The pulmonary vascular tree processes the entire volume of the body's blood circulation. This system is affected primarily and secondarily by cardiac and noncardiac disorders. Its relative inaccessibility for physical examination requires investigation with other means, primarily radiologic examinations.
Radiologic modalities used for assessment include lung scintigraphy, digital subtraction pulmonary angiography (DSPA), pulmonary computed tomography angiography (PCTA), and pulmonary magnetic resonance angiography (PMRA). These modalities are the methods most commonly used to study the pulmonary circulation, although central pulmonary arterial pathology may be seen with chest radiography and transesophageal echocardiography. [1, 2, 3, 4, 5, 6, 7]
See the images below.
Lung scintigraphy may serve for screening or as a definitive final test, depending on the indication. This technique provides functional vascular and airway detail, and it may aid in targeting pulmonary angiograms in the abnormal lung or lobe.
Lung scintigraphy requires the injection and inhalation of radionuclide agents. Examinations are prolonged, and the findings are most often nondiagnostic for pulmonary embolism (PE).
The interpretation of lung scintigraphic results is based on the presence of photopenic defects on the images. The scintigrams are acquired after the inhalation of a ventilation agent and the intravenous injection of a perfusion agent, by making use of the radioactive decay of the radionuclides. Ventilation agents include xenon-133, xenon-127, krypton-81m, technetium-99m diethylenetriamine aerosol, and, rarely, carbon dioxide tracers. This agent is usually administered before the injection of the perfusion agent to prevent its interference with higher-energy99m Tc. The patient inhales the agent via a mouthpiece with a disposable breathing unit.
For perfusion, the 2 agents used are99m Tc macroaggregated albumin (MAA) and99m Tc human-albumin microspheres. The former is the most common. Scintigraphic images of the lungs are obtained on the basis of the temporary occlusion of approximately 0.22% of the capillaries by trapping of the MAA particles.
Ventilation/perfusion (V/Q) mismatches and/or perfusion defects connote pulmonary parenchymal (related to airways) and vascular pathology (see the images below). These results are interpreted in conjunction with any chest radiographic abnormality, especially when the probability of PE is assigned. Currently, the most common classification used for PE is the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria, which are based on the largest study of PE to date. 
Other indications for an examination for PE and other diagnosable intrathoracic pathologies include airway disease (asthma, emphysema, bronchiectasis), congenital pulmonary disease (absent lung), vasculitis, vascular compression (pulmonary fibrosis, benign and malignant neoplasms, aortic aneurysm/dissection), and altered pulmonary circulation (absence or hypoplasia of the pulmonary artery, bronchopulmonary sequestration, congestive heart failure, mitral valvular disease).
Digital Subtraction Pulmonary Angiography
Digital subtraction pulmonary angiography (DSPA) is the criterion standard or definitive test in evaluating diseases involving the pulmonary vasculature. The technique allows visualization of all pulmonary arterial branches. It allows catheter-based measurement of pulmonary artery pressure, and it may be used for therapeutic intervention.
Such interventions include foreign body retrieval, most commonly embolized fractured catheters; catheter-directed thrombofragmentation and embolectomy for PE; and transcatheter embolization for the treatment of pulmonary arteriovenous malformations (AVMs) and pulmonary arterial pseudoaneurysms.
The technique requires percutaneous venous catheterization, intracardiac catheter manipulation, and catheterization of the pulmonary artery. Ionizing radiation and iodinated contrast agents are used to produce images of the pulmonary arteries and veins. The associated potential complications accentuate the relative invasiveness of this procedure. However, DSPA remains the criterion standard for the diagnosis of PE and for the evaluation of many pulmonary vascular disorders.
DSPA is the criterion standard in the diagnosis of PE and other arterial and venous disorders (see the images below). Currently, conventional or cut-film angiography is not used. The method is time consuming and labor intensive, and it requires the use of a relatively large amount of contrast material.
This method has been supplanted by digital subtraction angiography. This procedure can be performed rapidly and safely with minimal discomfort to the patient. Some older reports in the literature emphasize the risks of the procedure, which led to its underuse in some institutions. In 1982, Sostman et al demonstrated that 434 (72%) of 600 patients in a university hospital for whom scintigraphy results suggested PE, only 50 (12%) underwent pulmonary angiography. 
In another study in a university hospital, 525 (81%) of 650 patients who underwent V/Q scanning had results suggestive of PE. Only 71 (14%) of the 525 patients underwent pulmonary angiography. At the same hospital, 17 (16%) of 109 patients with low-probability scans and 31 (30%) of 102 patients with moderate-probability scans received anticoagulants without undergoing additional imaging. [10, 11]
These investigative studies provide a historical perspective; spiral CT is currently regarded as the primary imaging modality for the diagnosis of acute PE. The PIOPED II study that is now in progress specifically aims to "determine the sensitivity, specificity, positive predictive value, and negative predictive value of contrast-enhanced spiral CT for the diagnosis of acute PE" (Kyung J. Cho, personal communication, June 2002).
Most of the concern is related to the passage of the catheter through the heart with the possible induction of cardiac arrhythmias. Although premature atrial and ventricular contractions routinely occur when a catheter is advanced through the right side of the heart, sustained arrhythmias requiring treatment are extremely uncommon. Physical maneuvers, such as having the patient cough or performing carotid massage, may easily and quickly cause the cardiac rhythm to revert to normal. However, pharmacologic agents and facilities for cardiopulmonary resuscitation, including cardiac defibrillation, should be readily available.
At the author's institution, a crash cart always is left next to the door of the angiography room during pulmonary angiography. Catheters that cause less traumatic effects and that are more easily controlled have reduced the manipulation required to catheterize the pulmonary arteries. With these, the risk of cardiac perforation has essentially been eliminated. 
