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In vivo magnetic resonance spectroscopy (MRS) is a specialized technique associated with magnetic resonance imaging (MRI). [1] [2]
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Magnetic resonance spectroscopy (MRS), also known as nuclear magnetic resonance (NMR) spectroscopy, is a non-invasive, ionizing-radiation-free analytical technique that has been used to study metabolic changes in brain tumors, strokes, seizure disorders, Alzheimer's disease, depression, and other diseases affecting the brain. It has also been used to study the metabolism of other organs such as muscles. In the case of muscles, NMR is used to measure the intramyocellular lipids content (IMCL). [3]
Magnetic resonance spectroscopy is an analytical technique that can be used to complement the more common magnetic resonance imaging (MRI) in the characterization of tissue. Both techniques typically acquire signal from hydrogen protons (other endogenous nuclei such as those of Carbon, Nitrogen, and Phosphorus are also used), but MRI acquires signal primarily from protons which reside within water and fat, which are approximately a thousand times more abundant than the molecules detected with MRS. As a result, MRI often uses the larger available signal to produce very clean 2D images, whereas MRS very frequently only acquires signal from a single localized region, referred to as a "voxel". MRS can be used to determine the relative concentrations and physical properties of a variety of biochemicals frequently referred to as "metabolites" due to their role in metabolism.
Acquiring an MRS scan is very similar to that of MRI with a few additional steps preceding data acquisition. These steps include:
During data acquisition, the scan acquires raw data in the form of spectra. This raw data must be quantified to achieve a meaningful understanding of the spectrum. This quantification is achieved via linear combination. [5] Linear combination requires knowledge of the underlying spectral shapes, referred to as basis sets. Basis sets are acquired either via numerical simulation or experimentally measured in phantoms. There are numerous packages available to numerically simulate basis sets, including MARSS, [6] FID-A, [7] among others such as GAMMA, VESPA and Spinach. [8] With the basis sets, the raw data can now be quantified as measured concentrations of different chemical species. Software is used to complete this. LCModel, a commercial software, has been for most of the field's history the standard software quantification package. However, now there are many freeware packages for quantification: AMARES, AQSES, Gannet, INSPECTOR, jMRUI, TARQUIN, and more. [5]
Before linear combination, peak extraction used to be used for data quantification. However, this is no longer popular nor recommended. [5] Peak extraction is a technique which integrates the area underneath a signal. Despite its seemingly straightforwardness, there are several confounds with this technique. Chiefly, the individual Lorentzian shapes employed do not scale up to match the complexity of the spectral shapes of J-coupled metabolites and is too simple to discern between overlapping peaks. [5]
Similar to MRI, MRS uses pulse sequences to acquire signal from several different molecules to generate a spectra instead of an image. In MRS, STEAM (Stimulated Echo Acquisition Method) and PRESS (Point Resolved Spectroscopy) are the two primary pulse sequence techniques used. In terms of advantages, STEAM is best for imaging metabolites with shorter T2 and has lower SAR, while PRESS has higher SNR than STEAM. STEAM and PRESS are most widely used due to their implementation on the major vendors of MR scanners. Beyond STEAM and PRES there are sequences which utilize adiabatic pulses. Adiabatic pulses produce uniform flip angles even when there is extreme B1 inhomogeneity. Thus, these sequences allow us to achieve excitation that achieves the sought-for B1 insensitivity and off-resonance in the RF coil and sampled object. Specifically, adiabatic pulses solve the problem of signal dropout that comes from the different B1 flux patterns that result from the surface transmit coils used and the usage of normal pulses. [9] Adiabatic pulses are also useful for constraints on RF peak power for excitation and lowering tissue heating. Additionally, adiabatic pulses have substantially higher bandwidth, which reduces chemical shift displacement artefact, which is particularly important at high field strengths and when a large range of frequencies are desired to be measured (i.e., measuring both the signals upfield and downfield of water in proton MRS).
