magnetic resonance spectroscopy

In vivo MRS is a method related to magnetic resonance imaging and is a special examination performed with the aim of observing the increase and decrease of some building block molecules in vivo. It is also known as nuclear magnetic resonance spectroscopy (NMRS). MRS provides useful clinical information that cannot be obtained by any other method in the diagnosis, treatment planning and monitoring of some diseases in radiology. It is considered a safe method. In vivo Proton MRS was approved for use in the clinical setting by the US Food and Drug Administration (FDA) in 1996. The inconvenient conditions to use are general and similar to MR. In this article, I will try to explain MRS in simple terms without mentioning as much complex physics formulas as possible.

Scientists (biologists, medical physicists, and biochemists) often use MRS outside the clinic as a tool for research projects.

Brain MRS examines possible metabolic changes in tumors, stroke, seizures, Alzheimer’s disease, depression and some other diseases. MRS is a non-invasive (no cutting/bleeding) and analytical technique. It is also used to evaluate the metabolism of other organs such as muscle. NMRS is used to measure the intramyocellular lipid content (IMCL) of muscles.

In theory, MRS analysis can be done with molecules composed of all atoms with odd numbers of protons in their nuclei. MRS equipment can be tuned to receive signals from the core of different chemicals, such as a radio receiver. The most common core to be studied is hydrogen. However, phosphorus, carbon, sodium and fluorine can be used in MRS. Since current MR devices for practical and clinical use are optimized for the nucleus (proton) of the hydrogen atom, spectroscopic studies can also be performed for this nucleus.

Protons oscillate depending on the environment they are attached to, their molecular structure and the strength of the magnetic field they are in. The speed of this oscillating motion is called the Larmor frequency and is denoted by ω. Since most hydrogen is found in water and fat in the body, it is the concentrations of water and fat that make up the classic MR image. Apart from this, the image is affected by other factors such as iron, calcium, protein ratios. In MRS, it is desired to display some molecules that are found in small amounts in tissues other than water. Therefore, water is suppressed in MRS.

Reading MRS curves

H in Proton MRS + Since the biochemical substances or metabolites containing metabolites are released at different frequencies, they form peaks in different regions due to the ω frequency shift in MRS, just as in light spectroscopy. Because it is affected by Larmor frequency and environmental variables, the location of these peaks is shown in parts per million (ppm, parts per million) from the main frequency instead of in absolute units such as NMR frequency M.Hertz. The signal strength at the peaks is shown as integral or arbitrary units that vary from producer to producer.

In this context, the position of some frequently used metabolites can be summarized as follows. such as choline (3.2 ppm), creatine (3.0 ppm), N-acetyl aspartate NAA (2ppm), twin peaks of amino acid alanine (1.4 ppm). The most prominent of these, NAA is often used as a reference to locate others.

Since there is no certain standard in the absolute values ​​of the radio signal intensity, which shows the height of the peak and the concentration of the metabolite in the voxel, the shape of the curve and the ratios of these metabolites to each other can be looked at in the evaluations.

Knowing what the metabolites that can be seen in MRS do in the body are used to interpret what the mounds mean in the clinic. For example, Choline is one of the building blocks used in cell membrane construction. While it is expected to appear less in areas where the cell and membrane are absent, it is expected to increase in regions with increased membrane production. Creatine is a molecule we encounter in energy metabolism. N-acetyl aspartate is the indicator of neurons, which are the main nerve cells, and their extensions, axons, and a decrease is expected in regions where neurons are destroyed and destroyed. It is an indicator of anaerobic respiration of lactate cells and indicates that the amount of oxygen coming to the region is not enough for consumption. Inositol / myoinositol is an abundant metabolite in extraneuronal (glial) cells, especially astrocytes. Apart from that, the Glx hillock shows Glutamate and Glutamine together.

Obtaining the MRS

MRS is obtained from certain voxels in vivo. In imaging, the concept of voxel can be thought of as a volume with 3 dimensions in the form of a cube or rectangular prism, where the position of the body is predetermined, from which the sampling is made. Since the amount of measured metabolites is very small, the voxels used in MRS must be chosen large in order to receive the weak signal. Measurements in the form of single voxel, SV (single voxel spectroscopy) and multivoxel MV (multi voxel spectroscopy) are used. In SVS, 2 measurements are taken from the suspicious area of ​​the brain and from the opposite side. SVS has largely been replaced by MVS. In MVS, voxels, which can be reduced to the capacity of the device on a plane, take measurements from cubes that are arranged side by side like areas on a chessboard. Without going into details, PRESS and STEAM methods are used to obtain images in SVS, while chemical shift-based (CSI) data collection method is used in MVS. Although each of the SVS and MVS has advantages and disadvantages, factors such as standardization of the shot, ease of interpretation, and not overlooking possible changes in non-sampling areas move the weight needle to the direction of the MVS.