DSPA can be performed by using many venous approaches. The right common femoral vein is the vessel most commonly chosen. The jugular vein or an upper-arm vein may also be used. Preferably, the injection is made within each of the main pulmonary arterial branches and is positioned so as to allow all of the lobes of one lung to be well opacified. More selective injections may be performed when needed, although with a smaller volume of contrast agent and decreased injection pressure. Rapid-sequence images are acquired in multiple anteroposterior and oblique projections, depending on the indications of the study.
The rigidity and maneuverability of a 7F pigtail catheter makes it the standard choice. The shape virtually eliminates perforation of the vessel wall, and its distal side and end holes allow the rapid delivery of a bolus of contrast agent without any significant risk to the vessel wall. The stiff end of a routine guidewire is shaped and advanced to near the apex of the pigtail; it is directed across the tricuspid and pulmonic valves from the right atrium. Some interventional radiologists prefer the Grollman catheter, with its smaller and angled pigtail design. Other catheters currently in use are also designed with a distal curve and a small pigtail tip.
In a large series of pulmonary arteriograms, the most significant complication was acute cor pulmonale. Though uncommon, this was almost always related to a history of pulmonary hypertension. The only deaths that occurred (0.2% of patients) were in patients with severe pulmonary hypertension (>70 mm Hg) who had a profound decrease in blood pressure after the injection of contrast medium. This was followed by apnea and cardiac arrest, and death ensued despite resuscitative efforts. 
Therefore, pulmonary artery pressure should be measured before the injection of contrast material. If the pressure is severely elevated (>60-70 mm Hg), it may be prudent to discontinue the examination. However, in this patient population, pulmonary angiography can be performed more safely by tailoring the examination to the individual patient. Distal main or lobar pulmonary artery injections with reduced flow rates can target the site of suspected abnormality.
Experimental evidence shows that the hypertonicity of the contrast agent causes the elevation in pulmonary artery and right ventricular pressures. Hence, the use of nonionic agents may prove to be safer in this regard. The wide array of contrast media available, including iso-osmolar and hypo-osmolar ionic and nonionic agents, allows the physician to tailor the examination to the individual patient. 
Other major risk factors in pulmonary angiography include the presence of a left bundle branch block, a history of ventricular irritability, or a recent myocardial infarction. In the presence of a left bundle branch block, the transient right bundle branch block that may occur when the catheter is passed through the right heart may result in complete heart block. The electrical system on the right side of the heart is often irritated during catheter and guidewire manipulation, especially in the right ventricle. Another important risk factor is a severe elevation in pulmonary arterial pressure. Therefore, a temporary pacemaker should be in place before the procedure is performed. In the population with these conditions, use of DSPA should be questioned, because PCTA and PMRA are feasible alternatives. 
Although pulmonary angiography has morbidity (2-5%) and mortality (0.2%) rates lower than those of empiric anticoagulation (5-25% and 1-2%, respectively), it has not gained widespread acceptance, and it is not universally available. Although pulmonary angiography remains the criterion standard, the operator dependency in radiographic interpretation remains a concern. The rate of interobserver variability can approach 10-15%, and it may be even higher in the examination of smaller vessels. In the PIOPED study, angiographers agreed on whether subsegmental emboli were present in only 66% of patients. [16, 17, 18, 19]
Pulmonary Computed Tomography Angiography
In pulmonary computed tomography angiography (PCTA), contrast material can be injected via a peripheral intravenous line. [1, 2, 3] PCTA allows the detection of alternative or concomitant intrathoracic pathology, and it permits multiplanar reconstruction. CT venography (CTV) may be performed concomitantly with PCTA.
PCTA requires the use of ionizing radiation and iodinated contrast agents. It lacks sensitivity in the detection of subsegmental embolic disease, and its spatial resolution is lower than that of DSPA.
The advent of more-rapid image acquisition with helical, or spiral, CT has increased the resolution and detection rate of pulmonary vascular abnormalities. This improvement has led to a precipitous decrease in the number of digital subtraction pulmonary angiography (DSPA) procedures performed in many hospitals.
At this time, academic debate continues regarding whether helical CT is better than lung scintigraphy in screening for PE: lung scintigraphy versus helical CT. In addition, as a result of the less invasive nature and the capability for multiplanar reconstruction, PCTA has progressively replaced DSPA as the standard diagnostic modality in imaging the pulmonary circulation, especially for the evaluation of PE. However, because of its lack of sensitivity in detecting subsegmental emboli (fourth-order pulmonary arterial branches and smaller), DSPA has remained the standard with regard to PE (see the images below).
The clinical significance of such embolic disease is a subject of debate. Some investigators argue that subsegmental PE disease is of little clinical importance, at least for patients whose cardiopulmonary reserve is not limited by preexisting related disease. In the PIOPED study, with only 66% interobserver agreement for small PEs, subsegmental emboli must have remained undetected and untreated in many patients. In all patients in the PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) study who did not receive treatment, only 0.6% had symptoms of PE at 1-year follow-up. In the same study, 150 patients with low-probability or near-normal findings on scans withdrew from the study. None had received anticoagulants, and none were symptomatic for PE. This finding argues for the clinical insignificance of isolated subsegmental PE disease. [8, 18, 20]
Other investigators argue that subsegmental PE disease is of clinical significance, especially in patients with limited cardiopulmonary reserve (eg, patients with pulmonary edema, cor pulmonale, hypotension, respiratory insufficiency, or syncope) in whom a small embolus can be fatal. An 8% mortality rate associated with PE was noted (proved at autopsy) in a study of 77 patients with low-probability V/Q scans who did not receive anticoagulants. Small emboli may represent only the "tip of the iceberg" in a patient with pulmonary thromboembolic disease. In an autopsy series of patients who died of PE, both organizing and acute embolic material were recovered in 50%. This finding indicates that patients often have an initial nonfatal embolic event before a lethal event. In addition, clinically occult or unimportant small emboli may potentially cause chronic pulmonary hypertension. [21, 22, 23]
Further limitations of spiral CT include the poor visualization of horizontally oriented vessels in the middle lobe and lingula because of volume averaging. The presence of intersegmental lymph nodes may result in false-positive readings. Finally, peripheral areas of the upper and lower lobes may be scanned inadequately. [24, 25, 26, 27, 4]
As of the time of writing, the protocol for PE imaging at the New York University Medical Center was as follows:
Nonenhanced scout and axial scans are obtained for localization of the pulmonary arteries.