In PRESS, the two chief drawbacks are lengthy echo time (TE) and chemical shift displacement (CSD) artifacts. [10] Lengthy echo time arises from the fact that PRESS uses two 180° pulses, unlike STEAM which uses exclusively 90° pulses. The duration of 180° pulses are generally longer than 90° pulses because it takes more energy to flip a net magnetization vector completely as opposed to only 90°. Chemical shift displacement artifacts arises partly because of less optimal slice selection profiles. Multiple 180° pulses does not allow a very short TE, resulting in less optimal slice selection profile. Additionally, multiple 180° pulses means smaller bandwidth and thus larger chemical shift displacement. Specifically, the chemical shift displacement artifacts occur because signals with different chemical shifts experience different frequency-encoded slice selections and thus do not originate from same volume. Additionally, this effect becomes greater at higher magnetic field strengths.
SPECIAL consists of a spatially selective pre-excitation inversion pulse (typically AFP) followed by spatially selective excitation and refocusing pulses, both of which are usually SLR or truncated sinc pulses. [5]
SPECIAL is a hybrid of PRESS and Image-Selected In Vivo Spectroscopy (ISIS). ISIS achieves spatial localization in the three spatial dimensions through a series of eight slice-selective preinversion pulses that can be appropriately positioned so that the sum of the eight cycles removes all signal outside the desired 3D region. [5] SPECIAL obtains spatial localization from only a single dimension with pre-excitation inversion pulses (cycled on and off every other repetition time [TR]), making it a two-cycle sequence.
The use of the preinversion pulse to remove one refocusing pulse (as compared with PRESS) is what allows SPECIAL to achieve a short TE, reaching a minimum of 2.2 msec on a preclinical scanner in rat brain while being able to recover the full signal and as low as 6 msec on a clinical 3T scanner. [5]
The largest drawback of SPECIAL and SPECIAL-sLASER is that they are two-cycle schemes, and systematic variations between cycles will manifest in their difference spectrum. Lipid contamination is a particularly large problem with SPECIAL and similar sequences.
The state-of-the-art localization sequence is sLASER, [11] which utilizes two pairs of adiabatic refocusing pulses. This has recently been recommended by consensus. [12]
The first is through OVS, which will reduce the contamination of lipid signals that originate from outside the voxel, although this comes at the cost of an increase in SAR. The second is not to set the amplitude of the pre-excitation inversion pulse to zero every other TR, but instead to shift the location of this ISIS plane such that the excited volume for the off condition is outside the object. This has been shown to greatly reduce lipid contamination, speculated to have arisen from the interaction between the RF pulse and lipid compartments due to incomplete relaxation, magnetization transfer, or the homonuclear Overhauser effect, although the exact mechanism remains unknown. [5] The third is to use an echo-planar readout that dephases magnetization from outside the voxel, also shown to substantially reduce lipid artifacts. All three methods could be combined to overcome lipid contamination. [5]
One of the dimensions to understand about a pulse sequence is its coherence pathway. The coherence pathway is the sequence of quantum coherence number(s) the signal takes prior to its acquisition. All coherence pathways end in -1, as this is the only coherence pathway detected by quadrature coils. The spin echo-type sequences (PRESS, sLASER, LASER) simply alternate between +1 and -1. For example, the coherence pathway for PRESS (expressed as a vector) is [-1, 1, -1]. This indicates that after the initial RF pulse (excitation pulse) the spins have a -1 quantum coherence. The refocusing pulses then swap the -1 to +1, then back from +1 to -1 (where it is then detected). Similarly for sLASER the coherence pathway is [-1, 1, -1, 1, -1]. The coherence pathway for LASER is [-1, 1, -1, 1, -1, 1, -1]. The coherence pathway for sPECIAL is [0, 1, -1]. This indicates that after the first RF pulse the signal resides as a population, due to its 0 quantum coherence number. Coherence pathways are critical as the explain how the sequences are affected by crushers and phase cycling. As such, coherence pathway analysis has been used to develop optimized crusher schemes [13] and phase cycling schemes [14] for an arbitrary MRS experiment.
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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). [15]
For example, whereas MRI can be used to assist in the diagnosis of cancer, MRS could potentially be used to assist in information regarding to the aggressiveness of the tumor. [16] Furthermore, because many pathologies appear similar in diagnostic imaging (such as radiation-induced necrosis and recurring tumor following radiotherapy), MRS may in the future be used to assist in distinguishing between similarly appearing prognoses.
