Chapter 4
Magnetobiology
Magnetobiology is an approach in radiobiology of non-ionizing radiation; the line of investigation in biophysics that studies biological effects of mainly weak static and low-frequency magnetic fields, which do not cause heating of tissues. Magnetobiology corresponds to somewhat more general term bioelectromagnetics, which should not be mixed up with the term bioelectromagnetism.
Magnetobiological effects have unique features that obviously distinguish them from thermal effects: often they are observed for alternating magnetic fields just in separate frequency and amplitude intervals. Also, they are dependent of simultaneously present static magnetic or electric fields and their polarization.
4.1 Magnetic Resonance Imaging MRI
Magnetic resonance imaging (MRI), or nuclear magnetic resonance imaging (NMRI), is primarily a medical imaging technique most commonly used in radiology to visualize the structure and function of the body (see Figure 4.1). It provides detailed images of the body in any plane. MRI provides much greater contrast between the different soft tissues of the body than computed tomography (CT) does, making it especially useful in neurological (brain), musculoskeletal, cardiovascular, and oncological (cancer) imaging. Unlike CT, it uses no ionizing radiation. MRI is a relatively new technology, which has been in use for little more than 30 years (compared with over 110 years for X-ray radiography). The first MR Image was published in 1973 and the first study performed on a human took place on July 3, 1977.
Magnetic resonance imaging was developed from knowledge gained in the study of nuclear magnetic resonance. In its early years the technique was referred to as nuclear magnetic resonance imaging (NMRI). However, as the word nuclear was associated in the public mind with ionizing radiation exposure it is generally now referred to simply as MRI.
Figure 4.1 MRI Device
Scientists still use the term NMRI when discussing non-medical devices operating on the same principles. The term Magnetic Resonance Tomography (MRT) is also sometimes used. One of the contributors to modern MRI, Paul Lauterbur, originally named the technique zeugmatography, a Greek term meaning "that which is used for joining".[1] The term referred to the interaction between the static, radiofrequency, and gradient magnetic fields necessary to create an image, but this term was not adopted.
4.1.1 The Physics of Magnetic Resonance Imaging MRI
The body is mainly composed of water molecules which each contain two hydrogennuclei or protons. When a person goes inside the powerful magnetic field of the scanner these protons align with the direction of the field.A second radiofrequency electromagnetic field is then briefly turned on causing the protons to absorb some of its energy. When this field is turned off the protons release this energy at a radiofrequency which can be detected by the scanner. The position of protons in the body can be determined by applying additional magnetic fields during the scan which allows an image of the body to be built up.These are created by turning gradients coils on and off which creates the knocking sounds heard during an MR scan.Diseased tissue, such as tumors, can be detected because the protons in different tissues return to their equilibrium state at different rates. By changing the parameters on the scanner this effect is used to create contrast between different types of body tissue (see Figure 4.2 for the MR image of Knee).
Figure 4.2MR image of the knee
Contrast agents may be injected intravenously to enhance the appearance of blood vessels, tumors or inflammation. Contrast agents may also be directly injected into a joint, in the case of arthrograms, MR images of joints. Unlike CT scanning MRI uses no ionizing radiation and is generally a very safe procedure. Patients with some metal implants, cochlear implants, and cardiac pacemakers are prevented from having an MRI scan due to effects of the strong magnetic field and powerful radiofrequency pulses.MRI is used to image every part of the body, and is particularly useful in neurological conditions, disorders of the muscles and joints, for evaluating tumors and showing abnormalities in the heart and blood vessels.
4.1.2 The Advantages and Disadvantages of MRI
An MRI scan is a painless radiology technique that has the advantage of avoiding x-ray radiation exposure. There are no known side effects of an MRI scan. The benefits of an MRI scan relate to its precise accuracy in detecting structural abnormalities of the body. Patients who have any metallic materials within the body must notify their physician prior to the examination or inform the MRI staff. Metallic chips, materials, surgical clips, or foreign material (artificial joints, metallic bone plates, or prosthetic devices, etc.) can significantly distort the images obtained by the MRI scanner. Patients who have heart pacemakers, metal implants, or metal chips or clips in or around the eyeballs cannot be scanned with an MRI because of the risk that the magnet may move the metal in these areas. Similarly, patients with artificial heart valves, metallic ear implants, bullet fragments, and chemotherapy or insulin pumps should not have MRI scanning.
