Unlocking the Potential: Magnetic Resonance Spectroscopy (MRS) in Medical Diagnosis

Categories: PhysicsScience

The use of ’Nuclear Magnetic Resonance’ (NMR) is a fast-growing technique that was previously used in the physics and chemistry world. The ’Nuclear Magnetic Resonace’, was discovered around 1930, and soon they started using this promising technique. The most well-known application of NMR is ’Magnetic Res- onance Imaging’ (MRI), which made a major break- through in the medical world in the field of medical diagnosis. The MRI scanner is now indispensable in every hospital. But not for all tissue research is an image sufficient, here the MR Spectroscopy is useful.

This report reveals the full potential of NMR and focuses primarily on the ’Magnetic Resonance Spectroscopy’.

Magnetic Resonace Spectroscopy is currently mainly used in the medical world, this does not mean that it can also be used on more applications. In the hospital, MRS is used to analyze tissue in a specific region of the body part. Subsequently, it is investigated whether certain substances are present in the tissue and in what concentration they occur.

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By comparing this data with that of healthy tissue, it is possible to find out what type of tissue it is, what type of tumor there is and to determine the aggressiveness of the tumor. MRS is mainly applied to the brain, muscle and prostate. MRI and MRS are very similar, but the end result is different. In both processes the NMR principle is used, only with MRI the data is converted into an image and with MRS a graph is drawn up that shows the intensity of the signal on the Y-axis and the X-axis shows the ppm (parts per million).

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(Fig 1) In this report I would elaborate on how MRS works and what it is exactly. In addition, it will be explained how MRS is applied in the medical world and on which applications it is even more possible. To conclude, the potential of MRS is discussed and a conclusion is drawn. Fig. 1: Proton MR spectrum from Parietal White Metter measured at 3T in the normal human brain of a 19-year-old4

To understand what can be done with MRS/MRI, it is useful to first know the basic principles of this topic. These will be mentioned and elaborated in the following chapters. After the basis principles, more will be discussed about the result of MRS and where you can process the result. In the final chapter, we discuss the applications of MRS.

What is ’Nuclear Magnetic Resonance’(NMR) and how does it work NMR Spectroscopy is the use of NMR phenom- ena to study the physical, chemical, and biological properties of matter. Chemists use it to determine molecular identity and structure. Nuclear magnetic resonance (NMR) is a property that magnetic nuclei have in a magnetic field. When you apply an electromagnetic (EM) pulse or pulses, which will cause the nuclei to absorb energy from the EM pulse and radiate this energy back out. The energy radiated back out is at a specific resonance frequency which depends on the strength of the magnetic field and other factors.

This allows the observation of specific mechan- ical magnetic properties of an atomic nucleus. Many scientific techniques exploit NMR phenom- ena to study molecular physics, crystals and non- crystalline materials through NMR spectroscopy.11 Like electrons, some atomic nuclei have a spin that can be somewhat imagined by assuming that the atomic nucleus revolves around its axis, just like a spinning top. It is therefore assumed that the spin is a kind of indeterminate physical property.

Because an atomic nucleus is a charged particle, a magnetic field is created by this spin. If an external magnetic field is applied, then the magnetic field of such an atomic core can assume a number of states: a proton (hydrogen core) can stand with the field (parallel) or against the field (anti-parallel); these two states therefore have an energy difference because work must be done to turn a core from one state to the other. This energy difference is directly proportional to the magnetic field strength and with a sufficiently strong magnetic field the energy required is of the order of magnitude of a radio frequency (RF) photon.

The irradiation with radio wave fields of a sample containing protons will therefore cause a number of nuclear spins to reverse. If you then wait a while, the excited spins will also fall back (with a certain half-life, the so-called relaxation time), while transmitting radio radiation.6 We call this kind of spin the precession. When protons in our body are placed in a strong magnetic field, the magnetic fields from these pro- tons combine to form a net magnetization. This net magnetization points in a direction parallel to the main magnetic field (also called the longitudinal direction). As energy is absorbed from the RF pulse, the net magnetization rotates away from the longitudinal direction (Fig 2). The amount of rotation (flip angle) depends on the strength and duration of the RF pulse. If the RF pulse rotates the net magnetization into the transverse plane, that is termed a 90◦ RF pulse.

