Emergency Nuclear Radiology

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CHAPTER 12 Emergency Nuclear Radiology

The fast pace of modern life, the increasing mobility of a rapidly growing population, the increasing communicability of disease, and complications from complex medical surgical interventions have all combined to increase the incidence of emergency medical situations. Furthermore, increasing awareness that timely intervention could halt or forestall dangerous disease conditions, along with the ability to treat such conditions, has resulted in emergency medicine becoming a rapidly developing and expanding medical specialty. This, consequently, has required the increasing support of imaging services.

The staple of imaging support has always been conventional radiography. However, newer modalities have made inroads into the use of plain film. These modalities are interventional radiology, computed tomography (CT), magnetic resonance imaging (MR), ultrasound, and nuclear medicine.

Since the development and refinement of CT, MR, and ultrasound, the use of nuclear medicine in the emergency setting has undergone significant changes. However, with development of fusion imaging—combining the strengths of different modalities while minimizing their weaknesses—we can anticipate a resurgence in the use of nuclear medicine techniques.

To fully exploit the use of radionuclides in the emergent or urgent situation, it is essential to understand the basic premise and promise of the modality. Scintigraphic techniques are inherently exquisitely sensitive while limited in providing spatial resolution. Metabolic changes invariably precede the appearance of anatomic changes. This feature is fundamental to nuclear medicine and consequently provides the information sought.

It is vital to understand, even superficially, the physics of the modality and the kinetics and chemistry of the tracers used.

RADIONUCLIDES

Radionuclides used in nuclear medicine are produced by artificial means in either a nuclear reactor or a particle accelerator. Both production methods involve the bombardment of a target nucleus with high-energy particles, which results in the transformation of stable nuclides into radionuclides.

In a reactor, the target is bombarded with neutrons, producing radioactive products with an excess of neutrons. By contrast, in a cyclotron, the target is bombarded with charged particles such as protons, producing radioactive species whose nuclei contain a deficit of neutrons or an excess of protons. While reactor-produced radionuclides emit β− particles and cyclotron-produced radionuclides emit β+ particles, some of these products emit gamma rays, which makes them useful in nuclear medicine imaging. For an elegant and concise explanation of how reactors and cyclotrons work, the reader is referred to the third edition of Nuclear Medicine in Clinical Diagnosis and Treatment, by P.J. Ell and S.S. Gambhir.

Radionuclides used for imaging have to possess certain characteristics that make them suitable for imaging. These properties include the following: gamma emission, short half-life (minutes to hours), high tissue penetration, and high specific activity. When used in tagged (as a radiopharmaceutical) or untagged form, these radionuclides have to provide useful clinical information while exposing the patient to minimal radiation. The chemical properties of the radionuclide should allow for its incorporation into the tracer of choice. The physical half-life of the radionuclide and biologic and effective half-life of the tracer have to effectively allow the study of the organ/metabolic/pathologic process under consideration. Ideally, the emission should be a single gamma ray in the range of 100 to 250 keV allowing good detection efficiency with the thallium-doped sodium iodide (NaI) crystal used in conventional nuclear medicine cameras.

Several of the radionuclides that are made in accelerators or nuclear reactors have half-lives long enough to allow shipment to distant (health care) facilities. When a long-lived radionuclide decays to a shorter-lived radionuclide, the parent nuclide can potentially become a transportable source for the production of the daughter nuclide. Since the parent and daughter radionuclides are chemically different, the daughter can be extracted either for direct use or for tagging. The device for transporting and extracting the daughter radionuclide is called a generator.

The most widely used radionuclide in nuclear medicine is technetium-99m (Tc-99m). Some of the other radionuclides used for clinical emergency situations include xenon-133 and indium-111.

Technetium-99m

Technetium exists only in the form of radioactive isotopes. The first Tc-99m generator was developed in 1958. This allowed convenient transport of the radionuclide and an explosion in the development of medical applications of Tc-99m.

Tc-99m is the most widely used tracer in nuclear medicine, accounting for over 85% of routine diagnostic procedures in a nuclear medicine department. The following radiation characteristics of technetium-99m make it an ideal agent (Fig. 12-1).

