Health
How can hacking the immune system help slow aging?
Published
5 months agoon
How can hacking the immune system help slow aging?
Stem cell researcher Carolina Florian couldn’t believe what she was seeing. His old laboratory mice began to look younger. They were more lively and their fur was shinier. However, all he had done was a short treatment a few weeks earlier with a drug that modified the organization of proteins in a type of stem cell.
Stem cell researcher Carolina Florian couldn’t believe what she was seeing. His old laboratory mice began to look younger. They were more lively and their fur was shinier. However, all he had done was a short treatment a few weeks earlier with a drug that modified the organization of proteins in a type of stem cell.
When technicians repeating Florian’s experiment in two other laboratories reached the same conclusion, Florian became more confident that the treatment in question would rejuvenate the animals. In two papers in 2020 and 2022, his team explained how this process extended the lifespan of mice and kept them in good physical condition into old age.
The purpose of Florian Elixir is the immune system. The immune cells he targeted are called hematopoietic stem cells, which give rise to mature immune cells. By circulating the blood, a mixture of these cells enters all the organs and affects all the functions of the body. However the molecular composition of hematopoietic stem cells changes during aging, and this upsets the balance of the immune cells that these stem cells produce.
Florian, who works at the Bleuge Biomedical Research Institute in Barcelona, says reversing the misalignment that occurs over time appears to reverse many of the problems of aging, not only in the immune system but in the rest of the body as well.
Description Researchers think the immune system could be the key to healthy aging.
In a paper published in March in the journal Nature, researchers show that restoring the balance between two key types of immune cells rejuvenates the immune system of aging mice and improves the animals’ ability to respond to vaccines and ward off viral infections.
Other scientists have used different experimental methods to reach a similar conclusion: Rejuvenating the immune system rejuvenates many organs in animals, at least in mice. More interestingly, evidence shows that aging of the immune system may cause aging of those organs.
The potential of the findings to help people stay healthy in old age is tantalizing. But applying this knowledge and using it in clinics will be challenging. Tampering with the immune system can be dangerous. Therefore, researchers initially aimed at low-risk goals such as improving the response of the elderly to vaccination and improving the efficacy of cancer immunotherapy.
Vittorio Sebastiano, a stem cell scientist at the Stanford School of Medicine in California, says the prospect that reversing aging might curb age-related diseases is enticing, but we proceed with caution.
Weakened immunity
The human immune system is a complex system whose many cellular and molecular components work together to help a person grow, protect him from infection, help heal wounds, and destroy cells that are becoming cancerous. But along with aging and changing the composition of the system, its efficiency decreases. In old age, people become susceptible to a wide range of infectious and non-infectious diseases and become more resistant to the protective power of vaccines.
Aging of the immune system may cause aging of different body parts
The immune system has two main components: the innate system, which indiscriminately destroys invading pathogens, and the more precise adaptive immune system, whose components learn to recognize and produce antibodies against specific foreign bacteria and viruses.
Hematopoietic stem cells in the bone marrow produce both arms of the immune system. They differentiate into two main types (lymphoid cells and myeloid cells), which then undergo further differentiation.
Lymphoid cells are primarily responsible for adaptive immunity and include B cells that produce antibodies, T cells that help attack invaders and coordinate immune responses and natural killer cells that kill infectious cells. Myeloid cells comprise a group of cell types that are mainly involved in innate immunity.
Proteins in stem cells that produce immune cells become more symmetrical as they age (right).
One of the first changes in the immune system during aging is the shrinking of the thymus, which begins after puberty. The thymus is where T cells mature, but much of this tissue turns to fat by the third decade of life, reducing the production of new T cells and weakening the immune system.
In addition, the function of T cells changes with age and they are not as specialized in detecting infectious agents as before. The ratio of different types of immune cells in the circulation also changes. The ratio of myeloid to lymphoid cells is significantly skewed toward myeloid cells and this can cause inflammation. In addition, an increasing number of immune cells become senescent, meaning that they stop replicating but do not die.
Aging cells usually occur when they undergo mutations. When cells are in this condition, they begin to release inflammatory signals and mark themselves for destruction.
An important anti-cancer and wound-healing mechanism works best when young. But when too much damage accumulates with age and the immune cells themselves age, this mechanism is disrupted. Senescent immune cells, attracted by inflammatory signals from senescent tissues, secrete their own inflammatory molecules. Therefore, they are not cleared properly but instead, add to the inflammation that also damages the surrounding healthy tissues. This phenomenon is known as inflammatory aging. This turns into a terrible positive feedback loop, says Aran Akbar, an immunologist at University College London. Evidence shows that this feedback loop is initiated by the immune system.
Laura Niedernhofer from the University of Minnesota in Minneapolis has shown in a series of experiments in mice that the aging of immune cells causes the aging of other tissues. He says these cells are very dangerous.
His team used genetic methods to delete an important DNA repair enzyme in the immune system of mice. The animals remained healthy until adulthood, but after that, they were no longer able to correct the accumulated mutations, and different types of immune cells began to age.
A few months later, an increasing number of cells in organs such as the liver and kidney were also senescent, and signs of organ damage appeared. When the scientists gave old mice immune cells from the spleens of young, healthy mice, all of these effects were reversed. All of this suggests that modifying the aging properties of the immune system could help prevent or reduce age-related diseases, Niederenhofer says.
Fight against aging
Many scientists are trying to do this from very different angles. Many approaches suggest that very short treatment of the immune system may have long-term effects and minimize side effects.
One of the ways to deal with aging immune cells is to use drugs to remove or inhibit the inflammatory factors that these cells release. Aging immune cells in humans can be changed, Niederenhofer says. If you smoke, they increase and if you exercise, they decrease.
Modifying the immune system can help prevent or reduce aging-related diseases
Some drugs, such as dasatinib, which is approved for the treatment of certain cancers, and quercetin, which is marketed as an antioxidant dietary supplement but not approved as a drug, slow cellular aging, and several trials are testing their effects on aging-related diseases.
Niederneuhofer is conducting a small clinical trial in elderly people with sepsis. Sepsis is a condition that becomes more deadly with age. His team is also conducting experiments to assess which types of immune cells are most involved in aging in the body, and their results could help design more precise treatments. Two types of cells (T cells and natural killer cells) are emerging as the main contenders, he says. He plans to examine natural products and approved drugs for their ability to interact with these types of immune cells during aging.
