Ionization

IONIZATION 1.	Who discovered and what is ionization? In 1895, Whelm Conrad Roentgen discovered ionizing electromagnetic radiation and its potential for medical diagnosis. Ionizing radiation consists of subatomic particles or electromagnetic waves energetic enough to detach electrons from ions, atoms or molecules, thus ionizing them. The degree and nature of such ionization depends on the energy of the individual particles or waves, and not on their number. An intense flood of particles or waves will not cause ionization if these particles or waves don´t have enough energy to be ionizing (as explained by Einstein based on Max Planck’s theory).

Examples of ionizing particles are energetic alpha particles, beta particles and neutrons. One knows that if an electromagnetic wave - a photon - has high frequency it means that it has short-wavelength. Radiations as ultraviolet, x-rays, and gamma-rays, are ionizing. In Contrary, lower-energy radiation such as visible light, microwaves, and radio waves are not.

As the human senses cannot detect this radiation, instruments such as Geiger counters help to discover the presence of such radiation.

2.	Types of ionization

2.1	We can itemise two types of ionization:

2.1.1	Sequential (Classic Ionization) – Description of the ionization of an atom or molecule:

2.1.1.1	Positive Ionization – It happens with the release of an electron and the photon’s energy is higher or equal to the removing energy (if equal, the electron stays in the same place but in a “free state”; if energy it’s higher, the electron is released with some kinetic energy).

2.1.1.2	 Negative Ionization – it happens when the electron loses some energy. The type of energy lost depends on the levels before and after the ionization.

2.1.2	Non-Sequential (violates several laws of classical physics) – when it’s combined an electric field of light with tunnel ionization.

2.2	We can distinguish two sources of ionization:

2.2.1	Natural sources (86%): 	Gamma rays of earth 	Cosmic rays 	Decay of Uranium in the Earth

2.2.2	Artificial sources: 	X-ray machines 	Discharge of radioactive waste from nuclear industries 	Chernobyl accident 	Nuclear weapons tests

3.	Biological Effects Ionizing radiation has a biological damaging effect on all living organisms. Several factors influence this effect, such as the amount of absorbed energy [the amount of energy in one kilogram of an absorbing environment, dimension is J.Kg ^-1 and the unit is Gray (Gy)], the type of radiation and the composition of the irradiated object such as an organ or tissue. We can distinguish the attenuation coefficient of a tissue, which is a physical quantity that indicates how much that the tissue is capable of absorbing x-ray radiation.

A dose of ionizing radiation that can cause death in an organism is known as lethal dose. There are three levels of the lethal doses: 	Minimum lethal dose (LDmin) – it may cause death in a single organism in an exposed group; 	Median lethal (LD50/Time) dose – it may cause the killing of not less than half of the exposed group; 	Absolute lethal dose (100/Time) – it determines the death of all individuals within a period of time.

Radiation Exposure length may be identified as follows;

First of all, we have to understand that each tissue has a different value of radiosensitivity. 	High sensitivity: bone marrow stem cells, spermatogonia, granulosa cells surrounding the ovum 	Medium sensitivity: liver, thyroid, connective tissue, vascular endothelium 	Low sensitivity: nerve cells, sense organs

a)	Acute radiation exposure (Determinist effects) – it is manifested as a single, extremely high exposure of ionizing radiation (0,1Gy). In general, the severity of this effect corresponds to the amount of dose received. Normally, deterministic effects have a threshold level. Below this level, radiation exposure does not have any effect. Above the threshold level however, the severity of the effect will strengthened as the dose increases.

Ionizing radiation causes injury in the living tissue by transferring energy to atoms and molecules of the cells and (i) damaging DNA, RNA and proteins, (ii) breaking and producing chemical bonds, and (iii) creating free radicals.

Prompt effects are seen immediately after the exposition to a large dose of radiation in a short period of time (burns).

Delayed Effects are seen months or years after continuous radiation exposure (skin cancer).

E.g.: Radiation Sickness - is associated with acute radiation exposure and is accompanied by a characteristic set of symptoms like vomiting, diarrhoea, fatigue, headache, inflaming of mouth and throat, hair loss, burning, and permanent skin darkening, and bleeding spots under the skin. Both the type and magnitude of radiation influence the severity of the symptoms, in addition to the time of exposure and which body part being exposed (Hiroshima and Nagasaki in Japan during the 2nd World War and after the nuclear reactor accident).

b)	Chronic radiation exposure (Stochastic effects) – small radiation exposures that is spread over a long period of time causing stochastic effects, as it happens, per example with cosmic radiation. This type of exposure may increase the risk of premature aging, cancer and mutations. E.g.: Radiation Dermatitis - X-rays can, along with radiotherapy, cause radiation dermatitis. It is an inflammation of the skin associated with extended radiation exposure. When affected with radiation dermatitis, the skin may appear red, itchy, peeling and sometimes blistered. The majority of patients undergoing radiotherapy experience various degrees of radio dermatitis. Several factors influence the severity of radio dermatitis, including the total dose of radiation, the type and energy of beam, the area of skin exposed to the radiation and the overall treatment time. In addition, factors such as a patient’s age, physique, coexisting diseases like diabetes, and genetic syndromes may also affect the radio sensitivity.