Gamma rays are attenuated both in tissue and in detector material (thallium-doped NaI). Compton scatter is the predominant interaction in tissue while the photoelectric effect is the interaction occurring in the detector. Radionuclides emitting low-energy gamma rays are likely to be absorbed by photoelectric effect within the tissue and will not reach the detector. This leads to poor resolution images, often requiring larger doses than those with higher-energy gamma rays, which will make it through to the detector.

Tc-99m is obtained from “milking” a molybdenum-99 (Mo-99) generator (Fig. 12-2). Mo-99 is obtained as a by-product from the fission of uranium. Mo-99 is chemically separated from the other radionuclides in the reactor product. Purified Mo-99 as anionic molybdate solution is loaded on to the generator column, which contains alumina. The alumina, which is positively charged, is able to adsorb Mo-99 ions. The assembly is then autoclaved. Several normal saline washings of the column yield eluate containing Tc-99m. These washings are subjected to several quality control tests to determine eluate volume, radionuclide purity (“moly” breakthrough), radiochemical purity (proper chemical form of technetium as pertechnetate), pyrogenicity, sterility, and/or alumina breakthrough. The half-life of Mo-99 is 66 hours allowing for weekly delivery of the generator to elute Tc-99m.

The eluted technetium can now be tagged to the appropriate pharmaceutical for use. When radionuclides such as technetium are tagged to specific pharmaceuticals, they are called radiopharmaceuticals. The pharmaceutical portion of the diagnostic radiopharmaceutical is present in very small amounts and will not elicit any pharmacologic response in the patient. The radioactive component is present in even smaller amounts. The technetium-99m radiopharmaceuticals for use in the emergency situation are listed in Box 12-1.

The radiopharmaceuticals are made up from “cold kits” supplied by manufacturers. With the exception of HMPAO (hexamethylpropyleneamine oxime), the kits are generally stable for up to 12 months. These kits provide a very convenient method of preparing radiopharmaceuticals in facilities that may not be close to laboratories. Technetium-99m can assume oxidation states ranging from I to VII based on the number of electrons available for reaction with ligands. The lower the oxidation state the less stable it is and the most likely to react with ligands. The most stable electronic configuration for technetium is the state with the value of VII where it is present as the pertechnetate ion and unlikely to tag to a ligand. Consequently, in order to produce a Tc-99m–labeled radiopharmaceutical, the technetium has to be first reduced to a lower oxidation state. This is most commonly accomplished by the addition of tin. As well, some cold kits contain antioxidants such as ascorbic acid or gentisic acid, which not only retard oxidation of the radiolabeled product, but also improve the stability of the kit. Tin II (stannous) supplies electrons and in the process becomes oxidized to tin V (stannic) ion. The various oxidation states of technetium allow the formation of a variety of different radiopharmaceuticals, which adds to the value of technetium as a nuclear medicine staple.

Reagents in the “kit” vial are generally freeze-dried and packed under vacuum. Alternatively, they may be combined with an inert gas such as nitrogen. This ensures that the tin in stannous form will not get oxidized to stannic form by exposure to the atmosphere. The amount of tin in the reagent vial is critical to the preparation of the radiopharmaceutical. Inadequate amounts of tin allow the oxidation of free pertechnetate, which ultimately degrades the image obtained and could potentially render a study nondiagnostic.

Gallium-67 Citrate

While Ga-67 citrate cannot be used for an emergent situation requiring a diagnostic test within a few hours of requisition, it is an important radionuclide for the workup of infection, which constitutes an emergency of sorts.

Gallium-67 is produced in a cyclotron from the parent zinc-68. Gallium-67 decays by electron capture to stable zinc-67 in 3.26 days (Fig. 12-4). The transition energy, which is 0.997 MeV, is dissipated by several electron capture transitions. Several gamma photons are emitted that are used for imaging. The principal ones are 93 keV with 37% abundance, 185 keV with 20% abundance, 300 keV with 17% abundance, and 394 keV with 5% abundance.

The exact mechanism of uptake of Ga-67 citrate is not precisely known. After intravenous administration of Ga-67, the complex dissociates to become bound to transferrin.

