Medical equipment based on ionizing radiation principle

X-ray computed tomography, also computed tomography (CT scan) or computed axial tomography (CAT scan), is a medical imaging procedure that utilizes computer-processed X-rays to produce tomographic images or 'slices' of specific areas of the body. These cross-sectional images are used for diagnostic and therapeutic purposes in various medical disciplines.^[1] Digital geometry processing is used to generate a three-dimensional image of the inside of an object from a large series of two-dimensional X-ray images taken around a single axis of rotation.

 

A patient is receiving a CT scan for cancer. Outside of the scanning room is an imaging computer that reveals a 2D image of the body's interior.

Schematic representation of CT scanner.

CT produces a volume of data that can be manipulated, through a process known as "windowing", in order to demonstrate various bodily structures based on their ability to block the X-ray beam. Although historically the images generated were in the axial or transverse plane, perpendicular to the long axis of the body, modern scanners allow this volume of data to be reformatted in various planes or even as volumetric (3D) representations of structures. Although most common in medicine, CT is also used in other fields, such as nondestructive materials testing. Another example is archaeological uses such as imaging the contents of sarcophagi.

Usage of CT has increased dramatically over the last two decades in many countries.^[4] An estimated 72 million scans were performed in the United States in 2007.^[5] One study estimated that as many as 0.4% of current cancers in the United States are due to CTs performed in the past and that this may increase to as high as 1.5-2% with 2007 rates of CT usage;^[6] however, this estimate is disputed.^[7] Kidney problems following intravenous contrast agents may also be a concern in some types of studies.

 

General Characteristics of Natural Radioactivity

·              It is a nuclear phenomenon.

·              It is due to the instability of the nucleus.

·              It is a spontaneous, continuous and irreversible process.

·              It is independent of external factors such as pressure, temperature, state of substance, electrical field, magnetic field, catalyst etc.

·              A radioactive element emits α β and γ radiations.

·              Due to the emission of an α particle, atomic number decreases by 2 units and mass number decreases by 4 units.

·              Due to the emission of β particle, atomic number increases by 1 unit but the mass number remains the same.

·              A radioactive element does not emit α and β particles simultaneously.

·              The original radioactive nucleus or element is called a parent element and the new element formed is known as daughter element.

·              The physical and chemical properties of daughter element are different than that of the parent element.

Characteristics of Alpha Rays (i.e., a - particles)

·              Alpha rays consist of stream of positively charged particles carrying charge of +2 units and a mass of four units on the atomic weight scale (i.e., 4 amu). They consist of 2 protons and 2 neutrons. In other words, these particles are helium nuclei and therefore indicated as ₂He⁴.

·              They affect photographic plate

·              They are deflected only slightly towards the negative plate in electric field. They are also deflected by magnetic field.

·              These particles can ionize gases. Alpha rays have maximum ionizing power.

·              They have a velocity of the order of 1 x 10⁷ m s^-1.

·              They have very little penetrating power.

·              By emission of an - particle, atomic number of nucleus decreases by 2 units and mass number by 4 units.

Characteristics of Beta Rays (i.e., b - Particles)

·              Beta rays are made up of streams of negatively charged particles similar to electrons. Thus, - particle has a unit negative charge and a negligible mass. They are electrons. Hence, - particle is represented as _-1e⁰.

·              They affect photographic plate.

·              They get deflected to the maximum extent towards the positive plate in electric field. They are also deflected by magnetic field.

·              Their ionising power is less than that of - rays. (It is about one hundredth of - particles).

·              Their velocity varies with the source and is almost equal to the velocity of light, about 2.7 x 10⁸ m/s.

·              Their penetration power is about 100 times more than that of - particles.

·              By emission of a b - particle, atomic number of nucleus increases by one whereas mass number remains same. (this is because, the ejection of a b - particle results from the transformation of a neutron into a proton and an electron ).

Characteristics of Gamma (g) Rays

·              They are electromagnetic radiations like X-rays having very short wavelength, in the range of 10^-10 m to 10^-13 m.

·              They affect photographic plate.

·              They are unaffected by electric and magnetic fields.

·              Their ionizing power is low, (about one hundredth of  b - particles).

·              Their velocity is same as that of light.

·              Their penetrating power is very high, about 100 times more than that of  b - particles. Hence, they are also known as hard rays.

·              When a and b particles are emitted by an atom, there is always a rearrangement in the nucleus and during this process some energy is given out in the form of  g - rays. Thus, emission of gamma rays accompanies virtually all nuclear reactions. There is no change in the mass number or atomic number of the nucleus as g - rays have negligible mass.

Comparison between α, β particles and γ rays

 

Sl.No	Alpha	Beta	Gamma
1.	α - particle is the helium nucleus (2He4)	β - particle is an electron (-1e°).	γ - particle is an electromagnetic radiation
2.	It is +vely charged.	It is -vely charged.	It has no charge.
3.	The mass of each α - particle is 4 amu about 1/1836 amu	The mass of each β - particle is negligible.	It has no mass.
4.	Its velocity is less 107 cm/s.	Its velocity is less than the velocity of light and is equal to 2.7 x 108 m/s	Its velocity is the same as that of light and is equal to 3x108 m/s,
5.	Its has maximum ionization power. It is about 100 times more than that of β - particles	Its ionization power is about 100 times more than that of γ -rays.	The ionization power is the least
6.	Penetrating power is the least.	Penetrating power is less but 100 times more than penetrating power of α - particles	Penetrating power is maximum i.e., 100 times more than that of β - particles.

 

Uses of Radioactive Isotopes

All isotopes of a substance have the same chemical properties and behave in an identical manner. The advantage of a radioisotope is that its position can be detected very easily by the radiation which it emits. It has wide applications in various fields like:

In Medicine

Radio isotopes are used in detection of diseases and also in radio therapy:

·              The rays from radium is used in the treatment of skin diseases.

·              Radiation from Co⁶⁰ ( - rays) is used to diagnose and treat thyroid disorders.

·              Radio iodine (I¹³¹) is used to diagnose and treat thyroid disorders.

·              Radio phosphorus (P³²) is used in the treatment of leukaemia and tumours.

·              Radio sodium (Na²⁴) in the form NaCl is used to study circulation of blood.

In Agriculture

·              Radioactive phosphorus (P³²) is used in the study of metabolism of plants.

·              Radioactive sulphur (S³⁵) helps to study advantages and disadvantages of

fungicides.

·              Pests and insects on crops can be killed by - radiations.,

·              - rays are used for preservation of milk, potatoes etc.

·              Yield of crops like carrot, root, apples, grapes can be increased by irradiation with radioisotopes.

In Industry

·              In is used in the manufacture of paper, plastic and metal sheets. (Used to control the thickness of  the sheets.)

·              Radioisotopes can be used to estimate the amount of wear in bearings.

·              Leaks in pipes may be traced by introducing a small quantity of radioisotopes into the fluid in the pipe.

·              It is also used to detect the cracks in the welding, casting etc.

The sun is the most enormous and direct, source of energy. Where does this enormous energy that the sun radiates come from? The source of this energy was not known to mankind until the year 1939. It was a German physicist, Hans Bethe, who proposed that the sun contains hydrogen nuclei in its core, moving at large speeds. Whenever these nuclei fuse to form a nucleus of a heavier element, a large amount of energy is liberated. Such a reaction is known a nuclear fusion reaction.