A 20-mL test dose of nonionic contrast agent is administered, and a single section is obtained at the level of the main pulmonary arterial bifurcation at 5, 10, 15, and 20 seconds after the administration of contrast agent bolus. This is done to tailor the optimal imaging time (maximal contrast agent enhancement of the pulmonary artery) for each patient.
A 125-mL dose of nonionic contrast agent is administered at a rate of 3 mL/s via a peripheral intravenous line.
Sections include 3 X 2-mm sections from the aortic arch to the pulmonary veins, 7 X 6-mm sections from the pulmonary veins to level of the adrenal glands, and 7 X 6-mm sections from the apices to the aortic arch. A pitch of 1.6 is used.
Currently, for the clinical evaluation of PE, this and other institutions are combining PCTA with CTV of the lower extremities. The intravenous administration of contrast agent and delayed maximal contrast enhancement allow further imaging of the veins in the lower extremities, pelvis, and inferior vena cava without the additional administration of contrast material. This combination allows concurrent evaluation for PE and deep venous thrombosis (DVT).
Loud et al reported on 2 protocols that were used at 2 institutions in 650 consecutive patients.  CT imaging was performed from the diaphragm to the upper calves at 3 and 3.5 minutes after administration of contrast material (after completion of pulmonary angiography), yielding a typical total of 18-20 venous images (5- to 10-mm sections acquired at 5-cm intervals).
The sensitivity and specificity of CTV in detecting femoropopliteal DVT, compared with those of sonography, were 97% and 100%, respectively. Positive and negative predictive values were 100% and 99%, respectively. Therefore, by extrapolation, CTV results might compare favorably with those of contrast venography because the accuracy of lower-extremity venous sonography is comparable to that of contrast venography.  To this author's knowledge, no study has yet provided a direct comparison of CTV and contrast venography of the lower extremities.
Since 90% of PEs are believed to originate from the lower extremities and pelvis, CTV is an important adjunctive tool in the protocol of PE evaluation at the time of PCTA. The comparable sensitivity and specificity of CTV with its standards of reference and with venographic and sonographic examination of the extremities allows "one-stop shopping," that is, a single test. In addition, CTV further enables evaluation of the pelvic veins and the inferior vena cava, structures that are neither relatively accessible for sonography nor routinely imaged, respectively. Cost-analysis studies are needed to show an economic benefit of the combined protocol. [30, 31, 32, 5]
Pulmonary Magnetic Resonance Angiography
Pulmonary magnetic resonance angiography (PMRA) does not require the use of iodinated contrast agent or ionizing radiation. PMRA is reported to have sensitivity and specificity comparable to those of PCTA. Contrast material can be injected via a peripheral intravenous line. PMRA provides multiplanar reconstruction and can be performed concomitantly with magnetic resonance venography (MRV).
Currently, PMRA requires prolonged breath-holding by the patient. PMRA requires the use of contrast agent (with a minimal risk of an allergic reaction), and it may not be tolerated by patients with claustrophobia (if closed MRI systems are used).
Currently, PMRA has not been widely studied, used, or accepted. PMRA lacks sensitivity in detecting subsegmental embolic disease, and its spatial resolution is lower than that of DSPA.
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.
NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.
Because digital subtraction pulmonary angiography (DSPA) is perceived to be invasive and requires the use of iodinated contrast material, it has been underutilized. In addition, the need to use iodinated contrast medium often convinces the referring clinicians not to order CT for timely radiologic assessment of PE in patients with a known hypersensitivity to contrast material or in patients with renal insufficiency. These problems are inherently alleviated with PMRA. Although some patient hypersensitivity to MRI contrast agents has been reported, this is rare. In a study of 30 patients (who underwent both DSPA and PMRA within 24 h), all patients preferred PMRA. [33, 34]
PMRA is also less expensive than DSPA, although it is more expensive than lung scintigraphy. The contrast agents are not nephrotoxic. In initial reports dating back to 1989, the results were poor because of respiratory motion artifact and poor contrast between flowing blood and an embolus. Currently, the use of faster magnetic resonance hardware, electrocardiogram triggering, surface coils, pulse sequences with short echo times, and dynamic gadolinium enhancement have made it possible to perform high-resolution angiography during a single breath hold. [34, 35, 36, 37]
PMRA shares some shortfalls with pulmonary CT angiography. These include lower spatial resolution, which results in a low yield in the detection of lesions in the subsegmental and smaller pulmonary arteries and branches in clinical studies (see the image below). Because the number of patients in previous studies was small, wide acceptance of the techniques and validation of the results have not occurred yet. In the PMRA-aided detection of PE, several investigators reported a sensitivity of 100%, a specificity of 95%, and positive and negative predictive values of 87% and 100%, respectively. Gadolinium-based contrast agent was administered, and imaging was performed by using a body coil and a 1.5-T system with fast gradient-echo capability. 
