre of the nervous system, and “it is the task of neural science to explain behaviour in terms of the activities of the brain…how it marshals its millions of individual nerve cells to produce behaviour, and how these cells are influenced by the environment…” [5] Kandel et al. observed that the ultimate challenge for neuroscience is to understand the biological basis of consciousness and the mental processes by which we perceive, act, learn and remember. Several neuroscientists have garnered the Nobel Prize for their work. Each one contributed to the development of neuroscience, a better understanding of how the brain works, and established the foundations for future work at the cognitive level where fMRI is a useful tool. Golgi and Ramon y Cajal were awarded the 1906 Nobel Prize for their study of the neurons that make up the brain. In 1932, Adrian and Sherrington were recognised for their studies on the functions of neurons in the brain and the spinal cord in sending messages. Eccles, Hodgkin and Huxley got the 1963 Nobel Prize for discovering ionic mechanisms of nerve cell membrane. In 1981, Hubel, Sperry and Wiesel were awarded for their studies on the linkage between the visual system and the brain. Prior discoveries in the late 19th and early 20th centuries formed as key bases for later neuroscience discoveries. In 1790, Galvani studied the electrical stimulation of frog nerves. In 1850-51, DuBois-Reymond, Muller and von Helmholtz published experimental findings on the electrical excitability of neurons and their effect on the electrical state of adjacent neurons. Advances in neuroscience at the system, physiological and cognitive levels matched the findings at the cellular and molecular levels. In 1861, Broca discovered cortical localisation and published in 1878 his work on the “great limbic lobe.” He confirmed earlier (1808) studies by Gall on phrenology that language was localised and that certain psychological functions were localised in the cerebral cortex. [6][7] In 2000, Carlsson, Greengard and Kandel received the Nobel for their work on nervous system signal transduction. In 2004, Buck and Axel won for their discovery of odorant receptors and the organisation of the olfactory system. These and other neuroscientists studied how circuits are formed in the nervous system and produce physiological functions like reflexes, sensory integration such as the senses of smell, sight and hearing, motor coordination, emotional responses, learning and memory. They discovered how neural circuits generate specific modes of behaviour. Inherent in these experiments was the question of how to determine the behaviour of the brain, how the neural circuitry results in psychological and cognitive functions. For this, a physics professor by the name of Isidor Isaac Rabi of Columbia University played his part. In 1938, Rabi discovered magnetic resonance, which allowed scientists to “see” details of the internal interactions of molecules, how individual atoms are bound together and how their nuclei are affected by neighbouring atoms. These experiments and developing the molecular beam magnetic resonance as a technique for studying the magnetic properties and internal structure of molecules, atoms and nuclei won Rabi a 1944 Nobel Prize in Physics. A few missing pieces completed the puzzle. The discovery of single ion channels in cells, which play an important part in the transmission of signals along transduction pathways, by Neher and Sakmann won them the Nobel in 1991. In 2003, MacKinnon received the Nobel for his studies on the structural and mechanistic properties of ion channels. But MacKinnon was not alone in receiving the award that year. Two scientists, Lauterbur and Mansfield, won the 2003 Nobel Prize for their studies on magnetic resonance imaging, closing the loop on the key discoveries that allow neuroscientists to capture images of the brain as it performs its function of regulating the nervous system. 4. Neuroimaging: A Brief History Powerful techniques in neuroimaging combined with experimental techniques from cognitive psychology have given neuroscientists the ability to study how human cognition and emotion are linked to specific circuitries in the human brain. Since its discovery by Roentgen in 1895, X-ray or radiography technology has been applied to get images of the human brain. The problem is that ordinary x-rays cannot accurately capture brain matter, being mostly made up of soft tissue. Besides, large doses of x-ray, since it uses radioactive materials, have been discovered to be dangerous to the patient’s health. The first alternative was discovered in 1918 by Dandy, who introduced ventriculography, drilling small holes in the skull and injecting filtered air into one or both lateral ventricles of the brain to capture images of the ventricular system within the brain. The procedure was risky, causing haemorrhage, infection and dangerous changes in pressure within the brain. Dandy also developed pneumoencephalography by introducing air into the subarachnoid space via a lumbar spinal puncture. Whilst the procedure led to precise intracranial diagnosis, this invasive technique proved risky and unpleasantly painful. [8] Moniz, who won the 1949 Nobel Prize for his work on lobotomy, introduced cerebral angiography that could accurately visualize both the normal and abnormal blood vessels in and around the brain. This technique, though risky at the start, has been improved and remains important in neuroscience. Oldendorf in 1961, and Cormack