Emergency Nuclear Radiology

Advances in the understanding and knowledge of disease and the development of newer treatment methods, along with the increasing skill of health care providers and their expanding ability to treat disease, have made medicine a rapidly expanding frontier. The increasing availability of multiple modes of transport and increasing mobility, an aging population, armed conflicts worldwide, increasing communicability and spread of disease, and complications from complex medical and/or surgical interventions have all combined to increase the incidence of emergency medical situations. Timely intervention could, in most instances, halt or forestall dangerous disease conditions, which has required increasing support of imaging services to diagnose disease and evaluate the efficacy of treatment.

The staple of imaging support has long 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 (MRI), ultrasound, and nuclear medicine.

The development and refinement of CT, MRI, and ultrasound to bring superlative anatomic resolution, as well as their ease of access and availability, have produced changes in the utility and utilization of nuclear medicine in the arena of emergency medicine.

Significant delays in the acquisition of nuclear medicine images are imposed by the incorporation/inclusion of the radiopharmaceutical agent into a metabolic/functional process. This delay places nuclear medicine imaging at a disadvantage and delegates it to the position of being a second-line study in most instances. To assess the use of a nuclear medicine procedure, it is helpful to review the advantages and disadvantages of the modality, which can be accomplished by assessing the characteristics of the modality using a SWOT (strength, weaknesses, opportunities, and threats) overview:

The strength of nuclear medicine imaging lies in the ability to analyze and evaluate physiologic processes and, thereby, function. Nuclear medicine procedures allow imaging of physiologic or pathophysiologic processes that generally have long turnover cycles. However, emergency situations develop rapidly and must be resolved rapidly, which restricts the use of nuclear medicine imaging to a select few situations.
Some pathologic processes, such as gastrointestinal (GI) bleeding, occur intermittently or sporadically. Nuclear medicine imaging procedures are advantageous in such instances because they do not add further radiation exposure with repeated and or delayed imaging.
Nuclear medicine procedures provide invaluable sensitivity and specificity. Scintigraphic techniques are inherently exquisitely sensitive. Metabolic changes invariably precede the appearance of anatomic changes. This feature is fundamental to nuclear medicine and consequently provides the information sought much earlier along the course of the disease.
Scintigraphy highlights disease in an entire organ system, such as in skeletal scanning. This property is not easily obtained with other modalities. For example, with bone scanning, scintigraphy provides the ability to assess the skeletal system without additional radiation, allowing detection of unsuspected distant metastases, metabolic bone disease, and nonaccidental injuries (as in child abuse).
Scintigraphy offers a high signal-to-noise ratio. The accumulation of the administered radiopharmaceutical agent in an area of disease (such as in bone turnover) or its conspicuous absence from a normal physiologic process (such as with pulmonary emboli in pulmonary vasculature) utilizes this characteristic effectively.
Nuclear medicine procedures provide an alternative when other procedures are contraindicated, as in patients with compromised renal function or in patients with sensitivity to contrast material.
Flow and/or perfusion studies followed by delayed static images are achieved with relative ease and without the use of additional radiation, as is well illustrated in the evaluation of osteomyelitis.
The portability of a gamma camera is a great asset when performing imaging of patients in an intensive care unit, when transportation may be logistically challenging.

A similar SWOT analysis of other modalities such as sonography, CT, angiography, or MRI also may be of some value:

CT and MRI offer superlative spatial resolution that cannot be achieved with scintigraphy.
CT and MRI allow the visualization of structures in the proximity of the area of concern. For example, in the setting of trauma, the development of surgical complications such as biliary leakage and abscess formation allow the radiologist to view other or adjacent organs.
Sonography is an extremely useful modality because it is easily available and is portable. This feature is valuable when it might be difficult to transport the patient to the imaging suite.

However, these modalities also have disadvantages:

With conventional radiography, CT, or angiography, the issue of radiation exposure both to the patient and to the operator can be problematic, particularly when the procedures must be repeated frequently. With the easy availability of these modalities, it can become logistically easier to repeat the studies in order to evaluate progression of the disease process and thus easier to disregard the issue of exposure of the patient to unnecessary and additional radiation.
Repeated imaging using radiographic procedures is undesirable when intermittent, recurring, or sporadic events are part of the spectrum of the disease.
Reliance on the skill of the operator is a major issue in sonography, because the skill of the operator may not always be consistent.
Degradation of images by inherent issues, such as the presence of fat or air, can interfere with the quality of the images.