If the RF pulse rotates the net magnetization 180◦ into the z-direction, that is termed a 180◦ RF pulse. The strength and/or duration of the RF pulse can be controlled to rotate the net magnetization to any angle. We will see that 90◦ and 180◦ RF pulses are important when discussing the spin echo (SE) and that smaller flip angles are important when discussing fast imaging techniques as in gradient- recalled-echo (GRE) imaging.6 Fig. 2: Absorption of RF energy. Left: Prior to an RF pulse, the net magnetization (small black arrow) is aligned parallel to the main magnetic field and the z-axis. Center and right: An RF pulse at the Larmor frequency will allow energy to be absorbed by the protons,thus causing the net magnetization to rotate away from the z-axis.6

What is the ’Magnetic Resonance Spectroscopy (MRS)

The basic principle that enables MR spec- troscopy (MRS) is that the distribution of electrons around an atom cause nuclei in different molecules to experience a slightly different magnetic field. This results in slightly different resonant frequen- cies, which in turn return a slightly different sig- nal. The technique is identical to that of nuclear magnetic resonance (NMR) as used in chemistry, but the community commonly refers to in vivo NMR as MRS to avoid confusion (and, arguably, the word ”nuclear”). MR spectra can be acquired from any ”NMR- active” nucleus, which is a nucleus possessing non-zero spin: protons are the most commonly encountered, and in clinical practice essentially only proton spectra (which enable the resolution of metabolite profiles in vivo) are encountered.

If a raw signal was processed then the spec- tra would be dominated by water, which would make all other spectra invisible. Water suppression is therefore part of any MRS sequence, either via inversion recovery or chemical shift selective (CHESS). If water suppression is not successful then a general slope to the baseline can be demon- strated, changing the relative heights of peaks. (Fig 3) Magnetic resonance spectroscopy (MRS) is per- formed with a variety of pulse sequences.

The sim- plest sequence consists of a 90◦ radio frequency (RF) pulse, without any gradients, with reception of the signal by the RF coil immediately after the single RF pulse. Many sequences used for imaging can be used for spectroscopy also (such as the spin echo sequence). The important difference between an imaging se- quence and a spectroscopy sequence is that for spectroscopy, a read-out gradient is not used during the time the RF coil is receiving the signal from the person or object being examined. Instead of using the frequency information (provided by the read- out or frequency gradient) to provide spatial or positional information, the frequency information is used to identify different chemical compounds.

This is possible because the electron cloud sur- rounding different chemical compounds shields the resonant atoms of spectroscopic interest to vary- ing degrees depending on the specific compound and the specific position in the compound. This electron shielding causes the observed resonance frequency of the atoms to slightly different and therefore identifiable with MRS.1 When a sample is exposed to a Radio Frequency pulse, a nuclear magnetic resonance response will arise, but with response a free induction decay (FID) (T2*-decay) is obtained. It is a very weak signal, and requires sensitive radio receivers to pick up. A Fourier transform is carried out to extract the frequency- domain spectrum from the raw time-domain FID.

A spectrum from a single FID has a low signal-to- noise ratio, but it improves readily with averaging of repeated acquisitions.2 Following the pulse, the nuclei are excited to a cer- tain angle versus the spectrometer magnetic field. The extent of excitation can be controlled with the pulse width. The pulse width can be determined by plotting the intensity as a function of pulse width. It follows a sine curve, and accordingly, changes sign at pulse widths corresponding to 180◦ and 360◦ pulses.

Decay times of the excitation, depend on the effectiveness of relaxation, which is faster for lighter nuclei and in solids and slower for heavier nuclei and in solutions and they can be very long in gases. If the second excitation pulse is sent prematurely before the relaxation is complete, the average magnetization vector has not decayed to ground state, which affects the strength of the signal in an unpredictable manner. In 1H Magnetic Resonance Spectroscopy each proton can be visualized at a specific chemical shift (peak position along x-axis) depending on its chemical environment. This chemical shift is dic- tated by neighboring protons within the molecule. Therefore, metabolites can be characterized by their unique set of 1H chemical shifts. The metabo- lites that MRS probes for have known (1H) chem- ical shifts that have previously been identified in NMR spectra.7 Fig. 3: The effect of a non successful water sup- pression.

Reading the Magnetic Resonance Spectroscopy

The 1H (Proton) NMR experiment is the most common NMR experiment. The proton (1 Hydro- gen nucleus) is the most sensitive nucleus and usu- ally yields sharp signals. Even though its chemical shift range is narrow, its sharp signals make proton NMR very useful. An 1H-NMR will contain a unique signal for each different type of H atom present in the compound. Since the amount of shielding is dependent on the local chemical environment, the exact chemical shift for H atoms can vary widely.

To get the same result for every experiment, the settings have to be the same. But as this is hard to accomplice, a reference signal from a standard compound is added to the sample. Such a reference standard should be chemically un-reactive, and easily removed from the sample after the measurement. Also, it should give a single sharp NMR signal that does not interfere with the resonances normally observed for organic compounds. Tetramethylsilane ((CH3)4Si) usually referred to as TMS, meets all these characteristics, and is the reference compound of choice for proton NMR.7 There are several important pieces of information that you can obtain from an 1H-NMR. The first is the chemical shift of the peak. This will aid in identifying the type of H atom that produced the signal. The second is the integration ratios of the peaks. The area under a peak of a 1H-NMR is directly proportional to the number of H atoms that produced the peak. The area is calculated by integrating the area.