Akbar thinks targeting inflammation may be just as effective as targeting senescent cells. He and his colleagues conducted a study in healthy volunteers using the investigational compound lozepimod, which inhibits an enzyme involved in the production of a type of inflammatory molecule called cytokines. They treated volunteers with this drug for four days and then measured their skin’s response to an injection of the chickenpox virus over the course of a week. Most people are exposed to this virus during their life and this virus often stays in the body.
As people age, they lose their immunity to the chicken pox virus, and this time it can appear as shingles. The drug restored the immune response in the skin of older volunteers to a level similar to that of young volunteers. Akbar has found in unpublished studies that the same strong results persist up to three months later. Temporarily inhibiting inflammation in this way to keep the immune system functioning may similarly enhance the response of older patients to flu vaccinations, he says.
Boosting the immune system
The value of priming the elderly immune system prior to vaccination has been demonstrated in a series of clinical trials led by Joanne Mannick, CEO of Boston, Massachusetts-based Tornado Therapeutics. The trials tested analogs of the drug rapamycin and other drugs with similar mechanisms that target the immune system and are approved to prevent organ transplant rejection and to treat certain cancers.
The mentioned drugs inhibit an enzyme called mTOR, which is vital for many physiological functions and whose function is impaired in aging. Participants were treated with doses of the drug that were low enough to avoid side effects for several weeks before receiving the flu vaccine. This treatment regimen improved their response to the vaccine and increased their immune system’s ability to resist viral infections.
Vaccines are less effective in older people, but new approaches could increase their potency.
However the drug rapamycin can increase susceptibility to infection and affect metabolism, so Manick is planning trials with similar drugs that could be safer. “There are different ways to improve the immune system,” he notes.
Another way is to try to restore thymus function to maintain the production of new T cells. Jarrod Dudakoff, an immunologist at the Fred Hutchinson Cancer Center in Seattle, is studying the basic biology of thymus cells to understand how they regenerate after bouts of stress. Dudakov says it’s a little early to see how our understanding of this can be applied in the clinic. But he thinks it’s important to preserve the ability of the thymus to produce T cells.
Others try to fight aging by producing thymus tissue from powerful stem cells and then transplanting it. But Greg Fahey, chief scientific officer at Intervene Immune in Torrance, Calif., says there’s no need to wait to achieve those long-term prospects because synthetic growth hormone regenerates thymus tissue. He is conducting small studies in healthy volunteers using growth hormones as part of a mixture of compounds.
Preliminary results show that the amount of functional thymus tissue in the participants increased and their epigenetic clock (a biomarker of aging) was reversed by several years. Fahey is conducting further testing to see if the drug combination also improves the physical condition of the participants.
Turn back the clock
Another approach that has yet to reach the clinic is reprogramming immune cells to try to turn back the clock on cells that have aged. This procedure involves temporarily placing the cells in a dish exposed to a combination of transcription factors that induce a pluripotent state in mature cells.
Sebastiano and colleagues have shown in human cells that this corrects the epigenetic changes that accompany aging. He has founded a startup to use this technique to tackle a type of cancer treatment called CAR T, in which T cells are engineered outside the body to target and destroy a person’s cancer. However, the T cells may age before they are returned to the person. Rejuvenating them makes production faster and more powerful, says Sebastiano.
One of the challenges of aging studies is the inability to measure aging accurately
Florian’s approach also aims to produce healthier immune cells within the body. Hematopoietic stem cells in the blood develop epigenetic changes and their environment also changes with age. This causes the proteins to arrange themselves in a more symmetrical way in the cells (a process known as polarization), which shifts the balance of differentiation of stem cells towards myeloid cells.
In his studies, Florian used a four-day treatment with a compound called CASIN, which inhibited part of this process to correct polarization and help the mice live longer. When hematopoietic stem cells from aged mice that had received CASIN were transplanted into aged mice that had not received the treatment, the same life-extending effects were seen. Florian hopes to turn his results into a practical method in the clinic. He thinks his drug may help rebuild the immune system after receiving cancer chemotherapy.
The challenge of measuring aging
Research on immune aging faces major challenges. One of the challenges in aging studies of all organs is the inability to measure aging accurately. “We don’t know in a quantitative, measurable, predictable way what aging means at the molecular level in different cell types,” says Sebastiano. “Without these metrics, it is very difficult to demonstrate rejuvenation.”
Another challenge is the difficulty in determining the characteristics that make an immune cell unique. Until recently, it was difficult to show where each of the immune cell subsets lived and how they changed over time. But technologies such as single-cell RNA sequencing, which quantitatively measures genes expressed in single cells, have made the analysis more challenging. For example, a large study of immune cells in the blood of humans and mice across a range of ages, published last November, revealed 55 subpopulations. Only 12 subpopulations of cells changed with age.
By collaborating with different research areas, scientists hope to prove that the immune system plays an important role in healthy aging. Don’t expect an elixir of youth anytime soon, says Florian. Aging research will take a long time, but it can help design tools that will be transformative.
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usPronoun: me and at least one other person; the objective case of ‘we’.
Pronoun: me.
Pronoun: our.
Pronoun: Me (in all contexts).
Determiner: The speakers/writers, or the speaker/writer and at least one other person.
Symbol: : microsecond
۴۰Pronoun: me and at least one other person; the objective case of ‘we’.
Pronoun: me.
Pronoun: our.
Pronoun: Me (in all contexts).
Determiner: The speakers/writers, or the speaker/writer and at least one other person.
Symbol: : microsecond
The wonderful world of ultrasound
Ultrasound imaging is a non-invasive imaging method that is used in many medical fields. From diagnosing cardiovascular diseases and examining fetal growth during pregnancy to evaluating tumors and examining joints, ultrasound is considered an extremely valuable tool for doctors; Especially since ultrasound does not use X-rays, it is a more suitable method for patients of any age group, including pregnant women.
During World War I, French scientists used ultrasonic waves to locate enemy submarines. The use of ultrasound waves was considered a great achievement at that time. In 1956, Professor Ian Donald (Glasgow Royal Maternity Hospital) was the first to use ultrasound for medical diagnosis and measurement of fetal head diameter.