MRS equipment can be tuned (just like a radio receiver) to pick up signals from different chemical nuclei within the body. The most common nuclei to be studied are protons (hydrogen), phosphorus, carbon, sodium and fluorine.
The types of biochemicals (metabolites) which can be studied include choline-containing compounds (which are used to make cell membranes), creatine (a chemical involved in energy metabolism), inositol and glucose (both sugars), N-acetylaspartate, and alanine and lactate which are elevated in some tumors.
At present MRS is mainly used as a tool by scientists (e.g. medical physicists and biochemists) for medical research projects, but it is becoming clear that it also has the ability to give doctors useful clinical information, especially with the discovery that it can be used to probe the concentration of alpha-Hydroxyglutaric acid, which is only present in IDH1 and IDH2 mutated gliomas, which alters the prescribed treatment regimen.
MRS is 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. MRS has been used to diagnose pituitary tuberculosis. [17]
Prostate cancer: Combined with a magnetic resonance imaging (MRI) and given equal results, then the three-dimensional MRS can predict the prevalence of a malignant degeneration of prostate tissue by approximately 90%. The combination of both methods may be helpful in the planning of biopsies and therapies of the prostate, as well as to monitor the success of a therapy. [18]
Shown below is an MRI brain scan (in the axial plane, that is slicing from front-to-back and side-to-side through the head) showing a brain tumor (meningioma) at the bottom right. The red box shows the volume of interest from which chemical information was obtained by MRS (a cube with 2 cm sides which produces a square when intersecting the 5 mm thick slice of the MRI scan).
Each biochemical, or metabolite, has a different peak in the spectrum which appears at a known frequency. The peaks corresponding to the amino acid alanine, are highlighted in red (at 1.4 ppm). This is an example of the kind of biochemical information which can help doctors to make their diagnosis. Other metabolites of note are choline (3.2 ppm) and creatine (3.0 ppm).
Metabolite | Major Chemical Shift (ppm) | Function | in vivo MRS Applications | Clinical Applications |
---|---|---|---|---|
N-Acetyl Aspartate (NAA) [19] : 52–53 | 2.01 |
| Marker of neuronal density Concentration marker |
|
N-Acetyl Aspartyl Glutamate (NAAG) [19] : 53–54 | 2.04 |
| Sum of NAA and NAAG provides a reliable estimate of NAA-containing molecules |
|
Adenosine Triphosphate (ATP) [19] : 54–55 | 4.20 - 4.80, 6.13, 8.22 |
| Normally detected with 31P NMR spectroscopy, more difficult to detect by 1H NMR spectroscopy |
|
Alanine (Ala) [19] : 55–56 | 1.40 |
| None |
|
γ-aminobutyric acid (GABA) [19] : 56–57 | 3.00 |
| None |
|
Ascorbic Acid (Asc - Vitamin C) [19] : 57–58 | 4.49 |
| Target for hyperpolarized 13C applications to image the redox status in vivo |
|
Aspartic Acid (Asc) [19] : 58 | 3.89 |
| None |
|
Carnitine [19] : 82 | 3.21 |
| None |
|
Carnosine [19] : 84 | 7.09 |
| Noninvasive method to measure intracellular pH with 1H NMR in vivo |
|
Choline-containing Compounds (tCho) [19] : 59–61 | 3.20 |
| None |
|
Citric Acid | 2.57, 2.72 |
| None |
|
Creatine (Cr) and Phosphocreatine (PCr) [19] : 61–82 | 3.03 |
| None |
|
Deoxymyoglobin (DMb) [19] : 87 | 79.00 |
| None |
