++
The lungs, central nervous system (CNS), GI tract, and skeleton are the organ systems that are most amenable to diagnostic imaging. Disorders of the lungs and skeletal system are seen by plain radiography. For abdominal pathology, contrast studies and CT are more useful, although plain radiographs can diagnose intestinal obstruction, perforation, and radiopaque foreign bodies. Imaging of the CNS uses CT, MRI, and nuclear scintigraphy (PET and SPECT).
+++
Skeletal Changes Caused by Xenobiotics
++
A number of xenobiotics affect bone mineralization. Toxicologic effects on bone result in either increased or decreased density (Table 5–2). Some xenobiotics produce characteristic radiographic pictures, although exact diagnoses usually depend on correlation with the clinical scenario.10,145 Furthermore, alterations in skeletal structure develop gradually and are usually not visible unless the exposure continues for at least 2 weeks.
++
+++
Increase in Bone Density
++
Skeletal radiography may suggest the diagnosis of chronic lead poisoning even before the blood lead concentration is obtained. With lead poisoning, the metaphyseal regions of rapidly growing long bones develop transverse bands of increased density along the growth plate (Fig. 5–12).21,160,163,174 Characteristic locations are the distal femur and proximal tibia. Flaring of the distal metaphysis also occurs. Such lead lines are also seen in the vertebral bodies and iliac crest. Detected in approximately 80% of children with a mean lead concentration of 49 ± 17 µg/dL, lead lines usually occur in children between the ages of 2 and 9 years.21 In most children, it takes several weeks for lead lines to appear, although in very young infants (2–4 months old), lead lines may develop within days of exposure.221 After exposure ceases, lead lines diminish and may eventually disappear.
++
++
Lead lines are caused by the toxic effect of lead on bone growth and do not represent deposition of lead in bone. Lead impedes resorption of calcified cartilage in the zone of provisional calcification adjacent to the growth plate. This is termed chondrosclerosis.21,47 Other xenobiotics that cause metaphyseal bands are yellow phosphorus (Chap. 116), bismuth (Chap. 90), and vitamin D (Chap. 47).
++
Fluoride poisoning causes a diffuse increase in bone mineralization. Endemic fluorosis occurs where drinking water contains very high levels of fluoride (≥2 or more parts per million), as an occupational exposure among aluminum workers handling cryolite (sodium–aluminum fluoride), or with excessive tea drinking. The skeletal changes associated with fluorosis are osteosclerosis (hyperostosis deformans), osteophytosis, and ligament calcification (Fig. 5–13). Fluorosis primarily affects the axial skeleton, especially the vertebral column and pelvis. Thickening of the vertebral column may cause compression of the spinal cord and nerve roots. Without a history of fluoride exposure, the clinical and radiographic findings can be mistaken for osteoblastic skeletal metastases. The diagnosis of fluorosis is confirmed by histologic examination of the bone and measurement of fluoride levels in the bone and urine.22,210
++
++
Bisphosphonates such as alendronate (Fosamax) are commonly used to treat osteoporosis. They increase bone density by inhibiting osteoclast activity and decreasing bone resorption. However, by suppressing bone turnover and fracture healing, bisphosphonates are associated with accumulated microdamage to bone and skeletal weakening, which makes the bone vulnerable to fractures. Radiographically, there is thickening of the cortex of diaphyseal bone, typically the proximal femoral shaft. Such bone is associated with atypical proximal femoral shaft and subtrochanteric fractures after low-energy injuries such as a fall from standing. The fractures are transverse and have a characteristic “beaked” appearance caused by the cortical thickening (Fig. 5–14).
++
+++
Focal Loss of Bone Density.
++
Skeletal disorders associated with focal diminished bone density (or mixed rarefaction and sclerosis) include osteonecrosis, osteomyelitis, and osteolysis. Osteonecrosis, also known as avascular necrosis, most often affects the femoral head, humeral head, and proximal tibia.127 There are many causes of osteonecrosis. Xenobiotic causes include long-term corticosteroid use and alcoholism. Radiographically, focal skeletal lucencies and sclerosis are seen, ultimately with loss of bone volume and collapse (Fig. 5–15A).