Ian Donald, a pioneer in the use of ultrasound for medical diagnosis
This act was a turning point in the development of ultrasound as a practical tool in medical diagnosis, pregnancy care, and fetal health. Since then, ultrasound has become one of the most common and safest methods in diagnosing and monitoring the condition of the fetus during pregnancy. In ultrasound, we use ultrasound waves to image the internal organs of the body.
In this article, we will first get acquainted with the physics governing the ultrasound machine, then we will talk about imaging with it.
Physics governing the ultrasound machine
Sound is a type of mechanical energy and it needs a material environment (solid, liquid, and gas) to be transmitted from one point to another and it is transmitted through pressure waves. The number of oscillations or vibrations (cycle of movement) of the particles of the environment per second is called frequency, which is one of the important characteristics of sound waves.
Sound waves are transmitted to nearby molecules through the vibration of molecules and their pressure changes. This transfer is done mechanically through a process called diffusion. As we said, sound waves, unlike electromagnetic waves such as X-rays, need a material and elastic medium to propagate. Electromagnetic waves can travel through a vacuum, but sound waves need a material to travel through.
Sound travels at different speeds in different environments due to different physical characteristics. For example, sound waves travel faster in solid media than in liquids and gases because the molecules of solids are closer together and energy is transferred more efficiently. Therefore, the speed of sound in a solid substance is about 6000 m/s, in a liquid with a temperature of 20 degrees Celsius it is about 1481 m/s and in air, it is about 343 m/s.
Sound waves travel faster in solid materials
Let us explain this process with a simple example to better understand the propagation of sound waves in the environment. Suppose you have a speaker or a microphone and you are giving a speech to a crowd. When playing sound from the speaker, its diaphragm moves forward and backward. The vibrating movement of the diaphragm causes compression and condensation of air molecules near it. This means that the vibration of the diaphragm also vibrates the air molecules and this vibration will be transmitted to the nearby molecules.
Vibration of air molecules near the speaker
As you can see in the image above, the air molecules near the speaker (sound source) oscillate in a sinusoidal fashion. As we said, the ultrasound machine takes pictures of the internal organs of the body with the help of ultrasound waves. Ultrasound waves are sound waves that oscillate at frequencies higher than 20,000 Hz; That is, higher than the range of frequencies that the human ear can detect (between 20 and 20,000 Hz). Some animals, such as owls, can naturally produce ultrasonic waves and use them for communication and echolocation.
Echolocation is a method that bats use to find their way and identify objects or other animals in the environment. By producing an ultrasonic wave, the bat sends it to its surroundings. After hitting different objects, the sent wave becomes an echo and reaches the bat. After receiving the reflected wave, the bat identifies the location and distance of the objects by analyzing the return time and sound intensity.
Suppose we have two different environments, such as air and water, and the ultrasonic wave, moving from air to water, hits their separating boundary. what happens A part of the wave is reflected from the boundary separating the two environments and a part of it enters the water after crossing the boundary. This is called partial reflection because only part of the radiated wave is reflected. Therefore, whenever the ultrasonic wave hits the boundary separating two environments, part of it is reflected and another part enters the second environment.
Now suppose we shine ultrasound waves on an object that has different boundaries, therefore, a part of the waves will return to us after hitting each boundary. By knowing the speed of sound waves and the duration of their reflection, we can get the distance of each border. This mode is similar to when a bat uses ultrasound waves to determine the distance between different objects. By collecting and examining all the reflected waves, we get information about the different boundaries inside the object and its structure.
The important question is what factors determine the speed of sound waves in the environment. The density of the environment is one of the factors that determine the speed of sound. The denser the environment, the slower the sound travels in it. Also, the more compressible the medium, the slower the speed of sound in that medium. In addition to density and compressibility, the hardness of the environment also affects the speed of sound movement in the environment; More difficulty, more speed.
Here we come to a paradox. At the beginning of this section, we mentioned that sound travels faster in a solid than in a gas or liquid. But solid density is higher than liquid and gas! We must pay attention to the fact that the effect of each factor on the speed of sound is not the same and the effect of density on speed is less than the effect of compressibility. For example, although the density of mercury is 13.5 times that of water, sound travels at about the same speed in water and mercury. The reason for this is due to the compressibility of water 13.4 times compared to mercury.
This is very helpful in ultrasound imaging. When imaging soft tissues inside the body, we assume that sound travels at a constant speed inside all body tissues (such as the liver and kidney); Of course, the speed of sound is different in human tissues. For example, its amount in breast tissue is about 1430 m2 and in muscles about 1647 m2. Despite these differences, ultrasound machines usually use a fixed speed (1540 m/s) to reconstruct the images.
So far, we have learned about the physics governing the ultrasound machine. Next, we will talk about imaging with this device.
Ultrasound imaging
In the ultrasound machine, we use a device called “Transducer” for imaging. A transducer is a device that converts energy from one form to another. In ultrasound, with the help of transducers, we send sound waves into the body and receive reflected waves from internal tissues. These returning waves are converted into images that doctors use to examine the organs and internal tissues of the body.
For imaging, the doctor places the transducer on the skin as shown in the image below. Next, the transducer receives electrical energy and converts it into sound energy. After reaching the tissues, a part of the sent sound wave is reflected from them and hits the transducer. In other words, after sending a sound wave (sound pulse) into the body, the ultrasound device waits for the return or echo of that wave from the body tissues.
Based on the time required for the reflected waves to reach the transducer, the device calculates the exact location of the reflected waves (distance or depth from where the wave comes) and creates a corresponding pixel in the image. By repeating this process continuously, a two-dimensional image of the cross-section of tissues is formed.
The device simply calculates the depth or distance. We assumed the speed of sound to be constant in different tissues. Therefore, by measuring the time of sending, reflecting a part of the sound wave from the tissue, and reaching it again to the transducer, we can easily obtain the distance from which the wave was reflected. According to the intensity of the wave reaching the transducer, we can determine the brightness of the pixel.
According to the time of arrival of the waves reflected from the tissues to the transducer, we can obtain the location of the tissues.
Ambient temperature also affects the speed of sound; The higher the temperature, the faster the sound wave travels. But this case does not affect the imaging with ultrasound waves, because we can consider the body temperature to be constant with a good approximation.
In order to have a better understanding of ultrasound imaging, we need to get to know the behavior of these waves inside the body tissues. How ultrasound waves interact with the internal tissues of the body plays an important role in the created images. In the following, we will talk more about this.