|
Glucose (Glc) [19] : 63 | 5.22 |
| Common target in 13C applications to study metabolic pathways |
|
Glutamate (Glu) [19] : 64–65 | 2.20 - 2.40 |
| Separation between glutamate and glutamine becomes unreliable, although the sum (Glx) can be quantified with high accuracy |
|
Glutamine (Gln) [19] : 65–66 | 2.20 - 2.40 |
| Separation between glutamate and glutamine becomes unreliable, although the sum (Glx) can be quantified with high accuracy |
|
Glutathione (GSH) [19] : 66–67 > | 3.77 |
| None |
|
Glycerol [19] : 67–68 | 3.55, 3.64, 3.77 |
| Difficult to observe in 1H NMR spectra because of line broadening |
|
Glycine [19] : 68 | 3.55 |
| None |
|
Glycogen [19] : 68–69 | 3.83 |
| Routinely observed in 13C NMR, but remains elusive in 1H NMR |
|
Histidine [19] : 59–70 | 7.10, 7.80 |
| Establish intracellular pH in 1H NMR |
|
Homocarnosine [19] : 70 | 7.10, 8.10, 3.00 - 4.50 |
| Good choice for in vivo pH monitoring Because of the overlap between GABA and Homocarnosine resonances, the GABA H-4 resonance at 3.01 ppm is the "total GABA" representing the sum of GABA and homocarnosine |
|
β-Hydroxybutyrate (BHB) [19] : 70–71 | 1.19 |
| None |
|
2-Hydroxyglutarate (2HG) [19] : 71–72 | 1.90 |
| None |
|
myo-Inositol (mI) [19] : 72–73 | 3.52 |
| None |
|
scyllo-Inositol (sI) [19] : 72–73 | 3.34 |
| None |
|
Lactate (Lac) [19] : 73–74 | 1.31 |
| None |
|
Lipids [19] : 87 | 0.9 - 1.5 |
| High abundance of lipids is one of main reasons 1H NMR outside the brain has seen limited applications |
|
Macromolecules [19] : 74–76 | 0.93 (MM1), 1.24 (MM2), 1.43 (MM3), 1.72 (MM4), 2.05 (MM5), 2.29 (MM6), 3.00 (MM7), 3.20 (MM8), 3.8 - 4.0 (MM9), 4.3 (MM10) |
| Significant fraction of observed signal is macromolecular resonances underlying the rest of metabolites Short T2 relaxation time constants effectively eliminate macromolecular resonances from long-echo-time 1H NMR spectra Difference in T1 relaxations between metabolites and macromolecules is used to reduce contribution from extracranial lipid signal |
|
Nicotinamid Adenine Dinucleotide (NAD+) [19] : 76 | 9.00 |
| 31P NMR allows detection of both NAD+ and NADH, while 1H NMR does not allow detection for NADH |
|
Phenylalanine [19] : 76–77 | 7.30 - 7.45 |
| None |
|
Pyruvate [19] : 77–78 | 2.36 |
| Only FDA-approved compound for hyperpolarized 13C NMR |
|
Serine [19] : 78 | 3.80 - 4.00 |
| None |
|
Taurine (Tau) [19] : 79–80 | 3.25, 3.42 |
| None |
|
Threonine (Thr) [19] : 80 | 1.32 |
| None |
|
Tryptophan (Trp) [19] : 80 | 7.20, 7.28 |
| None |
|
Tyrosine (Tyr) [19] : 81 | 6.89 - 7.19 |
| None |
|
Water [19] : 81–82 | 4.80 |
| Internal concentration referencing Water chemical shift used to detect temperature changes noninvasively in vivo |
|
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 dictated by neighboring protons within the molecule. Therefore, metabolites can be characterized by their unique set of 1H chemical shifts. The metabolites that MRS probes for have known (1H) chemical shifts that have previously been identified in NMR spectra. These metabolites include:
The major limitation to MRS is its low available signal due to the low concentration of metabolites as compared to water. As such, it has inherently poor temporal and spatial resolution. Nevertheless, no alternate technique is able to quantify metabolism in vivo non-invasively and thus MRS remains a valuable tool for research and clinical scientists.