In a study of 20 patients, the sensitivity of PMRA in diagnosing PE was 100%, and its specificity was 62%. A 2-dimensional time-of-flight MRI angiographic technique was supplemented by fast gradient-recalled echo sequences. By using a 0.35-T magnet, multiphasic cardiac-gated spin-echo MRI was used to detect acute PE. Sensitivity and specificity of 90% and 77%, respectively, were obtained. [36, 38]
Patients in the last 2 studies described did not receive contrast agent, and findings were correlated with those of DSPA. Concerning these and other study results, Meaney et al wrote, "Because of the small number of patients and the even smaller number of positive studies, however, the confidence limits are large and optimism must be tempered by caution." 
Currently, some of the most important limitations of PMRA include the requirement of an extended breath hold (by patients with presumed respiratory distress) and image degradation resulting from breathing artifacts. Some pitfalls of MRI include incomplete suppression of pulmonary venous flow with presaturation pulses. Areas of atelectasis and perihilar or peribronchial fat have been misinterpreted as PE. [36, 38, 39]
Pulmonary Vascular Disorders
The most common indication for examination of the pulmonary vascular system is pulmonary embolism (PE). A mortality rate of almost 10% results from the initial episode, with an estimated prevalence of 600,000 cases in the United States. An annual rate of 23 cases per 100,000 population is ascribed to a first episode of recognized PE. The rate of detection is low, as evidenced by the fact that at autopsy, PE is identified in 20% of cases, with 5% involving massive PE. Currently, reports show that no more than 30% of cases are being recognized. Elderly patients and patients with concomitant pneumonia or congestive heart failure are much less likely to receive a correct diagnosis. [40, 41, 42, 43]
The incidence of PE in a general hospital was 400 cases in 175,730 patients. This incidence was linearly related to age, but PE mostly occurred in middle-aged and elderly patients; it was more prevalent in women. The impact of childbearing and the use of birth control pills were not significant factors, as evidenced by the fact that the incidence of PE was not higher in women younger than 50 years. Approximately 33% of patients with PE have recurrent emboli, and mortality rates in untreated patients are 18-38%. This mortality rate can be reduced to approximately 8% with appropriate therapy. [44, 45, 46, 47, 48]
Digital subtraction pulmonary angiography (DSPA) remains a secondary test after prior lung scintigraphy (if performed) in patients with suspected PE. Clinical referral for DSPA depends on the availability of nuclear medicine scanning, the degree of clinical suspicion for PE, and the clinical condition of the patient. Many requests for catheter pulmonary angiography are made when pulmonary computed tomography angiography (PCTA) is inadequate or when its results are equivocal. Knowing the limitations of PCTA, the referring physician often rejects a negative PCTA result and insists on catheter pulmonary angiography.
Using angiography, PE is diagnosed on visualization of endoluminal filling defects, thromboemboli, or abrupt vascular obstruction. With such findings, the examination can be terminated, because the demonstration of a further clot burden would not affect treatment. Indirect signs, such as delayed opacification or a diminished capillary stain, are nonspecific. The latter is seen randomly in patients whose findings are otherwise normal; findings of diminished capillary stain are seen especially in the midperiphery of the lung. Atelectasis is a common finding; it is shown as crowding of the vessels, usually at the lung bases. Blood flow is slowed in the setting of pneumonia, with intrinsically normal vessels and no intense blush. 
Another advantage of DSPA is that it allows one to perform therapeutic intervention in patients with PE. Usually, this procedure is reserved for patients with hemodynamic instability in the setting of a large thromboembolic burden. Therapeutic interventions include the following: (1) transvenous catheter pulmonary embolectomy, now rarely performed; (2) catheter-directed thrombofragmentation with mechanical or hydrodynamic devices; and (3) the intrathrombotic delivery of thrombolytic medication. No additional clinical benefit has been shown with catheter-directed thrombolytic therapy compared with the peripheral intravenous administration of agents.
Chronic pulmonary embolism
DSPA findings in chronic PE include arterial webs, stenoses, irregular occlusions, scalloped mural irregularities, and pouching defect (a concave edge of thrombus facing the opacified lumen) (see the image below). In this setting, surgical thromboendarterectomy is increasingly used as the treatment of choice. Pulmonary angiograms can be used as a roadmap to determine the surgical approach in this form of treatment. [49, 50]
A paucity of vascularity, decreased arborization, and stretching of the vessels are seen in emphysema, although lung scintigraphic findings are virtually always diagnostic.  The clinical presentation may not be easily distinguishable from that of primary pulmonary hypertension (PPH).
Unusual forms of pulmonary embolism
Unusual forms of PE include embolization caused by tumor, amniotic fluid, fat, or air. The diagnosis usually is made on the basis of clinical considerations, including the clinical setting, the sequence of events leading to the symptoms, and the severity and the rapidity of the onset of symptoms.