Interaction of ultrasound waves with internal body tissues
As we mentioned in the previous section, part of the ultrasound waves are reflected after reaching the boundary separating the two environments. This happens when this wave hits the internal tissues of the body. The texture border separates two different textures from each other. Ultrasound waves can reach fat after passing through muscle. We call the border between muscle and fat, tissue border.
When ultrasound waves hit the boundary between tissues, any of the following situations may occur:
- A part of the wave radiated to the boundary passes through it and the rest is reflected from the boundary.
- All the wave that hits the boundary is reflected from it in the direction of the radiated wave.
- The radiated wave is reflected from the boundary of two tissues in a mirror or non-mirror form.
- The wave radiated to the boundary of the tissue is scattered inside it. This state occurs when the constituent units of the tissue are smaller than the wavelength of the irradiated ultrasound. In this case, most of the wave energy radiated to the tissue is lost and a part of it is spread in all directions.
Types of interaction of ultrasound waves with tissue
What determines the type of interaction of ultrasound waves at the tissue boundary is called “acoustic impedance with acoustic resistance” (Acoustic Impedance or Z). Acoustic impedance is an inherent property of every tissue and is obtained from the product of tissue density and the speed of sound movement inside that tissue. In simple words, acoustic impedance indicates the resistance of a material to the passage of sound waves through it.
Suppose we send the ultrasound pulse to a specific tissue inside the patient’s body. When the pulse reaches the boundary of the tissue, it encounters another tissue with a different acoustic impedance. The value of the acoustic impedance difference between the two tissues determines the value of the ultrasound wave passing through the boundary and the value of the reflected wave (echo). The table below shows the sound impedance of different environments.
Material |
speed (ms) |
Acoustic impedance |
---|---|---|
air |
330 |
6^10 × 0,0004 |
lung |
600 |
6^10 × 0٫18 |
fat |
1450 |
6^10 × 1,34 |
water |
1480 |
6^10 × 1,48 |
soft texture (medium) |
1540 |
6^10 × 1,62 |
muscle |
1600 |
6^10 × 1,71 |
bone |
4080 |
6^10 × 7,8 |
As you can see in the table above, the amount of sound impedance in water and bone is significantly different from each other. If the acoustic impedance values of two tissues are very close to each other (such as fat and water), most of the ultrasound wave will pass through the boundary of the two tissues, and a small amount of it will be reflected as an echo. On the other hand, if the acoustic impedance values of two tissues are very different from each other (such as muscle and bone), most of the ultrasound wave will be reflected from the boundary of the two tissues and a small amount of it will pass through the boundary.
Reflection of ultrasound waves from tissue
As we mentioned in the previous section, due to the difference in acoustic impedance between the two tissues, part of the ultrasound waves pass through the border and another part is reflected perpendicularly to the border, in a mirrored, regular, or irregular way. Vertical reflection occurs when the boundary of the tissue on the radiating ultrasound wave is perpendicular and the boundary is also large and flat. This condition can occur in the renal capsule. Due to the difference in the acoustic impedance of the fat around the kidney and the kidney tissue, some of the radiated ultrasound waves is reflected and reach the transducer.
In some cases, all the ultrasound waves radiated to the tissue are reflected from it. This case occurs in a case where the difference in acoustic impedance between the two environments is very large. For this reason, we cannot take pictures of the lungs with the help of ultrasound waves, because the air inside the lungs has a much lower acoustic impedance compared to the surrounding soft tissue.
In some cases, instead of vertical radiation, the ultrasonic wave hits a flat and large surface with a specific angle. In this case, regular or mirror reflection occurs as shown below. When a surface is smooth (such as a mirror or the surface of a bone), sound waves are reflected in a specific and regular direction instead of being scattered in different directions. This is similar to the reflection of light from a mirror, where the light is reflected directly at a certain angle and not diffusely.
Regular or specular radiation
In most cases in regular irradiation, the reflected ultrasound beam does not return to the transducer. Fortunately, most large surfaces inside the body are not perfectly flat and smooth and do not reflect ultrasound waves in a mirror-like fashion. As a result, irregular or non-specular reflection occurs most of the time. In this case, the reflected wave is reflected in different directions. The intensity of the vertically reflected wave is much stronger than the irregularly reflected wave.
About 59% of the ultrasound waves radiated to the bone pass through it and 41% are reflected, but we cannot see the images of the tissues behind the bones with the help of ultrasound waves. The reason for this is that the amplitude of ultrasound waves decreases after entering the bone and moving through it.
Refraction of ultrasound waves from tissue
In the previous section, we learned about the reflection of ultrasound waves from body tissues. If the ultrasound wave hits the boundary of two tissues with a certain angle, after interacting with the tissue boundary, part of it will be reflected from it and another part of the boundary will pass and enter the second environment with a different angle (larger or smaller) than the radiation wave. . In this case, instead of the value of the wave transmitted or reflected from the boundary, we obtain the angle change by changing the speed of the ultrasonic wave in each environment.
Changing the angle of the ultrasonic wave based on its speed in different environments
Dispersion and reduction of the amplitude of ultrasound waves
When ultrasound waves interact with internal body tissues, they are reflected, scattered, or passed through them. Also, the amplitude of ultrasound waves decreases when entering bone or other tissues. Scattering occurs when the wavelength of the wave when hitting an object or part of it is smaller than the dimensions of that object.
When the ultrasonic wave passes through an environment with dimensions larger than its wavelength, it will pass without scattering. If the environment consists of components with dimensions smaller than the wavelength of the ultrasound beam, scattering occurs. As a result, the amplitude and intensity of ultrasound waves are reduced when passing through such environments (such as bone).
Dispersion of ultrasound waves
The lower the density of areas with dimensions smaller than the ultrasonic wavelength, the greater the scattering. Scattering is one of the main factors in creating the “echogenicity” of the tissue or the ability of the tissue to reflect sound waves. The greater the dispersion, the greater the echogenicity. In other words, the structures inside the tissue that cause the scattering of the waves help create a clearer image in the ultrasound.
Unlike ultrasound imaging, in X-ray imaging, we are not interested in scattering. When the ultrasound wave passes through a tissue such as the kidney, it is scattered by its smallest constituent units and a part of it reaches the transducer. Although the waves reaching the transducer are noisy and not very regular, they give us information about the kidney or any other tissue.
