Nuclear medicine

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Chapter 16 Nuclear medicine

Vicki Major, Marc Griffiths

KEY POINTS

The radiation dose from any diagnostic procedure should be as low as reasonably practicable, consistent with diagnostic results.¹

This is governed in nuclear medicine by the administration of strictly controlled amounts of radioactivity under a licensing arrangement and the use of optimum imaging conditions.²

Any person working within the nuclear medicine environment should have an awareness of the practical radiation protection considerations.

Nuclear medicine studies require the administration of less than a microgram of the radioactive substance under test. This has the advantage that it does not interfere with the physiological pathways but demonstrates their function.

The radioactive substances may be given in one of two forms: in their radionuclide form or attached to a drug and known as a radiopharmaceutical.

The radiopharmaceutical or radionuclide determines which system or organ the radioactive substance targets.

Most radioactive substances used in diagnostic imaging emit gamma radiation, which can subsequently be detected externally to the patient, and an image is produced of the uptake in the specific area.

Nuclear medicine studies can often detect certain disorders earlier than other diagnostic imaging procedures because they rely on functional rather than structural changes.

INTRODUCTION

Nuclear medicine is concerned with providing diagnostic information about patients following the administration of a radioactive product. The patient is imaged using a gamma camera. Images are produced of the distribution of the radioactive substance within different organs and systems. This can be compared with normal distribution to diagnose if a medical condition is present and assess its extent or severity.

A multidisciplinary healthcare team, comprising medical staff, hospital physicists, radiopharmacists, medical technologists, radiography practitioners, nurses and clerical support staff, delivers the nuclear medicine service. Nuclear medicine departments can be autonomous or part of a diagnostic imaging department.

Key terms

Radionuclide: a species of atom whose nucleus disintegrates by the emission of alpha particles, beta particles or gamma radiation.

Radiopharmaceutical: a medicinal product dependent for all or part of its action on a radioactive ingredient. It may be used for diagnostic, therapeutic or research purposes.²

Half-life: the time taken for the radioactivity to decay to half its original value. In the body this depends on the physical properties of the radionuclide and how quickly it is excreted from the body.

Gamma camera: the instrument used to detect the radiation and produce images.

Technetium: the most common radionuclide used in medical imaging.

RADIONUCLIDES USED IN MEDICAL IMAGING

TECHNETIUM

Technetium-99m (abbreviated to ^99mTc) is the most common radionuclide used in medical imaging. ^99mTc is attached to a pharmaceutical to produce a radiopharmaceutical, which is normally injected intravenously into the body. ^99mTc is used because:

a) It has a half-life of 6 hours.

• If a radionuclide had a very short half-life, such as 30 minutes, it would be very difficult to transport it from its site of manufacture in time to use it. If it had a long half-life, such as 30 years, the dose to the patients would be too great because their bodies would be receiving a radiation dose for the rest of their lives. The radiation dose to the patient to achieve a diagnostic medical image should be ‘as low as reasonably practicable’ (ALARP). A very short half-life would mean that the physiological uptake of the radiopharmaceutical could not be observed because it can take several hours for physiological uptake to occur in some systems. It is easy to deal with articles and waste contaminated with ^99mTc because it has a short half-life. After a few days of storage the radiation dose is low enough to be considered insignificant and therefore articles can be disposed of or used again in the department.

b) It is a pure gamma emitter.

• Gamma emitters are part of the electromagnetic spectrum. This means that they do not damage cells as much as alpha and beta particles, which are charged. Radioactive decay occurs when an element has an unstable arrangement of protons or neutrons and transforms into a stable element.³ Most elements emit alpha or beta particles as well as gamma radiation. The gamma radiation emission is normally instantaneous, but with some elements the atom stays in an excited state for a prolonged period of time. These are called ‘metastable radionuclides’ and they emit radiation at a discrete energy level that is characteristic of the radionuclide and normally only emit gamma radiation. The ‘m’ in ^99mTc indicates that technetium is metastable.

c) It has a 140 keV energy level.

• The energy level characteristic of ^99mTc is 140 kiloelectron volts (keV). This means that the energy is high enough to go through the patient and interact with the gamma camera. If it were too low, it would be attenuated in the patient and would not be able to interact with the camera. An energy level of 140 keV is low enough to be attenuated by the distance of a normal gamma camera room and therefore the practitioner will not be over-irradiated by the radionuclide.

d) It is cheap and easy to produce.