Tumor PE arises from solid tumors that seed the systemic circulation with individual cells or cell clusters that are filtered by the pulmonary circulation. It occurs in patients who are at high risk for thromboembolic events, especially those with mucin-producing adenocarcinomas, such as breast, stomach, or colon cancers. Large-fragment embolization has been reported in patients with a chondrosarcoma, renal cell carcinoma, right atrial myxoma, or Wilms tumor. Only in this setting may pulmonary angiography findings be abnormal. [52, 53, 54, 55]
Usually, only the V/Q scan demonstrates peripheral subsegmental perfusion defects, often with a mottled appearance. In microvascular tumor embolization during DSPA (in which findings are usually nearly normal, the microvascular cytologic findings in aspirated blood specimens obtained from the pulmonary artery catheter can reveal malignant cells in both tumor microembolism and lymphangitic carcinomatosis.) [56, 57, 58]
Rarely, DSPA or PCTA reveals a mimic of PE, such as angiosarcoma. Angiosarcoma is a malignant primary vascular tumor seen as an endoluminal mass that may expand the luminal diameter of the pulmonary artery. Other potential sites include the aorta, heart (right atrium), inferior vena cava, liver, face, scalp, breast (postirradiation), and uterus. Frequent embolization is associated with aortic angiosarcomas. The best method of analyzing pulmonary angiosarcoma is with multiplanar imaging (ie, CT and MRI); pulmonary arterial pressure measurement and intravascular biopsy may be performed during DSPA.
Amniotic fluid embolism
Although uncommon, amniotic fluid embolism (AFE) is a leading cause of maternal mortality in the United States, with an incidence of 1 case per 80,000 births. Associated fetal and maternal mortality rates are 40% and 80%, respectively. About 40% of patients develop a major coagulation disorder, and as many as 50% of patients die within 1 hour of the onset of symptoms. The rapid deterioration in the patient's condition and the presumptive diagnosis usually obviate pulmonary arterial imaging. A sudden onset of respiratory distress, cyanosis, convulsions or other signs of central nervous system irritability, and cardiovascular collapse during labor and delivery are encountered in the clinical setting. [45, 59, 60, 61]
The pathophysiology underlying the sequelae of AFE is not well understood; however, the sources of AFE are believed to be uterine endocervical tears occurring during labor and rupture of the fetal membranes in the setting of a favorable pressure gradient. Some have proposed that cytologic findings may confirm the diagnosis by revealing amniotic fluid components in blood specimens obtained from the pulmonary artery circulation. Traditionally, these results have not proven to be specific for AFE; however, one study showed some promising results. [62, 63]
The treatment of AFE consists of aggressive hemodynamic support. Predisposing factors related to AFE include first-trimester curettage abortion; second-trimester abortion involving sodium chloride solution, prostaglandin, or urea abortion; hysterectomy; cesarean delivery; abdominal trauma; and amniocentesis. 
Well-recognized criteria for the clinical diagnosis of fat embolism include respiratory insufficiency (which may be severe enough to meet standard criteria for adult respiratory distress syndrome [ARDS]), global neurologic deficits, and a petechial rash. Classically, symptoms manifest 24-72 hours after an initiating event, usually a long-bone fracture. Other nontraumatic clinical situations, such as liposuction, pancreatitis, steroid therapy, and bone marrow harvesting and transplantation, are less common.
The pathophysiology is believed to involve circulating fat globules that are hydrolyzed by lipase to release toxic fatty acids with ensuing lung injury. Intrapulmonary and intracardiac shunting allows small globules to pass into the systemic arterial circulation, leading to neurologic sequelae and a petechial rash. V/Q scans demonstrate a mottled pattern of subsegmental perfusion defects, as in tumor embolization, with a normal ventilatory component. The rapid onset of ARDS obviates any other pulmonary imaging. 
Aspirates of blood from the pulmonary circulation can demonstrate fat globules, but the sensitivity and specificity of this finding are completely unknown. Treatment includes hemodynamic support, steroid therapy, and appropriately timed surgical intervention for the fracture. [52, 66, 67]
An accurate history in the appropriate clinical setting helps the clinician definitively diagnose an air embolism in the pulmonary arteries. During fluoroscopy, air can be seen migrating from the right cardiac chambers into the pulmonary artery circulation. Air-fluid levels may be seen in the pulmonary vessels on chest radiographs; these are pathognomonic for an air embolism. Echocardiography performed immediately after the onset of symptoms can reveal air within the cardiac chambers. With cerebral air embolization, CT scans of the head can show intravascular air. As with the aforementioned unusual forms of PE, the rapid deterioration in the patient's condition, the accurate presumptive diagnosis, and the requirement for urgent therapy prevent the use of further pulmonary imaging. [68, 69, 70]
Most commonly, air embolism occurs during the insertion of a central venous catheter. It is a potentially serious complication when carbon dioxide is used as a contrast agent, especially in the venous system. Other predisposing factors include infant respiratory distress syndrome; barotrauma during positive-pressure ventilation, pneumothorax, pneumomediastinum, and lung biopsy; procedures in which gas (most commonly carbon dioxide) is insufflated into a body cavity (eg, endoscopy); surgical procedures in which the wound is situated above the heart; open heart surgery; and cesarean delivery. 
Air in the circulatory system causes mechanical obstruction and vasospasm. It can reach the coronary and cerebral circulations via microvascular intrapulmonary shunts or direct passage through a cardiac shunt, such as a patent foramen ovale. Physiologic responses include an acute increase in pulmonary arterial and right ventricular pressures, hypotension, and pulmonary edema. 
With immediate detection, therapeutic interventions include the nasal administration of oxygen and the placement of the patient in the left lateral decubitus or Trendelenburg position, with continuous monitoring of his or her vital signs (oxygen saturation, blood pressure, cardiac rate and rhythm). Clinical failure of these maneuvers may require further intervention, such as the removal of the air by using central catheters, closed chest cardiac massage, and hyperbaric therapy. 
Pulmonary arterial and venous anomalies
Although a pulmonary AVM (PAVM) can be diagnosed by using CT or PMRA, DSPA is uniquely suited for the diagnosis and treatment of this disorder. The standard treatment is transcatheter embolization. 
