Nuclear Magnetic Resonance Spectrometry - Essay Example

Magnetic Resonance Spectrometry Nuclear Magnetic Resonance Spectroscopy, or simply Magnetic Resonance Spectroscopy (MRS), is a non-invasive and non-destructive analytical technique that is used widely in the medical field for studying metabolic changes in brain tumors, Alzheimer's disease, seizure disorders, strokes, depression and other related diseases affecting the brain. This technique - which primarily which exploits the magnetic properties of certain nuclei - is based on nuclear magnetic resonance, a phenomenon first measured by Isidor Rabi in molecular beams, and then described fully by Bloch and Purcell who theorized and expanded the technique to both liquids and solids. A large variety information is obtainable through a nuclear MRS spectrum. Much like the way infrared spectroscopy is used to identify functional groups, the analysis of a 1-dimensional nuclear MRS spectrum provides information on the number and type of chemical entities in a molecule. The impact of MRS on the natural sciences has been substantial. It can, among other things, be used to study complex mixtures of analytes, understand dynamic effects like change in reaction mechanisms, pressure and temperature, and investigate protein and nucleic acid structures and functions. It is a method that can be applied to a wide variety of samples, both in solution and solid state. MRS is a tool used by biochemists for medical research projects, and by doctors to gather useful clinical information which can be helpful in the diagnosis and treatment of various diseases. It applications in the field of medicine are, in general, within the scope of detecting neurological disorders. For instance, it is used to identify Neural Progenitor Cells in the live human brain without any risky surgery of any sort (Manganas, et al., 2007). Neurological infections require immediate identification and treatment. Medical physicists and doctors have always found it difficult to accurately and rapidly diagnose such infections in both children and adults. MRS, however, has opened up new avenues and is now used as a safe, non-surgical method for the identification of brain infections like brain abscess and meningitis. Outside neurology, MRS is used to measure phosphate, phosphocreatine, ATP and phosphodiesters in fibromyalgic muscle tissue (Sprott et al., 2000). Furthermore, this technique is currently being investigated to study a number of other diseases in the human body, most notable of which include cancer, epilepsy and Huntington's Chorea. MRS methods can further be divided on the basis of the specific procedures and principles used during detection and investigation. Correlation spectroscopy is one of the several types of 2-dimensional nuclear MRS techniques. Others types of NMR spectroscopy techniques include Exchange spectroscopy, J-spectroscopy, Protein Nuclear MRS, Total Correlation spectroscopy, Solid-state Nuclear MRS, and Nuclear Overhauser effect spectroscopy (Wuthrich, 1990). Solid-state nuclear MRS is often related to structural investigations of membrane proteins, protein fibrils, polymers, and inorganic chemical analysis. Protein nuclear MRS, on the other hand, has major applications in pure structural biology, where it is used to obtain high resolution 3-dimensional protein structure and dynamics, much like what is produced by X-ray crystallography albeit in a less destructive manner using much lesser energy. The entire phenomenon of magnetic resonance is a result of the fact that a spinning charge generates a magnetic field around it having a magnetic moment proportional to the spin. When an external magnetic field is applied to a sample, two possible spin states exist for any atom- +1/2 and -1/2. The magnetic moment of the lower energy spin state (+1/2) is aligned with the external field, and that of the higher energy spin state (-1/2) is opposed to the external field. The difference in energies of the two spin states is dependent on the external magnetic field strength, and is usually kept very small. Though the spin states have the same energy when the external B-field around the sample is zero, they diverge as the magnitude of B-field increases. Irradiation of the sample with a radio frequency energy that corresponds exactly to the spin state separation of the specific set of nuclei excites the ones in the lower +1/2 spin state to the higher -1/2 spin state. This realignment of the magnetic fields induces another radio signal (this time in the output circuit) which is then used to generate the output signal. Fourier analysis is conducted on the complex output so as to produce the actual spectrum. The pulse is repeated several times over so as to allow the signals to be differentiated from the background noise. The energy required for the transition is dependent on the strength of the applied external magnetic field, and corresponds to the radio frequency range in the electromagnetic spectrum. It should be noted that this corresponding electromagnetic radiation falls in the radio and television broadcast spectrum. Thus, nuclear MRS is energetically the mildest examination which can be used to study the structure of molecules. The nuclear MRS procedure is carried out in an NMR spectrometer, which is basically a big cooler filled with liquid helium and liquid nitrogen to cool the superconducting coil within. There is a space at the top where the sample to be analysed is placed. Jets of air are used to rotate the sample at a high speed within the coil and external magnetic field. When a sample is made for solution nuclear MRS, the solvent used is ensured to be deuterated, that is, the hydrogen of the solvent molecule is replaced with deuterium atoms. This aids in locking the nuclear magnetic resonance on a specific frequency so that the spectrum does not drift around during acquisition, and accurate results can be produced. Also important in the examination of the MRS technology