During the MRI scan, patient lies in a closed area inside the magnetic tube. Some patients can experience a claustrophobic sensation during the procedure. Therefore, patients with any history of claustrophobia should relate this to the practitioner who is requesting the test, as well as the radiology staff. A mild sedative can be given prior to the MRI scan to help alleviate this feeling. It is customary that the MRI staff will be nearby during MRI scan. Furthermore, there is usually a means of communication with the staff (such as a buzzer held by the patient) which can be used for contact if the patient cannot tolerate the scan.
4.1.3 MRI versus CT
A computed tomography (CT) scanner uses X-rays, a type of ionizing radiation, to acquire its images, making it a good tool for examining tissue composed of elements of a higher atomic number than the tissue surrounding them, such as bone and calcifications (calcium based) within the body (carbon based flesh), or of structures (vessels, bowel). MRI, on the other hand, uses non-ionizing radio frequency (RF) signals to acquire its images and is best suited for non-calcified tissue, though MR images can also be acquired from bones and teeth as well as fossils. Contrast agents for MRI are those which have paramagnetic properties, e.g. gadolinium and manganese.Both CT and MRI scanners can generate multiple two-dimensional cross-sections (slices) of tissue and three-dimensional reconstructions. Unlike CT, which uses only X-ray attenuation to generate image contrast, MRI has a long list of properties that may be used to generate image contrast. By variation of scanning parameters, tissue contrast can be altered and enhanced in various ways to detect different features. MRI can generate cross-sectional images in any plane (including oblique planes). In the past, CT was limited to acquiring images in the axial (or near axial) plane. The scans used to be called Computed Axial Tomography scans (CAT scans). However, the development of multi-detector CT scanners with near-isotropic resolution, allows the CT scanner to produce data that can be retrospectively reconstructed in any plane with minimal loss of image quality.For purposes of tumor detection and identification in the brain, MRI is generally superior. However, in the case of solid tumors of the abdomen and chest, CT is often preferred due to less motion artifact. Furthermore, CT usually is more widely available, faster, much less expensive, and may be less likely to require the person to be sedated or anesthetized.MRI is also best suited for cases when a patient is to undergo the exam several times successively in the short term, because, unlike CT, it does not expose the patient to the hazards of ionizing radiation.
4.2 Nanotechnology
4.2.1 What is Nano?
Nano is a measurement not an object. A nanometer (nm) equal 1/1000000000 of a meter. The youngest and healthiest eyes can't see things much smaller that millimeter in size and a nonometer is a million times smaller than that. Even most microscopes can't see things on the nano-scale. It takes ten atoms of hydrogen lined up side by side to equal one nanometer.
4.2.2 Why Nano?
The discovery of novel materials, processes, and phenomena at the nanoscale, as well as the development of new experimental and theoretical techniques for research provide fresh opportunities for the development of innovative nanosystems and nanostructured materials. Nanosystems are expected to find various unique applications. Nanostructured materials can be made with unique nanostructures and properties. This field is expected to open new venues in science and technology.
4.2.1 What is Nanotechnology?
In its simplest form, nanotechnology concerns itself with the intentional production or manipulation of objects that measure between one and one hundred nanometers in at least one dimension. A nanometer is one billionth of a meter. A human hair is about ten thousand nanometers wide. Broadly speaking, nanotechnology deals with things that are larger than atoms and smaller than cells. The word nanotechnology covers hard metallic and ceramic particles; soft, polymeric molecules; nanoscale features etched into electronic and mechanical substrates; even bulk materials with nanoscale voids, called nanoporous materials.As a practice, nanotechnology has been around for hundreds of years. Medieval glassmakers used gold nanoparticles to make the ruby red color in stained glass. As a science, it is barely fifty years old. In 1959, Professor Richard Feynman delivered a lecture called “There’s Plenty of Room at the Bottom”, in which he predicted the advent of advanced microscopes and other instruments that would allow the precise positioning of atoms and molecules to enable molecular, or “bottom up” manufacturing. Thirty years later, in 1989, an IBM scientist named Don Eigler spelled out his employer’s initials by using a scanning tunneling microscope to position thirty five-xenon atoms on a nickel substrate. Nanotechnology is the manifestation of Dr. Feynman’s dream come true. Simultaneous with the development of advanced microscopes and other detection devices, over the past several decades advancements in computer technology have facilitated increasingly precise process sensing and controls instrumentation, which in turn, has facilitated the production of materials at particle sizes and molecular configurations that only rarely occur in nature.