• ^99mTc is produced in the morning, before work begins in the hospital, by passing saline over a column containing the radioactive element molybdenum in a radiopharmacy (Fig. 16.1). The molybdenum is contained in a radioactive generator. As the saline passes over the column of molybdenum the saline takes off the daughter product technetium, forming a radioactive saline. The parent molybdenum stays on the column.

• The radioactive saline is then tested to make sure it has not been contaminated by the parent because this would be dangerous to the patient due to the fact that molybdenum has a half-life of 67 hours and emits beta radiation. The ^99mTc is produced in sterile radiopharmacy (Fig. 16.2).

e) It binds easily to pharmaceuticals.

• ^99mTc in radioactive saline is added to freeze-dried pharmaceutical kits in the radiopharmacy (Fig. 16.3). The kits take about 10 minutes to bind to the radionuclide and then they are ready to sub dispense, so they can be injected into patients. Some kits have to be boiled before they bind. The radiopharmaceuticals are tested for chemical binding and sterility.

f) They are non-toxic.

• Unlike radiographic contrast media, technetium does not contain iodine and therefore reactions are very rare. Technetium radiopharmaceuticals contain microscopic amounts of pharmaceuticals and therefore allergic reactions do not normally occur.

Figure 16.1 Molybdenum generator.

Figure 16.2 Radiopharmacy.

Figure 16.3 Freeze dried radiopharmaceutical kit.

OTHER RADIONUCLIDES USED IN DIAGNOSTIC IMAGING

EQUIPMENT

The instrument used to detect the radiation and produce images is a gamma camera. An image can be formed from the information gathered by the camera and displayed in either a static or whole body form (planar images) or dynamic mode (related to time; e.g. renal). Modern imaging systems can also create images in three dimensions (single photon emission computed tomography, SPECT), similar to those observed in computed tomography (CT) or magnetic resonance imaging (MRI).

The basic design of a gamma camera has not significantly changed for over 40 years and the use of devices such as sodium iodine crystals and photomultiplier tubes are the main reasons why nuclear medicine images have such low resolution in comparison to CT. However, technology advancements may see the development and production of solid-state gamma cameras in the future. The modern gamma camera consists of a large detector (or two detectors in dual head systems, Fig. 16.4), which is positioned as close to the patient as possible during examinations.

Figure 16.4 Modern dual head gamma camera system with an imaging couch and collimator cart.

Other features of a modern gamma camera system include an imaging couch, which is curved for patient comfort, a gantry for the detector heads to manoeuvre and a positioning monitor. The gamma camera is linked to a computer system which reflects the relative uptake of radiopharmaceutical tracer within the patient in the form of a visual image.

Many nuclear medicine departments will utilise one gamma camera to undertake a range of examinations. Some larger departments may employ a dual and a single head gamma camera to perform clinical examinations. Dual head gamma camera systems allow the operator to perform certain examinations (e.g. whole body bone scans) quicker than single head units, which is particularly useful for patients who may be in considerable discomfort.

The detector unit comprises a number of components, which enables the visualisation of radiopharmaceutical uptake within the patient. The gamma camera is a robust piece of medical imaging equipment; however, there is a requirement to ensure the working temperature of the examination room is kept constant and extreme fluctuations in temperature are avoided as this may have an impact upon the quality of the images produced.

The basic components of a modern gamma camera detector unit are:

• collimator

• crystal

• photomultiplier tubes

• shielding and cooling devices

• remote operating monitor.

Collimator

This is employed to localise accurately the radiopharmaceutical uptake within the patient. The collimator is designed from perforated or folded lead and has a ‘honeycomb’ appearance. Of all the gamma photons emitted by a patient over 99% of them are wasted and not recorded by the final processing computer. The collimator is an essential component of the detector unit and a nuclear medicine department may have a range of parallel hole design collimators to suit the type of examination being performed. The term ‘parallel hole’ refers to the perpendicular design of the collimator’s long axis holes to the detector crystal. The walls (septa) between the holes of the collimator are made of lead and subsequently absorb any gamma events that are not perpendicular to the crystal. Parallel hole collimators are the most commonly used collimator within most nuclear medicine departments. Some departments may employ a pinhole collimator for thyroid examination. Pinhole collimators work in the same manner as traditional pinhole cameras, with the image being inverted on the monitor. Investigations involving the use of higher energy isotopes, such as indium-111 or gallium-67, require the use of collimators with thicker lead septa between the holes.