The principal organs that localize gallium are the liver, spleen, and bone marrow. The excretion of gallium is bimodal, initially through the kidneys and later through the GI tract. Persistence of gallium activity in the kidneys beyond 24 hours should be cause for further workup. There is some uptake in the lachrymal and salivary glands and the lactating breast. This is attributed to the high concentration of lactoferrin in these tissues. Both transferrin and lactoferrin are metabolized in the liver, which accounts for the uptake in the liver. Gallium is believed to behave like iron and utilizes the transferrin mechanism and responds to procedures like total body irradiation in a manner similar to iron saturation of transferrin.

IMAGING EQUIPMENT

The components of the detection system/gamma camera (Fig. 12-5) include the following:

Gamma rays emitted from the patient enter the NaI crystal after passing through the collimator. The collimator used varies with the situation. Gamma rays are converted into light within the crystal. An array of photomultiplier tubes is coupled to the scintillation crystal. The light from the crystal is converted into an electric signal, which is proportional to the amount of light generated in the crystal. The electric signals from the photomultiplier tubes are processed by the circuitry to generate position signals and the energy signal. The latter is proportional to the energy of the gamma ray emitted by the radionuclide. The pulse height analyzer analyzes and selects only the signals, which fall in the energy range preset for the radionuclide under consideration. The correction of the X and Y position of the signal, as well as the energy discrimination/pulse height analysis, is performed in the memory of the computer, which is integrated into the gamma camera. The information is recorded as an image in the memory of the computer and displayed on a color or black and white monitor. Each study (which could be composed of several images) is stored to be retrieved for review and reporting.

LUNG SCINTIGRAPHY

The most common indication for lung scintigraphy is to determine the likelihood of pulmonary embolism. Less common indications include lung transplantation, preoperative evaluation, and right-to-left shunt evaluation. We devote this section to the discussion of ventilation and perfusion scanning for pulmonary embolism.

Pulmonary Embolism

The incidence of pulmonary embolism (PE) and its detection have increased with the increasing frequency of long-distance travel and consequent loss of mobility. This has been further complicated by the aging of the population and the increasing incidence of underlying illness such as heart disease and peripheral vascular (including venous) disease.

PE is the third most common cause of death in the United States with 650,000 occurring each year. PE seems to present with greater preponderance in hospitalized patients. Given the high prevalence of the condition, its lethality, and the fact that a large number of patients with PE have atypical presentations, it is recommended that every patient with chest pain be worked up for PE.

Venous thrombosis, in contrast to arterial thrombosis, is caused by problems with the plasma clotting system. There is minimal platelet participation in the venous versus the arterial process. Furthermore, thrombus formation in the cardiac chambers is seen most commonly with slow flow conditions similar to venous thrombosis.

There is increasing evidence that an underlying coagulopathy may be responsible for spontaneous deep venous thrombosis (DVT) and PE. Hypercoagulability may be congenital or acquired. Primary or acquired deficiencies in protein C, protein S, or antithrombin III are known to be common causes of DVT and PE.

There are many risk factors for DVT and PE. It is well known that, among these, prolonged immobility, recent surgery, pregnancy, and underlying malignancy initiate DVT.

Radiopharmaceuticals and Techniques

The major function of the lungs is to effect the exchange of CO2 for O2 from the blood. This is accomplished by perfusion of the capillaries in the walls of the alveoli where inspired air brings in O2 and is exchanged for CO2 in the deoxygenated blood. The CO2 in the alveoli is then discharged to the outside via expiration. These two aspects of the respiratory anatomy and physiology are assessed in nuclear medicine. Pulmonary perfusion is assessed by the administration intravenously of technetium-99m macroaggregated albumin, whereas the various phases of ventilation are studied using gases or aerosols.

In pregnant women, a perfusion-only lung scan should be considered if the chest x-ray is normal and the patient has no history of smoking or lung disease. Since Tc-99m is excreted in the breast milk, the patient should be encouraged to express and store milk for 2 days until the radionuclide has decayed sufficiently.

Perfusion

Technetium-99m macroaggregated albumin (MAA) is the agent of choice for assessing pulmonary perfusion. The mechanism of accumulation with this agent is the blockade of capillaries in the pulmonary arterial circulation.

A minimum of 100,000 particles is necessary to obtain readable images. To obtain optimal images, approximately 200,000 to 600,000 particles are required. The size of the particles ranges from 5µ to 100µ with the majority measuring around 30µ. The desired particle concentration can be obtained by diluting the kit with normal saline. It is important to check the particle size using a microscope or a hemocytometer. Smaller fragments enter into the general circulation and are phagocytized by the liver and spleen.