In addition, despite recent efforts toward international expert consensus on methodological details like shimming, [21] motion correction, [22] spectral editing, [23] spectroscopic neuroimaging, [24] other advanced acquisition methods, [25] data processing and quantification, [26] application to brain, [27] proton spectroscopy application to skeletal muscle, [28] phosphorus application to skeletal muscle, [29] methods description, [30] results reporting, [31] and other considerations, currently published implementations of in vivo magnetic resonance spectroscopy cluster into literatures exhibiting a broad variety of individualized acquisition, processing, quantification, and reporting techniques. [32] This situation may contribute to a low sensitivity and specificity of, for example, in vivo proton magnetic resonance spectroscopy to disorders such as multiple sclerosis, that continue to fall below clinically beneficial thresholds for, e.g., diagnosis. [32]
31Phosphorus Magnetic Resonance Spectroscopy
1H MRS's clinical success is only rivaled by 31P MRS. This is in large part because of the relatively high sensitivity of phosphorus NMR (7% of protons) combined with a 100% natural abundance. [19] : 90–93 Consequently, high-quality spectra are acquired within minutes. Even at low field strengths, great spectra resolution is obtained because of the relatively large (~30 ppm) chemical shift dispersion for in vivo phosphates. Clinically, phosphorus NMR excels because it detects all metabolites playing key roles in tissue energy metabolism and can indirectly deduce intracellular pH. However, phosphorus NMR is chiefly challenged by the limited number of metabolites it can detect. [19] : 90–93
13Carbon Magnetic Resonance Spectroscopy
In contrast to phosphorus NMR, carbon NMR is an insensitive technique. This arises from the fact that 13C NMR has a low abundance (1.1%) and carbon's low gyromagnetic ratio. [19] : 93–96 This low abundance is because 12C does not have a magnetic moment, making it not NMR active, leading to 13C's use for spectroscopy purposes. However, this low sensitivity can be improved via decoupling, averaging, polarization transfer, and larger volumes. [19] : 93–96 Despite the low natural abundance and sensitivity of 13C, 13C MRS has been used to study several metabolites, especially glycogen and triglycerides. [19] : 93–96 It has proven especially useful at providing insight on the metabolic fluxes from 13C-labeled precursors. [19] : 93–96 There is great overlap in what 1H MRS and 13C MRS can obtain spectra-wise and large reason, combined with 1H MRS's high sensitivity, why 13C MRS has never seen wide application like 1H MRS. See also Hyperpolarized carbon-13 MRI.
23Sodium Magnetic Resonance Spectroscopy
Sodium NMR is infamous for its low sensitivity (9.2% relative to proton sensitivity) and low SNR because of its low sodium concentration (30 - 100 mM), especially compared to protons (40 - 50 M). [19] : 96–102 However, interest in sodium NMR has been reinspired by recent significant gains in SNR at high magnetic fields, along with improved coil designs and optimized pulse sequences. There is much hope for sodium NMR's clinical potential because the detection of abnormal intracellular sodium in vivo may have significant diagnostic potential and reveal new insights into tissue electrolysis homeostasis. [19] : 96–102
19Fluorine Magnetic Resonance Spectroscopy
Fluorine NMR has high sensitivity (82% relative to proton sensitivity) and 100% natural abundance. [19] : 102–104 However, it is important to note that no endogenous 19F containing compounds are found in biological tissues and thus the fluorine signal comes from an external reference compound. Because19F is not found in biological tissues, 19F does not have to deal with interference from background signals like in vivo 1H MRS does with water, making it especially powerful for pharmacokinetic studies. 1H MRI provides the anatomical landmarks, while 19F MRI/MRS allows us to follow and map the specific interactions of specific compounds. [19] : 102–104 in vivo 19F MRS can be used to monitor the uptake and metabolism of drugs, study the metabolism of anesthetic, determine cerebral blood flow, and measure, via fluorinated compounds ("probes"), various parameters like pH, oxygen levels, and metal concentration. [19] : 102–104
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves to generate images of the organs in the body. MRI does not involve X-rays or the use of ionizing radiation, which distinguishes it from computed tomography (CT) and positron emission tomography (PET) scans. MRI is a medical application of nuclear magnetic resonance (NMR) which can also be used for imaging in other NMR applications, such as NMR spectroscopy.
In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of a molecule. Chemical shifts are also used to describe signals in other forms of spectroscopy such as photoemission spectroscopy.
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic field. This re-orientation occurs with absorption of electromagnetic radiation in the radio frequency region from roughly 4 to 900 MHz, which depends on the isotopic nature of the nucleus and increased proportionally to the strength of the external magnetic field. Notably, the resonance frequency of each NMR-active nucleus depends on its chemical environment. As a result, NMR spectra provide information about individual functional groups present in the sample, as well as about connections between nearby nuclei in the same molecule. As the NMR spectra are unique or highly characteristic to individual compounds and functional groups, NMR spectroscopy is one of the most important methods to identify molecular structures, particularly of organic compounds.