Fusion Reaction between Isotopes of Hydrogen

Nuclear fusion is a reaction in which two or more light nuclei combine to form a heavy nucleus with the liberation of large amount of energy.

Example:

Note : One gram of hydrogen releases 6.2 x 10¹⁰ J of energy where as one gram of coal produces 33 KJ of energy.

Nuclear fusion takes place at a very high temperature which is equal to 4 x 10^{6 o}C. Fusion is the combination of two like light nuclei and the nuclei must have sufficiently high kinetic energy to overcome the force of repulsion between the like nuclei. Therefore, for fusion reactions to occur, the two hydrogen nuclei have to collide at very high speeds, which is possible only at a very high temperature, equal to 4 x 10^{6 o}C. Hence a fusion reaction is also known as thermonuclear reaction.

Fusion releases more energy than fission because the mass lost during fusion is more than that lost during fission.

One of the practical application of nuclear fusion is hydrogen bomb.

Hydrogen Bomb

The basic principle involved in the preparation of hydrogen bomb is nuclear fusion. A nuclear fission reaction initiates the fusion reaction. In a hydrogen bomb the set up for fission reaction is surrounded by a mixture of deuterium (²₁H) and lithium. The nuclear fission reaction liberates heat energy and neutrons. The heat energy released creates a temperature equal to 4 x 10^{6 o}C and the neutrons are used for converting ⁶₃Li to tritium. The reactions taking place in a hydrogen bomb is as follows:

Differences Between Nuclear Fission and Nuclear Fusion

Nuclear fission	Nuclear Fusion
Splitting of a heavy nucleus into two or more light nuclei	Combination of two light nuclei to form a heavy nucleus
Takes place at room temperature	Requires a very high temperature equal to 4 X 106 ºC
Comparatively less amount of energy is released	Enormous amount of energy is released
Fission reaction can be controlled and the energy released can be used to generate electricity	Fusion reaction cannot be controlled and hence the energy released cannot be used to generate electricity
It is a chain reaction	It is not a chain reaction
It leaves behind radioactive wastes	It does not leave behind any radio active wastes

 

Discovery of Radioactivity

The discovery of the phenomenon of radioactivity was purely accidental. In 1896, Henry Becquerel, a French scientist accidentally found that in presence of salt of uranium, photographic plates got heavily fogged even though they were wrapped in opaque paper. He concluded that the uranium salt must be giving off penetrating radiations similar to X-rays discovered one year earlier. Two years later, Madam Curie named the phenomenon radioactivity.

Radioactivity is the spontaneous random emission of particles from within the nucleus of the atom. Spontaneous random emission means that the particles are emitted in bursts at irregular intervals with no set pattern and are emitted in any direction. The number emitted per second varies between very wide limits. This process is unique in that the particles are emitted without any energy having been given to the atom. Thus, energy is obtained without energy being introduced, and so the atom itself is a source of energy. The atom is not the same after the emission of the particles. It has changed into an atom of another substance which may be unstable (will undergo further disintegration) or stable (will not emit any more particles), it is not possible to control this change. Neither is it possible to reverse it. Changing the temperature, changes the rate at which a chemical reaction takes place. It does not change the rate at which a radioactive substance decays. Radioactive decay is independent of temperature, pressure or chemical combination.

As mentioned earlier, different radioactive emissions have different penetration powers. The more massive a particle the greater the chance that it collides with other particles and the less likelihood that it will travel far.

Radioactivity

The phenomenon of spontaneous disintegration of an unstable nucleus of naturally occurring isotope accompanied by emission of active radiations line a, b and g radiations is known as Natural Radioactivity.

These radiations come from the breakup of the central core or nuclei of heavier elements like thorium, uranium etc. Elements with atomic number above 83 have very heavy and unstable nuclei. Being unstable, these nuclei spontaneously break up to form stable elements with lower atomic numbers. In the process of this breakup, the three types of radiations are given out.

Experiments by Becquerel, Rutherford and Marie Sklodowska Curie and her husband Pierre Curie had shown that uranium, radium and certain other radioactive substances gave off three types of radiations. They performed many experiments to discover the properties of these radiations.

Experiment:

·               The radioactive material was kept in a small cavity in a block of lead.

·              The whole apparatus was enclosed in an evacuated vessel as shown here.

·              An electric field was applied.

·              It was observed that the beam is split up into three components.

·              The radiations, which emerged from the radioactive material, were made to strike a photographic plate. These radiations produced three different spots on the photographic plate.

Conclusions:

·              The rays that deflected towards the negative plate consist of positively charged particles and these were called alpha rays.

·              The rays, which deflected towards the positive plate, consist of negatively charged particles and these rays were known as the beta rays.

·              The rays, which did not deflect, do not contain any charged particles and described these rays as gamma rays.

Note:

·              Beta particles deviate more than alpha particles showing that beta particles are lighter than alpha particles or vice versa.

·              Gamma rays do not deviate as they are electromagnetic waves and hence have no charge.

 

Radioactive Decay or Disintegration

A radioactive nucleus or element emits an alpha or a beta particle and gets converted into a new nucleus or element.

The process of destruction of the original nucleus during the formation of new nucleus due to radioactivity is called Radioactive decay or disintegration.

When a α - particle is emitted by a nucleus, the mass of the nucleus decreased by 4 units and the charge by 2 units.

In general if a radioactive element X of mass number A and atomic number Z emits an alpha particle, a new element Y (called the daughter product) is formed with mass number (A - 4) and atomic number (Z - 2). Hence the element changes into a new element with properties similar to those of an element 2 places earlier in the periodic table. The change can be represented by the following equation.

For example:

Radium - 226 decays with the emitting an a - particle and forms an inert gas radon The transformation is given by

Both the mass (226 - 4 = 222) and the charge (88 - 2 = 86) must be conserved.

Radon is unstable and also decays with the emission of an α - particle:

Radium emits γ - rays as well as α - particle but the emission of γ- rays has no effect on the charge or on the mass of the nucleus. During the emission of α - particle or - particles the nucleus is rearranged with a decrease in energy; the surplus energy is given off in the form of γ - rays. Polonium - 218 is also an α - particle emitter.

So far only α- particle emission has been considered.

When a b- particle is emitted there is effectively no change in the mass of the nucleus because the mass of the b - particle is very small. However, the charge increased by one unit.

If an element emits -particle and the new element Q has mass number A and atomic number Z+1.

Thus the element changes into a new element with properties similar to those of an element one place later in the periodic table.

For example:

Lead-214 decays with the emission of a - particle.

The equation for charge is 82 - (-1) = 82 + 1 = 93. But the nucleus is supposed to be made up of protons and neutrons only, so how can a - particle be emitted? A neutron in the nucleus has changed into a proton by emitting an electron. This leaves one more proton and one less neutron in the nucleus. Thus the nucleon number does not change, but the proton number increased by one.

(When a - particle is emitted the number of protons increases by one hence the atom is +vely charged. It acquires the deficit electron from the atmosphere and becomes neutral)

 

 

The products of the disintegration of radium atoms.

Half-life

Radioactive decay is a random process and different radioactive substances decay at different rates. The time taken for the number of particles emitted per unit time to drop to half of its original value is known as the half-life of the substance. In this time half of the atoms of the original material will have given off radioactive particles and changed into another substance. This new substance may or may not be unstable.

 

Radiation: effects and detection

As we make use of nuclear power and other sources of radiation, the effects of radiation on the human body and on materials we use becomes important. A good deal can be learned about high-energy radiation by studying the more or less typical properties of a  particles, b particles, neutrons, and g rays. For example, the interaction of protons with atoms is closely akin to the behavior of a particles,and similarities exist within the other groups mentioned.