Approximately 0.1% of capillaries are blocked with one injection. Ordinarily this degree of blockade is of little or no consequence. However, in patients whose pulmonary arterial circulation is tenuous, such as patients with pulmonary hypertension, blockade of the reduced capillary bed can precipitate cardiac complications or exacerbate the underlying condition. In patients with right-to-left shunts, transfer of particles into the systemic arterial circulation could potentially cause adverse coronary or cerebral events. For these patients as well as pediatric patients, we recommend the administration of a lower dose of particles (100,000 to 200,000).

Technetium-99m MAA is produced by the addition of Tc-99m pertechnetate to a sterile “cold kit” containing stannous albumin aggregates as lyophilized powder. Tc-99m pertechnetate is added to the cold kit. The tagged kit is allowed to stand at room temperature for 15 minutes to ensure maximum tagging. The usual administered activity in adults is 3 to 5 mCi (111–185 MBq). The pediatric dose is 25 to 50 mCi/kg of body weight. The lung is the critical organ in this procedure, receiving an absorbed radiation dose of 0.22 rad/mCi.

Tc-99m MAA is administered intravenously in a peripheral vein. Withdrawal of blood back into the syringe could produce clots, which could appear as “hot spots” on the lung scans. Injection into central venous access such as Swan-Ganz catheters is to be avoided. The syringe should be gently agitated to avoid the settling out of the MAA particles. Injecting the dose slowly over three to five deep breaths, as well as having the patient supine, will ensure the even distribution of particles.

The patient is imaged in a sitting position, although images could be obtained with the patient supine. Ideally, the patient is imaged on a large field-of-view (FOV) gamma camera using a parallel-hole collimator. A diverging collimator may be necessary in larger patients to encompass both lungs on the anterior and posterior views. The standard views are the anterior, posterior, right and left laterals, both right and left posterior oblique, and both right and left anterior oblique (Fig. 12-6). Generally, a minimum of 500,000 counts is accumulated per image.

In our institution, we have found single photon emission CT (SPECT) to be of use in determining whether the perfusion defect is segmental or nonsegmental.

Ventilation

Inert gases can be used to perform ventilation studies of the lung in tandem with technetium perfusion studies. Their short biologic half-life allows relatively complete clearance of the lung providing a clean slate, so to speak, for lung imaging with a longer-lived perfusion agent.

Xenon-133

Xenon-133 is relatively inexpensive and is the most commonly used agent for ventilation. Overlying soft tissue easily attenuates the principal gamma emission of 81 keV. Consequently, images of the lungs are generally obtained in the posterior projection. Additional images may be obtained in the posterior oblique projections. Images are rarely obtained in the anterior, anterior oblique, and lateral projections because of the degradation caused by overlying soft tissues such as breast. Consequently, any abnormalities that are seen only in the anterior areas of the lungs will be missed. Exhausting the xenon is a cumbersome and complex process requiring a charcoal trap or a venting system. To avoid contamination with xenon, which is heavier than air, a negative pressure room is required. Furthermore, xenon is fat soluble and will adhere to plastic drapes, floor wax, and instrument grease. Consequently, the background level will gradually rise during the workweek.

Xenon can be used to assess all phases of ventilation. The most commonly used technique involves having the patient breathe xenon through a spirometer. The patient exhales as deeply as possible and then inhales 10 to 20 mCi of Xe-133. The respiration is suspended at the end of the inhalation for 15 seconds, while the first image is obtained. The patient breathes xenon out into a spirometer, which constitutes a closed system. Approximately 2 L of oxygen are used to dilute the expired xenon (Fig. 12-7). The patient rebreathes this mixture for 2 to 3 minutes, at which time another static image is obtained. This constitutes the equilibrium image. After equilibrium has been reached, fresh air is breathed in until the xenon is completely washed out. Images are obtained every 15 seconds for 2 to 3 minutes. For patients with chronic obstructive pulmonary disease (COPD), the washout phase may be delayed up to 5 minutes to image areas of regional airway trapping. This entire process presupposes that the patient is able to cooperate with breathing into a spirometer or a closed system. The initial/single breath reflects the regional ventilatory rate. The equilibrium phase depicts the aerated volume of the lungs, while the washout phase delineates trapping. Xenon is fat soluble and partially soluble in blood, which will cause deposition in the liver, particularly in patients with fatty replacement in the liver.