Because nanomaterials exist at the boundary of the bulk regime, which is governed by the laws of classical mechanics, and the atomic regime, which is governed by theories of quantum physics, nanomaterials tend to behave differently than their everyday bulk counterparts. Most significant among these differences are those associated with increased surface area resultant of smaller particle size. Because chemical reactions take place on surfaces, as opposed to within the internal mass of an object, nano-particles have more external surface area on which chemical reactions may take place. Although research is ongoing, we know that some nanoscale materials exhibit different physical, chemical, reactive, morphological, optical, conductive, thermal and catalytic characteristics than they do at bulk scale. These differences affect many of the physical and chemical characteristics of various elements in different ways. For instance, gold nano-particles melt at a lower temperature than their bulk scale counterparts. Carbon nano-tubes are made of the same atoms as pencil lead, but due to their nano-structure, are stronger than steel.
4.3 Magnetic Nanoparticles for Biological and medical Applications
In recent years an increasing interest in using magnetic nanoparticles for biological and medical applications developed. The size ofthe particles can range from a few nanometers to severalmicrometers and thus is compatible with biological entities ranging fromproteins (a few nm) to cells and bacteria (several μm). Generally themagnetic particles are coated with a suitable ligand,which allows chemically binding of the particles todifferent biological systems. This combination ofbiology and magnetism is useful, because the biochemistryenables a selective binding of theparticles, while the magnetism enables easy manipulationand detection. Using magnetic fieldgradients the magnetic particles can be subjected tosignificant forces even when they are embedded ina biological environment. Conversely, the absenceof ferromagnetism in most biological systems,which typically have only weak dia- or paramagnetism,means that the magnetic moment from theferromagnetic particles can be detected with littlenoise in a biological environment.Based on these ideas a variety of different applicationsemerged. A straightforward application isto bind magnetic particles to the biological systemof interest, which then allows manipulatingthe biological material via magnetic fieldgradients.
4.3.1 Fighting cancer using magnetic nanoparticles
The center piece of the MagForce nano cancer therapy is the nanoparticle consisting of iron oxide. The particle is covered by a paint coating which insure the good stability and division of iron oxide particles in the tumor tissues. It additionaly support the process by which the particles are absorbed into the cancer cells. The small size of the particles is decided for theraby the diameter measure some 20nm and this is 500 times smaller than red blood cell. One milliliter of particle solution contains nearly 17 trillion single nanoparticles. This high density made efficient treatment possible. At the beginning of the therapy nanoparticles are injected directed to the tumor. The tumor in this particular case is glioblastoma a malignant brain tumor characterized by aggressive growing cells. After being injected the nanoparticles are spread out in the spaces between the tumor cells. The patient now entering the therapy device in whichis alternating magnetic field is produced which has no dangerous to humans. This field effect is 1000 times alternation of the magnetic poles within the particles per second creating north which is precise regulated from outside.The warm forces the particles into spaces between tumor cells which make it easy for them to be absorb into the cells. The application is repeated and the thermal effect increases visibly. The particles begin to oscillate causing the cancer cells to die either from active self destruction or from swelling until they little burst. Tumor growth stopped and the destroyed cells as well as the nanoparticles are discharged by the body in a natural process. As a rule the one hour minimum invasive treatment is repeated six times however the particles only injected once, thus making the therapy is specially gentile on the patient.
4.3.2 New Approach to Biomagnetic Sensors
The ability to tag biological molecules with functionalized magneticparticles has been already exploited for biological sensors. Traditionallymany biological sensors, like a DNA-microarray, use fluorescentmarkers for the detection of specific biological molecules. For examplethe DNA under investigation can be bound to a fluorescent molecule.Then the DNA is exposed to an array with many different well-definedDNA-strands and it will only stick to complementary matching DNA.The position of the light signal from the fluorescent marker thenindicates which are the right complementary DNA strands. Similarly ithas been demonstrated that magnetic particles can be used as tags andthe binding can thus be identified by detecting the stray magnetic fieldof the particles . Key advantages of using magnetic particles vs.fluorescent molecules are that (i) magnetic particles typically have anunlimited shelf-life (unlike fluorescent marker, which deteriorate withtime) and (ii) the use of magnetic particles together with magnetoelectronicsensors (i.e., based on giant magnetoresistance) allow for acomplete electronic readout of the sensors. At the same time thesensitivity of the sensors based on magnetic vs. fluorescent tagging arealready comparable. Additionally the magnetic tags allow for manipulationof the target molecules such that they canbe moved towards the magnetic field sensorusing magnetic field gradients.
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