++
++
Acroosteolysis is bone resorption of the distal phalanges and is associated with occupational exposure to vinyl chloride monomer. Protective measures have reduced its incidence since it was first described in the early 1960s.164
++
Osteomyelitis is a serious complication of injection drug use. It usually affects the axial skeleton, especially the vertebral bodies, as well as the sternomanubrial and sternoclavicular joints (Figs. 5–15B and C).74,79 Back pain or neck pain in injection drug users warrants careful consideration. A spinal epidural abscess causing spinal cord compression may accompany vertebral osteomyelitis.92,125 Radiographic findings are negative early in the disease course before skeletal changes are visible and the diagnosis is confirmed by MRI or CT (Fig. 5–15D).
++
Certain abnormalities in soft tissues, predominantly as a consequence of infectious complications of injection drug use, are amenable to radiographic diagnosis.74,75,79,99,198 In an injection drug user who presents with signs of local soft tissue infections, radiography is indicated to detect a retained metallic foreign body, such as a needle fragment, or subcutaneous gas, as may be seen in a necrotizing soft tissue infection such as necrotizing fasciitis. CT is more sensitive at detecting soft tissue gas than is conventional radiography. CT and ultrasonography can also detect subcutaneous or deeper abscesses that require surgical or percutaneous drainage.
+++
Pulmonary and Other Thoracic Problems
++
Many xenobiotics that affect intrathoracic organs produce pathologic changes that can be detected on chest radiographs.9,12,24,49,63,75,140,172,219 The lungs are most often affected, resulting in dyspnea or cough, but the pleura, hilum, heart, and great vessels may also be involved.6 Patients with chest pain may have a pneumothorax, pneumomediastinum, or aortic dissection. Patients with fever, with or without respiratory symptoms, may have a focal infiltrate, pleural effusion, or hilar lymphadenopathy.
++
Chest radiographic findings may suggest certain diseases, although the diagnosis ultimately depends on a thorough clinical history. When a specific xenobiotic exposure is known or suspected, the chest radiograph can confirm the diagnosis and help in assessment. If a history of xenobiotic exposure is not obtained, a patient with an abnormal chest radiograph may initially be misdiagnosed as having pneumonia or another disorder that is more common than xenobiotic-mediated lung disease.166 Therefore, patients with chest radiographic abnormalities should be carefully questioned regarding possible xenobiotic exposures at work or at home, as well as the use of medications or other drugs.
++
Many pulmonary disorders are radiographically detectable because they result in fluid accumulation within the normally air-filled lung. Fluid may accumulate within the alveolar spaces or interstitial tissues of the lung, producing the two major radiographic patterns of pulmonary disease: airspace filling and interstitial lung disease (Table 5–3). Most xenobiotics are widely distributed throughout the lungs and produce a diffuse rather than a focal radiographic abnormality.
++
+++
Diffuse Airspace Filling.
++
Overdose with various xenobiotics, including salicylates, opioids, and paraquat, may cause acute respiratory distress syndrome (ARDS) (formerly known as noncardiogenic pulmonary edema or acute lung injury) with or without diffuse alveolar damage and characterized by leaky capillaries (Fig. 5–16).75,85,89,123,184,191,218 There are, of course, many other causes of ARDS, including sepsis, anaphylaxis, and major trauma.213 Other xenobiotic exposures that may result in diffuse airspace filling include inhalation of irritant gases that are of low water solubility such as phosgene (COC12), nitrogen dioxide (silo filler’s disease), chlorine, hydrogen sulfide, and sulfur dioxide (Chaps. 124 and 126).79,102 Organic phosphorus insecticide poisoning causes cholinergic hyperstimulation, resulting in bronchorrhea (Chap. 113). Smoking “crack” cocaine is associated with diffuse alveolar hemorrhage (Chap. 78).60,75,79,165,219
++
+++
Focal Airspace Filling.