Carbon-13 (C13) nuclear magnetic resonance is the application of nuclear magnetic resonance (NMR) spectroscopy to carbon. It is analogous to proton NMR and allows the identification of carbon atoms in an organic molecule just as proton NMR identifies hydrogen atoms. 13C NMR detects only the 13
C
isotope. The main carbon isotope, 12
C
does not produce an NMR signal. Although ca. 1 mln. times less sensitive than 1H NMR spectroscopy, 13C NMR spectroscopy is widely used for characterizing organic and organometallic compounds, primarily because 1H-decoupled 13C-NMR spectra are more simple, have a greater sensitivity to differences in the chemical structure, and, thus, are better suited for identifying molecules in complex mixtures. At the same time, such spectra lack quantitative information about the atomic ratios of different types of carbon nuclei, because nuclear Overhauser effect used in 1H-decoupled 13C-NMR spectroscopy enhances the signals from carbon atoms with a larger number of hydrogen atoms attached to them more than from carbon atoms with a smaller number of H's, and because full relaxation of 13C nuclei is usually not attained, and the nuclei with shorter relaxation times produce more intense signals.
Proton nuclear magnetic resonance is the application of nuclear magnetic resonance in NMR spectroscopy with respect to hydrogen-1 nuclei within the molecules of a substance, in order to determine the structure of its molecules. In samples where natural hydrogen (H) is used, practically all the hydrogen consists of the isotope 1H.
The heteronuclear single quantum coherence or heteronuclear single quantum correlation experiment, normally abbreviated as HSQC, is used frequently in NMR spectroscopy of organic molecules and is of particular significance in the field of protein NMR. The experiment was first described by Geoffrey Bodenhausen and D. J. Ruben in 1980. The resulting spectrum is two-dimensional (2D) with one axis for proton (1H) and the other for a heteronucleus, which is usually 13C or 15N. The spectrum contains a peak for each unique proton attached to the heteronucleus being considered. The 2D HSQC can also be combined with other experiments in higher-dimensional NMR experiments, such as NOESY-HSQC or TOCSY-HSQC.
Two-dimensional nuclear magnetic resonance spectroscopy is a set of nuclear magnetic resonance spectroscopy (NMR) methods which give data plotted in a space defined by two frequency axes rather than one. Types of 2D NMR include correlation spectroscopy (COSY), J-spectroscopy, exchange spectroscopy (EXSY), and nuclear Overhauser effect spectroscopy (NOESY). Two-dimensional NMR spectra provide more information about a molecule than one-dimensional NMR spectra and are especially useful in determining the structure of a molecule, particularly for molecules that are too complicated to work with using one-dimensional NMR.
Fast low angle shot magnetic resonance imaging is a particular sequence of magnetic resonance imaging. It is a gradient echo sequence which combines a low-flip angle radio-frequency excitation of the nuclear magnetic resonance signal with a short repetition time. It is the generic form of steady-state free precession imaging.
During nuclear magnetic resonance observations, spin–lattice relaxation is the mechanism by which the longitudinal component of the total nuclear magnetic moment vector (parallel to the constant magnetic field) exponentially relaxes from a higher energy, non-equilibrium state to thermodynamic equilibrium with its surroundings (the "lattice"). It is characterized by the spin–lattice relaxation time, a time constant known as T1.
Magnetization transfer (MT), in NMR and MRI, refers to the transfer of nuclear spin polarization and/or spin coherence from one population of nuclei to another population of nuclei, and to techniques that make use of these phenomena. There is some ambiguity regarding the precise definition of magnetization transfer, however the general definition given above encompasses all more specific notions. NMR active nuclei, those with non-zero spin, can be energetically coupled to one another under certain conditions. The mechanisms of nuclear-spin energy-coupling have been extensively characterized and are described in the following articles: Angular momentum coupling, Magnetic dipole–dipole interaction, J-coupling, Residual dipolar coupling, Nuclear Overhauser effect, Spin–spin relaxation, and Spin saturation transfer. Alternatively, some nuclei in a chemical system are labile and exchange between non-equivalent environments. A more specific example of this case is presented in the section Chemical Exchange Magnetization transfer.