The majority of investigations performed within a nuclear medicine department involve the use of technetium-99m based radiopharmaceutical agents. Technetium-99m has a photopeak energy of 140 keV and low energy collimators are used to absorb any gamma events that are not perpendicular to the crystal. For dynamic renal examinations a ‘low energy all purpose’ (LEAP) collimator may be employed and the holes are of a particular design to allow more gamma events to interact with the crystal than a ‘low energy high resolution’ (LEHR) collimator. The collection of counts on a dynamic examination is crucial if image processing is to take place afterwards. Figure 16.5 depicts a set of collimators being exchanged on a dual head gamma camera system. This process is mainly automated and requires minimal practitioner involvement. Caution should, however, be exercised when collimators are being exchanged, as the detector crystal is exposed and the collimators themselves are very heavy.

Figure 16.5 Collimator exchange cart containing a set of collimators.

Crystal

Gamma events passing through the collimator holes interact with the sodium iodide crystal and this subsequently produces a pulse of fluorescent light. The brightness of the pulse is proportional to the initial intensity of the incident gamma event. The crystal within a gamma camera is extremely fragile and is protected by an aluminium container within the detector head. Standard sodium iodide crystals are sensitive to humidity, moisture, external light and extreme temperature changes. Maximum caution needs to be exercised by practitioners when the collimator has been removed from a detector unit during routine quality control tests. The aluminium container will only protect the crystal from very minor physical damage. Most modern crystals are rectangular in design and are approximately 9.5 mm thick.

Photomultiplier (PM) tubes

The fundamental purpose of a PM tube is to convert a light pulse into an electrical signal. A number of PM tubes are positioned behind the crystal and protected with black plastic covers (Fig. 16.6).

Figure 16.6 Detector head with outer casing removed demonstrating electronic circuitry and PM tube covers.

These covers protect the PM tubes from any potential external light, which may be incorrectly processed. A scintillation event within the crystal is detected by a PM tube and is converted into a weak electrical signal. This weak signal is amplified using a series of dynodes within the PM tubes. The electrical outputs from the PM tubes are converted into the spatial coordinates (X and Y) required for the image appearance on the monitor (pulse arithmetic circuitry) and a Z signal, which identifies the incident gamma photon energy value during its interaction with the crystal. The Z signal passes through a pulse height analyser (PHA), which is able to discriminate against background or scatter radiation from a particular isotope. It is normal practice in nuclear medicine to place a 10% ‘window’ either side of an isotope’s photopeak value. For example, with technetium-99m, which has a photopeak energy value of 140 keV, the lowest ‘accepted’ gamma photons would be 126 keV and the highest ‘accepted’ gamma photons would be 154 keV.

Shielding and cooling devices

The shielding encases the detector head and accommodates the collimator. On modern gamma cameras it is lead lined to prevent any radiation interference occurring during scanning. Due to the amount of electronics on most modern gamma cameras, a number of cooling fans may also be situated near the top of the detector head. The filters surrounding these fans should be checked routinely and cleaned if necessary. Caution must be exercised during examinations involving the use of radioactive respiratory gases (e.g. technetium-99m aerosol ventilation gas), as particles may become lodged within the cooling fans and have an adverse affect on image quality.

Remote operating monitor and gantry/table controls

This small, flat panel monitor is situated on a boom from the gamma camera gantry, which permits the practitioner to commence an examination remotely rather than having to do so from the main operator’s console. This is particularly useful if the practitioner is performing a dynamic examination, requiring a quick start after intravenous injection of a radiopharmaceutical.

Figure 16.7 gives a representation of a gamma camera system.

Figure 16.7 Diagrammatic representation of the features of a gamma camera.

CREATION OF AN IMAGE

Gamma events leaving the patient’s body may be travelling at various angles – some may be perpendicular to the detector of the gamma camera (gamma event A in Fig. 16.8). Gamma events that are perpendicular to the crystal within the detector unit have to pass through the collimator; those that are not perpendicular to the crystal are absorbed by the collimator (gamma event B in Fig. 16.8). The collimator is the first tool used to ensure the accurate representation of physiological tracer uptake within the patient and without it there would not be any recognisable image on the monitor.