Relatively uncommon, pulmonary arteriovenous malformations (PAVMs) are most frequently congenital. They are associated with hereditary hemorrhagic telangiectasia or Osler-Weber-Rendu disease; PAVMs can also be isolated, without any such association. These are most frequently singular. Less common are the acquired forms (termed fistulas) in patients with cirrhosis (hepatogenic pulmonary angiodysplasia), cancer, trauma, history of surgery, or infection (actinomycosis, schistosomiasis).
Osler-Weber-Rendu disease is an autosomal dominant disorder characterized by telangiectasias and AVMs of the lungs; skin; mucosa; brain; liver; and, potentially, any organ. The reported prevalence is 2-15 cases per 100,000 population, and pulmonary involvement occurs in 25% of patients.  Classically, PAVMs are direct communications between branches of the pulmonary arteries and veins, with an intervening vascular nidus.
On chest radiographs, a PAVM most commonly appears as a nodular opacity associated with a tubular structure leading to and emanating from it; this structure represents the enlarged feeding artery and draining vein. Similar findings are noted on CT scans in which the degree of enhancement usually parallels that of the main pulmonary arteries. A PAVM represents a left-to-right shunt in which blood filtration by the pulmonary circulation is bypassed. This situation potentially leads to cyanosis and paradoxical embolization, which may manifest as a brain abscess.
Patients, especially those with a single PAVM, may remain asymptomatic until their third decade of life. Clinical manifestations include gastrointestinal bleeding, epistaxis, and symptoms of pulmonary and cerebral AVMs. Symptoms referable to the PAVM include dyspnea on exertion, exercise intolerance, palpitation, hemoptysis, and chest pain. Under low pressure, PAVMs are rarely associated with hemodynamic disturbance, and they are usually not associated with heart failure.
When detected, PAVMs should be treated to prevent potential complications, especially brain abscess. The mainstay of therapy is transcatheter embolization by using detachable balloons and coils. Dynamic anatomic detail is provided by conventional angiography, in which the angiographic run, similar to that of cineangiography, provides anatomic landmarks for targeting the embolization (see the images below). Different projections show the branch of the origin of each feeding artery, the size of the nidus, the territory of pulmonary parenchymal involvement, and the enlarged draining vein.
Intrapulmonary arteriovenous shunting is the hallmark of hepatopulmonary syndrome in the setting of chronic liver disease. The alveolar-arterial oxygen gradient increases with room air. Diagnostic modalities include perfusion imaging with99m Tc-MAA or contrast-enhanced echocardiography with sodium chloride microbubbles. 
Two angiographic patterns have been described.  The more common pattern consists of an increased number of visible vessels, especially at the lower lobes. Visible arteriovenous fistulas and/or subpleural telangiectasias with marked early venous filling are seen in the other type.
Aneurysmal dilatation of the main pulmonary arteries may occur with long-standing pulmonary arterial hypertension, with chronic obstructive pulmonary disease, and with left-to-right cardiac shunts. Aneurysms and pseudoaneurysms of the main, lobar, or segmental pulmonary arteries may occur with trauma, neoplasm,  or infection, or they may be of idiopathic etiology.
Infectious causes of aneurysm
Rasmussen aneurysm may be seen in cavitary tuberculosis as a result of erosion by the cavity into a pulmonary artery. DSPA may demonstrate pseudoaneurysms and the formation of arteriovenous fistulas.  Invasive pulmonary aspergillosis can lead to transbronchial vascular invasion, causing thrombosis of pulmonary arterioles and ischemic parenchymal necrosis. Aspergillosis affects patients who are severely immunocompromised, especially those with hematologic malignancies; these patients can present with hemoptysis and radiographic evidence of pneumonia. The diagnosis can usually be made on clinical grounds or on the basis of plain radiographic findings and CT results, obviating the need of pulmonary angiography.
Septic embolization most commonly affects the pulmonary parenchyma in the form of infiltrates, nodular consolidation, and cavitation. In addition, the potential exists for pseudoaneurysm formation, usually involving the smaller branches of the pulmonary arterial circulation, especially in the lower lobes. This is related to gravity and greater volume of blood circulation. An infected thrombus becomes lodged in a pulmonary arterial branch, most commonly from a peripheral or central intravascular source such as an infected venous catheter or cardiac pacemaker wires. Patients who abuse intravenous drugs are at particular risk, with or without concomitant tricuspid valve endocarditis. Patients may also develop an aneurysm after thoracotomy for the resection of a malignancy. This can occur at the site of the pulmonary artery transection or in adjoining tissues. 
Idiopathic causes of aneurysm
The triad of Behçet disease includes oral and genital ulcers, eye and skin lesions, and thrombophlebitis. Pulmonary artery aneurysms are a poor prognostic sign; they are seen in 2% of patients. Large-vein occlusion is also a manifestation of this rare idiopathic multisystemic disease. 
Pulmonary artery aneurysms also occur in Hughes-Stovin syndrome. Venous thrombosis, especially in the vena cavae, and angioplastic changes of the bronchial artery can affect young men. 
DSPA is of indirect value in diagnosing bronchopulmonary sequestration (see the images below). Findings demonstrate lack of perfusion of the involved pulmonary segment, in which the anomalous arterial supply is most commonly from the thoracic aorta, as shown with adjunctive thoracoabdominal aortography. This congenital bronchopulmonary malformation consists of a nonfunctioning or malfunctioning lung segment, a lack of communication with the tracheobronchial tree, and a systemic arterial supply. A lower lobe predominance is noted, more commonly in the left lung.