An a particle is relatively large (4 u) and carries a double charge (+2e). When such a particle is shot at atoms, we would expect it to collied rather frequently. In fact it is found that a particle ionize air very rapidly. As they travel though the air, they occasionally strike an atom and tear an electron loose from it. (the word “strike” is used rather inexactly here. Even if the positive a particle passes close to an atom, the electrical attraction between it and the negative electron can cause ionization.)

By using methods to be discusses later in this section, the path of charged particles through air can actually be seen. In fact, even the individual ions thay  produce can be counted. It is found that  even quite energetic a particles cannot travel far through       air before stopping. For example, the range of the 7.7-MeV a particles emitted from radium C is only about 7 cm in air. The range is, of course, much smaller in denser materials. In aluminum the same a particle would penetrate only about 0.004 cm. As we see,a particles are quite easily stopped.

We should point out that an a particle does not stop after one collision with an atom. Measurements show that about 35 eV of energy is lost for each atom ionized in air. Hence, a 7.7-MeV particle would create about 0.2 million ions before coming to rest. The number of ions created by the particle, or alternatively its range, can be used as a measure of the energy of the particle.

A proton has properties similar to the a particle. Since it is only one-fourth as large in mass and one-half as large in charge, the proton would be expected not ionize air as an a particle would. This turns out to be true. A proton will travel about 5 to 10 times as far through matter as an a particle of the same energy. From this it is apparent that protons are less then one-fifth as effective as a particle in ionizing atoms.

The b particle is considerably different from the two particles thus far discussed. It has only about 1/1830 as much mass as the proton. A bombarding b particle is capably of tearing an atomic electron loose, but in this case this is the result of a repulsive force. In spite of this difference between the overall ionization effect of a positive and a negative bombarding particle provided that the bombarding particles have the same mass.

A great difference between the action of b and a particles is apparent, however, because of their mass difference. An a particle striking an electron is much like a 10,000-kg truck striking a 2-kg toy truck. The a particle continues on almost as though it had hit nothing. On the other hand, an electron or b particle colliding with another electron in an atom  is like two equal-sized objects colliding. The b particle is deflected considerably when it undergoes a near-head-on collision. Depending upon how the particles collide, a large share of the b-particle energy may be lost in just one collision. However, head-on collisions are rather rare events, and so particle deflections are usually not too large. The b particle will undergo relatively few ionizing collisions, because its mass and charge are small.

The range of a b particle in air is considerably large then that of an a particle with the same energy. As a round order-of-magnitude estimate, a b particle will penetrate matter hundreds of times farther than an a particle of similar energy. Although a piece of paper will stop many a particle, it is not uncommon for a b particle to pass through absorbers much thicker than this. Compared with neutrons and g rays, though b particles are relatively easily stopped.

Neutrons have no charge and a mass very close to that of a proton. As a result, there is no ordinary electrostatic repulsion or attraction between these particles and the various portion of the atom. Consequently, a neutron will undergo collision only rarely. A direct hit on an electron or nucleus must occur before any disturbance to its travel is noticed. A b or a particle can ionize an atom by a near  miss, since the electrostatic forces between the charges act strongly upon the atom even though a true collision does not occur. This is impossible for a neutron, however. Hence, the neutron is a highly penetrating, very slightly ionizing particle.

Until now we have discussed the behavior of particles only g rays are quite different in character from any of these, since they are electromagnetic radiation, having neither charge nor rest mass. Nevertheless, we have already discussed instances where light and x-rays interact with matter, namely, in the photoelectric and Compton effects. Since,g rays, we would expect them to show similar characteristics. This is indeed true.

A g ray, being a photon, will ordinarily lose all its energy in one event, except in the case of Compton scattering. When a beam of g rays, or photons, passes through a gas, many of them are stopped when they strike atomic electrons and eject them from the atom. This is simply  the photoelectric Geiger counters.

Geiger counters are devices to detect and measure ionizing radiation, as emitted by radioactive sources. The heart of a geiger counter is the Geiger-Mueller-Tube (GM tube). This is a gas filled tube, to which a voltage of several 100V is applied. Normally, the gas insulates and no current is drawn. When a radiation particle or quantum passes the tube, it triggers a gas discharge, i.e. the gas becomes conducting. The resulting current pulse can be amplified and indicated visibly or audibly ("clicking").

The GM tube is the most expensive and most difficult to obtain part or a geiger counter. There are two main types of tubes:

• Glas mantle tubes are only suitable for beta and gamma rays, as any alphas are absorbed in the glass. They can be used for quantitative measurement of gamma dose rate. Glas mantle tubes are relatively cheap, they can be bought from electronics shops from about 50 EUR.
• Window tubes have a window (usually at one end), which is sealed with very thin foil or mica. Alphas can penetrate this window, and thus can be detected, as well as betas and gammas. As the window is very thin, it is extremely prone to puncture. Window tubes are more expensive and less common, they can be bought from about 80 EUR.

Geiger counter circuits can be bought complete or as kits from many electronic and surplus stores, often cheaper than a GM tube alone. An integrated electronic counter is very useful. The electronic circuit of a geiger counter (hv generation and amplifier) is fairly easy to build, and there are many more or less detailed plans around.

        The number of pulses ("clicks") over a certain time (count rate) is a quantitative measure of radiation. The count rate (often in cpm = counts per minute) depends, among others, on the geiger mueller tube, the type and energy of radiation and the geometry of the measurement, and therefore is difficult to convert to dose rate (Sv/h) or activity (Bq or Ci). However, it can be used as a relative measure to compare radioactive sources.

Some commercial geiger counters are "calibrated" to diplay the dose rate in µSv/h or mR/h directly, but unless the device is a really professional one, this is quite inaccurate for the reasons stated above. It may be useful to get a rough estimate of the dose rate, but it may also be dangerously misleading in some cases (in particular for low-energy x-rays).

"Scintillation Detectors" work by the radiation striking a suitable material (such as Sodium Iodide), and producing a tiny flash of light. This is amplified by a "photomultiplier tube" which results in a burst of electrons large enough to be detected. Scintillation detectors form the basis of the hand-held instruments used to monitor contamination in nuclear power stations. They can recognise the difference between a, b and g radiation, and make different noises (such as bleeps or clicks) accordingly.

        "Solid-State Detectors" are the most up-to-date instruments. They are used in particle-accelerator laboratories to show the results of high-energy collisions,  with banks of them clustered around the collision site, feeding data into huge computers. The way they work is way beyond what we need for GCSEs, but basically they are similar to the CCD Silicon chips used in video cameras.

Radiation dose.

As we saw in the previous section, high-energy radiation is capable of ionizing atoms, and it can tear molecules apart. The resultant damage is of  importance and we shell discuss it in due course. Fist let us learn some of the units used to describe the effects of radiation.

In many applications of radiation, the beneficial (or deleterious) effects of the radiation are roughly proportional to the amount of radiation energy absorbed. Therefore, a unit is needed to measure the energy absorbed from a radiation beam by a material. The unit of absorbed radiation energy is called the rad (rd).   It is defined as follows: When 1 g of material exposed to the beam absorbs 10^-5J of radiation energy, the absorbed dose is 1rd. Notice that the rad is a measure of absorbed energy per unit mass.