++
Focal infiltrates are usually caused by bacterial pneumonia, although aspiration of gastric contents also causes localized airspace disease.75,195 Aspiration may occur during sedative–hypnotic or alcohol intoxication or during a seizure. During ingestion, low-viscosity hydrocarbons often enter the lungs while they are being swallowed (Figs. 5–17 and 108–1). There may be a delay in the development of radiographic abnormalities, and the chest radiograph may not appear to be abnormal until 6 hours after the ingestion.8 During aspiration, the most dependent portions of the lung are affected. When the patient is upright at the time of aspiration, the lower lung segments are involved. When the patient is supine, the posterior segments of the upper and lower lobes are affected.62
++
+++
Multifocal Airspace Filling.
++
Multifocal airspace filling occurs with septic pulmonary emboli, which is a complication of injection drug use and right-sided bacterial endocarditis. The foci of pulmonary infection often undergo necrosis and cavitation (Fig. 5–18).75,79
++
+++
Interstitial Lung Diseases.
++
Toxicologic causes of interstitial lung disease include hypersensitivity pneumonitis, use of medications with direct pulmonary toxicity, and inhalation or injection of inorganic particulates.75 Interstitial lung diseases may have an acute, subacute, or chronic course. On the chest radiograph, acute and subacute disorders cause a fine reticular or reticulonodular pattern (Fig. 5–19). Chronic interstitial disorders cause a coarse reticular “honeycomb” pattern.
++
+++
Hypersensitivity Pneumonitis.
++
Hypersensitivity pneumonitis is a delayed-type hypersensitivity reaction to an inhaled or ingested allergen.40,96,166 Inhaled organic allergens such as those in moldy hay (farmer’s lung) and bird droppings (pigeon breeder’s lung) cause hypersensitivity pneumonitis in sensitized individuals. There are two clinical syndromes: an acute, recurrent illness and a chronic, progressive disease. The acute illness presents with fever and dyspnea. In these cases, the chest radiograph findings are normal or may show fine interstitial or alveolar infiltrates. Chronic hypersensitivity pneumonitis causes progressive dyspnea, and the radiograph shows interstitial fibrosis.
++
The most common medication causing hypersensitivity pneumonitis is nitrofurantoin. Respiratory symptoms occur after taking the medication for 1 to 2 weeks. Other medications that may cause hypersensitivity pneumonitis include sulfonamides and penicillins.
++
Various chemotherapeutic agents, such as busulfan, bleomycin, cyclophosphamide, and methotrexate, cause pulmonary injury by their direct cytotoxic effect on alveolar cells.39,65 The radiographic pattern is usually interstitial (reticular or nodular) but may include airspace filling or mixed patterns. The patient presents with dyspnea, fever, and pulmonary infiltrates that begin after several weeks of therapy. Other causes of these clinical and radiographic findings must be considered, including opportunistic infection, pulmonary carcinomatosis, pulmonary edema, and intraparenchymal hemorrhage. Symptoms usually resolve with discontinuation of the offending medication.
++
Amiodarone toxicity causes phospholipid accumulation within alveolar cells and may result in pulmonary fibrosis. An interstitial radiographic pattern is seen, although airspace filling may also occur (Fig. 5–19) (Chap. 64).
++
Inhaled inorganic particulates, such as asbestos, silica, and coal dust, cause pneumoconiosis. This is a chronic interstitial lung disease characterized by interstitial fibrosis and loss of lung volume.32,138,167,215 IV injection of illicit xenobiotics that have particulate contaminants, such as talc, causes a chronic interstitial lung disease known as talcosis.1,55,212
++
Asbestos-related calcified pleural plaques develop many years after asbestos exposure (Fig. 5–20). These lesions do not cause clinical symptoms and have only a minor association with malignancy and interstitial lung disease. Asbestos-related pleural plaques should not be called asbestosis because that term refers specifically to the interstitial lung disease caused by asbestos. Pleural plaques must be distinguished from mesotheliomas, which are not calcified, enlarge at a rapid rate, and erode into nearby structures such as the ribs.
++
++
Pleural effusions occur with drug-induced systemic lupus erythematosus (SLE).140 The medications most frequently implicated are procainamide, hydralazine, isoniazid, and methyldopa. The patient presents with fever as well as other symptoms of SLE.