Intralobar sequestration tends to appear in adulthood. This is enclosed by the visceral pleura of the adjacent normal lobe and appears with pulmonary venous drainage. Patients report recurrent pulmonary infections. Associated congenital anomalies (skeletal and foregut anomalies) are present in 14% of patients. [82, 83]
Invested in its own pleura, extralobar sequestration tends to have systemic venous drainage (into the inferior vena cava, azygos or hemiazygos, or portal venous system). Patients more commonly present during infancy; they are often asymptomatic, with extralobar sequestration as an incidental finding. Respiratory distress and congestive heart failure (related to the shunting of blood) can be presenting symptoms in affected newborns. Compared with intralobar sequestration, extralobar sequestration has a stronger association with other congenital anomalies, such as diaphragmatic, cardiac, and gastrointestinal anomalies (60% of cases). 
The diagnosis can be made by using axial imaging. Traditionally, treatment has been symptomatic management and surgical resection of the affected lobar segment; however, transcatheter coil embolization has been reported. [84, 85, 86]
DSPA is uniquely suited to help in differentiating an AVM from a pulmonary varix. Although the diagnosis can be made by using cross-sectional imaging and echocardiography, the dynamic nature of the angiographic series shows no enlarged feeding artery or vascular nidus in the setting of a pulmonary varix. [87, 88, 89, 90, 91]
A pulmonary varix (ie, an enlargement of the pulmonary vein near its insertion into the left atrium) appears late, during the venographic phase. Most cases are congenital, with a minority of cases associated with pulmonary venous hypertension and cirrhosis of the liver. A rare and often asymptomatic disorder, pulmonary varix is usually diagnosed incidentally; further radiologic imaging is performed to confirm suggestive chest radiographic findings. Patients can present with hemoptysis,  and the anomaly may serve as a potential thrombogenic nidus and a source in the setting of atrial fibrillation. [90, 92, 93, 94]
Anomalous pulmonary venous return
Total anomalous pulmonary venous return is usually diagnosed during the first few days of infancy because of its resultant severe hemodynamic disturbance. Although improved surgical techniques have dramatically improved survival rates, operative mortality and postoperative long-term complications remain significant. The different types of disorders are most often diagnosed by using angiocardiography, although noninvasive imaging, echocardiography, and MRI have been used. [95, 96]
Partial anomalous pulmonary venous return (PAPVR) can be seen in children and adults. This can occur in the form of hypogenetic lung syndrome or scimitar syndrome in association with pulmonary sequestration. PAPVR can occur independently when it emanates from the left upper lobe. Scimitar syndrome is a form of lung hypoplasia or aplasia that affects 1 or more lobes; it is accompanied by PAPVR.
With a right-sided predominance, this condition can often be diagnosed by using chest radiographs or axial images. The smaller lung is associated with the scimitar vein, which is a caudally oriented enlarged vein that can connect to a systemic infradiaphragmatic vein (inferior vena cava, portal vein, hepatic vein) or to the right atrium.  DSPA can be used to demonstrate vascular anomalies, including ipsilateral pulmonary artery hypoplasia and an anomalous pulmonary venous return.
Partial anomalous pulmonary venous drainage of the left upper lobe is a less common anomaly. This isolated pulmonary venous return to the right side of the heart occurs via the left brachiocephalic vein. Occasionally, it is found in conjunction with cardiac anomalies such as mitral stenosis, pulmonary stenosis, patent ductus arteriosus, and atrial septal defects. Patients with this disorder are usually asymptomatic, and the condition is usually incidentally diagnosed during routine radiographic examination performed for other reasons. [98, 99, 100, 101, 102, 103, 104]
Primary pulmonary hypertension
Primary pulmonary hypertension (PPH) is an uncommon disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance without an obvious cause. Its association with high levels of antinuclear antibodies suggests an immunologic mediator. PPH is a diagnosis of exclusion (with a female predominance). Patients most commonly present in the third and fourth decades of life with the insidious onset of dyspnea.
Three histologic pathologic patterns have been described: plexogenic pulmonary arteriopathy, thrombotic pulmonary arteriopathy, and pulmonary veno-occlusive disease. [105, 106] Mural medial hypertrophy and intimal fibrosis are common in the first 2 types, with plexiform lesions found in plexogenic pulmonary arteriopathy. Intimal proliferation and fibrosis of the intrapulmonary veins and venules, with occasional extension into the arteriolar bed, are found in pulmonary veno-occlusive disease.
The diagnosis is made by the exclusion of secondary causes of pulmonary hypertension. The characteristic history of gradual onset of shortness of breath, with normal cardiac function, and the characteristic physical findings, including abnormal cardiac sounds, are sufficient to support the diagnosis. Electrocardiographic and echocardiographic findings also are characteristic. Chest radiographs show enlarged central pulmonary arteries and clear lungs (see the image below). Pulmonary scintigraphic findings are unpredictably normal or abnormal. In cases with abnormal findings, multiple diffuse and patchy perfusion defects of a segmental or nonsegmental nature may be seen; these may be suggestive of PE.
Pressures in the right side of the heart and pulmonary artery may be measured during DSPA. These can be used as prognostic indicators of survival. Elevated pressures pose an increased risk with contrast agent injections. Selective or subselective injections are advocated in this setting, with the use of iso-osmolar or hypo-osmolar nonionic contrast material.
A mean survival period of 2-3 years from the time of diagnosis has been reported. Behavior modification, symptomatic treatment, and preventive therapy are the main forms of treatment. Although the approaches are not optimal, they include the use of vasodilator drugs (calcium channel blockers), inhalational iloprost, or intravenous prostacyclin; anticoagulation; and heart-lung transplantation. 