Because of the way the rad is defined, the same beam will result in different doses for different materials. A beam passing through human flesh might well be less absorbed than when passing through bone. As a result, a single beam passing through a person would cause a higher dose to the bone through which it passed than to the flesh.

Unfortunately, the rad is not a very good unit for measuring the effect of radiation on people. The difficulty lies in the fact that different types of radiation cause different  types of damage to human tissue. For example, a dose of 1 rd from an electron beam causes only about one-tenth as much damage as an equal dose from a beam of neutron or protons. Although the rad is a convenient unit for comparing effects of the same type of beam, it does lend itself well when difference types of radiation  are compared. For that reason, we make use of another unit.

The biological effect of absorbed radiation is measured in terms of a unit called the rem ( rad equivalent-man). It is a comparative unit in the sense that is measured the effect by comparing it to the effect caused by a 1-MeV x-ray beam. When one rad of x-radiation absorbed, a certain amount of biological damage  occurs. We define the rem  in such a way that a dose of 1 rem causes biological equivalent to a dose of 1 rad of 1-MeV x-rays.

To place the rem unit in a more useful relation to the rad, a quantity called the quality factor (QF) of radiation is introduced. It consists of a ratio arrived at in the following way. The radiation in question is used to irradiate the biological material so as to cause an absorbed dose of 1 rd. This same type of material is then irradiated by a 1-MeV x-ray beam until an equal amount of  biological damage is done. The absorbed dose in rads for this process is noted. We then define the quality factor as the ratio of these two doses:

 

QF=equivalent dose of x-rays / 1 rd of radiation in question

 

As a typical example, an x-ray dose of 20 rd is required to cause the same damage as a 1-rd dose of fast a particles. The QF for fast a particles is therefore 20. (The QF is often called the RBE, relative biological effectiveness.) Typical approximate values of QF are given in Table 1. ( By reference to the ideas of the previous section, can you explain quatitatively why a particles should be much more damaging than electrons?)

 

Table 1.

Approximate values of QF (or RBE)
RADIATION	APPROXIMATE qf
x-rays,electrons	1.0
fast neutrons and proton	10
effect of eye	30
a particles	10-20
slow neutrons	4-5

 

From the definition of the rem and QF, we can write the following relation:

 

Dose in rem = (QF)(dose in rad)

 

Notice that the units of QF are rems per rad.

Illustration How large a dose of fast neutron is equivalent to a 50-mrd dose of slow neutrons?

 

Reasoning. Let us first find the number of rems in a 50-mrd of slow neutrons. We have

Dose in rems=(QF)(dose in rads)

With QF=4.5. Therefore, for slow neutrons,

Dose in rems=(4.5rems/rd)(50x10^-3 rd)=0.225 rem

 

It is now possible to apply this same equation to the fast neutrons by use of QF=10 and dose in rem =0.225 rem. Then for fast neutron,

0.225 rem=(10 rems/rd)(dose in rads)

which gives 0.0225 rd as the required dose of fast neutrons.

There is yet another unit often used to describe radiation. It is called the Roentgen ®

And is used primarily for x-rays; 1 R is defined to be the amount of radiation which will produce 2.1x10⁹ ion pairs in 1 cm³ of air under standard conditions.

 

Radiation damage.

Since radiation can tear apart molecules, it is capable of damaging materials.

One of the most common types of radiation damage is due to the ultraviolet rays in sunlight. These lead to sunburn and  tanning of the skin. The high-energy photons disrupt skin molecules upon impact and cause these easily observed effects. In this case, the damage is usually of little importance. Most of the sun’s ultraviolet rays are absorbed by ozone in the upper atmosphere so normal exposure to the sun’s rays need not be avoided. However, in recent years we have become aware that a serious hazard could arise if we deplete the ozone layer with man-made chemicals. There is danger then that the increased ultraviolet radiation reaching us could increase the incidence of skin cancer.

We are constinuously exposed to other radiation in addition to sunlight. Nearly all materials contain a slight amount of radioactive substances. As a result, you body is unavoidably exposed to a low level of background radiation.

Typically, each person experiences a background radiation dose of about 0.15 rem each year. Let us now examine the effects of different levels of radiation dose upon the body.

High levels of radiation covering the whole body disrupt the blood cells so seriously that life cannot be maintained. For whole-body doses in excess of 500 rem, death is likely to occur. Even a whole-body dose of 100 rem can cause radiation sickness of a very serious, although nonfatal, nature. Blood abnormalities occur for doses in the range of 30 rem and above. At still lower whole-body doses, the overall effects on the body are less apparent but nevertheless can cause serious consequences.

Even very low radiation doses reaching the reproductive regions of the body are potentially dangerous. The giant molecules in our bodies which carry reproductive information can be disrupted by a single radiation impact. If enough of these molecules are damaged, defective reproduction information will be furnished to a fetus as it develops. As a result, birth abnormalities will occur. Even though there is some evidence that a low level of reproduction abnormalities may be beneficial to mankind, most birth defects are not desirable. For this reason, no one of child-bearing age should be exposed to unnecessary radiation of the reproductive organs. Of course a properly given arm x-ray, for example, presents no such danger.

In addition to causing birth abnormalities, low levels of radiation present two other hazards. First, there appears to be a delayed cancer effect. Although cancer may not appear at once, low levels of radiation may cause cancer to develop many years later. Second, a child is particularly vulnerable to radiation. Because the child is growing rapidly, any cell mutation caused by radiation could have serious consequences. For this reason, most doctors are reluctant to prescribe x-ray scans for children unless absolutely necessary.

There is no “safe” limit of body  exposure to radiation. It can only be said that radiation should be kept to the least value possible within reason. For example, since we are all subjected to a background radiation of about 0.15 rem/yr, there is no reason to disrupt our lives to avoid radiation doses less than this. Even though a person who  lives in the mountains may experience an annual background dose 0.05 rem higher than at sea level, the difference is not large enough to warrant moving. In the last analysis, one must often make a compromise between radiation safety and other considerations. Despite that fact, maximum occupational radiation doses are of value and have been specified. As a rough rule, the maximum yearly dose, except for the eyes and reproductive organs, is about 15 rems.

Modern Physics Summary

·              When certain metals are heated to a high temperature, they emit thermions (electrons) and the phenomenon is called thermionic emission

·              Cathode rays are a stream of negatively charged particles emitted from the cathode of an evacuated bulb, when a voltage of nearly 3000 volts given across the terminals.

·              Certain heavy elements when they become unstable, they disintegrate giving out certain radiations - α,β  particles and  γ  radiations.

·              All living things contain carbon and the amount of carbon 14 in them is enough to make them slightly radioactive.

·              Exposure to large amounts of radiation is harmful to health.

·              The nucleus of a radioactive substance spontaneously decays, giving off various kinds of radiations and getting transformed into the nucleus of another element.

·              Uranium and radium are two important naturally radioactive substances.

·              When a nucleus emits radiation it is said to decay.

·              Rays from radioactive isotopes are dangerous to living things but are also useful in variety of ways.

·              Exposure to large amounts of radiation is harmful to health.

·              All radioactive materials should always be handled with care and kept inside lead boxes.

·              An alpha decay causes the mass number to decrease by 4 and atomic number by 2.

·              Beta decay causes no change in the mass number, but the atomic number increases by 1.

·              Gamma emission has no effect on either the mass or atomic number.