With the development of sophisticated fusion technology, it has become common to combine the high sensitivity of nuclear medicine with the superlative resolution of other imaging modalities.

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, the physics of the modality, and the kinetics and chemistry of the tracers used.

Radionuclides

The 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. Whereas 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.

P.J. Ell and S.S. Gambhir provide an elegant and concise explanation of how reactors and cyclotrons work in the third edition of Nuclear Medicine in Clinical Diagnosis and Treatment (see Suggested Readings ).

Radionuclides used for imaging must possess certain characteristics that make them suitable for imaging, including the following properties:

Gamma emission
Short half-life (minutes to hours)
High tissue penetration
High specific activity

In addition, when used in tagged (as a radiopharmaceutical) or untagged form, these radionuclides must 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 the biologic and effective half-life of the tracer must 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 that is 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 become a transportable source for the production of the daughter nuclide. Because 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 the generator.

The most widely used radionuclide in nuclear medicine is technetium-99m ( ^99m Tc). 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 ^99m Tc generator was developed in 1958. The ability to conveniently transport the radionuclide using a generator ushered in an explosion in the development of medical applications of ^99m Tc.

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

140.5-keV gamma emissions provide ideal tissue penetration, allowing easy collimation and excellent absorption in the thallium-doped NaI crystal.
^99m Tc decays to technetium-99, which has a half-life of 21,000 years! However, ⁹⁹ Tc is a low-energy beta emitter.
Gamma emission allows the use of higher doses, while absorbed radiation dose is maintained at acceptable levels.

FIGURE 12-1, Decay scheme showing the isomeric transition of technetium-99m ( 99m Tc). 99 Mo, Molybdenum-99.

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 phenomenon leads to poor-resolution images, often requiring larger doses than those with higher-energy gamma rays, which will make it through to the detector.

^99m Tc is obtained from “milking” a molybdenum-99 ( ⁹⁹ Mo) generator ( Fig. 12-2 ). ⁹⁹ Mo is obtained as a by-product from the fission of uranium. ⁹⁹ Mo is chemically separated from the other radionuclides in the reactor product. Purified ⁹⁹ Mo as anionic molybdate solution is loaded onto the generator column, which contains alumina. The alumina, which is positively charged, is able to adsorb ⁹⁹ Mo ions. The assembly is then autoclaved. Several normal saline solution washings of the column yield eluate-containing ^99m Tc. 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 ⁹⁹ Mo is 66 hours, allowing for weekly delivery of the generator to elute ^99m Tc.

FIGURE 12-2, Molybdenum-technetium generator. Tc-99m, Technetium-99m; Mo-99, molybdenum-99.

The eluted technetium can now be tagged to the appropriate pharmaceutical agent for use. When radionuclides such as technetium are tagged to specific pharmaceutical agents, 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 ^99m Tc radiopharmaceuticals for use in emergency situations are listed in Box 12-1 .

BOX 12-1

Technetium-99m Radiopharmaceuticals

^99m Tc pertechnetate for scrotal scanning
^99m Tc macroaggregated albumin for perfusion lung scans
^99m Tc sulfur colloid for gastrointestinal bleeding
^99m Tc diethylene triamine pentaacetic acid
^99m Tc methylene diphosphonate for bone scanning
^99m Tc pertechnetate
^99m Tc hexamethylpropyleneamine oxime (exametazime) or technetium-99m ethyl cysteinate dimer
^99m Tc mercaptoacetyltriglycine (MAG3) for renal scanning
^99m Tc-labeled red blood cells for gastrointestinal bleeding

The radiopharmaceuticals are made from “cold kits” supplied by manufacturers. With the exception of hexamethylpropyleneamine oxime (HMPAO), 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. ^99m Tc 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 it is 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, to produce a ^99m Tc-labeled radiopharmaceutical, the technetium first must be reduced to a lower oxidation state. This reduction is most commonly accomplished through the addition of tin. 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, which ensures that the tin in stannous form will not undergo oxidization to the 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 render a study nondiagnostic.

Indium-111

Indium-111 ( ¹¹¹ In) is produced in a cyclotron from parent Cd and has a half-life of 67 hours (2.8 days). The principal photons are 171 keV and 247 keV. The relatively long half-life of ¹¹¹ In allows sequential imaging ( Fig. 12-3 ).