In addition to scattering, heat generation in tissues can also reduce the amplitude of ultrasound waves. Ultrasound waves may be absorbed by tissues as they pass through them, leading to heat generation. The attenuation of ultrasound waves varies from one tissue to another and depends on the attenuation coefficient of each tissue and the frequency of the ultrasound wave.
texture |
Tissue attenuation coefficient |
---|---|
water |
0,0002 |
blood |
0,18 |
soft texture |
0,3-0,8 |
liver |
0,4-0,7 |
fat |
0,5-2 |
tendon |
1 |
bone |
20 |
lung |
40 |
Suppose we send an ultrasound wave with a frequency of 4 MHz from the transducer to one of the internal tissues of the body. After traveling a distance of 5 cm, this wave reaches the boundary of the tissue shown in the image below. The intensity of this wave after traveling a distance of five centimeters and reaching the border of the tissue becomes about one tenth. After reaching the boundary, the wave reflects and moves towards the transducer.
The intensity of the wave after reflecting from the boundary and reaching the transducer also decreases by another tenth. As a result, the wave reaching the transducer is about one hundredth of the original ultrasonic wave. Of course, this is the case if the ultrasonic wave is perpendicular to the boundary and all of it is reflected.
Transducer and its components
So far, we have learned about the interaction of ultrasound waves with the internal tissues of the body. In the ultrasound machine, the transducer receives the reflected waves by producing ultrasound waves and irradiating them to the tissues. The reflected waves are converted to a digital signal by the transducer and then analyzed.
The piezoelectric material in the transducer is responsible for creating ultrasound waves and sending these waves to the body tissues. Also, this part receives reflected and scattered ultrasound waves from tissues and converts them into electrical signals. As you can see in the picture above, the piezoelectric material is located in front of the transducer.
The piezoelectric material has a unique feature; Squeezing this material induces an electric current and the current passing through it causes the material to vibrate and move. In the ultrasound machine, sound waves hit the piezoelectric material between two electrodes and compress it. This compression creates an electric current corresponding to the intensity and frequency of the sound waves, which will be transmitted as a signal to the ultrasound machine.
At the same time, the ultrasound device can cause the piezoelectric material to vibrate and produce sound waves by applying an electric current. This feature allows the ultrasound device to convert signals received from the body into images and send sound waves to examine body tissues. Electrodes also play an important role in enhancing the piezoelectric effect and conducting electric current.
The piezoelectric material in the transducer is responsible for creating ultrasound waves
Piezoelectric crystals are the beating heart of ultrasound transducers. Each of these crystals acts like a small spring that sends sound waves at a certain angle to the body and receives the reflected waves from that angle. This feature allows the device to create a 2D and in some cases 3D image of the body’s internal structures.
An array of crystals is used to improve image resolution, especially in the horizontal direction (side-to-side resolution). Using these arrays, the ultrasound machine can detect very small details such as small blood vessels or the internal structures of organs in the body tissues. In addition to the number of crystals, other factors such as the frequency of sound waves, the angle of radiation, and image processing techniques are also influential in the quality of the final image.
In ultrasound, we use different transducers with different frequencies. We cannot easily change the frequency of transducers, because two factors determine the frequency value:
- Speed of sound passing through piezoelectric material
- The thickness of the piezoelectric material
The smaller the thickness of the piezoelectric material, the higher the frequency of the emitted wave. The depth of penetration of waves with different frequencies is different. Waves with smaller frequencies have a lower penetration depth and waves with larger frequencies have a greater penetration depth.
In ultrasound, we use different transducers with different frequencies to take images of tissues
The speed of sound in piezoelectric material is much higher than the speed of its movement in body tissues. As a result, these two environments (piezoelectric material and tissue boundary) have a high acoustic impedance difference. The large difference in acoustic impedance between these two environments causes a large part of the energy of sound waves to be wasted when passing through the crystal to the body. The adaptation layer in the transducer prevents the loss of energy of the sound waves during transmission from the piezoelectric material to the internal tissues of the body.
As you can see in the image above, the matching layer is located on the front of the transducer and protects the piezoelectric crystals and internal body tissues. Also, the acoustic impedance of this layer is a number between the acoustic impedance of the piezoelectric material and the internal tissues of the body. The adaptation layer, by adjusting and adjusting the audio impedance, increases the transmission of waves and improves the quality of the ultrasound image.
Our skin is not a perfectly smooth surface, so the matching layer can’t sit on it very well. Hence, some air is trapped between the matching layer and the texture. The acoustic impedance of air is very small, as a result, the acoustic impedance difference becomes very large and the sound waves cannot be easily transmitted from the transducer to the tissue. “Coupling Gel” is used to solve this problem.
Coupling gel is a water-based material with acoustic impedance close to the tissue, which is placed between the transducer and the patient’s skin, and its main function is to remove air between the probe and the skin. By removing the air, the gel causes better transmission of sound waves from the device to the body and vice versa. This helps create clearer and more detailed images of the inside of the body.
So far, we got acquainted with the piezoelectric material and the matching layer that is placed in front of the transducer. With a little distance from the front of the transducer and before the piezoelectric material, we reach a part called damping. The main purpose of attenuation is to improve image quality and reduce noise. As we said, ultrasound waves are produced by the vibration of piezoelectric material with a specific frequency. The vibration of the piezoelectric material continues for a certain period of time, but the damping part can shorten the period of its oscillation.
When the piezoelectric material contracts and expands, part of the generated waves move towards the patient and another part returns to the transducer. The damping piece prevents the generated waves from returning to the transducer and directs them to the target tissue.
So far, we have learned about the interaction of ultrasound waves with the internal tissues of the body and the internal structure of the transducer. In the following, we will talk a little about the details of imaging with ultrasound waves in the ultrasound machine.
Image formation in the ultrasound machine
The ultrasound image is a cross-section of the patient’s body, which is formed line by line in front of the transducer. The transducer sends ultrasound waves to the internal tissues of the body. After hitting different tissues, the sent waves are reflected from them and hit the transducer. Each line of the image is created based on these reflections and in this order, with the movement of the transducer on the body, successive lines are formed and the final image is made of the internal structure of the body.