Nuclear fission is the splitting of a heavy atom such as uranium into two lighter parts, accompanied with release of energy

Computed Tomography

Computed Tomography (CT) is a powerful nondestructive evaluation (NDE) technique for producing 2-D and 3-D cross-sectional images of an object from flat X-ray images. Characteristics of the internal structure of an object such as dimensions, shape, internal defects, and density are readily available from CT images. Shown below is a schematic of a CT system.

The test component is placed on a turntable stage that is between a radiation source and an imaging system. The turntable and the imaging system are connected to a computer so that x-ray images collected can be correlated to the position of the test component. The imaging system produces a 2-dimensional shadowgraph image of the specimen just like a film radiograph. Specialized computer software makes it possible to produce cross-sectional images of the test component as if it was being sliced.

 

How a CT System Works

The imaging system provides a shadowgraph of an object, with the 3-D structure compressed onto a 2-D plane. The density data along one horizontal line of the image is uncompressed and stretched out over an area. This information by itself is not very useful, but when the test component is rotated and similar data for the same linear slice is collected and overlaid, an image of the cross-sectional density of the component begins to develop. To help comprehend how this works, look at the animation below.

        In the animation, a single line of density data was collected when a component was at the starting position and then when it was rotated 90 degrees. Use the pull-ring to stretch out the density data in the vertical direction. It can be seen that the lighter area is stretched across the whole region. This lighter area would indicate an area of less density in the component because imaging systems typically glow brighter when they are struck with an increased amount of radiation. When the information from the second line of data is stretched across and averaged with the first set of stretched data, it becomes apparent that there is a less dense area in the upper right quadrant of the component's cross-section. Data collected at more angles of rotation and merged together will further define this feature. In the movie below, a CT image of a casting is produced. It can be seen that the cross-section of the casting becomes more defined as the casting is rotated, X-rayed and the stretched density information is added to the image.

In the image below left is a set of cast aluminum tensile specimens. A radiographic image of several of these specimens is shown below right.

  
  
CT slices through several locations of a specimen are shown in the set of images below.

A number of slices through the object can be reconstructed to provide a 3-D view of internal and external structural details. As shown below, the 3-D image can then be manipulated and sliced in various ways to provide thorough understanding of the structure.

 

Positron emission tomography

Positron emission tomography (PET) is a nuclear medical imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. Three-dimensional images of tracer concentration within the body are then constructed by computer analysis. In modern scanners, three dimensional imaging is often accomplished with the aid of a CT X-ray scan performed on the patient during the same session, in the same machine.

If the biologically active molecule chosen for PET is FDG, an analogue of glucose, the concentrations of tracer imaged then give tissue metabolic activity, in terms of regional glucose uptake. Use of this tracer to explore the possibility of cancer metastasis (i.e., spreading to other sites) is the most common type of PET scan in standard medical care (90% of current scans). However, on a minority basis, many other radiotracers are used in PET to image the tissue concentration of many other types of molecules of interest.

 

Image of a typical positron emission tomography (PET) facility

History

The concept of emission and transmission tomography was introduced by David E. Kuhl, Luke Chapman and Roy Edwards in the late 1950s. Their work later led to the design and construction of several tomographic instruments at the University of Pennsylvania. Tomographic imaging techniques were further developed by Michel Ter-Pogossian, Michael E. Phelps and others at Washington University School of Medicine.

Work by Gordon Brownell, Charles Burnham and their associates at the Massachusetts General Hospital beginning in the 1950s contributed significantly to the development of PET technology and included the first demonstration of annihilation radiation for medical imaging. Their innovations, including the use of light pipes and volumetric analysis, have been important in the deployment of PET imaging. In 1961, James Robertson and his associates at Brookhaven National Laboratory built the first single-plane PET scan, nicknamed the "head-shrinker."

One of the factors most responsible for the acceptance of positron imaging was the development of radiopharmaceuticals. In particular, the development of labeled 2-fluorodeoxy-D-glucose (2FDG) by the Brookhaven group under the direction of Al Wolf and Joanna Fowler was a major factor in expanding the scope of PET imaging. The compound was first administered to two normal human volunteers by Abass Alavi in August 1976 at the University of Pennsylvania. Brain images obtained with an ordinary (non-PET) nuclear scanner demonstrated the concentration of FDG in that organ. Later, the substance was used in dedicated positron tomographic scanners, to yield the modern procedure.

The logical extension of positron instrumentation was a design using two 2-dimensional arrays. PC-I was the first instrument using this concept and was designed in 1968, completed in 1969 and reported in 1972. The first applications of PC-I in tomographic mode as distinguished from the computed tomographic mode were reported in 1970. It soon became clear to many of those involved in PET development that a circular or cylindrical array of detectors was the logical next step in PET instrumentation. Although many investigators took this approach, James Robertson and Z.H. Cho were the first to propose a ring system that has become the prototype of the current shape of PET.

The PET/CT scanner, attributed to Dr David Townsend and Dr Nutt was named by TIME Magazine as the medical invention of the year in 2000.

PET/CT-System with 16-slice CT; the ceiling mounted device is an injection pump for CT contrast agent

Descriptions

Operation

To conduct the scan, a short-lived radioactive tracer isotope is injected into the living subject (usually into blood circulation). The tracer is chemically incorporated into a biologically active molecule. There is a waiting period while the active molecule becomes concentrated in tissues of interest; then the subject is placed in the imaging scanner. The molecule most commonly used for this purpose is fluorodeoxyglucose (FDG), a sugar, for which the waiting period is typically an hour. During the scan a record of tissue concentration is made as the tracer decays.

Fluorodeoxyglucose (¹⁸F) or fludeoxyglucose (¹⁸F) (INN), commonly abbreviated ¹⁸F-FDG or FDG, is a radiopharmaceutical used in the medical imaging modality positron emission tomography (PET). Chemically, it is 2-deoxy-2-(¹⁸F)fluoro-D-glucose, a glucose analog, with the positron-emitting radioactive isotope fluorine-18 substituted for the normal hydroxyl group at the 2' position in the glucose molecule.

After ¹⁸F-FDG is injected into a patient, a PET scanner can form images of the distribution of FDG around the body. The images can be assessed by a nuclear medicine physician or radiologist to provide diagnoses of various medical conditions.

¹⁸F-FDG was first synthesized via electrochemical fluorination with ¹⁸F. Subsequently, a nucleophilic synthesis was devised with the same radioisotope.

As with all radioactive ¹⁸F-labeled radioligands, the ¹⁸F must be made initially as the fluoride anion in a cyclotron. Synthesis of complete FDG radioactive tracer begins with synthesis of the unattached fluoride radiotracer, since cyclotron bombardment destroys organic molecules of the type usually used for ligands, and in particular, would destroy glucose.

Cyclotron production of ¹⁸F may be accomplished by bombardment of neon-20 with deuterons, but usually is done by proton bombardment of ¹⁸O-enriched water, causing a (p,n) reaction (sometimes called a "knockout reaction"—a common type of nuclear reaction with high probability) in the ¹⁸O. This produces "carrier-free" dissolved ¹⁸F-fluoride (¹⁸F^–) ions in the water. The 109.8 minute half-life of ¹⁸F makes rapid and automated chemistry necessary after this point.

To do this chemistry, the ¹⁸F^– is separated from the aqueous solvent by trapping it on an ion-exchange column, and eluted with an acetonitrile solution of 2,2,2-cryptand and potassium carbonate, which gives [(crypt-222)K]^+ 18F⁻ when dried.

