Nuclear Engineering

Radioisotopes and Their Use in Medical Diagnostics

Applications of nuclear radiation in diagnosis are of paramount importance in recent times. With the advancement of nuclear electronics and detector technology, nuclear radiation can be used to image different parts of the body with high sensitivity and resolution.

Let us first see examples of some radioisotopes and their important applications in biology.

Radioactive isotopes

Major number of natural isotopes is not radioactive, but they can be made radioactive artificially by bombardment of α-particles in a cyclotron or uranium pile. These nuclei again disintegrate by the emission of other particles. The half-lives of these isotopes may vary from few hours to several years. Some biologically important radioisotopes1, their mass number, type of radiation emitted, and half-lives are given in table m4.4.

TABLE m4.4 Some biologically important radioisotopes

Element	Mass Number	Type of radiation	Half-life
Potassium	42	β^– , γ	12.5 hours
Sodium	24	β^– , γ	15 hours
Iodine	131	β^– , γ	8.1 days
Phosphorous	32	β^– , γ	14.3 days
Iron	59	β^–	45.1 days
Cobalt	60	β^– , γ	5.2 years
Carbon	14	β^–	5,570 years

The radioisotope produced in the nuclear reactor is basically by the bombardment of neutrons and in cyclotrons they are produced by α-particle bombardment. The radioisotopes produced in cyclotron are mostly having shorter half-lives as compared to the radioisotope produced in the nuclear reactor. There are many applications of radioisotopes in medicine and biology. The following are the radinuclides having immense applications in nuclear medicine⁶:

1. Iodine-123 and Iodine-125 are used in medicine as tracers for imaging and evaluating the function of the thyroid.

1. Iodine-131 is used in medicine for treatment of thyroid cancer and Grave’s disease.3

1. Cobalt-60 is largely used in radiotherapy.

1. Strontium-89 and Samarium-153 are used for the relief of cancer-induced bone pain.

1. Boron-10 is used in Boron neutron capture therapy a recent technique in cancer treatment.

1. Thallium-201 and Technetium-99 are used to detect the coronary artery disease and myocardial imaging.

1. Phosphorous-32 is used to control the growth of excess red blood corpuscles in bone marrow.

1. Chromium-51 is used to label red blood cells and quantify gastro-intestinal protein loss.

1. Copper-64 is used to study genetic diseases affecting copper metabolism, such as Wilson’s and Menke’s diseases.

1. Xenon-133 is used for pulmonary (lung) ventilation studies.

There are many other applications of radioisotopes as nuclear medicine. Radioisotopes are also used in Biochemical applications. They are under regular use to label the molecules of biological samplesin vitro (out of the body). Many methods have been devised to determine the constituents of blood, serum, urine, hormones, antigens and many drugs by means of associated radioisotopes.

Now I am going to discuss two important techniques routinely used in modern medical science for imaging biological samples, organs and even the whole human body. The first imaging technique discussed here is Positron emission tomography (PET) where positron emitting radioisotope is used as a source and the second is magnetic resonance imaging (MRI), where not radioisotope is required. In MRI the magnetic moment of protons inside the body is used to get the information about any organ, pathology, fluid flow etc.

Positron Emission Tomography:

Positron emission tomography (PET) utilizes positron emitting radioisotopes for scanning. This technique provides valuable information regarding regional tissue biochemistry, physiology, and pharmacology. Gamma-ray emitting radioisotopes of the elements which constitutes the organic substances of the body are taken up for labeling and the selected biochemical or pharmacological compounds. The radionuclides selected for this technique are

1. Oxygen -15 (O¹⁵)

1. Nitrogen-13 (N¹³)

1. Carbon-11 (C¹¹)

1. Fluorine-18 (F¹⁸)

These radioisotopes are manufactured by bombarding the stable elements with high-energy ion beams in a cyclotron. During disintegration, they emit a positron and eventually gamma rays by pair annihilation process with electron [Fig. m4.5]. Each gamma photon has energy of 511 keV and they travel in opposite directions.

FIGURE m4.5 Annihilation of electron and positron in PET

Correlated pairs of gamma rays emerge from a body containing positron-emitting radioisotopes. These are detected when they reach a scintillator material 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. Photons which do not arrive in pairs (i.e., within a few nanoseconds) are ignored.

The most significant fraction of electron-positron decay results 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 formally 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 recovery time of the detectors is in the picosecond range rather than the 10’s of nanosecond range, it is possible to calculate the single point on the LOR at which an annihilation event originated, by measuring the “time of flight” of the two photons.,⁷

Few applications of PET are given below:

1. Brain utilizes glucose as a primary source of energy, for which detection of regional glucose metabolism using F¹⁸ can be successfully done by PET scanning. It is very much sensitive indicator of brain damage and recovery, and has better performance than tissue perfusion studies.

1. PET scanning is very much useful for detection of epileptic patients because the areas show less metabolism and the visualized areas get activated during seizures.