and Hounsfield in 1973 discovered computerised axial tomography, or CAT, scanning. Brain images from a CAT scan were more detailed and, therefore, more useful for research and diagnosis. Besides, CAT scans were non-invasive, painless, safer and repeatable, thus contributing substantially to the advancement of neuroscience discoveries. Cormack and Hounsfield were awarded the Nobel Prize in 1979. Radioactive or nuclear neuroimaging with the inhalation of the isotope xenon-133 gas allowed scientists to more precisely map blood flow in the brain. Discovered by a team [9] in the early 1960s, this technique could produce a two-dimensional coloured image that showed the brain’s behaviour from speaking, reading, seeing or hearing, and voluntary motion. In 1974, Phelps, Hoffman and Ter Pogossian developed the Positron Emission Tomography (PET) scanner that was made possible by the development of radioligands, substances injected into the bloodstream and bind to brain receptors. Since radioligands emit photons or positrons, their images could be captured by single photon emission computed tomography (SPECT) and PET scans. Other substances like FDG, a positron-emitting sugar derivative that is distributed in the brain with local metabolic activity allowed sharper and safer PET scans. Jackson in 1968, Damadian in 1972, and Abe and Lauterbur in 1973 developed MRI technology. Instead of using ionising or x-radiation, magnetic resonance imaging (MRI) uses the variation in signals produced by protons in the body when exposed in a strong magnetic field. Later technological refinements led to the multiplication of MRI applications, helping neuroscientists in discovering new insights into brain behaviour. Functional MRI (fMRI) technology began when scientists discovered that MRI also imaged changes in blood flow measured in PET scans. Since then, more discoveries in basic science of blood characteristics and the discovery of BOLD allowed scientists to refine the applications of fMRI techniques for neuroscientific applications. Other refined techniques for neuroimaging based on MRI technology are magnetic resonance spectroscopy that measures key metabolites within the living brain, diffusion tensor imaging that measures the inter-area connectivity in the brain, and multimodal neuroimaging that combines MRI’s spatial accuracy and measurements of brain electrical activity from electroencephalograph (EEG) scans to get a sophisticated record of brain activity. fMRI and EEG are complimentary techniques that may be used simultaneously. A more recent development is anatomically constrained magnetoencephalography (aMEG), which combines the spatial resolution of MRI with the temporal resolution of MEG. Transcranial magnetic stimulation (TMS) used in combination with MRI allows scientists to generate maps of the brain performing very specific functions. TMS can be used with EEG and near-infrared spectroscopy (NIRS). Whilst nuclear magnetic resonance (NMR) led to MRI and fMRI, recent developments have enhanced NMR technology, with promising results. It was, however, the advances in computer technology that resulted in a better understanding of the data from MRI and fMRI. The ease of applying the existing technology and better ways of interpreting information gathered over the years resulted in a deeper understanding of brain activity and a greater ability to share research findings. 5. fMRI Achievements: Past and Present fMRI boasts of several achievements, notably in the area of brain-computer interface. Through the use of fMRI brain images, scientists in 1998 were able to let a paralysed stroke patient control a pointer on a computer display, improving his functionality. Figure 1 shows a sample fMRI image [10]. According to Raichle, one of the world’s expert neuroscientists, this image looks at the default mode network or DMN region of the human brain and provides a “new, large-scale view of the organisation of the brain’s intrinsic activity” in contrast with what scientists call the brain’s reflexive or evoked activity driven by the momentary demands of the environment. Raichle adds that scientists discovered that the brain’s intrinsic activity, which involves the acquisition and maintenance of information for interpreting, responding to, and even predicting environmental demands, makes up most of the brain’s operations and uses up much energy. Raichle reveals that fMRI was the tool that made discovery of DMN possible by allowing scientists to find patterns of spatial coherence in the spontaneous fluctuations (i.e., “noise”) of the fMRI BOLD signal. Related discovery of slow cortical potential (SCP) is likewise a key to discovering the basis for human consciousness. This Raichle cites as the “paradigm shift” in functional brain imaging: that fMRI would help neuroscience to focus more on the brain’s intrinsic activity in the coming years. 