The fluoride anion is not ordinarily very nucleophilic. Anhydrous conditions are required to avoid the competing reaction with hydroxide. The use of the cryptand to sequester the potassium ions avoids ion-pairing between free potassium and fluoride ions, making the fluoride anion more reactive.

Intermediate is reacted with a protected mannose triflate; the fluoride anion displaces the triflate leaving group in an S_N2 reaction, giving the protected fluorinated deoxyglucose. Base hydrolysis removes the acetyl protecting groups, giving the desired product after removing the cryptand via ion-exchange.

As the radioisotope undergoes positron emission decay (also known as positive beta decay), it emits a positron, an antiparticle of the electron with opposite charge. The emitted positron travels in tissue for a short distance (typically less than 1 mm, but dependent on the isotope), during which time it loses kinetic energy, until it decelerates to a point where it can interact with an electron.The encounter annihilates both electron and positron, producing a pair of annihilation (gamma) photons moving in approximately opposite directions. These are detected when they reach a scintillator in the scanning device, creating a burst of light which is detected by photomultiplier tubes or silicon avalanche photodiodes (Si APD). The technique depends on simultaneous or coincident detection of the pair of photons moving in approximately opposite direction (it would be exactly opposite in their center of mass frame, but the scanner has no way to know this, and so has a built-in slight direction-error tolerance). Photons that do not arrive in temporal "pairs" (i.e. within a timing-window of a few nanoseconds) are ignored.

Whole-body PET scan using ¹⁸F-FDG

Localization of the positron annihilation event

The most significant fraction of electron-positron decays result in two 511 keV gamma photons being emitted at almost 180 degrees to each other; hence, it is possible to localize their source along a straight line of coincidence (also called the line of response, or LOR). In practice, the LOR has a finite width as the emitted photons are not exactly 180 degrees apart. If the resolving time of the detectors is less than 500 picoseconds rather than about 10 nanoseconds, it is possible to localize the event to a segment of a chord, whose length is determined by the detector timing resolution. As the timing resolution improves, the signal-to-noise ratio (SNR) of the image will improve, requiring fewer events to achieve the same image quality. This technology is not yet common, but it is available on some new systems.

Image reconstruction using coincidence statistics

A technique much like the reconstruction of computed tomography (CT) and single-photon emission computed tomography (SPECT) data is more commonly used, although the data set collected in PET is much poorer than CT, so reconstruction techniques are more difficult (see Image reconstruction of PET).

Using statistics collected from tens of thousands of coincidence events, a set of simultaneous equations for the total activity of each parcel of tissue along many LORs can be solved by a number of techniques, and, thus, a map of radioactivities as a function of location for parcels or bits of tissue (also called voxels) may be constructed and plotted. The resulting map shows the tissues in which the molecular tracer has become concentrated, and can be interpreted by a nuclear medicine physician or radiologist in the context of the patient's diagnosis and treatment plan.

 

Schematic view of a detector block and ring of a PET scanner

 

 

Schema of a PET acquisition process

Combination of PET with CT or MRI

PET scans are increasingly read alongside CT or magnetic resonance imaging (MRI) scans, with the combination (called "co-registration") giving both anatomic and metabolic information (i.e., what the structure is, and what it is doing biochemically). Because PET imaging is most useful in combination with anatomical imaging, such as CT, modern PET scanners are now available with integrated high-end multi-detector-row CT scanners (so-called "PET/CT"). Because the two scans can be performed in immediate sequence during the same session, with the patient not changing position between the two types of scans, the two sets of images are more-precisely registered, so that areas of abnormality on the PET imaging can be more perfectly correlated with anatomy on the CT images. This is very useful in showing detailed views of moving organs or structures with higher anatomical variation, which is more common outside the brain.

At the Jülich Institute of Neurosciences and Biophysics, the world's largest PET/MRI device began operation in April 2009: a 9.4-tesla magnetic resonance tomograph (MRT) combined with a positron emission tomograph (PET). Presently, only the head and brain can be imaged at these high magnetic field strengths.

Radionuclides and radiotracers

Radionuclides used in PET scanning are typically isotopes with short half-lives such as carbon-11 (~20 min), nitrogen-13 (~10 min), oxygen-15 (~2 min), fluorine-18 (~110 min)., or rubidum-82(~1.27 min). These radionuclides are incorporated either into compounds normally used by the body such as glucose (or glucose analogues), water, or ammonia, or into molecules that bind to receptors or other sites of drug action. Such labelled compounds are known as radiotracers. PET technology can be used to trace the biologic pathway of any compound in living humans (and many other species as well), provided it can be radiolabeled with a PET isotope. Thus, the specific processes that can be probed with PET are virtually limitless, and radiotracers for new target molecules and processes are continuing to be synthesized; as of this writing there are already dozens in clinical use and hundreds applied in research. At present, however, by far the most commonly used radiotracer in clinical PET scanning is fluorodeoxyglucose (also called FDG or fludeoxyglucose), an analogue of glucose that is labeled with fluorine-18. This radiotracer is used in essentially all scans for oncology and most scans in neurology, and thus makes up the large majority of all of the radiotracer (> 95%) used in PET and PET/CT scanning.

Due to the short half-lives of most positron-emitting radioisotopes, the radiotracers have traditionally been produced using a cyclotron in close proximity to the PET imaging facility. The half-life of fluorine-18 is long enough that radiotracers labeled with fluorine-18 can be manufactured commercially at offsite locations and shipped to imaging centers. Recently rubidium-82 generators have become commercially available.These contain strontium-82, which decays by electron capture to positron-emitting rubidium-82.

Limitations

The minimization of radiation dose to the subject is an attractive feature of the use of short-lived radionuclides. Besides its established role as a diagnostic technique, PET has an expanding role as a method to assess the response to therapy, in particular, cancer therapy, where the risk to the patient from lack of knowledge about disease progress is much greater than the risk from the test radiation.

Limitations to the widespread use of PET arise from the high costs of cyclotrons needed to produce the short-lived radionuclides for PET scanning and the need for specially adapted on-site chemical synthesis apparatus to produce the radiopharmaceuticals after radioisotope preparation. Organic radiotracer molecules that will contain a positron-emitting radioisotope cannot be synthesized first and then the radioisotope prepared within them, because bombardment with a cyclotron to prepare the radioisotope destroys any organic carrier for it. Instead, the isotope must be prepared first, then afterward, the chemistry to prepare any organic radiotracer (such as FDG) accomplished very quickly, in the short time before the isotope decays. Few hospitals and universities are capable of maintaining such systems, and most clinical PET is supported by third-party suppliers of radiotracers that can supply many sites simultaneously. This limitation restricts clinical PET primarily to the use of tracers labelled with fluorine-18, which has a half-life of 110 minutes and can be transported a reasonable distance before use, or to rubidium-82 (used as rubidium-82 chloride) with a half-ife of 1.27 minutes, which is created in a portable generator and is used for myocardial perfusion studies. Nevertheless, in recent years a few on-site cyclotrons with integrated shielding and "hot labs" (automated chemistry labs that are able to work with radioisotopes) have begun to accompany PET units to remote hospitals. The presence of the small on-site cyclotron promises to expand in the future as the cyclotrons shrink in response to the high cost of isotope transportation to remote PET machines

Because the half-life of fluorine-18 is about two hours, the prepared dose of a radiopharmaceutical bearing this radionuclide will undergo multiple half-lives of decay during the working day. This necessitates frequent recalibration of the remaining dose (determination of activity per unit volume) and careful planning with respect to patient scheduling.