++
Pneumothorax and pneumomediastinum are associated with illicit drug use. These complications are related to the route of administration rather than to the particular drug. Barotrauma associated with the Valsalva maneuver or intense inhalation with breath holding during the smoking of “crack” cocaine or marijuana results in pneumomediastinum (Fig. 5–21A).20,50,75,150 Pneumomediastinum is one cause of cocaine-related chest pain that can be diagnosed by chest radiography. Forceful vomiting after ingestion of syrup of ipecac or alcohol may produce a Mallory-Weiss syndrome, pneumomediastinum, and mediastinitis (Boerhaave syndrome).220 IV drug users who attempt to inject into the subclavian and internal jugular veins may cause a pneumothorax.46
++
++
Phenytoin may cause drug-induced lymphoid hyperplasia with hilar lymphadenopathy.140 Chronic beryllium exposure results in hilar lymphadenopathy that mimics sarcoidosis, with granulomatous changes in the lung parenchyma. Silicosis is associated with “eggshell” calcification of hilar lymph nodes.
+++
Cardiovascular Abnormalities.
++
Dilated cardiomyopathy occurs in chronic alcoholism and exposure to cardiotoxic medications such as doxorubicin (Adriamycin). Enlargement of the cardiac silhouette may also be caused by a pericardial effusion, which may accompany drug-induced SLE. Aortic dissection is associated with use of cocaine and amphetamines.66,75,114,152,162 The chest radiograph may show an enlarged or indistinct aortic knob and an ascending or descending aorta (Figs. 5–21B to D).
++
Abdominal imaging modalities include conventional radiography, CT, GI contrast studies, and angiography.68 Conventional radiography is limited in its ability to detect most intraabdominal pathology because most pathologic processes involve soft tissue structures that are not well seen. Plain radiography readily visualizes gas in the abdomen and is therefore usable to diagnose pneumoperitoneum (free intraperitoneal air) and bowel distension caused by mechanical obstruction or diminished gut motility (adynamic ileus). Other abnormal gas collections, such as intramural gas associated with intestinal infarction, are seen infrequently (Table 5–4).73,120,128,137,186
++
++
GI perforation is diagnosed by seeing free intraperitoneal air under the diaphragm on an upright chest radiograph. Peptic ulcer perforation is associated with crack cocaine use.2,29,107 Esophageal or gastric perforation (or tear) can be a complication of forceful emesis induced by syrup of ipecac or alcohol intoxication or attempted placement of a large-bore orogastric tube (Fig. 5–22).220 Esophageal and gastric perforation may also occur after the ingestion of caustics such as iron, alkali, or acid.103 Esophageal perforation causes pneumomediastinum and mediastinitis.
++
+++
Obstruction and Ileus.
++
Both mechanical bowel obstruction and adynamic ileus (diminished gut motility) cause bowel distension. With mechanical obstruction, there is a greater amount of intestinal distension proximal to the obstruction and a relative paucity of gas and intestinal collapse distal to the obstruction. In adynamic ileus, the bowel distension is relatively uniform throughout the entire intestinal tract. On the upright abdominal radiograph, both mechanical obstruction and adynamic ileus show air-fluid levels. In mechanical obstruction, air-fluid levels are seen at different heights and produce a “stepladder” appearance.
++
Mechanical bowel obstruction may be caused by large intraluminal foreign bodies such as a body packer’s packets or a medication bezoar.64,197 Adynamic ileus may result from the use of opioids, anticholinergics, and tricyclic antidepressants (Fig. 5–23).15,68 Because adynamic ileus occurs in many diseases, the radiographic finding of an ileus is not helpful diagnostically. When the distinction between obstruction and adynamic ileus cannot be made based on the abdominal radiographs, abdominal CT can clarify the diagnosis.135
++
++
In most patients with intestinal ischemia, plain abdominal radiographs show only a nonspecific or adynamic ileus pattern. In a small proportion of patients with ischemic bowel (5%), intramural gas is seen.15 Rarely, gas is also seen in the hepatic portal venous system. CT is better able to detect signs of mesenteric ischemia, particularly bowel wall thickening (Fig. 5–24).14
++
++
Intestinal ischemia and infarction may be caused by use of cocaine; other sympathomimetics; and the ergot alkaloids, all of which induce mesenteric vasoconstriction.79,110,130 Calcium channel blocker overdoses cause splanchnic vasodilation and hypotension that may result in intestinal ischemia. Superior mesenteric vein thrombosis may be caused by hypercoagulability associated with chronic oral contraceptive use.