¹¹¹ In has the following medical diagnostic applications:

¹¹¹ In oxine for isotopic labeling of blood cell components such as platelets for detection of thrombi
¹¹¹ In-labeled leukocytes for localization of inflammation and abscesses
¹¹¹ In-labeled leukocytes are also used for evaluation of leukocyte kinetics
¹¹¹ In used in labeling peptides for diagnosis of certain neoplastic disorders such as ¹¹¹ In octreotide for carcinoids, paragangliomas, and pheochromocytomas

Ordinarily, the uses of indium such as for tumor detection are not considered emergency procedures. ¹¹¹ In-labeled leukocytes can be used for localizing abscesses and other inflammatory procedures. Although CT, MRI, and sonography may be the first-line modalities for investigation of infections, scintigraphy is an excellent adjunct not only for detecting the inflammatory/infectious processes but also for verifying if the abnormality noted on the other studies is indeed an inflammatory process.

Xenon-133

Xenon is an inert and relatively insoluble gas produced by the fission of uranium-235. Xenon is used in its radioactive form most commonly for ventilation studies. Xenon-133 ( ¹³³ Xe) has a physical half-life of 5.3 days and, in the face of normal pulmonary function, a biologic half-life of approximately 30 seconds.

The main disadvantages of ¹³³ Xe are the low photon abundance (36%) and low tissue penetration of the 81-keV gamma ray. The low photon energy generally mandates the initial use of the xenon—that is, before the administration of the technetium lung perfusion agent. Overlying soft tissue, such as breast tissue, can produce artifacts on the xenon images.

Gallium-67

Gallium-67 ( ⁶⁷ Ga) is used as gallium citrate. Although ⁶⁷ Ga 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.

⁶⁷ Ga is produced in a cyclotron from the parent zinc-68. ⁶⁷ Ga 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.

FIGURE 12-4, Decay scheme for gallium-67 ( 67 Ga). 67 Zn, Zinc-67.

The exact mechanism of uptake of ⁶⁷ Ga citrate is not precisely known. After intravenous administration of ⁶⁷ Ga, 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. Some uptake occurs in the lachrymal and salivary glands and the lactating breast, which 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; it utilizes the transferrin mechanism and responds to procedures such as 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:

Collimator
Scintillation crystal and optical coupling
Array of photomultiplier tubes
Signal processor, which analyzes the X-Y position of the signal
Pulse height analyzer
Computer integrated into the camera

FIGURE 12-5, Components of a gamma camera.

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, perioperative evaluation, and evaluation of right-to-left shunt.

Pulmonary Embolism

The incidence of pulmonary embolism (PE) and its detection have increased with the increasing frequency of long-distance travel and the consequent loss of mobility. Aging of the population and the increasing incidence of comorbidities such as cardiac and peripheral vascular (including venous) disease increase the likelihood of the occurrence of PE. There are many risk factors for deep vein thrombosis (DVT) and PE. It is well known that, among these risk factors, prolonged immobility, recent surgery, pregnancy, and underlying malignancy may actually initiate DVT.

PE is the third most common cause of death in the United States, with 650,000 instances of PE occurring each year. PE seems to present with a 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 undergo testing for PE.

Venous thrombosis, in contrast to arterial thrombosis, is caused by problems with the plasma clotting system. Minimal platelet participation is present in the venous versus the arterial process. Increasing evidence shows that an underlying coagulopathy may be responsible for spontaneous 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.

Radiopharmaceuticals and Techniques

The major function of the lungs is to effect the exchange of carbon dioxide (CO ₂ ) for oxygen (O ₂ ) from the blood. This exchange is accomplished by perfusion of the capillaries in the walls of the alveoli, where inspired air brings in O ₂ and is exchanged for CO ₂ in the deoxygenated blood. The CO ₂ in the alveoli is then discharged to the outside of the body via expiration. Both of these aspects of the respiratory anatomy and physiology are assessed in nuclear medicine. Pulmonary perfusion is assessed by the intravenous administration of ^99m Tc 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 a chest radiograph is normal and the patient has no history of smoking or lung disease. Because ^99m Tc is excreted in breast milk, the patient should be encouraged to express and store breast milk for 2 days until the radionuclide has decayed sufficiently.

Perfusion

^99m Tc 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 5 μ to 100 μ, with the majority measuring around 30 μ. The desired particle concentration can be obtained by diluting the kit with normal saline solution. 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 cause adverse coronary or cerebral events. For these patients, as well as pediatric patients, we recommend administration of a lower dose of particles (100,000 to 200,000).