Figure 16.8 Schematic diagram demonstrating the pathway of two gamma ray events; perpendicular to the crystal (A) and not perpendicular to the crystal (B).

The second tool is the PHA, which as previously mentioned, discriminates against scatter or background radiation. Like in most clinical examinations, the nuclear medicine practitioner will have access to a number of preset protocols, which are stored on an operator’s computer console. Modern computer consoles use software driven platforms and graphical user interfaces (GUI). These permit quick access to a range of common clinical protocols and radioisotopes. The photopeak energy value per second of these isotopes is stored within the gamma camera’s computer and, as a result, determines the energy ‘window’ for that particular isotope. The practitioner has the ability to adjust the energy window if circumstances require this action. Nuclear medicine images may also be presented in different colour scales. Grey scale is normally utilised for skeletal and respiratory images and colour may be used for renal and cardiac examinations. Colour intensity scales are also presented with the images to assess the degree of tracer uptake within a particular part of the area under examination (Figs 16.9 and 16.10).

Figure 16.9 Skeletal scan demonstrating Paget’s disease with intense uptake in multiple areas of the left femur, pelvis and right humerus.

Figure 16.10 Cardiac scan demonstrating a patient who had experienced a myocardial infarction.

ACCESSORY EQUIPMENT FEATURES

A typical nuclear medicine department will utilise a range of ancillary items to position patients and ensure the production of optimal quality images. Paediatric patients require considerable preparation for examinations within nuclear medicine and the practitioner may employ the use of special imaging pallets, sandbags and immobilisation devices during the scan. It is crucial that patients do not move during examinations, as image unsharpness will occur. If patient movement occurs during a dynamic renal examination, this could potentially lead to an incorrect assessment of renal function. Some departments also use DVD and audio equipment to distract paediatric patients during examinations. The use of such equipment also reduces the close contact between the practitioner and patients and therefore helps to reduce the radiation dose received.

SPECIALISED EQUIPMENT

As previously mentioned, the majority of nuclear medicine departments also perform SPECT imaging. Common SPECT procedures undertaken within clinical practice include cardiac and skeletal examinations. However, some departments may also use SPECT techniques to perform neurological and oncology related procedures. SPECT imaging involves the collection of a number of views around the patient using the detector head/s. Most gamma cameras employed in clinical practice are dual head and can be configured to perform different SPECT examinations. As the detector head/s move around the patient (normally in a step fashion) each view collects a preset number of gamma photon events. Figure 16.11 demonstrates the set-up for a cardiac examination, with the detector heads presented in an inverted ‘V’ fashion. Performing SPECT examinations permits the presentation of data in three image planes: transaxial, sagittal and coronal. Powerful computers process the collected data and the practitioner may manipulate the generated data to provide the final images.

Figure 16.11 Dual head gamma camera with the detector heads prepared for a cardiac examination.

Recently the use of ‘hybrid’ gamma cameras has been introduced into clinical practice. Inherently, nuclear medicine images possess inferior spatial resolution compared to computed tomography. This is mainly due to the aforementioned inefficiencies of current gamma camera technology. The introduction of a low power X-ray tube and detector bank on the same gantry as the gamma camera heads is allowing practitioners to ‘fuse’ anatomical and functional data from the same imaging environment. Such technology is beginning to redefine the physical layout of nuclear medicine departments (given the use of an X-ray source) and is assisting in the localisation of certain physiological tracers. Figure 16.12 demonstrates an example of hybrid imaging.

Figure 16.12 Anatomical, functional and ‘fused’ data sets from a SPECT/CT system.

HANDLING AND SAFETY

SAFETY OF THE GAMMA CAMERA

The area of camera movement should be free from any objects. If a chair or other object is left in the path of travel the camera or object could be damaged. Some centres mark the footprint of camera movement on the floor to clearly show the extent of the exclusion zone.

The gamma camera interlocks should be checked every day and every time the collimators are changed.

