Radionuclide Imaging (Isotope Scan)

Knee investigations

What is a Radionuclide (Isotope) Scan?

This type of scan also involves the use of radiation. In this case, a radioactive isotope is injected into your blood. The isotope which is attached to a component of bone tissue which is taken up by active bony tissue is then incorporated into the bone. You then sit in front of a camera at various times following the injection to detect where areas of increased activity are occurring. Radionuclide scanning is a very sensitive but nonspecific imaging modality. It will pick up areas of increased turnover, but does not necessarily tell you the cause of the increased turnover. The most common cause of bone turnover is degenerative disease (osteoarthritis). As osteoarthritis starts to develop, the affected bones increase their activity for various reasons. Into these areas of increased activity the radioisotope marker will be taken up and these will be shown up as ‘hot spots’.

What Does Radionuclide Scanning Detect?

Radionuclide scanning is commonly used to detect the spread of tumours in the body. It is a modality that will allow imaging of the whole skeleton at no extra increased radiation dose. It is also used for detecting degenerative disease. In the case of a person with what appears to be single compartment arthritis within the knee joint, who may be a candidate for a single compartment minimally invasive joint replacement, a bone scan be used to confirm the diagnosis. If the isotope scan shows that the activity is truly limited to one compartment, this lends further support to the patient’s potential suitability for a partial joint replacement, as opposed to a joint replacement, with the added advantages of the former.

There are variations of bone scans such as three-phase bone scanning which allows differentiation of increase uptake due to increased blood flow, increased activity in soft tissues or increased activity in bone. With a three-phase bone scan, a first picture is taken within a few seconds of injecting the dye over the particular area of interest such as the knee joint. A second image is taken half an hour or so later. This will highlight the soft tissue. Final delayed images are then taken three to four hours after the injection to highlight the bone. Sometimes further delayed images can be taken 24 hours later for more information.

Another variation on bone scanning is a white cell labelled scan. In this case, a sample of the patient’s blood is withdrawn and the white cells are labelled with a radioisotope. The blood is then injected back into the patient and the scanning protocols are followed. In this case, any areas of increased uptake will be due to the concentration of white cells in the body. This is commonly used to diagnose bone infections, especially around total joint replacements. This type of scan has now moved on and is now done using monoclonal antibodies to the white cells so that a sample of the patient’s blood does not have to be taken and the radioisotope is attached to an antibody to the white cells, and therefore when injected into the body, the antibody and the white cells will join together and so the white cells will be marked in this manner.

Uses of Radionuclide (Isotope) Imaging

Radionuclide imaging is based on differences in uptake of radionuclides containing radioisotopes when normal and abnormal tissue because of physiological and biological differences, rather than anatomical differences, as with radiographs and MRI and CT scans. The radioisotope emits gamma energy until it decays to a stable state. Gamma rays are detected by gamma camera using a sodium iodide crystal. When the crystal absorbs gamma ray or x-ray, it scintillates, i.e. it emits light. The light is converted to an electrical impulse by a photomultiplier tube and is amplified. This sequence of events allows creation of an image based on intensity and distribution of radioactivity in the body. Routine images of a gamma camera are two-dimensional (plainer). Tomographic images can be obtained by rotating the gamma camera in an elliptical or circular arc around the image body part. This is known as single photon emission computed tomography (SPECT). Computerised reconstruction of the data allows tomographic images to be obtained in axial, coronal and sagittal planes. SPECT scanning does require additional scanning time and is not routinely used.