^99m Tc MAA is produced by the addition of ^99m Tc pertechnetate to a sterile “cold kit” containing stannous albumin aggregates as lyophilized powder. ^99m Tc 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.

^99m Tc 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 sites of central venous access, such as Swan-Ganz catheters, should be avoided. The syringe should be gently agitated to prevent the MAA particles from settling out. 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 undergoes imaging in a sitting position, although images could be obtained with the patient supine. Ideally, the patient undergoes imaging with a large field-of-view 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.

FIGURE 12-6, Normal findings of a technetium-99m perfusion lung scan. Images show a standard six-view study: anterior, posterior, and left anterior oblique views (top row, left to right) , and left posterior oblique, right posterior oblique, and right anterior oblique views (bottom row, left to right) .

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

¹³³ Xe 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 tissue. 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 ¹³³ Xe. 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 O ₂ 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, which 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 perform the necessary breathing into a spirometer or a closed system.

FIGURE 12-7, Normal findings of a xenon-133 ( 133 Xe) ventilation lung scan. The ventilation is usually performed before the perfusion study. Because of the rapid clearance of lung activity of 133 Xe, a posterior view study is performed to maximize the area of the lung seen. Comparison with perfusion is less than optimal.

The initial/single breath reflects the regional ventilatory rate. The equilibrium phase depicts the aerated volume of the lungs, and 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.

Krypton-81m

Krypton-81m ( ^81m Kr) also has been used for ventilation imaging. The photon emissions of 176 and 192 keV and the short half-life of 13 seconds allow equilibrium imaging of the lungs in multiple projections. However, the short half-life precludes the ability to obtain single-breath and washout images. ^81m Kr is obtained from rubidium-81 ( ⁸¹ Rb), which has a half-life of 4.6 hours. Although krypton generators are available, the cost of the generator can be quite high because of the short half-life of ⁸¹ Rb. The activity administered is 1 to 10 mCi.

Radiolabeled Aerosols

Radiolabeled aerosols are the agents most often used to study ventilator function. Aerosol studies do not allow dynamic imaging. Although dynamic imaging may be of value in studying airways disease, it is not required in the suspected clinical setting of PE.

The most commonly used aerosol is ^99m Tc diethylene triamine pentaacetic 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 ^99m Tc 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 ^99m Tc DTPA as it is with xenon. The second major advantage of using ^99m Tc DTPA is that the imaging characteristics are ideal. Therefore, the ^99m Tc DTPA study can be performed either before or after the ^99m Tc MAA study. If the ventilation study is performed before the perfusion study, the amount of activity required is between 1 and 2 mCi. However, if the perfusion study is performed first, the number of counts accumulated for the ventilation study must be three to four times greater than for the perfusion study.

In the workup for PE, use of ^99m Tc DTPA aerosol is ideal, because 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. After inhalation, the technetium 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, and it is much faster in patients whose epithelial barrier may be deficient, as in patients with COPD or in smokers. The technetium 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 ).

FIGURE 12-8, Technetium-99m diethylene triamine pentaacetic acid aerosol images. Normal study findings show six views, and corresponding six views are obtained for perfusion. Comparable images make interpretation of a lung scan much easier than with a single posterior (Post) view xenon-133 study. Ant, Anterior; LAO, left anterior oblique; LPO, left posterior oblique; RAO, right anterior oblique; RPO, right posterior oblique.

Technegas

Technegas is composed of ultrafine particles of ^99m Tc-labeled carbon produced by combustion of pertechnetate at 2500°C in a graphite crucible. A Technegas generator is portable and produces fine images. The smaller particle size makes Technegas a better agent than technetium DTPA aerosol, particularly in patients with COPD.

Chest Radiograph

It is good practice to obtain a radiograph within 24 hours of performing the ventilation-perfusion (VQ) scan. It is preferable to have a chest radiograph for evaluation before performing the VQ scan ( Fig. 12-9 ). Having a full-inspiration posteroanterior (PA) and lateral chest radiograph available for interpretation would be ideal. However, a large percentage of the patients who are at risk for PE in the hospital or intensive care unit setting may be experiencing several other cardiopulmonary pathologic processes that could interfere with the reading of the VQ scan.

Symptomatology and chest radiograph findings in patients with PE are often nonspecific. Although Hampton’s hump and the Westermark sign, when found, are pathognomonic of PE; their absence on a chest radiograph does not denote the absence of pulmonary embolic. Additionally, in patients who are in intensive care, a portable chest radiograph is the first diagnostic procedure to be performed, but these radiographs do not have the quality of standing PA and lateral chest radiographs.