Image reconstruction

The raw data collected by a PET scanner are a list of 'coincidence events' representing near-simultaneous detection (typically, within a window of 6 to 12 nanoseconds of each other) of annihilation photons by a pair of detectors. Each coincidence event represents a line in space connecting the two detectors along which the positron emission occurred (i.e., the line of response (LOR)). Modern systems with a higher time resolution (roughly 3 nanoseconds) also use a technique (called "Time-of-flight") where they more precisely decide the difference in time between the detection of the two photons and can thus localize the point of origin of the annihilation event between the two detectors to within 10 cm.

Coincidence events can be grouped into projection images, called sinograms. The sinograms are sorted by the angle of each view and tilt (for 3D images). The sinogram images are analogous to the projections captured by computed tomography (CT) scanners, and can be reconstructed in a similar way. However, the statistics of the data are much worse than those obtained through transmission tomography. A normal PET data set has millions of counts for the whole acquisition, while the CT can reach a few billion counts. As such, PET data suffer from scatter and random events much more dramatically than CT data does.

In practice, considerable pre-processing of the data is required—correction for random coincidences, estimation and subtraction of scattered photons, detector dead-time correction (after the detection of a photon, the detector must "cool down" again) and detector-sensitivity correction (for both inherent detector sensitivity and changes in sensitivity due to angle of incidence).

Filtered back projection (FBP) has been frequently used to reconstruct images from the projections. This algorithm has the advantage of being simple while having a low requirement for computing resources. However, shot noise in the raw data is prominent in the reconstructed images and areas of high tracer uptake tend to form streaks across the image. Also, FBP treats the data deterministically—it does not account for the inherent randomness associated with PET data, thus requiring all the pre-reconstruction corrections described above.

Iterative expectation-maximization algorithms are now the preferred method of reconstruction. These algorithms compute an estimate of the likely distribution of annihilation events that led to the measured data, based on statistical principles. The advantage is a better noise profile and resistance to the streak artifacts common with FBP, but the disadvantage is higher computer resource requirements.

Recent research has shown that Bayesian methods that involve a Poisson likelihood function and an appropriate prior (e.g., a smoothing prior leading to total variation regularization or a Laplacian prior leading to -based regularization in a wavelet or other domain) may yield superior performance to expectation-maximization-based methods which involve a Poisson likelihood function but do not involve such a prior.

Attenuation correction: Attenuation occurs when photons emitted by the radiotracer inside the body are absorbed by intervening tissue between the detector and the emission of the photon. As different LORs must traverse different thicknesses of tissue, the photons are attenuated differentially. The result is that structures deep in the body are reconstructed as having falsely low tracer uptake. Contemporary scanners can estimate attenuation using integrated x-ray CT equipment, however earlier equipment offered a crude form of CT using a gamma ray (positron emitting) source and the PET detectors.

While attenuation-corrected images are generally more faithful representations, the correction process is itself susceptible to significant artifacts. As a result, both corrected and uncorrected images are always reconstructed and read together.

2D/3D reconstruction: Early PET scanners had only a single ring of detectors, hence the acquisition of data and subsequent reconstruction was restricted to a single transverse plane. More modern scanners now include multiple rings, essentially forming a cylinder of detectors.

There are two approaches to reconstructing data from such a scanner: 1) treat each ring as a separate entity, so that only coincidences within a ring are detected, the image from each ring can then be reconstructed individually (2D reconstruction), or 2) allow coincidences to be detected between rings as well as within rings, then reconstruct the entire volume together (3D).

3D techniques have better sensitivity (because more coincidences are detected and used) and therefore less noise, but are more sensitive to the effects of scatter and random coincidences, as well as requiring correspondingly greater computer resources. The advent of sub-nanosecond timing resolution detectors affords better random coincidence rejection, thus favoring 3D image reconstruction.

Applications

PET is both a medical and research tool. It is used heavily in clinical oncology (medical imaging of tumors and the search for metastases), and for clinical diagnosis of certain diffuse brain diseases such as those causing various types of dementias. PET is also an important research tool to map normal human brain and heart function.

PET is also used in pre-clinical studies using animals, where it allows repeated investigations into the same subjects. This is particularly valuable in cancer research, as it results in an increase in the statistical quality of the data (subjects can act as their own control) and substantially reduces the numbers of animals required for a given study.

Alternative methods of scanning include x-ray computed tomography (CT), magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI), ultrasound and single-photon emission computed tomography (SPECT).

While some imaging scans such as CT and MRI isolate organic anatomic changes in the body, PET and SPECT are capable of detecting areas of molecular biology detail (even prior to anatomic change). PET scanning does this using radiolabelled molecular probes that have different rates of uptake depending on the type and function of tissue involved. Changing of regional blood flow in various anatomic structures (as a measure of the injected positron emitter) can be visualized and relatively quantified with a PET scan.

PET imaging is best performed using a dedicated PET scanner. However, it is possible to acquire PET images using a conventional dual-head gamma camera fitted with a coincidence detector. The quality of gamma-camera PET is considerably lower, and acquisition is slower. However, for institutions with low demand for PET, this may allow on-site imaging, instead of referring patients to another center, or relying on a visit by a mobile scanner.

PET is a valuable technique for some diseases and disorders, because it is possible to target the radio-chemicals used for particular bodily functions.

Oncology

Oncology: PET scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG), called FDG-PET, is widely used in clinical oncology. This tracer is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form is greatly elevated in rapidly growing malignant tumours). A typical dose of FDG used in an oncological scan is 200-400 MBq for an adult human. Because the oxygen atom that is replaced by F-18 to generate FDG is required for the next step in glucose metabolism in all cells, no further reactions occur in FDG. Furthermore, most tissues (with the notable exception of liver and kidneys) cannot remove the phosphate added by hexokinase. This means that FDG is trapped in any cell that takes it up, until it decays, since phosphorylated sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the brain, the liver, and most cancers. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin's lymphoma, non-Hodgkin lymphoma, and lung cancer. Many other types of solid tumors will be found to be very highly labeled on a case-by-case basis—a fact that becomes especially useful in searching for tumor metastasis, or for recurrence after a known highly active primary tumor is removed. Because individual PET scans are more expensive than "conventional" imaging with computed tomography (CT) and magnetic resonance imaging (MRI), expansion of FDG-PET in cost-constrained health services will depend on proper health technology assessment; this problem is a difficult one because structural and functional imaging often cannot be directly compared, as they provide different information. Oncology scans using FDG make up over 90% of all PET scans in current practice.

A few other isotopes and radiotracers are slowly being introduced into oncology for specific purposes. For example, 11C-Metomidate has been used to detect tumors of adrenocortical origin. Also, FDOPA PET/CT, in centers which offer it, has proven to be a more sensitive alternative to finding, and also localizing pheochromocytoma than the MIBG scan.

PET scan of the human brain.