In isotope scanning Technetium 99M is combined with diphosphonate complexes which carry the Technetium to the bone. The only absolute contraindication to radionuclide scanning is pregnancy. Technetium 99M has a relatively short physical half life of six hours and a gamma energy of 140 kev. The relatively short half life limits the radiation dose to the body. For evaluation of localised or joint pain, three-phase bone scanning is done. The first phase consists of a radionuclide angiogram in which scans are done every two to five seconds for one to two minutes after the injection. This shows the radionuclide in the blood vessels including flow in the arteries, capillaries and veins. The second phase is a blood pool scan which is done immediately after the first phase. This shows radionuclide in the soft tissues and extra-vascular space. The third phase, known as the delayed phase is done two to four hours after injection and shows radionuclide uptake by bone. By two to four hours 50% or more of the injected dose is taken up by the skeleton. The radionuclide is excreted by the kidneys into the urine. The early phase evaluates the regional vascularity. Increased vascularity can be seen in soft tissue abnormality such as cellulitis and in some soft tissue tumours. Increased vascularity is a nonspecific finding present in the early phase of many bone abnormalities including fractures, tumours, infections and other conditions. The most important factor in causing increased uptake in the bone on the delayed scan is increased bone turnover. High bone turnover and new bone formation cause increased uptake of the diphosphonate complexes.

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Bone scanning can be used to detect traumatic fractures within 24 hours of the injury. Initially the flow and blood pool scans test positive showing increased vascularity. The delayed scans can show increased uptake for up to six months or more after a fracture.
Bone bruises or trabecular fractures cause increased vascularity and uptake and maybe associated with ligamentous injuries such as an anterior cruciate ligament injury, a tear which shows bone bruise patterns in the lateral femoral condyle and posterolateral tibial plateau.
Meniscus tears have been shown to cause increased uptake on a bone scan.
Isotope scanning is very sensitive at showing stress fractures from overuse such as running, which can occur in the shaft of the tibia, the fibula or the femur. Osteoporotic tibial plateau fractures are also diagnosed well on bone scanning.
Osteoarthritis causes increased uptake of radionuclide around the articular surface of the bone because of increased bone turnover. Increased uptake on both sides of a joint is characteristic of osteoarthritis. However, the tibial plateau is usually affected earlier and more severely than the femoral condyle.
In the acute phase of reflex sympathetic dystrophy syndrome, there is increased vascularity and diffuse increased uptake. In the subacute phase, there is usually normal vascularity and diffuse increased uptake. In the atrophic phase, there may be normal or decreased vascularity and uptake.
Bone scanning is very useful for detecting bone tumours both primary tumours originating within the bone and metastatic spread from a distant tumour.
Bone infection (osteomyelitis) shows increased vascularity and increased uptake on a three phase bone scan. Cellulitis (soft tissue infection), presents with increased vascularity and flow and blood pool scans, but are either normal or only mild increased uptake in the delayed images.

In order to improve this specificity for evaluation and infection, inflammation specific radiopharmaceuticals have been developed. The two most widely used are Gallium 67 citrate and Indium 111 or Technetium 99M labelled white blood cells. Gallium 67 citrate is taken up in infection owing to a number of factors, but also localises in bone that has increased uptake in tumours, fractures and other areas of increased bone turnover. The comparison of the Gallium scan with bone scan helps increase specificity. Mis-match uptake on the Gallium scan compared to the bone scan is suggestive of infection. Matched bone scan Gallium uptake is indeterminate for infection. Gallium scanning has been largely replaced by radiolabeled white cell scanning.

White cell scanning has a higher specificity for diagnosing infection. With white cell labelled imaging, 50 ml of blood is obtained from the patient, with subsequent separation of the white blood cells. Labelling of the white blood cells occurs with the radioisotope within 15 to 30 minutes. These labelled white blood cells are then re-suspended in the patient’s plasma and reinjected. Following Indium 111 labelled injection, white cell labelled injection scans are done at approximately 24 hours after injection. With Technetium 99M labelled white cell imaging begins three hours after injection. Increased uptake is seen where there is localisation of white blood cells resulting from infection or inflammation. The labelling of white cells is time consuming and may be expensive. Some new isotopes have been developed without the need for labelling. Some of these include radio labelled monoclonal anti-granulosa antibodies.

In recent years MRI scanning is largely replaced bone scanning for the diagnosis of localised knee pain.

Written by Professor Jari

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