With the introduction of multidetector CT scanners, the majority of patients who need a PE workup undergo direct imaging with CT pulmonary angiography. In patients with impending renal compromise, CT angiography with use of contrast material may be risky. Increasingly, the CT angiogram has become the gold standard for diagnosis of PE. Clinical suspicion of PE is the most common indication for lung scanning. Although CT angiography has become the first method used in diagnosing PE, pulmonary scintigraphy is the method of choice for patients who are allergic to iodinated contrast material.

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 persons with acute PE. The PIOPED criteria were based on the use of xenon ventilation scans. With the development of CT pulmonary angiography, the algorithms proposed by the PIOPED study have had to be modified. Several guidelines have been used for interpreting VQ scintigraphy in the setting of increased risk for PE, including the McNeill, Biello, and PIOPED methods. The results of the VQ scan are reported as the probability of PE being present on the information used as a basis for the study—that is, high, intermediate/indeterminate, and low probability. William Klingensmith and Steve Holt (see Suggested Readings ) have proposed a physiologic approach to the interpretation of VQ scans that has the advantage of being intuitive, as opposed to other approaches.

The most important diagnostic feature of PE on VQ scans is the mismatched defect, when there is a perfusion defect but no abnormality on the ventilation scan. The finding of segmental perfusion defects is characteristic of a PE.

The following outline is a practical and simple algorithm for use in the workup of PE:

The first step is to obtain a chest radiograph for comparison with the VQ scans.

The second step is to scrutinize the perfusion scan for perfusion defects. These defects should be characterized on the basis of whether they are segmental/subsegmental or nonsegmental. Nonsegmental defects do not correspond anatomically to a segment and therefore are unlikely to be the result of a PE. If the defect appears to conform to a segment or a portion of a segment, we proceed to the next step.

The third step is to determine the size of the segmental perfusion defect. A classic segmental perfusion defect corresponds anatomically to a bronchopulmonary segment; these are pleural based and wedge shaped. The defect is categorized as large when it occupies 75% or more of the segment, moderate when it occupies 25% to 75% of the segment, and small when it occupies less than 25% of the segment.

The fourth step is to ascertain whether the segmental or subsegmental defects observed on the perfusion scan are matched on the ventilation study and the chest radiograph.

The fifth step is to discuss the likelihood of PE based on the scans in light of the pretest likelihood of PE. If no abnormalities are noted on the perfusion study, the study is considered normal. The likelihood of PE is less than 5%.

Unmatched perfusion defects are likely a result of acute or chronic PE. PEs are multiple in 90% of cases and bilateral in 85% of cases. In the first few days, the defects may disappear or become smaller. New defects may occur because of fragmentation. Changes in regional perfusion pressure could transform a partially obstructing clot into a fully obstructing clot.

The methods for ascertaining the likelihood of PE based on abnormal examinations have undergone changes, modifications, and iterations over the years. The probability of having a PE is determined by the size and the number of perfusion abnormalities and concomitant abnormalities (or absence of abnormalities) on the ventilation scan and chest radiographs. The following system of classification is used:

A high-probability scan has two or more large, mismatched segmental defects (or equivalents in moderate/large defects) with no abnormality on the ventilation study ( Fig. 12-10 ). In the clinical setting in which PE is highly likely, a high-probability VQ scan indicates a probability of PE greater than 90%. If the mismatched perfusion defects should resolve within days or weeks, the probability of a recent embolism is higher.

FIGURE 12-10, A high-probability lung scan with technetium-99m diethylene triamine pentaacetic acid aerosol and macroaggregated albumin. The superior segment of the right lower lobe and a major portion of the left lower lobe show perfusion deficit with good ventilation, a ventilation perfusion mismatch. Ant, Anterior; LAO, left anterior oblique; Lat, laterial; LPO, left posterior oblique; Post, posterior; RAO, right anterior oblique; RPO, right posterior oblique.

In a low-probability scan, the perfusion scans are smaller than 25% of a segment regardless of the results of the ventilation scan or appearance of the chest radiograph ( Fig. 12-11 ).

FIGURE 12-11, A xenon-133 ventilation study (A) and technetium-99m macroaggregated albumin study (B) show nonsegmental matching abnormalities, suggesting a low probability for pulmonary embolism.

An intermediate-probability scan is one that does not fit into the high or low categories.