In the following, we will examine together how the image of the kidney (right kidney) is formed in the ultrasound machine. First, an electric current is applied to the transducer and the piezoelectric material, and an ultrasonic wave is created. As we said, the ultrasound wave moves at a speed of about 1540 meters per second inside the body tissues. Part of the ultrasound waves, upon reaching the internal structure of the kidney and the tissue border, are reflected and move toward the transducer. The black-and-white image of the kidney is produced after processing the reflected waves. Because sound travels at a certain speed, the ultrasound machine can interpret the received signals and show the structures exactly where they are located on the monitor.
In ultrasound, the depth of the structures in the tissue is directly related to their position in the image. Ultrasound waves reflected from structures close to the surface of the tissue reach the transducer earlier, so they are displayed in the upper parts of the image. In contrast, deeper structures need more time to send and receive sound waves, so they will appear in the lower parts of the image. This basic principle in ultrasound allows us to view a cross-section of the body and estimate the depth of each structure relative to the surface of the skin.
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As we mentioned in the previous sections, tissues are heated by absorbing ultrasound waves, and the amplitude of these waves decreases with increasing depth of penetration. Therefore, it is more difficult to see deeper structures on ultrasound, because the ultrasound waves are too weak to reach them. To compensate for this attenuation, most ultrasound systems use a feature called “Time Gain Compensation” (TGC). TGC amplifies the return signals from deeper layers so that we can have better and clearer images of deeper structures.
Some structures, such as bones, are strong reflectors of ultrasound waves, and most of the ultrasound waves irradiated to them are reflected. In this case, the acoustic shadow is created as shown in the image below.
Acoustic shadow formed by diseased ribs
As we mentioned in the previous sections, ultrasound waves are scattered after hitting a heterogeneous surface. Dispersion of ultrasound waves in the body tissues leads to the appearance of speckles in ultrasound images. These stains may reduce image resolution and make it harder to accurately identify structures.
Frequency greatly affects the resolution of images taken with ultrasound waves. Ultrasound waves with a smaller frequency can travel a greater distance inside the body and penetrate the deep structures of the body better than ultrasound waves with a larger frequency. In contrast, higher-frequency ultrasound waves are suitable for imaging surface structures. As a result, to get the best image of the internal organs of the body, we must choose a transducer with a suitable frequency.
The ultrasound waves used in ultrasound have turned from a war tool to track submarines into one of the main pillars of medical diagnosis. Ultrasound technology allows us to penetrate deep into our body without pain or risk. From diagnosing cardiovascular diseases to examining the growth of the fetus in the mother’s womb, ultrasound plays a vital role in maintaining human health.
The future of ultrasound is very bright with significant advances in imaging technologies and artificial intelligence. 3D and 4D ultrasound can provide more detailed images of internal body tissues and organs. Artificial intelligence will also be used as a key tool in faster and more accurate analysis and interpretation of images and can reduce human error.
Also, a portable ultrasound that can be used at home makes access to this method easier for doctors and patients even in remote areas. The use of augmented reality and virtual reality technologies in ultrasound will also make it possible to analyze images interactively and in more detail.
Finally, it can be predicted that ultrasound will revolutionize medical diagnosis and treatment in the future with higher accuracy, wider access, and more diverse applications.
Pronoun: An indefinite large number of people or things.
Noun: A multitude; a great aggregate; a mass of people; the generality; the common herd.
Noun: A considerable number.
Adjective: Existing in large number; numerous.
How does loneliness affect the brain and body?
People were alone even before Corona. Before the spread of Corona, people approached each other without anxiety; But now researchers have found that Americans are lonelier than ever. According to Cigna Health Center research in 2018, almost 54% of the 20,000 Americans who participated in this research felt lonely. In a period of more than a year, this figure reached 61%. Generation Z adults between the ages of 18 and 22 can be considered the only generation to surpass Boomers, Generation X, and Millennials. (Generation Z refers to those born from the mid-90s to the 2010s. The boomer generation or the boom generation refers to those born between 1946 and 1964, Generation X refers to those born in the early 1960s to 1980s, and the millennial generation refers to those born in the 1980s to the early 2000s. will be).
According to Doug Namek, Cigna’s chief medical officer, loneliness can throw off the worldly equation. According to many researchers, staying alone for a certain period of time is harmful to people’s mental and physical health. Signal research has also placed the health risks of loneliness alongside smoking and obesity. A Lancet research in 2018 describes loneliness as follows:
Conditions that cause irritability, depression and self-centeredness have a direct relationship with a 26% increase in the risk of premature death.
On the other hand, due to the spread of Covid-19, maintaining distance is the safest way to stay healthy. Although social distancing can increase feelings of isolation. As a result, COVID-19 can be seen as a new reason for the effect of loneliness on the brain, heart, and immune system.
Why are we lonely?
Loneliness can mean separation from friends and family, but the feeling of loneliness is much deeper than not having a companion on holidays or not going to various celebrations and ceremonies. From an evolutionary point of view, membership in groups and communities has always meant self-protection, division of labor, and increased chances of survival. On the other hand, humans have evolved over a long period of time and need their tribes. According to Julian Hutt Lundstad, professor of psychology and neuroscience at the University of Birmingham:
Loneliness and lack of membership in groups leads to anxiety. In this situation, we have to deal with the environment alone without the help of others, that’s why our brain is on alert and also sends a warning signal to other parts of the body.
Alertness leads to increased stress. Stress hormones, including cortisol and norepinephrine, can affect sleepiness, weight gain, and anxiety over long periods of time. According to Halt Lundstedt, the coronavirus is one of the most stressful situations that many people have experienced in their lifetime. Daily life has been disrupted, unemployment has risen dramatically, and more than 6 million people worldwide have been infected with the virus. Usually, people in difficult situations need the support of family and friends. Due to the nature of the coronavirus, people are now more alone than before and can hardly communicate with each other.
The genetic structure of lonely people is more prone to disease
Study alone
Almost everyone can cope with loneliness, but scientists are still looking to investigate its effects on health. On the other hand, loneliness is a subjective feeling that cannot be measured. Even the social circle of people is not a guarantee that they are not alone.
According to Holt Lundstedt, surveys usually ask people about loneliness either directly (how lonely do you usually feel?) or indirectly (do you feel friendless?).
NASA has been investigating the effects of isolation and the enclosed environment on astronauts for years and has reached similar results to other studies: isolation conditions can lead to behavioral and cognitive problems. Researchers are also looking to investigate the biological dimensions of loneliness as well as its physical effects on the body in other places.
