Nuclear medicine

Nuclear medicine is a branch of medicine and medical imaging that uses unsealed radioactive substances in diagnosis and therapy. These substances consist of radionuclides, or pharmaceuticals that have been labelled with radionuclides (radiopharmaceuticals). In diagnosis, radioactive substances are administered to patients and the radiation emitted is measured. The majority of these diagnostic tests involve the formation of an image using a gamma camera. Imaging may also be referred to as radionuclide imaging or nuclear scintigraphy. Other diagnostic tests use probes to acquire measurements from parts of the body, or counters for the measurement of samples taken from the patient. In therapy, radionuclides are administered to treat disease or provide palliative pain relief. For example, administration of iodine-131 is often used for the treatment of thyrotoxicosis and thyroid cancer.

Nuclear medicine imaging tests differ from most other imaging modalities in that the tests primarily show the physiological function of the system being investigated as opposed to the anatomy. In some centres, the nuclear medicine images can be superimposed on images from modalities such as CT or MRI to highlight which part of the body the radiopharmaceutical is concentrated in. This practice is often referred to as image fusion.

Nuclear medicine diagnostic tests are usually provided by a dedicated department within a hospital and may include facilities for the preparation of radiopharmaceuticals. The specific name of a department can vary from hospital to hospital, with the most common names being the nuclear medicine department and the radioisotope department.

Diagnostic tests
Diagnostic tests in nuclear medicine exploit the way that the body handles substances differently when there is disease or pathology present. The radionuclide introduced into the body is often chemically bound to a complex that acts characteristically within the body; this is commonly known as a tracer. In the presence of disease, a tracer will often be distributed around the body and/or processed differently. For example, the ligand methylene-diphosphonate (MDP) can be preferentially taken up by bone. By chemically attaching technetium-99m to MDP, radioactivity can be transported and attached to bone for imaging. Any increased physiological function, such as due to a fracture in the bone, will usually mean increased concentration of the tracer. This often results in the appearance of a 'hot-spot' which is a focal increase in radio-accumulation, or a general increase in radio-accumulation throughout the physiological system. Some disease processes result in the exclusion of a tracer, resulting in the appearance of a 'cold-spot'. Many tracer complexes have been developed in order to image or treat many different organs, glands, and physiological processes. The types of tests can be split into two broad groups: in-vivo and in-vitro:


 * In-vivo tests are measurements directly involving the patient. By far the most common are gamma camera imaging investigations, though non-imaging probes are also used to measure the levels of radioactivity within a patient.


 * In-vitro tests are measurements of samples taken from the patient (e.g. blood, urine, breath).

Types of studies
A typical nuclear medicine study involves administration of a radionuclide into the body by injection in liquid or aggregate form, inhalation in gaseous form or, rarely, injection of a radionuclide that has undergone micro-encapsulation. Some specialist studies require the labeling of a patient's own cells with a radionuclide (lymphocyte scintigraphy and red cell scintigraphy). Most diagnostic radionuclides emit gamma rays, while the cell-damaging properties of beta particles are used in therapeutic applications. Refined radionuclides for use in nuclear medicine are derived from fission or fusion processes in nuclear reactors or cyclotrons, or take advantage of natural decay processes in dedicated generators, i.e. Molybdenum/Technetium or Strontium/Rubidium.

The most commonly used liquid radionuclides are:
 * technetium-99m
 * iodine-123 and 131
 * thallium-201
 * gallium-67
 * fluorine-18

The most commonly used gaseous/aerosol radionuclides are:
 * xenon-133
 * krypton-81m
 * technetium-99m Technegas&reg;
 * technetium-99m DTPA

Administration of radiopharmaceuticals
The routes of administration for radiopharmaceuticals include:


 * Intravenous injection: The radiopharmaceutical is injected into a vein. Many investigations use this method including the technetium-99m-MDP bone scan.
 * Subcutaneous injection: The radiopharmaceutical is injected under the skin. This method is used when investigating the lymphatic system.
 * Intrasynovial injection: The radiopharmaceutical is injected directly into a joint space. For example, imaging of the knee joint using yttrium-90.
 * Inhalation: Some radiopharmaceuticals and radioisotopes are inhaled by the patient, typically to investigate the function of the lungs. Examples include the gas krypton-81m and aerosols containing technetium-99m.
 * Ingestion: Radiopharmaceuticals can be ingested. For instance, technetium-99m added to scrambled eggs can be used to investigate gastric emptying.
 * Topical application: Application of the radiopharmaceutical directly to the area to be investigated, such as the administration of technetium-99m eyedrops to investigate tear-duct flow.

Imaging equipment
The radiation emitted from the radionuclide inside the body is usually detected using a gamma camera. Traditionally, gamma-cameras have consisted of a gamma-ray detector, such as a single large sodium iodide NaI(Tl) scintillation crystal, coupled with an imaging sub-system such as an array of photomultiplier tubes and associated electronics. Solid-state gamma-ray detectors are available, but are not yet commonplace. Gamma-cameras employ lead collimators to increase the image resolution by limiting the detection of unwanted gamma-rays.

Gamma-camera performance is usually a balance of spatial resolution against sensitivity. A typical gamma-camera will have a resolution of 4 to 6mm and will be able to capture several hundred thousand gamma-ray 'events' per second. The gamma-camera detects the X and Y position of each gamma-ray event, using these coordinates to place a pixel in an image matrix to build a recognisable image. The units of a raw nuclear medicine image is 'counts' or 'kilocounts', referring to the number of gamma-ray events detected. In nuclear medicine, the value of an image pixel is the integral of gamma-ray events in that pixel position over time. That is, the pixel appears brighter as more counts are detected in that position. In non-tomographic images, the pixel can also be thought of as the line integral of radionuclide distribution of a perpendicular line extending from the pixel position through the body of the patient.

Since each nuclear medicine radionuclide has a unique gamma-ray emission energy spectrum, and since the energy of a gamma-ray is detected in a gamma-camera by the brightness of the scintillation associated with an event, gamma-cameras employ energy 'windows' to gate or limit the imaging process to gamma-ray events of particular energies. An energy window is usually tailored to the peak of the energy spectrum of a particular radionuclide, and to ignore other gamma-rays that would otherwise contribute noise to the image. This allows noise caused by Compton scattering to be gated out.

Analysis
The end result of the nuclear medicine imaging process is a "dataset" comprising one or more images. In multi-image datasets the array of images may represent a time sequence (ie. cine or movie) often called a "dynamic" dataset, a cardiac gated time sequence, or a spatial sequence where the gamma-camera is moved relative to the patient. SPECT (single photon emission computed tomography) is the process by which images acquired from a rotating gamma-camera are reconstructed to produce an image of a "slice" through the patient at a particular position. A collection of parallel slices form a slice-stack, a three-dimensional representation of the distribution of radionuclide in the patient.

The nuclear medicine computer may require millions of lines of source code to provide quantitative analysis packages for each of the specific imaging techniques available in nuclear medicine.

Radiation dose
A patient undergoing a nuclear medicine procedure will receive a radiation dose. Under present international guidelines it is assumed that any radiation dose, however small, presents a risk. The radiation doses delivered to a patient in a nuclear medicine investigation present a very small risk of inducing cancer.

The radiation dose from a nuclear medicine investigation is expressed as an effective dose with units of millisieverts (mSv). The effective dose resulting from an investigation is influenced by the amount of radioactivity administered in megabecquerels (MBq), the physical properties of the radiopharmaceutical used, its distribution in the body and its rate of clearance from the body.

Effective doses can range from 0.006 mSv for a 3 MBq chromium-51 EDTA measurement of glomerular filtration rate to 37 mSv for a 150 MBq thallium-201 non-specific tumour imaging procedure. The common bone scan with 600 MBq of technetium-99m-MDP has an effective dose of 3 mSv (1).

Reference
1. Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. Administration of radioactive substances committee UK 1998.