4.	Applications of ionizing radiation in medicine Ionizing radiation has two very different uses in medicine ― for diagnosis and therapy. Both benefit patients and, as with any use of radiation, the benefit must outweigh the risk. Ionizing radiation revolutionised the ability to carry out an examination of the inner body by non-surgical means. It’s now possible to study the brain or the heart without need to open the body. Images are recorded in voxels (volumetric picture element), which have both area and depth (3D), as opposed to computer pixels which represented only a two dimensional area (2D). 5.	Diagnostic application of Ionizing Radiation

•	Radiology In radiology, x-rays, ultrasound (etc.) are used and given to the body of the patient externally. They are produced and interact with tissues in the patient’s body either through absorption or scattering. This procedure is one of the most important, as it is widely available. Its low in cost leads to its use as the first tool in the diagnosis of several diseases. However, the interaction between the human tissue and ionizing radiation might bring some dangerous problems like the deposit of some radiation in the patient which can be destructive to all living tissues and it can damage de DNA, causing mutations.

•	 Radiography Ionizing radiation was used, in the first place, as an imaging technique through the use of x-rays, between a range of 0,01 to 10 nm. X-rays can be used to reveal the internal structure of the body on film by highlighting these differences using attenuation, or the absorption of X-ray photons by the denser substances (like calcium-rich bones). X-rays are generated in an x-ray tube. These rays pass through the patient and are filtered by a device called x-ray filter (aluminium). After the x-rays pass through the patient a capture device convert them to visible light forming an image in impregnated silver-films. Radiographs work on the principle that bone absorbs the x-rays by photoelectric processes, soft tissue does not. In the bones, radiography allows us to see fractures, tumours, demineralization, like osteoporosis; in dentistry, caries. The x-rays helped to the appearance of computer tomography.

•	Computed Tomography (CT) – X-Rays This technique gives us the attenuation coefficient. The imaging device splits the patient into a 3D set of Voxels. Each 2D plane of voxels (coronal, sagittal or transverse) is called a tomogram. Computed Axial Tomography are used to combine x-rays beams from different angles producing the tomogram, enabling the achievement of detailed images of soft tissues. Like in radiography, x-rays are produced in an x-ray tube. These rays are directed by a collimator and sent through a patient. Some of them are absorbed, attenuated, and the others pass through a detector on the other side. A software measure the attenuation, forming an image based on the differences of the values of the x-ray absorbance, between the tissues. The device is constituted by a slip ring arrangement which rotates 360º around the person, like a helical or spiral scan.

•	Fluoroscopy Fluoroscopy is an imaging technique that uses X-rays to obtain real-time moving images of the internal structures of a patient through the use of a fluoroscope. In its simplest form, a fluoroscope consists of an X-ray source and fluorescent screen between which a patient is placed. Fluoroscope is the device used in interventional surgeries, in which medical images are needed to guide the placement or positioning of medical devices, such biopsy needles, drainage catheters, angioplasty balloon catheters, stents... As many images need to be taken, we have to protect the patient against the radiation, so they are used low intensity x-rays beams. The doctor must avoid direct self-exposure to x-ray, as such the interventionist must carry protective coats and eyewear because of scattered radiation from the patient. Before the doctor switch on the device, he must take a step back.

•	Magnetic Resonance Imaging (MRI) MRI is a “medical imaging technique used in radiology to visualize internal structures of the body in detail” It´s the technique that measures the hydrogen concentration. Proton nuclear magnetic resonance detects the presence of hydrogen protons by subjecting them to a large magnetic field polarizing nuclear spins, exciting them with tuned radio frequency. After detecting weak radio frequency radiation from the protons is the time when they relax from the magnetic interaction. As the proton signal frequency is proportional to that magnetic field, a given proton signal frequency can be assigned to a location in the tissue. This provides the information to map the tissue in terms of the protons presence there. Since the proton density varies with the type of tissue, a certain amount of contrast is achieved to image the organs and other tissues variations in the subject tissue. Many of those protons are in the water. Bones of the skull don’t have many protons, so they are shown up dark, as well as, the sinus cavities.