Perhaps, to understand the feeling of loneliness, it is necessary to examine people’s brains. Researchers at the Rush Alzheimer’s Disease Center in Chicago studied 823 adults over a four-year period. They used questionnaires to assess loneliness, categorize Alzheimer’s disease and dementia, as well as test participants’ thinking, learning, and memory, and set loneliness scores between 1 and 5. According to the results, the risk measure of Alzheimer’s disease increases by 51% for each point of the scale.
Loneliness puts the body in a state of alert and leads to an increase in anxiety
Also, the dead people were autopsied during the investigation period. According to the results, loneliness is the cause of brain changes associated with Alzheimer’s disease, including plaques and neural tangles or tissue damage due to lack of blood flow. However, Robert S. Wilson, one of the researchers of this study, believes that loneliness can make people vulnerable to the neurodegenerative effects associated with aging. According to Turhan Connelly, professor of neuroscience at Stony Brook University: “Loneliness can be a predictor of cognitive decline.”
The exact relationship between loneliness and health problems is still unclear. According to Connelly, if a person is lonely and feels bad about themselves, they will take less care of themselves. For example, these people don’t eat well usually drink a lot, have a lot of worries, or lack sleep. Such habits will have long-term consequences. Connelly also discussed a collaboration with David Bennett, another researcher at the Rush Alzheimer’s Center who has studied the genes of people who are not alone.
Bennett began a long research almost thirty years ago. In this research, the participants agreed to give their brains to researchers after death in exchange for an annual physical and mental check-up. The researchers investigated two points of the brain related to cognition and emotion. According to the results, genes related to cancer, cardiovascular, and inflammatory diseases appeared more in single people. According to Connelly:
There is usually a network of relationships between different genes that can influence each other. For this reason, the effect of loneliness on the occurrence of diseases can have a genetic reason.
Of course, the above findings do not mean that loneliness leads to heart disease. Rather, more research is necessary, such as the role of heredity in the occurrence of genes. Early research by UCLA researcher Steve Cole suggests one possibility: the release of certain hormones under conditions of stress and loneliness can activate specific genes that cause health problems. According to Connelly:
The mental experience of the brain can become a biological process, which is our goal to investigate this process.
A better understanding of the above relationships can affect the treatment methods of patients.
The future and loneliness
Despite the reduction in the intensity of quarantine and the gradual removal of restrictions on the activities of restaurants and public places, the impact of social distancing on society is still unclear. According to Harvard researchers in April, compliance with social distancing is necessary until 2022. NASA astronaut Scott Kelly spent 340 days alone in space, and in March published an op-ed based on his experiences in the New York Times Magazine. Kelly recommends reading magazines, keeping a schedule and discipline, as well as having fun in your alone time. Namek from the Cigna Institute also believes that it is necessary to examine loneliness in people and have an honest conversation about loneliness with people who struggle with this problem. According to him:
We need to contact our friends maintain our relationships and have meaningful conversations. It is necessary to always feel comfortable in asking the feelings of the other party.
Noun: The condition or state of being alone or having no companions.
Noun: The state of being unfrequented or devoid of human activity (of a place or time).
Noun: A desire to be alone; disposition to solitude.
Noun: A feeling of depression resulting from being alone or from having no companions.
Noun: The condition or state of being alone or having no companions.
Noun: The state of being unfrequented or devoid of human activity (of a place or time).
Noun: A desire to be alone; disposition to solitude.
Why is the loneliness epidemic so hard to cure?
Richard Weisbord, a psychologist and lecturer at Harvard University, started a new study in the early months of 2020 along with the worldwide quarantine of Covid-19. In his opinion, loneliness or its specter is everywhere. Two years ago, Weisbord read a study from insurance provider Cigna that found 46 percent of Americans sometimes or always feel lonely, a number that rose to 52 percent in 2019 when the study was repeated. Weisbord thought, in quarantine, this number has increased a lot.
Weisbord wanted to know how loneliness feels for lonely people. What are its possible consequences? And what causes it? It is difficult to answer these questions; Because loneliness is a complex or multidimensional emotion; That is, it includes the elements of sadness and anxiety, fear and heartbreak. The experience of loneliness is personal and highly subjective (internal) and depends on a person’s way of thinking. A clerk in a busy grocery store can be intensely lonely, just as a recluse living in a cave can endure solitude in complete happiness.
Loneliness should not be confused with isolation. For convenience, most researchers still use the definition coined by social psychologists almost three decades ago, in the early 1980s. Loneliness is described as “the difference between desired and achieved levels in one’s social relationships” which, unfortunately, is also very subjective.
To understand the current loneliness crisis, Weisbord, who leads a Harvard project on health and well-being, created a 66-question survey and sent it to about 950 people across the United States. With the exception of a few direct statements such as “In the past four weeks, how often have you felt lonely?”, most questions indirectly explore loneliness from different angles; For example, are there people in your life who ask for your opinion on things that are important to you?
Loneliness is an epidemic that is more felt in today’s society
Some of the other questions in the questionnaire included: “Do you feel that you connect with people more than they connect with you?” or “Has anyone ever taken more than a few minutes to ask you how you’re doing in a way that makes you feel like they really care?”
When the results came in, Weisbord was shocked by the extent of the loneliness problem; 36% of respondents experienced chronic loneliness, and 37% experienced occasional loneliness in the last month. Among those who felt lonely, 46 percent said they interacted with people more than people interacted with them, and 19 percent felt that no one outside of their family cared about them at all.
In February 2021, as Harvard planned to resume face-to-face classes, the Weissboard team released the results of the survey, highlighting deep social issues in America. These findings attracted a lot of attention and many saw themselves as partners.
A 2021 Gallup poll found that 25 percent of adults often feel lonely, and nearly 40 percent of young adults do so regularly. Although these numbers have improved slightly, 25 percent of Americans still feel more lonely than before they were born.
Last year, U.S. Surgeon General Vivek Murthy released a report calling loneliness an epidemic that affects Americans more than diabetes or obesity. The World Health Organization also classified loneliness as a global public health concern. Like depression and anxiety, loneliness has become a hot topic in culture and has spawned numerous articles, self-help books, podcasts, and even startups focused on loneliness.