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field and respond by producing an electromagnetic signal with a frequency characteristic of the magnetic field at the nucleus. This process occurs near resonance, when the oscillation frequency matches the intrinsic frequency of the nuclei, which depends on the strength of the static magnetic field, the chemical environment, and the magnetic properties of the isotope involved; in practical applications with static magnetic fields up to ca. 20 tesla, the frequency is similar to VHF and UHF television broadcasts (60–1000 MHz). NMR results from specific magnetic properties of certain atomic nuclei. High-resolution nuclear magnetic resonance spectroscopy is widely used to determine the structure of organic molecules in solution and study molecular physics and crystals as well as non-crystalline materials. NMR is also routinely used in advanced medical imaging techniques, such as in magnetic resonance imaging (MRI). The original application of NMR to condensed matter physics is nowadays mostly devoted to strongly correlated electron systems. It reveals large many-body couplings by fast broadband detection and should not be confused with solid state NMR, which aims at removing the effect of the same couplings by Magic Angle Spinning techniques.
Magnetic resonance imaging (MRI) is a medical imaging technique mostly used in radiology and nuclear medicine in order to investigate the anatomy and physiology of the body, and to detect pathologies including tumors, inflammation, neurological conditions such as stroke, disorders of muscles and joints, and abnormalities in the heart and blood vessels among others. Contrast agents may be injected intravenously or into a joint to enhance the image and facilitate diagnosis. Unlike CT and X-ray, MRI uses no ionizing radiation and is, therefore, a safe procedure suitable for diagnosis in children and repeated runs. Patients with specific non-ferromagnetic metal implants, cochlear implants, and cardiac pacemakers nowadays may also have an MRI in spite of effects of the strong magnetic fields. This does not apply on older devices, and details for medical professionals are provided by the device's manufacturer.
Functional magnetic resonance spectroscopy of the brain (fMRS) uses magnetic resonance imaging (MRI) to study brain metabolism during brain activation. The data generated by fMRS usually shows spectra of resonances, instead of a brain image, as with MRI. The area under peaks in the spectrum represents relative concentrations of metabolites.
Perfusion MRI or perfusion-weighted imaging (PWI) is perfusion scanning by the use of a particular MRI sequence. The acquired data are then post-processed to obtain perfusion maps with different parameters, such as BV, BF, MTT and TTP.
Nitrogen-15 nuclear magnetic resonance spectroscopy is a version of nuclear magnetic resonance spectroscopy that examines samples containing the 15N nucleus. 15N NMR differs in several ways from the more common 13C and 1H NMR. To circumvent the difficulties associated with measurement of the quadrupolar, spin-1 14N nuclide, 15N NMR is employed in samples for detection since it has a ground-state spin of ½. Since14N is 99.64% abundant, incorporation of 15N into samples often requires novel synthetic techniques.
Sodium MRI is a specialised magnetic resonance imaging technique that uses strong magnetic fields, magnetic field gradients, and radio waves to generate images of the distribution of sodium in the body, as opposed to more common forms of MRI that utilise protons present in water (1H-MRI). Like the proton, sodium is naturally abundant in the body, so can be imaged directly without the need for contrast agents or hyperpolarization. Furthermore, sodium ions play a role in important biological processes via their contribution to concentration and electrochemical gradients across cellular membranes, making it of interest as an imaging target in health and disease.
Hyperpolarized carbon-13 MRI is a functional medical imaging technique for probing perfusion and metabolism using injected substrates.
An MRI pulse sequence in magnetic resonance imaging (MRI) is a particular setting of pulse sequences and pulsed field gradients, resulting in a particular image appearance.
Rolf Gruetter is a Swiss physicist and neurobiologist specialized in magnetic resonance, biomedical imaging and brain metabolism. He is a professor of physics at EPFL and the head of the Laboratory Functional and Metabolic Imaging at the School of Basic Sciences.
Michael Albert Thomas is an Indian-American physicist, academic, and clinical researcher. He is a Professor-in-Residence of Radiological Sciences, and Psychiatry at the Geffen School of Medicine, University of California, Los Angeles (UCLA). He is most known for developing novel single voxel based 2D NMR techniques, multi-voxel 2D MRS techniques using hybrid Cartesian as well as non-Cartesian spatio-temporal encoding such as concentric ring, radial and rosette trajectories.
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