6. Conclusion: Future Perspectives of FMRI The improvement of neuroimaging has brought about tremendous potential not only to medicine but to other fields as well, such as in law and education. Medical oncology, or cancer treatment, will be aided by advances in fMRI, which allows the elimination of unwanted cell types such as tumours. fMRI can guide nanotech devices into the brain or any body part to inject toxins that would destroy the tumour. fMRI can also help people with epileptic seizures using the same technology of guiding a nanodevice to fix a nerve or a cell. This is also one way of curing blindness, aneurysms, or other internal diseases, including mental diseases like Alzheimer’s, Parkinson’s, Lyme disease, schizophrenia, and depression. By giving doctors a clear map of where to safely and effectively intervene, the chances of a cure have increased. fMRI can help not only in neurosurgical planning, but in pain management and deepen our understanding of neurological disorders. It can also help armies predict how soldiers would react to stress and determine their susceptibility to post-traumatic stress disorder. In the field of child education, fMRI with its ability for more accurate neuroimaging technology can give parents and teachers a better understanding of a child’s mental capacities. The progress of early education efforts can be monitored using fMRI, which can tell us how the brain reacts to outside stimuli. fMRI can help if future doctors and parents want their children to develop special abilities or overcome limitations. fMRI can also help reform, defend or convict criminals and psychopaths. With the potentials of TMS to affect human behaviour, there would also be a need for new laws to address concerns. Perhaps, the biggest role for fMRI is in helping us understand the physiological basis for cognitive and perceptual events. With the improved ability to image the entire brain, fMRI can isolate many simultaneous and coordinated brain events, including high-level cognitive tasks, allowing scientists and philosophers to better understand how we see, speak, think, understand, use our imagination and memory, and to explore the previously uncharted shores of what makes us humans, what makes us different amongst ourselves and compared to other animals, and also to help us understand what makes each one unique. [11, 12, 13, 14, 15] Given its accomplished history, fMRI can, with its ability to capture accurately the way the brain functions, help us learn about ourselves and prepare us to accept, and utilise, that knowledge. It will be our window into the human soul. 7. Works Cited [1] Roy, C.S. and Sherrington, C.S. “On the Regulation of the Blood Supply of the Brain”. Journal of Physiology 11.1-2 (1890): 85–158.17. [2] Pauling L. and Coryell C. D., (1936) “The Magnetic Properties and Structure of Hemoglobin, Oxyhemoglobin and Carbon Monoxyhemoglobin.” Proceedings of the National Academy of Sciences (USA) 22 (1936): 210-216. [3] Ogawa S., Lee T.M., Kay A.K. and Tank D.W. “Brain Magnetic Resonance Imaging with Contrast Dependent on Blood Oxygenation.” Proceedings of the National Academy of Sciences (USA) 87 (1990): 9868-9872. [4] Thulborn K.R., Warterton C.J., Matthews P.M. and Radda G.K. “Oxygenation Dependence of the Transverse Relaxation Time of Water Protons in Whole Blood at High Field. Biochem Biophys Acta 714 (1982): 265-70. [5] Kandel, E.R., Schwartz, J.H. and Jessell, T.M. Principles of Neural Science (4th ed.). New York: McGraw-Hill, 2000. [6] Greenblatt, S.H. “Phrenology in the Science and Culture of the 19th Century” Neurosurgery 37 (1995): 790-805. [7] Bear, M. F., Connors, B.W. and Paradiso, M.A. Neuroscience: Exploring the Brain. Baltimore: Lippincott, 2001. [8] Filler, A.G. “The History, Development, and Impact of Computed Imaging in Neurological Diagnosis and Neurosurgery: CT, MRI, DTI.” Nature Procedings (2009). DOI: 10.1038/npre.2009.3267.5. [9] Lassen, N.A., Ingvar, D.H. and Skinhoj, E. “Brain Function and Blood Flow.” Scientific American 239.4 (1978): 50-59. [10] Raichle, M.E. “A Paradigm Shift in Functional Brain Imaging” Journal of Neuroscience 29.41 (2009):12729-12734. [11] Conlan, R., Ernst, R., Hahn, E., Kleppner, D., Redfield, A.G., Slichter C., Shulman, R.G. and Mansfield, P. “A Life-Saving Window on the Mind and Body: The Development of Magnetic Resonance Imaging” Beyond Discovery: The Path from Research to Human Benefit National Academy of Sciences (2001). 27 Oct 2009 [12] “The Future Role of functional MRI in Medical Applications” About Functional MRI. Columbia University Program for Imaging and Cognitive Sciences (PICS). 28 Oct 2009 [13] Singer, E. “Mind Reading with Functional MRI: Scientists use brain imaging to predict what someone is looking at.” Technology Review (5 Mar 2008). 31 Oct 2009 [14] “Functional MRI Forecasts Which Soldiers Might Be Vulnerable to Suicide”. Science Daily (3 Sep 2009). 30 Oct 2009 [15] “Men Are From Mars: Neuroscientists Find That Men And Women Respond Differently To Stress”. Science Daily (1 Apr 2008). 30 Oct 2009 LaTex Program for fMRI Article \documentclass[a4paper, twocolumn, 11pt]{article} ... \begin{document} \twocolumn[ \begin{@twocolumnfalse} \title {Functional Magnetic Resonance Imaging (fMRI): Past, Present & Future} \author{Name of Author,\\E-mail of Author} \date{dd Month 2009} \maketitle \begin{abstract} Type abstract here. \end{abstract} \end{@twocolumnfalse} \section{Introduction} Type Section 1 here. An empty line, obtained by pressing the [Enter] key twice, marks the end of a paragraph. \section {Basic Science of fMRI} Type Section 2 here. \section {Developments in Neuroscience and Imaging Technology} Type Section 3 here. \section {Neuroimaging: A Brief History| Type Section 4 here. \section {fMRI Achievements: Past and Present} Type Section 5 here. After the first line of the second paragraph: \begin{center} Copy the figure to be centered here. \end{center} Continue typing the rest of Section 5 here. \section {Conclusion: Future Perspectives of FMRI} Type Section 6 here. \begin{thebibliography}{[00]} \bibitem{Type the 15 items in the bibliography here} \end{thebibliography} \end{document} Read More