RADIATION SAFETY

Radiopharmaceuticals can be shielded before they are injected into the patient. Tungsten syringe shields and lead and tungsten pots can be used. Radiopharmaceuticals are unsealed sources and therefore have the potential to contaminate through spillage. Pots and shields may be contaminated with radioactivity and therefore should not be touched. Treat all pots and shields as if they are contaminated and wear gloves and use tongs or other devices to keep a distance from them.

Gloves should be worn for handling radioactive materials, contaminated objects and if a suspected spillage has occurred. It is important to check for contamination: hands should be monitored after contact with radioactive products and departments should be monitored regularly (Fig. 16.13). A radioactive trefoil sign indicates areas containing radioactive materials or patients.

Figure 16.13 Radiographer monitoring a gamma camera room.

Radioactive waste has to be disposed of in the correct manner. ^99mTc waste is normally stored for at least a week. Empty syringes and needles may also be radioactive these should be disposed of in a shielded sharps box.

After the radiation has been injected into the patient then the best radiation protection is distance from the patient. The inverse square law means that if the distance is doubled then the radiation dose will be reduced by 75%.

A spill kit should be available in case some unsealed radioactivity has been spilt (Fig. 16.14). The nuclear medicine department should have a contingency plan in case of a spill.¹ If a spill has occurred, the radiation may have been spread and door handles and the bottom of shoes should be monitored as well as any area that might have been contaminated. The area of any spillage should be demarked. After donning protective clothing the spill should be wiped up, from the outside in, to avoid further spread. If the radiopharmaceutical is short lived it might be easier to close the area until decay has occurred. Records should be kept of the incident.

Figure 16.14 A spill kit for radioactivity.

EXAMINATION OVERVIEWS

BONE SCANS

Main indications

Metastases, Paget’s disease, infection, loose prosthesis, primary bone tumours, osteomyelitis, fractures, avascular necrosis, osteomalacia and hyperparathyroidism.

For fractures, avascular necrosis, osteomyelitis and prosthesis an image can be taken at injection and at 5 minutes post injection to give an idea of the blood supply to the area, as well as an image at 3 hours. This is called a three-phase bone scan.

Radiopharmaceutical and rationale

^99mTc-MDP (methylene diphosphonate) or ^99mTc-HDP (hydoxydiphosphonate):

• Clearance occurs by combination of skeletal uptake and urinary excretion. There is fairly rapid blood clearance – less than 10% remaining in the blood 1 h post injection.

• Skeletal blood flow influences local uptake of the radiopharmaceutical.

• Crucial influence on uptake appears to be osteoblastic activity. Osteoblasts build new bone, osteoclasts resorb bone.

• Radiopharmaceutical accumulates on bone surface, tracer being incorporated into the bone mineral crystal hydroxyapatite.

Collimators used

• Low Energy High Resolution.

STATIC RENAL SCANS

Main indications

Scarring from urinary tract infections, ectopic kidney, horseshoe kidney, failure to visualise a kidney with other imaging modalities. Renal failure, evidence of functioning renal tissue.

Radiopharmaceutical and rationale

^99mTc-DMSA (dimercaptosuccinic acid):

• Radiopharmaceutical binds to plasma proteins and accumulates in renal cortex.

Collimators used

• Low Energy High Resolution, or Low Energy General Purpose for very young children.

DYNAMIC RENAL SCANS (RENOGRAM)

Main indications

Assessment of renal function, obstructed kidney.

Radiopharmaceutical and rationale

^99mTc-MAG3 (mercaptoacetyltriglycine):

• The radiopharmaceutical is excreted from the kidneys via tubular excretion.⁴

Collimators used

• Low Energy High Resolution or Low Energy General Purpose.

INDIRECT MICTURATING CYSTOGRAM

If a child is potty trained and can cooperate well then the acquisition of an indirect cystogram can occur. This demonstrates reflux, which can cause scarring to the kidneys. The child micturates into a bedpan whilst sitting against the gamma camera and time/activity curves can be drawn. If urine is refluxing back to the kidneys it will show on the curves. This examination avoids the need for catheterisation of the child. Adults can also have a cystogram in this way, although requests for adult patients are not a common occurrence.

PATIENT CARE AND ADVICE

PATIENT CARE PRIOR TO THE SCAN

Children and pregnant women are not normally allowed to accompany patients to the nuclear medicine department to prevent them receiving a radiation dose from other patients. They can enter if they need to have a scan, normally by prior arrangement with the department.