 

Neuroimaging

Neurology: PET neuroimaging is based on an assumption that areas of high radioactivity are associated with brain activity. What is actually measured indirectly is the flow of blood to different parts of the brain, which is, in general, believed to be correlated, and has been measured using the tracer oxygen-15. However, because of its 2-minute half-life, O-15 must be piped directly from a medical cyclotron for such uses, which is difficult. In practice, since the brain is normally a rapid user of glucose, and since brain pathologies such as Alzheimer's disease greatly decrease brain metabolism of both glucose and oxygen in tandem, standard FDG-PET of the brain, which measures regional glucose use, may also be successfully used to differentiate Alzheimer's disease from other dementing processes, and also to make early diagnosis of Alzheimer's disease. The advantage of FDG-PET for these uses is its much wider availability. PET imaging with FDG can also be used for localization of seizure focus: A seizure focus will appear as hypometabolic during an interictal scan. Several radiotracers (i.e. radioligands) have been developed for PET that are ligands for specific neuroreceptor subtypes such as [¹¹C] raclopride and [¹⁸F] fallypride for dopamine D2/D3 receptors, [¹¹C]McN 5652 and [¹¹C] DASB for serotonin transporters, or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses. The development of a number of novel probes for noninvasive, in vivo PET imaging of neuroaggregate in human brain has brought amyloid imaging to the doorstep of clinical use. The earliest amyloid imaging probes included 2-(1-{6-[(2-[¹⁸F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([¹⁸F]FDDNP) developed at the University of California, Los Angeles and N-methyl-[¹¹C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (termed Pittsburgh compound B) developed at the University of Pittsburgh. These amyloid imaging probes permit the visualization of amyloid plaques in the brains of Alzheimer's patients and could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies. [¹¹C]PMP (N-[¹¹C]methylpiperidin-4-yl propionate) is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetylcholinergic neurotransmitter system by acting as a substrate for acetylcholinesterase. Post-mortem examination of AD patients have shown decreased levels of acetylcholinesterase. [¹¹C]PMP is used to map the acetylcholinesterase activity in the brain, which could allow for pre-mortem diagnosis of AD and help to monitor AD treatments.Avid Radiopharmaceuticals of Philadelphia has developed a compound called 18F-AV-45 that uses the longer-lasting radionuclide fluorine-18 to detect amyloid plaques using PET scans.

A Brain PET / MRI Fusion image

A complete body PET / CT Fusion image

 

2.   Neuropsychology / Cognitive neuroscience: To examine links between specific psychological processes or disorders and brain activity.

3.   Psychiatry: Numerous compounds that bind selectively to neuroreceptors of interest in biological psychiatry have been radiolabeled with C-11 or F-18. Radioligands that bind to dopamine receptors (D1, D2, reuptake transporter), serotonin receptors (5HT1A, 5HT2A, reuptake transporter) opioid receptors (mu) and other sites have been used successfully in studies with human subjects. Studies have been performed examining the state of these receptors in patients compared to healthy controls in schizophrenia, substance abuse, mood disorders and other psychiatric conditions.

Cardiology

Cardiology, atherosclerosis and vascular disease study: In clinical cardiology, FDG-PET can identify so-called "hibernating myocardium", but its cost-effectiveness in this role versus SPECT is unclear. FDG-PET imaging of atherosclerosis to detect patients at risk of stroke is also feasible and can help test the efficacy of novel anti-atherosclerosis therapies.

Cardiac PET (or cardiac positron emission tomography) is a form of diagnostic imaging in which the presence of heart disease is evaluated using a PET scanner. Intravenous injection of a radiotracer is performed as part of the scan. Commonly used radiotracers are Rubidium-82, Nitrogen-13 ammonia and Oxygen-15 water.

The requirements to perform Cardiac PET imaging include:

• Facility: taking into consideration clinical workflow, as well as regulatory requirements such as requisite shielding from radiation exposure
• Capital equipment: PET or PET/CT scanner
• Radiopharmaceutical: Rubidium-82 generator system or close access to cyclotron produced isotopes such as Nitrogen-13 ammonia
• Personnel: including specialty trained physician, radiation safety, physics, nursing, and technologist support
• Operations: stress test monitoring, as well as emergency response equipment, processing and review workstations, administrative and support personnel are additional considerations

This form of diagnostic imaging has traditionally been perceived as cost-prohibitive in comparison to general nuclear medicine cardiac stress testing using single photon emission computed tomography (SPECT). However, due to significant gains in access to scanners, related to the widely accepted role of PET/CT in clinical oncology, cardiac PET is likely to become more widely available, particularly given various clinical and technical advantages that might make this a potential test of choice in the diagnosis of coronary artery/heart disease.

Cardiac PET imaging has now been expanded to mobile services to facilitate rural areas by a company called Nuclear Imaging Services located in Houston, TX, USA. They now have the first Medicare approved mobile Cardiac PET scanner available for patient use.

 

Pharmacology

Pharmacology: In pre-clinical trials, it is possible to radiolabel a new drug and inject it into animals. Such scans are referred to as biodistribution studies. The uptake of the drug, the tissues in which it concentrates, and its eventual elimination, can be monitored far more quickly and cost effectively than the older technique of killing and dissecting the animals to discover the same information. Much more commonly, however, drug occupancy at a purported site of action can be inferred indirectly by competition studies between unlabeled drug and radiolabeled compounds known apriori to bind with specificity to the site. A single radioligand can be used this way to test many potential drug candidates for the same target. A related technique involves scanning with radioligands that compete with an endogenous (naturally occurring) substance at a given receptor to demonstrate that a drug causes the release of the natural substance.

The following is an excerpt from an article by Harvard University staff writer Peter Reuell, featured in HarvardScience, part of the online version of the Harvard Gazette newspaper, which discusses research by the team of Harvard Associate Professor of Organic Chemistry and Chemical Biology Tobias Ritter: "A new chemical process ... may increase the utility of positron emission tomography (PET) in creating real-time 3-D images of chemical activity occurring inside the body. This new work ... holds out the tantalizing possibility of using PET scans to peer into a number of functions inside animals and humans by simplifying the process of using “tracer” molecules to create the 3-D images." (by creating a novel electrophilic fluorination reagent as an intermediate molecule; the research could be used in drug development).

 

Small animal imaging

PET technology for small animal imaging: A miniature PE tomograph has been constructed that is small enough for a fully conscious and mobile rat to wear on its head while walking around. This RatCAP (Rat Conscious Animal PET) allows animals to be scanned without the confounding effects of anesthesia. PET scanners designed specifically for imaging rodents or small primates are marketed for academic and pharmaceutical research.

 

Musculo-skeletal imaging

Musculo-Skeletal Imaging: PET has been shown to be a feasible technique for studying skeletal muscles during exercises like walking. One of the main advantages of using PET is that it can also provide muscle activation data about deeper lying muscles such as the vastus intermedialis and the gluteus minimus, as compared to other muscle studying techniques like electromyography, which can be used only on superficial muscles (i.e., directly under the skin). A clear disadvantage, however, is that PET provides no timing information about muscle activation, because it has to be measured after the exercise is completed. This is due to the time it takes for FDG to accumulate in the activated muscles.

 

Safety

PET scanning is non-invasive, but it does involve exposure to ionizing radiation. The total dose of radiation is significant, usually around 5–7 mSv. However, in modern practice, a combined PET/CT scan is almost always performed, and for PET/CT scanning, the radiation exposure may be substantial—around 23–26 mSv (for a 70 kg person—dose is likely to be higher for higher body weights). When compared to the classification level for radiation workers in the UK of 6 mSv, it can be seen that use of a PET scan needs proper justification.This can also be compared to 2.2 mSv average annual background radiation in the UK, 0.02 mSv for a chest x-ray and 6.5–8 mSv for a CT scan of the chest, according to the journal Chest and ICRP. A policy change suggested by the IFALPA member associations in year 1999 mentioned that an aircrew member is likely to receive a radiation dose of 4–9 mSv per year.