Short echo times of <30ms (echo time) in acquiring MRS results in a more bumpy curve. More numerous and atypical metabolites can be identified in these curves. However, it carries the risk of mixing some metabolite peaks with each other. Curves appear smoother in MRSs obtained with a long reverberation time >135ms. Interpretation is facilitated but fewer metabolites are identified. Long echo times are often used for focal brain diseases. Short echo times are mostly used in metabolic diseases and diffuse brain diseases.

Since MRS is a sensitive method, it can be easily affected by artifacts. Therefore, spectra that have not been obtained properly should not be interpreted as it requires expertise to be obtained.

MVS Views

MVS color maps: An image can be obtained by matching the abundance and abundance of each of the metabolites (Glx, Cho, Cr, NAA, MI, La, Li) obtained in MVS with a color map. This colormap is up to user request. For example: A color scale from black (a little) to white (a lot), or a scale from blue (a little) to yellow (a lot) can be used. The available scales are limited to the selections provided by the machine manufacturer. In this way, abnormal abundance and abundance of a metabolite in a region can be detected more easily. Likewise, the proportional values ​​of metabolites (such as Cho/NAA, Cr/NAA) can be displayed as a color map. These color maps are superimposed on the anatomical image so that experts can spatially detect and locate changes. With the development of technology, the size of voxels will decrease and these maps will have higher spatial resolution. Images created in this way are called MRSI (Magnetic resonance Spectroscopic Imaging) MRSG Magnetic resonance spectroscopic imaging.

Locations and importance of metabolites

1. N-acetyl aspartate (Naa) NAA is a marker that exists in the bodies and axons of neurons, which are nerve cells. It shows the density and viability of neurons and axons. Its production takes place in the mitochondria of brain tissue. Tumor tissue declines when neuronal loss such as ischemia and degenerative diseases. NAA increases in MRS in diseases where NAA cannot be destroyed in the body, such as Canavan disease. NAA degradation deficiency is mostly observed in congenital defect of aspartoacylase enzyme. The presence of Naa is around 2.02 (ppm).

2. Creatine (Cr) this is an indicator of aerobic energy metabolism of brain cells. Apart from white, it is found in large concentrations in gray matter. Since the creatine peak height is almost constant, it can be used as a control value for other metabolites. Different metabolites, such as creatine phosphate, contribute to this peak. Sometimes metastases and brain tumors can lead to a decrease in the Cr peak. The peak for Cr is seen at 3.02 ppm; However, an additional and second peak for creatine can be seen at 3.94 ppm.

3. Choline (Cho) It is a molecule that is the product of phospholipid metabolism of the cell membrane and reflects the membrane destruction production process. Its concentration is slightly higher in white matter and less in gray matter. An increase in choline indicates increased membrane production and intense cell proliferation. Its concentration usually increases in the presence of neoplastic processes of the brain. Phosphocholine and glycerophosphocholine contribute to this peak. The peak occurs at 3.2 ppm.

4. Lactate usually not detected on proton spectroscopy of normal brain tissue. Its presence should be interpreted in relation to the end products of anaerobic metabolism. It is an indirect finding of insufficient oxygen supply due to increased oxygen demand in the tissue or ischemia. Cysts may increase. The presence of lactate may indicate cysts, hypoxic/ischemic tissues, and some tumors. The lactate peak can be seen as an inverted double peak at 1.33 ppm (136 ms echo time).

5. lipids In normal brain tissue, protons are not detected by MRS. The occurrence of necrosis increases in pathological conditions. Lipid peak can be observed in malignancies, inflammatory/infectious processes, as well as in processes that symbolize cell membrane destruction. This peak is between 0.9 and 1.3 ppm

6. Myoinositol MI is considered a marker of glial function. It is also an important osmotic regulator inside the cell. Changes are usually observed in Alzheimer’s disease and hepatic encephalopathy. Myoinositol peak occurs at 3.56 ppm.

7. Alanine It is an amino acid and is not observed in normal spectroscopy. In pathological conditions, it can be detected by proton magnetic resonance spectroscopy. Amino acids are observed in protein degradation processes. As there is intense protein destruction in abscesses, an increase in alanine can be observed. It can also be observed in meningiomas. Inverted double (twin) peak (1.48 ppm with 136 ms reverb time)

8. From other metabolites acetates and succinates Abscess and neurocysticercosis can also be observed. (1.92 and 2.4 ppm, respectively)

9. Glx (Glutamate and Glutamine), It increases in some special conditions such as hepatic encephalopathy. Glx is observed between 2.1-2.5 ppm.