Takayasu arteritis and Behçet disease are idiopathic forms of systemic vasculitis that can affect the pulmonary arteries. In addition, infectious vasculitis is acquired in the form of local or embolic disease. Behçet disease, Hughes-Stovin syndrome, tuberculous infection, and septic embolization leading to aneurysmal disease are discussed elsewhere in this article.
Takayasu arteritis type IV involves the pulmonary arteries. Stenotic or occlusive lesions and recanalization of previously thrombosed vessels are found in the segmental and subsegmental branches of the pulmonary arteries, with upper lobe branch predominance. This finding is caused by granulomatous inflammatory infiltrate resulting in intimal fibrosis of the vessel walls in this chronic inflammatory panarteritis of unknown etiology of the aorta and its branches. 
In this disease of young adulthood, a female predominance is noted. The disease affects persons of Asian, South American, or African descent. Patients present with constitutional symptoms such as fever, malaise, and weight loss. The mainstay of treatment is immunosuppression with steroids and other immunosuppressive agents. Angioplasty is reserved for those with peripheral arterial disease after any active disease phase resolves.
Peripheral pulmonary artery stenoses
Acquired and congenital forms have been identified in this uncommon condition in which a localized luminal stenosis or long tubular hypoplasia of the main, lobar, or segmental pulmonary arteries may occur. Bronchogenic or mediastinal malignancy may result in central arterial stenosis. Vascular obstruction, encasement, dislocation, and intraluminal invasion are other angiographic findings. 
The advent of axial imaging has obviated DSPA in the evaluation of pulmonary and mediastinal neoplasms. DSPA is of modicum value in revealing the blood supply to pulmonary and other intrathoracic tumors, because the blood supply is principally derived from systemic arteries.  Surgical and other types of trauma may result in stenosis. This also may be a manifestation of chronic PE.
Peripheral pulmonary artery stenosis may be associated with a long list of congenital disorders. Most notably, these include post-rubella syndrome, Noonan syndrome (ie, male Turner syndrome), tetralogy of Fallot, and cardiac septal defects. 
Pulmonary artery stenosis most commonly includes multiple lesions and usually involves the pulmonary trunk or its bifurcation. It may also appear as solitary or multiple peripheral pulmonary artery stenoses. The condition usually resolves spontaneously, although it may be present in as many as 5% of premature infants. 
Enlargement or aneurysmal dilatation of the main pulmonary arteries can be seen in a number of disorders. Primary and secondary causes are possible. The single primary cause is PPH. Secondary causes include chronic pulmonary thromboembolism, chronic obstructive lung disease, interstitial lung disease, left-to-right cardiac shunts, and left-sided heart disease. Pulmonary arterial hypertension is also associated with connective tissue disorders and liver disease, the use of appetite-suppressing drugs (phentermine and fenfluramine), the use of oral contraceptives, hyperuricemia,  and HIV disease. [111, 112, 113]
Diagnostic use of the D-dimer test and alveolar dead-space determination as potential screening tests for PE remains under study, especially in the emergency department setting. The variability of specific assays and their poor performance in patients with cancer currently limit the use of the D-dimer test. [114, 115]
Other technical innovations have contributed to the evolution of imaging of the pulmonary circulation. With the advent of newer techniques in existing modalities, diagnostic pathways in the imaging of pulmonary vascular disease are being redefined constantly. Current debate centers on the choice of the most appropriate first-line examination in the diagnosis of PE.
Depending on the preference of the referring physician, CTA often replaces V/Q scanning as the initial diagnostic investigation. With the diagnostic limitations in PE, CTA offers more clinically relevant information than nuclear scintigraphy. This becomes important in the differential diagnosis of other structural intrathoracic diseases in which the clinical presentation may mimic that of PE. However, one author recently opined that, in comparison with V/Q scanning, the increased cost and higher radiation dose needed with CTA do not support the complete replacement of scintigraphy with CT imaging. 
The debate is further compounded by recent improvements in the CT detection of emboli in subsegmental and smaller arterial branches. Although the clinical significance is still argued, multidetector-row CT has been shown to improve visualization in such branches. This refined CT technique has significantly improved arterial imaging of the pulmonary circulation and elsewhere in the body, as compared with single–detector-row CT, the conventional type of spiral CT. 
To a certain degree, volume averaging has decreased with the ability to perform imaging with the thinner collimation offered by multidetector-row CT technology. More specifically, the rate of detection of subsegmental pulmonary arterial emboli increased an average of 40% with the use of 1-mm-thick rather than 3-mm-thick sections.  In addition, the number of indeterminate case reportedly decreased by 70%, and greater agreement was found among image interpreters. However, to the author's knowledge, no study has compared multidetector-row CT with the criterion standard of conventional catheter pulmonary angiography in the diagnosis of PE.
Although chest radiography remains a primary screening tool for thoracic vascular and nonvascular disease, many options remain for the further diagnostic workup of other pulmonary arterial diseases. Currently, the imaging modalities of choice for the diagnostic evaluation of bronchopulmonary sequestration are CT and MRI. Each affords the evaluation of the venous drainage and an associated aberrant systemic arterial supply. In this clinical scenario, conventional pulmonary angiography can serve as a problem-solving tool when findings on cross-sectional images are not definitive. For example, a pulmonary varix can be confused with a sequestration on CT scans. DSPA retains an active role not only in the treatment of an AVM but also in its diagnosis. According to McGuinness, anecdotal evidence suggests a greater detection rate of PAVMs with DSPA rather than with CT scanning (personal communication, 2002).
Innovations in MRI and MRA may widen the clinical assessments of pulmonary vascular disease. In the future, the use of phased-array body coils, the application of navigator pulse sequences, and 3-dimensional time-resolved ultrafast MRA may overcome the limitations of current MRI techniques. [117, 118]