MRS allows doctors and researchers to obtain biochemical information about the tissues of the human body in a non-invasive way (without the need for a biopsy), whereas MRI only gives them information about the structure of the body (the distribution of water and fat). For example, whereas MRI can be used to assist in the diagnosis of cancer, MRS could potentially Fig. 4: The display of a 1,2-dichloroethane with TMS as reference compound.7 be used to assist in information regarding to the aggressiveness of the tumor.

How is MRS applied to the medical world MRS is used to detect many different dis- eases or tumors in different parts of the human body. MRS is also currently used to investigate a number of diseases in the human body, most notably cancer (in brain, breast and prostate), epilepsy, Alzheimer’s Disease, Parkinson’s disease and Huntington’s chorea.9 MRS is occasionally used as an addition to the common MRI. But it will be an improvement in the healthcare to use this technique more often. This is also emphasized according an article in PubMed (2016). In this article they determine if it is useful to routinely add magnetic resonance spectroscopy (MRS) to magnetic resonance imaging (MRI) in the evaluation of seizure in the pediatric patient.

”In 100 of 233 cases (43%), MRS contributed information additional to MRI. In 40 cases, MRS contributed information relevant to patient man- agement by prompting an evaluation for an un- derlying inborn error of metabolism. MRS con- tributed information relevant to diagnosis in 24 of 100 cases (e.g., neoplasm versus dysplasia). MRS contributed information relevant to prognosis in 36 cases (e.g., hypoxic-ischemic injury). MRS added more information in cases where the patients had a diagnosis relevant to seizure before imaging. Inter- estingly, in 25 cases where the MRI was normal, MRS was found to be abnormal, which prompted evaluation for an inborn error of metabolism.”8 This article concludes the result that suggest that MRS is a useful evaluation tool in addition to MRI for patients undergoing imaging for the evaluation of seizures.

References

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  2. B. J. Elster AD. Relaxation effects in nuclear magnetic resonance absorption. http://mriquestions.com/free-induction- decay.html, 2001. Accessed: 21-05-2019.
  3. M. Ertsen, J. Murphy, L. Purdue, and T. Zhu. A journey of a thousand miles begins with one small step–human agency, hy- drological processes and time in socio-hydrology. Hydrology and Earth System Sciences, 18(4):1369–1382, 2014.
  4. I. T. EvanthiaKousi and K. Eftychia. Novel frontiers of advanced neuroimaging, proton magnetic resonance spectroscopy of the central nervous system. https://www.intechopen.com/books/novel-frontiers-of- advanced-neuroimaging/proton-magnetic-resonance- spectroscopy-of-the-central-nervous-system, January 9th 2013. Accessed: 14-05-2019.
  5. S. S. L.M Jackman. ”xenograft models: In vivo imaging”, application of nuclear magnetic resonance spectroscopy in organic chemistry. 2016.
  6. R. A. Pooley. Fundamental physics of mr imaging. AAPM/RSNA Physics Tutorial for Residents, 25(4):1087– 1099, 2005.
  7. W. Reusch. Nuclear magnetic resonance spectroscopy. https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/spectrpy/nmr/nmr1.htm,May 2013. Accessed: 20-05-2019.
  8. C. P. G. R. T. R. R. E. Rincon SP, Blitstein MB.The use of magnetic resonance spectroscopy inthe evaluation of pediatric patients with seizures.https://www.ncbi.nlm.nih.gov/pubmed/26948493, 2016.Accessed: 25-05-2019.
  9. S. W. M. L. P. S. Saini KS, Patel AL. Magnetic resonancespectroscopy in pituitary tuberculoma. Singapore MedicalJournal, 48, August 2007.
  10. D. R. Spinney. Purdue: Chem 26505: Organic chemistryi (lipton), nuclear magnetic resonance (nmr) spectroscopy.https://chem.libretexts.org/Courses/Purdue/Purdue2014. Ac-cessed: 23-05-2019.
  11. R. University. About nmr (nuclear magnetic reso-nance). https://www.ru.nl/systemschemistry/equipment/nmr-0/about-nmr/, 2019. Accessed: 14-05-2019.
Updated: Feb 21, 2024
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Unlocking the Potential: Magnetic Resonance Spectroscopy (MRS) in Medical Diagnosis. (2024, Feb 21). Retrieved from https://studymoose.com/document/unlocking-the-potential-magnetic-resonance-spectroscopy-mrs-in-medical-diagnosis

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