+++
Gastrointestinal Hemorrhage and Hepatotoxicity.
++
Radiography is not usually helpful in the diagnosis of such common abdominal complications as GI bleeding and hepatotoxicity.
++
The now obsolete radiocontrast agent thorium dioxide (Thorotrast; thorium, atomic number 90) provides a unique example of pharmaceutical-induced hepatotoxicity. It was used as an angiographic contrast agent until 1947, when it was found to cause hepatic malignancies. The radioactive isotope of thorium has a half-life of 400 years. It accumulates within the reticuloendothelial system and remains there for the life of the patient. It had a characteristic radiographic appearance, with multiple punctate opacities in the liver, spleen, and lymph nodes (Fig. 5–25). Patients who received thorium before its removal from the market may still present with hepatic malignancies.18,204
++
+++
Contrast Esophagram and Upper Gastrointestinal Series.
++
Ingestion of a caustic may cause severe damage to the mucosal lining of the esophagus. This can be demonstrated by a contrast esophagram. However, in the acute setting, upper endoscopy should be performed rather than an esophagram because it provides more information about the extent of injury and prognosis.111 In addition, administration of barium will coat the mucosa, making endoscopy difficult. For later evaluation, a contrast esophagram identifies mucosal defects, scarring, and stricture formation (Figs. 5–26 and 106–4).129
++
++
The choice of radiographic contrast agent (barium or water-soluble material) depends on the clinical situation. If the esophagus is severely strictured and there is a risk of aspiration, barium should be used because water-soluble contrast material is damaging to the pulmonary parenchyma. If, on the other hand, esophageal or gastric perforation is suspected, water-soluble contrast is safer because extravasated barium is highly irritating to mediastinal and peritoneal tissues, but extravasated water-soluble contrast is gradually absorbed into the circulation.
++
Ingested foreign bodies may cause esophageal and gastric outlet obstruction. Esophageal obstruction caused by a drug packet can be demonstrated by a contrast esophagram. Concretions of ingested material in the stomach may cause gastric outlet obstruction. This has been reported with potassium chloride tablets and enteric-coated aspirin.11,185
+++
Abdominal Computed Tomography.
++
CT provides great anatomic definition of intraabdominal organs and plays an important role in the diagnosis of a wide variety of abdominal disorders. In most cases, both oral and IV contrast are administered. Oral contrast delineates the intestinal lumen. IV contrast is needed to reliably detect lesions in hepatic and splenic parenchyma, the kidneys, and the bowel wall.
++
Certain abdominal complications of poisonings are amenable to CT diagnosis. Intestinal ischemia causes bowel wall thickening; intramural hemorrhage; and at a later stage, intramural gas and hepatic portal venous gas (Fig. 5–24).14 Hepatic portal venous gas can also be seen after ingestion of 3% hydrogen peroxide. Splenic infarction and splenic and psoas abscesses are complications of IV drug use that may be diagnosed on CT.15 Radiopaque foreign substances such as intravenously injected elemental mercury may be detected and accurately localized by CT.126 Radiolucent foreign bodies, such as a body packer’s packets, may be detected by using enteric contrast.83,85
++
Angiography may detect such complications of injection drug use as venous thrombosis and arterial laceration causing pseudoaneurysm formation (Figs. 5–27 and 5–28). IV injection of amphetamine, cocaine, or ergotamine causes necrotizing angiitis that is associated with microaneurysms, segmental stenosis, and arterial thrombosis. These lesions are seen in the kidneys, small bowel, liver, pancreas, and cerebral circulation (Fig. 5–29).34,161 Complications include aneurysm rupture and visceral infarction. Renal lesions cause severe hypertension and acute kidney injury.175
++
++
++
++
Diagnostic imaging studies have revolutionized the management of CNS disorders.57,71 Both acute brain lesions and chronic degenerative changes can be detected (Table 5–5).118 Some xenobiotics have a direct toxic effect on the CNS; others indirectly cause neurologic injury by causing hypoxia, hypotension, hypertension, cerebral vasoconstriction, head trauma, or infection.