Patients are normally sent information leaflets in advance of their scan that explain the procedure and precautions to be taken afterwards. All patients who receive radiation should be given clear written advice which sets out the risks associated with ionising radiation and specifies how doses resulting from their exposure during the scan can be restricted as far as reasonably possible so as to protect persons in contact with them (IR(ME)R 2000, see p. 14). Most patients have to avoid prolonged close contact with pregnant women and children for the rest of the day. These precautions may be longer for scans involving higher radiation doses or a radionuclide other than ^99mTc.

Most patients have to wait for several hours between injection and scan and should be given clear instructions as to any precautions that apply during this period. The patient’s ability to understand the precautions and comply with them is checked prior to injection of the radiopharmaceutical. The request form has to be justified by an ARSAC certificate holder, although this can be delegated under guidelines. The radiopharmaceutical can only be injected by a person who has had adequate training. This is normally a radiologist, nuclear medicine physician, radiographer or technologist. All female patients of reproductive age should be asked if they are pregnant or breastfeeding as they should not receive a radiopharmaceutical injection except under very special circumstances, which would need to be justified by the ARSAC certificate holder. For most examinations patients need to drink plenty of fluids throughout the day and empty their bladder frequently to reduce the radiation dose.

When a ward patient has a nuclear medicine scan information informing ward staff of radiation precautions and length of time that they apply should be provided.

PATIENT CARE DURING THE SCAN

Most nuclear medicine scans take about 30 minutes to run and the patient is unable to move during this time. Patients must be made as comfortable as possible during acquisition of the image because any movement means the procedure has to be repeated.

Patients are required to lie flat on the scanning table, with no more than one pillow under their head, in order to enable the gamma camera to be positioned as close as possible to their body. The scanning tables are very narrow and the armrests are normally hard Perspex (Fig. 16.18). The scan must start on an empty bladder, so patients are instructed to visit the toilet before the scan commences and then should be warned about the length of time they will have to spend on the scanning table. Metal objects such as coins and keys, which could cause artefacts, have to be removed from the patients before they get on the table. Patients usually keep their clothes on and do not change into gowns. The gamma camera rooms are air-conditioned and can feel cold to the patients, so blankets should be available to keep them warm. A pillow or knee support should be placed under the knees to increase comfort.

Figure 16.18 Gamma camera scanning table.

When the patient is lying comfortably on the scanning table a check should be made to make sure there are no tubes or lines hanging from the patient and that no parts of the patient’s anatomy are likely to get caught when the camera or table moves. Music can be played during the scan to help patient relaxation; in some departments DVDs are available for the patients to watch during scan. The gamma camera has to come as close as possible to the patient, so the patient should be warned about this. It is useful to put your hand between the patient and the gamma camera head when moving it towards the patient, so the camera hits your hand before touching any part of the patient. For patient safety a member of staff should always be present when the gamma camera is acquiring a scan.

When the scan has finished the patient is warned not to move until the table and camera have stopped moving. The table should be at its lowest level before the patient sits up and gets off. Some patients feel dizzy after getting up from lying flat, so they need time to get their bearings back.

After the scan the patients are advised about how and when they will receive the results of their scan. A check is made to ensure that each patient remembers any radiation precautions that still apply and how long they apply for.

PATIENT PATHWAYS

These pathways can be seen in Appendix 2.^5,⁶ These are simple generic pathways, which may differ from patient to patient depending on the imaging modalities available and the patient’s condition. Nuclear medicine involvement in the pathway is in bold type.

References

1 The Ionising Radiations Regulations. (SI 1999/3232). London: HMSO. 1999.

2 Administration of Radioactive Substances Advisory Committee. Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. Oxford: Health Protection Agency, 2006.

3 Sampson C. Textbook of radiopharmacy; theory and practice, 3rd edn. Amsterdam: Gordon and Breach, 1999.

4 Sharp PF, Gemmell HG, Smith FW, editors. Practical nuclear medicine. Oxford: Oxford University Press, 1998.

5 Eisenberg R, Johnson N. Comprehensive radiographic pathology. St. Louis: Mosby, 2003.

6 Underwood J., editor. General and systematic pathology. London: Churchill Livingstone, 2004.