A description of the abnormalities and whether they are accompanied by matched defects on the ventilation scan and correlate with the chest radiograph would make interpretation much easier. The descriptions we propose are as follows:

Mismatched abnormality —a defect observed on the perfusion scan is not seen on the ventilation study, and there is no corresponding abnormality on a chest radiograph. This presentation is characteristic of an uncomplicated PE in which the ventilatory architecture remains intact in the presence of a perfusion abnormality. A caveat to this presentation is when the vascular occlusion is incomplete. A partial occlusion may present as a mildly decreased perfusion, which is then labeled (erroneously) as a nonspecific finding. Additionally, the size of the vessel can affect the perfusion scan.
Complete match —a defect on the perfusion scan is matched by a defect on the ventilation scan without the presence of an infiltrate on the chest radiograph. The complete match of VQ abnormalities is commonly seen in patients with obstructive lung disease.
Triple match —there is complete matching of the VQ defects and a corresponding abnormality on the radiograph.
Reverse mismatch —the ventilatory abnormality is worse than the perfusion abnormality. This presentation can be seen with mucus plugging of the airways, atelectasis, and a right-to left shunt.
Circumferential and perifissural hypoperfusion— this presentation is seen with microemboli.

Repeat Scans

Because the perfusion picture can evolve over the ensuing weeks or months, it is advisable to repeat the study after 3 weeks. Defects persisting at 3 months are unlikely to resolve. The larger the defect and the older the patient, the less likely it is that the perfusion scan will revert to normal. In patients with diffuse lung disease, emboli are less likely to resolve completely. Patients with high-probability or intermediate-probability scans who have been treated for PE should undergo follow-up imaging after 3 months.

Lung scans are also of value in patients with a lung transplant to ascertain if the venous anastomosis has been compromised, especially while the patient is restricted to the intensive care unit.

Brain Death

CT and MRI are the modalities of choice for studying acute events involving the central nervous system. Scintigraphic brain perfusion studies are usually reserved for assessment of whether perfusion of the brain is effective. The harvesting of organs for transplantations requires that the diagnosis of irreversible cessation of brain function be made accurately and quickly. The requirement for alacrity of diagnosis is to prevent the organ degradation that occurs with death.

A second use of scintigraphy is to establish cerebrospinal fluid shunt patency, although establishing this patency rarely qualifies as an absolute emergency.

The diagnosis of brain death is primarily a clinical one; clinicians frequently rely on the patient being in a coma with a total absence of brainstem reflexes and spontaneous respiration, along with electrocerebral silence. The findings of death must be present for a finite period of observation (6 to 24 hours). States that mimic brain death include alcohol and barbiturate intoxication, sedative overdose, hypothermia, and hypoglycemic coma. In these instances, electrocerebral activity may drop to a level so low as to be undetectable. Additionally, the Lazarus sign (spinal reflexes and spontaneous movement of arms and shoulders that may be present after cessation of ventilation) may cause some confusion.

Confirmation of absent intracranial perfusion offers confirmation of brain death. This confirmation can be obtained by demonstrating the absence of intracranial perfusion and the absence of sagittal sinus activity after intravenous administration of tracer material. Occasionally the sagittal sinus may be perfused from the external carotid circulation ( Fig. 12-12 ).

FIGURE 12-12, Technetium-99m ethyl cysteinate dimer planar imaging study shows no perfusion and no delayed activity in the skull—the “empty skull” appearance. These findings are better seen with single photon emission computed tomography imaging of the brain if clinically feasible.

Brain death is diagnosed primarily clinically. However, complicating situations such as hypothermia and drug overdose may make a clinical or electroencephalogram (EEG) diagnosis difficult or impossible. Scintigraphic examinations are not affected by these conditions. Lack of perfusion on a radionuclide study is considered compatible with a diagnosis of brain death, more so than an isoelectric EEG. However, the actual pathophysiologic process producing the lack of cerebral perfusion on a scan is due to cerebral edema, which occurs because of elevation of intracranial pressures above systemic arterial pressure. It must be noted that the degree of cerebral edema from increased intracranial pressure that causes an absence of perfusion in itself carries a grave prognosis.

Patients being evaluated for brain death are usually in the intensive care unit. Transferring these patients to the imaging suite is often extremely difficult and quite labor intensive. Hence the use of scintigraphy for evaluation of brain perfusion, which can be obtained with ease at the patient’s bedside, is the first-line option.

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