++
++
CT can directly visualize brain tissue and many intracranial lesions.70 CT is the imaging study of choice in the emergency setting because it readily detects acute intracranial hemorrhage as well as parenchymal lesions that are causing mass effect. CT is fast, is widely available on an emergency basis, and can accommodate critical support and monitoring devices. Infusion of IV contrast further delineates intracerebral mass lesions such as tumors and abscesses.
++
MRI has largely supplanted CT in nonemergency neurodiagnosis. It offers better anatomic discrimination of brain tissues and areas of cerebral edema and demyelination. However, MRI is no better than CT in detecting acute blood collections or mass lesions. In the emergency setting, the disadvantages of MRI outweigh its strengths. MRI is usually not readily available on an emergency basis, image acquisition time is long, and critical care supportive and monitoring devices are often incompatible with MR scanning machines.121
++
Nuclear scintigraphy that uses CT technology (SPECT and PET) is being used as a tool to elucidate functional characteristics of the CNS. Examples include both immediate and long-term effects of various xenobiotics on regional brain metabolism, blood flow, and neurotransmitter function.115,154,207
+++
Emergency Head Computed Tomography Scanning.
++
An emergency noncontrast head CT scan is obtained to detect acute intracranial hemorrhage and focal brain lesions causing cerebral edema and mass effect. Patients with these lesions present with focal neurologic deficits, seizures, headache, or altered mental status. Toxicologic causes of intraparenchymal and subarachnoid hemorrhage include cocaine and other sympathomimetics (Fig. 5–30).113,117 Cocaine-induced vasospasm may cause ischemic infarction, although this is not well seen by CT until 6 to 24 or more hours after onset of the neurologic deficit (Fig. 5–31). Drug-induced CNS depression, most commonly ethanol intoxication, predisposes the patient to head trauma, which may result in a subdural hematoma or cerebral contusion (Fig. 5–32). Toxicologic causes of intracerebral mass lesions include septic emboli complicating injection drug use and HIV-associated CNS toxoplasmosis and lymphoma (Fig. 5–33).19,74,79,149 On a contrast CT, such tumors and focal infections exhibit a pattern of “ring enhancement.”
++
++
++
++
+++
Xenobiotic-Mediated Neurodegenerative Disorders.
++
A number of xenobiotics directly damage brain tissue, producing morphologic changes that may be detectable using CT and MRI. Such changes include generalized atrophy, focal areas of neuronal loss, demyelinization, and cerebral edema. Imaging abnormalities may help establish a diagnosis or predict prognosis in a patient with neurologic dysfunction after a xenobiotic exposure. In some cases, the imaging abnormality will suggest a toxicologic diagnosis in a patient with a neurologic disorder in whom a xenobiotic exposure was not suspected clinically.4,13,57,100,104,155,165,214
++
Ethanol is the most widely used neurotoxin. With long-term ethanol use, there is a widespread loss of neurons and resultant atrophy. In some individuals with alcoholism, the loss of brain tissue is especially prominent in the cerebellum. However, the amount of cerebral or cerebellar atrophy does not always correlate with the extent of cognitive impairment or gait disturbance.42,67,84,86,106,209,211 Chronic solvent exposure, such as to toluene (occupational and illicit use), also causes diffuse cerebral atrophy.93,171
+++
Focal Degenerative Lesions.