1. PET imaging accurately selects the patients for brain surgery and determines the areas of the brain for surgery.

1. PET is also useful for detection of ischemic areas of myocardium.

Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI), formerly referred to as magnetic resonance tomography (MRT), or in chemistry nuclear magnetic resonance (NMR), is a non-invasive method used to render images of the inside of an object. It is primarily used in medical imaging to demonstrate pathological or other physiological alterations of living tissues. The basic physics of MRI is nuclear magnetic resonance (NMR). The basic principle of NMR is the resonance of a radiofrequency signal with the Larmor precessional frequency. The angular momentum vector of a nucleon precesses with a uniform angular frequency around the axis of the magnetic field, in a manner similar to the precession of a mechanical top in a gravitational field. This is known as Larmor precession. Larmor frequency ( ν_L) is related to magnetic field (B) by a relation:

Where g is the g-factor of the nucleus. It is clear from the relation that ν_L is independent of L and is a function of charge and mass of the particle and of the magnitude of the applied field B. Clearly, ν_L= 0 if B = 0 or e = 0. Magnetic moment, associated with the angular momentum also precesses about the field direction. The magnetic field does not change the orientation of the magnetic moment with respect to the field direction. The interaction energy between the magnetic moment μand the field B is

where

and

μ_N= nuclear magneton,

m_p = proton mass

and

I = total angular momentum

Let us now estimate the Larmor frequency of a proton under an applied field 0.1 W/m²:

For

This frequency corresponds to the short radiofrequencies. If such a frequency is applied perpendicular to the external field and when the Larmor frequency becomes exactly equal to this frequency the system becomes resonant.

The proton being a fermion, the possible magnetic quantum numbers are +1/2 and -1/2. Also the possible values of the vector components of the magnetic moment in the direction of the applied magnetic field will be +μ_B and -μ_B. In the absence of the magnetic field, there is no preference for one or other of the two possible magnetic quantum numbers for protons. Thus, in a large sample of protons they are exactly of equal numbers. In the presence of magnetic field, the protons with m = 1/2 will have more tendency to align as compared to the protons with m = -1/2. The population of protons in these two quantum states at equilibrium can be determined by Boltzmann law:

where m_+1/2 and m_-1/2 are the population of protons in +1/2 and -1/2 states respectively, k is the Boltzmann constant, T is the temperature in absolute scale and E is the interaction energy E_intof Eqn. 8.6. Using Eqns. 8.6 and 8.10, we get

For B = 1/10 W/m², T ^~300⁰K, the fractional difference would be ^~ 10⁷. A sample of water of volume ^~1/10 c.c. contains about 10²² protons. Therefore, in this sample, the excess populations in the lower energy state are ^~10¹⁵ protons. One important parameter that plays role in this is the relaxation time, which is defined as the average lifetime of the excess nuclei in the non-relaxedstate. In other words, it is the decay time for reaching thermal equilibrium. We have seen that energy state m = -1/2 being antiparallel to field B, is energetically less favorable than m = +1/2 state. Thus, if an equilibrium distribution (in which both the states have same population) is to be obtained, it is necessary that energy should be lost to the surroundings by the process of nuclear relaxation. Having a knowledge of nuclear magnetic resonance let us ask question:

What is Magnetic resonance imaging (MRI)?

MRI is basically dependent on the relaxation properties of excited hydrogen nuclei. For imaging of any object (selective imaging of different voxels i.e. volume picture elements), orthogonal magnetic gradients are applied. Magnetic gradients are generated by three orthogonal coils, oriented in the x, y and z directions of the scanner. Typical gradient systems are capable of producing gradients from 20 mT/m to 100 mT/m. Basically, the plane of imaging is determined by the field gradients. In a 1.5 T magnetic field (at room temperature), this difference refers to only about one in a million nuclei, since the thermal energy far exceeds the energy difference between the parallel and antiparallel states. Yet the vast quantity of nuclei in a small volume sum to produce a detectable change in field. The bulk collection of nuclei can be partitioned into a set whose sum spin are aligned parallel and a set whose sum spin are anti-parallel. All spatial encoding is obtained by applying magnetic field gradients that encode the position within the phase of the signal. In one dimension, a linear phase with respect to position can be obtained by collecting data in the presence of a magnetic field gradient. In three dimensions (3D), a plane can be defined by “slice selection”, in which an RF pulse of defined bandwidth is applied in the presence of a magnetic field gradient in order to reduce spatial encoding to two dimensions (2D). The RF transmission system consists of a RF synthesizer, power amplifier and transmitting coil and is usually built into the body of the MRI scanner.

How image contrast is achieved in MRI?

The contrast of the MRI image is dependent on two time constants, which are involved in relaxation processes that establish equilibrium following RF excitation. The first one is known as longitudinal relaxation, which is basically relaxation of high-energy nuclei, followed by realignment of nuclear spin with the magnetic field. This is known as ‘time 1 or T1’ and is typically of the order of 1 sec. The second one is the transverse relaxation, which is related to the local dephasing of spins following the application of the transverse energy pulse. This is known as ‘time 2 or T2’ and is typically of the order of 100 ms. In order to delineate the areas under interest contrast agents like water, paramagnetic element (gadolinium) or superparamagnetic element (iron oxide nanoparticles) are added. Detailed mathematical analysis for processing the MRI image is based on k-space formalism and is independently formulated by Ljunggren⁸ and Tweig⁹.

Detailed discussion on this is out of scope of this book. In clinical practice, MRI is used to distinguish pathologic tissue (such as a brain tumor) from normal tissue. 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.

The most important advantage of MRI is that as there is no radioactive isotope present in this, no radiation induced effects/damage takes place during imaging.

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Radioisotopes and Their Use in Medical Diagnostics

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