•	Nuclear Medicine Nuclear medicine is the medical and laboratory speciality that takes up the nuclear properties of radioactive and stable nuclides to evaluate metabolic, physiologic and pathologic conditions of the body. It relies on the radiopharmaceuticals which are categorized by pharmaceuticals marked with a radioactive agent so that they may be traced. So, in nuclear medicine, radiology acts internally.

In this type of imaging, doctors inject small amounts of radiopharmaceuticals into patients or have patients to inhale or ingest those. These radionuclides plus pharmaceutical compounds are posteriorly distributed through the body (specific organs or cellular receptors). As the half-life of the radionuclide decreases, the fraction of the total decay occurs, leading to the emission of gamma rays and, consequently, to the image acquisition.

However, the images produced by this technique have lower resolution comparing to the ones produced by radiography. But, in the end, this is not a big problem as doctors in this kind of diagnosis pay more attention to detection and measurement of the abnormal organ rather that to an altered organ structure.

•	Positron Emission Tomography (PET)

This is a technique where is usually used glucose, because it easily crosses highly selectively blood barriers. This biologically and active molecule (containing radio nuclides) is injected in the patient body. The patient has to wait about 30 – 45 minutes. During this time the concentration of these nuclides will increase in the tissues of interest. The radioisotopes decay and emit positrons (e+). The emitted positron travels in the tissue for a short distance loosing kinetic energy to a point where it can interact with an electron producing gama-photon (moving in opposite directions). These are detected when photons reach the scanning device (gamma camera) (photons that are not arriving in pairs are ignored).

•	Single Photon Emission Computed Tomography (SPECT) SPECT is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.

The main difference comparing to the PET is that it only requires one single radiation, not a simultaneous double one (like in PET). This causes poorer image sensitivity as well as cheaper prices, because radioactive materials used have longer lifetime.

•	Therapeutic Applications Ionizing radiation can be classified in 2 categories: it can be external – used externally to a patient – or it can be internal – used internally to a patient. (a)	External Sources (or Teletherapy) The intention of this treatment is to destroy tumour cells with radiation. Curative treatment is possible only for tumours that are not metastasised. Radiation alleviates pain from metastases to bone, controls bleeding, as well as, obstruction caused by tumour and growth and neurological symptoms due to brain or spindle metastases. Teletherapy options include gamma rays (from radioative cobalto) and photons or electrons.

There are several types of therapeutic applications using external sources:

i)	Stereotactic radiation It uses focused radiation beams targeting a well-defined tumour using extremely detailed imaging scans. There are two types of stereotactic radiation: Stereotactic radiosurgery (SRS) – used in the brain or spine; and Stereotactic body radiation therapy (SBRT) – used in the body, such as the lungs. Advantage: this treatment delivers the right amount of radiation to the cancer in a shorter amount of time than common treatments. Plus, these treatments are given with extreme accuracy, which limits the effect of the radiation on healthy tissues. Disadvantage: they are only suitable for certain small tumours.

ii)	Conventional external beam radiation It is delivered via 2D beams using linear accelerator machines (2DXRT), which consists of a single beam of radiation delivered to the patient from several directions. Conventional refers to the way this treatment is planned or simulated on a special calibrated diagnostic x-ray machine. The aim of simulation is to target and measure the tumour which is to be treated. Disadvantage: some high dose treatments may be limited by the radiation toxicity capacity of healthy tissues which lay close to the tumour.

iii)	Particle therapy It uses beams of energetic protons, neutrons or positive ions, directly in the tumour. The dose increases while the particle penetrates the tissue, up to a maximum, and then drops to almost zero. Advantage: less energy is deposited into the healthy tissue surrounding the target tissue.

(b)	 Internal Sources (Brachytherapy) It is delivered by placing radiation sources inside or next to the area requiring treatment. This means that the irradiation only affects a very localised area, which provide advantages over external beam radiation therapy. The tumour can be treated with very high doses of localized radiation reducing the probability of an unnecessary damage to surrounding tissues. A course of this therapy can often be completed in less time than other radiation therapy techniques. This can help reduce the chance of surviving cancer cells dividing and growing in the intervals between each dose.

(c)	Radioisotope therapy (RIT) It’s a form of targeted therapy due to the chemical properties of the isotope such as radioiodine which is specifically absorbed by the thyroid gland. Targeting is possible by attaching the radioisotope to another molecule or antibody to guide it to the target tissue. The radioisotopes are given through infusion or ingestion.

Done by: Ana Catarina Palhau & Maria Francisca Batista