are the concepts of Chemical Shift and J-Coupling. Different protons in a molecule resonate at slightly different frequencies depending on the local chemical environment. Since both the frequency shift and the fundamental resonant frequency are directly proportional to the strength of the applied magnetic field, the shift is converted to a field-independent dimensionless value known as the chemical shift, which is reported as a relative measure from some reference resonance frequency. J-coupling is the phenomenon responsible for the splitting-up of MRS signals during analysis. It arises from the interaction of different spin states through the chemical bonds of a specific molecule. Much of the information about structures in a 1-dimensional spectrum comes from J-coupling between NMR active nuclei. Coupling combined with the chemical shift yields valuable analytical information like the chemical environment of the nuclei, and the number of neighboring NMR active nuclei within the molecule. In more complex spectra which have multiple peaks at similar chemical shifts, J-coupling is perhaps the only way to distinguish various nuclei. In 2006, Willmann et al evaluated the additional pre-operative value of (1)H-MRS in identifying the epileptogenic zone for epilepsy surgery by performing a meta-analysis. Their findings indicated the connection of ipsilateral MRS abnormality to high quality and good outcome. It was concluded that MRS was a research tool with a huge clinical potential, and that the current evidence on the accuracy of (1)H-MRS in the characterization of brain tumors was very promising. Furthermore, in a meta-analysis of the accuracy of prostate cancer studies using MRS, Wang et al (2008) concluded that MRS has a better applied value compared to other common modalities as a diagnostic tool for prostate cancer. However, though an important and highly-researched field based on a very innovative concept, the role of MRS in diagnosis and therapeutic planning has not yet been fully established by adequate clinical studies. Aetna, Inc. - a major American diversified health care benefits providing company - considers magnetic resonance spectroscopy inconclusive, experimental and investigational due to lack of evidence of its efficacy in the medical literature at present. A recent study of MRS prepared by the Tuft's-New England Medical Center Evidence-Based Practice Center for the Agency for Healthcare Research and Quality concluded that human studies conducted on the use of MRS for brain tumors demonstrated that this non-invasive method was technically feasible and suggested potential benefits for some of the proposed indications. However, there was a paucity of high quality direct evidence that demonstrated the impact on diagnostic thinking and therapeutic decision-making, and the techniques of acquiring the MRS spectra and interpreting the results have yet to be well standardized. While there have been a large number of studies that confirm the technical feasibility of MRS, there seems to be very little literature on the evaluation of the diagnostic accuracy and effects of MRS. The studies that do address these issues are often those having significant designing and execution flaws like inadequate sample size, retrospective design and other biased limitations. In a 2004 study conducted by the Center for Medicare and Medicaid Services, it was determined that there was insufficient evidence existing that deemed MRS reasonable and necessary for brain tumor diagnosis. Gluch (2005) developed ex-vivo and in-vivo applications of MRS which aid in distinguishing malignant tissues from normal ones. Nevertheless, it was noted that for the time being, the verification of these non-invasive tests to supplant conventional histology in obtaining spatial diagnostic and chemical prognostic information has largely been illusive. Thus, MRS imaging can not be considered a routine diagnostic tool. Though improvements in diagnostic accuracy and staging have recently been reported, MRS imaging is a technically demanding and time consuming job. Specifically, no clinical trials have been conducted to examine improved outcomes in patients evaluated with MRS compared to patients evaluated with conventional imaging modalities. This technique is yet to be proven in multi-institutional trials, and clinical trials for the same are currently underway at the American College of Radiology Imaging Network. Therefore, the consensus in the medical field largely is that further studies are required to determine the role of MRS in the diagnosis and treatment- planning of neurological diseases conclusively. References Aetna, Inc. (2002). Magnetic Resonance Spectroscopy (MRS). Retrieved April 27, 2009, from Clinical Policy Bulletin: http://www.aetna.com/cpb/medical/data/200_299/0202.html Gluch, L. (2005). Magnetic resonance in surgical oncology: II - literature review. ANZ J Surg , 6 (75), 464-470. Manganas, L., Zhang, X., Li, Y., Hazel, R., Smith, S., Wagshul, M., et al. (2007). Magnetic Resonance Spectroscopy Identifies Neural Progenitor Cells in the Live Human Brain. Science , 318, 980 - 985. Sprott, H., Rzanny, R., Reichenbach, J. R., Kaiser, W. A., Hein, G., & Stein, G. (2000). 31P magnetic resonance spectroscopy in fibromyalgic muscle. Rheumatology 2000 , 39, 1121-1125. Wang, P., Guo, Y., & Liu, M. (2008). A meta-analysis of the accuracy of prostate cancer studies which use magnetic resonance spectroscopy as a diagnostic tool. Korean J Radiol. , 5 (9), 432-438. Wikimedia Foundation, Inc. (2009, March 30). NMR spectroscopy. Retrieved 27 April, 2009, from Wikipedia: http://en.wikipedia.org/wiki/NMR_spectroscopy Willmann, O., Wennberg, R., & May, T. (2006). The role of 1H magnetic resonance spectroscopy in pre-operative evaluation for epilepsy surgery- A meta-analysis. Epilepsy Res. , 2-3 (71), 149-158. Wuthrich, K. (1990). Protein structure determination in solution by NMR spectroscopy. J Biol Chem , 265 (36), 59-62. Read More