Radiolabeled Aerosols

Radiolabeled aerosols are used for studying lung ventilation. Aerosol studies do not allow dynamic imaging. Dynamic imaging, while excellent for assessment of respiratory function, is not required for PE studies.

The most commonly used aerosol is Tc-99m diethylene triamine penta-acetic acid (DTPA) in a volume of 2 mL put into the nebulizer of an aerosol delivery system. The aerosol is prepared by injecting 30 mCi of Tc-99m DTPA into the nebulizer of the delivery system. Side tubing in the system allows oxygen to flow through a flow meter at the rate of 8 to 10 L/min. Generally, only a small amount of activity (1 to 2 mCi) is delivered. The trachea is the critical organ in the aerosol ventilation study. One of the major advantages of this system is that it can be attached to an endotracheal or tracheostomy tube. In patients without airway tubing, the aerosol is inhaled through the mouth while a nose clip is applied. In either circumstance, little or no patient effort or cooperation is required to deliver the aerosol into the airway. The aerosol is usually delivered with the patient in a supine position so that it is distributed evenly. No special venting is required with Tc-99m DTPA as it is with xenon. The second major advantage of using Tc-99m DTPA is that the imaging characteristics are ideal. Therefore, the Tc-99m DTPA study can be performed either before or after the Tc-99m MAA study. If the ventilation study is performed before the perfusion, the amount of activity required is between 1 and 2 mCi. However, if the perfusion study is obtained first, the number of counts accumulated for the ventilation study has to be 3 to 4 times greater than for the perfusion.

In the workup for PE, Tc-99m DTPA aerosol is ideal, since images can be obtained in projections to match the ventilation images. After inhalation, aerosol particles are deposited in the distal airways and not the alveoli. Following inhalation, the Tc DTPA particles dissolve in the fluids within the alveoli and ultimately diffuse across the epithelial barrier into the circulation. As long as the epithelial barrier is intact, the aerosol diffuses relatively slowly into the circulation. The half-time disappearance of the aerosol from the alveoli is about 80 minutes. This is much faster in patients whose epithelial barrier may be deficient, as in COPD or in smokers. The Tc DTPA that has entered into the circulation is cleared via the kidneys. Larger particles are deposited in the central airways, the mouth, and the alimentary tract (from swallowed particles) (Fig. 12-8).

Chest X-Ray

It is important to have a chest x-ray for evaluation before performing the ventilation-perfusion (VQ) scan (Fig. 12-9). It is good practice to have one that has been obtained within 24 hours of performing the VQ scan. It would be ideal to have a full-inspiration posteroanterior (PA) and lateral chest x-ray available for interpretation. However, a large percentage of the patients who are at risk for PE in the hospital or the intensive care unit setting may have several other cardiopulmonary pathologic processes that could interfere with the reading of the VQ scan. In these patients, one has to be satisfied with the portable radiograph, which is rarely of the quality of the standard PA and lateral radiographic study.

Symptomatology and chest x-ray findings in patients with PE are frequently nonspecific. Hampton’s hump and the Westermark sign are findings on chest x-rays that are seen in PE. However, these signs are not often visualized on the chest radiograph. With the introduction of multidetector CT scanners, the majority of patients for PE workup are directly imaged using CT pulmonary angiography. In patients with impending renal compromise, CT angiography with contrast may be fraught with danger. Increasingly, the CTPE has become the gold standard for diagnosis of pulmonary embolism. As well, VQ lung scanning is important for establishing the diagnosis of PE. These studies can indicate whether or not the patient is likely to have PE.

The Prospective Investigation Of Pulmonary Embolism Diagnosis (PIOPED) study, completed in the 1990s, provided a comprehensive look at the value of ventilation and perfusion scans in acute PE. The PIOPED criteria were based on the use of Xe ventilation scans. With the development of CT pulmonary angiography, the algorithms proposed by the PIOPED study have had to be modified.

A pragmatic approach to the interpretation of VQ scans has been proposed, and the following facts have to be taken into consideration:

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