++
Carbon monoxide poisoning produces focal degenerative lesions in the brain. In about half of patients with severe neurologic dysfunction after carbon monoxide poisoning, CT scans show bilateral symmetric lucencies in the basal ganglia, particularly the globus pallidus (Figs. 5–34 and 125–1).27,94,100,141,155,158,159,177,178,182,200,206 The basal ganglia are especially sensitive to hypoxic damage because of their limited blood supply and high metabolic requirements. Subcortical white matter lesions also occur after carbon monoxide poisoning. Although less frequent than lesions of the basal ganglia, white matter lesions are more clearly associated with a poor neurologic outcome. MRI is more sensitive than CT at detecting these white matter abnormalities.27,57,104,159,200
++
++
Basal ganglion lucencies, white matter lesions, and atrophy are caused by other xenobiotics such as methanol,12,41,69,82,142,173 ethylene glycol, cyanide,58,139 hydrogen sulfide, inorganic and organic mercury,131 manganese,13,190 heroin,104,108 barbiturates, chemotherapeutic agents, solvents such as toluene,57,93,171,50,83,156 and podophyllin.28,144 Nontoxicologic disorders may cause similar imaging abnormalities, including hypoxia, hypoglycemia, and infectious encephalitis.82,88
+++
Nuclear Scintigraphy.
++
Whereas both CT and MRI display cerebral anatomy, nuclear medicine studies provide functional information about the brain. Nuclear scintigraphy uses radioactive isotopes that are bound to carrier molecules (ligands). The choice of ligand depends on the biologic function being studied. Brain cells take up the radiolabeled ligand in proportion to their physiologic activity or the regional blood flow. The radioactive emission from the isotope is detected by a scintigraphic camera, which produces an image showing the quantity and distribution of tracer. Better anatomic detail is provided by using CT techniques to generate cross-sectional images. There are two such technologies: SPECT and PET. These imaging modalities are used in the research and clinical settings to study the neurologic effects of particular xenobiotics and the mechanisms of xenobiotic-induced neurologic dysfunction.
++
SPECT uses conventional isotopes such as technetium-99m and iodine-123.115 These isotopes are bound to ligands that are taken up in the brain in proportion to regional blood flow, reflecting the local metabolic rate.
++
PET uses radioactive isotopes of biologic elements such as carbon-11, oxygen-15, nitrogen-13, and fluoride-18 (a substitute for hydrogen).154 These radioisotopes have very short half-lives so that PET scanning requires an onsite cyclotron to produce the isotope. The isotopes are incorporated into molecules such as glucose, oxygen, water, various neurotransmitters, and drugs. Labeled glucose is taken up in proportion to the local metabolic rate for glucose. Uptake of labeled oxygen demonstrates the local metabolic rate for oxygen. Labeled neurotransmitters generate images reflecting their concentration and distribution within the brain.
++
Both PET and SPECT have been used to study the effects of various xenobiotics on cerebral function. For example, although both CT and MRI can detect cerebellar atrophy in individuals with chronic alcoholism, there is a poor correlation between the magnitude of cerebellar atrophy and the clinical signs of cerebellar dysfunction. PET scans may demonstrate diminished cerebellar metabolic rate for glucose, which correlates more accurately with the patient’s clinical status.72,209
++
In patients with severe neurologic dysfunction after carbon monoxide poisoning, SPECT regional blood flow measurements show diffuse hypometabolism in the frontal cortex.30 In one patient, severe perfusion abnormalities improved slightly over several months in proportion to the patient’s gradual clinical improvement.98 In another patient treated with hyperbaric oxygen, a SPECT scan revealed increased blood flow in the frontal lobes, although the blood flow still remained significantly less than normal.124
++
In patients who chronically use cocaine, SPECT blood flow scintigraphy demonstrates focal cortical perfusion defects. The extent of these perfusion defects correlates with the frequency of drug use. Focal perfusion defects probably represent local vasculitis or small areas of infarction.92,202 PET scanning has been used to demonstrate the effects of cocaine on cerebral blood flow and regional glucose metabolism. PET neurotransmitter studies show promise in elucidating potential mechanisms of action of cocaine. Using radiolabeled dopamine analogs, downregulation of dopamine (D2) receptors has been noted after a cocaine binge. This finding may be responsible for cocaine craving that occurs during cocaine withdrawal. Using11 C-labeled cocaine, uptake of cocaine can be demonstrated in the basal ganglia, a region rich in dopamine receptors.207
++
Much has been learned about these imaging modalities, and initial applications can be applied to patient care. These imaging modalities are capable of demonstrating abnormalities in many patients with xenobiotic exposures, although other patients with significant cerebral dysfunction have normal study findings.