10. There are informative arrangements within MR devices to identify many of the atypical peaks. When a peak is observed in an atypical location, the type of metabolite that rises can be found with the help of peak identification software in the device.

MRS in the diagnosis of brain diseases


Decreased NAA has been observed in tumors that cause destruction and displacement of neurons since the early days of MRS use. In addition, choline is often found high in tumors with a high turnover. Although the increase in choline is observed in other diseases, it is the main indicator of neoplastic diseases. Demyelinating processes can be given as an example to diseases followed by increased choline from non-tumor conditions. In cases where tumor nutrition is not sufficient, lactate may increase. It is often accompanied by tissue destruction with lipid peaks. The presence of lipids is often associated with necrotic processes and high grade tumor (GBM). High Cho/NAA ratios in tumors, when observed together with lactate and lipid peaks, indicate a poor prognosis. The possibility of areas of necrosis (dead tissue) should always be considered when evaluating tumors. As NAA decreased in these areas, Cho levels also decreased. However, when the periphery of the same tumor that continues to grow actively is sampled, an increase in choline levels can be observed. Metastases do not usually show an increase in choline, as long as they are small. MI levels may be increased in tumors composed mostly of glial cells (brain connective tissue). However, when these tumors begin to become malignant, MI levels decrease again.

Although the diagnosis of meningiomas is relatively easy on routine MRI, MRS may be helpful in cases of hesitation. NAA is rarely or not encountered in meningioma tissues. Choline levels are markedly increased and Alanine double peak can be observed.


It is not always easy to distinguish between tumors and infections with tissue destruction by routine MRI examination. A large lipid mound is observed in infections such as Toxoplasmosis, Tuberculosis, and Cryptococcosis followed together with AIDS. Low NAA, mild choline increase, and lactate peak have been described but not always observed.

NAA and Cho hills, which we normally observe in pyogenic abscesses, are not observed. However, peaks of amino acids such as alanine, succinate, and acetate, which are not observed in normal situations, are seen with the effect of tissue-degrading enzymes formed by bacteria.

Alzheimer’s disease

In Alzheimer’s disease, a decrease in NAA and an increase in MI are observed in the frontoparietal, temporal and hippocampus regions. These changes can be observed even in the mild form of the disease. The use of MRS in Alzheimer’s is an area where developments and specificity/sensitivity discussions continue.

Ischemic lesions

MRI with diffusion sequence is considered the gold standard in ischemic lesions. However, it is useful to know the changes observed in MRS. Lactate levels increase from the first minutes due to anaerobic respiration, but lactate levels begin to decrease as tissue necrosis develops. A decrease in NAA and a slight increase in choline levels can be observed. These increases and decreases can give an idea about the ongoing process and prognosis.

Demyelinating diseases

Demyelinating diseases are often easily distinguished from tumors by routine MRI. Considering the decrease in NAA and increase in lactate in demyelinating diseases, it becomes difficult to distinguish them from tumors with MRS alone.

hepatic encephalopathy
Early diagnosis of hepatic encephalopathy with MRI is one of the problems that are difficult. Observation of Glx (Glutamate and Glutamine between 2.1 and 2.5 ppm) peaks in MRS, and decrease in choline and MI levels before any changes are observed in routine MR images are the main changes that help the diagnosis.

Multimodality assessment

The diagnostic accuracy of MRS increases in evaluations with contrast-enhanced MRI, brain perfusion (rCBV, blood supply) and anatomical images.

Detection of the biopsy site

MV-MRS is a helpful method in detecting the biopsy site. This examination may reduce the likelihood of a negative biopsy being taken from the correct site. High Cho and low NAA regions are suitable areas for MR guided biopsy.

Monitoring the treatment

Relapse should be considered when a treated patient begins to experience increased Cho/NAA and Cho/Cr levels. On the contrary, if Cho levels are low, radiation necrosis can be considered. Lactate and lipids do not provide benefit in monitoring, and they can be observed high in necrosis and recurrences. Biopsy studies have shown that the MRS examination is misleading in areas containing mixed rates of necrosis and relapse tissue.

MRS has been used in specific areas such as epilepsy, Parkinson’s disease and Huntington’s chorea, pituitary tuberculosis diagnosis, apart from the diseases mentioned above.

Apart from the brain, MRS has been used in breast and prostate studies.

Disclaimer: MRS is an advanced imaging modality and it is an area where developments continue rapidly and actively. This article has been prepared for the purpose of providing general information in order for you to briefly familiarize yourself with the method. This article has not gone through the so-called peer review process. It may contain errors. Do not use the article for diagnostic purposes or to evaluate the specialist physician who helps you.

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