Meninges membranes enveloping central nervous system

On average, the human brain contains about 100 billion neurons that receive, store, process and transmit information using electrical and chemical signals. The interaction between a neuron and other nerve cells and organs occurs with the help of short (dendrites) and long (axon) processes.

Each axon, like a wire, is covered with an insulating material — a myelin sheath, which provides a higher rate of passage of nerve impulses and protects nerve fibers from damage. In addition, this shell has a supporting function, and also, according to recent data, serves as a kind of “filling station” for an axon that needs a lot of energy.

All damage to the myelin sheath or defects that have arisen during its formation lead to serious, sometimes incurable diseases. Among them, the most famous is multiple sclerosis, a chronic autoimmune disease that affects mainly young people.

Myelin is also destroyed in strokes, which occur not only in adults (primarily, as is commonly believed, in the elderly), but also in children, including the unborn. Intrauterine stroke most often occurs after the 28th week of pregnancy, in children – a month after birth. A stroke in the fetus leads to the development of brain defects, and in children it can cause cerebral palsy at an early age.

At the same time, we judge the “quality” of the myelination of the brain of a particular person today only by indirect clinical symptoms or magnetic resonance imaging (MRI) data, with the help of which it is usually possible to detect myelin defects already at a late, often irreversible stage.
In the brain, the myelin sheath is created by oligodendrocytes, in the peripheral nervous system — Schwann cells.

Not everyone knows that myelin is a set of layers of the cell membrane, many times “wound” on the axon. Myelin is formed by flat outgrowths of “service” glial cells, in which there is practically no cytoplasm. The myelin sheath is not continuous, but discrete, with intervals (Ranvier interceptions). Therefore, the axon has a faster jump-like conductivity: the speed of signal transmission through fibers with and without myelin can differ hundreds of times. As for the molecular composition of the “insulator”, it, like all cell membranes, consists mainly of lipids and proteins.

Defects of nervous “isolation”

Fetal brain development is a complex process in which rapid rearrangements of the morphology and microstructure of the nervous tissue occur. In some areas of the brain, the process of myelin formation begins as early as the 18th-20th week of pregnancy, and continues until about the age of ten.

It is myelination disorders that often underlie delays in the physical and mental development of a child, and also cause the formation of a number of neurological and psychiatric pathologies. In addition to diseases such as stroke, delays in the development of the fetal brain with impaired myelination are sometimes observed in multiple pregnancies. At the same time, desynchronization in the development of the brain of twins is quite difficult to assess “by eye”.

But how to identify myelin defects during intrauterine development? Currently, obstetricians and gynecologists use only biometric indicators (for example, brain size), but they have high variability and do not give a complete picture. In pediatrics, even if there are obvious functional abnormalities in the brain activity of a child, traditional images of MRI or neurosonography (ultrasound examination of the brain of newborns) often do not show structural abnormalities.

Therefore, the search for accurate quantitative criteria for assessing the formation of myelin during pregnancy is an urgent task, which also needs to be solved with the help of non-invasive diagnostic methods already tested in obstetrics.

On a conventional tomograph

Any pathology of the fetal brain that doctors suspect during an ultrasound examination of a pregnant woman is usually an indication for MRI. MRI results can confirm, clarify, refute or even change the preliminary diagnosis and, accordingly, the tactics of pregnancy management.

The fact is that the amount of myelin and the size of individual brain structures in the embryo are so small that any measurements are very complex and time-consuming. In addition, the fetus is constantly moving, which makes it very difficult to obtain high-quality images and reliable quantitative data. Therefore, we need a technology that allows us to obtain images quickly and with high resolution, even on small objects.

This turned out to be the method of rapid mapping of the macromolecular proton fraction —MPF), a biophysical parameter that describes the proportion of protons in the macromolecules of tissues involved in the formation of an MRI signal, whereas usually the source of the signal is protons contained in water.
The method of macromolecular proton fraction (MPF) is based on the effect of magnetization transfer.

The method is based on a specialized procedure for mathematical processing of MRI images, which allows you to isolate the signal components associated with the MPF of cell membranes. And in the brain of humans and animals, the main part of them is contained in myelin. MPF maps are reconstructed based on the initial data that can be obtained on almost any clinical tomograph.

To reconstruct the MPF maps, four initial images obtained by various traditional MRI methods are used. The correctness of this approach was confirmed by the results of its testing on laboratory animals at Tomsk State University: in mice injected with a solution that causes the destruction of myelin, the results of MPF mapping coincided with the data of histological examination of tissues.

Myelin – normal and pathological

Pilot studies performed as part of clinical diagnostic MRI examinations of embryos aged 20 weeks and older have shown that the new technology allows very small amounts of myelin to be detected in a short (less than 5 min.) scanning time.

They also confirmed the ability of the method to reliably assess the spatio-temporal “development trajectories” of myelin in various brain structures. Judging by the results of the study, in the central structures (stem, thalamus, cerebellum), the process of myelination begins earlier, and its degree is proportional to age. At the same time, myelin is practically not detected in the white matter of the cerebral hemispheres during the prenatal period. The results obtained by the new non-invasive method are in good agreement with the already known pathomorphological data.

In addition, it turned out that the images obtained using the new technology are the most informative for the intrauterine diagnosis of one of the types of medulloblastoma – a congenital malignant tumor of the cerebellum. In the fetus, the tumor could not be clearly detected using a traditional MRI examination, but it was well traced using the quantitative MPF method.

The fact is that in the fetus, the MPF index for medulloblastoma tissue is twice as high as the values for the surrounding healthy tissue due to the higher content of connective tissue collagen fibrillar protein in the tumor, which is widely represented in this type of tumor. After birth and up to one and a half years, these differences were smoothed out due to the increasing myelination of the cerebellum, while the values of MPF in the tumor remained virtually unchanged.
The highest values of MFP and, accordingly, the degree of myelination were found in the stem structures of the fetal brain.

The highest values of MFP and, accordingly, the degree of myelination were found in the stem structures of the fetal brain. Lower values of MPF were found in the thalamus and cerebellum, and minimal values were found in the hemispheres of the brain. At the same time, the amount of myelin in the central brain structures steadily increases with embryonic age

These results suggest that the diagnostic significance of the MPF method is highest in the intrauterine period. And this is very important, because after the birth of a child, the arsenal of MRI (including using contrasting means), which allows you to visualize all the details of a malignant lesion, expands significantly.

Over the past decade, various quantitative MRI methods have been used to study the prenatal period of brain maturation. But it turned out that among all the methods known today, the most sensitive to the content of myelin in the brain of an adult and a fetus was the method of mapping MPF.

Medulloblastoma is a malignant tumor of the central nervous system that develops from embryonic cells and is localized mainly in the cerebellum. It accounts for a fifth of all brain tumors in children. The formation of congenital medulloblastoma in a child was traced from the intrauterine period. On traditional MRI images of the brain, a tumor can be diagnosed after birth: for example, it is clearly visible at the age of 4 months. However, in the last semester of pregnancy, the tumor does not stand out against the background of the surrounding tissue, but it can be seen on the MPF map, because the medulloblastoma contains a large amount of collagen, which affects the magnitude of the detected MRI signal.

With its help, specialists for the first time managed to develop quantitative criteria for normal intrauterine myelination, on the basis of which it is possible to assess the timeliness of the formation of the internal structure of the brain from the second trimester to the birth of a child. These criteria can be further used in clinical practice. In addition, in some cases, the new method helps to diagnose a congenital malformation of the brain before birth, which can be difficult using only traditional MRI methods.

Meninges membranes enveloping central nervous system

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