Japan and Britain have even appointed single ministers tasked with monitoring and ameliorating the depth of the crisis, either through public awareness campaigns or initiatives such as a scheme in the UK where letter carriers were asked to meet elderly residents on routes. Call yourself.
Attempts to address loneliness often show that simple actions such as a phone call, email, or meeting can solve the problem by restoring lost social connections. However, this view misunderstands the complexities of modern life and may distract from deeper problems such as alienation, isolation, mistrust, and disconnection. These issues stem from the weakening of institutions and traditions that once bound people together, and addressing them requires more than a return to the past.
Unlike anxiety or depression, loneliness is a relatively modern concern. Historian Fei Bond Alberti notes in his book A Biography of Loneliness that loneliness, as we understand it today, did not become widespread in the world until after the 1800s. The West was not discussed.
Loneliness is a relatively modern concern
It is not correct to say that no one knew the word loneliness before the 1800s, But loneliness was not always associated with negative feelings. While the word appeared in Shakespeare and Robinson Crusoe, solitude was often seen as a positive experience, especially in the busy past.
Prior to the 19th century, loneliness did not carry the same emotional weight as it does today, Alberti notes. His research shows that there was no mention of “solitude” in English literature until about the 1820s when the term suddenly became very popular. This change coincided with rapid changes in society, such as war, industrialization, and urbanization, which tore apart traditional societies and led people to seek new ways to express the emotional effects of these changes.
In the 1950s, American scholars began to explore loneliness as a modern subject, paving the way for loneliness studies. Sociologist David Reisman linked loneliness to social changes in post-war America. In his book The Lonely Population, Reisman explained how prosperity leads Americans to focus on material possessions and social comparisons; A behavior that he called “other-oriented”. This phenomenon is similar to today’s term FOMO (fear of being left behind). When people can’t get what others enjoy, the feeling of loneliness starts.
Some experts consider loneliness a severe medical condition, similar to depression, with debilitating effects. American psychologists Louise Hawkley and John Cacioppo used hypnosis in an experiment to induce loneliness in participants. This led to an increase in people’s blood pressure and inflammation, showing that loneliness directly affects health. When the loneliness induction ended, their health indicators improved.
Loneliness is a biological signal designed to motivate us to seek social connection and support
In another study by Hawkley and Cacioppo, participants were removed from a social activity to show that loneliness, similar to physical pain, triggers a pain response in the brain. Like hunger, this response is a biological signal designed to motivate us to seek social connections and support.
Loneliness can become a self-reinforcing cycle, where fear and anxiety convince people that they are not worth connecting with, making them feel trapped and increasingly isolated. A 2021 study by psychologist Daniel Maitland found that when lonely people are asked to share personal details, they experience a lot of stress, suggesting that vulnerability is a big challenge for them. This makes the traditional advice to join social activities ineffective, as such gatherings are outdated and unattractive to many.
In his book “Bowling Alone”, Robert Putnam noted the decline of American participation in organizations and social groups. Almost 25 years later in 2024, fewer Americans are getting married than in the middle of the 20th century. The number of people living alone has more than tripled to 29%. But being married doesn’t necessarily prevent loneliness, because a bad marriage can be very isolating, and likewise, living alone doesn’t always mean being alone.
Less attendance at religious ceremonies is also an example of reducing the traditional activities of society. Weisbord believes religious communities are places where adults engage with children, defend moral values, and engage children with big moral questions. He says he does not suggest becoming more religious; But in those aspects of religion where you feel an obligation to your ancestors and children, there is a structure to deal with grief. We have to figure out how to reproduce those aspects of religion in secular life.
Weisbord and Milena Batanova, the project’s director of research and evaluation, found in a follow-up survey that many respondents attributed their loneliness to a lack of “meaningful connection”; Even when surrounded by others. Emotional closeness rather than physical presence was often the main issue, and some felt devalued or disconnected from those around them.
Working doesn’t bring much relief, as fewer Americans find meaning in their careers, especially as the rise of remote work complicates community building. Older people are more likely to have found meaningful relationships and close friends at work, while younger people struggle with dating due to the shift to telecommuting and virtual communication.
The epidemic of loneliness has left lasting effects on social interactions; So many people with poor social skills were released from quarantine. Simultaneously with the rise of frictionless forms of digital interaction such as automated payment systems and food delivery, a phenomenon has emerged that some experts call “cocooning”; It means retreating to the digital world that lacks meaningful communication with people.
Julian Holt Lanstad, professor of psychology and neuroscience at Brigham Young University, noted that from 2003 to 2020, Americans spent more time alone and less time with friends and family. The data backs this up, showing that many people struggle with relationship issues and feel like they don’t connect well with people. This suggests that many Americans are not getting the social support they need, either because of loneliness or actual isolation.
Historically, the peak of loneliness has coincided with major social changes. Sociologist Eric Kleinenberg notes that loneliness often became a major concern during times of cultural change, such as the advent of radio in the early 1900s, the rise of car culture, and the social upheavals of the 1960s and 1970s. According to Kleinenberg, loneliness is often used to explain the discomfort that people feel when cultural change happens too quickly and people cannot adapt.
The epidemic of loneliness today is very deep; Because it is happening on an unprecedented scale, driven by drastic changes in social life, including political dysfunction, mental health crises, and the transformation of communication through the Internet. Many people express longing for the past when social connections seem stronger, but this nostalgia may not provide a realistic solution to the current crisis. Instead, efforts such as encouraging face-to-face activities and fostering traditional forms of community may help, but perhaps not completely solve the problem.
Perhaps the solution to loneliness is new ways of interacting
History shows that social change often leads to new forms of society rather than a return to old forms. For example, during the Industrial Revolution, people adapted to building new urban societies instead of retreating to rural life. Similarly, the way out of today’s loneliness may involve embracing new forms of communication, such as those enabled by smartphones and the Internet, that can create meaningful relationships despite physical distance.
The evolution of social interactions today, with online platforms allowing people to communicate in ways that were previously impossible. Such an opportunity may be part of a broader adaptation process. In other words, the current period of loneliness can be a transitional phase in which society adapts to new realities and finds new ways to connect and support each other.
Finally, the crisis of loneliness may represent an evolutionary step toward new forms of togetherness; Where, despite physical separation, people find ways to reconnect and create meaningful relationships in the modern world.
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